Fundamentals of Anatomy and Physiology

Fundamentals of Anatomy and Physiology

Anna Chruścik, Kate Kauter, Louisa Windus, and Eliza Whiteside

Leanne Dooley

University of Southern Queensland

Contents

1

About the Authors

Dr Anna Chruścik is an academic at the University of Southern Queensland, Springfield, Australia. Anna has taught courses in human anatomy and physiology; histopathology and cytology; techniques in comparative physiology; pathophysiology; cells, tissues and regeneration; metabolism; immunology; biomolecular sciences laboratory; biochemistry and biochemical pathways in Australian universities. Her research background focused on the relationship between transforming growth factor and colon cancer stem cells. Anna strives to excite and inspire students about science by providing relatable guidance, support and knowledge. 

Dr Kate Kauter is an Associate Professor in biomedical science at the University of Southern Queensland. She has taught anatomy, physiology, pathophysiology, pharmacology and microbiology to students from many disciplines including nursing, biomedical sciences, food sciences and agricultural sciences, among others. Kate has developed a number of digital activities to increase student interaction with these content areas and has deployed the use of current technologies, including use of 3D and animations in practical classes to inspire students’ learning. The latest venture is the provision of an open education resource for the study of anatomy and physiology to allow all students access to the fundamental information needed in the understanding of the human body.

Dr Louisa Windus is a lecturer and researcher in the school of Health and Wellbeing (Biomedical Sciences) at the University of Southern Queensland, Australia. Louisa has a passion for developing methods that foster engagement and empower students to learn. Outside of the classroom, Louisa’s research focusses on biomarkers or molecular factors that mediate cancer progression and growth. She has collaborated extensively with research institutes across Australia and has been influential in developing novel 3D in vitro models that have helped expediate the drug discovery pipeline.

Dr Eliza Whiteside is a biomedical science researcher and Associate Professor at the University of Southern Queensland, Toowoomba, Australia. For the past two decades, Eliza has taught courses in introductory biomedical science, cell and molecular biology, anatomy and physiology, laboratory methods, pathophysiology andbiotechnology in universities in Australia and in the United Kingdom. Eliza’s passion is in improving the lives of others through accessible knowledge building, using learning and teaching scholarship, research and community outreach. Her research background is investigating dysregulated cell biology in cancer and chronic wounds. Her community outreach includes cancer education to the public and hands on science, particularly in underserved communities such as regional and remote schools 

2

Acknowledgments

This book is predominantly based on the open textbook Anatomy and Physiology by J. Gordon Betts, Kelly A. Young, James A. Wise, Eddie Johnson, Brandon Poe, Dean H. Kruse, Oksana Korol, Jody E. Johnson, Mark Womble and Peter DeSaix. Our team of biomedical science academics and librarians at the University of Southern Queensland have a desire to help students succeed in their studies of anatomy and physiology by providing equitable access to information resources. This has driven us to adapt Anatomy and Physiology for Australian tertiary students in biomedical and health disciplines.

In Fundamentals of Anatomy and Physiology, you will find an Australian perspective on the fundamentals of anatomy and physiology along with career perspectives, with content especially re-worked for Australian students. Our team has also added new contributions including interactive quizzes, appendices and a glossary. Our sincere thanks to each team member for their tireless efforts, enthusiastic support of the project and their valued work on this book. Please see About the Authors for the list of our contributors. We would also like to thank Leanne Dooley for her review and original contributions to Chapter 6 Blood.

This book would also not have been possible without the outstanding contribution of our Open Education Content Librarian Nikki Andersen. We offer our sincere thanks to Nikki for her expertise, insightful guidance and dedicated approach in stepping us through this new process.  Nikki, you made the journey enjoyable, exciting and achievable. Thank you. We also extend our appreciation to Adrian Stagg, Manager (Open Educational Practice) for his support, advice and expertise in open textbooks.

Finally, we thank Dr Anna Chruscik and Associate Professor Kate Kauter who committed their substantial skills and enthusiasm to create a seamless project which harnessed the writing talents of our team. Their writing and editing expertise supported us in producing this open textbook.

Acknowledgment of Country

The authors wish to acknowledge the Aboriginal and Torres Strait Islander peoples of this nation. We acknowledge the traditional owners of the country throughout Australia and their continuing connection to the land, culture and community. We acknowledge the traditional custodians of the lands on which we live and work, and where the book was written. We acknowledge the cultural diversity of all Aboriginal and Torres Strait Islander peoples and pay respect to Elders past, present and future. We celebrate the continuous living cultures of First Australians and acknowledge the important contributions Aboriginal and Torres Strait Islander people have and continue to make in Australian society.

3

The University of Southern Queensland (USQ) is committed to advancing the use of open textbooks in higher education. This textbook is a tool to support first year anatomy and physiology courses taught in Australia, aiming to provide students with an increased access to free, high-quality learning materials.

The material in this textbook is largely based on  OpenStax’s Anatomy & Physiology textbook, however, has been modified for Australian course curriculum.

The coverage and scope of the current text includes:

  1. Levels of organisation, homeostasis and nomenclature
  2. Cells: structure and reproduction
  3. Tissues, organs, and Systems
  4. Integumentary System
  5. Blood
  6. Cardiovascular system
  7. Lymphatic system and immunity
  8. Respiratory systems
  9. Muscle system
  10. Skeletal system
  11. Musculoskeletal system
  12. Digestive system
  13. Nervous system
  14. Endocrine system
  15. Reproductive System
  16. Pregnancy and human development
  17. Urinary system

I

Levels of Organisation, Homeostasis and Nomenclature

1.1 Overview of Anatomy and Physiology

Learning Objectives

By the end of this section you will be able to:

  • Compare and contrast anatomy and physiology, including their specialisations and methods of study
  • Discuss the fundamental relationship between anatomy and physiology

Human anatomy is the scientific study of the body’s structures. Some of these structures are very small and can only be observed and analysed with the assistance of a microscope. Other larger structures can readily be seen, manipulated, measured, and weighed. The word “anatomy” comes from a Greek root that means “to cut apart.” Human anatomy was first studied by observing the exterior of the body and observing the wounds of soldiers and other injuries. Later, physicians could dissect bodies of the dead anatomy to augment their knowledge. When a body is dissected, its structures are cut apart in order to observe their physical attributes and their relationships to one another. Dissection is still used in medical schools, anatomy courses, and in pathology labs. In order to observe structures in living people, however, several imaging techniques have been developed. These techniques allow clinicians to visualise structures inside the living body such as a cancerous tumour or a fractured bone.

Like most scientific disciplines, anatomy has areas of specialisation. Gross anatomy is the study of the larger structures of the body, those visible without the aid of magnification (Figure 1.1.1a). Macro- means “large,” thus, gross anatomy is also referred to as macroscopic anatomy. In contrast, micro- means “small,” and microscopic anatomy is the study of structures that can be observed only with the use of a microscope or other magnification devices (Figure 1.1.1b). Microscopic anatomy includes cytology, the study of cells and histology, the study of tissues. As the technology of microscopes has advanced, anatomists have been able to observe smaller and smaller structures of the body, from slices of large structures like the heart, to the three-dimensional structures of large molecules in the body.

 

microscopic anatomy
Figure 1.1.1 Gross and microscopic anatomy. (a) Gross anatomy considers large structures such as the brain. (b) Microscopic anatomy can deal with the same structures, though at a different scale. This is a micrograph of nerve cells from the brain. (Credit a: “WriterHound”/Wikimedia Commons; credit b: Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Anatomists take two general approaches to the study of the body’s structures: regional and systemic. Regional anatomy is the study of the interrelationships of all the structures in a specific body region, such as the abdomen. Studying regional anatomy helps us appreciate the interrelationships of body structures, such as how muscles, nerves, blood vessels, and other structures work together to serve a particular body region. In contrast, systemic anatomy is the study of the structures that make up a discrete body system—that is, a group of structures that work together to perform a unique body function, for example, a systemic anatomical study of the muscular system would consider all the skeletal muscles of the body.

Whereas anatomy is about structure, physiology is about function. Human physiology is the scientific study of the chemistry and physics of the structures of the body and the ways in which they work together to support the functions of life. Much of the study of physiology centres on the body’s tendency toward homeostasis. Homeostasis is the state of steady internal conditions maintained by living things. The study of physiology certainly includes observation, both with the naked eye and with microscopes, as well as manipulations and measurements. However, current advances in physiology usually depend on carefully designed laboratory experiments that reveal the functions of the many structures and chemical compounds that make up the human body.

Like anatomists, physiologists typically specialise in a particular branch of physiology, for example, neurophysiology is the study of the brain, spinal cord, and nerves and how they work together to perform functions as complex and diverse as vision, movement, and thinking. Physiologists may work from the organ level (exploring, for example, what different parts of the brain do) to the molecular level (such as exploring how an electrochemical signal travels along nerves).

Form is closely related to function in all living things, for example, the thin flap of your eyelid can snap down to clear away dust particles and almost instantaneously slide back up to allow you to see again. At the microscopic level, the arrangement and function of the nerves and muscles that serve the eyelid allow for its quick action and retreat. At a smaller level of analysis, the function of these nerves and muscles likewise relies on the interactions of specific molecules and ions. Even the three-dimensional structure of certain molecules is essential to their function.

Your study of anatomy and physiology will make more sense if you continually relate the form of the structures you are studying to their function. In fact, it can be somewhat frustrating to attempt to study anatomy without an understanding of the physiology that a body structure supports. Imagine, for example, trying to appreciate the unique arrangement of the bones of the human hand if you had no conception of the function of the hand. Fortunately, your understanding of how the human hand manipulates tools—from pens to cell phones—helps you appreciate the unique alignment of the thumb in opposition to the four fingers, making your hand a structure that allows you to pinch and grasp objects and type text messages.

Section Review

Human anatomy is the scientific study of the body’s structures. In the past, anatomy has primarily been studied via observing injuries, and later by the dissection of anatomical structures of cadavers, but in the past century, computer-assisted imaging techniques have allowed clinicians to look inside the living body. Human physiology is the scientific study of the chemistry and physics of the structures of the body. Physiology explains how the structures of the body work together to maintain life. It is difficult to study structure (anatomy) without knowledge of function (physiology). The two disciplines are typically studied together because form and function are closely related in all living things.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=5

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=5

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=5

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=5

1.2 Structural Organisation of the Human Body

Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure of the human body in terms of six levels of organisation
  • List the eleven organ systems of the human body and identify at least one organ and one major function of each

Before you begin to study the different structures and functions of the human body, it is helpful to consider its basic architecture; that is, how its smallest parts are assembled into larger structures. It is convenient to consider the structures of the body in terms of fundamental levels of organisation that increase in complexity: subatomic particles, atoms, molecules, organelles, cells, tissues, organs, organ systems, organisms and biosphere (Figure 1.2.1).

Levels of structure of human body
Figure 1.2.1. Levels of structural organisation of the human body. The organisation of the body often is discussed in terms of six distinct levels of increasing complexity, from the smallest chemical building blocks to a unique human organism.

The Levels of Organisation

To study the chemical level of organisation, scientists consider the simplest building blocks of matter: subatomic particles, atoms and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of which are hydrogen, oxygen, carbon, nitrogen, calcium, and iron. The smallest unit of any of these pure substances (elements) is an atom. Atoms are made up of subatomic particles such as the proton, electron and neutron. Two or more atoms combine to form a molecule, such as the water molecules, proteins, and sugars found in living things. Molecules are the chemical building blocks of all body structures.

A cell is the smallest independently functioning unit of a living organism. Even bacteria, which are extremely small, independently-living organisms, have a cellular structure. Each bacterium is a single cell. All living structures of human anatomy contain cells, and almost all functions of human physiology are performed in cells or are initiated by cells.

A human cell typically consists of flexible membranes that enclose cytoplasm, a water-based cellular fluid together with a variety of tiny functioning units called organelles. In humans, as in all organisms, cells perform all functions of life. A tissue is a group of many similar cells (though sometimes composed of a few related types) that work together to perform a specific function. An organ is an anatomically distinct structure of the body composed of two or more tissue types. Each organ performs one or more specific physiological functions. An organ system is a group of organs that work together to perform major functions or meet physiological needs of the body.

This book covers eleven distinct organ systems in the human body (Figure 1.2.2 and Figure 1.2.3). Assigning organs to organ systems can be imprecise since organs that “belong” to one system can also have functions integral to another system. In fact, most organs contribute to more than one system.

 

Organ systems in human body
Figure 1.2.2. Organ systems of the human body. Organs that work together are grouped into organ systems.

 

Organ systems of the human body
Figure 1.2.3. Organ systems of the human body (continued). Organs that work together are grouped into organ systems.

The organism level is the highest level of organisation. An organism is a living being that has a cellular structure and that can independently perform all physiologic functions necessary for life. In multicellular organisms, including humans, all cells, tissues, organs, and organ systems of the body work together to maintain the life and health of the organism.

Section Review

Life processes of the human body are maintained at several levels of structural organisation. These include the chemical, cellular, tissue, organ, organ system, and the organism level. Higher levels of organisation are built from lower levels. Therefore, molecules combine to form cells, cells combine to form tissues, tissues combine to form organs, organs combine to form organ systems and organ systems combine to form organisms.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=24

Critical Thinking Question

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=24

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=24

1.3 Homeostasis

Learning Objectives

By the end of this section, you will be able to:

  • Discuss the role of homeostasis in healthy functioning
  • Recognise negative and positive feedback, giving one physiologic example of each mechanism

Maintaining homeostasis requires that the body continuously monitor its internal conditions. From body temperature to blood pressure to levels of certain nutrients, each physiological condition has a particular set point. A set point is the physiological value around which the normal range fluctuates. A normal range is the restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F) Physiological parameters, such as body temperature and blood pressure, tend to fluctuate within a normal range a few degrees above and below that point. Control centres in the brain and other parts of the body monitor and react to deviations from homeostasis using negative feedback. Negative feedback is a mechanism that reverses a deviation from the set point. Therefore, negative feedback maintains body parameters within their normal range. The maintenance of homeostasis by negative feedback goes on throughout the body, at all times, and an understanding of negative feedback is thus fundamental to an understanding of human physiology.

Negative Feedback

A negative feedback system has three basic components (Figure 1.3.1). A sensor, also referred to a receptor, is a component of a feedback system that monitors a physiological value. This value is reported to the control centre. The control centre is the component in a feedback system that compares the value to the normal range. If the value deviates too much from the set point, then the control centre activates an effector. An effector is the component in a feedback system that causes a change to reverse the situation and return the value to the normal range.

Negative feedback loop
Figure 1.3.1. Negative feedback loop. In a negative feedback loop, a stimulus—a deviation from a set point—is resisted through a physiological process that returns the body to homeostasis. (a) A negative feedback loop has four basic parts. (b) Body temperature is regulated by negative feedback.

In order to set the system in motion, a stimulus must drive a physiological parameter beyond its normal range (that is, beyond homeostasis). This stimulus is “heard” by a specific sensor. For example, in the control of blood glucose, specific endocrine cells in the pancreas detect excess glucose (the stimulus) in the bloodstream. These pancreatic beta cells respond to the increased level of blood glucose by increased secretion of the hormone insulin into the bloodstream (ie more than the normal basal secretion). The insulin signals skeletal muscle fibres, fat cells (adipocytes), and liver cells to take up the excess glucose, removing it from the bloodstream. As glucose concentration in the bloodstream drops, the decrease in concentration—the actual negative feedback—is detected by pancreatic alpha cells, and insulin release stops. This prevents blood glucose levels from continuing to drop below the normal range.

Humans have a similar temperature regulation feedback system that works by promoting either heat loss or heat gain (Figure 1.3.1b). When the brain’s temperature regulation centre receives data from the sensors indicating that the body’s temperature exceeds its normal range, it stimulates a cluster of brain cells referred to as the “heat-loss centre.” This stimulation has three major effects:

Blood vessels in the skin begin to dilate allowing more blood from the body core to flow to the surface of the skin allowing the heat to radiate into the environment.

As blood flow to the skin increases, sweat glands are activated to increase their output. As the sweat evaporates from the skin surface into the surrounding air, it takes heat with it.

The depth of respiration increases, and a person may breathe through an open mouth instead of through the nasal passageways. This further increases heat loss from the lungs.

In contrast, activation of the brain’s heat-gain centre by exposure to cold reduces blood flow to the skin, and blood returning from the limbs is diverted into a network of deep veins. This arrangement traps heat closer to the body core and restricts heat loss. If heat loss is severe, the brain triggers an increase in random signals to skeletal muscles, causing them to contract and producing shivering. The muscle contractions of shivering release heat while using up ATP. The brain triggers the thyroid gland in the endocrine system to release thyroid hormone, which increases metabolic activity and heat production in cells throughout the body. The brain also signals the adrenal glands to release adrenaline (US: epinephrine), a hormone that causes the breakdown of glycogen into glucose, which can be used as an energy source. The breakdown of glycogen into glucose also results in increased metabolism and heat production.

Positive Feedback

Positive feedback intensifies a change in the body’s physiological condition rather than reversing it. A deviation from the normal range results in more change, and the system moves farther away from the normal range. Positive feedback in the body is normal only when there is a definite end point. Childbirth and the body’s response to blood loss are two examples of positive feedback loops that are normal but are activated only when needed.

Childbirth at full term is an example of a situation in which the maintenance of the existing body state is not desired. Enormous changes in the mother’s body are required to expel the baby at the end of pregnancy, and the events of childbirth, once begun, must progress rapidly to a conclusion or the life of the mother and the baby are at risk. The extreme muscular work of labour and delivery are the result of a positive feedback system (Figure 1.3.2).

Positive feedback loop through labour
Figure 1.3.2. Positive feedback loop. Normal childbirth is driven by a positive feedback loop. A positive feedback loop results in a change in the body’s status, rather than a return to homeostasis.

The first contractions of labour (the stimulus) push the baby toward the cervix (the lowest part of the uterus). The cervix contains stretch-sensitive nerve cells that monitor the degree of stretching (the sensors). These nerve cells send messages to the brain, which in turn causes the pituitary gland at the base of the brain to release the hormone oxytocin into the bloodstream. Oxytocin causes stronger contractions of the smooth muscles in of the uterus (the effectors), pushing the baby further down the birth canal. This causes even greater stretching of the cervix. The cycle of stretching, oxytocin release, and increasingly more forceful contractions stops only when the baby is born. At this point, the stretching of the cervix halts, stopping the release of oxytocin.

A second example of positive feedback centres on reversing extreme damage to the body. Following a penetrating wound, the most immediate threat is excessive blood loss. Less blood circulating means reduced blood pressure and reduced perfusion (penetration of blood) to the brain and other vital organs. If perfusion is severely reduced, vital organs will shut down and the person will die. The body responds to this potential catastrophe by releasing substances in the injured blood vessel wall that begin the process of blood clotting. As each step of clotting occurs, it stimulates the release of more clotting substances. This accelerates the processes of clotting and sealing off the damaged area. Clotting is contained in a local area based on the tightly controlled availability of clotting proteins. This is an adaptive, life-saving cascade of events.

Thermoregulation

Animals, such as humans, that maintain a constant body temperature in the face of differing environmental temperatures, are called endotherms. We are able to maintain this temperature by generating internal heat (a waste product of the cellular chemical reactions of metabolism) that keeps the cellular processes operating optimally even when the environment is cold.

Endotherms use their circulatory systems to help maintain body temperature. Vasodilation, the opening up of arteries to the skin by relaxation of their smooth muscles, brings more blood and heat to the body surface, facilitating radiation and evaporative heat loss, cooling the body. Vasoconstriction, the narrowing of blood vessels to the skin by contraction of their smooth muscles, reduces blood flow in peripheral blood vessels, forcing blood toward the core and vital organs, conserving heat.

Thermoregulation is coordinated by the nervous system. The processes of temperature control are centred in a region of the brain called the hypothalamus. The hypothalamus maintains the set point for body temperature through reflexes that cause vasodilation or vasoconstriction and shivering or sweating. The hypothalamus directs the responses that effect the changes in temperature loss or gain that return the body to the set point. The set point may be adjusted in some instances. During an infection, compounds called pyrogens are produced and circulate to the hypothalamus resetting the thermostat to a higher value. This allows the body’s temperature to increase to a new homeostatic equilibrium point in what is commonly called a fever. The increase in body heat makes the body less optimal for bacterial growth and increases the activities of cells so they are better able to fight the infection.

Section Review

Homeostasis is the activity of cells throughout the body to maintain the physiological state within a narrow range that is compatible with life. Homeostasis is regulated by negative feedback loops and, much less frequently, by positive feedback loops. Both have the same components of a stimulus, sensor, control centre, and effector; however, negative feedback loops work to prevent an excessive response to the stimulus, whereas positive feedback loops intensify the response until an end point is reached.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=26

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=26

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=26

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=26

1.4 Anatomical Terminology

Learning Objectives

By the end of this section, you will be able to:

  • Demonstrate the anatomical position
  • Describe the human body using directional and regional terms
  • Identify three planes most commonly used in the study of anatomy
  • Recognise the posterior (dorsal) and the anterior (ventral) body cavities, identifying their subdivisions and representative organs found in each
  • Describe serous membranes and explain the functions

Anatomists and health care providers use terminology that can be bewildering to the uninitiated. However, the purpose of this language is not to confuse, but rather to increase precision and reduce medical errors. For example, is a scar “above the wrist” located on the forearm two or three inches away from the hand? Or is it at the base of the hand? Is it on the palm-side or back-side? By using precise anatomical terminology, we eliminate ambiguity. Anatomical terms derive from ancient Greek and Latin words. Because these languages are no longer used in everyday conversation, the meaning of their words does not change.

Anatomical terms are made up of roots, prefixes, and suffixes. The root of a term often refers to an organ, tissue, or condition, whereas the prefix or suffix often describes the root. For example, in the disorder hypertension, the prefix “hyper-” means “high” or “over,” and the root word “tension” refers to pressure, so the word “hypertension” refers to abnormally high blood pressure.

Anatomical Position

To further increase precision, anatomists standardise the way in which they view the body. Just as maps are normally oriented with north at the top, the standard body “map,” or anatomical position, is that of the body standing upright, with the feet at shoulder width and parallel, toes forward. The upper limbs are held out to each side, and the palms of the hands face forward as illustrated in Figure 1.4.1. Using this standard position reduces confusion. It does not matter how the body being described is oriented, the terms are used as if it is in anatomical position. For example, a scar in the “anterior (front) carpal (wrist) region” would be present on the palm side of the wrist. The term “anterior” would be used even if the hand were palm down on a table.

 

Regions of human body
Figure 1.4.1. Regions of the human body. The human body is shown in anatomical position in an (a) anterior view and a (b) posterior view. The regions of the body are labelled in boldface.

A body that is lying down is described as either prone or supine. Prone describes a face-down orientation and supine describes a face up orientation. These terms are sometimes used in describing the position of the body during specific physical examinations or surgical procedures.

Regional Terms

The human body’s numerous regions have specific terms to help increase precision (see Figure 1.4.1). Notice that the term “brachium” or “arm” is reserved for the “upper arm” and “antebrachium” or “forearm” is used rather than “lower arm.” Similarly, “femur” or “thigh” is correct, and “leg” or “crus” is reserved for the portion of the lower limb between the knee and the ankle. You will be able to describe the body’s regions using the terms from the figure.

Directional Terms

Certain directional anatomical terms appear throughout this and any other anatomy textbook (Figure 1.4.2). These terms are essential for describing the relative locations of different body structures. For instance, an anatomist might describe one band of tissue as “inferior to” another or a physician might describe a tumour as “superficial to” a deeper body structure. Commit these terms to memory to avoid confusion when you are studying or describing the locations of particular body parts.

Anterior (or ventral) Describes the front or direction toward the front of the body. The toes are anterior to the foot.

Posterior (or dorsal) Describes the back or direction toward the back of the body. The popliteus is posterior to the patella.

Superior (or cranial) describes a position above or higher than another part of the body proper. The orbits are superior to the oris.

Inferior (or caudal) describes a position below or lower than another part of the body proper; near or toward the tail (in humans, the coccyx, or lowest part of the spinal column). The pelvis is inferior to the abdomen.

Lateral describes the side or direction toward the side of the body. The thumb (pollex) is lateral to the digits.

Medial describes the middle or direction toward the middle of the body. The hallux is the medial toe.

Proximal describes a position in a limb that is nearer to the point of attachment or the trunk of the body. The brachium is proximal to the antebrachium.

Distal describes a position in a limb that is farther from the point of attachment or the trunk of the body. The crus is distal to the femur.

Superficial describes a position closer to the surface of the body. The skin is superficial to the bones.

Deep describes a position farther from the surface of the body. The brain is deep to the skull.

Directional terms applied to human body
Figure 1.4.2. Directional terms applied to the human body. Paired directional terms are shown as applied to the human body.

Body Planes

A section is a two-dimensional surface of a three-dimensional structure that has been cut. Modern medical imaging devices enable clinicians to obtain “virtual sections” of living bodies. We call these scans. Body sections and scans can be correctly interpreted, however, only if the viewer understands the plane along which the section was made. A plane is an imaginary two-dimensional surface that passes through the body. There are three planes commonly referred to in anatomy and medicine, as illustrated in Figure 1.4.3.

The sagittal plane is the plane that divides the body or an organ vertically into right and left sides. If this vertical plane runs directly down the middle of the body, it is called the midsagittal or median plane. If it divides the body into unequal right and left sides, it is called a parasagittal plane or less commonly a longitudinal section.

The frontal plane is the plane that divides the body or an organ into an anterior (front) portion and a posterior (rear) portion. The frontal plane is often referred to as a coronal plane. (“Corona” is Latin for “crown.”)

The transverse plane is the plane that divides the body or organ horizontally into upper and lower portions. Transverse planes produce images referred to as cross sections.

Planes of the body
Figure 1.4.3. Planes of the body. The three planes most commonly used in anatomical and medical imaging are the sagittal, frontal (or coronal), and transverse plane.

Body Cavities and Serous Membranes

The body maintains its internal organisation by means of membranes, sheaths, and other structures that separate compartments. The dorsal (posterior) cavity and the ventral (anterior) cavity are the largest body compartments (Figure 1.4.4). These cavities contain and protect delicate internal organs, and the ventral cavity allows for significant changes in the size and shape of the organs as they perform their functions. The lungs, heart, stomach, and intestines, for example, can expand and contract without distorting other tissues or disrupting the activity of nearby organs.

Diagram of body cavities
Figure 1.4.4. Dorsal and ventral body cavities. The ventral cavity includes the thoracic and abdominopelvic cavities and their subdivisions. The dorsal cavity includes the cranial and spinal cavities.

Subdivisions of the Posterior (Dorsal) and Anterior (Ventral) Cavities

The posterior (dorsal) and anterior (ventral) cavities are each subdivided into smaller cavities. In the posterior (dorsal) cavity, the cranial cavity houses the brain, and the spinal cavity (or vertebral cavity) encloses the spinal cord. Just as the brain and spinal cord make up a continuous, uninterrupted structure, the cranial and spinal cavities that house them are also continuous. The brain and spinal cord are protected by the bones of the skull and vertebral column and by cerebrospinal fluid, a colourless fluid produced by the brain, which cushions the brain and spinal cord within the posterior (dorsal) cavity.

The anterior (ventral) cavity has two main subdivisions: the thoracic cavity and the abdominopelvic cavity (see Figure 1.4.4). The thoracic cavity is the more superior subdivision of the anterior cavity, and it is enclosed by the rib cage. The thoracic cavity contains the lungs and the heart, which is located in the mediastinum. The diaphragm forms the floor of the thoracic cavity and separates it from the more inferior abdominopelvic cavity. The abdominopelvic cavity is the largest cavity in the body. Although no membrane physically divides the abdominopelvic cavity, it can be useful to distinguish between the abdominal cavity, the division that houses the digestive organs, and the pelvic cavity, the division that houses the organs of reproduction.

Abdominal Regions and Quadrants

To promote clear communication, for instance about the location of a patient’s abdominal pain or a suspicious mass, health care providers typically divide up the cavity into either nine regions or four quadrants (Figure 1.4.5).

Regions and quadrants of the peritoneal cavity
Figure 1.4.5. Regions and quadrants of the peritoneal cavity. There are (a) nine abdominal regions and (b) four abdominal quadrants in the peritoneal cavity.

The more detailed regional approach subdivides the cavity with one horizontal line immediately inferior to the ribs and one immediately superior to the pelvis, and two vertical lines drawn as if dropped from the midpoint of each clavicle (collarbone). There are nine resulting regions. The simpler quadrants approach, which is more commonly used in medicine, subdivides the cavity with one horizontal and one vertical line that intersect at the patient’s umbilicus (navel).

Membranes of the Anterior (Ventral) Body Cavity

serous membrane (also referred to a serosa) is one of the thin membranes that cover the walls and organs in the thoracic and abdominopelvic cavities. The parietal layers of the membranes line the walls of the body cavity (pariet- refers to a cavity wall). The visceral layer of the membrane covers the organs (the viscera). Between the parietal and visceral layers is a very thin, fluid-filled serous space, or cavity (Figure 1.4.6).

Serous membrane
Figure 1.4.6. Serous membrane. Serous membrane lines the pericardial cavity and reflects back to cover the heart—much the same way that an underinflated balloon would form two layers surrounding a fist.

There are three serous cavities and their associated membranes. The pleura is the serous membrane that surrounds the lungs in the pleural cavity; the pericardium is the serous membrane that surrounds the heart in the pericardial cavity; and the peritoneum is the serous membrane that surrounds several organs in the abdominopelvic cavity. The serous membranes form fluid-filled sacs, or cavities, that are meant to cushion and reduce friction on internal organs when they move, such as when the lungs inflate or the heart beats. Both the parietal and visceral serosa secrete the thin, slippery serous fluid located within the serous cavities. The pleural cavity reduces friction between the lungs and the body wall. Likewise, the pericardial cavity reduces friction between the heart and the wall of the pericardium. The peritoneal cavity reduces friction between the abdominal and pelvic organs and the body wall. Therefore, serous membranes provide additional protection to the viscera they enclose by reducing friction that could lead to inflammation of the organs.

Section Review

Ancient Greek and Latin words are used to build anatomical terms. A standard reference position for mapping the body’s structures is the normal anatomical position. Regions of the body are identified using terms such as “occipital” that are more precise than common words and phrases such as “the back of the head.” Directional terms such as anterior and posterior are essential for accurately describing the relative locations of body structures. Images of the body’s interior commonly align along one of three planes: the sagittal, frontal, or transverse. The body’s organs are organised in one of two main cavities—dorsal (also referred to posterior) and ventral (also referred to anterior)—which are further sub-divided according to the structures present in each area. The serous membranes have two layers—parietal and visceral—surrounding a fluid filled space. Serous membranes cover the lungs (pleural serosa), heart (pericardial serosa), and some abdominopelvic organs (peritoneal serosa).

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=28

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=28

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=28

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=28

II

Cells and Reproduction

2.1 Synthesis of Biological Macromolecules

Learning Objectives

By the end of this section, you will be able to:

  • Describe macromolecule synthesis
  • Explain dehydration (or condensation) and hydrolysis reactions

As you have learned, biological macromolecules are large molecules, necessary for life, that are built from smaller organic molecules. There are four major biological macromolecule classes (carbohydrates, lipids, proteins, and nucleic acids). Each is an important cell component and performs a wide array of functions. Combined, these molecules make up most of the cell’s dry mass (recall that water makes up most of its complete mass). Biological macromolecules are organic, meaning they contain carbon. In addition, they may contain hydrogen, oxygen, nitrogen, and additional minor elements.

Dehydration Synthesis

Most macromolecules are made from single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers. In doing so, monomers release water molecules as by-products. This type of reaction is dehydration synthesis, which means “to put together while losing water.”

dehydration synthesis reaction
Figure 2.1.1. Dehydration synthesis. In the dehydration synthesis reaction above, two glucose molecules link to form the disaccharide maltose. In the process, it forms a water molecule.

In a dehydration synthesis reaction (Figure 2.1.1), the hydrogen of one monomer combines with the hydroxyl group of another monomer, releasing a water molecule. At the same time, the monomers share electrons and form covalent bonds. As additional monomers join, this chain of repeating monomers forms a polymer. Different monomer types can combine in many configurations, giving rise to a diverse group of macromolecules. Even one kind of monomer can combine in a variety of ways to form several different polymers. For example, glucose monomers are the constituents of starch, glycogen, and cellulose.

Hydrolysis

Polymers break down into monomers during hydrolysis. A chemical reaction occurs when inserting a water molecule across the bond. Breaking a covalent bond with this water molecule in the compound achieves this (Figure 2.1.2). During these reactions, the polymer breaks into two components: one part gains a hydrogen atom (H+) and the other gains a hydroxyl molecule (OH–) from a split water molecule.

hydrolysis reaction
Figure 2.1.2Hydrolysis reaction. In the hydrolysis reaction here, the disaccharide maltose breaks down to form two glucose monomers by adding a water molecule. Note that this reaction is the reverse of the synthesis reaction in Figure 2.1.1.

Dehydration and hydrolysis reactions are catalysed, or “sped up,” by specific enzymes; dehydration reactions involve the formation of new bonds, requiring energy, while hydrolysis reactions break bonds and release energy. These reactions are similar for most macromolecules, but each monomer and polymer reaction is specific for its class, for example, catalytic enzymes in the digestive system hydrolyse or break down the food we ingest into smaller molecules. This allows cells in our body to easily absorb nutrients in the intestine. A specific enzyme breaks down each macromolecule. For instance, amylase, sucrase, lactase, or maltase break down carbohydrates. Enzymes called proteases, such as pepsin and peptidase, and hydrochloric acid break down proteins. Lipases break down lipids. These broken-down macromolecules provide energy for cellular activities.

Section Review

Carbohydrates, lipids, proteins and nucleic acids are the four major classes of biological macromolecules—large molecules necessary for life that are built from smaller organic molecules. Macromolecules are comprised of single units scientists call monomers that are joined by covalent bonds to form larger polymers. The polymer is more than the sum of its parts: it acquires new characteristics and leads to an osmotic pressure that is much lower than that formed by its ingredients. This is an important advantage in maintaining cellular osmotic conditions. A monomer joins with another monomer with water molecule release, leading to a covalent bond forming. Scientists call these dehydration or condensation reactions. When polymers break down into smaller units (monomers), they use a water molecule for each bond broken by these reactions. Such reactions are hydrolysis reactions. Dehydration and hydrolysis reactions are similar for all macromolecules, but each monomer and polymer reaction is specific to its class. Dehydration reactions typically require an investment of energy for new bond formation, while hydrolysis reactions typically release energy by breaking bonds.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=103

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=103

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=103

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=103

Note: Content and images from this chapter have been adapted from Biology 2nd edition by Mary Ann Clark, Jung Choi and Matthew Douglas, used under a CC-BY license.

2.2 Carbohydrates

Learning Objectives

By the end of this section, you will be able to:

  • Discuss the role of carbohydrates in cells and in the extracellular materials of animals and plants
  • Explain carbohydrate classifications
  • List common monosaccharides, disaccharides and polysaccharides

Most people are familiar with carbohydrates, one type of macromolecule, especially when it comes to what we eat. To lose weight, some individuals adhere to “low-carb” diets. Athletes, in contrast, often “carb-load” before important competitions to ensure that they have enough energy to compete at a high level. Carbohydrates are, in fact, an essential part of our diet. Grains, fruits, and vegetables are all-natural carbohydrate sources that provide energy to the body, particularly through glucose, a simple sugar that is a component of starch and an ingredient in many staple foods. Carbohydrates also have other important functions in humans, animals, and plants.

Molecular Structures

The stoichiometric formula (CH2O)n, where n is the number of carbons in the molecule represents carbohydrates. In other words, the ratio of carbon to hydrogen to oxygen is 1:2:1 in carbohydrate molecules. This formula also explains the origin of the term “carbohydrate”: the components are carbon (“carbo”) and the components of water (hence, “hydrate”). Scientists classify carbohydrates into three subtypes: monosaccharides, disaccharides and polysaccharides.

Monosaccharides

Monosaccharides (mono- = “one”; sacchar- = “sweet”) are simple sugars, the most common of which is glucose. In monosaccharides, the number of carbons usually ranges from three to seven. Most monosaccharide names end with the suffix-ose. If the sugar has an aldehyde group (the functional group with the structure R-CHO), it is an aldose, and if it has a ketone group (the functional group with the structure RC(=O)R’), it is a ketose. Depending on the number of carbons in the sugar, they can be trioses (three carbons), pentoses (five carbons), and/or hexoses (six carbons). Figure 2.2.1 illustrates monosaccharides.

 

Classifications of monosaccharides
Figure 2.2.1. Classifications of monosaccharides. Scientists classify monosaccharides based on the position of their carbonyl group and the number of carbons in the backbone. Aldoses have a carbonyl group (indicated in green) at the end of the carbon chain, and ketoses have a carbonyl group in the middle of the carbon chain. Trioses, pentoses, and hexoses have three-, five-, and six- carbon backbones, respectively.

The chemical formula for glucose is C6H12O6. In humans, glucose is an important source of energy. During cellular respiration, energy releases from glucose, and that energy helps make adenosine triphosphate (ATP). Plants synthesise glucose using carbon dioxide and water, and glucose in turn provides energy requirements for the plant. Humans and other animals that feed on plants often store excess glucose as catabolised (cell breakdown of larger molecules) starch.

Galactose (part of lactose, or milk sugar) and fructose (found in sucrose, in fruit) are other common monosaccharides. Although glucose, galactose, and fructose all have the same chemical formula (C6H12O6), they differ structurally and chemically (and are isomers) because of the different arrangement of functional groups around the asymmetric carbon. All these monosaccharides have more than one asymmetric carbon (Figure 2.2.2).

Glucose isomers. Glucose, galactose, and fructose
Figure 2.2.2. Glucose isomers. Glucose, galactose, and fructose are all hexoses. They are structural isomers, meaning they have the same chemical formula (C6H12O6) but a different atom arrangement.

What kind of sugars are these, aldose or ketose?

Glucose, galactose, and fructose are isomeric monosaccharides (hexoses), meaning they have the same chemical formula but have slightly different structures. Glucose and galactose are aldoses, and fructose is a ketose.

Monosaccharides can exist as a linear chain or as ring-shaped molecules. In aqueous solutions they are usually in ring forms (Figure 2.2.3). Glucose in a ring form can have two different hydroxyl group arrangements (OH) around the anomeric carbon (carbon 1 that becomes asymmetric in the ring formation process). If the hydroxyl group is below carbon number 1 in the sugar, it is in the alpha (α) position, and if it is above the plane, it is in the beta (β) position.

Conversion between linear and ring forms of glucose
Figure 2.2.3. Ring forms of glucose. Five and six carbon monosaccharides exist in equilibrium between linear and ring forms. When the ring forms, the side chain it closes on locks into an α or β position. Fructose and ribose also form rings, although they form five-membered rings as opposed to the six-membered ring of glucose.

Disaccharides

Disaccharides (di- = “two”) form when two monosaccharides undergo a dehydration reaction (or a condensation reaction or dehydration synthesis). During this process, one monosaccharide’s hydroxyl group combines with another monosaccharide’s hydrogen, releasing a water molecule and forming a covalent bond. A covalent bond forms between a carbohydrate molecule and another molecule (in this case, between two monosaccharides). Scientists call this a glycosidic bond (Figure 2.2.4). Glycosidic bonds (or glycosidic linkages) can be an alpha or beta type. An alpha bond is formed when the OH group on the carbon-1 of the first glucose is below the ring plane, and a beta bond is formed when the OH group on the carbon-1 is above the ring plane.

Figure 2.2.4. Sucrose. Sucrose forms when a glucose monomer and a fructose monomer join in a dehydration reaction to form a glycosidic bond. In the process, a water molecule is lost. By convention, the carbon atoms in a monosaccharide are numbered from the terminal carbon closest to the carbonyl group. In sucrose, a glycosidic linkage forms between carbon 1 in glucose and carbon 2 in fructose.
Figure 2.2.4. Sucrose. Sucrose forms when a glucose monomer and a fructose monomer join in a dehydration reaction to form a glycosidic bond. In the process, a water molecule is lost. By convention, the carbon atoms in a monosaccharide are numbered from the terminal carbon closest to the carbonyl group. In sucrose, a glycosidic linkage forms between carbon 1 in glucose and carbon 2 in fructose.

Common disaccharides include lactose, maltose, and sucrose (Figure 2.2.5). Lactose is a disaccharide consisting of the monomers; glucose and galactose. It is naturally in milk. Maltose, or malt sugar, is a disaccharide formed by a dehydration reaction between two glucose molecules. The most common disaccharide is sucrose, or table sugar, which is comprised of glucose and fructose monomers.

 

Figure 2.2.5. Common disaccharides. Common disaccharides include maltose (grain sugar), lactose (milk sugar) and sucrose (table sugar).
Figure 2.2.5. Common disaccharides. Common disaccharides include maltose (grain sugar), lactose (milk sugar) and sucrose (table sugar).

Polysaccharides

A long chain of monosaccharides linked by glycosidic bonds is a polysaccharide (poly- = “many”). The chain may be branched or unbranched, and it may contain different types of monosaccharides. The molecular weight (MW) may be 100,000 Daltons or more depending on the number of joined monomers. Starch, glycogen, cellulose and chitin are primary examples of polysaccharides.

Plants store sugars in the form of starch. In plants, an amylose and amylopectin mixture (both glucose polymers) comprise these sugars. Plants can synthesise glucose, and they store the excess glucose, beyond their immediate energy needs, as starch in different plant parts, including roots and seeds. The starch in the seeds provides food for the embryo as it germinates and can also act as a food source for humans and animals. Enzymes break down the starch that humans consume, for example, an amylase present in saliva catalyses, or breaks down this starch into smaller molecules, such as maltose and glucose. The cells can then absorb the glucose.

Glucose starch comprises monomers that are joined by α 1-4 or α 1-6 glycosidic bonds. The numbers 1-4 and 1-6 refer to the carbon number of the two residues that have joined to form the bond. As Figure 2.2.6 illustrates, unbranched glucose monomer chains (only α 1-4 linkages) form the starch; whereas, amylopectin is a branched polysaccharide (α 1-6 linkages at the branch points).

Starch forms
Figure 2.2.6. Starch forms. Amylose and amylopectin are two different starch forms. Unbranched glucose monomer chains comprise amylose by α 1-4 glycosidic linkages. Unbranched glucose monomer chains comprise amylopectin by α 1-4 and α 1-6 glycosidic linkages. Because of the way the subunits are joined, the glucose chains have a helical structure. Glycogen (not shown) is similar in structure to amylopectin but more highly branched.

Glycogen is the storage form of glucose in humans and other vertebrates and is comprised of monomers of glucose. Glycogen is the animal equivalent of starch and is a highly branched molecule usually stored in liver and muscle cells. Whenever blood glucose levels decrease, glycogen breaks down to release glucose in a process scientists call glycogenolysis.

Cellulose is the most abundant natural biopolymer. Cellulose mostly comprises a plant’s cell wall. This provides the cell structural support. Wood and paper are mostly cellulosic in nature. Glucose monomers comprise cellulose that β 1-4 glycosidic bonds link (Figure 2.2.7).

Figure 2.2.7. Figure 2.2.7. A) Scanning electron microscopy of single cellulose fibres (i) hemp, (ii) ramie, (iii) viscose, (iv) Tencel and their carbonised counterparts (v-viii) together with a low-magnification image of carbonised natural hemp fibres (ix) and Tencel regenerated cellulose fibres (x). Arrowheads in (ix) indicate cracks across the diameter of carbonised fibres leading to easy fragmentation as shown in the inset (note that a pair of fibres is shown in vi) (https://link.springer.com/article/10.1007/s10853-020-04743-y); B) Cellulose structure in cellulose, glucose monomers are linked in unbranched chains by β 1-4 glycosidic linkages. Because of the way the glucose subunits are joined, every glucose monomer is flipped relative to the next one resulting in a linear, fibrous structure.
Figure 2.2.7.  Figure 2.2.7. A) Scanning electron microscopy of single cellulose fibres (i) hemp, (ii) ramie, (iii) viscose, (iv) Tencel and their carbonised counterparts (v-viii) together with a low-magnification image of carbonised natural hemp fibres (ix) and Tencel regenerated cellulose fibres (x). Arrowheads in (ix) indicate cracks across the diameter of carbonised fibres leading to easy fragmentation as shown in the inset (note that a pair of fibres is shown in vi) (https://link.springer.com/article/10.1007/s10853-020-04743-y used under CC-BY licence); B) Cellulose structure in cellulose, glucose monomers are linked in unbranched chains by β 1-4 glycosidic linkages. Because of the way the glucose subunits are joined, every glucose monomer is flipped relative to the next one resulting in a linear, fibrous structure.

As Figure 2.2.7 shows, every other glucose monomer in cellulose is flipped over, and the monomers are packed tightly as extended long chains. This gives cellulose its rigidity and high tensile strength—which is so important to plant cells. While human digestive enzymes cannot break down the β 1-4 linkage, herbivores such as cows, koalas, and buffalos are able, with the help of the specialised microorganisms in their stomach, to digest plant material that is rich in cellulose and use it as a food source. In some of these animals, certain species of bacteria and protists reside in the rumen (part of the herbivore’s digestive system) and secrete the enzyme cellulase. The appendix of grazing animals also contains bacteria that digest cellulose, giving it an important role in ruminants’ digestive systems. Cellulases can break down cellulose into glucose monomers that animals use as an energy source. Termites are also able to break down cellulose because of the presence of other organisms in their bodies that secrete cellulases.

Bee on flower
Figure 2.2.8. Bee exoskeleton. Insects have a hard-outer exoskeleton made of chitin, a type of polysaccharide. (credit: Louise Docker).

Carbohydrates serve various functions in different animals. Arthropods (insects, crustaceans, and others) have an outer skeleton, the exoskeleton, which protects their internal body parts (as we see in the bee in Figure 2.2.8). This exoskeleton is made of the biological macromolecule chitin, which is a nitrogen-containing polysaccharide. It is made of repeating N-acetyl-β-d-glucosamine units, which are a modified sugar. Chitin is also a major component of fungal cell walls. Fungi are neither animals nor plants and form a kingdom of their own in the domain Eukarya.

Benefits of Carbohydrates

Are carbohydrates good for you? Some people believe that carbohydrates are bad and they should avoid them. Some diets completely forbid carbohydrate consumption, claiming that a low-carbohydrate diet helps people to lose weight faster. However, carbohydrates have been an important part of the human diet for thousands of years. Artifacts from ancient civilizations show the presence of wheat, rice, and corn in our ancestors’ storage areas.

As part of a well-balanced diet, we should supplement carbohydrates with proteins, vitamins, and fats. Calorie-wise, a gram of carbohydrate provides 4.3 Kcal. For comparison, fats provide 9 Kcal/g, a less desirable ratio. Carbohydrates contain soluble and insoluble elements. The insoluble part, fibre, is mostly cellulose. Fibre has many uses. It promotes regular bowel movement by adding bulk, and it regulates the blood glucose consumption rate. Fibre also helps to remove excess cholesterol from the body. Fibre binds to the cholesterol in the small intestine, then attaches to the cholesterol and prevents the cholesterol particles from entering the bloodstream. Cholesterol then exits the body via the faeces. Fibre-rich diets also have a protective role in reducing the occurrence of colon cancer. In addition, a meal containing whole grains and vegetables gives a feeling of fullness. As an immediate source of energy, glucose breaks down during the cellular respiration process, which produces ATP, the cell’s energy currency. Without consuming carbohydrates, we reduce the availability of “instant energy”. Eliminating carbohydrates from the diet may be necessary for some people, but such a step may not be healthy for everyone.

Career Connections: Registered Dietitian

Obesity is a worldwide health concern, and many diseases such as diabetes and heart disease are becoming more prevalent because of obesity. This is one of the reasons why people increasingly seek out registered dietitians for advice. Registered dietitians help plan nutrition programs for individuals in various settings. They often work with patients in health care facilities, designing nutrition plans to treat and prevent diseases. For example, dietitians may teach a patient with diabetes how to manage blood sugar levels by eating the correct types and amounts of carbohydrates. Dietitians may also work in nursing homes, schools, and private practices.

To become a registered dietitian, one needs to earn at least a bachelor’s degree in dietetics, nutrition, food technology, or a related field. In addition, registered dietitians must complete a supervised internship program and pass a national exam. Those who pursue careers in dietetics take courses in nutrition, chemistry, biochemistry, biology, microbiology, and human physiology. Dietitians must become experts in the chemistry and physiology (biological functions) of food (proteins, carbohydrates, and fats).

Biomedical Scientist

A biomedical scientist has at least a bachelor’s degree in biomedical science or science with a major in biomedical science. The majority of biomedical scientists also have an Honours degree (popular in countries such as Australia, Singapore, India and the United Kingdom) or a Masters degree (United States, Canada, Americas, Europe, parts of Asia and Africa), with PhDs also common. Biomedical scientists work in university, research institutes and commercial laboratories undertaking basic through to translational research projects aimed at improving our understanding of the human body in health and disease and investigating better ways to prevent, treat and diagnose diseases. Funding may be public in the form of government grants or commercial investment from the pharmaceutical and biotechnology industries.

Section Review

Carbohydrates are a group of macromolecules that are a vital energy source for the cell and provide structural support to plant cells, fungi, and all of the arthropods that include lobsters, crabs, shrimp, insects, and spiders. Scientists classify carbohydrates as monosaccharides, disaccharides, and polysaccharides depending on the number of monomers in the molecule. Monosaccharides are linked by glycosidic bonds that form as a result of dehydration reactions, forming disaccharides and polysaccharides with eliminating a water molecule for each bond formed. Glucose, galactose, and fructose are common monosaccharides; whereas, common disaccharides include lactose, maltose, and sucrose. Starch and glycogen, examples of polysaccharides, are the storage forms of glucose in plants and animals, respectively. The long polysaccharide chains may be branched or unbranched. Cellulose is an example of an unbranched polysaccharide; whereas, amylopectin, a constituent of starch, is a highly branched molecule. Glucose storage, in the form of polymers like starch of glycogen, makes it slightly less accessible for metabolism; however, this prevents it from leaking out of the cell or creating a high osmotic pressure that could cause the cell to uptake excessive water.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=105

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=105

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=105

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=105

Note: Content and images from this chapter have been adapted from Biology 2nd edition by Mary Ann Clark, Jung Choi and Matthew Douglas, used under a CC-BY license.

 

2.3 Lipids

Learning Objectives

By the end of this section, you will be able to:

  • Describe the four major types of lipids
  • Explain the role of fats in storing energy
  • Differentiate between saturated and unsaturated fatty acids
  • Describe phospholipids and their role in cells
  • Define the basic structure of a steroid and some steroid functions
  • Explain how cholesterol helps maintain the plasma membrane’s fluid nature
Otto in water
Figure 2.3.1. Otter fur. Hydrophobic lipids in aquatic mammals’ fur, such as this river otter, protect them from the elements. (credit: Ken Bosma).

Lipids include a diverse group of compounds that are largely nonpolar in nature. This is because they are hydrocarbons that include mostly nonpolar carbon–carbon or carbon–hydrogen bonds. Non-polar molecules are hydrophobic (“water fearing”), or insoluble in water. Lipids perform many different functions in a cell. Cells store energy for long-term use in the form of fats. Lipids also provide insulation from the environment for plants and animals (Figure 2.3.1). For example, they help keep aquatic birds and mammals dry when forming a protective layer over fur or feathers because of their water-repellent hydrophobic nature. Lipids are also the building blocks of many hormones and are an important constituent of all cellular membranes. Lipids include fats and oils, waxes, phospholipids and steroids.

Fats and Oils

A fat molecule consists of two main components—glycerol and fatty acids. Glycerol is an organic compound (alcohol) with three carbons, five hydrogens, and three hydroxyl (OH) groups. Fatty acids have a long chain of hydrocarbons to which a carboxyl group is attached, hence the name “fatty acid.” The number of carbons in the fatty acid may range from 4 to 36. The most common are those containing 12–18 carbons. In a fat molecule, the fatty acids attach to each of the glycerol molecule’s three carbons with an ester bond through an oxygen atom (Figure 2.3.2).

Fatty acid dehydration reaction
Figure 2.3.2. Fatty acid dehydration reaction. Joining three fatty acids to a glycerol backbone in a dehydration reaction forms triacylglycerol. Three water molecules release in the process.

During this ester bond formation, three water molecules are released. The three fatty acids in the triacylglycerol may be similar or dissimilar. We also call fats triacylglycerols (TAGs) or triglycerides (TGs) because of their chemical structure. Some fatty acids have common names that specify their origin, for example, palmitic acid, a saturated fatty acid, is derived from the palm tree. Arachidic acid (also known as eicosanoic acid) is derived from Arachis hypogea, the scientific name for groundnuts or peanuts.

Fatty acids may be saturated or unsaturated. In a fatty acid chain, if there are only single bonds between neighbouring carbons in the hydrocarbon chain, the fatty acid is saturated. Saturated fatty acids are saturated with hydrogen. In other words, the number of hydrogen atoms attached to the carbon skeleton is maximised. Stearic acid is an example of a saturated fatty acid (Figure 2.3.3).

Stearic acid
Figure 2.3.3. Stearic acid. Stearic acid is a common saturated fatty acid.

When the hydrocarbon chain contains a double bond, the fatty acid is unsaturated. Oleic acid is an example of an unsaturated fatty acid (Figure 2.3.4).

Oleic acid
Figure 2.3.4. Oleic acid. Oleic acid is a common unsaturated fatty acid.

Most unsaturated fats are liquid at room temperature. We call these oils. If there is one double bond in the molecule, then it is a monounsaturated fat (e.g., olive oil), and if there is more than one double bond, then it is a polyunsaturated fat (e.g., canola oil).

When a fatty acid has no double bonds, it is a saturated fatty acid because it is not possible to add more hydrogen to the chain’s carbon atoms. A fat may contain similar or different fatty acids attached to glycerol. Long straight fatty acids with single bonds generally pack tightly and are solid at room temperature. Animal fats with stearic acid and palmitic acid (common in meat) and the fat with butyric acid (common in butter) are examples of saturated fats. Mammals store fats in specialised cells, or adipocytes, where fat globules occupy most of the cell’s volume. Plants store fat or oil in many seeds and use them as a source of energy during seedling development. Unsaturated fats or oils are usually of plant origin and contain cis unsaturated fatty acids. Cis and trans indicate the configuration of the molecule around the double bond. If hydrogens are present in the same plane, it is a cis fat. If the hydrogen atoms are on two different planes, it is a trans-fat. The cis double bond causes a bend or a “kink” that prevents the fatty acids from packing tightly, keeping them liquid at room temperature (Figure 2.3.5). Olive oil, corn oil, canola oil, and cod liver oil are examples of unsaturated fats. Unsaturated fats help to lower blood cholesterol levels; whereas, saturated fats contribute to plaque formation in the arteries.

Saturated fatty acids
Figure 2.3.5. Saturated fatty acids. Saturated fatty acids have hydrocarbon chains connected by single bonds only. Unsaturated fatty acids have one or more double bonds. Each double bond may be in a cis or trans configuration. In the cis configuration, both hydrogens are on the same side of the hydrocarbon chain. In the trans configuration, the hydrogens are on opposite sides. A cis double bond causes a kink in the chain.

Trans Fats

The food industry artificially hydrogenates oils to make them semi-solid and of a consistency desirable for many processed food products. Simply speaking, hydrogen gas is bubbled through oils to solidify them. During this hydrogenation process, double bonds of the cis– conformation in the hydrocarbon chain may convert to double bonds in the trans– conformation.

Margarine, some types of peanut butter, and shortening are examples of artificially hydrogenated trans fats. Recent studies have shown that an increase in trans fats in the human diet may lead to higher levels of low-density lipoproteins (LDL), or “bad” cholesterol, which in turn may lead to plaque deposition in the arteries, resulting in heart disease. Many fast-food restaurants have recently banned using trans fats, and food labels are required to display the trans-fat content.

Omega Fatty Acids

Essential fatty acids are those that the human body requires but does not synthesise. Consequently, they must be supplemented through ingestion via the diet. Omega-3 fatty acids (like those in Figure 2.3.6) fall into this category and are one of only two known for humans (the other is omega-6 fatty acid). These are polyunsaturated fatty acids and are omega-3 because a double bond connects the third carbon from the hydrocarbon chain’s end to its neighbouring carbon.

Fatty acid omega-3
Figure 2.3.6. Fatty acid omega-3. Alpha-linolenic acid is an example of an omega-3 fatty acid. It has three cis double bonds and, as a result, a curved shape. For clarity, the diagram does not show the carbons. Each singly bonded carbon has two hydrogens associated with it, which the diagram also does not show.

The farthest carbon away from the carboxyl group is numbered as the omega (ω) carbon, and if the double bond is between the third and fourth carbon from that end, it is an omega-3 fatty acid. Nutritionally important because the body does not make them, omega-3 fatty acids include alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), all of which are polyunsaturated. Salmon, trout, and tuna are good sources of omega-3 fatty acids. Research indicates that omega-3 fatty acids reduce the risk of sudden death from heart attacks, lower triglycerides in the blood, decrease blood pressure, and prevent thrombosis by inhibiting blood clotting. They also reduce inflammation and may help lower the risk of some cancers in animals.

Like carbohydrates, fats have received considerable bad publicity. It is true that eating an excess of fried foods and other “fatty” foods leads to weight gain. However, fats do have important functions. Many vitamins are fat soluble, and fats serve as a long-term storage form of fatty acids: a source of energy. They also provide insulation for the body. Therefore, we should consume “healthy” fats in moderate amounts on a regular basis.

Waxes

Waxy leaves
Figure 2.3.7. Waxy leaves. Lipids comprise waxy coverings on some leaves. (Credit: Roger Griffith).

Wax covers some aquatic birds’ feathers and some plants’ leaf surfaces. Because of waxes’ hydrophobic nature, they prevent water from sticking on the surface (Figure 2.3.7). Long fatty acid chains esterified to long-chain alcohols comprise waxes.

Phospholipids

Phospholipids are major plasma membrane constituents that comprise cells’ outermost layer. Like fats, they are comprised of fatty acid chains attached to a glycerol or sphingosine backbone. However, instead of three fatty acids attached as in triglycerides, there are two fatty acids forming diacylglycerol, and a modified phosphate group occupies the glycerol backbone’s third carbon (Figure 2.3.8). A phosphate group alone attached to a diacylglycerol does not qualify as a phospholipid. It is phosphatidate (diacylglycerol 3-phosphate), the precursor of phospholipids. An alcohol modifies the phosphate group. Phosphatidylcholine and phosphatidylserine are two important phospholipids that are in plasma membranes.

Diagram of Phospholipid
Figure 2.3.8. Phospholipid. A phospholipid is a molecule with two fatty acids and a modified phosphate group attached to a glycerol backbone. Adding a charged or polar chemical group may modify the phosphate.

A phospholipid is an amphipathic molecule, meaning it has a hydrophobic and a hydrophilic part. The fatty acid chains are hydrophobic and cannot interact with water; whereas, the phosphate-containing group is hydrophilic and interacts with water (Figure 2.3.9).

Phospholipid bilayer
Figure 2.3.9. Phospholipid bilayer. The phospholipid bilayer is the major component of all cellular membranes. The hydrophilic head groups of the phospholipids face the aqueous solution. The hydrophobic tails are sequestered in the middle of the bilayer.

The head is the hydrophilic part, and the tail contains the hydrophobic fatty acids. In a membrane, a bilayer of phospholipids forms the structure’s matrix, phospholipids’ fatty acid tails face inside, away from water; whereas, the phosphate group faces the outside, aqueous side (Figure 2.3.9).

Phospholipids are responsible for the plasma membrane’s dynamic nature. If a drop of phospholipids is placed in water, it spontaneously forms a structure that scientists call a micelle, where the hydrophilic phosphate heads face the outside and the fatty acids face the structure’s interior.

Steroids

Unlike the phospholipids and fats that was discussed earlier, steroids have a fused ring structure. Although they do not resemble the other lipids, scientists group them with them because they are also hydrophobic and insoluble in water. All steroids have four linked carbon rings and several of them, like cholesterol, have a short tail (Figure 2.3.10). Many steroids also have the –OH functional group, which puts them in the alcohol classification (sterols).

Steroids
Figure 2.3.10. Steroids. Four fused hydrocarbon rings comprise steroids such as cholesterol and cortisol.

Cholesterol is the most common steroid. The liver synthesises cholesterol and is the precursor to many steroid hormones such as testosterone and oestradiol, which gonads and endocrine glands secrete. It is also the precursor to Vitamin D. Cholesterol is also the precursor of bile salts, which help emulsifying fats and their subsequent absorption by cells. Although lay people often speak negatively about cholesterol, it is necessary for the body’s proper functioning. Sterols (cholesterol in animal cells, phytosterol in plants) are components of the plasma membrane of cells and are found within the phospholipid bilayer.

Section Review

Lipids are a class of macromolecules that are nonpolar and hydrophobic in nature. Major types include fats and oils, waxes, phospholipids and steroids. Fats are a stored form of energy and are also known as triacylglycerols or triglycerides. Fats are comprised of fatty acids and either glycerol or sphingosine. Fatty acids may be unsaturated or saturated, depending on the presence or absence of double bonds in the hydrocarbon chain. If only single bonds are present, they are saturated fatty acids. Unsaturated fatty acids may have one or more double bonds in the hydrocarbon chain. Phospholipids comprise the membrane’s matrix. They have a glycerol or sphingosine backbone to which two fatty acid chains and a phosphate-containing group are attached. Steroids are another class of lipids. Their basic structure has four fused carbon rings. Cholesterol is a type of steroid and is an important constituent of the plasma membrane, where it helps to maintain the membrane’s fluid nature. It is also the precursor of steroid hormones such as testosterone.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=107

Note: Content and images from this chapter have been adapted from Biology 2nd edition by Mary Ann Clark, Jung Choi and Matthew Douglas, used under a CC-BY license.

 

2.4 Protein

Learning Objectives

By the end of this section, you will be able to:

  • Describe the functions proteins perform in the cell and in tissues
  • Discuss the relationship between amino acids and proteins
  • Explain the four levels of protein organisation
  • Describe the ways in which protein shape and function are linked

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Each cell in a living system may contain thousands of proteins, each with a unique function. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.

Types and Functions of Proteins

Enzymes, which living cells produce, are catalysts in biochemical reactions (like digestion) and are usually complex or conjugated proteins. Each enzyme is specific for the substrate (a reactant that binds to an enzyme) upon which it acts. The enzyme may help in breakdown, rearrangement, or synthesis reactions. We call enzymes that break down their substrates catabolic enzymes. Those that build more complex molecules from their substrates are anabolic enzymes, and enzymes that affect the rate of reaction are catalytic enzymes. Note that all enzymes increase the reaction rate and, therefore, are organic catalysts. An example of an enzyme is salivary amylase, which hydrolyses its substrate amylose, a component of starch.

Hormones are chemical-signalling molecules, usually small proteins or steroids, secreted by endocrine cells that act to control or regulate specific physiological processes, including growth, development, metabolism, and reproduction. For example, insulin is a protein hormone that helps regulate the blood glucose level. Table 2.4.1 lists the primary types and functions of proteins.

Protein Types and Functions

Table 2.4.1. Types of proteins and their functions.

Type Examples Functions
Digestive Enzymes Amylase, lipase, pepsin, trypsin Help in food by catabolising nutrients into monomeric units
Transport Haemoglobin, albumin Carry substances in the blood or lymph throughout the body
Structural Actin, tubulin, keratin Construct different structures, like the cytoskeleton
Hormones Insulin, thyroxine Coordinate different body systems’ activity
Defences Immunoglobulins Protect the body from foreign pathogens
Contractile Actin, myosin Effect muscle contraction
Storage Legume storage proteins, egg white (albumin) Provide nourishment in early embryo development and the seeding

Proteins have different shapes and molecular weights. Some proteins are globular in shape; whereas, others are fibrous in nature, for example, haemoglobin is a globular protein, but collagen, located in our skin, is a fibrous protein. Protein shape is critical to its function, and many different types of chemical bonds maintain this shape. Changes in temperature, pH, and exposure to chemicals may lead to permanent changes in the protein’s shape, leading to loss of function, or denaturation. Different arrangements of the same 20 types of amino acids comprise all proteins. Two rare new amino acids were discovered recently (selenocystein and pirrolysine), and additional new discoveries may be added to the list.

Amino Acids

Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (-NH2), a carboxyl group (-COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group (Figure 2.4.1).

Amino acids
Figure 2.4.1. Amino acids. Amino acids have a central asymmetric carbon to which an amino group, a carboxyl group, a hydrogen atom, and a side chain (R group) are attached.

Scientists use the name “amino acid” because these acids contain both amino group and carboxyl-acid-group in their basic structure. As we mentioned, there are 20 common amino acids present in proteins. Nine of these are essential amino acids in humans because the human body cannot produce them and we obtain them from our diet. For each amino acid, the R group (or side chain) is different (Figure 2.4.2).

 

Diagram of Common amino acids
Figure 2.4.2. Common amino acids. There are 20 common amino acids commonly found in proteins, each with a different R group (variant group) that determines its chemical nature.

Which categories of amino acid would you expect to find on a soluble protein’s surface, and which would you expect to find in the interior? What distribution of amino acids would you expect to find in a protein embedded in a lipid bilayer?

The chemical nature of the side chain determines the amino acid’s nature (that is, whether it is acidic, basic, polar, or nonpolar). For example, the amino acid glycine has a hydrogen atom as the R group. Amino acids such as valine, methionine, and alanine are nonpolar or hydrophobic in nature, while amino acids such as serine, threonine, and cysteine are polar and have hydrophilic side chains. The side chains of lysine and arginine are positively charged, and therefore these amino acids are also basic amino acids. Proline has an R group that is linked to the amino group, forming a ring-like structure. Proline is an exception to the amino acid’s standard structure since its amino group is not separate from the side chain (Figure 2.4.2).

A single upper-case letter or a three-letter abbreviation represents amino acids, for example, the letter ‘V’ or the three-letter symbol ‘val’ represent the amino acid, valine. Just as some fatty acids are essential to a diet, some amino acids also are necessary. These essential amino acids in humans include isoleucine, leucine, and cysteine. Essential amino acids refer to those necessary to build proteins in the body, but not those that the body produces. Which amino acids are essential varies from organism to organism.

The sequence and the number of amino acids ultimately determine the protein’s shape, size, and function. A covalent bond, or peptide bond, attaches to each amino acid, which a dehydration reaction forms. One amino acid’s carboxyl group and the incoming amino acid’s amino group combine, releasing a water molecule. The resulting bond is the peptide bond (Figure 2.4.3).

Peptide bond
Figure 2.4.3. Peptide bond. Peptide bond formation is a dehydration synthesis reaction. The carboxyl group of one amino acid is linked to the incoming amino acid’s amino group. In the process, it releases a water molecule.

The products that such linkages form are peptides. As more amino acids join to this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end the N terminal, or the amino terminal, and the other end has a free carboxyl group, also the C or carboxyl terminal. While the terms polypeptide and protein are sometimes used interchangeably, a polypeptide is technically a polymer of amino acids, whereas the term protein is used for a polypeptide or polypeptides that have combined together, often have bound non-peptide prosthetic groups, have a distinct shape, and have a unique function. After protein synthesis (translation), most proteins are modified. These are known as post-translational modifications. They may undergo cleavage, phosphorylation, or may require adding other chemical groups. Only after these modifications is the protein completely functional.

Evolution Connection

The Evolutionary Significance of Cytochrome c

Cytochrome c is an important component of the electron transport chain, a part of cellular respiration, and it is normally located in the cellular organelle, the mitochondrion. This protein has a haem prosthetic group, and the haem’s central ion alternately reduces and oxidises during electron transfer. Because this essential protein’s role in producing cellular energy is crucial, it has changed very little over millions of years. Protein sequencing has shown that there is a considerable amount of cytochrome c amino acid sequence homology among different species. In other words, we can assess evolutionary kinship by measuring the similarities or differences among various species’ DNA or protein sequences.

Scientists have determined that human cytochrome c contains 104 amino acids. For each cytochrome c molecule from different organisms that scientists have sequenced to date, 37 of these amino acids appear in the same position in all cytochrome c samples. This indicates that there may have been a common ancestor. On comparing the human and chimpanzee protein sequences, scientists did not find a sequence difference. When researchers compared human and rhesus monkey sequences, the single difference was in one amino acid. In another comparison, human to yeast sequencing shows a difference in the 44th position.

Protein Structure

As was discussed earlier, a protein’s shape is critical to its function, for example, an enzyme can bind to a specific substrate at an active site. If this active site is altered because of local changes or changes in overall protein structure, the enzyme may be unable to bind to the substrate. To understand how the protein gets its final shape or conformation, we need to understand the four levels of protein structure: primary, secondary, tertiary, and quaternary.

Primary Structure

Amino acids’ unique sequence in a polypeptide chain is its primary structure. For example, the pancreatic hormone insulin has two polypeptide chains, A and B, and they are linked together by disulphide bonds. The N terminal amino acid of the A chain is glycine; whereas, the C terminal amino acid is asparagine (Figure 2.4.4). The amino acid sequences in the A and B chains are unique to insulin.

Bovine serum insulin amino acid sequence
Figure 2.4.4. Bovine serum insulin amino acid sequence. Bovine serum insulin is a protein hormone comprised of two peptide chains, A (21 amino acids long) and B (30 amino acids long). In each chain, three-letter abbreviations that represent the amino acids’ names in the order they are present indicate primary structure. The amino acid cysteine (cys) has a sulfhydryl (SH) group as a side chain. Two sulfhydryl groups can react in the presence of oxygen to form a disulphide (S-S) bond. Two disulphide bonds connect the A and B chains together, and a third helps the A chain fold into the correct shape. Note that all disulphide bonds are the same length, but we have drawn them different sizes for clarity.

The gene encoding the protein ultimately determines the unique sequence for every protein. A change in nucleotide sequence of the gene’s coding region may lead to adding a different amino acid to the growing polypeptide chain, causing a change in protein structure and function. In sickle cell anaemia, the haemoglobin β chain (a small portion of which we show in Figure 2.4.5) has a single amino acid substitution, causing a change in protein structure and function. Specifically, valine in the β chain substitutes the amino acid glutamic. What is most remarkable to consider is that a haemoglobin molecule is comprised of two alpha and two beta chains that each consist of about 150 amino acids. The molecule, therefore, has about 600 amino acids. The structural difference between a normal haemoglobin molecule and a sickle cell molecule—which dramatically decreases life expectancy—is a single amino acid of the 600. What is even more remarkable is that three nucleotides each encode those 600 amino acids, and a single base change (point mutation), 1 in 1800 bases causes the mutation.

Haemoglobin amino acid composition
Figure 2.4.5. Haemoglobin amino acid composition. The beta chain of haemoglobin is 147 residues in length, yet a single amino acid substitution leads to sickle cell anaemia. In normal haemoglobin, the amino acid at position seven is glutamate. In sickle cell haemoglobin, a valine replaces glutamate.

Because of this change of one amino acid in the chain, haemoglobin molecules form long fibres that distort the biconcave, or disc-shaped, red blood cells and causes them to assume a crescent or “sickle” shape, which clogs blood vessels (Figure 2.4.6). This can lead to myriad serious health problems such as breathlessness, dizziness, headaches and abdominal pain for those affected by this disease.

Blood smear
Figure 2.4.6. Blood smear. In this blood smear, visualised at 535x magnification using bright field microscopy, sickle cells are crescent shaped, while normal cells are disc-shaped. (Credit: modification of work by Ed Uthman; scale-bar data from Matt Russell).

Secondary Structure

The local folding of the polypeptide in some regions gives rise to the secondary structure of the protein. The most common are the α-helix and β-pleated sheet structures (Figure 2.4.7). Both structures are held in shape by hydrogen bonds. The hydrogen bonds form between the oxygen atom in the carbonyl group in one amino acid and another amino acid that is four amino acids farther along the chain.

Secondary protein structure
Figure 2.4.7. Secondary protein structure. The α-helix and β-pleated sheet are secondary structures of proteins that form because of hydrogen bonding between carbonyl and amino groups in the peptide backbone. Certain amino acids have a propensity to form an α-helix, while others have a propensity to form a β-pleated sheet.

Every helical turn in an alpha helix has 3.6 amino acid residues. The polypeptide’s R groups (the variant groups) protrude out from the α-helix chain. In the β-pleated sheet, hydrogen bonding between atoms on the polypeptide chain’s backbone form the “pleats”. The R groups are attached to the carbons and extend above and below the pleat’s folds. The pleated segments align parallel or antiparallel to each other, and hydrogen bonds form between the partially positive hydrogen atom in the amino group and the partially negative oxygen atom in the peptide backbone’s carbonyl group. The α-helix and β-pleated sheet structures are in most globular and fibrous proteins and they play an important structural role.

Tertiary Structure

The polypeptide’s unique three-dimensional structure is its tertiary structure (Figure 2.4.8). This structure is in part due to chemical interactions at work on the polypeptide chain. Primarily, the interactions among R groups create the protein’s complex three-dimensional tertiary structure. The nature of the R groups in the amino acids involved can counteract forming the hydrogen bonds we described for standard secondary structures. For example, R groups with like charges repel each other and those with unlike charges are attracted to each other (ionic bonds). When protein folding takes place, the nonpolar amino acids’ hydrophobic R groups lie in the protein’s interior; whereas, the hydrophilic R groups lie on the outside. Scientists also call the former interaction types hydrophobic interactions. Interaction between cysteine side chains forms disulphide linkages in the presence of oxygen, the only covalent bond that forms during protein folding.

Protein tertiary structure
Figure 2.4.8. Protein tertiary structure. A variety of chemical interactions determine the proteins’ tertiary structure. These include hydrophobic interactions, ionic bonding, hydrogen bonding, and disulphide linkages.

All these interactions, weak and strong, determine the protein’s final three-dimensional shape. When a protein loses its three-dimensional shape, it may no longer be functional.

Quaternary Structure

In nature, some proteins form from several polypeptides, or subunits, and the interaction of these subunits forms the quaternary structure. Weak interactions between the subunits help to stabilise the overall structure. For example, insulin (a globular protein) has a combination of hydrogen and disulphide bonds that cause it to mostly clump into a ball shape. Insulin starts out as a single polypeptide and loses some internal sequences in the presence of post-translational modification after forming the disulphide linkages that hold the remaining chains together. Silk (a fibrous protein), however, has a β-pleated sheet structure that is the result of hydrogen bonding between different chains.

Figure 2.4.9 illustrates the four levels of protein structure (primary, secondary, tertiary, and quaternary).

Protein structure levels.
Figure 2.4.9. Protein structure levels. Observe the four levels of protein structure in these illustrations. (Credit: modification of work by National Human Genome Research Institute).

Denaturation and Protein Folding

Each protein has its own unique sequence and shape that chemical interactions hold together. If the protein is subject to changes in temperature, pH, or exposure to chemicals, the protein structure may change, losing its shape without losing its primary sequence in what scientists call denaturation. Denaturation is often reversible because the polypeptide’s primary structure is conserved in the process if the denaturing agent is removed, allowing the protein to resume its function. Sometimes denaturation is irreversible, leading to loss of function. One example of irreversible protein denaturation is frying an egg. The albumin protein in the liquid egg white denatures when placed in a hot pan. Not all proteins denature at high temperatures. For instance, bacteria that survive in hot springs have proteins that function at temperatures close to boiling. The stomach is also very acidic, has a low pH and denatures proteins as part of the digestion process; however, the stomach’s digestive enzymes retain their activity under these conditions.

Protein folding is critical to its function. Scientists originally thought that the proteins themselves were responsible for the folding process. Only recently researchers discovered that often they receive assistance in the folding process from protein helpers, or chaperones (or chaperonins) that associate with the target protein during the folding process. They act by preventing polypeptide aggregation that comprise the complete protein structure, and they disassociate from the protein once the target protein is folded.

Section Review

Proteins are a class of macromolecules that perform a diverse range of functions for the cell. They help in metabolism by acting as enzymes, carriers, or hormones, and provide structural support. The building blocks of proteins (monomers) are amino acids. Each amino acid has a central carbon that bonds to an amino group, a carboxyl group, a hydrogen atom, and an R group or side chain. There are 20 commonly occurring amino acids, each of which differs in the R group. A peptide bond links each amino acid to its neighbours. A long amino acid chain is a polypeptide.

Proteins are organised at four levels: primary, secondary, tertiary, and (optional) quaternary. The primary structure is the amino acids’ unique sequence. The polypeptide’s local folding to form structures such as the α-helix and β-pleated sheet constitutes the secondary structure. The overall three-dimensional structure is the tertiary structure. When two or more polypeptides combine to form the complete protein structure, the configuration is the protein’s quaternary structure. Protein shape and function are intricately linked. Any change in shape caused by changes in temperature or pH may lead to protein denaturation and a loss in function.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=109

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=109

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=109

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=109

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=109

Note: Content and images from this chapter have been adapted from Biology 2nd edition by Mary Ann Clark, Jung Choi and Matthew Douglas, used under a CC-BY license.

2.5 Nucleic Acid

Learning Objectives

By the end of this section, you will be able to:

  • Describe nucleic acids’ structure and define the two types of nucleic acids
  • Explain DNA structure and role
  • Explain RNA structure and roles

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell’s genetic blueprint and carry instructions for its functioning.

DNA and RNA

The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes, the DNA is not enclosed in a membranous envelope.

The cell’s entire genetic content is its genome, and the study of genomes is genomics. In eukaryotic cells but not in prokaryotes, DNA forms a complex with histone proteins to form chromatin, the substance of eukaryotic chromosomes. A chromosome may contain tens of thousands of genes. Many genes contain the information to make protein products. Other genes code for RNA products. DNA controls all the cellular activities by turning the genes “on” or “off.”

The other type of nucleic acid, RNA, is mostly involved in protein synthesis. The DNA molecules never leave the nucleus but instead use an intermediary to communicate with the rest of the cell. This intermediary is the messenger RNA (mRNA). Other types of RNA—like rRNA, tRNA, and microRNA—are involved in protein synthesis and its regulation.

DNA and RNA are comprised of monomers that scientists call nucleotides. The nucleotides combine with each other to form a polynucleotide, DNA or RNA. Three components comprise each nucleotide: a nitrogenous base, a pentose (five-carbon) sugar, and a phosphate group (Figure 2.5.1). Each nitrogenous base in a nucleotide is attached to a sugar molecule, which is attached to one or more phosphate groups.

 

Nucleotide components
Figure 2.5.1. Nucleotide components. Three components comprise a nucleotide: a nitrogenous base, a pentose sugar, and one or more phosphate groups. Carbon residues in the pentose are numbered 1′ through 5′ (the prime distinguishes these residues from those in the base, which are numbered without using a prime notation). The base is attached to the ribose’s 1′ position, and the phosphate is attached to the 5′ position. When a polynucleotide forms, the incoming nucleotide’s 5′ phosphate attaches to the 3′ hydroxyl group at the end of the growing chain. Two types of pentose are in nucleotides, deoxyribose (found in DNA) and ribose (found in RNA). Deoxyribose is similar in structure to ribose, but it has an H instead of an OH at the 2′ position. We can divide bases into two categories: purines and pyrimidines. Purines have a double ring structure, and pyrimidines have a single ring.

The nitrogenous bases, important components of nucleotides, are organic molecules and are so named because they contain carbon and nitrogen. They are bases because they contain an amino group that has the potential of binding an extra hydrogen, and thus decreasing the hydrogen ion concentration in its environment, making it more basic. Each nucleotide in DNA contains one of four possible nitrogenous bases: adenine (A), guanine (G) cytosine (C), and thymine (T).

Scientists classify adenine and guanine as purines. The purine’s primary structure is two carbon-nitrogen rings. Scientists classify cytosine, thymine, and uracil as pyrimidines which have a single carbon-nitrogen ring as their primary structure (Figure 2.5.1). Each of these basic carbon-nitrogen rings has different functional groups attached to it. In molecular biology shorthand, we know the nitrogenous bases by their symbols A, T, G, C, and U. DNA contains A, T, G, and C; whereas, RNA contains A, U, G, and C.

The pentose sugar in DNA is deoxyribose, and in RNA, the sugar is ribose (Figure 3.5.1). The difference between the sugars is the presence of the hydroxyl group on the ribose’s second carbon and hydrogen on the deoxyribose’s second carbon. The carbon atoms of the sugar molecule are numbered as 1′, 2′, 3′, 4′, and 5′ (1′ is read as “one prime”). The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′–3′ phosphodiester linkage. A simple dehydration reaction like the other linkages connecting monomers in macromolecules does not form the phosphodiester linkage. Its formation involves removing two phosphate groups. A polynucleotide may have thousands of such phosphodiester linkages.

DNA Double-Helix Structure

Native DNA
Figure 2.5.2. Native DNA is an antiparallel double helix. The phosphate backbone (indicated by the curvy lines) is on the outside, and the bases are on the inside. Each base from one strand interacts via hydrogen bonding with a base from the opposing strand. (Credit: Jerome Walker/Dennis Myts).

DNA has a double-helix structure (Figure 2.5.2). The sugar and phosphate lie on the outside of the helix, forming the DNA’s backbone. The nitrogenous bases are stacked in the interior, like a pair of staircase steps. Hydrogen bonds bind the pairs to each other. Every base pair in the double helix is separated from the next base pair by 0.34 nm. The helix’s two strands run in opposite directions, meaning that the 5′ carbon end of one strand will face the 3′ carbon end of its matching strand. (Scientists call this an antiparallel orientation and is important to DNA replication and in many nucleic acid interactions.)

Only certain types of base pairing are allowed. For example, a certain purine can only pair with a certain pyrimidine. This means A can pair with T, and G can pair with C, as Figure 2.5.3 shows. This is the base complementary rule. In other words, the DNA strands are complementary to each other. If the sequence of one strand is AATTGGCC, the complementary strand would have the sequence TTAACCGG. During DNA replication, each strand copies itself, resulting in a daughter DNA double helix containing one parental DNA strand and a newly synthesised strand.

Hydrogen bonds in a double stranded DNA molecule.
Figure 2.5.3. Hydrogen bonds in a double stranded DNA molecule. In a double stranded DNA molecule, the two strands run antiparallel to one another so that one strand runs 5′ to 3′ and the other 3′ to 5′. The phosphate backbone is located on the outside, and the bases are in the middle. Adenine forms hydrogen bonds (or base pairs) with thymine, and guanine base pairs with cytosine.

A mutation occurs, and adenine replaces cytosine. What impact do you think this will have on the DNA structure?

RNA

Ribonucleic acid, or RNA, is mainly involved in the process of protein synthesis under the direction of DNA. RNA is usually single-stranded and is comprised of ribonucleotides that are linked by phosphodiester bonds. A ribonucleotide in the RNA chain contains ribose (the pentose sugar), one of the four nitrogenous bases (A, U, G, and C), and the phosphate group.

There are four major types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and microRNA (miRNA). The first, mRNA, carries the message from DNA, which controls all the cellular activities in a cell. If a cell requires synthesising a certain protein, the gene for this product turns “on” and the messenger RNA synthesises in the nucleus. The RNA base sequence is complementary to the DNA’s coding sequence from which it has been copied. However, in RNA, the base T is absent and U is present instead. If the DNA strand has a sequence AATTGCGC, the sequence of the complementary RNA is UUAACGCG. In the cytoplasm, the mRNA interacts with ribosomes and other cellular machinery (Figure 2.5.4).

Diagram of ribosome
Figure 2.5.4. Ribosome. A ribosome has two parts: a large subunit and a small subunit. The mRNA sits in between the two subunits. A tRNA molecule recognises a codon on the mRNA, binds to it by complementary base pairing, and adds the correct amino acid to the growing peptide chain.

The mRNA is read in sets of three bases known as codons. Each codon codes for a single amino acid. In this way, the mRNA is read and the protein product is made. Ribosomal RNA (rRNA) is a major constituent of ribosomes on which the mRNA binds. The rRNA ensures the proper alignment of the mRNA and the Ribosomes. The ribosome’s rRNA also has an enzymatic activity (peptidyl transferase) and catalyses peptide bond formation between two aligned amino acids. Transfer RNA (tRNA) is one of the smallest of the four types of RNA, usually 70–90 nucleotides long. It carries the correct amino acid to the protein synthesis site. It is the base pairing between the tRNA and mRNA that allows for the correct amino acid to insert itself in the polypeptide chain. MicroRNAs are the smallest RNA molecules and their role involves regulating gene expression by interfering with the expression of certain mRNA messages. Table 2.5.1 summarises DNA and RNA features.

Table 2.5.1 DNA and RNA Features

DNA RNA
Function Carries genetic information Involved in protein synthesis
Location Remains in the nucleus Leaves the nucleus
Structure Double helix Usually single-stranded
Sugar Deoxyribose Ribose
Pyrimidines Cytosine, thymine Cytosine, uracil
Purines Adenine, guanine Adenine, guanine

Even though the RNA is single stranded, most RNA types show extensive intramolecular base pairing between complementary sequences, creating a predictable three-dimensional structure essential for their function.

As you have learned, information flow in an organism takes place from DNA to RNA to protein. DNA dictates the structure of mRNA in a process scientists call transcription, and RNA dictates the protein’s structure in a process scientists call translation. This is the Central Dogma of Life, which holds true for all organisms; however, exceptions to the rule occur in connection with viral infections.

Section Review

Nucleic acids are molecules comprised of nucleotides that direct cellular activities such as cell division and protein synthesis. Pentose sugar, a nitrogenous base, and a phosphate group comprise each nucleotide. There are two types of nucleic acids: DNA and RNA. DNA carries the cell’s genetic blueprint and passes it on from parents to offspring (in the form of chromosomes). It has a double-helical structure with the two strands running in opposite directions, connected by hydrogen bonds, and complementary to each other. RNA is a single-stranded polymer composed of linked nucleotides made up of a pentose sugar (ribose), a nitrogenous base, and a phosphate group. RNA is involved in protein synthesis and its regulation. Messenger RNA (mRNA) copies from the DNA, exports itself from the nucleus to the cytoplasm, and contains information for constructing proteins. Ribosomal RNA (rRNA) is a part of the ribosomes at the site of protein synthesis; whereas, transfer RNA (tRNA) carries the amino acid to the site of protein synthesis. The microRNA regulates using mRNA for protein synthesis.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=111

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=111

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=111

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=111

Note: Content and images from this chapter have been adapted from Biology 2nd edition by Mary Ann Clark, Jung Choi and Matthew Douglas, used under a CC-BY license.

 

2.6 The Cell Membrane

Learning Objectives

By the end of this section, you will be able to:

  • Describe the molecular components that make up the cell membrane
  • Explain the major features and properties of the cell membrane
  • Differentiate between materials that can and cannot diffuse through the lipid bilayer
  • Recognise different types of passive transport and active transport, providing examples of each

Despite differences in structure and function, all living cells in multicellular organisms have a surrounding cell membrane. As the outer layer of your skin separates your body from its environment, the cell membrane (also known as the plasma membrane) separates the inner contents of a cell from its exterior environment. This cell membrane provides a protective barrier around the cell and regulates which materials can pass in or out.

Structure and Composition of the Cell Membrane

The cell membrane is an extremely pliable structure composed primarily of back-to-back phospholipids (a “bilayer”). Cholesterol is also present, which contributes to the fluidity of the membrane, and there are various proteins embedded within the membrane that have a variety of functions.

A single phospholipid molecule has a phosphate group on one end, called the “head,” and two side-by-side chains of fatty acids that make up the lipid tails (Figure 2.6.1). The phosphate group is negatively charged, making the head polar and hydrophilic—or “water loving.” A hydrophilic molecule (or region of a molecule) is one that is attracted to water. The phosphate heads are thus attracted to the water molecules of both the extracellular and intracellular environments. The lipid tails, on the other hand, are uncharged, or nonpolar, and are hydrophobic—or “water fearing.” A hydrophobic molecule (or region of a molecule) repels and is repelled by water. Some lipid tails consist of saturated fatty acids and some contain unsaturated fatty acids. This combination adds to the fluidity of the tails that are constantly in motion. Phospholipids are thus amphipathic molecules. An amphipathic molecule is one that contains both a hydrophilic and a hydrophobic region. In fact, soap works to remove oil and grease stains because it has amphipathic properties. The hydrophilic portion can dissolve in water while the hydrophobic portion can trap grease in micelles that then can be washed away.

Diagram of Phospholipid structure
Figure 2.6.1. Phospholipid structure. A phospholipid molecule consists of a polar phosphate “head,” which is hydrophilic and a non-polar lipid “tail,” which is hydrophobic. Unsaturated fatty acids result in kinks in the hydrophobic tails.

The cell membrane consists of two adjacent layers of phospholipids. The lipid tails of one layer face the lipid tails of the other layer, meeting at the interface of the two layers. The phospholipid heads face outward, one layer exposed to the interior of the cell and one layer exposed to the exterior (Figure 2.6.2). Because the phosphate groups are polar and hydrophilic, they are attracted to water in the intracellular fluid. Intracellular fluid (ICF) is the fluid interior of the cell. The phosphate groups are also attracted to the extracellular fluid. Extracellular fluid (ECF) is the fluid environment outside the enclosure of the cell membrane. Interstitial fluid (IF) is the term given to extracellular fluid not contained within blood vessels. Because the lipid tails are hydrophobic, they meet in the inner region of the membrane, excluding watery intracellular and extracellular fluid from this space. The cell membrane has many proteins, as well as other lipids (such as cholesterol), that are associated with the phospholipid bilayer. An important feature of the membrane is that it remains fluid; the lipids and proteins in the cell membrane are not rigidly locked in place.

Phospholipid bilayer diagram
Figure 2.6.2. Phospholipid bilayer. The phospholipid bilayer consists of two adjacent sheets of phospholipids, arranged tail to tail. The hydrophobic tails associate with one another, forming the interior of the membrane. The polar heads contact the fluid inside and outside of the cell.

Membrane Proteins

The lipid bilayer forms the basis of the cell membrane, but it is peppered throughout with various proteins. Two different types of proteins that are commonly associated with the cell membrane are the integral proteins and peripheral protein (Figure 2.6.3). As its name suggests, an integral protein is a protein that is embedded in the membrane. A channel protein is an example of an integral protein that selectively allows particular materials, such as certain ions, to pass into or out of the cell.

 

Diagram of cell membrane
Figure 2.6.3. Cell Membrane. The cell membrane of the cell is a phospholipid bilayer containing many different molecular components, including proteins and cholesterol, some with carbohydrate groups attached.

Another important group of integral proteins are cell recognition proteins, which serve to mark a cell’s identity so that it can be recognised by other cells. A receptor is a type of recognition protein that can selectively bind a specific molecule outside the cell, and this binding induces a chemical reaction within the cell. A ligand is the specific molecule that binds to and activates a receptor. Some integral proteins serve dual roles as both a receptor and an ion channel. One example of a receptor-ligand interaction is the receptors on nerve cells that bind neurotransmitters, such as dopamine. When a dopamine molecule binds to a dopamine receptor protein, a channel within the transmembrane protein opens to allow certain ions to flow into the cell.

Some integral membrane proteins are glycoproteins. A glycoprotein is a protein that has carbohydrate molecules attached, which extend into the extracellular matrix. The attached carbohydrate tags on glycoproteins aid in cell recognition. The carbohydrates that extend from membrane proteins and even from some membrane lipids collectively form the glycocalyx. The glycocalyx is a fuzzy-appearing coating around the cell formed from glycoproteins and other carbohydrates attached to the cell membrane. The glycocalyx can have various roles. For example, it may have molecules that allow the cell to bind to another cell, it may contain receptors for hormones, or it might have enzymes to break down nutrients. The glycocalyces found in a person’s body are products of that person’s genetic makeup. They give each of the individual’s trillions of cells the “identity” of belonging in the person’s body. This identity is the primary way that a person’s immune defence cells “know” not to attack the person’s own body cells, but it also is the reason organs donated by another person might be rejected.

Peripheral proteins are typically found on the inner or outer surface of the lipid bilayer but can also be attached to the internal or external surface of an integral protein. These proteins typically perform a specific function for the cell. Some peripheral proteins on the surface of intestinal cells, for example, act as digestive enzymes to break down nutrients to sizes that can pass through the cells and into the bloodstream.

Transport Across the Cell

One of the great wonders of the cell membrane is its ability to regulate the concentration of substances inside the cell. These substances include ions such as Ca2+, Na+, K+ and Cl; nutrients including sugars, fatty acids, and amino acids; and waste products, particularly carbon dioxide (CO2), which must leave the cell.

The membrane’s lipid bilayer structure provides the first level of control. The phospholipids are tightly packed together, and the membrane has a hydrophobic interior. This structure causes the membrane to be selectively permeable. A membrane that has selective permeability allows only substances meeting certain criteria to pass through it unaided. In the case of the cell membrane, only relatively small, nonpolar materials can move through the lipid bilayer (remember, the lipid tails of the membrane are nonpolar). Some examples of these are other lipids, oxygen and carbon dioxide gases, and alcohol. However, water-soluble materials—like glucose, amino acids, and electrolytes—need some assistance to cross the membrane because they are repelled by the hydrophobic tails of the phospholipid bilayer. All substances that move through the membrane do so by one of two general methods, which are categorised based on whether or not energy is required. Passive transport is the movement of substances across the membrane without the expenditure of cellular energy. In contrast, active transport is the movement of substances across the membrane using energy from adenosine triphosphate (ATP).

Passive Transport

In order to understand how substances move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is the difference in concentration of a substance across a space. Molecules (or ions) will spread/diffuse from where they are more concentrated to where they are less concentrated until they are equally distributed in that space. (When molecules move in this way, they are said to move down their concentration gradient.) Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. A couple of common examples will help to illustrate this concept. Imagine being inside a closed bathroom. If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the bathroom, and this diffusion would go on until no more concentration gradient remains. Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. In both cases, if the room is warmer or the tea hotter, diffusion occurs even faster as the molecules are bumping into each other and spreading out faster than at cooler temperatures. Having an internal body temperature around 37oC (98.6° F) thus also aids in diffusion of particles within the body.

Whenever a substance exists in greater concentration on one side of a semipermeable membrane, such as the cell membranes, any substance that can move down its concentration gradient across the membrane will do so. Consider substances that can easily diffuse through the lipid bilayer of the cell membrane, such as the gases oxygen (O2) and CO2. O2 generally diffuses into cells because it is more concentrated outside of them, and CO2 typically diffuses out of cells because it is more concentrated inside of them. Neither of these examples requires any energy on the part of the cell, and therefore they use passive transport to move across the membrane.

Before moving on, you need to review the gases that can diffuse across a cell membrane. Because cells rapidly use up oxygen during metabolism, there is typically a lower concentration of O2 inside the cell than outside. As a result, oxygen will diffuse from the interstitial fluid directly through the lipid bilayer of the membrane and into the cytoplasm within the cell. On the other hand, because cells produce CO2 as a by-product of metabolism, CO2 concentrations rise within the cytoplasm; therefore, CO2 will move from the cell through the lipid bilayer and into the interstitial fluid, where its concentration is lower. This mechanism of molecules moving across a cell membrane from the side where they are more concentrated to the side where they are less concentrated is a form of passive transport called simple diffusion (Figure 2.6.4).

 

Simple diffusion across the cell (plasma) membrane
Figure 2.6.4. Simple diffusion across the cell (plasma) membrane. The structure of the lipid bilayer allows small, uncharged substances such as oxygen and carbon dioxide, and hydrophobic molecules such as lipids, to pass through the cell membrane, down their concentration gradient, by simple diffusion.

Large polar or ionic molecules, which are hydrophilic, cannot easily cross the phospholipid bilayer. Very small polar molecules, such as water, can cross via simple diffusion due to their small size. Charged atoms or molecules of any size cannot cross the cell membrane via simple diffusion as the charges are repelled by the hydrophobic tails in the interior of the phospholipid bilayer. Solutes dissolved in water on either side of the cell membrane will tend to diffuse down their concentration gradients, but because most substances cannot pass freely through the lipid bilayer of the cell membrane, their movement is restricted to protein channels and specialised transport mechanisms in the membrane. Facilitated diffusion is the diffusion process used for those substances that cannot cross the lipid bilayer due to their size, charge, and/or polarity (Figure 2.6.5). A common example of facilitated diffusion is the movement of glucose into the cell, where it is used to make ATP. Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialised carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion.

Facilitated diffusion. (a) Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually mildly discriminate between their cargo based on size and charge. (b) Carrier proteins are more selective, often only allowing one particular type of molecule to cross.
Figure 2.6.5. Facilitated diffusion. (a) Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually mildly discriminate between their cargo based on size and charge. (b) Carrier proteins are more selective, often only allowing one particular type of molecule to cross.

As an example, even though sodium ions (Na+) are highly concentrated outside of cells, these electrolytes are charged and cannot pass through the nonpolar lipid bilayer of the membrane. Their diffusion is facilitated by membrane proteins that form sodium channels (or “pores”), so that Na+ ions can move down their concentration gradient from outside the cells to inside the cells. There are many other solutes that must undergo facilitated diffusion to move into a cell, such as amino acids, or to move out of a cell, such as wastes. Because facilitated diffusion is a passive process, it does not require energy expenditure by the cell.

Water also can move freely across the cell membrane of all cells, either through protein channels or by slipping between the lipid tails of the membrane itself. Osmosis is the diffusion of water through a semipermeable membrane (Figure 2.6.6).

Diagram of Osmotic diffusion
Figure 2.6.6. Osmotic diffusion. Osmosis is the diffusion of water through a semipermeable membrane down its concentration gradient. If a membrane is permeable to water, though not to a solute, water will equalise its own concentration by diffusing to the side of lower water concentration (and thus the side of higher solute concentration). In the beaker on the left, the solution on the right side of the membrane is hypertonic.

The movement of water molecules is not itself regulated by cells, so it is important that cells are exposed to an environment in which the concentration of solutes outside of the cells (in the extracellular fluid) is equal to the concentration of solutes inside the cells (in the cytoplasm). Two solutions that have the same concentration of solutes are said to be isotonic (equal tension). When cells and their extracellular environments are isotonic, the concentration of water molecules is the same outside and inside the cells, and the cells maintain their normal shape (and function).

Osmosis occurs when there is an imbalance of solutes outside of a cell versus inside the cell. A solution that has a higher concentration of solutes than another solution is said to be hypertonic, and water molecules tend to diffuse into a hypertonic solution (Figure 2.6.7). Cells in a hypertonic solution will shrivel as water leaves the cell via osmosis. In contrast, a solution that has a lower concentration of solutes than another solution is said to be hypotonic, and water molecules tend to diffuse out of a hypotonic solution. Cells in a hypotonic solution will take on too much water and swell, with the risk of eventually bursting. A critical aspect of homeostasis in living things is to create an internal environment in which all of the body’s cells are in an isotonic solution. Various organ systems, particularly the kidneys, work to maintain this homeostasis.

Diagram of concetration of solutions
Figure 2.6.7. Concentration of solutions. A hypertonic solution has a solute concentration higher than another solution. An isotonic solution has a solute concentration equal to another solution. A hypotonic solution has a solute concentration lower than another solution.

Another mechanism besides diffusion to passively transport materials between compartments is filtration. Unlike diffusion of a substance from where it is more concentrated to less concentrated, filtration uses a hydrostatic pressure gradient that pushes the fluid—and the solutes within it—from a higher pressure area to a lower pressure area. Filtration is an extremely important process in the body. For example, the circulatory system uses filtration to move plasma and substances across the endothelial lining of capillaries and into surrounding tissues, supplying cells with the nutrients. Filtration pressure in the kidneys provides the mechanism to remove wastes from the bloodstream.

Active Transport

For all the transport methods described above, the cell expends no energy. Membrane proteins that aid in the passive transport of substances do so without the use of ATP. During active transport, ATP is required to move a substance across a membrane, often with the help of protein carriers, and usually against its concentration gradient.

One of the most common types of active transport involves proteins that serve as pumps. The word “pump” probably conjures up thoughts of using energy to pump up the tire of a bicycle or a basketball. Similarly, energy from ATP is required for these membrane proteins to transport substances—molecules or ions—across the membrane, usually against their concentration gradients (from an area of low concentration to an area of high concentration).

The sodium-potassium pump, which is also called Na+/KATPase, transports sodium out of a cell while moving potassium into the cell. The Na+/Kpump is an important ion pump found in the membranes of many types of cells. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes. An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na+/K+ pump moves three Na+ ions out of the cell and two K+ ions into the cell for each ATP molecule that is used (Figure 2.6.8). This process is so important for nerve cells that it accounts for the majority of their ATP usage.

 

Sodium-potassium pump
Figure 2.6.8. Sodium-potassium pump. The sodium-potassium pump is found in many cell (plasma) membranes. Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. In a single cycle of the pump, three sodium ions are extruded from and two potassium ions are imported into the cell.

Active transport pumps can also work together with other active or passive transport systems to move substances across the membrane. For example, the sodium-potassium pump maintains a high concentration of sodium ions outside of the cell. Therefore, if the cell needs sodium ions, all it has to do is open a passive sodium channel, as the concentration gradient of the sodium ions will drive them to diffuse into the cell. In this way, the action of an active transport pump (the sodium-potassium pump) powers the passive transport of sodium ions by creating a concentration gradient. When active transport powers the transport of another substance in this way, it is called secondary active transport.

Symporters are secondary active transporters that move two substances in the same direction. For example, the sodium-glucose symporter uses sodium ions to “pull” glucose molecules into the cell. Because cells store glucose for energy, glucose is typically at a higher concentration inside of the cell than outside. However, due to the action of the sodium-potassium pump, sodium ions will easily diffuse into the cell when the symporter is opened. The flood of sodium ions through the symporter provides the energy that allows glucose to move through the symporter and into the cell, against its concentration gradient.

Conversely, antiporters are secondary active transport systems that transport substances in opposite directions. For example, the sodium-hydrogen ion antiporter uses the energy from the inward flood of sodium ions to move hydrogen ions (H+) out of the cell. The sodium-hydrogen antiporter is used to maintain the pH of the cell’s interior.

Other forms of active transport do not involve membrane carriers. Endocytosis (bringing “into the cell”) is the process of a cell ingesting material by enveloping it in a portion of its cell membrane, and then pinching off that portion of membrane (Figure 2.6.9). Once pinched off, the portion of membrane and its contents becomes an independent, intracellular vesicle. A vesicle is a membranous sac—a spherical and hollow organelle bounded by a lipid bilayer membrane. Endocytosis often brings materials into the cell that must be broken down or digested. Phagocytosis (“cell eating”) is the endocytosis of large particles. Many immune cells engage in phagocytosis of invading pathogens. Like little Pac-men, their job is to patrol body tissues for unwanted matter, such as invading bacterial cells, phagocytose them, and digest them. In contrast to phagocytosis, pinocytosis (“cell drinking”) brings fluid containing dissolved substances into a cell through membrane vesicles.

Daiagram of Three forms of endocytosis.
Figure 2.6.9. Three forms of endocytosis. Endocytosis is a form of active transport in which a cell envelopes extracellular materials using its cell membrane. (a) In phagocytosis, which is relatively nonselective, the cell takes in a large particle. (b) In pinocytosis, the cell takes in small particles in fluid. (c) In contrast, receptor-mediated endocytosis is quite selective. When external receptors bind a specific ligand, the cell responds by endocytosing the ligand.

Phagocytosis and pinocytosis take in large portions of extracellular material, and they are typically not highly selective in the substances they bring in. Cells regulate the endocytosis of specific substances via receptor-mediated endocytosis. Receptor-mediated endocytosis is endocytosis by a portion of the cell membrane that contains many receptors that are specific for a certain substance. Once the surface receptors have bound enough of the specific substance (the receptor’s ligand), the cell will endocytose the part of the cell membrane containing the receptor-ligand complexes. Iron, a required component of haemoglobin, is endocytosed by red blood cells in this way. Iron is bound to a protein called transferrin in the blood. Specific transferrin receptors on red blood cell surfaces bind the iron-transferrin molecules, and the cell endocytoses the receptor-ligand complexes.

In contrast with endocytosis, exocytosis (taking “out of the cell”) is the process of a cell exporting material using vesicular transport (Figure 2.6.10). Many cells manufacture substances that must be secreted, like a factory manufacturing a product for export. These substances are typically packaged into membrane-bound vesicles within the cell. When the vesicle membrane fuses with the cell membrane, the vesicle releases its contents into the interstitial fluid. The vesicle membrane then becomes part of the cell membrane. Cells of the stomach and pancreas produce and secrete digestive enzymes through exocytosis (Figure 2.6.11). Endocrine cells produce and secrete hormones that are sent throughout the body, and certain immune cells produce and secrete large amounts of histamine, a chemical important for immune responses.

Exocytosis.
Figure 2.6.10. Exocytosis. Exocytosis is much like endocytosis in reverse. Material destined for export is packaged into a vesicle inside the cell. The membrane of the vesicle fuses with the cell membrane, and the contents are released into the extracellular space.

 

Image of Pancreatic cells’ enzyme products
Figure 2.6.11. Pancreatic cells’ enzyme products. The pancreatic acinar cells produce and secrete many enzymes that digest food. The tiny black granules in this electron micrograph are secretory vesicles filled with enzymes that will be exported from the cells via exocytosis. LM × 2900. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

Diseases of the Cell: Cystic Fibrosis

Over 3,000 Australians are living with cystic fibrosis (CF), with an estimated 1 out of every 2,500 babies being born with CF every week. In the United States, approximately 1,000 new cases are reported each year, with an approximate 30,000 people affected by CF. The genetic disease is most well-known for its damage to the lungs, causing breathing difficulties and chronic lung infections, but it also affects the liver, pancreas, and intestines. Only about 50 years ago, the prognosis for children born with CF was very grim—a life expectancy rarely over 10 years. Today, with advances in medical treatment, many CF patients live into their 30s.

The symptoms of CF result from a malfunctioning membrane ion channel called the cystic fibrosis transmembrane conductance regulator, or CFTR. In healthy people, the CFTR protein is an integral membrane protein that transports Cl– ions out of the cell. In a person who has CF, the gene for the CFTR is mutated, thus, the cell manufactures a defective channel protein that typically is not incorporated into the membrane but is instead degraded by the cell.

The CFTR requires ATP in order to function, making its Cl transport a form of active transport. This characteristic puzzled researchers for a long time because the Cl– ions are actually flowing down their concentration gradient when transported out of cells. Active transport generally pumps ions against their concentration gradient, but the CFTR presents an exception to this rule.

In normal lung tissue, the movement of Cl– out of the cell maintains a Cl-rich, negatively charged environment immediately outside of the cell. This is particularly important in the epithelial lining of the respiratory system. Respiratory epithelial cells secrete mucus, which serves to trap dust, bacteria, and other debris. A cilium (plural = cilia) is one of the hair-like appendages found on certain cells. Cilia on the epithelial cells move the mucus and its trapped particles up the airways away from the lungs and toward the outside. In order to be effectively moved upward, the mucus cannot be too viscous; rather it must have a thin, watery consistency. The transport of Cl– and the maintenance of an electronegative environment outside of the cell attract positive ions such as Na+ to the extracellular space. The accumulation of both Cl and Na+ ions in the extracellular space creates solute-rich mucus, which has a low concentration of water molecules. As a result, through osmosis, water moves from cells and extracellular matrix into the mucus, “thinning” it out. This is how, in a normal respiratory system, the mucus is kept sufficiently watered-down to be propelled out of the respiratory system.

If the CFTR channel is absent, Cl– ions are not transported out of the cell in adequate numbers, thus preventing them from drawing positive ions. The absence of ions in the secreted mucus results in the lack of a normal water concentration gradient. Thus, there is no osmotic pressure pulling water into the mucus. The resulting mucus is thick and sticky, and the ciliated epithelia cannot effectively remove it from the respiratory system. Passageways in the lungs become blocked with mucus, along with the debris it carries. Bacterial infections occur more easily because bacterial cells are not effectively carried away from the lungs.

Section Review

The cell membrane provides a barrier around the cell, separating its internal components from the extracellular environment. It is composed of a phospholipid bilayer, with hydrophobic internal lipid “tails” and hydrophilic external phosphate “heads.” Various membrane proteins are scattered throughout the bilayer, both inserted within it and attached to it peripherally. The cell membrane is selectively permeable, allowing only a limited number of materials to diffuse through its lipid bilayer. All materials that cross the membrane do so using passive (non energy-requiring) or active (energy-requiring) transport processes. During passive transport, materials move by simple diffusion or by facilitated diffusion through the membrane, down their concentration gradient. Water passes through the membrane in a diffusion process called osmosis. During active transport, energy is expended to assist material movement across the membrane in a direction against their concentration gradient. Active transport may take place with the help of protein pumps or through the use of vesicles.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=113

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=113

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=113

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=113

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=113

2.7 The Cytoplasm and Cellular Organelles

Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure and function of the cellular organelles associated with the endomembrane system, including the endoplasmic reticulum, Golgi apparatus, and lysosomes
  • Describe the structure and function of mitochondria and peroxisomes
  • Explain the three components of the cytoskeleton, including their composition and functions

Now that you have learned that the cell membrane surrounds all cells, you can dive inside of a prototypical human cell to learn about its internal components and their functions. All living cells in multicellular organisms contain an internal cytoplasmic compartment, and a nucleus within the cytoplasm. Cytosol, the jelly-like substance within the cell, provides the fluid medium necessary for biochemical reactions. Eukaryotic cells, including all animal cells, also contain various cellular organelles. An organelle (“little organ”) is one of several different types of membrane-enclosed bodies in the cell, each performing a unique function. Just as the various bodily organs work together in harmony to perform all of a human’s functions, the many different cellular organelles work together to keep the cell healthy and performing all of its important functions. The organelles and cytosol, taken together, compose the cell’s cytoplasm. The nucleus is a cell’s central organelle, which contains the cell’s DNA (Figure 2.7.1).

Prototypical human cell
Figure 2.7.1. Prototypical human cell. While this image is not indicative of any one particular human cell, it is a prototypical example of a cell containing the primary organelles and internal structures.

Organelles of the Endomembrane System

A set of three major organelles together form a system within the cell called the endomembrane system. These organelles work together to perform various cellular jobs, including the task of producing, packaging, and exporting certain cellular products. The organelles of the endomembrane system include the endoplasmic reticulum, Golgi apparatus, and vesicles.

Endoplasmic Reticulum

The endoplasmic reticulum (ER) is a system of channels that is continuous with the nuclear membrane (or “envelope”) covering the nucleus and composed of the same lipid bilayer material. The ER can be thought of as a series of winding thoroughfares like the waterway canals in Venice. The ER provides passages throughout much of the cell that function in transporting, synthesising, and storing materials. The winding structure of the ER results in a large membranous surface area that supports its many functions (Figure 2.7.2).

Endoplasmic reticulum diagram
Figure 2.7.2. Endoplasmic reticulum (ER). (a) The ER is a winding network of thin membranous sacs found in close association with the cell nucleus. The smooth and rough endoplasmic reticula are very different in appearance and function (source: mouse tissue). (b) Rough ER is studded with numerous ribosomes, which are sites of protein synthesis (source: mouse tissue). EM × 110,000. (c) Smooth ER synthesises phospholipids, steroid hormones, regulates the concentration of cellular Ca2+, metabolises some carbohydrates, and breaks down certain toxins (source: mouse tissue). EM × 110,510. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Endoplasmic reticulum can exist in two forms: rough ER and smooth ER. These two types of ER perform some very different functions and can be found in very different amounts depending on the type of cell. Rough ER (RER) is so-called because its membrane is dotted with embedded granules—organelles called ribosomes, giving the RER a bumpy appearance. A ribosome is an organelle that serves as the site of protein synthesis. It is composed of two ribosomal RNA subunits that wrap around mRNA to start the process of translation, followed by protein synthesis. Smooth ER (SER) lacks these ribosomes.

One of the main functions of the smooth ER is in the synthesis of lipids. The smooth ER synthesises phospholipids, the main component of biological membranes, as well as steroid hormones. For this reason, cells that produce large quantities of such hormones, such as those of the female ovaries and male testes, contain large amounts of smooth ER. In addition to lipid synthesis, the smooth ER also sequesters (i.e., stores) and regulates the concentration of cellular Ca2+, a function extremely important in cells of the nervous system where Ca2+  is the trigger for neurotransmitter release. The smooth ER additionally metabolises some carbohydrates and performs a detoxification role, breaking down certain toxins.

In contrast with the smooth ER, the primary job of the rough ER is the synthesis and modification of proteins destined for the cell membrane or for export from the cell. For this protein synthesis, many ribosomes attach to the ER (giving it the studded appearance of rough ER). Typically, a protein is synthesised within the ribosome and released inside the channel of the rough ER, where sugars can be added to it (by a process called glycosylation) before it is transported within a vesicle to the next stage in the packaging and shipping process: the Golgi apparatus.

The Golgi Apparatus

The Golgi apparatus is responsible for sorting, modifying, and shipping off the products that come from the rough ER, much like a post-office. The Golgi apparatus looks like stacked flattened discs, almost like stacks of oddly shaped pancakes. Like the ER, these discs are membranous. The Golgi apparatus has two distinct sides, each with a different role. One side of the apparatus receives products in vesicles. These products are sorted through the apparatus, and then they are released from the opposite side after being repackaged into new vesicles. If the product is to be exported from the cell, the vesicle migrates to the cell surface and fuses to the cell membrane, and the cargo is secreted (Figure 2.7.3).

Golgi apparatus diagram
Figure 2.7.3. Golgi apparatus. (a) The Golgi apparatus manipulates products from the rough ER, and also produces new organelles called lysosomes. Proteins and other products of the ER are sent to the Golgi apparatus, which organises, modifies, packages, and tags them. Some of these products are transported to other areas of the cell and some are exported from the cell through exocytosis. Enzymatic proteins are packaged as new lysosomes (or packaged and sent for fusion with existing lysosomes). (b) An electron micrograph of the Golgi apparatus.

Lysosomes

Some of the protein products packaged by the Golgi include digestive enzymes that are meant to remain inside the cell for use in breaking down certain materials. The enzyme-containing vesicles released by the Golgi may form new lysosomes, or fuse with existing, lysosomes. A lysosome is an organelle that contains enzymes that break down and digest unneeded cellular components, such as a damaged organelle. (A lysosome is like a wrecking crew that takes down old and unsound buildings in a neighbourhood.) Autophagy (“self-eating”) is the process of a cell digesting its own structures. Lysosomes are also important for breaking down foreign material, for example, when certain immune defence cells (white blood cells) phagocytose bacteria, the bacterial cell is transported into a lysosome and digested by the enzymes inside. As one might imagine, such phagocytic defence cells contain large numbers of lysosomes.

Under certain circumstances, lysosomes perform a more grand and dire function. In the case of damaged or unhealthy cells, lysosomes can be triggered to open up and release their digestive enzymes into the cytoplasm of the cell, killing the cell. This “self-destruct” mechanism is called autolysis, and makes the process of cell death controlled (a mechanism called “apoptosis”).

Organelles for the Energy Production and Detoxification

In addition to the jobs performed by the endomembrane system, the cell has many other important functions. Just as you must consume nutrients to provide yourself with energy, so must each of your cells take in nutrients, some of which convert to chemical energy that can be used to power biochemical reactions. Another important function of the cell is detoxification. Humans take in all sorts of toxins from the environment and also produce harmful chemicals as by-products of cellular processes. Cells called hepatocytes in the liver detoxify many of these toxins.

Mitochondria

mitochondrion (plural = mitochondria) is a membranous, bean-shaped organelle that is the “energy transformer” of the cell. Mitochondria consist of an outer lipid bilayer membrane as well as an additional inner lipid bilayer membrane (Figure 2.7.4). The inner membrane is highly folded into winding structures with a great deal of surface area, called cristae. It is along this inner membrane that a series of proteins, enzymes, and other molecules perform the biochemical reactions of cellular respiration. These reactions convert energy stored in nutrient molecules (such as glucose) into adenosine triphosphate (ATP), which provides usable cellular energy to the cell. Cells use ATP constantly, and so the mitochondria are constantly at work. Oxygen molecules are required during cellular respiration, which is why you must constantly breathe it in. One of the organ systems in the body that uses huge amounts of ATP is the muscular system because ATP is required to sustain muscle contraction. As a result, muscle cells are packed full of mitochondria. Nerve cells also need large quantities of ATP to run their sodium-potassium pumps. Therefore, an individual neuron will be loaded with over a thousand mitochondria. On the other hand, a bone cell, which is not nearly as metabolically active, might only have a couple hundred mitochondria.

Mitochondrion diagram
Figure 2.7.4. Mitochondrion. The mitochondria are the energy-conversion factories of the cell. (a) A mitochondrion is composed of two separate lipid bilayer membranes. Along the inner membrane are various molecules that work together to produce ATP, the cell’s major energy currency. (b) An electron micrograph of mitochondria. EM × 236,000. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Peroxisomes

Like lysosomes, a peroxisome is a membrane-bound cellular organelle that contains mostly enzymes (Figure 2.7.5). Peroxisomes perform a couple of different functions, including lipid metabolism and chemical detoxification. In contrast to the digestive enzymes found in lysosomes, the enzymes within peroxisomes serve to transfer hydrogen atoms from various molecules to oxygen, producing hydrogen peroxide (H2O2). In this way, peroxisomes neutralise poisons such as alcohol. In order to appreciate the importance of peroxisomes, it is necessary to understand the concept of reactive oxygen species.

Peroxisome diagram
Figure 2.7.5. Peroxisome. Peroxisomes are membrane-bound organelles that contain an abundance of enzymes for detoxifying harmful substances and lipid metabolism.

 

Reactive oxygen species (ROS) such as peroxides and free radicals are the highly reactive products of many normal cellular processes, including the mitochondrial reactions that produce ATP and oxygen metabolism. Examples of ROS include the hydroxyl radical OH, H2O2, and superoxide (O2−). Some ROS are important for certain cellular functions, such as cell signalling processes and immune responses against foreign substances. Free radicals are reactive because they contain free unpaired electrons; they can easily oxidise other molecules throughout the cell, causing cellular damage and even cell death. Free radicals are thought to play a role in many destructive processes in the body, from cancer to coronary artery disease.

Peroxisomes, on the other hand, oversee reactions that neutralise free radicals. Peroxisomes produce large amounts of the toxic H2O2 in the process, but peroxisomes contain enzymes that convert H2O2 into water and oxygen. These by-products are safely released into the cytoplasm. Like miniature sewage treatment plants, peroxisomes neutralise harmful toxins so that they do not wreak havoc in the cells. The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body, and liver cells contain an exceptionally high number of peroxisomes.

Defence mechanisms such as detoxification within the peroxisome and certain cellular antioxidants serve to neutralise many of these molecules. Some vitamins and other substances, found primarily in fruits and vegetables, have antioxidant properties. Antioxidants work by being oxidised themselves, halting the destructive reaction cascades initiated by the free radicals. Sometimes though, ROS accumulate beyond the capacity of such defences.

Oxidative stress is the term used to describe damage to cellular components caused by ROS. Due to their characteristic unpaired electrons, ROS can set off chain reactions where they remove electrons from other molecules, which then become oxidised and reactive, and do the same to other molecules, causing a chain reaction. ROS can cause permanent damage to cellular lipids, proteins, carbohydrates, and nucleic acids. Damaged DNA can lead to genetic mutations and even cancer. A mutation is a change in the nucleotide sequence in a gene within a cell’s DNA, potentially altering the protein coded by that gene. Other diseases believed to be triggered or exacerbated by ROS include Alzheimer’s disease, cardiovascular diseases, diabetes, Parkinson’s disease, arthritis, Huntington’s disease and schizophrenia, among many others. It is noteworthy that these diseases are largely age-related. Many scientists believe that oxidative stress is a major contributor to the ageing process.

Ageing and the Cell: The Free Radical Theory

The free radical theory on ageing was originally proposed in the 1950s, and still remains under debate. Generally speaking, the free radical theory of ageing suggests that accumulated cellular damage from oxidative stress contributes to the physiological and anatomical effects of ageing. There are two significantly different versions of this theory: one states that the ageing process itself is a result of oxidative damage, and the other states that oxidative damage causes age-related disease and disorders. The latter version of the theory is more widely accepted than the former. However, many lines of evidence suggest that oxidative damage does contribute to the ageing process. Research has shown that reducing oxidative damage can result in a longer lifespan in certain organisms such as yeast, worms, and fruit flies. Conversely, increasing oxidative damage can shorten the lifespan of mice and worms. Interestingly, a manipulation called calorie-restriction (moderately restricting the caloric intake) has been shown to increase life span in some laboratory animals. It is believed that this increase is at least in part due to a reduction of oxidative stress. However, a long-term study of primates with calorie-restriction showed no increase in their lifespan. A great deal of additional research will be required to better understand the link between reactive oxygen species and ageing.

The Cytoskeleton

Much like the bony skeleton structurally supports the human body, the cytoskeleton helps the cells to maintain their structural integrity. The cytoskeleton is a group of fibrous proteins that provide structural support for cells, but this is only one of the functions of the cytoskeleton. Cytoskeletal components are also critical for cell motility, cell reproduction, and transportation of substances within the cell.

The cytoskeleton forms a complex thread-like network throughout the cell consisting of three different kinds of protein-based filaments: microfilaments, intermediate filaments, and microtubules (Figure 2.7.6). The thickest of the three is the microtubule, a structural filament composed of subunits of a protein called tubulin. Microtubules maintain cell shape and structure, help resist compression of the cell, and play a role in positioning the organelles within the cell. Microtubules also make up two types of cellular appendages important for motion: cilia and flagella. Cilia are found on many cells of the body, including the epithelial cells that line the airways of the respiratory system. Cilia move rhythmically; they beat constantly, moving waste materials such as dust, mucus, and bacteria upward through the airways, away from the lungs and toward the mouth. Beating cilia on cells in the female fallopian tubes move egg cells from the ovary towards the uterus. A flagellum (plural = flagella) is an appendage larger than a cilium and specialised for cell locomotion. The only flagellated cell in humans is the sperm cell that must propel itself towards female egg cells.

The three components of the cytoskeleton
Figure 2.7.6. The three components of the cytoskeleton. The cytoskeleton consists of (a) microtubules, (b) microfilaments, and (c) intermediate filaments. The cytoskeleton plays an important role in maintaining cell shape and structure, promoting cellular movement, and aiding cell division.

A very important function of microtubules is to set the paths (somewhat like railroad tracks) along which the genetic material can be pulled (a process requiring ATP) during cell division, so that each new daughter cell receives the appropriate set of chromosomes. Two short, identical microtubule structures called centrioles are found near the nucleus of cells. A centriole can serve as the cellular origin point for microtubules extending outward as cilia or flagella or can assist with the separation of DNA during cell division. Microtubules grow out from the centrioles by adding more tubulin subunits, like adding additional links to a chain.

In contrast with microtubules, the microfilament is a thinner type of cytoskeletal filament (see Figure 2.7.6b). Actin, a protein that forms chains, is the primary component of these microfilaments. Actin fibres, twisted chains of actin filaments, constitute a large component of muscle tissue and, along with the protein myosin, are responsible for muscle contraction. Like microtubules, actin filaments are long chains of single subunits (called actin subunits). In muscle cells, these long actin strands, called thin filaments, are “pulled” by thick filaments of the myosin protein to contract the cell.

Actin also has an important role during cell division. When a cell is about to split in half during cell division, actin filaments work with myosin to create a cleavage furrow that eventually splits the cell down the middle, forming two new cells from the original cell.

The final cytoskeletal filament is the intermediate filament. As its name would suggest, an intermediate filament is a filament intermediate in thickness between the microtubules and microfilaments (see Figure 2.7.6c). Intermediate filaments are made up of long fibrous subunits of a protein called keratin that are wound together like the threads that compose a rope. Intermediate filaments, in concert with the microtubules, are important for maintaining cell shape and structure. Unlike the microtubules, which resist compression, intermediate filaments resist tension—the forces that pull apart cells. There are many cases in which cells are prone to tension, such as when epithelial cells of the skin are compressed, tugging them in different directions. Intermediate filaments help anchor organelles together within a cell and link cells to other cells by forming special cell-to-cell junctions.

Section Review

The internal environmental of a living cell is made up of a fluid, jelly-like substance called cytosol, which consists mainly of water, but also contains various dissolved nutrients and other molecules. The cell contains an array of cellular organelles, each one performing a unique function and helping to maintain the health and activity of the cell. The cytosol and organelles together compose the cell’s cytoplasm. Most organelles are surrounded by a lipid membrane like the cell membrane of the cell. The endoplasmic reticulum (ER), Golgi apparatus, and lysosomes share a functional connectivity and are collectively referred to as the endomembrane system. There are two types of ER: smooth and rough. While the smooth ER performs many functions, including lipid synthesis and ion storage, the rough ER is mainly responsible for protein synthesis using its associated ribosomes. The rough ER sends newly made proteins to the Golgi apparatus where they are modified and packaged for delivery to various locations within or outside of the cell. Some of these protein products are enzymes destined to break down unwanted material and are packaged as lysosomes for use inside the cell.

Cells also contain mitochondria and peroxisomes, which are the organelles responsible for producing the cell’s energy supply and detoxifying certain chemicals, respectively. Biochemical reactions within mitochondria transform energy-carrying molecules into the usable form of cellular energy known as ATP. Peroxisomes contain enzymes that transform harmful substances such as free radicals into oxygen and water. Cells also contain a miniaturised “skeleton” of protein filaments that extend throughout its interior. Three different kinds of filaments compose this cytoskeleton (in order of increasing thickness): microfilaments, intermediate filaments, and microtubules. Each cytoskeletal component performs unique functions as well as provides a supportive framework for the cell.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=115

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=115

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=115

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=115

 

2.8 The Nucleus and DNA Replication

Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure and features of the nuclear membrane
  • List the contents of the nucleus
  • Explain the organisation of the DNA molecule within the nucleus
  • Describe the process of DNA replication

The nucleus is the largest and most prominent of a cell’s organelles (Figure 2.8.1). The nucleus is generally considered the control centre of the cell because it stores all of the genetic instructions for manufacturing proteins. Interestingly, some cells in the body, such as muscle cells, contain more than one nucleus (Figure 2.8.2), which is known as multinucleated. Other cells, such as mammalian red blood cells (RBCs), do not contain nuclei at all. RBCs eject their nuclei as they mature, making space for the large numbers of haemoglobin molecules that carry oxygen throughout the body (Figure 2.8.3). Without nuclei, the life span of RBCs is short, and so the body must produce new ones constantly.

Diagram of nucleus
Figure 2.8.1. The nucleus. The nucleus is the control centre of the cell. The nucleus of living cells contains the genetic material that determines the entire structure and function of that cell.

 

Multinucleate muscle cell
Figure 2.8.2. Multinucleate muscle cell. Unlike cardiac muscle cells and smooth muscle cells, which have a single nucleus, a skeletal muscle cell contains many nuclei, and is referred to as “multinucleated.” These muscle cells are long and fibrous (often referred to as muscle fibres). During development, many smaller cells fuse to form a mature muscle fibre. The nuclei of the fused cells are conserved in the mature cell, thus imparting a multinucleate characteristic to mature muscle cells. LM × 104.3. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

 

Red blood cell extruding its nucleus.
Figure 2.8.3. Red blood cell extruding its nucleus. Mature red blood cells lack a nucleus. As they mature, erythroblasts extrude their nucleus, making room for more haemoglobin. The two panels here show an erythroblast before and after ejecting its nucleus, respectively. (credit: modification of micrograph provided by the Regents of University of Michigan Medical School © 2012).

Inside the nucleus lies the blueprint that dictates everything a cell will do and all the products it will make. This information is stored within DNA. The nucleus sends “commands” to the cell via molecular messengers that translate the information from DNA. Each cell in your body (with the exception of germ cells) contains the complete set of your DNA. When a cell divides, the DNA must be duplicated so that each new cell receives a full complement of DNA. The following section will explore the structure of the nucleus and its contents, as well as the process of DNA replication.

Organisation of the Nucleus and its DNA

Like most other cellular organelles, the nucleus is surrounded by a membrane called the nuclear envelope. This membranous covering consists of two adjacent lipid bilayers with a thin fluid space in between them. Spanning these two bilayers are nuclear pores. A nuclear pore is a tiny passageway for the passage of proteins, RNA, and solutes between the nucleus and the cytoplasm. Proteins called pore complexes lining the nuclear pores regulate the passage of materials into and out of the nucleus.

Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesised, newly made ribosomal subunits exit the cell’s nucleus through the nuclear pores.

The genetic instructions that are used to build and maintain an organism are arranged in an orderly manner in strands of DNA. Within the nucleus are threads of chromatin composed of DNA and associated proteins (Figure 2.8.4). Along the chromatin threads, the DNA is wrapped around a set of histone proteins. A nucleosome is a single, wrapped DNA-histone complex. Multiple nucleosomes along the entire molecule of DNA appear like a beaded necklace, in which the string is the DNA and the beads are the associated histones. When a cell is in the process of division, the chromatin condenses into chromosomes, so that the DNA can be safely transported to the “daughter cells.” The chromosome is composed of DNA and proteins; it is the condensed form of chromatin. It is estimated that humans have almost 22,000 genes distributed on 46 chromosomes.

Diagram of DNA macrostructure
Figure 2.8.4. DNA macrostructure. Strands of DNA are wrapped around supporting histones. These proteins are increasingly bundled and condensed into chromatin, which is packed tightly into chromosomes when the cell is ready to divide.

DNA Replication

In order for an organism to grow, develop, and maintain its health, cells must reproduce themselves by dividing to produce two new daughter cells, each with the full complement of DNA as found in the original cell. Billions of new cells are produced in an adult human every day. Only very few cell types in the body do not divide, including nerve cells, skeletal muscle fibres and cardiac muscle cells. The division time of different cell types varies. Epithelial cells of the skin and gastrointestinal lining, for instance, divide very frequently to replace those that are constantly being rubbed off the surface by friction.

A DNA molecule is made of two strands that “complement” each other in the sense that the molecules that compose the strands fit together and bind to each other, creating a double-stranded molecule that looks much like a long, twisted ladder. Each side rail of the DNA ladder is composed of alternating sugar and phosphate groups (Figure 2.8.5). The two sides of the ladder are not identical, but are complementary. These two backbones are bonded to each other across pairs of protruding bases, each bonded pair forming one “rung,” or cross member. The four DNA bases are adenine (A), thymine (T), cytosine (C), and guanine (G). Because of their shape and charge, the two bases that compose a pair always bond together. Adenine always binds with thymine, and cytosine always binds with guanine. The particular sequence of bases along the DNA molecule determines the genetic code. Therefore, if the two complementary strands of DNA were pulled apart, you could infer the order of the bases in one strand from the bases in the other, complementary strand. For example, if one strand has a region with the sequence AGTGCCT, then the sequence of the complementary strand would be TCACGGA.

Diagram of Molecular structure of DNA
Figure 2.8.5. Molecular structure of DNA. The DNA double helix is composed of two complementary strands. The strands are bonded together via their nitrogenous base pairs using hydrogen bonds.

DNA replication is the copying of DNA that occurs before cell division can take place. After a great deal of debate and experimentation, the general method of DNA replication was deduced in 1958 by two scientists in California, Matthew Meselson and Franklin Stahl. This method is illustrated in Figure 2.8.6 and described below.

Diagram of DNA replication
Figure 2.8.6. DNA replication. DNA replication faithfully duplicates the entire genome of the cell. During DNA replication, a number of different enzymes work together to pull apart the two strands so each strand can be used as a template to synthesise new complementary strands. The two new daughter DNA molecules each contain one pre-existing strand and one newly synthesised strand. Thus, DNA replication is said to be “semiconservative.”

Stage 1: Initiation. The two complementary strands are separated, much like unzipping a zipper. Special enzymes, including helicase, untwist and separate the two strands of DNA.

Stage 2: Elongation. Each strand becomes a template along which a new complementary strand is built. DNA polymerase brings in the correct bases to complement the template strand, synthesising a new strand base by base. A DNA polymerase is an enzyme that adds free nucleotides to the end of a chain of DNA, making a new double strand. This growing strand continues to be built until it has fully complemented the template strand.

Stage 3: Termination. Once the two original strands are bound to their own, finished, complementary strands, DNA replication is stopped and the two new identical DNA molecules are complete.

Each new DNA molecule contains one strand from the original molecule and one newly synthesised strand. The term for this mode of replication is “semiconservative,” because half of the original DNA molecule is conserved in each new DNA molecule. This process continues until the cell’s entire genome, the entire complement of an organism’s DNA, is replicated. As you might imagine, it is very important that DNA replication take place precisely so that new cells in the body contain the exact same genetic material as their parent cells. Mistakes made during DNA replication, such as the accidental addition of an inappropriate nucleotide, have the potential to render a gene dysfunctional or useless. Fortunately, there are mechanisms in place to minimise such mistakes. A DNA proofreading process enlists the help of special enzymes that scan the newly synthesised molecule for mistakes and corrects them. Once the process of DNA replication is complete, the cell is ready to divide. You will explore the process of cell division later in the chapter.

Section Review

The nucleus is the command centre of the cell, containing the genetic instructions for all the materials a cell will make (and thus all of its functions it can perform). The nucleus is encased within a membrane of two interconnected lipid bilayers, side-by-side. This nuclear envelope is studded with protein-lined pores that allow materials to be trafficked into and out of the nucleus. The nucleus contains one or more nucleoli, which serve as sites for ribosome synthesis. The nucleus houses the genetic material of the cell: DNA. DNA is normally found as a loosely contained structure called chromatin within the nucleus, where it is wound up and associated with a variety of histone proteins. When a cell is about to divide, the chromatin coils tightly and condenses to form chromosomes.

There is a pool of cells constantly dividing within your body. The result is billions of new cells being created each day. Before any cell is ready to divide, it must replicate its DNA so that each new daughter cell will receive an exact copy of the organism’s genome. A variety of enzymes are enlisted during DNA replication. These enzymes unwind the DNA molecule, separate the two strands, and assist with the building of complementary strands along each parent strand. The original DNA strands serve as templates from which the nucleotide sequence of the new strands are determined and synthesised. When replication is completed, two identical DNA molecules exist. Each one contains one original strand and one newly synthesised complementary strand.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=117

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=117

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=117

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=117

2.9 Protein Synthesis

Learning Objectives

By the end of this section, you will be able to:

  • Explain how the genetic code stored within DNA determines the protein that will form
  • Describe the process of transcription
  • Describe the process of translation
  • Discuss the function of ribosomes

It was mentioned earlier that DNA provides a “blueprint” for the cell structure and physiology. This refers to the fact that DNA contains the information necessary for the cell to build one very important type of molecule: the protein. Most structural components of the cell are made up, at least in part, by proteins and virtually all the functions that a cell carries out are completed with the help of proteins. One of the most important classes of proteins is enzymes, which help speed up necessary biochemical reactions that take place inside the cell. Some of these critical biochemical reactions include building larger molecules from smaller components (such as occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). Whatever the cellular process may be, it is almost sure to involve proteins. Just as the cell’s genome describes its full complement of DNA, a cell’s proteome is its full complement of proteins. Protein synthesis begins with genes. A gene is a functional segment of DNA that provides the genetic information necessary to build a protein. Each particular gene provides the code necessary to construct a particular protein. Gene expression, which transforms the information coded in a gene to a final gene product, ultimately dictates the structure and function of a cell by determining which proteins are made.

The interpretation of genes works in the following way. Recall that proteins are polymers, or chains, of many amino acid building blocks. The sequence of bases in a gene (that is, its sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A triplet is a section of three DNA bases in a row that codes for a specific amino acid. Similar to the way in which the three-letter code d-o-g signals the image of a dog, the three-letter DNA base code signals the use of a particular amino acid. For example, the DNA triplet CAC (cytosine, adenine, and cytosine) specifies the amino acid valine. Therefore, a gene, which is composed of multiple triplets in a unique sequence, provides the code to build an entire protein, with multiple amino acids in the proper sequence (Figure 2.9.1). The mechanism by which cells turn the DNA code into a protein product is a two-step process, with an RNA molecule as the intermediate.

Diagram of genetic code
Figure 2.9.1. The genetic code. DNA holds all of the genetic information necessary to build a cell’s proteins. The nucleotide sequence of a gene is ultimately translated into an amino acid sequence of the gene’s corresponding protein.

From DNA to RNA: Transcription

DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that leaves the nucleus and manages protein synthesis. This intermediate messenger is messenger RNA (mRNA), a single-stranded nucleic acid that carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm where it is used to produce proteins.

There are several different types of RNA, each having different functions in the cell. The structure of RNA is similar to DNA with a few small exceptions. For one thing, unlike DNA, most types of RNA, including mRNA, are single-stranded and contain no complementary strand. Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA. Finally, instead of the base thymine, RNA contains the base uracil. This means that adenine will always pair up with uracil during the protein synthesis process.

Gene expression begins with the process called transcription, which is the synthesis of a strand of mRNA that is complementary to the gene of interest. This process is called transcription because the mRNA is like a transcript, or copy, of the gene’s DNA code. Transcription begins in a fashion somewhat like DNA replication, in that a region of DNA unwinds and the two strands separate, however, only that small portion of the DNA will be split apart. The triplets within the gene on this section of the DNA molecule are used as the template to transcribe the complementary strand of RNA (Figure 2.9.2). A codon is a three-base sequence of mRNA, so-called because they directly encode amino acids. Like DNA replication, there are three stages to transcription: initiation, elongation, and termination.

Image of Transcription: from DNA to mRNA.
Figure 2.9.2. Transcription: from DNA to mRNA. In the first of the two stages of making protein from DNA, a gene on the DNA molecule is transcribed into a complementary mRNA molecule.

Stage 1: Initiation. A region at the beginning of the gene called a promoter—a particular sequence of nucleotides—triggers the start of transcription.

Stage 2: Elongation. Transcription starts when RNA polymerase unwinds the DNA segment. One strand, referred to as the coding strand, becomes the template with the genes to be coded. The polymerase then aligns the correct nucleic acid (A, C, G, or U) with its complementary base on the coding strand of DNA. RNA polymerase is an enzyme that adds new nucleotides to a growing strand of RNA. This process builds a strand of mRNA.

Stage 3: Termination. When the polymerase has reached the end of the gene, one of three specific triplets (UAA, UAG, or UGA) codes a “stop” signal, which triggers the enzymes to terminate transcription and release the mRNA transcript.

Before the mRNA molecule leaves the nucleus and proceeds to protein synthesis, it is modified in several ways. For this reason, it is often called a pre-mRNA at this stage. For example, your DNA, and thus complementary mRNA, contains long regions called non-coding regions that do not code for amino acids. Their function is still a mystery, but the process called splicing removes these non-coding regions from the pre-mRNA transcript (Figure 2.9.3). A spliceosome—a structure composed of various proteins and other molecules—attaches to the mRNA and “splices” or cuts out the non-coding regions. The removed segment of the transcript is called an intron. The remaining exons are pasted together. An exon is a segment of RNA that remains after splicing. Interestingly, some introns that are removed from mRNA are not always non-coding. When different coding regions of mRNA are spliced out, different variations of the protein will eventually result, with differences in structure and function. This process results in a much larger variety of possible proteins and protein functions. When the mRNA transcript is ready, it travels out of the nucleus and into the cytoplasm.

Image of splicing DNA
Figure 2.9.3. Splicing DNA. In the nucleus, a structure called a spliceosome cuts out introns (noncoding regions) within a pre-mRNA transcript and reconnects the exons.

From RNA to Protein: Translation

Like translating a book from one language into another, the codons on a strand of mRNA must be translated into the amino acid alphabet of proteins. Translation is the process of synthesising a chain of amino acids called a polypeptide. Translation requires two major aids: first, a “translator,” the molecule that will conduct the translation, and second, a substrate on which the mRNA strand is translated into a new protein, like the translator’s “desk.” Both of these requirements are fulfilled by other types of RNA. The substrate on which translation takes place is the ribosome.

Remember that many of a cell’s ribosomes are found associated with the rough ER, and carry out the synthesis of proteins destined for the Golgi apparatus. Ribosomal RNA (rRNA) is a type of RNA that, together with proteins, composes the structure of the ribosome. Ribosomes exist in the cytoplasm as two distinct components, a small and a large subunit. When an mRNA molecule is ready to be translated, the two subunits come together and attach to the mRNA. The ribosome provides a substrate for translation, bringing together and aligning the mRNA molecule with the molecular “translators” that must decipher its code.

The other major requirement for protein synthesis is the translator molecules that physically “read” the mRNA codons. Transfer RNA (tRNA) is a type of RNA that ferries the appropriate corresponding amino acids to the ribosome, and attaches each new amino acid to the last, building the polypeptide chain one-by-one. Thus, tRNA transfers specific amino acids from the cytoplasm to a growing polypeptide. The tRNA molecules must be able to recognise the codons on mRNA and match them with the correct amino acid. The tRNA is modified for this function. On one end of its structure is a binding site for a specific amino acid. On the other end is a base sequence that matches the codon specifying its particular amino acid. This sequence of three bases on the tRNA molecule is called an anticodon. For example, a tRNA responsible for shuttling the amino acid glycine contains a binding site for glycine on one end. On the other end it contains an anticodon that complements the glycine codon (GGA is a codon for glycine, and so the tRNAs anticodon would read CCU). Equipped with its particular cargo and matching anticodon, a tRNA molecule can read its recognised mRNA codon and bring the corresponding amino acid to the growing chain (Figure 2.9.4).

Diagram of Translation from RNA to protein
Figure 2.9.4. Translation from RNA to protein. During translation, the mRNA transcript is “read” by a functional complex consisting of the ribosome and tRNA molecules. tRNAs bring the appropriate amino acids in sequence to the growing polypeptide chain by matching their anti-codons with codons on the mRNA strand.

Much like the processes of DNA replication and transcription, translation consists of three main stages: initiation, elongation, and termination. Initiation takes place with the binding of a ribosome to an mRNA transcript. The elongation stage involves the recognition of a tRNA anticodon with the next mRNA codon in the sequence. Once the anticodon and codon sequences are bound (remember, they are complementary base pairs), the tRNA presents its amino acid cargo and the growing polypeptide strand is attached to this next amino acid. This attachment takes place with the assistance of various enzymes and requires energy. The tRNA molecule then releases the mRNA strand, the mRNA strand shifts one codon over in the ribosome, and the next appropriate tRNA arrives with its matching anticodon. This process continues until the final codon on the mRNA is reached which provides a “stop” message that signals termination of translation and triggers the release of the complete, newly synthesised protein. Thus, a gene within the DNA molecule is transcribed into mRNA, which is then translated into a protein product (Figure 2.9.5).

Diagram of DNA to protein
Figure 2.9.5. From DNA to protein: transcription through translation. Transcription within the cell nucleus produces an mRNA molecule, which is modified and then sent into the cytoplasm for translation. The transcript is decoded into a protein with the help of a ribosome and tRNA molecules.

Commonly, an mRNA transcription will be translated simultaneously by several adjacent ribosomes. This increases the efficiency of protein synthesis. A single ribosome might translate an mRNA molecule in approximately one minute; so multiple ribosomes aboard a single transcript could produce multiple times the number of the same protein in the same minute. A polyribosome is a string of ribosomes translating a single mRNA strand.

Section Review

DNA stores the information necessary for instructing the cell to perform all its functions. Cells use the genetic code stored within DNA to build proteins, which ultimately determine the structure and function of the cell. This genetic code lies in the particular sequence of nucleotides that make up each gene along the DNA molecule. To “read” this code, the cell must perform two sequential steps. In the first step, transcription, the DNA code is converted into a RNA code. A molecule of messenger RNA that is complementary to a specific gene is synthesised in a process like DNA replication. The molecule of mRNA provides the code to synthesise a protein. In the process of translation, the mRNA attaches to a ribosome. Next, tRNA molecules shuttle the appropriate amino acids to the ribosome, one-by-one, coded by sequential triplet codons on the mRNA, until the protein is fully synthesised. When completed, the mRNA detaches from the ribosome, and the protein is released. Typically, multiple ribosomes attach to a single mRNA molecule at once such that multiple proteins can be manufactured from the mRNA concurrently.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=119

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=119

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=119

Click the drop down below to review the terms learnt from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=119

2.10 Cell Growth and Division

Learning Objectives

By the end of this section, you will be able to:

  • Describe the stages of the cell cycle
  • Discuss how the cell cycle is regulated
  • Describe the implications of losing control over the cell cycle
  • Describe the stages of mitosis and cytokinesis, in order

So far in this chapter, you have read numerous times of the importance and prevalence of cell division. While there are a few cells in the body that do not undergo cell division (such as gametes, red blood cells, most neurons, and some muscle cells), most somatic cells divide regularly. A somatic cell is a general term for a body cell, and all human cells, except for the cells that produce eggs and sperm (which are referred to as germ cells), are somatic cells. Somatic cells contain two copies of each of their chromosomes (one copy received from each parent). A homologous pair of chromosomes is the two copies of a single chromosome found in each somatic cell. The human is a diploid organism, having 23 homologous pairs of chromosomes in each of the somatic cells. The condition of having pairs of chromosomes is known as diploidy.

Cells in the body replace themselves over the lifetime of a person. For example, the cells lining the gastrointestinal tract must be frequently replaced when constantly “worn off” by the movement of food through the gut. But what triggers a cell to divide, and how does it prepare for and complete cell division? The cell cycle is the sequence of events in the life of the cell from the moment it is created at the end of a previous cycle of cell division until it then divides itself, generating two new cells.

The Cell Cycle

One “turn” or cycle of the cell cycle consists of two general phases: interphase, followed by mitosis and cytokinesis. Interphase is the period of the cell cycle during which the cell is not dividing. The majority of cells are in interphase most of the time. Mitosis is the division of genetic material, during which the cell nucleus breaks down and two new, fully functional, nuclei are formed. Cytokinesis divides the cytoplasm into two distinctive cells.

Interphase

Diagram of the cycle of a cell
Figure 2.10.1. Cell cycle. The two major phases of the cell cycle include mitosis (cell division), and interphase, when the cell grows and performs all of its normal functions. Interphase is further subdivided into G1, S, and G2 phases.

A cell grows and carries out all normal metabolic functions and processes in a period called G1 (Figure 2.10.1). G1 phase (gap 1 phase) is the first gap, or growth phase in the cell cycle. For cells that will divide again, G1 is followed by replication of the DNA, during the S phase. The S phase (synthesis phase) is period during which a cell replicates its DNA.

After the synthesis phase, the cell proceeds through the G2 phase. The G2 phase is a second gap phase, during which the cell continues to grow and makes the necessary preparations for mitosis. Between G1, S, and G2 phases, cells will vary the most in their duration of the G1 phase. It is here that a cell might spend a couple of hours, or many days. The S phase typically lasts between 8-10 hours and the G2 phase approximately 5 hours. In contrast to these phases, the G0 phase is a resting phase of the cell cycle. Cells that have temporarily stopped dividing and are resting (a common condition) and cells that have permanently ceased dividing (like nerve cells) are said to be in G0.

The Structure of Chromosomes

Billions of cells in the human body divide every day. During the synthesis phase (S, for DNA synthesis) of interphase, the amount of DNA within the cell precisely doubles. Therefore, after DNA replication but before cell division, each cell contains two copies of each chromosome. Each copy of the chromosome is referred to as a sister chromatid and is physically bound to the other copy. The centromere is the structure that attaches one sister chromatid to another. Because a human cell has 46 chromosomes, during this phase, there are 92 chromatids (46 × 2) in the cell. Make sure not to confuse the concept of a pair of chromatids (one chromosome and its exact copy attached during mitosis) and a homologous pair of chromosomes (two paired chromosomes which were inherited separately, one from each parent) (Figure 2.10.2).

A homologous pair of chromosomes with their attached sister chromatids.
Figure 2.10.2. A homologous pair of chromosomes with their attached sister chromatids. The red and blue colours correspond to a homologous pair of chromosomes. Each member of the pair was separately inherited from one parent. Each chromosome in the homologous pair is also bound to an identical sister chromatid, which is produced by DNA replication, and results in the familiar “X” shape.

Mitosis and Cytokinesis

The mitotic phase of the cell typically takes between 1 and 2 hours. During this phase, a cell undergoes two major processes. First, it completes mitosis, during which the contents of the nucleus are equitably pulled apart and distributed between its two halves. Cytokinesis then occurs, dividing the cytoplasm and cell body into two new cells. Mitosis is divided into four major stages that take place after interphase (Figure 2.10.3) and in the following order: prophase, metaphase, anaphase, and telophase. The process is then followed by cytokinesis.

 

Diagram of Cell division: mitosis followed by cytokinesis.
Figure 2.10.3. Cell division: mitosis followed by cytokinesis. The stages of cell division oversee the separation of identical genetic material into two new nuclei, followed by the division of the cytoplasm.

Prophase is the first phase of mitosis, during which the loosely packed chromatin coils and condenses into visible chromosomes. During prophase, each chromosome becomes visible with its identical partner attached, forming the familiar X-shape of sister chromatids. The nucleolus disappears early during this phase, and the nuclear envelope also disintegrates.

A major occurrence during prophase concerns a very important structure that contains the origin site for microtubule growth. Recall the cellular structures called centrioles that serve as origin points from which microtubules extend. These tiny structures also play a very important role during mitosis. A centrosome is a pair of centrioles together. The cell contains two centrosomes side-by-side, which begin to move apart during prophase. As the centrosomes migrate to two different sides of the cell, microtubules begin to extend from each like long fingers from two hands extending toward each other. The mitotic spindle is the structure composed of the centrosomes and their emerging microtubules.

Near the end of prophase there is an invasion of the nuclear area by microtubules from the mitotic spindle. The nuclear membrane has disintegrated, and the microtubules attach themselves to the centromeres that adjoin pairs of sister chromatids. The kinetochore is a protein structure on the centromere that is the point of attachment between the mitotic spindle and the sister chromatids. This stage is referred to as late prophase or “prometaphase” to indicate the transition between prophase and metaphase.

Metaphase is the second stage of mitosis. During this stage, the sister chromatids, with their attached microtubules, line up along a linear plane in the middle of the cell. A metaphase plate forms between the centrosomes that are now located at either end of the cell. The metaphase plate is the name for the plane through the centre of the spindle on which the sister chromatids are positioned. The microtubules are now poised to pull apart the sister chromatids and bring one from each pair to each side of the cell.

Anaphase is the third stage of mitosis. Anaphase takes place over a few minutes, when the pairs of sister chromatids are separated from one another, forming individual chromosomes once again. These chromosomes are pulled to opposite ends of the cell by their kinetochores, as the microtubules shorten. Each end of the cell receives one partner from each pair of sister chromatids, ensuring that the two new daughter cells will contain identical genetic material.

Telophase is the final stage of mitosis. Telophase is characterised by the formation of two new daughter nuclei at either end of the dividing cell. These newly formed nuclei surround the genetic material, which uncoils such that the chromosomes return to loosely packed chromatin. Nucleoli also reappear within the new nuclei, and the mitotic spindle breaks apart, each new cell receiving its own complement of DNA, organelles, membranes, and centrioles. At this point, the cell is already beginning to split in half as cytokinesis begins.

The cleavage furrow is a contractile band made up of microfilaments that forms around the midline of the cell during cytokinesis. (Recall that microfilaments consist of actin.) This contractile band squeezes the two cells apart until they finally separate. Two new cells are now formed. One of these cells (the “stem cell”) enters its own cell cycle; able to grow and divide again at some future time. The other cell transforms into the functional cell of the tissue, typically replacing an “old” cell there.

Imagine a cell that completed mitosis but never underwent cytokinesis. In some cases, a cell may divide its genetic material and grow in size, but fail to undergo cytokinesis. This results in larger cells with more than one nucleus. Usually this is an unwanted aberration and can be a sign of cancerous cells.

Cell Cycle Control

A very elaborate and precise system of regulation controls direct the way cells proceed from one phase to the next in the cell cycle and begin mitosis. The control system involves molecules within the cell as well as external triggers. These internal and external control triggers provide “stop” and “advance” signals for the cell. Precise regulation of the cell cycle is critical for maintaining the health of an organism, and loss of cell cycle control can lead to cancer.

Mechanisms of Cell Cycle Control

As the cell proceeds through its cycle, each phase involves certain processes that must be completed before the cell should advance to the next phase. A checkpoint is a point in the cell cycle at which the cycle can be signalled to move forward or stopped. At each of these checkpoints, different varieties of molecules provide the stop or go signals, depending on certain conditions within the cell. A cyclin is one of the primary classes of cell cycle control molecules (Figure 2.10.4). A cyclin-dependent kinase (CDK) is one of a group of molecules that work together with cyclins to determine progression past cell checkpoints. By interacting with many additional molecules, these triggers push the cell cycle forward unless prevented from doing so by “stop” signals, if for some reason the cell is not ready. At the G1 checkpoint, the cell must be ready for DNA synthesis to occur. At the G2 checkpoint the cell must be fully prepared for mitosis. Even during mitosis, a crucial stop and go checkpoint in metaphase ensures that the cell is fully prepared to complete cell division. The metaphase checkpoint ensures that all sister chromatids are properly attached to their respective microtubules and lined up at the metaphase plate before the signal is given to separate them during anaphase.

Diagram of control of cell cycle
Figure 2.10.4. Control of the cell cycle. Cells proceed through the cell cycle under the control of a variety of molecules, such as cyclins and cyclin-dependent kinases. These control molecules determine whether or not the cell is prepared to move into the following stage.

The Cell Cycle Out of Control: Implications

Most people understand that cancer or tumours are caused by abnormal cells that multiply continuously. If the abnormal cells continue to divide unstopped, they can damage the tissues around them, spread to other parts of the body, and eventually result in death. In healthy cells, the tight regulation mechanisms of the cell cycle prevent this from happening, while failures of cell cycle control can cause unwanted and excessive cell division. Failures of control may be caused by inherited genetic abnormalities that compromise the function of certain “stop” and “go” signals. Environmental insult that damages DNA can also cause dysfunction in those signals. Often, a combination of both genetic predisposition and environmental factors lead to cancer.

The process of a cell escaping its normal control system and becoming cancerous may actually happen throughout the body quite frequently. Fortunately, certain cells of the immune system are capable of recognising cells that have become cancerous and destroying them. However, in certain cases the cancerous cells remain undetected and continue to proliferate. If the resulting tumour does not pose a threat to surrounding tissues, it is said to be benign and can usually be easily removed. If capable of damage, the tumour is considered malignant and the patient is diagnosed with cancer.

Homeostatic Imbalances

Cancer Arises from Homeostatic Imbalances

Cancer is an extremely complex condition, capable of arising from a wide variety of genetic and environmental causes. Typically, mutations or aberrations in a cell’s DNA that compromise normal cell cycle control systems lead to cancerous tumours. Cell cycle control is an example of a homeostatic mechanism that maintains proper cell function and health. While progressing through the phases of the cell cycle, a large variety of intracellular molecules provide stop and go signals to regulate movement forward to the next phase. These signals are maintained in an intricate balance so that the cell only proceeds to the next phase when it is ready. This homeostatic control of the cell cycle can be thought of like a car’s cruise control. Cruise control will continually apply just the right amount of acceleration to maintain a desired speed, unless the driver hits the brakes, in which case the car will slow down. Similarly, the cell includes molecular messengers, such as cyclins, that push the cell forward in its cycle.

In addition to cyclins, a class of proteins that are encoded by genes called proto-oncogenes provide important signals that regulate the cell cycle and move it forward. Examples of proto-oncogene products include cell-surface receptors for growth factors, or cell-signalling molecules, two classes of molecules that can promote DNA replication and cell division. In contrast, a second class of genes known as tumours suppressor genes sends stop signals during a cell cycle. For example, certain protein products of tumours suppressor genes signal potential problems with the DNA and thus stop the cell from dividing, while other proteins signal the cell to die if it is damaged beyond repair. Some tumours suppressor proteins also signal a sufficient surrounding cellular density, which indicates that the cell need not presently divide. The latter function is uniquely important in preventing tumours growth: normal cells exhibit a phenomenon called “contact inhibition;” thus, extensive cellular contact with neighbouring cells causes a signal that stops further cell division.

These two contrasting classes of genes, proto-oncogenes and tumour suppressor genes, are like the accelerator and brake pedal of the cell’s own “cruise control system,” respectively. Under normal conditions, these stop and go signals are maintained in a homeostatic balance. Generally speaking, there are two ways that the cell’s cruise control can lose control: a malfunctioning (overactive) accelerator, or a malfunctioning (underactive) brake. When compromised through a mutation, or otherwise altered, proto-oncogenes can be converted to oncogenes, which produce oncoproteins that push a cell forward in its cycle and stimulate cell division even when it is undesirable to do so. For example, a cell that should be programmed to self-destruct (a process called apoptosis) due to extensive DNA damage might instead be triggered to proliferate by an oncoprotein. On the other hand, a dysfunctional tumours suppressor gene may fail to provide the cell with a necessary stop signal, also resulting in unwanted cell division and proliferation.

A delicate homeostatic balance between the many proto-oncogenes and tumours suppressor genes delicately controls the cell cycle and ensures that only healthy cells replicate. Therefore, a disruption of this homeostatic balance can cause aberrant cell division and cancerous growths.

Section Review

The life of cell consists of stages that make up the cell cycle. After a cell is ‘born’, it passes through an interphase before it is ready to replicate itself and produce daughter cells. This interphase includes two gap phases (G1 and G2), as well as an S phase, during which its DNA is replicated in preparation for cell division. The cell cycle is under precise regulation by chemical messengers both inside and outside the cell that provide “stop” and “go” signals for movement from one phase to the next. Failures of these signals can result in cells that continue to divide uncontrollably, which can lead to cancer.

Once a cell has completed interphase and is ready for cell division, it proceeds through four separate stages of mitosis (prophase, metaphase, anaphase, and telophase). Telophase is followed by the division of the cytoplasm (cytokinesis), which generates two daughter cells. This process takes place in all normally dividing cells of the body except for the germ cells that produce eggs and sperm.

Review Questions 

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=121

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=121

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=121

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=121

2.11 Cellular Differentiation

Learning Objectives

By the end of this section, you will be able to:

  • Discuss how the generalised cells of a developing embryo or the stem cells of an adult organism become differentiated into specialised cells
  • Distinguish between the categories of stem cells

How does a complex organism such as a human develop from a single cell—a fertilised egg—into the vast array of cell types such as nerve cells, muscle cells, and epithelial cells that characterise the adult? Throughout development and adulthood, the process of cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialised cells become specialised to carry out distinct functions.

Stem Cells

stem cell is an unspecialised cell that can divide without limit as needed and can, under specific conditions, differentiate into specialised cells. Stem cells are divided into several categories according to their potential to differentiate.

The first embryonic cells that arise from the division of the zygote are the ultimate stem cells; these stems cells are described as totipotent because they have the potential to differentiate into any of the cells needed to enable an organism to grow and develop.

The embryonic cells that develop from totipotent stem cells and are precursors to the fundamental tissue layers of the embryo are classified as pluripotent. A pluripotent stem cell is one that has the potential to differentiate into any type of human tissue but cannot support the full development of an organism. These cells then become slightly more specialised and are referred to as multipotent cells.

multipotent stem cell has the potential to differentiate into different types of cells within a given cell lineage or small number of lineages, such as a red blood cell or white blood cell.

Finally, multipotent cells can become further specialised oligopotent cells. An oligopotent stem cell is limited to becoming one of a few different cell types. In contrast, a unipotent cell is fully specialised and can only reproduce to generate more of its own specific cell type.

Stem cells are unique in that they can also continually divide and regenerate new stem cells instead of further specialising. There are different stem cells present at different stages of a human’s life. They include the embryonic stem cells of the embryo, foetal stem cells of the foetus, and adult stem cells in the adult. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of skin. Adult bone marrow has three distinct types of stem cells: hematopoietic stem cells, which give rise to red blood cells, white blood cells and platelets (Figure 2.11.1); endothelial stem cells, which give rise to the endothelial cell types that line blood and lymph vessels; and mesenchymal stem cells, which give rise to the different types of muscle cells.

Diagram of Haematopoiesis.
Figure 2.11.1. Haematopoiesis. The process of haematopoiesis involves the differentiation of multipotent cells into blood and immune cells. The multipotent hematopoietic stem cells give rise to many different cell types, including the cells of the immune system and red blood cells.

Differentiation

When a cell differentiates (becomes more specialised), it may undertake major changes in its size, shape, metabolic activity, and overall function. Because all cells in the body, beginning with the fertilised egg, contain the same DNA, how do the different cell types come to be so different? The answer is analogous to a movie script. The different actors in a movie all read from the same script, however, they are each only reading their own part of the script. Similarly, all cells contain the same full complement of DNA, but each type of cell only “reads” the portions of DNA that are relevant to its own function. In biology, this is referred to as the unique genetic expression of each cell.

In order for a cell to differentiate into its specialised form and function, it need only manipulate those genes (and thus those proteins) that will be expressed, and not those that will remain silent. The primary mechanism by which genes are turned “on” or “off” is through transcription factors. A transcription factor is one of a class of proteins that bind to specific genes on the DNA molecule and either promote or inhibit their transcription (Figure 2.11.2).

Diagram of gene expression regulation
Figure 2.11.2. Transcription factors regulate gene expression. While each body cell contains the organism’s entire genome, different cells regulate gene expression with the use of various transcription factors. Transcription factors are proteins that affect the binding of RNA polymerase to a particular gene on the DNA molecule.

Everyday Connection

Stem Cell Research

Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of ageing and lose their ability to divide and repair themselves. Stem cells do not display a particular morphology or function. Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialised cells generally formed by that tissue. These cells enable the body to renew and repair body tissues.

The mechanisms that induce a non-differentiated cell to become a specialised cell are poorly understood. In a laboratory setting, it is possible to induce stem cells to differentiate into specialised cells by changing the physical and chemical conditions of growth. Several sources of stem cells are used experimentally and are classified according to their origin and potential for differentiation. Human embryonic stem cells (hESCs) are extracted from embryos and are pluripotent. The adult stem cells that are present in many organs and differentiated tissues, such as bone marrow and skin, are multipotent, being limited in differentiation to the types of cells found in those tissues. The stem cells isolated from umbilical cord blood are also multipotent, as are cells from deciduous teeth (baby teeth). Researchers have recently developed induced pluripotent stem cells (iPSCs) from mouse and human adult stem cells. These cells are genetically reprogrammed multipotent adult cells that function like embryonic stem cells; they are capable of generating cells characteristic of all three germ layers.

Because of their capacity to divide and differentiate into specialised cells, stem cells offer a potential treatment for diseases such as diabetes and heart disease (Figure 2.11.3). Cell-based therapy refers to treatment in which stem cells induced to differentiate in a growth dish are injected into a patient to repair damaged or destroyed cells or tissues. Many obstacles must be overcome for the application of cell-based therapy. Although embryonic stem cells have a nearly unlimited range of differentiation potential, they are seen as foreign by the patient’s immune system and may trigger rejection. Also, the destruction of embryos to isolate embryonic stem cells raises considerable ethical and legal questions.

 

Types of stem cells
Figure 2.11.3. Stem cells. The capacity of stem cells to differentiate into specialised cells make them potentially valuable in therapeutic applications designed to replace damaged cells of different body tissues.

In contrast, adult stem cells isolated from a patient are not seen as foreign by the body, but they have a limited range of differentiation. Some individuals bank the cord blood or deciduous teeth of their child, storing away those sources of stem cells for future use, should their child need it. Induced pluripotent stem cells are considered a promising advance in the field because using them avoids the legal, ethical and immunological pitfalls of embryonic stem cells.

Section Review

One of the major areas of research in biology is that of how cells specialise to assume their unique structures and functions, since all cells essentially originate from a single fertilised egg. Cell differentiation is the process of cells becoming specialised as they body develops. A stem cell is an unspecialised cell that can divide without limit as needed and can, under specific conditions, differentiate into specialised cells. Stem cells are divided into several categories according to their potential to differentiate. While all somatic cells contain the exact same genome, different cell types only express some of those genes at any given time. These differences in gene expression ultimately dictate a cell’s unique morphological and physiological characteristics. The primary mechanism that determines which genes will be expressed and which ones will not is through the use of different transcription factor proteins, which bind to DNA and promote or hinder the transcription of different genes. Through the action of these transcription factors, cells specialise into one of hundreds of different cell types in the human body.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=123

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=123

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=123

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=123

III

Tissues, Organs, Systems

3.1 Types of Tissues

Learning Objectives

By the end of this section, you will be able to:

  • Identify the four main tissue types
  • Discuss the functions of each tissue type
  • Relate the structure of each tissue type to their function
  • Discuss the embryonic origin of tissue
  • Identify the three major germ layers
  • Identify the main types of tissue membranes

The term tissue is used to describe a group of cells found together in the body. The cells within a tissue share a common embryonic origin. Microscopic observation reveals that the cells in a tissue share morphological features and are arranged in an orderly pattern that achieves the tissue’s functions. From the evolutionary perspective, tissues appear in more complex organisms. For example, multicellular protists, ancient eukaryotes, do not have cells organised into tissues.

Although there are many types of cells in the human body, they are organised into four broad categories of tissues: epithelial, connective, muscle, and nervous. Each of these categories is characterised by specific functions that contribute to the overall health and maintenance of the body. A disruption of the structure is a sign of injury or disease. Such changes can be detected through histology, the microscopic study of tissue appearance, organisation, and function.

The Four Types of Tissues

Epithelial tissue, also referred to as epithelium, refers to the sheets of cells that cover exterior surfaces of the body, lines internal cavities and passageways, and forms certain glands. Connective tissue, as its name implies, binds the cells and organs of the body together and functions in the protection, support, and integration of all parts of the body. Muscle tissue is excitable, responding to stimulation and contracting to provide movement, and occurs as three major types: skeletal (voluntary) muscle, smooth muscle, and cardiac muscle in the heart. Nervous tissue is also excitable, allowing the propagation of electrochemical signals in the form of nerve impulses that communicate between different regions of the body (Figure 3.1.1).

The next level of organisation is the organ, where several types of tissues come together to form a working unit. Just as knowing the structure and function of cells helps you in your study of tissues, knowledge of tissues will help you understand how organs function. The epithelial and connective tissues are discussed in detail in this chapter. Muscle and nervous tissues will be discussed only briefly in this chapter.

Diagram of human body highlighting the four types of tissue- nervous tissue, epithelial tissue, muscle tissue and connective tissue
Figure 3.1.1. Four types of tissue: body. The four types of tissues are exemplified in nervous tissue, stratified squamous epithelial tissue, cardiac muscle tissue, and connective tissue in small intestine. Clockwise from nervous tissue, LM × 872, LM × 282, LM × 460, LM × 800. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Embryonic Origin of Tissues

The zygote, or fertilised egg, is a single cell formed by the fusion of an egg and sperm. After fertilisation the zygote gives rise to rapid mitotic cycles, generating many cells to form the embryo. The first embryonic cells generated can differentiate into any type of cell in the body and, as such, are called totipotent, meaning each has the capacity to divide, differentiate, and develop into a new organism. As cell proliferation progresses, three major cell lineages are established within the embryo. Each of these lineages of embryonic cells forms the distinct germ layers from which all the tissues and organs of the human body eventually form. Each germ layer is identified by its relative position: ectoderm (ecto- = “outer”), mesoderm (meso- = “middle”), and endoderm (endo- = “inner”). Figure 3.1.2 shows the types of tissues and organs associated with the each of the three germ layers. Note that epithelial tissue originates in all three layers, whereas nervous tissue derives primarily from the ectoderm and muscle tissue from mesoderm.

Diagram of origins of tissues dividied into Ectoderm, Mesoderm and Endoderm
Figure 3.1.2. Embryonic origin of tissues and major organs.

Tissue Membranes

tissue membrane is a thin layer or sheet of cells that covers the outside of the body (for example, skin), the organs (for example, pericardium), internal passageways that lead to the exterior of the body (for example, abdominal mesenteries), and the lining of the moveable joint cavities. There are two basic types of tissue membranes: connective tissue and epithelial membranes (Figure 3.1.3).

Diagram of human body highlighting tissue membrances ncluding mucous membrances, serous membranes, cutaneous membrane and synovial membranes
Figure 3.1.3. Tissue membranes. The two broad categories of tissue membranes in the body are (1) connective tissue membranes, which include synovial membranes, and (2) epithelial membranes, which include mucous membranes, serous membranes, and the cutaneous membrane, in other words, the skin.

Connective Tissue Membranes

The connective tissue membrane is formed solely from connective tissue. These membranes encapsulate organs, such as the kidneys, and line our movable joints. A synovial membrane is a type of connective tissue membrane that lines the cavity of a freely movable joint. For example, synovial membranes surround the joints of the shoulder, elbow, and knee. Fibroblasts in the inner layer of the synovial membrane release hyaluronan into the joint cavity. The hyaluronan effectively traps available water to form the synovial fluid, a natural lubricant that enables the bones of a joint to move freely against one another without much friction. This synovial fluid readily exchanges water and nutrients with blood, as do all body fluids.

Epithelial Membranes

The epithelial membrane is composed of epithelium attached to a layer of connective tissue, for example, your skin. The mucous membrane is also a composite of connective and epithelial tissues. Sometimes called mucosae, these epithelial membranes line the body cavities and hollow passageways that open to the external environment, and include the digestive, respiratory, excretory, and reproductive tracts. Mucous, produced by the epithelial exocrine glands, covers the epithelial layer. The underlying connective tissue, called the lamina propria (literally “own layer”), help support the fragile epithelial layer.

serous membrane is an epithelial membrane composed of mesodermally derived epithelium called the mesothelium that is supported by connective tissue. These membranes line the coelomic cavities of the body, that is, those cavities that do not open to the outside, and they cover the organs located within those cavities. They are essentially membranous bags, with mesothelium lining the inside and connective tissue on the outside. Serous fluid secreted by the cells of the thin squamous mesothelium lubricates the membrane and reduces abrasion and friction between organs. Serous membranes are identified according locations. Three serous membranes line the thoracic cavity; the two pleura that cover the lungs and the pericardium that covers the heart. A fourth, the peritoneum, is the serous membrane in the abdominal cavity that covers abdominal organs and forms double sheets of mesenteries that suspend many of the digestive organs.

The skin is an epithelial membrane also called the cutaneous membrane. It is a stratified squamous epithelial membrane resting on top of connective tissue. The apical surface of this membrane is exposed to the external environment and is covered with dead, keratinised cells that help protect the body from desiccation and pathogens.

Section Review

The human body contains more than 200 types of cells that can all be classified into four types of tissues: epithelial, connective, muscle, and nervous. Epithelial tissues act as coverings controlling the movement of materials across the surface. Connective tissue integrates the various parts of the body and provides support and protection to organs. Muscle tissue allows the body to move. Nervous tissues propagate information.

The study of the shape and arrangement of cells in tissue is called histology. All cells and tissues in the body derive from three germ layers in the embryo: the ectoderm, mesoderm, and endoderm.

Different types of tissues form membranes that enclose organs, provide a friction-free interaction between organs, and keep organs together. Synovial membranes are connective tissue membranes that protect and line the joints. Epithelial membranes are formed from epithelial tissue attached to a layer of connective tissue. There are three types of epithelial membranes: mucous, which contain glands; serous, which secrete fluid; and cutaneous which makes up the skin.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=276

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=276

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=276

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=276

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=276

3.2 Epithelial Tissue

Learning Objectives

By the end of this section, you will be able to:

  • Explain the structure and function of epithelial tissue
  • Distinguish between tight junctions, anchoring junctions, and gap junctions
  • Distinguish between simple epithelia and stratified epithelia, as well as between squamous, cuboidal, and columnar epithelia
  • Describe the structure and function of endocrine and exocrine glands and their respective secretions

Most epithelial tissues are essentially large sheets of cells covering all the surfaces of the body exposed to the outside world and lining the outside of organs. Epithelium also forms much of the glandular tissue of the body. Skin is not the only area of the body exposed to the outside. Other areas include the airways, the digestive tract, as well as the urinary and reproductive systems, all of which are lined by an epithelium. Hollow organs and body cavities that do not connect to the exterior of the body, which includes, blood vessels and serous membranes, are lined by endothelium (plural = endothelia), which is a type of epithelium.

Epithelial cells derive from all three major embryonic layers. The epithelia lining the skin, parts of the mouth and nose, and the anus develop from the ectoderm. Cells lining the airways and most of the digestive system originate in the endoderm. The epithelium that lines vessels in the lymphatic and cardiovascular system derives from the mesoderm and is called an endothelium.

All epithelia share some important structural and functional features. This tissue is highly cellular, with little or no extracellular material present between cells. Adjoining cells form a specialised intercellular connection between their cell membranes called a cell junction. The epithelial cells exhibit polarity with differences in structure and function between the exposed or apical facing surface of the cell and the basal surface close to the underlying body structures. The basal lamina, a mixture of glycoproteins and collagen, provides an attachment site for the epithelium, separating it from underlying connective tissue. The basal lamina attaches to a reticular lamina, which is secreted by the underlying connective tissue, forming a basement membrane that helps hold it all together.

Epithelial tissues are nearly completely avascular. For instance, no blood vessels cross the basement membrane to enter the tissue, and nutrients must come by diffusion or absorption from underlying tissues or the surface. Many epithelial tissues are capable of rapidly replacing damaged and dead cells. Sloughing off damaged or dead cells is a characteristic of surface epithelium and allows our airways and digestive tracts to rapidly replace damaged cells with new cells.

Generalised Functions of Epithelial Tissue

Epithelial tissues provide the body’s first line of protection from physical, chemical, and biological wear and tear. The cells of an epithelium act as gatekeepers of the body controlling permeability and allowing selective transfer of materials across a physical barrier. All substances that enter the body must cross an epithelium. Some epithelia often include structural features that allow the selective transport of molecules and ions across their cell membranes.

Many epithelial cells are capable of secretion and release mucous and specific chemical compounds onto their apical surfaces. The epithelium of the small intestine releases digestive enzymes, for example. Cells lining the respiratory tract secrete mucous that traps incoming microorganisms and particles. A glandular epithelium contains many secretory cells.

The Epithelial Cell

Epithelial cells are typically characterised by the polarised distribution of organelles and membrane-bound proteins between their basal and apical surfaces. Particular structures found in some epithelial cells are an adaptation to specific functions. Certain organelles are segregated to the basal sides, whereas other organelles and extensions, such as cilia, when present, are on the apical surface.

Cilia are microscopic extensions of the apical cell membrane that are supported by microtubules. They beat in unison and move fluids as well as trapped particles. Ciliated epithelium lines the ventricles of the brain where it helps circulate the cerebrospinal fluid. The ciliated epithelium of your airway forms a mucociliary escalator that sweeps particles of dust and pathogens trapped in the secreted mucous toward the throat. It is called an escalator because it continuously pushes mucous with trapped particles upward. In contrast, nasal cilia sweep the mucous blanket down towards your throat. In both cases, the transported materials are usually swallowed, and end up in the acidic environment of your stomach.

Cell to Cell Junctions

Cells of epithelia are closely connected and are not separated by intracellular material. Three basic types of connections allow varying degrees of interaction between the cells: tight junctions, anchoring junctions, and gap junctions (Figure 3.2.1).

Diagram of differnt types of cell junctions - tight junctions, gap junctions and anchoring junctions
Figure 3.2.1. Types of cell junctions. The three basic types of cell-to-cell junctions are tight junctions, gap junctions, and anchoring junctions.

At one end of the spectrum is the tight junction, which separates the cells into apical and basal compartments. An anchoring junction includes several types of cell junctions that help stabilise epithelial tissues. Anchoring junctions are common on the lateral and basal surfaces of cells where they provide strong and flexible connections. There are three types of anchoring junctions: desmosomes, hemidesmosomes, and adherens. Desmosomes occur in patches on the membranes of cells. The patches are structural proteins on the inner surface of the cell’s membrane. The adhesion molecule, cadherin, is embedded in these patches and projects through the cell membrane to link with the cadherin molecules of adjacent cells. These connections are especially important in holding cells together. Hemidesmosomes, which look like half a desmosome, link cells to the extracellular matrix, for example, the basal lamina. While similar in appearance to desmosomes, they include the adhesion proteins called integrins rather than cadherins. Adherens junctions use either cadherins or integrins depending on whether they are linking to other cells or matrix. The junctions are characterised by the presence of the contractile protein actin located on the cytoplasmic surface of the cell membrane. The actin can connect isolated patches or form a belt-like structure inside the cell. These junctions influence the shape and folding of the epithelial tissue.

In contrast with the tight and anchoring junctions, a gap junction forms an intercellular passageway between the membranes of adjacent cells to facilitate the movement of small molecules and ions between the cytoplasm of adjacent cells. These junctions allow electrical and metabolic coupling of adjacent cells, which coordinates function in large groups of cells.

Classification of Epithelial Tissues

Epithelial tissues are classified according to the shape of the cells and number of the cell layers formed (Figure 3.2.2). Cell shapes can be squamous (flattened and thin), cuboidal (boxy, as wide as it is tall), or columnar (rectangular, taller than it is wide). Similarly, the number of cell layers in the tissue can be one—where every cell rests on the basal lamina—which is a simple epithelium, or more than one, which is a stratified epithelium and only the basal layer of cells rests on the basal lamina. Pseudostratified (pseudo- = “false”) describes tissue with a single layer of irregularly shaped cells that give the appearance of more than one layer. Transitional describes a form of specialised stratified epithelium in which the shape of the cells can vary.

Diagram of cells of epithelial tissue including squamous, cudoidal and columnar
Figure 3.2.2. Cells of epithelial tissue. Simple epithelial tissue is organised as a single layer of cells and stratified epithelial tissue is formed by several layers of cells.

Simple Epithelium

The shape of the cells in the single cell layer of simple epithelium reflects the functioning of those cells. The cells in simple squamous epithelium have the appearance of thin scales. Squamous cell nuclei tend to be flat, horizontal, and elliptical, mirroring the form of the cell. The endothelium is the epithelial tissue that lines vessels of the lymphatic and cardiovascular system, and it is made up of a single layer of squamous cells. Simple squamous epithelium, because of the thinness of the cell, is present where rapid passage of chemical compounds is observed. The alveoli of lungs where gases diffuse, segments of kidney tubules, and the lining of capillaries are also made of simple squamous epithelial tissue. The mesothelium is a simple squamous epithelium that forms the surface layer of the serous membrane that lines body cavities and internal organs. Its primary function is to provide a smooth and protective surface. Mesothelial cells are squamous epithelial cells that secrete a fluid that lubricates the mesothelium.

In simple cuboidal epithelium, the nucleus of the box-like cells appears round and is generally located near the centre of the cell. These epithelia are active in the secretion and absorptions of molecules. Simple cuboidal epithelia are observed in the lining of the kidney tubules and in the ducts of glands.

In simple columnar epithelium, the nucleus of the tall column-like cells tends to be elongated and located in the basal end of the cells. Like the cuboidal epithelia, this epithelium is active in the absorption and secretion of molecules. Simple columnar epithelium forms the lining of some sections of the digestive system and parts of the female reproductive tract. Ciliated columnar epithelium is composed of simple columnar epithelial cells with cilia on their apical surfaces. These epithelial cells are found in the lining of the fallopian tubes and parts of the respiratory system, where the beating of the cilia helps remove particulate matter.

Pseudostratified columnar epithelium is a type of epithelium that appears to be stratified but instead consists of a single layer of irregularly shaped and differently sized columnar cells. In pseudostratified epithelium, nuclei of neighbouring cells appear at different levels rather than clustered in the basal end. The arrangement gives the appearance of stratification; but in fact, all the cells are in contact with the basal lamina, although some do not reach the apical surface. Pseudostratified columnar epithelium is found in the respiratory tract, where some of these cells have cilia.

Both simple and pseudostratified columnar epithelia are heterogeneous epithelia because they include additional types of cells interspersed among the epithelial cells. For example, a goblet cell is a mucous-secreting unicellular “gland” interspersed between the columnar epithelial cells of mucous membranes (Figure 3.2.3).

Diagram and photograph of goblet cell
Figure 3.2.3. Goblet cell. (a) In the lining of the small intestine, columnar epithelium cells are interspersed with goblet cells. (b) The arrows in this micrograph point to the mucous-secreting goblet cells. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Stratified Epithelium

A stratified epithelium consists of several stacked layers of cells. This epithelium protects against physical and chemical wear and tear. The stratified epithelium is named by the shape of the most apical layer of cells, closest to the free space. Stratified squamous epithelium is the most common type of stratified epithelium in the human body. The apical cells are squamous, whereas the basal layer contains either columnar or cuboidal cells. The top layer may be covered with dead cells filled with keratin. Mammalian skin is an example of this dry, keratinised, stratified squamous epithelium. The lining of the mouth cavity is an example of an unkeratinised, stratified squamous epithelium. Stratified cuboidal epithelium and stratified columnar epithelium can also be found in certain glands and ducts but are uncommon in the human body.

Another kind of stratified epithelium is transitional epithelium, so-called because of the gradual changes in the shapes of the apical cells as the bladder fills with urine. It is found only in the urinary system, specifically the ureters and urinary bladder. When the bladder is empty, this epithelium is convoluted and has cuboidal apical cells with convex, umbrella shaped, apical surfaces. As the bladder fills with urine, this epithelium loses its convolutions and the apical cells transition from cuboidal to squamous. It appears thicker and more multi-layered when the bladder is empty, and more stretched out and less stratified when the bladder is full and distended. Figure 3.2.4 summarises the different categories of epithelial cell tissue cells.

Summary table of epithelial tissue cells
Figure 3.2.4. Summary of epithelial tissue cells.

Glandular Epithelium

A gland is a structure made up of one or more cells modified to synthesise and secrete chemical substances. Most glands consist of groups of epithelial cells. A gland can be classified as an endocrine gland, a ductless gland that releases secretions directly into surrounding tissues and fluids (endo- = “inside”), or an exocrine gland whose secretions leave through a duct that opens directly, or indirectly, to the external environment (exo- = “outside”).

Endocrine Glands

The secretions of endocrine glands are called hormones. Hormones are released into the interstitial fluid, diffused into the bloodstream, and delivered to targets, in other words, cells that have receptors to bind the hormones. The endocrine system is part of a major regulatory system coordinating the regulation and integration of body responses. A few examples of endocrine glands include the anterior pituitary, thymus, adrenal cortex, and gonads.

Exocrine Glands

Exocrine glands release their contents through a duct that leads to the epithelial surface. Mucous, sweat, saliva, and breast milk are all examples of secretions from exocrine glands. They are all discharged through tubular ducts. Secretions into the lumen of the gastrointestinal tract, technically outside of the body, are of the exocrine category.

Glandular Structure

Exocrine glands are classified as either unicellular or multicellular. The unicellular glands are scattered single cells, such as goblet cells, found in the mucous membranes of the small and large intestine.

The multicellular exocrine glands known as serous glands develop from simple epithelium to form a secretory surface that secretes directly into an inner cavity. These glands line the internal cavities of the abdomen and chest and release their secretions directly into the cavities. Other multicellular exocrine glands release their contents through a tubular duct. The duct is single in a simple gland but in compound glands is divided into one or more branches (Figure 3.2.5). In tubular glands, the ducts can be straight or coiled, whereas tubes that form pockets are alveolar (acinar), such as the exocrine portion of the pancreas. Combinations of tubes and pockets are known as tubuloalveolar (tubuloacinar) compound glands. In a branched gland, a duct is connected to more than one secretory group of cells.

Diagram of types of exocrine glands such as mammary glands, salivary glands and mucous glands
Figure 3.2.5. Types of exocrine glands. Exocrine glands are classified by their structure.

Methods and Types of Secretion

Exocrine glands can be classified by their mode of secretion and the nature of the substances released, as well as by the structure of the glands and shape of ducts (Figure 3.2.6). Merocrine secretion is the most common type of exocrine secretion. The secretions are enclosed in vesicles that move to the apical surface of the cell where the contents are released by exocytosis. For example, watery mucous containing the glycoprotein mucin, a lubricant that offers some pathogen protection is a merocrine secretion. The eccrine glands that produce and secrete sweat are another example.

Diagram of modes of glandular secrtion including mercocrine, apocrine and holocrine secretion
Figure 3.2.6. Modes of glandular secretion. (a) In merocrine secretion, the cell remains intact. (b) In apocrine secretion, the apical portion of the cell is released, as well. (c) In holocrine secretion, the cell is destroyed as it releases its product and the cell itself becomes part of the secretion.

Apocrine secretion accumulates near the apical portion of the cell. That portion of the cell and its secretory contents pinch off from the cell and are released. The sweat glands of the armpit are classified as apocrine glands. Both merocrine and apocrine glands continue to produce and secrete their contents with little damage caused to the cell because the nucleus and Golgi regions remain intact after secretion.

In contrast, the process of holocrine secretion involves the rupture and destruction of the entire gland cell. The cell accumulates its secretory products and releases them only when it bursts. New gland cells differentiate from cells in the surrounding tissue to replace those lost by secretion. The sebaceous glands that produce the oils on the skin and hair are holocrine glands/cells (Figure 3.2.7).

Diagram and image of sebaceous glands
Figure 3.2.7. Sebaceous glands. These glands secrete oils that lubricate and protect the skin. They are holocrine glands and they are destroyed after releasing their contents. New glandular cells form to replace the cells that are lost. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Glands are also named after the products they produce. The serous gland produces watery, blood-plasma-like secretions rich in enzymes such as alpha amylase, whereas the mucous gland releases watery to viscous products rich in the glycoprotein mucin. Both serous and mucous glands are common in the salivary glands of the mouth. Mixed exocrine glands contain both serous and mucous glands and release both types of secretions.

Section Review

In epithelial tissue, cells are closely packed with little or no extracellular matrix except for the basal lamina that separates the epithelium from underlying tissue. The main functions of epithelia are protection from the environment, coverage, secretion and excretion, absorption, and filtration. Cells are bound together by tight junctions that form an impermeable barrier. They can also be connected by gap junctions, which allow free exchange of soluble molecules between cells, and anchoring junctions, which attach cell to cell or cell to matrix. The different types of epithelial tissues are characterised by their cellular shapes and arrangements: squamous, cuboidal, or columnar epithelia. Single cell layers form simple epithelia, whereas stacked cells form stratified epithelia. Very few capillaries penetrate these tissues.

Glands are secretory tissues and organs that are derived from epithelial tissues. Exocrine glands release their products through ducts. Endocrine glands secrete hormones directly into the interstitial fluid and blood stream. Glands are classified both according to the type of secretion and by their structure. Merocrine glands secrete products as they are synthesised. Apocrine glands release secretions by pinching off the apical portion of the cell, whereas holocrine gland cells store their secretions until they rupture and release their contents. In this case, the cell becomes part of the secretion.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=278

Critical Thinking Question

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=278

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=278

3.3 Connective Tissue Supports and Protects

Learning Objectives

By the end of this section, you will be able to:

  • Identify and distinguish between the types of connective tissue: proper, supportive, and fluid
  • Explain the functions of connective tissues

As may be obvious from its name, one of the major functions of connective tissue is to connect tissues and organs. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. The matrix plays a major role in the functioning of this tissue. The major component of the matrix is a ground substance often crisscrossed by protein fibres. This ground substance is usually a fluid, but it can also be mineralised and solid, as in bones. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibres. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialised cells; for example, a phagocytic cell that engulfs pathogens and rids tissue of cellular debris.

Functions of Connective Tissues

Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues; from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Specialised cells in connective tissue defend the body from microorganisms that enter the body. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialised fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body.

Embryonic Connective Tissue

All connective tissues derive from the mesodermal layer of the embryo. The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibres found within the matrix (Table 3.3.1). Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibres suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibres that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibres are loosely organised, leaving large spaces in between. Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibres in a matrix characterise these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue, in other words, lymph and blood, various specialised cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.

Table 3.3.1. Connective Tissue Examples

Connective Tissue Proper Supportive Connective Tissue Fluid Connective Tissue
Loose connective tissue Cartilage Blood
• Areolar • Hyaline
• Adipose • Fibrocartilage
• Reticular • Elastic
Dense connective tissue Bones Lymph
• Regular elastic • Compact bone
• Irregular elastic • Cancellous bone

Connective Tissue Proper

Fibroblasts are present in all connective tissue proper (Figure 3.3.1). Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body.

Connective tissue proper
Figure 3.3.1. Connective tissue proper. Fibroblasts produce this fibrous tissue. Connective tissue proper includes the fixed cells fibrocytes, adipocytes, and mesenchymal cells. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Cell Types

The most abundant cell in connective tissue proper is the fibroblast. Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins, forms the extra-cellular matrix. As you might expect, a fibrocyte, a less active form of fibroblast, is the second most common cell type in connective tissue proper.

Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population.

The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue.

The macrophage cell is a large cell derived from a monocyte, a type of blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body’s defence against potential pathogens and degraded host cells. When stimulated, macrophages release cytokines, small proteins that act as chemical messengers. Cytokines recruit other cells of the immune system to infected sites and stimulate their activities. Roaming, or free, macrophages move rapidly by amoeboid movement, engulfing infectious agents and cellular debris. In contrast, fixed macrophages are permanent residents of their tissues.

The mast cell, found in connective tissue proper, has many cytoplasmic granules. These granules contain the chemical signals histamine and heparin. When irritated or damaged, mast cells release histamine, an inflammatory mediator, which causes vasodilation and increased blood flow at a site of injury or infection, along with itching, swelling, and redness you recognise as an allergic response. Like blood cells, mast cells are derived from hematopoietic stem cells and are part of the immune system.

Connective Tissue Fibres and Ground Substance

Three main types of fibres are secreted by fibroblasts: collagen fibres, elastic fibres, and reticular fibres. Collagen fibres is made from fibrous protein subunits linked together to form a long and straight fibres. Collagen fibres, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibres hold connective tissues together, even during the movement of the body.

Elastic fibres contain the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibres are prominent in elastic tissues found in skin and the elastic ligaments of the vertebral column.

Reticular fibres are also formed from the same protein subunits as collagen fibres; however, these fibres remain narrow and are arrayed in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as liver and spleen, where they anchor and provide structural support to the parenchyma (the functional cells, blood vessels, and nerves of the organ).

All these fibres types are embedded in ground substance. Secreted by fibroblasts, ground substance is made of polysaccharides, specifically hyaluronic acid, and proteins. These combine to form a proteoglycan with a protein core and polysaccharide branches. The proteoglycan attracts and traps available moisture forming the clear, viscous, colourless matrix you now know as ground substance.

Loose Connective Tissue

Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or imbedded cells and tissues.

Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 3.3.2). Many capillaries allow rapid storage and mobilisation of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its colour to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys and cushioning the back of the eye. Brown adipose tissue is more common in infants, hence the term “baby fat.” In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolising stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism.

Diagram of adipose tissue
Figure 3.3.2. Adipose tissue. This is a loose connective tissue that consists of fat cells with little extracellular matrix. It stores fat for energy and provides insulation. LM × 800. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Areolar tissue shows little specialisation. It contains all the cell types and fibres previously described and is distributed in a random, web-like fashion. It fills the spaces between muscle fibres, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes, which are described further in a later section.

Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure 3.3.3). Reticular cells produce the reticular fibres that form the network onto which other cells attach. It derives its name from the Latin reticulus, which means “little net.”

Diagram and image of reticular tissue
Figure 3.3.3. Reticular tissue. This is a loose connective tissue made up of a network of reticular fibres that provides a supportive framework for soft organs. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Dense Connective Tissue

Dense connective tissue contains more collagen fibres than does loose connective tissue. Consequently, it displays greater resistance to stretching. There are two major categories of dense connective tissue: regular and irregular. Dense regular connective tissue fibres are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fibre’s orientation. Ligaments and tendons are made of dense regular connective tissue, but in ligaments not all fibres are parallel. Dense regular elastic tissue contains elastin fibres in addition to collagen fibres, which allows the ligament to return to its original length after stretching. The ligaments in the vocal folds and between the vertebrae in the vertebral column are elastic.

In dense irregular connective tissue, the direction of fibres is random. This arrangement gives the tissue greater strength in all directions and less strength in one particular direction. In some tissues, fibres crisscross and form a mesh. In other tissues, stretching in several directions is achieved by alternating layers where fibres run in the same orientation in each layer, and it is the layers themselves that are stacked at an angle. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibres. Dense irregular elastic tissues give arterial walls the strength and the ability to regain original shape after stretching (Figure 3.3.4).

Images of dense connective tissue
Figure 3.3.4. Dense connective tissue. (a) Dense regular connective tissue consists of collagenous fibres packed into parallel bundles. (b) Dense irregular connective tissue consists of collagenous fibres interwoven into a mesh-like network. From top, LM × 1000, LM × 200. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Disorders of the Connective Tissue: Tendinitis

Your opponent stands ready as you prepare to hit the serve, but you are confident that you will smash the ball past your opponent. As you toss the ball high in the air, a burning pain shoots across your wrist and you drop the tennis racket. That dull ache in the wrist that you ignored through the summer is now an unbearable pain. The game is over for now.

After examining your swollen wrist, the doctor in the emergency room announces that you have developed wrist tendinitis. She recommends icing the tender area, taking non-steroidal anti-inflammatory medication to ease the pain and to reduce swelling, and complete rest for a few weeks. She interrupts your protests that you cannot stop playing. She issues a stern warning about the risk of aggravating the condition and the possibility of surgery. She consoles you by mentioning that well known tennis players such as Venus and Serena Williams and Rafael Nadal have also suffered from tendinitis related injuries.

What is tendinitis and how did it happen? Tendinitis is the inflammation of a tendon, the thick band of fibrous connective tissue that attaches a muscle to a bone. The condition causes pain and tenderness in the area around a joint. On rare occasions, a sudden serious injury will cause tendinitis. Most often, the condition results from repetitive motions over time that strain the tendons needed to perform the tasks.

Persons whose jobs and hobbies involve performing the same movements over and over again are often at the greatest risk of tendinitis. You hear of tennis and golfer’s elbow, jumper’s knee, and swimmer’s shoulder. In all cases, overuse of the joint causes a microtrauma that initiates the inflammatory response. Tendinitis is routinely diagnosed through a clinical examination. In case of severe pain, X-rays can be examined to rule out the possibility of a bone injury. Severe cases of tendinitis can even tear loose a tendon. Surgical repair of a tendon is painful. Connective tissue in the tendon does not have abundant blood supply and heals slowly.

While older adults are at risk for tendinitis because the elasticity of tendon tissue decreases with age, active people of all ages can develop tendinitis. Young athletes, dancers, and computer operators; anyone who performs the same movements constantly is at risk for tendinitis. Although repetitive motions are unavoidable in many activities and may lead to tendinitis, precautions can be taken that can lessen the probability of developing tendinitis. For active individuals, stretches before exercising and cross training or changing exercises are recommended. For the passionate athlete, it may be time to take some lessons to improve technique. All of the preventive measures aim to increase the strength of the tendon and decrease the stress put on it. With proper rest and managed care, you will be back on the court to hit that slice-spin serve over the net.

Supportive Connective Tissues

Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs.

Cartilage

The distinctive appearance of cartilage is due to polysaccharides called chondroitin sulphates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes, or cartilage cells, and the space they occupy are called lacunae (singular = lacuna). A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage. Cartilaginous tissue is avascular, thus all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues.

The three main types of cartilage tissue are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure 3.3.5). Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibres and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and covers bones where they meet to form moveable joints. It makes up a template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood. Fibrocartilage is tough because it has thick bundles of collagen fibres dispersed through its matrix. The knee and jaw joints and the intervertebral discs are examples of fibrocartilage. Elastic cartilage contains elastic fibres as well as collagen and proteoglycans. This tissue gives rigid support as well as elasticity. Tug gently at your ear lobes and notice that the lobes return to their initial shape. The external ear contains elastic cartilage.

Image of different types of cartilage including hyaline cartilage, fibrocartilage and elastic cartilage
Figure 3.3.5. Types of cartilage. Cartilage is a connective tissue consisting of collagenous fibres embedded in a firm matrix of chondroitin sulphates. (a) Hyaline cartilage provides support with some flexibility. The example is from dog tissue. (b) Fibrocartilage provides some compressibility and can absorb pressure. (c) Elastic cartilage provides firm but elastic support. From top, LM × 300, LM × 1200, LM × 1016. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Bone

Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone’s rigid extracellular matrix contains mostly collagen fibres embedded in a mineralised ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. Osteocytes, bone cells like chondrocytes, are located within lacunae. The histology of transverse tissue from long bone shows a typical arrangement of osteocytes in concentric circles around a central canal. Bone is a highly vascularised tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time.

Cancellous bone looks like a sponge under the microscope and contains empty spaces between trabeculae, or arches of bone proper. It is lighter than compact bone and found in the interior of some bones and at the end of long bones. Compact bone is solid and has greater structural strength.

Fluid Connective Tissue

Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from hematopoietic stem cells located in bone marrow (Figure 3.3.6). Erythrocytes, red blood cells, transport oxygen and some carbon dioxide. Leukocytes, white blood cells, are responsible for defending against potentially harmful microorganisms or molecules. Platelets are cell fragments involved in blood clotting. Some white blood cells can cross the endothelial layer that lines blood vessels and enter adjacent tissues. Nutrients, salts, and wastes are dissolved in the liquid matrix and transported through the body.

Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are extremely permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph drains into blood vessels, delivering molecules to the blood that could not otherwise directly enter the bloodstream. In this way, specialised lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood.

Image of blood
Figure 3.3.6. Blood: a fluid connective tissue. Blood is a fluid connective tissue containing erythrocytes and various types of leukocytes that circulate in a liquid extracellular matrix. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Section Review

Connective tissue is a heterogeneous tissue with many cell shapes and tissue architecture. Structurally, all connective tissues contain cells that are embedded in an extracellular matrix stabilised by proteins. The chemical nature and physical layout of the extracellular matrix and proteins vary enormously among tissues, reflecting the variety of functions that connective tissue fulfills in the body. Connective tissues separate and cushion organs, protecting them from shifting or traumatic injury. Connect tissues provide support and assist movement, store and transport energy molecules, protect against infections, and contribute to temperature homeostasis.

Many different cells contribute to the formation of connective tissues. They originate in the mesodermal germ layer and differentiate from mesenchyme and hematopoietic tissue in the bone marrow. Fibroblasts are the most abundant and secrete many protein fibres, adipocytes specialise in fat storage, hematopoietic cells from the bone marrow give rise to all the blood cells, chondrocytes form cartilage, and osteocytes form bone. The extracellular matrix contains fluid, proteins, polysaccharide derivatives, and, in the case of bone, mineral crystals. Protein fibres fall into three major groups: collagen fibres that are thick, strong, flexible, and resist stretch; reticular fibres that are thin and form a supportive mesh; and elastin fibres that are thin and elastic.

The major types of connective tissue are connective tissue proper, supportive tissue, and fluid tissue. Loose connective tissue proper includes adipose tissue, areolar tissue, and reticular tissue. These serve to hold organs and other tissues in place and, in the case of adipose tissue, isolate and store energy reserves. The matrix is the most abundant feature for loose tissue although adipose tissue does not have much extracellular matrix. Dense connective tissue proper is richer in fibres and may be regular, with fibres oriented in parallel as in ligaments and tendons, or irregular, with fibres oriented in several directions. Organ capsules (collagenous type) and walls of arteries (elastic type) contain dense irregular connective tissue. Cartilage and bone are supportive tissue. Cartilage contains chondrocytes and is somewhat flexible. Hyaline cartilage is smooth and clear, covers joints, and is found in the growing portion of bones. Fibrocartilage is tough because of extra collagen fibres and forms, among other things, the intervertebral discs. Elastic cartilage can stretch and recoil to its original shape because of its high content of elastic fibres. The matrix contains very few blood vessels. Bones are made of a rigid, mineralised matrix containing calcium salts, crystals, and osteocytes lodged in lacunae. Bone tissue is highly vascularised. Cancellous bone is spongy and less solid than compact bone. Fluid tissue, for example blood and lymph, is characterised by a liquid matrix and no supporting fibres.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=280

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=280

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=280

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=280

3.4 Muscle Tissue and Motion

Learning Objectives

By the end of this section, you will be able to:

  • Identify the three types of muscle tissue
  • Compare and contrast the functions of each muscle tissue type
  • Explain how muscle tissue can enable motion

Muscle tissue is characterised by properties that allow movement. Muscle cells are excitable; they respond to a stimulus. They are contractile, meaning they can shorten and generate a pulling force. When attached between two movable objects, in other words, bones, contractions of the muscles cause the bones to move. Some muscle movement is voluntary, which means it is under conscious control. For example, a person decides to open a book and read a chapter on anatomy. Other movements are involuntary, meaning they are not under conscious control, such as the contraction of your pupil in bright light. Muscle tissue is classified into three types according to structure and function: skeletal, cardiac, and smooth (Table 3.4.1).

Table 3.4.1. Comparison of structure and properties of muscle tissue types

Tissue Histology Function Location
Skeletal Long cylindrical fibre, striated, many peripherally located nuclei Voluntary movement, produces heat, protects organs Attached to bones and around entrance points to body (e.g., mouth, anus)
Cardiac Short, branched, striated, single central nucleus Contracts to pump blood Heart
Smooth Short, spindle-shaped, no evident striation, single nucleus in each fibre Involuntary movement, moves food, involuntary control of respiration, moves secretions, regulates flow of blood in arteries by contraction Walls of major organs and passage ways

Skeletal muscle is attached to bones and its contraction makes possible locomotion, facial expressions, posture, and other voluntary movements of the body. Forty percent of your body mass is made up of skeletal muscle. Skeletal muscles generate heat as a by-product of their contraction and thus participate in thermal homeostasis. Shivering is an involuntary contraction of skeletal muscles in response to perceived lower than normal body temperature. The muscle cell, or myocyte, develops from myoblasts derived from the mesoderm. Myocytes and their numbers remain relatively constant throughout life. Skeletal muscle tissue is arranged in bundles surrounded by connective tissue. Under the light microscope, muscle cells appear striated with many nuclei squeezed along the membranes. The striation is due to the regular alternation of the contractile proteins, actin and myosin, along with the structural proteins that couple the contractile proteins to connective tissues. The cells are multinucleated as a result of the fusion of the many myoblasts that fuse to form each long muscle fibre.

Cardiac muscle forms the contractile walls of the heart. The cells of cardiac muscle, known as cardiomyocytes, also appear striated under the microscope. Unlike skeletal muscle fibres, cardiomyocytes are single cells typically with a single centrally located nucleus. A principal characteristic of cardiomyocytes is that they contract on their own intrinsic rhythms without any external stimulation. Cardiomyocyte attach to one another with specialised cell junctions called intercalated discs. Intercalated discs have both anchoring junctions and gap junctions. Attached cells form long, branching cardiac muscle fibres that are, essentially, a mechanical and electrochemical syncytium allowing the cells to synchronise their actions. The cardiac muscle pumps blood through the body and is under involuntary control. The attachment junctions hold adjacent cells together across the dynamic pressures changes of the cardiac cycle.

Smooth muscle tissue contraction is responsible for involuntary movements in the internal organs. It forms the contractile component of the digestive, urinary, and reproductive systems as well as the airways and arteries. Each cell is spindle shaped with a single nucleus and no visible striations (Figure 3.4.1).

Photos of muscle tissue
Figure 3.4.1. Muscle tissue. (a) Skeletal muscle cells have prominent striation and nuclei on their periphery. (b) Smooth muscle cells have a single nucleus and no visible striations. (c) Cardiac muscle cells appear striated and have a single nucleus. From top, LM × 1600, LM × 1600, LM × 1600. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Section Review

The three types of muscle cells are skeletal, cardiac, and smooth. Their morphologies match their specific functions in the body. Skeletal muscle is voluntary and responds to conscious stimuli. The cells are striated and multinucleated appearing as long, unbranched cylinders. Cardiac muscle is involuntary and found only in the heart. Each cell is striated with a single nucleus and they attach to one another to form long fibres. Cells are attached to one another at intercalated disks. The cells are interconnected physically and electrochemically to act as a syncytium. Cardiac muscle cells contract autonomously and involuntarily. Smooth muscle is involuntary. Each cell is a spindle-shaped fibre and contains a single nucleus. No striations are evident because the actin and myosin filaments do not align in the cytoplasm.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=282

Critical Thing Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=282

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=282

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=282

3.5 Nervous Tissue Mediates Perception and Response

Learning Objectives

By the end of this section, you will be able to:

  • Identify the classes of cells that make up nervous tissue
  • Discuss how nervous tissue mediates perception and response

Nervous tissue is characterised as being excitable and capable of sending and receiving electrochemical signals that provide the body with information. Two main classes of cells make up nervous tissue: the neuron and neuroglia (Figure 3.5.1). Neurons propagate information via electrochemical impulses, called action potentials, which are biochemically linked to the release of chemical signals. Neuroglia play an essential role in supporting neurons and modulating their information propagation.

Diagram and photo of neuron
Figure 3.5.1. The neuron. The cell body of a neuron, also called the soma, contains the nucleus and mitochondria. The dendrites transfer the nerve impulse to the soma. The axon carries the action potential away to another excitable cell. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Neurons display distinctive morphology, well suited to their role as conducting cells, with three main parts. The cell body includes most of the cytoplasm, the organelles, and the nucleus. Dendrites branch off the cell body and appear as thin extensions. A long “tail,” the axon, extends from the neuron body and can be wrapped in an insulating layer known as myelin, which is formed by accessory cells. The synapse is the gap between nerve cells, or between a nerve cell and its target, for example, a muscle or a gland, across which the impulse is transmitted by chemical compounds known as neurotransmitters. Neurons categorised as multipolar neurons have several dendrites and a single prominent axon. Bipolar neurons possess a single dendrite and axon with the cell body, while unipolar neurons have only a single process extending out from the cell body, which divides into a functional dendrite and into a functional axon. When a neuron is sufficiently stimulated, it generates an action potential that propagates down the axon towards the synapse. If enough neurotransmitters are released at the synapse to stimulate the next neuron or target, a response is generated.

The second class of neural cells comprises the neuroglia or glial cells, which have been characterised as having a simple support role. The word “glia” comes from the Greek word for glue. Recent research is shedding light on the more complex role of neuroglia in the function of the brain and nervous system. Astrocyte cells, named for their distinctive star shape, are abundant in the central nervous system. The astrocytes have many functions, including regulation of ion concentration in the intercellular space, uptake and/or breakdown of some neurotransmitters, and formation of the blood-brain barrier, the membrane that separates the circulatory system from the brain. Microglia protect the nervous system against infection but are not nervous tissue because they are related to macrophages. Oligodendrocyte cells produce myelin in the central nervous system (brain and spinal cord) while the Schwann cell produces myelin in the peripheral nervous system (Figure 3.5.2).

Diagram and phto of nervous tissue
Figure 3.5.2. Nervous tissue. Nervous tissue is made up of neurons and neuroglia. The cells of nervous tissue are specialised to transmit and receive impulses. LM × 872. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Section Review

The most prominent cell of the nervous tissue, the neuron, is characterised mainly by its ability to receive stimuli and respond by generating an electrical signal, known as an action potential, which can travel rapidly over great distances in the body. A typical neuron displays a distinctive morphology: a large cell body branches out into short extensions called dendrites, which receive chemical signals from other neurons, and a long tail called an axon, which relays signals away from the cell to other neurons, muscles, or glands. Many axons are wrapped by a myelin sheath, a lipid derivative that acts as an insulator and speeds up the transmission of the action potential. Other cells in the nervous tissue, the neuroglia, include the astrocytes, microglia, oligodendrocytes, and Schwann cells.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=288

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=288

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=288

3.6 Tissue Injury and Ageing

Learning Objectives

By the end of this section, you will be able to:

  • Identify the cardinal signs of inflammation
  • List the body’s response to tissue injury
  • Explain the process of tissue repair
  • Discuss the progressive impact of ageing on tissue
  • Describe cancerous mutations’ effect on tissue

Tissues of all types are vulnerable to injury and, inevitably, ageing. In the former case, understanding how tissues respond to damage can guide strategies to aid repair. In the latter case, understanding the impact of ageing can help in the search for ways to diminish its effects.

Tissue Injury and Repair

Inflammation is the standard, initial response of the body to injury. Whether biological, chemical, physical, or radiation burns, all injuries lead to the same sequence of physiological events. Inflammation limits the extent of injury, partially or fully eliminates the cause of injury, and initiates repair and regeneration of damaged tissue. Necrosis, or accidental cell death, causes inflammation. Apoptosis is programmed cell death, a normal step-by-step process that destroys cells no longer needed by the body. By mechanisms still under investigation, apoptosis does not initiate the inflammatory response. Acute inflammation resolves over time by the healing of tissue. If inflammation persists, it becomes chronic and leads to diseased conditions. Arthritis and tuberculosis are examples of chronic inflammation. The suffix “-itis” denotes inflammation of a specific organ or type, for example, peritonitis is the inflammation of the peritoneum, and meningitis refers to the inflammation of the meninges, the tough membranes that surround the central nervous system

The four cardinal signs of inflammation—redness, swelling, pain and local heat—were first recorded in antiquity. Cornelius Celsus is credited with documenting these signs during the days of the Roman Empire, as early as the first century AD. A fifth sign, loss of function, may also accompany inflammation.

Upon tissue injury, damaged cells release inflammatory chemical signals that evoke local vasodilation, the widening of the blood vessels. Increased blood flow results in apparent redness and heat. In response to injury, mast cells present in tissue degranulate, releasing the potent vasodilator histamine. Increased blood flow and inflammatory mediators recruit white blood cells to the site of inflammation. The endothelium lining the local blood vessel becomes “leaky” under the influence of histamine and other inflammatory mediators allowing neutrophils, macrophages, and fluid to move from the blood into the interstitial tissue spaces. The excess liquid in tissue causes swelling, more properly called oedema. The swollen tissues squeezing pain receptors cause the sensation of pain. Prostaglandins released from injured cells also activate pain neurons. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce pain because they inhibit the synthesis of prostaglandins. High levels of NSAIDs reduce inflammation. Antihistamines decrease allergies by blocking histamine receptors and as a result the histamine response.

After containment of an injury, the tissue repair phase starts with removal of toxins and waste products. Clotting (coagulation) reduces blood loss from damaged blood vessels and forms a network of fibrin proteins that trap blood cells and bind the edges of the wound together. A scab forms when the clot dries, reducing the risk of infection. Sometimes a mixture of dead leukocytes and fluid called pus accumulates in the wound. As healing progresses, fibroblasts from the surrounding connective tissues replace the collagen and extracellular material lost by the injury. Angiogenesis, the growth of new blood vessels, results in vascularisation of the new tissue known as granulation tissue. The clot retracts pulling the edges of the wound together, and it slowly dissolves as the tissue is repaired. When a large amount of granulation tissue forms and capillaries disappear, a pale scar is often visible in the healed area. A primary union describes the healing of a wound where the edges are close together. When there is a gaping wound, it takes longer to refill the area with cells and collagen. The process called secondary union occurs as the edges of the wound are pulled together by what is called wound contraction. When a wound is more than one quarter of an inch deep, sutures (stitches) are recommended to promote a primary union and avoid the formation of a disfiguring scar. Regeneration is the addition of new cells of the same type as the ones that were injured (Figure 3.6.1).

Diagram of healing tissue
Figure 3.6.1. Tissue healing. During wound repair, collagen fibres are laid down randomly by fibroblasts that move into repair the area.

Tissue and Ageing

According to poet Ralph Waldo Emerson, “The surest poison is time.” In fact, biology confirms that many functions of the body decline with age. All the cells, tissues, and organs are affected by senescence, with noticeable variability between individuals owing to different genetic makeup and lifestyles. The outward signs of ageing are easily recognisable. The skin and other tissues become thinner and drier, reducing their elasticity, contributing to wrinkles and high blood pressure. Hair turns grey because follicles produce less melanin, the brown pigment of hair and the iris of the eye. The face looks flabby because elastic and collagen fibres decrease in connective tissue and muscle tone is lost. Glasses and hearing aids may become parts of life as the senses slowly deteriorate, all due to reduced elasticity. Overall height decreases as the bones lose calcium and other minerals. With age, fluid decreases in the fibrous cartilage disks intercalated between the vertebrae in the spine. Joints lose cartilage and stiffen. Many tissues, including those in muscles, lose mass through a process called atrophy. Lumps and rigidity become more widespread. As a consequence, the passageways, blood vessels, and airways become more rigid. The brain and spinal cord lose mass. Nerves do not transmit impulses with the same speed and frequency as in the past. Some loss of thought clarity and memory can accompany ageing. More severe problems are not necessarily associated with the ageing process and may be symptoms of underlying illness.

As exterior signs of ageing increase, so do the interior signs, which are not as noticeable. The incidence of heart diseases, respiratory syndromes, and type 2 diabetes increases with age, though these are not necessarily age-dependent effects. Wound healing is slower in the elderly, accompanied by a higher frequency of infection as the capacity of the immune system to fend off pathogen declines.

Ageing is also apparent at the cellular level because all cells experience changes with ageing. Telomeres, regions of the chromosomes necessary for cell division, shorten each time cells divide. As they do, cells are less able to divide and regenerate. Because of alterations in cell membranes, transport of oxygen and nutrients into the cell and removal of carbon dioxide and waste products from the cell are not as efficient in the elderly. Cells may begin to function abnormally, which may lead to diseases associated with ageing, including arthritis, memory issues, and some cancers.

The progressive impact of ageing on the body varies considerably among individuals, with some studies indicating that exercise and healthy lifestyle choices may slow down the deterioration of the body that comes with old age.

Homeostatic Imbalances

Tissues and Cancer

Cancer is a generic term for many diseases in which cells escape regulatory signals. Uncontrolled growth, invasion into adjacent tissues, and colonisation of other organs, if not treated early enough, are its hallmarks. Health suffers when tumours “rob” blood supply from the “normal” organs.

A mutation is defined as a permanent change in the DNA of a cell. Epigenetic modifications, changes that do not affect the code of the DNA but alter how the DNA is decoded, are also known to generate abnormal cells. Alterations in the genetic material may be caused by environmental agents, infectious agents, or errors in the replication of DNA that accumulate with age. Many mutations do not cause any noticeable change in the functions of a cell. However, if the modification affects key proteins that have an impact on the cell’s ability to proliferate in an orderly fashion, the cell starts to divide abnormally. As changes in cells accumulate, they lose their ability to form regular tissues. A tumour, a mass of cells displaying abnormal architecture, forms in the tissue. Many tumours are benign, meaning they do not metastasise nor cause disease. A tumour becomes malignant, or cancerous, when it breaches the confines of its tissue, promotes angiogenesis, attracts the growth of capillaries, and metastasises to other organs (Figure 3.6.2). The specific names of cancers reflect the tissue of origin. Cancers derived from epithelial cells are referred to as carcinomas. Cancer in myeloid tissue or blood cells form myelomas. Leukemias are cancers of white blood cells, whereas sarcomas derive from connective tissue. Cells in tumours differ both in structure and function. Some cells, called cancer stem cells, appear to be a subtype of cell responsible for uncontrolled growth. Recent research shows that contrary to what was previously assumed, tumours are not disorganised masses of cells, but have their own structures.

Diagram on the deelopment of cancer in the body
Figure 3.6.2. Development of cancer. Note the change in cell size, nucleus size and organisation in the tissue.

Cancer treatments vary depending on the disease’s type and stage. Traditional approaches, including surgery, radiation, chemotherapy, and hormonal therapy, aim to remove or kill rapidly dividing cancer cells, but these strategies have their limitations. Depending on a tumour’s location, for example, cancer surgeons may be unable to remove it. Radiation and chemotherapy are difficult, and it is often impossible to target only the cancer cells. The treatments inevitably destroy healthy tissue as well. To address this, researchers are working on pharmaceuticals that can target specific proteins implicated in cancer-associated molecular pathways.

Section Review

Inflammation is the classic response of the body to injury and follows a common sequence of events. The area is red, feels warm to the touch, swells, and is painful. Injured cells, mast cells, and resident macrophages release chemical signals that cause vasodilation and fluid leakage in the surrounding tissue. The repair phase includes blood clotting, followed by regeneration of tissue as fibroblasts deposit collagen. Some tissues regenerate more readily than others. Epithelial and connective tissues replace damaged or dead cells from a supply of adult stem cells. Muscle and nervous tissues undergo either slow regeneration or do not repair at all.

Age affects all the tissues and organs of the body. Damaged cells do not regenerate as rapidly as in younger people. Perception of sensation and effectiveness of response are lost in the nervous system. Muscles atrophy, and bones lose mass and become brittle. Collagen decreases in some connective tissue, and joints stiffen.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=290

IV

Integumentary System

4.1 Layers of the Skin

Learning Objectives

By the end of this section, you will be able to:

  • Identify the components of the integumentary system
  • Describe the layers of the skin and the functions of each layer
  • Identify and describe the hypodermis and deep fascia
  • Describe the role of keratinocytes and their life cycle
  • Describe the role of melanocytes in skin pigmentation

Although you may not typically think of the skin as an organ, it is in fact made of tissues that work together as a single structure to perform unique and critical functions. The skin and its accessory structures make up the integumentary system, which provides the body with overall protection. The skin is made of multiple layers of cells and tissues, which are held to underlying structures by connective tissue (Figure 4.1.1). The deeper layer of skin is well vascularised (has numerous blood vessels). It also has numerous sensory, and autonomic and sympathetic nerve fibres ensuring communication to and from the brain.

Diagram on the layers of skin
Figure 4.1.1. Layers of skin. The skin is composed of two main layers: the epidermis, made of closely packed epithelial cells, and the dermis, made of dense, irregular connective tissue that houses blood vessels, hair follicles, sweat glands, and other structures. Beneath the dermis lies the hypodermis, which is composed mainly of loose connective and fatty tissues.

The Epidermis

The epidermis is composed of keratinised, stratified squamous epithelium. It is made of four or five layers of epithelial cells, depending on its location in the body. It does not have any blood vessels within it (i.e., it is avascular). Skin that has four layers of cells is referred to as “thin skin.” From deep to superficial, these layers are the stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. Most of the skin can be classified as thin skin. “Thick skin” is found only on the palms of the hands and the soles of the feet. It has a fifth layer, called the stratum lucidum, located between the stratum corneum and the stratum granulosum (Figure 4.1.2).

Image of thin skin and thick skin
Figure 4.1.2. Thin skin versus thick skin. These images show cross-sections of the epidermis and dermis of (a) thin and (b) thick skin. Note the significant difference in the thickness of the epithelial layer of the thick skin. From top, LM × 40, LM × 40. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

The cells in all of the layers except the stratum basale are called keratinocytes. A keratinocyte is a cell that manufactures and stores the protein keratin. Keratin is an intracellular fibrous protein that gives hair, nails, and skin their hardness and water-resistant properties. The keratinocytes in the stratum corneum are dead and regularly slough away, being replaced by cells from the deeper layers (Figure 4.1.3).

Cell image if epidermis
Figure 4.1.3. Epidermis. The epidermis is epithelium composed of multiple layers of cells. The basal layer consists of cuboidal cells, whereas the outer layers are squamous, keratinised cells, so the whole epithelium is often described as being keratinised stratified squamous epithelium. LM × 40. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Stratum Basale

The stratum basale (also called the stratum germinativum) is the deepest epidermal layer and attaches the epidermis to the basal lamina, below which lie the layers of the dermis. The cells in the stratum basale bond to the dermis via intertwining collagen fibres, referred to as the basement membrane. A finger-like projection, or fold, known as the dermal papilla (plural = dermal papillae) is found in the superficial portion of the dermis. Dermal papillae increase the strength of the connection between the epidermis and dermis; the greater the folding, the stronger the connections made (Figure 4.1.4).

Diagram of layers of epidermis
Figure 4.1.4. Layers of the epidermis. The epidermis of thick skin has five layers: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.

The stratum basale is a single layer of cells primarily made of basal cells. A basal cell is a cuboidal-shaped stem cell that is a precursor of the keratinocytes of the epidermis. All of the keratinocytes are produced from this single layer of cells, which are constantly going through mitosis to produce new cells. As new cells are formed, the existing cells are pushed superficially away from the stratum basale. Two other cell types are found dispersed among the basal cells in the stratum basale. The first is a Merkel cell, which functions as a receptor and is responsible for stimulating sensory nerves that the brain perceives as touch. These cells are especially abundant on the surfaces of the hands and feet. The second is a melanocyte, a cell that produces the pigment melanin. Melanin gives hair and skin its colour, and also helps protect the living cells of the epidermis from ultraviolet (UV) radiation damage.

In a growing foetus, fingerprints form where the cells of the stratum basale meet the papillae of the underlying dermal layer (papillary layer), resulting in the formation of the ridges on your fingers that you recognise as fingerprints. Fingerprints are unique to each individual and are used for forensic analyses because the patterns do not change with the growth and ageing processes.

Stratum Spinosum

As the name suggests, the stratum spinosum is spiny in appearance due to the protruding cell processes that join the cells via a structure called a desmosome. The desmosomes interlock with each other and strengthen the bond between the cells. It is interesting to note that the “spiny” nature of this layer is an artifact of the staining process. Unstained epidermis samples do not exhibit this characteristic appearance. The stratum spinosum is composed of eight to 10 layers of keratinocytes, formed as a result of cell division in the stratum basale (Figure 4.1.5). Interspersed among the keratinocytes of this layer is a type of dendritic cell called the Langerhans cell, which functions as a macrophage by engulfing bacteria, foreign particles, and damaged cells that occur in this layer.

 

Cells of the epidermis
Figure 4.1.5. Cells of the epidermis. The cells in the different layers of the epidermis originate from basal cells located in the stratum basale, yet the cells of each layer are distinctively different. EM × 2700. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

The keratinocytes in the stratum spinosum begin the synthesis of keratin and release a water-repelling glycolipid that helps prevent water loss from the body, making the skin relatively waterproof. As new keratinocytes are produced atop the stratum basale, the keratinocytes of the stratum spinosum are pushed into the stratum granulosum.

Stratum Granulosum

The stratum granulosum has a grainy appearance due to further changes to the keratinocytes as they are pushed from the stratum spinosum. The cells (three to five layers deep) become flatter, their cell membranes thicken, and they generate large amounts of the proteins keratin, which is fibrous, and keratohyalin, which accumulates as lamellar granules within the cells (see Figure 4.1.4 and Figure 4.1.5). These two proteins make up the bulk of the keratinocyte mass in the stratum granulosum and give the layer its grainy appearance. The nuclei and other cell organelles disintegrate as the cells die, leaving behind the keratin, keratohyalin, and cell membranes that will form the stratum lucidum, the stratum corneum, and the accessory structures of hair and nails.

Stratum Lucidum

The stratum lucidum is a smooth, seemingly translucent layer of the epidermis located just above the stratum granulosum and below the stratum corneum. This thin layer of cells is found only in the thick skin of the palms, soles, and digits. The keratinocytes that compose the stratum lucidum are dead and flattened (see Figure 4.1.4 and Figure 4.1.5). These cells are densely packed with eleidin, a clear protein rich in lipids, derived from keratohyalin, which gives these cells their transparent (i.e., lucid) appearance and provides a barrier to water.

Stratum Corneum

The stratum corneum is the most superficial layer of the epidermis and is the layer exposed to the outside environment (see Figure 4.1.4 and Figure 4.1.5). The increased keratinisation (also called cornification) of the cells in this layer gives it its name. There are usually 15 to 30 layers of cells in the stratum corneum. This dry, dead layer helps prevent the penetration of microbes and the dehydration of underlying tissues and provides a mechanical protection against abrasion for the more delicate, underlying layers. Cells in this layer are shed periodically and are replaced by cells pushed up from the stratum granulosum (or stratum lucidum in the case of the palms and soles of feet). The entire layer is replaced during a period of about 4 weeks. Cosmetic procedures, such as microdermabrasion, help remove some of the dry, upper layer and aim to keep the skin looking “fresh” and healthy.

Dermis

The dermis might be considered the “core” of the integumentary system (derma- = “skin”), as distinct from the epidermis (epi- = “upon” or “over”) and hypodermis (hypo- = “below”). It contains blood and lymph vessels, nerves, and other structures, such as hair follicles and sweat glands. The dermis is made of two layers of connective tissue that compose an interconnected mesh of elastin and collagenous fibres, produced by fibroblasts (Figure 4.1.6).

Diagram of layers of the dermis
Figure 4.1.6. Layers of the dermis. This stained slide shows the two components of the dermis—the papillary layer and the reticular layer. Both are made of connective tissue with fibres of collagen extending from one to the other, making the border between the two somewhat indistinct. The dermal papillae extending into the epidermis belong to the papillary layer, whereas the dense collagen fibre bundles below belong to the reticular layer. LM × 10. (credit: modification of work by “kilbad”/Wikimedia Commons).

Papillary Layer

The papillary layer is made of loose, areolar connective tissue, which means the collagen and elastin fibres of this layer form a loose mesh. This superficial layer of the dermis projects into the stratum basale of the epidermis to form finger-like dermal papillae (see Figure 4.1.6). Within the papillary layer are fibroblasts, a small number of fat cells (adipocytes), and an abundance of small blood vessels. In addition, the papillary layer contains phagocytes, defensive cells that help fight bacteria or other infections that have breached the skin. This layer also contains lymphatic capillaries, nerve fibres, and touch receptors called the Meissner corpuscles.

Reticular Layer

Underlying the papillary layer is the much thicker reticular layer, composed of dense, irregular connective tissue. This layer is well vascularised and has a rich sensory and sympathetic nerve supply. The reticular layer appears reticulated (net-like) due to a tight meshwork of fibres. Elastin fibres provide some elasticity to the skin, enabling movement. Collagen fibres provide structure and tensile strength, with strands of collagen extending into both the papillary layer and the hypodermis. In addition, collagen binds water to keep the skin hydrated. Collagen injections and Retin-A creams help restore skin turgor by either introducing collagen externally or stimulating blood flow and repair of the dermis, respectively.

Hypodermis

The hypodermis (also called the subcutaneous layer or superficial fascia) is a layer directly below the dermis and serves to connect the skin to the underlying fascia (fibrous tissue) of the bones and muscles. It is not strictly a part of the skin, although the border between the hypodermis and dermis can be difficult to distinguish. The hypodermis consists of well-vascularised, loose, areolar connective tissue and adipose tissue, which functions as a mode of fat storage and provides insulation and cushioning for the integument.

Everyday Connection

Lipid Storage

The hypodermis is home to most of the fat that concerns people when they are trying to keep their weight under control. Adipose tissue present in the hypodermis consists of fat-storing cells called adipocytes. This stored fat can serve as an energy reserve, insulate the body to prevent heat loss, and act as a cushion to protect underlying structures from trauma.

Where the fat is deposited and accumulates within the hypodermis depends on hormones (testosterone, oestrogen, insulin, glucagon, leptin and others), as well as genetic factors. Fat distribution changes as our bodies mature and age. Men tend to accumulate fat in different areas (neck, arms, lower back, and abdomen) than do women (breasts, hips, thighs, and buttocks). The body mass index (BMI) is often used as a measure of fat, although this measure is, in fact, derived from a mathematical formula that compares body weight (mass) to height. Therefore, its accuracy as a health indicator can be called into question in individuals who are extremely physically fit.

In many animals, there is a pattern of storing excess calories as fat to be used in times when food is not readily available. In much of the developed world, insufficient exercise coupled with the ready availability and consumption of high-calorie foods have resulted in unwanted accumulations of adipose tissue in many people. Although periodic accumulation of excess fat may have provided an evolutionary advantage to our ancestors, who experienced unpredictable bouts of famine, it is now becoming chronic and considered a major health threat. Recent studies indicate that a distressing percentage of our population is overweight and/or clinically obese. Not only is this a problem for the individuals affected, but it also has a severe impact on our healthcare system. Changes in lifestyle, specifically in diet and exercise, are the best ways to control body fat accumulation, especially when it reaches levels that increase the risk of heart disease and diabetes.

Pigmentation

The colour of skin is influenced by a number of pigments, including melanin, carotene and haemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred into the keratinocytes via a cellular vesicle called a melanosome (Figure 4.1.7).

 

Diagram of skin pigmentation in cells
Figure 4.1.7. Skin pigmentation. The relative colouration of the skin depends on the amount of melanin produced by melanocytes in the stratum basale and taken up by keratinocytes.

Melanin occurs in two primary forms. Eumelanin exists as black and brown, whereas pheomelanin provides a red colour. Dark-skinned individuals produce more melanin than those with pale skin. Exposure to the UV rays of the sun or a tanning salon causes melanin to be manufactured and built up in keratinocytes, as sun exposure stimulates keratinocytes to secrete chemicals that stimulate melanocytes. The accumulation of melanin in keratinocytes results in the darkening of the skin, or a tan. This increased melanin accumulation protects the DNA of epidermal cells from UV ray damage and the breakdown of folic acid, a nutrient necessary for our health and well-being. In contrast, too much melanin can interfere with the production of vitamin D, an important nutrient involved in calcium absorption. Thus, the amount of melanin present in our skin is dependent on a balance between available sunlight and folic acid destruction, and protection from UV radiation and vitamin D production.

It requires about 10 days after initial sun exposure for melanin synthesis to peak, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially. Dark-skinned individuals can also get sunburned but are more protected than are pale-skinned individuals. Melanosomes are temporary structures that are eventually destroyed by fusion with lysosomes; this fact, along with melanin-filled keratinocytes in the stratum corneum sloughing off, makes tanning impermanent.

Too much sun exposure can eventually lead to wrinkling due to the destruction of the cellular structure of the skin, and in severe cases, can cause sufficient DNA damage to result in skin cancer. When there is an irregular accumulation of melanocytes in the skin, freckles appear. Moles are larger masses of melanocytes, and although most are benign, they should be monitored for changes that might indicate the presence of cancer (Figure 4.1.8).

Photos of different types of moles
Figure 4.1.8. Moles. Moles range from benign accumulations of melanocytes to melanomas. These structures populate the landscape of our skin. (credit: the National Cancer Institute).

Disorders of the Integumentary System

Photo of back of man's neck, showing vitligo, where there is different coloured patches of skin
Figure 4.1.9. Vitiligo. Individuals with vitiligo experience depigmentation that results in lighter coloured patches of skin. The condition is especially noticeable on darker skin. (credit: Klaus D. Peter).

The first thing a clinician sees is the skin, and so the examination of the skin should be part of any thorough physical examination. Most skin disorders are relatively benign, but a few, including melanomas, can be fatal if untreated. A couple of the more noticeable disorders, albinism and vitiligo, affect the appearance of the skin and its accessory organs. Although neither is fatal, it would be hard to claim that they are benign, at least to the individuals so afflicted.

Albinism is a genetic disorder that affects (completely or partially) the colouring of skin, hair, and eyes. The defect is primarily due to the inability of melanocytes to produce melanin. Individuals with albinism tend to appear white or very pale due to the lack of melanin in their skin and hair. Recall that melanin helps protect the skin from the harmful effects of UV radiation. Individuals with albinism tend to need more protection from UV radiation, as they are more prone to sunburns and skin cancer. They also tend to be more sensitive to light and have vision problems due to the lack of pigmentation on the retinal wall. Treatment of this disorder usually involves addressing the symptoms, such as limiting UV light exposure to the skin and eyes. In vitiligo, the melanocytes in certain areas lose their ability to produce melanin, possibly due to an autoimmune reaction. This leads to a loss of colour in patches (Figure 4.1.9). Neither albinism nor vitiligo directly affects the lifespan of an individual.

 

 

 

 

Section Review

The skin is composed of two major layers: a superficial epidermis and a deeper dermis. The epidermis consists of several layers beginning with the innermost (deepest) stratum basale (germinatum), followed by the stratum spinosum, stratum granulosum, stratum lucidum (when present), and ending with the outermost layer, the stratum corneum. The topmost layer, the stratum corneum, consists of dead cells that shed periodically and is progressively replaced by cells formed from the basal layer. The stratum basale also contains melanocytes, cells that produce melanin, the pigment primarily responsible for giving skin its colour. Melanin is transferred to keratinocytes in the stratum spinosum to protect cells from UV rays.

The dermis connects the epidermis to the hypodermis and provides strength and elasticity due to the presence of collagen and elastin fibres. It has only two layers: the papillary layer with papillae that extend into the epidermis and the lower, reticular layer composed of loose connective tissue. The hypodermis, deep to the dermis of skin, is the connective tissue that connects the dermis to underlying structures; it also harbors adipose tissue for fat storage and protection.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=365

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=365

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=365

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=365

4.2 Accessory Structures of the Skin

Learning Objectives

By the end of this section, you will be able to:

  • Identify the accessory structures of the skin
  • Describe the structure and function of hair and nails
  • Describe the structure and function of sweat glands and sebaceous glands

Accessory structures of the skin include hair, nails, sweat glands, and sebaceous glands. These structures embryologically originate from the epidermis and can extend down through the dermis into the hypodermis.

Hair

Hair is a keratinous filament growing out of the epidermis. It is primarily made of dead, keratinised cells. Strands of hair originate in an epidermal penetration of the dermis called the hair follicle. The hair shaft is the part of the hair not anchored to the follicle, and much of this is exposed at the skin’s surface. The rest of the hair, which is anchored in the follicle, lies below the surface of the skin and is referred to as the hair root. The hair root ends deep in the dermis at the hair bulb and includes a layer of mitotically active basal cells called the hair matrix. The hair bulb surrounds the hair papilla, which is made of connective tissue and contains blood capillaries and nerve endings from the dermis (Figure 4.2.1).

diagram of hair and hair follicles
Figure 4.2.1. Hair. Hair follicles originate in the epidermis and have many different parts.

Just as the basal layer of the epidermis forms the layers of epidermis that get pushed to the surface as the dead skin on the surface sheds, the basal cells of the hair bulb divide and push cells outward in the hair root and shaft as the hair grows. The medulla forms the central core of the hair, which is surrounded by the cortex, a layer of compressed, keratinised cells that is covered by an outer layer of very hard, keratinised cells known as the cuticle. These layers are depicted in a longitudinal cross-section of the hair follicle (Figure 4.2.2), although not all hair has a medullary layer. Hair texture (straight, curly) is determined by the shape and structure of the cortex, and to the extent that it is present, the medulla. The shape and structure of these layers are, in turn, determined by the shape of the hair follicle. Hair growth begins with the production of keratinocytes by the basal cells of the hair bulb. As new cells are deposited at the hair bulb, the hair shaft is pushed through the follicle toward the surface. Keratinisation is completed as the cells are pushed to the skin surface to form the shaft of hair that is externally visible. The external hair is completely dead and composed entirely of keratin. For this reason, our hair does not have sensation. Furthermore, you can cut your hair or shave without damaging the hair structure because the cut is superficial. Most chemical hair removers also act superficially; however, electrolysis and yanking both attempt to destroy the hair bulb so hair cannot grow.

Cell image of hair follicle
Figure 4.2.2. Hair Follicle. The slide shows a cross-section of a hair follicle. Basal cells of the hair matrix in the centre differentiate into cells of the inner root sheath. Basal cells at the base of the hair root form the outer root sheath. LM × 4. (credit: modification of work by “kilbad”/Wikimedia Commons).

The wall of the hair follicle is made of three concentric layers of cells. The cells of the internal root sheath surround the root of the growing hair and extend just up to the hair shaft. They are derived from the basal cells of the hair matrix. The external root sheath, which is an extension of the epidermis, encloses the hair root. It is made of basal cells at the base of the hair root and tends to be more keratinous in the upper regions. The glassy membrane is a thick, clear connective tissue sheath covering the hair root, connecting it to the tissue of the dermis.

Hair serves a variety of functions, including protection, sensory input, thermoregulation and communication, for example, hair on the head protects the skull from the sun. The hair in the nose and ears, and around the eyes (eyelashes) defends the body by trapping and excluding dust particles that may contain allergens and microbes. Hair of the eyebrows prevents sweat and other particles from dripping into and bothering the eyes. Hair also has a sensory function due to sensory innervation by a hair root plexus surrounding the base of each hair follicle. Hair is extremely sensitive to air movement or other disturbances in the environment, much more so than the skin surface. This feature is also useful for the detection of the presence of insects or other potentially damaging substances on the skin surface. Each hair root is connected to a smooth muscle called the arrector pili that contracts in response to nerve signals from the sympathetic nervous system, making the external hair shaft “stand up.” The primary purpose for this is to trap a layer of air to add insulation. This is visible in humans as goose bumps and even more obvious in animals, such as when a frightened cat raises its fur. Of course, this is much more obvious in organisms with a heavier coat than most humans, such as dogs and cats.

Hair Growth

Hair grows and is eventually shed and replaced by new hair. This occurs in three phases. The first is the anagen phase, during which cells divide rapidly at the root of the hair, pushing the hair shaft up and out. The length of this phase is measured in years, typically from 2 to 7 years. The catagen phase lasts only 2 to 3 weeks and marks a transition from the hair follicle’s active growth. Finally, during the telogen phase, the hair follicle is at rest and no new growth occurs. At the end of this phase, which lasts about 2 to 4 months, another anagen phase begins. The basal cells in the hair matrix then produce a new hair follicle, which pushes the old hair out as the growth cycle repeats itself. Hair typically grows at the rate of 0.3 mm per day during the anagen phase. On average, 50 hairs are lost and replaced per day. Hair loss occurs if there is more hair shed than what is replaced and can happen due to hormonal or dietary changes. Hair loss can also result from the ageing process, or the influence of hormones.

Hair Colour

Similar to the skin, hair gets its colour from the pigment melanin, produced by melanocytes in the hair papilla. Different hair colour results from differences in the type of melanin, which is genetically determined. As a person ages, the melanin production decreases, and hair tends to lose its colour and becomes grey and/or white.

Nails

The nail bed is a specialised structure of the epidermis that is found at the tips of our fingers and toes. The nail body is formed on the nail bed, and protects the tips of our fingers and toes as they are the farthest extremities and the parts of the body that experience the maximum mechanical stress (Figure 4.2.3). In addition, the nail body forms a back-support for picking up small objects with the fingers. The nail body is composed of densely packed dead keratinocytes. The epidermis in this part of the body has evolved a specialised structure upon which nails can form. The nail body forms at the nail root, which has a matrix of proliferating cells from the stratum basale that enables the nail to grow continuously. The lateral nail fold overlaps the nail on the sides, helping to anchor the nail body. The nail fold that meets the proximal end of the nail body forms the nail cuticle, also called the eponychium. The nail bed is rich in blood vessels, making it appear pink, except at the base, where a thick layer of epithelium over the nail matrix forms a crescent-shaped region called the lunula (the “little moon”). The area beneath the free edge of the nail, furthest from the cuticle, is called the hyponychium. It consists of a thickened layer of stratum corneum.

Diagram of different parts of the nail
Figure 4.2.3. Nails. The nail is an accessory structure of the integumentary system.

Sweat Glands

When the body becomes warm, sudoriferous glands produce sweat to cool the body. Sweat glands develop from epidermal projections into the dermis and are classified as merocrine glands; that is, the secretions are excreted by exocytosis through a duct without affecting the cells of the gland. There are two types of sweat glands, each secreting slightly different products.

An eccrine sweat gland is type of gland that produces a hypotonic sweat for thermoregulation. These glands are found all over the skin’s surface, but are especially abundant on the palms of the hand, the soles of the feet, and the forehead (Figure 4.2.4). They are coiled glands lying deep in the dermis, with the duct rising up to a pore on the skin surface, where the sweat is released. This type of sweat, released by exocytosis, is hypotonic and composed mostly of water, with some salt, antibodies, traces of metabolic waste, and dermicidin, an antimicrobial peptide. Eccrine glands are a primary component of thermoregulation in humans and thus help to maintain homeostasis.

Diagram of eccrine gland
Figure 4.2.4. Eccrine Gland. Eccrine glands are coiled glands in the dermis that release sweat that is mostly water.

An apocrine sweat gland is usually associated with hair follicles in densely hairy areas, such as armpits and genital regions. Apocrine sweat glands are larger than eccrine sweat glands and lie deeper in the dermis, sometimes even reaching the hypodermis, with the duct normally emptying into the hair follicle. In addition to water and salts, apocrine sweat includes organic compounds that make the sweat thicker and subject to bacterial decomposition and subsequent smell. The release of this sweat is under both nervous and hormonal control and plays a role in the poorly understood human pheromone response. Most commercial antiperspirants use an aluminium-based compound as their primary active ingredient to stop sweat. When the antiperspirant enters the sweat gland duct, the aluminium-based compounds precipitate due to a change in pH and form a physical block in the duct, which prevents sweat from coming out of the pore.

Sebaceous Glands

sebaceous gland is a type of oil gland that is found all over the body and helps to lubricate and waterproof the skin and hair. Most sebaceous glands are associated with hair follicles. They generate and excrete sebum, a mixture of lipids, onto the skin surface, thereby naturally lubricating the dry and dead layer of keratinised cells of the stratum corneum, keeping it pliable. The fatty acids of sebum also have antibacterial properties and prevent water loss from the skin in low-humidity environments. The secretion of sebum is stimulated by hormones, many of which do not become active until puberty. Thus, sebaceous glands are relatively inactive during childhood.

Section Review

Accessory structures of the skin include hair, nails, sweat glands, and sebaceous glands. Hair is made of dead keratinised cells and gets its colour from melanin pigments. Nails, also made of dead keratinised cells, protect the extremities of our fingers and toes from mechanical damage. Sweat glands and sebaceous glands produce sweat and sebum, respectively. Each of these fluids has a role to play in maintaining homeostasis. Sweat cools the body surface when it gets overheated and helps excrete small amounts of metabolic waste. Sebum acts as a natural moisturiser and keeps the dead, flaky, outer keratin layer healthy.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=367

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=367

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=367

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=367

4.3 Functions of the Integumentary System

Learning Objectives

By the end of this section, you will be able to:

  • Describe the different functions of the skin and the structures that enable them
  • Explain how the skin helps maintain body temperature

The skin and accessory structures perform a variety of essential functions, such as protecting the body from invasion by microorganisms, chemicals, and other environmental factors; preventing dehydration; acting as a sensory organ; modulating body temperature and electrolyte balance; and synthesising vitamin D. The underlying hypodermis has important roles in storing fats, forming a “cushion” over underlying structures, and providing insulation from cold temperatures.

Protection

The skin protects the rest of the body from the basic elements of nature such as wind, water, and UV sunlight. It acts as a protective barrier against water loss, due to the presence of layers of keratin and glycolipids in the stratum corneum. It also is the first line of defence against abrasive activity due to contact with grit, microbes, or harmful chemicals. Sweat excreted from sweat glands deters microbes from over-colonising the skin surface by generating dermicidin, which has antibiotic properties.

Everyday Connection

Tattoos and Piercings

The word “armour” evokes several images. You might think of a Roman centurion or a medieval knight in a suit of armour. The skin, in its own way, functions as a form of armour—body armour. It provides a barrier between your vital, life-sustaining organs and the influence of outside elements that could potentially damage them.

For any form of armour, a breach in the protective barrier poses a danger. The skin can be breached when a child skins a knee, or an adult has blood drawn—one is accidental and the other medically necessary. However, you also breach this barrier when you choose to “accessorise” your skin with a tattoo or body piercing. Because the needles involved in producing body art and piercings must penetrate the skin, there are dangers associated with the practice. These include allergic reactions; skin infections; blood-borne diseases, such as tetanus, hepatitis C and hepatitis D; and the growth of scar tissue. Despite the risk, the practice of piercing the skin for decorative purposes has become increasingly popular. According to the American Academy of Dermatology, 24 percent of people from ages 18 to 50 have a tattoo.

Sensory Function

The fact that you can feel an ant crawling on your skin, allowing you to flick it off before it bites, is because the skin, and especially the hairs projecting from hair follicles in the skin, can sense changes in the environment. The hair root plexus surrounding the base of the hair follicle senses a disturbance, and then transmits the information to the central nervous system (brain and spinal cord), which can then respond by activating the skeletal muscles of your eyes to see the ant and the skeletal muscles of the body to act against the ant.

The skin acts as a sense organ because the epidermis, dermis, and the hypodermis contain specialised sensory nerve structures that detect touch, surface temperature, and pain. These receptors are more concentrated on the tips of the fingers, which are most sensitive to touch, especially the Meissner corpuscle (tactile corpuscle) (Figure 4.3.1), which responds to light touch, and the Pacinian corpuscle (lamellated corpuscle), which responds to vibration. Merkel cells, seen scattered in the stratum basale, are also touch receptors. In addition to these specialised receptors, there are sensory nerves connected to each hair follicle, pain and temperature receptors scattered throughout the skin, and motor nerves innervate the arrector pili muscles and glands. This rich innervation helps us sense our environment and react accordingly.

Light micrograph of a Meissner corpuscle
Figure 4.3.1. Light micrograph of a Meissner corpuscle. In this micrograph of a skin cross-section, you can see a Meissner corpuscle (arrow), a type of touch receptor located in a dermal papilla adjacent to the basement membrane and stratum basale of the overlying epidermis. LM × 100. (credit: “Wbensmith”/Wikimedia Commons).

Thermoregulation

The integumentary system helps regulate body temperature through its tight association with the sympathetic nervous system, the division of the nervous system involved in our fight-or-flight responses. The sympathetic nervous system is continuously monitoring body temperature and initiating appropriate motor responses. Recall that sweat glands, accessory structures to the skin, secrete water, salt, and other substances to cool the body when it becomes warm. Even when the body does not appear to be noticeably sweating, approximately 500 mL of sweat (insensible perspiration) are secreted a day. If the body becomes excessively warm due to high temperatures, vigorous activity (Figure 4.3.2ac), or a combination of the two, sweat glands will be stimulated by the sympathetic nervous system to produce large amounts of sweat, as much as 0.7 to 1.5 L per hour for an active person. When the sweat evaporates from the skin surface, the body is cooled as body heat is dissipated.

In addition to sweating, arterioles in the dermis dilate so that excess heat carried by the blood can dissipate through the skin and into the surrounding environment (Figure 4.3.2b). This accounts for the skin redness that many people experience when exercising.

Three images: one of man skiing, one of man running and a diagram that shows how heat is retained and radiated through body
Figure 4.3.2. Thermoregulation. During strenuous physical activities, such as skiing (a) or running (c), the dermal blood vessels dilate and sweat secretion increases (b). These mechanisms prevent the body from overheating. In contrast, the dermal blood vessels constrict to minimise heat loss in response to low temperatures (b). (credit a: “Trysil”/flickr; credit c: Ralph Daily).

When body temperatures drop, the arterioles constrict to minimise heat loss, particularly in the ends of the digits and tip of the nose. This reduced circulation can result in the skin taking on a whitish hue. Although the temperature of the skin drops as a result, passive heat loss is prevented, and internal organs and structures remain warm. If the temperature of the skin drops too much (such as environmental temperatures below freezing), the conservation of body core heat can result in the skin actually freezing, a condition called frostbite.

Ageing and the Integumentary System

All systems in the body accumulate subtle and some not-so-subtle changes as a person ages. Among these changes are reductions in cell division, metabolic activity, blood circulation, hormonal levels, and muscle strength (Figure 4.3.3). In the skin, these changes are reflected in decreased mitosis in the stratum basale, leading to a thinner epidermis. The dermis, which is responsible for the elasticity and resilience of the skin, exhibits a reduced ability to regenerate, which leads to slower wound healing. The hypodermis, with its fat stores, loses structure due to the reduction and redistribution of fat, which in turn contributes to the thinning and sagging of skin.

Photo of young woman and old woman
Figure 4.3.3. Ageing. Generally, skin, especially on the face and hands, starts to display the first noticeable signs of ageing, as it loses its elasticity over time. (credit: Janet Ramsden).

The accessory structures also have lowered activity, generating thinner hair and nails, and reduced amounts of sebum and sweat. A reduced sweating ability can cause some elderly to be intolerant to extreme heat. Other cells in the skin, such as melanocytes and dendritic cells, also become less active, leading to a paler skin tone and lowered immunity. Wrinkling of the skin occurs due to breakdown of its structure, which results from decreased collagen and elastin production in the dermis, weakening of muscles lying under the skin, and the inability of the skin to retain adequate moisture.

Many anti-ageing products can be found in stores today. In general, these products try to rehydrate the skin and thereby fill out the wrinkles, and some stimulate skin growth using hormones and growth factors. Additionally, invasive techniques include collagen injections to plump the tissue and injections of BOTOX® (the name brand of the botulinum neurotoxin) that paralyse the muscles that crease the skin and cause wrinkling.

Vitamin D Synthesis

The epidermal layer of human skin synthesises vitamin D when exposed to UV radiation. In the presence of sunlight, a form of vitamin D3 called cholecalciferol is synthesised from a derivative of the steroid cholesterol in the skin. The liver converts cholecalciferol to calcidiol, which is then converted to calcitriol (the active chemical form of the vitamin) in the kidneys. Vitamin D is essential for normal absorption of calcium and phosphorous, which are required for healthy bones. The absence of sun exposure can lead to a lack of vitamin D in the body, leading to a condition called rickets, a painful condition in children where the bones are misshapen due to a lack of calcium, causing bowleggedness. Elderly individuals who suffer from vitamin D deficiency can develop a condition called osteomalacia, a softening of the bones. In present day society, vitamin D is added as a supplement to many foods, including milk and orange juice, compensating for the need for sun exposure.

In addition to its essential role in bone health, vitamin D is essential for general immunity against bacterial, viral, and fungal infections. Recent studies are also finding a link between insufficient vitamin D and cancer.

Section Review

The skin plays important roles in protection, sensing stimuli, thermoregulation, and vitamin D synthesis. It is the first layer of defence to prevent dehydration, infection, and injury to the rest of the body. Sweat glands in the skin allow the skin surface to cool when the body gets overheated. Thermoregulation is also accomplished by the dilation or constriction of heat-carrying blood vessels in the skin. Immune cells present among the skin layers patrol the areas to keep them free of foreign materials. Fat stores in the hypodermis aid in both thermoregulation and protection. Finally, the skin plays a role in the synthesis of vitamin D, which is necessary for our well-being but not easily available in natural foods.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=369

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=369

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=369

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=369

4.4 Diseases, Disorders and Injuries of the Integumentary System

Learning Objectives

By the end of this section, you will be able to:

  • Describe several different diseases and disorders of the skin
  • Describe the effect of injury to the skin and the process of healing

The integumentary system is susceptible to a variety of diseases, disorders and injuries. These range from annoying but relatively benign bacterial or fungal infections that are categorised as disorders, to skin cancer and severe burns, which can be fatal. In this section, you will learn several of the most common skin conditions.

Diseases

One of the most talked about diseases is skin cancer. Cancer is a broad term that describes diseases caused by abnormal cells in the body dividing uncontrollably. Most cancers are identified by the organ or tissue in which the cancer originates. One common form of cancer is skin cancer. The Skin Cancer Foundation reports that one in five Americans will experience some type of skin cancer in their lifetime. The degradation of the ozone layer in the atmosphere and the resulting increase in exposure to UV radiation has contributed to its rise. Overexposure to UV radiation damages DNA, which can lead to the formation of cancerous lesions. Although melanin offers some protection against DNA damage from the sun, often it is not enough. The fact that cancers can also occur on areas of the body that are normally not exposed to UV radiation suggests that there are additional factors that can lead to cancerous lesions.

In general, cancers result from an accumulation of DNA mutations. These mutations can result in cell populations that do not die when they should and uncontrolled cell proliferation that leads to tumours. Although many tumours are benign (harmless), some produce cells that can mobilise and establish tumours in other organs of the body; this process is referred to as metastasis. Cancers are characterised by their ability to metastasise.

Basal Cell Carcinoma

Image of Basal cell carcinoma
Figure 4.4.1. Basal cell carcinoma. Basal cell carcinoma can take several different forms. Similar to other forms of skin cancer, it is readily cured if caught early and treated. (credit: John Hendrix, MD).

Basal cell carcinoma is a form of cancer that affects the mitotically active stem cells in the stratum basale of the epidermis. It is the most common of all cancers that occur in the United States and is frequently found on the head, neck, arms, and back, which are areas that are most susceptible to long-term sun exposure. Although UV rays are the main culprit, exposure to other agents, such as radiation and arsenic, can also lead to this type of cancer. Wounds on the skin due to open sores, tattoos, burns, etc. may be predisposing factors as well. Basal cell carcinomas start in the stratum basale and usually spread along this boundary. At some point, they begin to grow toward the surface and become an uneven patch, bump, growth, or scar on the skin surface (Figure 4.4.1). Like most cancers, basal cell carcinomas respond best to treatment when caught early. Treatment options include surgery, freezing (cryosurgery), and topical ointments (Mayo Clinic 2012).

Squamous Cell Carcinoma

Lesion on person's nose
Figure 4.4.2. Squamous cell carcinoma. Squamous cell carcinoma presents here as a lesion on an individual’s nose. (credit: the National Cancer Institute).

Squamous cell carcinoma is a cancer that affects the keratinocytes of the stratum spinosum and presents as lesions commonly found on the scalp, ears, and hands (Figure 4.4.2). It is the second most common skin cancer. The American Cancer Society reports that two of 10 skin cancers are squamous cell carcinomas, and it is more aggressive than basal cell carcinoma. If not removed, these carcinomas can metastasise. Surgery and radiation are used to cure squamous cell carcinoma.

Melanoma

melanoma is a cancer characterised by the uncontrolled growth of melanocytes, the pigment-producing cells in the epidermis. Typically, a melanoma develops from a mole. It is the most fatal of all skin cancers, as it is highly metastatic and can be difficult to detect before it has spread to other organs. Melanomas usually appear as asymmetrical brown and black patches with uneven borders and a raised surface (Figure 4.4.3). Treatment typically involves surgical excision and immunotherapy.

Photo of melanoma
Figure 4.4.3. Melanoma. Melanomas typically present as large brown or black patches with uneven borders and a raised surface. (credit: the National Cancer Institute).

Doctors often give their patients the following ABCDE mnemonic to help with the diagnosis of early-stage melanoma. If you observe a mole on your body displaying these signs, consult a doctor.

Asymmetry – the two sides are not symmetrical

Borders – the edges are irregular in shape

Colour – the colour is varied shades of brown or black

Diameter – it is larger than 6 mm (0.24 in)

Evolving – its shape has changed

Some specialists cite the following additional signs for the most serious form, nodular melanoma:

Elevated – it is raised on the skin surface

Firm – it feels hard to the touch

Growing – it is getting larger

Skin Disorders

Two common skin disorders are eczema and acne. Eczema is an inflammatory condition and occurs in individuals of all ages. Acne involves the clogging of pores, which can lead to infection and inflammation, and is often seen in adolescents. Other disorders, not discussed here, include seborrheic dermatitis (on the scalp), psoriasis, cold sores, impetigo, scabies, hives, and warts.

Eczema

eczema on arms
Figure 4.4.4. Eczema. Eczema is a common skin disorder that presents as a red, flaky rash. (credit: “Jambula”/Wikimedia Commons).

Eczema is an allergic reaction that manifests as dry, itchy patches of skin that resemble rashes (Figure 4.4.4). It may be accompanied by swelling of the skin, flaking, and in severe cases, bleeding. Many who suffer from eczema have antibodies against dust mites in their blood, but the link between eczema and allergy to dust mites has not been proven. Symptoms are usually managed with moisturisers, corticosteroid creams and immunosuppressants.

Acne

Acne is a skin disturbance that typically occurs on areas of the skin that are rich in sebaceous glands (face and back). It is most common along with the onset of puberty due to associated hormonal changes but can also occur in infants and continue into adulthood. Hormones, such as androgens, stimulate the release of sebum. An overproduction and accumulation of sebum along with keratin can block hair follicles. This plug is initially white. The sebum, when oxidised by exposure to air, turns black. Acne results from infection by acne-causing bacteria (Propionibacterium and Staphylococcus), which can lead to redness and potential scarring due to the natural wound healing process (Figure 4.4.5).

Diagram of acne production process
Figure 4.4.5. Acne. Acne is a result of over-productive sebaceous glands, which leads to formation of blackheads and inflammation of the skin.

Career Connection

Dermatologist
Have you ever had a skin rash that did not respond to over-the-counter creams, or a mole that you were concerned about? Dermatologists help patients with these types of problems and more, on a daily basis. Dermatologists are medical doctors who specialise in diagnosing and treating skin disorders. Like all medical doctors, dermatologists earn a medical degree and then complete several years of residency training. In addition, dermatologists may then participate in a dermatology fellowship or complete additional, specialised training in a dermatology practice. In Australia, the pathway of becoming a dermatologist has four stages. Firstly, a completion of a medical school degree (medical doctor) which takes roughly four to six years. Second step is a completion of a yearlong in-hospital internship. Third step requires a minimum of one year residency at a hospital. The fourth and final stage requires further vocational training at the Fellowship of the Australasian College of Dermatologists (FACD) for approximately four years.

Most dermatologists work in a medical office or private practice setting. They diagnose skin conditions and rashes, prescribe oral and topical medications to treat skin conditions, and may perform simple procedures, such as mole or wart removal. In addition, they may refer patients to an oncologist if skin cancer that has metastasised is suspected. Recently, cosmetic procedures have also become a prominent part of dermatology. Botox injections, laser treatments, and collagen and dermal filler injections are popular among patients, hoping to reduce the appearance of skin ageing.

Dermatology is a competitive specialty in medicine. Limited openings in dermatology residency programs mean that many medical students compete for a few select spots. Dermatology is an appealing specialty to many prospective doctors, because unlike emergency room physicians or surgeons, dermatologists generally do not have to work excessive hours or be “on-call” weekends and holidays. Moreover, the popularity of cosmetic dermatology has made it a growing field with many lucrative opportunities. It is not unusual for dermatology clinics to market themselves exclusively as cosmetic dermatology centres, and for dermatologists to specialise exclusively in these procedures.

Injuries

Because the skin is the part of our bodies that meets the world most directly, it is especially vulnerable to injury. Injuries include burns and wounds, as well as scars and calluses. They can be caused by sharp objects, heat, or excessive pressure or friction to the skin.

Skin injuries set off a healing process that occurs in several overlapping stages. The first step to repairing damaged skin is the formation of a blood clot that helps stop the flow of blood and scabs over with time. Many different types of cells are involved in wound repair, especially if the surface area that needs repair is extensive. Before the basal stem cells of the stratum basale can recreate the epidermis, fibroblasts mobilise and divide rapidly to repair the damaged tissue by collagen deposition, forming granulation tissue. Blood capillaries follow the fibroblasts and help increase blood circulation and oxygen supply to the area. Immune cells, such as macrophages, roam the area and engulf any foreign matter to reduce the chance of infection.

Burns

A burn results when the skin is damaged by intense heat, radiation, electricity, or chemicals. The damage results in the death of skin cells, which can lead to a massive loss of fluid. Dehydration, electrolyte imbalance, and renal and circulatory failure follow, which can be fatal. Burn patients are treated with intravenous fluids to offset dehydration, as well as intravenous nutrients that enable the body to repair tissues and replace lost proteins. Another serious threat to the lives of burn patients is infection. Burned skin is extremely susceptible to bacteria and other pathogens, due to the loss of protection by intact layers of skin.

Diagram of human body split into percentages to calculate size of burns
Figure 4.4.6. Calculating the size of a burn. The size of a burn will guide decisions made about the need for specialised treatment. Specific parts of the body are associated with a percentage of body area.

Burns are sometimes measured in terms of the size of the total surface area affected. This is referred to as the “rule of nines”, which associates specific anatomical areas with a percentage that is a factor of nine (Figure 4.4.6). Burns are also classified by the degree of their severity. In Australia, burns are divided into three main categories: superficial, partial thickness, and full thickness. In other countries, such as United States, these are classified by first, second, third and fourth degree burns. Superficial burns (first-degree) appear pink or red in colour with no visible blisters, and only affect the epidermis and dermal papillae. There are no texture changes to the epidermis, however they tend to be hypersensitive to touch. Although the skin may be painful and swollen, these burns typically heal on their own within a few days. Mild sunburn fits into the category of a superficial burn.  Partial thickness burns (second-degree), sometimes referred to as mid or deep dermal burns, refer to burns in which the entire epidermal layer had been destroyed and the injury reaches the dermis. The depth to which dermal layer is injured determines whether it is classified as a mid or deep dermal burn. Generally, partial thickness burns are distinguished by a creamy coloured base. In a mid-partial burn, sweat glands and hair follicles remain undamaged, however they are affected in a deep partial thickness burn. These burns result in swelling and a painful blistering of the skin. It is important to keep the burn site clean and sterile to prevent infection. If this is done, the burn will heal within several weeks. Full thickness burns (third-degree) are classified as those in which all layers of the epidermis, epithelial elements, dermal appendages, and nerve endings are injured. These burns are distinguished by a leathery appearance which may range from a white, brown, deep red or black. Additionally, the texture of these layers appears leathery and tough. Full-thickness burns cannot be repaired by the body, because the local tissues used for repair are damaged and require excision (debridement), or amputation in severe cases, followed by grafting of the skin from an unaffected part of the body, or from skin grown in tissue culture for grafting purposes. Oddly, full thickness burns are usually not as painful because the nerve endings themselves are damaged. A fourth-degree burn is even more severe, affecting the underlying muscle and bone.

Scars and Keloids

Most cuts or wounds, with the exception of ones that only scratch the surface (the epidermis), lead to scar formation. A scar is collagen-rich skin formed after the process of wound healing that differs from normal skin. Scarring occurs in cases in which there is repair of skin damage, but the skin fails to regenerate the original skin structure. Fibroblasts generate scar tissue in the form of collagen, and the bulk of repair is due to the basket-weave pattern generated by collagen fibres and does not result in regeneration of the typical cellular structure of skin. Instead, the tissue is fibrous in nature and does not allow for the regeneration of accessory structures, such as hair follicles, sweat glands, or sebaceous glands.

Sometimes, there is an overproduction of scar tissue, because the process of collagen formation does not stop when the wound is healed; this results in the formation of a raised or hypertrophic scar called a keloid. In contrast, scars that result from acne and chickenpox have a sunken appearance and are called atrophic scars.

Scarring of skin after wound healing is a natural process and does not need to be treated further. Application of mineral oil and lotions may reduce the formation of scar tissue. However, modern cosmetic procedures, such as dermabrasion, laser treatments, and filler injections have been invented as remedies for severe scarring. All of these procedures try to reorganise the structure of the epidermis and underlying collagen tissue to make it look more natural.

Bedsores and Stretch Marks

Skin and its underlying tissue can be affected by excessive pressure. One example of this is called a bedsore. Bedsores, also called decubitis ulcers, are caused by constant, long-term, unrelieved pressure on certain body parts that are bony, reducing blood flow to the area and leading to necrosis (tissue death). Bedsores are most common in elderly patients who have debilitating conditions that cause them to be immobile. Most hospitals and long-term care facilities have the practice of turning the patients every few hours to prevent the incidence of bedsores. If left untreated by removal of necrotised tissue, bedsores can be fatal if they become infected.

The skin can also be affected by pressure associated with rapid growth. A stretch mark results when the dermis is stretched beyond its limits of elasticity, as the skin stretches to accommodate the excess pressure. Stretch marks usually accompany rapid weight gain during puberty and pregnancy. They initially have a reddish hue but lighten over time. Other than for cosmetic reasons, treatment of stretch marks is not required. They occur most commonly over the hips and abdomen.

Calluses

When you wear shoes that do not fit well and are a constant source of abrasion on your toes, you tend to form a callus at the point of contact. This occurs because the basal stem cells in the stratum basale are triggered to divide more often to increase the thickness of the skin at the point of abrasion to protect the rest of the body from further damage. This is an example of a minor or local injury, and the skin manages to react and treat the problem independent of the rest of the body. Calluses can also form on your fingers if they are subject to constant mechanical stress, such as long periods of writing, playing string instruments, or video games. A corn is a specialised form of callus. Corns form from abrasions on the skin that result from an elliptical-type motion.

Section Review

Skin cancer is a result of damage to the DNA of skin cells, often due to excessive exposure to UV radiation. Basal cell carcinoma and squamous cell carcinoma are highly curable and arise from cells in the stratum basale and stratum spinosum, respectively. Melanoma is the most dangerous form of skin cancer, affecting melanocytes, which can spread/metastasise to other organs. Burns are an injury to the skin that occur as a result of exposure to extreme heat, radiation, or chemicals. Epidermal, superficial dermal and mid dermal usually heal quickly, but deep dermal and full thickness burns can be fatal because they penetrate the full thickness of the skin. Scars occur when there is repair of skin damage. Fibroblasts generate scar tissue in the form of collagen, which forms a basket-weave pattern that looks different from normal skin.

Bedsores and stretch marks are the result of excessive pressure on the skin and underlying tissue. Bedsores are characterised by necrosis of tissue due to immobility, whereas stretch marks result from rapid growth. Eczema is an allergic reaction that manifests as a rash, and acne results from clogged sebaceous glands. Eczema and acne are usually long-term skin conditions that may be treated successfully in mild cases. Calluses and corns are the result of abrasive pressure on the skin.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=371

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=371

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=371

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=371

V

Blood

5.1 An Overview of Blood

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Identify the primary functions of blood in transportation, defence and maintenance of homeostasis
  • Name the fluid component of blood and the three major types of cellular components (formed elements), and identify their relative proportions in a blood sample
  • Discuss the unique physical characteristics of blood
  • Identify the composition of blood plasma, including its most important solutes and plasma proteins

Recall that blood is a connective tissue. Like all connective tissues, it is made up of cellular elements and an extracellular matrix. The cellular elements—referred to as the cellular components or formed elements—include red blood cells (RBCs)white blood cells (WBCs), and cell fragments called platelets. The extracellular matrix, called plasma, makes blood unique among connective tissues because it is fluid. This fluid, which is mostly water, perpetually suspends the cellular components and enables them to circulate throughout the body within the cardiovascular system.

Function of Blood

The primary function of blood is to deliver oxygen and nutrients to, and remove wastes from, body tissues and cells, but that is only the beginning of the story. The specific functions of blood also include defence, distribution of heat, and maintenance of homeostasis.

Transportation

Nutrients from the foods we eat are absorbed in the digestive tract. Most of these travel in the bloodstream directly to the liver, where they are processed and released back into the bloodstream for delivery to body cells. Oxygen from the air we breathe diffuses into the blood, which moves from the lungs to the heart, which then pumps it out to the rest of the body. Moreover, endocrine glands scattered throughout the body release their products, called hormones, into the bloodstream, which carries them to distant target cells. Blood also picks up cellular wastes and by-products and transports them to various organs for removal. For instance, blood moves carbon dioxide to the lungs for exhalation from the body, and various other waste products are transported to the kidneys and liver for excretion from the body in the form of urine or bile.

Defence

Many types of WBCs protect the body from external threats, such as disease-causing bacteria that have entered the tissues. Other WBCs seek out and destroy internal threats, such as cells with mutated DNA that could multiply to become cancerous, or body cells infected with viruses.

When damage to the blood vessels results in bleeding, blood platelets and certain proteins dissolved in the plasma, the fluid portion of the blood, interact to patch the ruptured areas of the blood vessels involved. This helps to protect the body from further blood loss and initiates the healing process.

Maintenance of Homeostasis

Recall that body temperature is regulated via a classic negative-feedback loop. If you were exercising on a warm day, your rising core body temperature would trigger several homeostatic mechanisms, including increased transport of blood from your core to your body periphery, which is typically cooler. As blood passes through the vessels of the skin, heat would be dissipated to the environment, and the blood returning to your body core would be cooler. In contrast, on a cold day, blood is diverted away from the skin to maintain a warmer body core. In extreme cases, this may result in frostbite.

Blood also helps to maintain the chemical balance of the body. For example, proteins and other compounds in blood act as pH buffers, which thereby help to regulate the pH of body fluids and cells. Blood also helps to regulate the water content of body cells and tissues.

Composition of Blood

You may have had blood drawn from a superficial vein in your arm, which was then sent to a lab for analysis. Some of the most common blood tests—for instance, those measuring lipid or glucose levels in plasma—determine which substances are present within blood and in what concentrations. Other blood tests check for the composition of the blood itself, including the quantities and types of cellular components.

One such test, called a haematocrit, measures the percentage of RBCs, clinically known as erythrocytes, in a blood sample. It is typically performed by automated analysers but can be performed by spinning the blood sample in a specialised centrifuge, a process that causes the heavier elements suspended within the blood sample to separate from the lightweight, liquid plasma (Figure 5.1.1). Because the heaviest elements in blood are the erythrocytes, these settle at the very bottom of the haematocrit tube. Located above the erythrocytes is a pale, thin layer composed of the remaining cellular components of blood. These are the WBCs, clinically known as leukocytes, and the platelets, cell fragments also called thrombocytes. This layer is referred to as the buffy coat because of its buff colour; it normally constitutes less than 1 percent of a blood sample. Above the buffy coat is the blood plasma, normally a pale, straw-coloured fluid, which constitutes the remainder of the sample.

The volume of erythrocytes after centrifugation is also commonly referred to as packed cell volume (PCV). In normal blood, about 45 percent of a sample is erythrocytes. The haematocrit of any one sample can vary significantly, between about 36 and 50 percent, according to gender and other factors. Normal haematocrit values for females range from 37 to 47, with a mean value of 41; for males, haematocrit ranges from 42 to 52, with a mean of 47. The percentage of other cellular components, the WBCs and platelets, is extremely small so it is not normally considered with the haematocrit. The mean plasma percentage is the percent of blood that is not erythrocytes: for females, it is approximately 59 (or 100 minus 41), and for males, it is approximately 53 (or 100 minus 47).

Three viles of blood. One reprsenting normla blood, one representing anemia and one polcyhemia
Figure 5.1.1. Composition of blood. The cellular elements of blood include a vast number of erythrocytes and comparatively fewer leukocytes and platelets. Plasma is the fluid in which the cellular components are suspended. A sample of blood spun in a centrifuge reveals that plasma is the lightest component. It floats at the top of the tube separated from the heaviest elements, the erythrocytes, by a buffy coat of leukocytes (WBCs) and platelets. Haematocrit is the percentage of the total sample that is comprised of erythrocytes. Depressed and elevated haematocrit levels are shown for comparison.

Characteristics of Blood

When you think about blood, the first characteristic that probably comes to mind is its colour. Blood that has just taken up oxygen in the lungs is bright red, and blood that has released oxygen in the tissues is a darker red colour. This is because the major component of red blood cells, a protein called haemoglobin that binds oxygen, is a pigment that changes colour depending upon the degree of oxygen saturation. Blood is viscous and somewhat sticky to the touch. It has a viscosity approximately five times greater than water. Viscosity is a measure of a fluid’s thickness or resistance to flow and is influenced by the presence of the plasma proteins and cellular components within the blood. The viscosity of blood has a dramatic impact on blood pressure and flow. Consider the difference in flow between water and honey. The more viscous honey would demonstrate a greater resistance to flow than the less viscous water. The same principle applies to blood.

The normal temperature of blood is slightly higher than normal body temperature—about 38°C (or 100.4°F), compared to 37°C (or 98.6°F) for an internal body temperature reading, although daily variations of 0.5 °C are normal. Although the surface of blood vessels is relatively smooth, as blood flows through them, it experiences some friction and resistance, especially as vessels age and lose their elasticity, thereby producing heat. This accounts for its slightly higher temperature.

The pH of blood averages about 7.4; however, it can range from 7.35 to 7.45 in a healthy person. Blood is therefore somewhat more basic (alkaline) on a chemical scale than pure water, which has a pH of 7.0. Blood contains numerous buffers, including bicarbonate, haemoglobin and proteins, that help to regulate pH.

Blood constitutes approximately eight percent of adult body weight. Adult males typically average about five to six litres of blood. Adult females average four to five litres.

Blood Plasma

Like other fluids in the body, plasma is composed primarily of water. In fact, it is about 92 percent water. Dissolved or suspended within this water is a mixture of substances, most of which are proteins. Although there are hundreds of substances dissolved or suspended in the plasma, many of them are present only in very small quantities.

Plasma Proteins

About seven percent of the volume of plasma—nearly all that is not water—is made up of proteins. These include several plasma proteins (proteins that are unique to the plasma), plus a much smaller number of regulatory proteins, including enzymes and some hormones. The major components of plasma are summarised in Figure 5.1.2.

The three major groups of plasma proteins are as follows:

  1. Albumin is the most abundant of the plasma proteins. Manufactured by the liver, albumin molecules serve as binding proteins—transport vehicles for fatty acids, calcium and steroid hormones. Recall that lipids are hydrophobic; however, their binding to albumin enables their transport in the watery plasma. Albumin is also the most significant contributor to the osmotic pressure of blood; that is, its presence holds water inside the blood vessels and draws water from the tissues, across blood vessel walls, and into the bloodstream. This in turn helps to maintain both blood volume and blood pressure. Albumin normally accounts for approximately 54 percent of the total plasma protein content, in clinical levels of 35–50 g/L blood.
  2. The second most common plasma proteins are the globulins. A heterogeneous group, there are three main subgroups known as alpha, beta, and gamma globulins. The alpha and beta globulins transport iron, lipids, and the fat-soluble vitamins A, D, E, and K to the cells; like albumin, they also contribute to osmotic pressure. The gamma globulins are proteins involved in immunity and are better known as an antibodies or immunoglobulins. Although other plasma proteins are produced by the liver, immunoglobulins are produced by specialised leukocytes known as plasma cells. Antibodies assist in protection against infection by binding to invading microorganisms and marking them for destruction by specialised WBCs. Globulins make up approximately 38 percent of the total plasma protein volume, in clinical levels of 10–15 g/L blood.
  3. The least abundant plasma protein is fibrinogen. Like albumin and the alpha and beta globulins, fibrinogen is produced by the liver. It is essential for blood clotting, a process described later in this chapter. Fibrinogen accounts for about 7 percent of the total plasma protein volume, in clinical levels of 2–4.5 g/L blood.

Other Plasma Solutes

In addition to proteins, plasma contains a wide variety of other substances. These include various electrolytes, such as sodium, potassium, and calcium ions; dissolved gases, such as oxygen, carbon dioxide, and nitrogen; various organic nutrients, such as vitamins, lipids, glucose, and amino acids; and metabolic wastes. All these nonprotein solutes combined contribute approximately 1 percent to the total volume of plasma.

Table of major blood components
Figure 5.1.2. Major blood components.

Career Connection

Phlebotomy and Medical Laboratory Science

Phlebotomists are medical professionals trained to draw blood (phleb- = “a blood vessel”; -tomy = “to cut”). When more than a few drops of blood are required, phlebotomists perform a venepuncture, typically of a surface vein in the arm. They perform a capillary stick on a finger, an earlobe, or the heel of an infant when only a small quantity of blood is required. An arterial stick is collected from an artery and used to analyse blood gases. After collection, the blood may be analysed by medical laboratories or perhaps used for transfusions, donations, or research. While many allied health professionals practice phlebotomy, the American Society of Phlebotomy Technicians issues certificates to individuals passing a national examination, and some large labs and hospitals hire individuals expressly for their skill in phlebotomy. In Australia, individuals are required to complete a Certificate III in Pathology Collection or undertake on-the-job training by experienced phlebotomists.

Medical or clinical laboratories employ a variety of individuals in technical positions:

  • Medical laboratory scientists, also known as clinical laboratory scientists, typically hold a bachelor degree. They perform a wide variety of tests on various body fluids, including blood. The information they provide is essential to the primary care providers in screening for disease and increased risk of disease, determining a diagnosis and in monitoring the course of a disease and response to treatment.
  • Medical laboratory technicians typically have an associate degree and perform duties similar to those of a medical laboratory scientist but with some restrictions on career advancement.
  • Most pathology laboratories also employ pathology assistants who are responsible for processing patient samples and carrying out routine tasks within the lab. Although clinical training is required, this is usually provided by pathology staff.

Section Review

Blood is a fluid connective tissue critical to the transportation of nutrients, gases, and wastes throughout the body; to defend the body against infection and other threats; and to the homeostatic regulation of pH, temperature, and other internal conditions. Blood is composed of cellular components—erythrocytes, leukocytes, and cell fragments called platelets—and a fluid extracellular matrix called plasma. More than 90 percent of plasma is water. The remainder is mostly plasma proteins—mainly albumin, globulins and fibrinogen—and other dissolved solutes such as glucose, lipids, electrolytes, hormones, metabolic waste products and dissolved gases. Because of the cellular components and the plasma proteins and other solutes, blood is sticky and more viscous than water. It is also slightly alkaline and its temperature is slightly higher than normal body temperature.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=423

Critical Thinking question

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=423

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=423

5.2 Production of the Formed Elements

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Trace the generation of the formed elements (cellular components) of blood from bone marrow stem cells
  • Discuss the role of haemopoietic growth factors in promoting the production of the formed elements

The lifespan of the formed elements is very brief. Although one type of leukocyte called memory cells can survive for years, most erythrocytes, leukocytes, and platelets normally live only a few hours to a few months. Thus, the body must form new blood cells and platelets quickly and continuously. When you donate a unit of blood during a blood drive (approximately 475 mL), your body typically replaces the donated plasma within 24 hours, but it takes about 4 to 6 weeks to replace the blood cells. This restricts the frequency with which donors can contribute their blood. The process by which this replacement occurs is called haemopoiesis, or haematopoiesis (from the Greek root haima- = “blood”; -poiesis = “production”).

Sites of Haemopoiesis

Prior to birth, haemopoiesis occurs in a number of tissues, beginning with the yolk sac of the developing embryo and continuing in the foetal liver, spleen, lymphatic tissue and eventually the red bone marrow. Following birth, most haemopoiesis occurs in the red marrow, a connective tissue within the spaces of spongy (cancellous) bone tissue. In children, haemopoiesis can occur in all bones including the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus.

Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements. This process is referred to as extramedullary haemopoiesis (meaning haemopoiesis outside the medullary cavity of adult bones). When a disease such as bone cancer destroys the bone marrow, causing medullary haemopoiesis to fail, extramedullary haemopoiesis may be initiated.

Differentiation of Formed Elements from Stem Cells

All formed elements arise from stem cells of the red bone marrow. Recall that stem cells undergo mitosis plus cytokinesis (cellular division) to give rise to new daughter cells: One of these remains a stem cell and the other differentiates into one of any number of diverse cell types. Stem cells may be viewed as occupying a hierarchal system, with some loss of the ability to diversify at each step. The totipotent stem cell is the zygote, or fertilised egg. The totipotent (toti- = “all”) stem cell gives rise to all cells of the human body. The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting foetal membranes. Beneath this level, the mesenchymal cell is a stem cell that develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood, but not epithelium, muscle, and nervous tissue. One step lower on the hierarchy of stem cells is the haemopoietic stem cell, or haemocytoblast. All the formed elements of blood originate from this specific type of cell.

Haemopoiesis begins when the haemopoietic stem cell is exposed to appropriate chemical stimuli collectively called haemopoietic growth factors, which prompt it to divide and differentiate. One daughter cell remains a haemopoietic stem cell, allowing haemopoiesis to continue. The other daughter cell becomes either of two types of more specialised stem cells (Figure 5.2.1):

Webebd diagram of Haematopoietic system of bone marrow.
Figure 5.2.1. Haematopoietic system of bone marrow. Haemopoiesis is the proliferation and differentiation of the formed elements of blood.

Lymphoid and myeloid stem cells do not immediately divide and differentiate into mature formed elements. There are several intermediate stages of precursor cells, many of which can be recognised by their names, which have the suffix -blast. For instance, megakaryoblasts are the precursors of megakaryocytes, and proerythroblasts become reticulocytes, having lost their nucleus and other organelles yet retaining residual ribosomal RNA, before maturing into erythrocytes as illustrated in Figure 5.2.1.

Haemopoietic Growth Factors

Development from stem cells to precursor cells to mature cells is again initiated and controlled by haemopoietic growth factors. These include the following:

Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels. It prompts the production of haemoglobin and erythrocytes. Some athletes use synthetic EPO as a performance-enhancing drug (called blood doping) to increase RBC counts haemoglobin concentration and subsequently increase oxygen delivery to tissues throughout the body. EPO is a banned substance in most organised sports, but it is also used medically in the treatment of certain types of anaemia, specifically those triggered by certain types of cancer, and other disorders in which increased erythrocyte counts and oxygen levels are desirable.

Thrombopoietin, another glycoprotein hormone, is produced by the liver and kidneys. It triggers the production of megakaryoblasts and the development of megakaryocytes into platelets.

Cytokines are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. They act locally as autocrine or paracrine factors, stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease. There are two major subtypes of cytokines known as colony-stimulating factors and interleukins.

Colony-stimulating factors (CSFs) are glycoproteins that act locally, as autocrine or paracrine factors. Some trigger the differentiation of myeloblasts into granular leukocytes, namely, neutrophils, eosinophils, and basophils. These are referred to as granulocyte CSFs. A different CSF induces the production of monocytes, called monocyte CSF. Both granulocytes and monocytes are stimulated by GM-CSF; granulocytes, monocytes, platelets, and erythrocytes are stimulated by multi-CSF. Synthetic forms of these hormones are often administered to patients, with various forms of cancer who are receiving chemotherapy, to revive their WBC counts.

Interleukins are another class of cytokine signalling molecules important in haemopoiesis. They were initially thought to be secreted uniquely by leukocytes and to communicate only with other leukocytes, and were named accordingly, but are now known to be produced by a variety of cells including bone marrow and endothelium. Researchers now suspect that interleukins may play other roles in body functioning, including differentiation and maturation of cells, producing immunity and inflammation. To date, more than a dozen interleukins have been identified, with others likely to follow. They are generally numbered IL-1, IL-2, IL-3, etc.

Everyday Connection

Blood Doping

In its original intent, the term blood doping was used to describe the practice of injecting by transfusion supplemental RBCs into an individual, typically to enhance performance in a sport. Additional RBCs would deliver more oxygen to the tissues, providing extra aerobic capacity, clinically referred to as VO2 max. The source of the cells was either from the recipient (autologous) or from a donor with compatible blood (homologous). This practice was aided by the well-developed techniques of harvesting, concentrating, and freezing of the RBCs that could be later thawed and injected, yet still retain their functionality. These practices are considered illegal in virtually all sports and run the risk of causing infection, significantly increasing the viscosity of the blood and the potential for transmission of blood-borne pathogens if the blood was collected from another individual.

With the development of synthetic EPO in the 1980s, it became possible to provide additional RBCs by artificially stimulating RBC production in the bone marrow. Originally developed to treat patients suffering from anaemia due to renal failure or cancer treatment, large quantities of EPO can be generated by recombinant DNA technology. Synthetic EPO is injected under the skin and can increase haematocrit for many weeks. It may also induce polycythaemia and raise haematocrit to 70 or greater. This increased viscosity raises the resistance of the blood and forces the heart to pump more powerfully; in extreme cases, it has resulted in death. Other drugs such as cobalt II chloride have been shown to increase natural EPO gene expression. Blood doping has become problematic in many sports, especially cycling. Lance Armstrong, winner of seven Tour de France and many other cycling titles, was stripped of his victories and admitted to blood doping in 2013.

Bone Marrow Sampling and Transplants

Sometimes, a healthcare provider will order a bone marrow biopsy, a diagnostic test of a sample of red bone marrow. This involves inserting a large-bore needle into the region near the posterior iliac crest of the pelvic bones (os coxae) and collecting an aspirate of bone marrow fluid and a core biopsy of bone marrow matrix. These samples are required for the diagnosis and differentiation of various types of leukaemia and other diseases of bone marrow.

bone marrow (haemopoietic stem cell) transplant is a treatment in which a donor’s healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient suffering from diseases such as aplastic anaemia, thalassaemia, sickle cell anaemia and leukaemia. This type of transplant is called an allogeneic transplant. In many cases of leukaemia, the patient’s own haemopoietic stem cells can be harvested when the patient is in remission and transferred back to the patient if the leukaemia reoccurs.  This type of transplant is called an autologous transplant.

In the past, when haemopoietic stem cells were collected from a bone marrow donor, the procedure involved harvesting the stem cells directly from the marrow as described above for bone marrow biopsy: a very invasive and painful procedure. These days, bone marrow donors are pre-treated with CSFs, which mobilise the stem cells from the bone marrow to the peripheral blood where they are easily collected via simple venepuncture. The stem cells are isolated from the other cellular components of the blood and then frozen for later use.

For an individual requiring a transplant, a donor with a matching tissue type is essential to prevent the immune system from destroying the transplanted donor cells—a phenomenon known as tissue rejection. To treat patients with haemopoietic stem cells, it is first necessary to destroy the patient’s own diseased marrow through radiation and/or chemotherapy. Donor bone marrow stem cells are then intravenously infused into the transplant recipient. From the bloodstream, they establish themselves in the recipient’s bone marrow and repopulate the marrow and the blood with healthy blood cells.

Section Review

Through the process of haemopoiesis, the formed elements of blood are continually produced, replacing the relatively short-lived erythrocytes, leukocytes, and platelets. Haemopoiesis begins in the red bone marrow, with haemopoietic stem cells that differentiate into myeloid and lymphoid lineages. Myeloid stem cells give rise to most of the formed elements. Lymphoid stem cells give rise only to the various lymphocytes designated as B and T cells, and NK cells. Haemopoietic growth factors, including erythropoietin, thrombopoietin, colony-stimulating factors, and interleukins, promote the proliferation and differentiation of formed elements.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=426

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=426

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=426

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=426

5.3 Erythrocytes

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Describe the anatomy of erythrocytes
  • Discuss the various steps in the lifecycle of an erythrocyte
  • Explain the composition and function of haemoglobin

The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microlitre (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7–8 micrometres (µm) (Figure 5.3.1). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

 

Table that summarises formed elements in blood
Figure 5.3.1. Summary of formed elements in blood.

Shape and Structure of Erythrocytes

As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. Reticulocytes should comprise approximately 1–2 percent of the erythrocyte count and provide a rough estimate of the rate of RBC production, with abnormally low or high rates indicating deviations in the production of these cells. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. Lacking mitochondria, for example, they rely on anaerobic respiration. This means that they do not utilise any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesise proteins. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. This includes the protein spectrin, a cytoskeletal protein element. They also contain enzymes that protect haemoglobin from oxidisation.

Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the centre (Figure 5.3.2). Since they lack most organelles, there is more interior space for the presence of the haemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll.”

 

Images that show the shape of red blood cells
Figure 5.3.2. Shape of red blood cells. a) Erythrocytes are biconcave discs with very shallow centres. This shape optimises the ratio of surface area to volume, facilitating gas exchange. It also enables them to fold up as they move through narrow blood vessels; b) An image from a peripheral blood smear showing normochromic, normocytic red blood cells. A small lymphocyte is present from comparison. 100x oil immersion. From MLS Collection, University of Alberta, https://doi.org/10.7939/R3W669Q69.

Haemoglobin

Haemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figure 5.3.3a). Each of these globin molecules is bound to a red pigment molecule called haem, which contains an ion of iron (Fe2+) (Figure 5.3.3b).

Diagram of haemoglobin
Figure 5.3.3. Haemoglobin. (a) A molecule of haemoglobin contains four globin proteins, each of which is bound to one molecule of the iron-containing pigment haem. (b) A single erythrocyte can contain 300 million haemoglobin molecules, and thus more than 1 billion oxygen molecules.

Each iron ion in the haem can bind to one oxygen molecule; therefore, each haemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million haemoglobin molecules and therefore can bind to and transport up to 1.2 billion oxygen molecules (see Figure 5.3.3b).

In the lungs, haemoglobin picks up oxygen, which binds to the iron ions, forming oxyhaemoglobin. The bright red, oxygenated haemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced haemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so haemoglobin rarely if ever leaves all its oxygen behind. In the capillaries, carbon dioxide enters the bloodstream. About 76 percent dissolves in the plasma, some of it remaining as dissolved CO2, and the remainder forming bicarbonate ion. About 23–24 percent of it binds to the amino acids in haemoglobin, forming a molecule known as carbaminohemoglobin. From the capillaries, the haemoglobin carries carbon dioxide back to the lungs, where it releases it for exchange of oxygen.

Changes in the levels of RBCs can have significant effects on the body’s ability to effectively deliver oxygen to the tissues. Ineffective haematopoiesis results in insufficient numbers of RBCs and results in one of several forms of anaemia. An overproduction of RBCs produces a condition called polycythaemia. The primary drawback with polycythaemia is not a failure to directly deliver enough oxygen to the tissues, but rather the increased viscosity of the blood, which makes it more difficult for the heart to circulate the blood and increases the risk of thrombosis (excessive blood clot formation).

In patients with insufficient haemoglobin, the tissues may not receive sufficient oxygen, resulting in another form of anaemia. In determining oxygenation of tissues, the value of greatest interest in healthcare is the percent saturation; that is, the percentage of haemoglobin sites occupied by oxygen in a patient’s blood. Clinically this value is commonly referred to simply as “percent sat.”

Percent saturation is normally monitored using a device known as a pulse oximeter, which is applied to a thin part of the body, typically the tip of the patient’s finger. The device works by sending two different wavelengths of light (one red, the other infrared) through the finger and measuring the light with a photodetector as it exits. Haemoglobin absorbs light differentially depending upon its saturation with oxygen. The machine calibrates the amount of light received by the photodetector against the amount absorbed by the partially oxygenated haemoglobin and presents the data as percent saturation. Normal pulse oximeter readings range from 95–100 percent. Lower percentages reflect hypoxaemia, or low blood oxygen. The term hypoxia is more generic and simply refers to low oxygen levels. Oxygen levels are also directly monitored from free oxygen in the plasma typically following an arterial stick. When this method is applied, the amount of oxygen present is expressed in terms of partial pressure of oxygen or simply pO2 and is typically recorded in units of millimetres of mercury, mm Hg.

The kidneys filter about 180 litres (~380 pints) of blood in an average adult each day and thus serve as ideal sites for receptors that determine oxygen saturation. In response to hypoxaemia, less oxygen will exit the vessels supplying the kidney, resulting in hypoxia (low oxygen concentration) in the tissue fluid of the kidney where oxygen concentration is monitored. Interstitial fibroblasts within the kidney secrete EPO, thereby increasing erythrocyte and haemoglobin production and restoring oxygen levels. In a classic negative-feedback loop, as oxygen saturation rises, EPO secretion falls, and vice versa, thereby maintaining homeostasis. Populations dwelling at high altitudes, with inherently lower levels of oxygen in the atmosphere, naturally maintain a haematocrit higher than people living at sea level. Consequently, people traveling to high altitudes may experience symptoms of hypoxaemia, such as fatigue, headache, and shortness of breath, for a few days after their arrival. In response to the hypoxaemia, the kidneys secrete EPO to step up the production of erythrocytes until homeostasis is achieved once again. To avoid the symptoms of hypoxaemia, or altitude sickness, mountain climbers typically rest for several days to a week or more at a series of camps situated at increasing elevations to allow EPO levels and, consequently, erythrocyte counts to rise. When climbing the tallest peaks, such as Mt. Everest and K2 in the Himalayas, many mountain climbers rely upon bottled oxygen as they near the summit.

Lifecycle of Erythrocytes

Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, several raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids. However, erythrocyte production also requires several micronutrients including trace elements and vitamins:

Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a type of myeloid phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen. The components of the degraded erythrocytes’ haemoglobin are further processed as follows:

Globin, the protein portion of haemoglobin, is broken down into amino acids, which can be sent back to the liver for construction of new proteins.

The iron contained in the haem portion of haemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes.

The non-iron portion of haem is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which excretes it in bile, a fluid released into the intestines to help emulsify dietary fats. In the large intestine, bacteria break the bilirubin apart from the bile and convert it to urobilinogen and then into stercobilin. It is then eliminated from the body in the faeces. Broad-spectrum antibiotics typically eliminate these “good” bacteria as well and this may alter the colour of faeces. The kidneys also remove any circulating bilirubin and other related metabolic by-products such as urobilins and secrete them into the urine.

The breakdown pigments formed from the destruction of haemoglobin can be seen in a variety of situations. At the site of an injury, biliverdin from damaged RBCs produces some of the dramatic colours associated with bruising. With a failing liver, bilirubin cannot be removed effectively from circulation and causes the body to assume a yellowish tinge associated with jaundice. Stercobilins within the faeces produce the typical brown colour associated with this waste and the yellow of urine is associated with the urobilins.

The erythrocyte lifecycle is summarised in Figure 5.3.4.

Diagram of Erythrocyte lifecycle
Figure 5.3.4. Erythrocyte lifecycle. Erythrocytes are produced in the bone marrow and sent into the circulation. At the end of their lifecycle, they are destroyed by macrophages in the spleen, and their components are recycled.

Disorders of Erythrocytes

The size, shape, and number of erythrocytes, and the number of haemoglobin molecules can have a major impact on a person’s health. When the number of RBCs or amount of haemoglobin is deficient, the general condition is called anaemia. There are more than 400 types of anaemia and approximately 4.5% of Australian adults are at risk of anaemia. Anaemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased RBC production, and those caused by excessive destruction of RBCs. Clinicians often use two groupings in diagnosis: The kinetic approach focuses on evaluating the production, destruction, and removal of RBCs, whereas the morphological approach examines the RBCs themselves, paying particular emphasis to their size. A common test is the mean cell volume (MCV), which measures RBC size. Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than-normal cells are referred to as macrocytic. Reticulocyte counts are also important and may reveal inadequate production of RBCs. The effects of the various anaemias are widespread, because reduced numbers of RBCs or haemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anaemia produces fatigue, lethargy, and an increased risk for infection. An oxygen deficit in the brain impairs the ability to think clearly and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.

Anaemias resulting from acute blood loss are usually easy to identify. In addition to bleeding from external wounds or other visible lesions, blood loss anaemias may be due to chronic bleeding from ulcers, haemorrhoids, inflammation of the stomach (gastritis) and some cancers of the gastrointestinal tract. The excessive use of aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen can trigger ulceration and gastritis leading to chronic blood loss. Excessive menstruation and loss of blood during childbirth are also potential causes of anaemia.

Anaemias caused by faulty or decreased RBC production include sickle cell anaemia, iron deficiency, vitamin deficiency anaemia and diseases of the bone marrow and stem cells.

Image of sickle cells
Figure 5.3.5. Sickle cells. Sickle cell anaemia is caused by a mutation in one of the haemoglobin genes. Erythrocytes produce an abnormal type of haemoglobin, which causes the cell to take on a sickle or crescent shape. (credit: Janice Haney Carr).

A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anaemia).  Sickle cell anaemia is caused by production of an abnormal type of haemoglobin, called haemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle (or crescent) shape, especially at low oxygen concentrations (Figure 5.3.5). These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents (strokes). Sickle cell anaemia is a genetic or inherited blood disorder more commonly found in individuals of African, Middle Eastern, Asian, Indian and Mediterranean descent.

Iron deficiency anaemia is the most common type of anaemia and results when the amount of available iron is insufficient to allow production of sufficient haemoglobin. This condition can occur in individuals with a deficiency of iron in the diet and is especially common in teens and children as well as in vegans and vegetarians. Additionally, iron deficiency anaemia may be caused by either an inability to absorb and transport iron, or slow chronic bleeding usually from the gastrointestinal tract or through heavy menstruation.

Vitamin-deficient anaemias generally involve insufficient vitamin B12 and folate.

Megaloblastic anaemia is the result of a deficiency of vitamin B12 and/or folate, and often involves diets deficient in these essential nutrients. Lack of animal products or viable alternate sources in the diet can lead to a lack of vitamin B12 and overcooking or eating insufficient amounts of vegetables may lead to a lack of folate.

Pernicious anaemia is a type of megaloblastic anaemia caused by poor absorption of vitamin B12 and is often seen in patients with Crohn’s disease (a severe intestinal disorder often treated by surgery), surgical removal of the intestines or stomach (common in some weight loss surgeries), the presence of intestinal parasites and AIDS.

Pregnancies, some medications, excessive alcohol consumption, and some diseases such as coeliac disease are also associated with vitamin deficiencies. It is essential to provide sufficient folic acid during the early stages of pregnancy to reduce the risk of neurological defects, including spina bifida, a failure of the neural tube to close.

Assorted disease processes can also interfere with the production and formation of RBCs and haemoglobin. If myeloid stem cells are defective or replaced by cancer cells, there will be insufficient quantities of RBCs produced.

Aplastic anaemia is the condition in which there are deficient numbers of RBC stem cells. Aplastic anaemia is often inherited, or it may be triggered by radiation, medication, chemotherapy, or infection, particularly by Parvo virus B19.

Thalassaemia is an inherited condition typically occurring in individuals from the Middle East, the Mediterranean, Africa, and Southeast Asia, in which the lifespan of RBCs is shortened due to unbalanced production of globin chains.

Hereditary spherocytosis is another inherited form of anaemia associated with shortened RBC survival. In this case the spectrin in the RBC membrane is defective resulting in loss of membrane without loss of cell contents as the cells circulate through small capillaries. This change in the surface area to volume ratio causes the RBCs to lose their bi-concave disc shape and become spherical (spherocytes). Spherocytes are less flexible than normal RBC and become trapped in the spleen, where they are removed by splenic macrophages.

Lead exposure from industrial sources or even dust from paint chips of iron-containing paints or pottery that has not been properly glazed may also lead to destruction of the red marrow.

Various disease processes can also lead to anaemias. These include chronic kidney diseases often associated with decreased production of EPO, hypothyroidism, some forms of cancer, especially leukaemia and bone cancers, and autoimmune diseases such as lupus, and rheumatoid arthritis.

In contrast to anaemia, an elevated RBC count is called polycythaemia and is detected in a patient’s elevated haematocrit. It can occur transiently in a person who is dehydrated; when water intake is inadequate or water losses are excessive, the plasma volume falls. As a result, the haematocrit rises. For reasons mentioned earlier, a mild form of polycythaemia is chronic but normal in people living at high altitudes. Some elite athletes train at high altitudes specifically to induce this phenomenon. Finally, a type of bone marrow disease called polycythaemia vera (from the Greek vera = “true”) causes an excessive production of immature erythrocytes. Polycythaemia vera can dangerously elevate the viscosity of blood, raising blood pressure and making it more difficult for the heart to pump blood throughout the body. It is a relatively rare disease that occurs more often in men than women and is more likely to be present in people over 60 years of age.

Section Review

The most abundant formed elements in blood, erythrocytes, are red, biconcave disks packed with an oxygen-carrying compound called haemoglobin. The haemoglobin molecule contains four globin chains each bound to a pigment molecule called haem, which contains an ion of iron. In the bloodstream, iron picks up oxygen in the lungs and drops it off in the tissues; the amino acids in haemoglobin then transport carbon dioxide from the tissues back to the lungs. Erythrocytes live only 120 days on average, and thus must be continually replaced. Worn-out erythrocytes are phagocytosed by macrophages and their haemoglobin is broken down. The breakdown products are recycled or removed as wastes: Globin is broken down into amino acids for synthesis of new proteins; iron is stored in the liver or spleen or used by the bone marrow for production of new erythrocytes; and the remnants of haem are converted into bilirubin, or other waste products that are taken up by the liver and excreted in the bile or removed by the kidneys. Anaemia is a deficiency of RBCs and/or haemoglobin, whereas polycythaemia is an excess of RBCs.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=428

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=428

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=428

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=428

5.4 Leukocytes and Platelets

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Describe the general characteristics of leukocytes
  • Classify leukocytes according to their lineage, their main structural features and their primary functions
  • Discuss the most common malignancies involving leukocytes
  • Identify the lineage, basic structure and function of platelets

The leukocyte, commonly known as a white blood cell (or WBC), is a major component of the body’s defences against disease. Leukocytes protect the body against invading microorganisms and body cells with mutated DNA, and they clean up debris. Platelets are essential for the repair of damaged blood vessels; they also provide growth factors for healing and repair.

Characteristics of Leukocytes

Although leukocytes and erythrocytes both originate from hematopoietic stem cells in the bone marrow, they are very different from each other in many significant ways. For instance, leukocytes are far less numerous than erythrocytes: Typically, there are only 5000 to 10,000 per µL. They are also larger than erythrocytes and are the only formed elements that are complete cells, possessing a nucleus and organelles. And although there is just one type of erythrocyte, there are many types of leukocytes. Most of these types have a much shorter lifespan than that of erythrocytes, some as short as a few hours or even a few minutes in the case of cells responding to acute infection.

One of the most distinctive characteristics of leukocytes is their movement. Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body’s tissues. For leukocytes, the vascular network is simply a highway they travel and soon exit to reach their true destination. When they arrive, they are often given distinct names, such as macrophage or microglia, depending on their function. As shown in Figure 5.4.1, they leave the capillaries—the smallest blood vessels—or other small vessels through a process known as emigration (from the Latin for “removal”) or diapedesis (dia- = “through”; -pedan = “to leap”) or extravasation (extra = “outside”; vas = “vessel”) in which they squeeze through adjacent cells in a blood vessel wall.

Once they have exited the capillaries, some leukocytes will take up fixed positions in lymphatic tissue, bone marrow, the spleen, the thymus, liver or other organs. Others will move about through the tissue spaces very much like amoebas, continuously extending their plasma membranes, sometimes wandering freely, and sometimes moving toward the direction in which they are drawn by chemical signals. This attracting of leukocytes occurs because of positive chemotaxis (movement in response to chemicals), a phenomenon in which injured or infected cells and nearby leukocytes emit the equivalent of a chemical “000” (or “911” in U.S.A) call, attracting more leukocytes to the site.

Figure 5.4.1. Emigration. Leukocytes exit the blood vessel and then move through the connective tissue of the dermis toward the site of a wound. Some leukocytes, such as the eosinophil and neutrophil, are characterised as granular leukocytes. They release chemicals from their granules that destroy pathogens; they are also capable of phagocytosis. The monocyte, sometimes referred to as an agranular leukocyte, differentiates into a macrophage that then phagocytises the pathogens.
Figure 5.4.1. Emigration. Leukocytes exit the blood vessel and then move through the connective tissue of the dermis toward the site of a wound. Some leukocytes, such as the eosinophil and neutrophil, are characterised as granular leukocytes. They release chemicals from their granules that destroy pathogens; they are also capable of phagocytosis. The monocyte, sometimes referred to as an agranular leukocyte, differentiates into a macrophage that then phagocytises the pathogens.

Classification of Leukocytes

When scientists first began to observe stained blood slides, it quickly became evident that leukocytes could be divided into two groups, according to whether their cytoplasm contained highly visible granules:

Granular leukocytes, or granulocytes, contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils.

While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious on stained blood slides. Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.

Granular Leukocytes

We will consider the granular leukocytes in order from most common to least common. All of these are produced in the red bone marrow and have a short lifespan of hours to days. They typically have a lobed nucleus and are classified according to which type of stain best highlights their granules (Figure 5.4.2).

Granular leukocytes
Figure 5.4.2. Granular leukocytes. A neutrophil has small granules that stain light lilac and a nucleus with two to five lobes. An eosinophil’s granules are slightly larger and stain reddish-orange, and its nucleus has two to three lobes. A basophil has large granules that stain dark blue to purple and a two-lobed nucleus that is often obscured by the granules.

The most common of all the leukocytes, neutrophils will normally comprise 50–70 percent of the total leukocyte count. They are 10–12 µm in diameter, significantly larger than erythrocytes. They are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic). The granules are numerous but quite fine and normally appear light lilac. The nucleus has a distinct lobed appearance and may have two to five lobes, the number increasing with the age of the cell. Older neutrophils have increasing numbers of lobes and are often referred to as polymorphonuclear (a nucleus with many forms), or simply “polys.” Younger and immature neutrophils begin to develop lobes and are known as “bands.”

Neutrophils are rapid responders to the site of infection and are efficient phagocytes with a preference for bacteria. Their granules contain lysozyme, an enzyme capable of lysing, or breaking down, bacterial cell walls; oxidants such as hydrogen peroxide; and defensins, proteins that bind to and puncture bacterial and fungal plasma membranes, so that the cell contents leak out. Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin. Low counts may be caused by drug toxicity and other disorders, including leukaemia and bone marrow failure, and may increase an individual’s susceptibility to infection.

Eosinophils typically represent 2–4 percent of the total leukocyte count. They are also 10–12 µm in diameter. The granules of eosinophils stain best with an acidic stain known as eosin. The nucleus of the eosinophil will typically have two to three lobes and, if stained properly, the granules will have a distinct red to orange colour.

The granules of eosinophils contain antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced by basophils and mast cells. Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat. Eosinophils are also capable of phagocytosis and are particularly effective when antibodies bind to the target and form an antigen-antibody complex. High counts of eosinophils are associated with allergies, parasitic worm infestations, and some autoimmune diseases. Low counts may be due to drug toxicity and stress.

Basophils are the least common leukocytes, typically comprising less than one percent of the total leukocyte count. They are slightly smaller than neutrophils and eosinophils at 8–10 µm in diameter. The granules of basophils stain best with basic (alkaline) stains. Basophils contain large granules that pick up a dark blue stain and are so dark and numerous they may make it difficult to see the two-lobed nucleus.

In general, basophils intensify the inflammatory response. They share this trait with mast cells. In the past, mast cells were considered to be basophils that had left the circulation. However, this appears not to be the case, as the two cell types develop from different lineages.

The granules of basophils release histamines, which contribute to inflammation, and heparin, which opposes blood clotting. High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism. Low counts are associated with pregnancy, stress, and hyperthyroidism.

Agranular Leukocytes

Agranular leukocytes contain smaller, less-visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes.

Lymphocytes are the only formed element of blood that arises from lymphoid stem cells. Although they form initially in the bone marrow, much of their subsequent development and proliferation occurs in the lymphatic tissues. Lymphocytes are the second most common type of leukocyte, accounting for about 20–30 percent of all leukocytes, and are essential for the immune response. The size range of lymphocytes is quite extensive, with some authorities recognising two size classes and others three. Typically, the large cells are 10–14 µm and have a smaller nucleus-to-cytoplasm ratio and more obvious granules. The smaller cells, referred to as “small resting lymphocytes” or “naive lymphocytes” are typically 6–9 µm with a larger volume of nucleus to cytoplasm. A few cells may fall outside these ranges, at 14–17 µm. This finding has led to the three size range classification.

The three major groups of lymphocytes include natural killer cells, B cells, and T cells. Natural killer (NK) cells are capable of recognising cells that do not express “self” proteins on their plasma membrane or that contain foreign or abnormal markers. These “non-self” cells include cancer cells, cells infected with a virus, and other cells with atypical surface proteins. Thus, they provide generalised, nonspecific immunity. The larger more granular lymphocytes are typically NK cells.

B cells and T cells, also called B lymphocytes and T lymphocytes, play prominent roles in defending the body against specific pathogens (disease-causing microorganisms) and are involved in specific immunity. One form of B cells (plasma cells) produces the antibodies or immunoglobulins that bind to specific foreign or abnormal components of plasma membranes. These B cells and the antibodies they produce form part of the immune response referred to as humoral (body fluid) immunity. T cells provide cell-mediated immunity by physically attacking foreign or diseased cells. A memory cell is a variety of both B and T cells that develops after exposure to a pathogen and mounts rapid responses upon subsequent exposures to the same pathogen. Unlike other leukocytes, memory cells live for many years. B cells undergo a maturation process in the bone marrow, whereas T cells undergo maturation in the thymus. This site of the maturation process gives rise to the name B and T cells. The functions of lymphocytes are complex and will be covered in detail in the chapter covering the lymphatic system and immunity. Smaller lymphocytes are either B or T cells that have not yet encountered a foreign invader, although they cannot be differentiated in a normal blood smear.

Abnormally high lymphocyte counts are characteristic of viral infections and Bordetella pertussis (Whooping cough) as well as some types of cancer, particularly lymphomas. Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids.

Monocytes originate from myeloid stem cells. They normally represent 2–8 percent of the total leukocyte count. They are typically easily recognised by their large size of 12–20 µm and indented or horseshoe-shaped nuclei. Macrophages are monocytes that have left the circulation and they phagocytose debris, foreign pathogens, aged or damaged erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release antimicrobial defensins and chemotactic chemicals that attract other leukocytes to the site of an infection or tissue damage. Some macrophages occupy fixed locations, whereas others wander through the tissue fluid.

Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukaemia and other chronic diseases. Abnormally low counts are typically caused by suppression of the bone marrow. Figure 5.4.4 illustrates the five main types of circulating leukocytes. In clinical medicine, the differential counts of the types and percentages of leukocytes present in a blood sample are often key indicators in making a diagnosis and selecting a treatment.

Leukocytes
Figure 5.4.4. Leukocytes. (Micrographs provided by the Regents of University of Michigan Medical School © 2012).

Lifecycle of Leukocytes

Most leukocytes have a relatively short lifespan, typically measured in hours or days. Production of all leukocytes begins in the bone marrow under the influence of CSFs and interleukins. Secondary production and maturation of lymphocytes occurs in specific regions of lymphatic tissue known as germinal centres. Lymphocytes are fully capable of mitosis and may produce clones of cells with identical properties. This capacity enables an individual to maintain immunity throughout life to many threats that have been encountered in the past.

Disorders of Leukocytes

Leukopenia is a condition in which too few leukocytes are produced. Leukopenic individuals may be unable to ward off infectious diseases. Excessive leukocyte proliferation is known as leukocytosis. Leukocytosis is often an indicator of the presence of infection or inflammation.

Leukaemia is a cancer involving over production of abnormal leukocytes. It usually involves only one specific type of leukocyte from either the myeloid line (myeloid leukaemia) or the lymphoid line (lymphocytic leukaemia). In chronic leukaemia, mature leukocytes accumulate and fail to die. In acute leukaemia, there is an overproduction of abnormal immature leukocytes. Both conditions arise from a genetic mutation in a single cell and in both conditions the cells do not function properly.

Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver and other tissues. As in leukaemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection. Some forms of lymphoma tend to progress slowly and respond well to treatment. Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.

Platelets

You may occasionally see platelets referred to as thrombocytes, but because this name suggests they are a type of cell, it is not accurate. A platelet is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane. Megakaryocytes are descended from myeloid stem cells and are large, typically 50–100 µm in diameter, and contain an enlarged, multi-lobed nucleus. As noted earlier, thrombopoietin, a glycoprotein secreted by the kidneys and liver, stimulates the proliferation of megakaryoblasts, which mature into megakaryocytes. These remain within bone marrow tissue and ultimately form platelet-precursor extensions that extend through the walls of bone marrow capillaries to release into the circulation thousands of cytoplasmic fragments, each enclosed in a plasma membrane. These enclosed fragments are platelets. Each megakaryocyte releases 2000–3000 platelets during its lifespan. Following platelet release, megakaryocyte remnants, which are little more than a cell nucleus, are consumed by macrophages. The process of platelet production, thrombopoiesis, is summarised in figure 5.4.4.

Platelets are relatively small, 2–4 µm in diameter, but numerous, with typically 150,000–160,000 per µL of blood. After entering the circulation, approximately one-third migrate to the spleen for storage for later release in response to any rupture in a blood vessel. When a blood vessel is damaged, platelets become activated to perform their primary function, which is to limit blood loss. Platelets remain in the circulation for only about 10 days and are then phagocytosed by macrophages.

In addition to their critical role in haemostasis, the stoppage of blood loss following damage to a blood vessel. Platelets also secrete a variety of growth factors essential for growth and repair of tissue, particularly connective tissue. Infusions of concentrated platelets are now being used in some therapies to stimulate healing. Platelet rich plasma injections are also used by beauty therapists to “reinvigorate” the skin of their clients.

Disorders of Platelets

Thrombocytosis is a condition in which there are too many platelets. This may trigger formation of unwanted blood clots (thrombosis), a potentially fatal disorder. If there is an insufficient number of platelets, called thrombocytopenia, blood may not clot properly, and excessive bleeding may result. Inherited and acquired disorders of platelet function can also lead to excessive bleeding despite normal platelet numbers.

Diagram of Platelets
Figure 5.4.4. Platelets. Platelets are derived from cells called megakaryocytes.

Section Review

Leukocytes function in body defences. They squeeze out of the walls of blood vessels through emigration or diapedesis, then may move through connective tissue, lymphatic fluid or become residents in various organs where they fight against pathogenic organisms, diseased cells, or other threats to health. Granular leukocytes or granulocytes, which include neutrophils, eosinophils, and basophils, originate from myeloid stem cells, as do monocytes. The other so called agranular leukocytes, NK cells, B cells, and T cells, arise from the lymphoid stem cell line. The most abundant leukocytes are the neutrophils, which are first responders to infections, especially bacterial infections. About 20–30 percent of all leukocytes are lymphocytes, which are critical to the body’s defences against specific threats. Leukaemia and lymphoma are malignancies involving leukocytes. Platelets are fragments of cells known as megakaryocytes that dwell within the bone marrow. While many platelets are stored in the spleen, others enter the circulation and are essential for haemostasis; they also produce several growth factors important for repair and healing.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=430

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=430

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=430

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=430

5.5 Haemostasis

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Describe the three mechanisms involved in haemostasis
  • Explain how the extrinsic and intrinsic coagulation pathways lead to the common pathway and the coagulation factors involved in each
  • Discuss disorders affecting haemostasis

Platelets are key players in haemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Although rupture of larger vessels usually requires medical intervention, haemostasis is quite effective in dealing with small, simple wounds and small internal bleeds. There are three steps to the process: vascular spasm, the formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will result in haemorrhage—excessive bleeding. The vascular response and platelet plug formation are referred to as primary haemostasis and coagulation is referred to a secondary haemostasis.

Vascular Spasm

When a blood vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically. This smooth muscle has both circular layers; larger vessels also have longitudinal layers. The circular layers tend to constrict, which narrows the vessel lumen, and slows the flow of blood. The longitudinal layers, when present, draw the vessel back into the surrounding tissue, often making it more difficult for a surgeon to locate, clamp, and tie off a severed vessel. The vascular spasm response is believed to be triggered by several chemicals called endothelins that are released by vessel-lining (endothelial) cells and by pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes, although it can last for hours.

Formation of the Platelet Plug

In the second step, platelets, which normally float free in the plasma, encounter exposed underlying connective tissue and collagenous fibres at the site of blood vessel damage. The platelets bind (adhesion) to the exposed collagen and become activated. Activated platelets are spiked and sticky and bind to other activated platelets (aggregation) and the endothelial lining. Platelet adhesion is assisted by a glycoprotein released from neighbouring endothelial cells called von Willebrand factor, which helps stabilise the growing platelet plug. Platelet aggregation is aided by the plasma protein, fibrinogen, which forms bridges between adjacent platelets at the site of bleed vessel damage. As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to haemostasis. Among the substances released by the platelets are:

A platelet plug can temporarily seal a small opening in a blood vessel. Plug formation, in essence, buys the body time while more sophisticated and durable repairs are being made. In a similar manner, even modern naval warships still carry an assortment of wooden plugs to temporarily repair small breaches in their hulls until permanent repairs can be made.

Coagulation

Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot. The process is sometimes characterised as a cascade, because one event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from fibrinogen, the plasma protein introduced earlier—in which platelets and blood cells are trapped. Figure 5.5.1 summarises the three steps of haemostasis.

. (a) An injury to a blood vessel initiates the process of haemostasis. Blood clotting involves three steps. First, vascular spasm slows the flow of blood. Next, a platelet plug forms to temporarily seal small openings in the vessel. Coagulation then enables the repair of the vessel wall once the leakage of blood has stopped. (b) The synthesis of fibrin in blood clots involves both an intrinsic pathway and an extrinsic pathway, both of which lead to a common pathway
Figure 5.5.1. Haemostasis. (a) An injury to a blood vessel initiates the process of haemostasis. Blood clotting involves three steps. First, vascular spasm slows the flow of blood. Next, a platelet plug forms to temporarily seal small openings in the vessel. Coagulation then enables the repair of the vessel wall once the leakage of blood has stopped. (b) The synthesis of fibrin in blood clots involves both an intrinsic pathway and an extrinsic pathway, both of which lead to a common pathway. (credit a: Kevin MacKenzie).

Clotting Factors Involved in Coagulation

In the coagulation cascade, plasma proteins called clotting factors (or coagulation factors) prompt reactions that activate still more coagulation factors. The process is complex, but is initiated along two basic pathways:

Both of these pathways merge into a third pathway, referred to as the common pathway (see Figure 5.5.1b). All three pathways are dependent upon the 12 known clotting factors, including Ca2+ and vitamin K (Table 5.5.1). Clotting factors are secreted as inactive enzymes primarily by the liver and the platelets. The liver requires the fat-soluble vitamin K to produce many of them. Vitamin K (along with biotin and folate) is somewhat unusual among vitamins in that it is not only consumed in the diet but is also synthesised by bacteria residing in the large intestine. The calcium ion, considered factor IV, is derived from the diet and from the breakdown of bone. Some recent evidence indicates that activation of various clotting factors occurs on specific receptor sites on the surfaces of activated platelets.

The 12 clotting factors are numbered I through XIII according to the order of their discovery. Factor VI was once believed to be a distinct clotting factor, but is now thought to be identical to factor V. Rather than renumber the other factors, factor VI was allowed to remain as a placeholder and also a reminder that knowledge changes over time. Activated factors are denoted by the additions of the letter “a” after the factor number. For example, factor Va denotes activated factor five.

Table 5.5.1. Clotting factors

*Vitamin K Required

Factor number Name Type of molecule Source Pathway(s)
I Fibrinogen Plasma protein Liver Common; converted into fibrin
II Prothrombin Plasma protein Liver* Common; converted into thrombin
III Tissue thromboplastin or tissue factor Lipoprotein mixture Damaged cells and platelets Extrinsic
IV Calcium ions Inorganic ions in plasma Diet, platelets, bone matrix Entire process
V Proaccelerin Plasma protein Liver, platelets Extrinsic and intrinsic
VI Not used Not used Not used Not used
VII Proconvertin Plasma protein Liver* Extrinsic
VIII Antihemophilic factor A Plasma protein factor Platelets and endothelial cells Intrinsic; deficiency results in haemophilia A
IX Antihemophilic factor B (plasma thromboplastin component) Plasma protein Liver* Intrinsic; deficiency results in haemophilia B
X Stuart-Power factor (thrombokinase) Protein Liver* Extrinsic and intrinsic
XI Plasma thromboplastin antecedent Plasma protein Liver Intrinsic; deficiency results in haemophilia C
XII Hageman factor Plasma protein Liver Intrinsic; initiates clotting in vitro also activates plasmin
XIII Fibrin-stabilising factor Plasma protein Liver, platelets Stabilises fibrin; slows fibrinolysis

Extrinsic Pathway

The quicker responding and more direct extrinsic pathway (also known as the tissue factor pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury. Damaged extravascular cells, which are extrinsic to the bloodstream, express factor III, also known as tissue factor or thromboplastin. When factor VII in the plasma comes into contact with exposed factor III, it becomes activated to factor VIIa. Factor VIII, Factor VIIa and Ca2+ then form an active enzyme complex. This enzyme complex leads to activation of factor X (Stuart–Prower Factor), which activates the common pathway discussed below. The events in the extrinsic pathway are completed in a matter of seconds.

Intrinsic Pathway

The intrinsic pathway (also known as the contact activation pathway) is longer and more complex. In this case, the factors involved are intrinsic to (present within) the bloodstream. The pathway can be prompted by damage to the tissues, resulting from internal factors such as arterial disease; however, it is most often initiated when factor XII (Hageman factor) comes into contact with negatively charged molecules, such as phospholipids expressed on the surface of activated platelets. Factor XII can also be activated by contact with foreign materials such as artificial heart valves and the surface of some bacteria. Factor XII is also activated when blood comes into contact with glass, in a test tube for example. Factor XIIa sets off a series of reactions that in turn activates factor XI (plasma thromboplastin antecedent) then factor IX (antihemophilic factor B or plasma thromboplasmin). In the meantime, substances released by the platelets increase the rate of these activation reactions. Finally, factor IXa binds to its cofactor, factor VIII (antihemophilic factor A) to form an enzyme complex that activates factor X (Stuart-Prower Factor or thrombokinase), leading to the common pathway. The events in the intrinsic pathway are completed in a few minutes.

Common Pathway

Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel. Once factor X has been activated to become the enzyme prothrombinase (factor Xa) by either the intrinsic or extrinsic pathway, it converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. (Note that if the enzyme thrombin were not normally in an inactive form, clots would form spontaneously, a condition not consistent with life.) Then, thrombin converts factor I, the soluble plasma protein fibrinogen, into the insoluble protein fibrin protein strands. Fibrin molecules spontaneously join together to form a mesh, which is stabilised by cross-linking reactions catalysed by Factor XIIIa.

Fibrinolysis

The stabilised clot undergoes contraction via the action of contractile proteins within platelets. As these proteins contract, they pull on the fibrin threads, bringing the edges of the clot more tightly together, somewhat as we do when tightening loose shoelaces. This process also wrings out of the clot a small amount of fluid called serum, which is blood plasma without its clotting factors.

To restore normal blood flow as the vessel heals, the clot must eventually be removed. The process by which the clot is gradually degraded is called fibrinolysis. Like coagulation, fibrinolysis involves a fairly complicated series of protein catabolising reactions. During this process, the inactive protein plasminogen, released by endothelial cells around the site of blood vessel damage, is converted into the active enzyme plasmin, which gradually breaks down the fibrin of the clot. Additionally, bradykinin, a vasodilator, released from damaged tissues as a pain signal, reverses the effects of the serotonin and prostaglandins secreted by the platelets. This allows the smooth muscle in the walls of the vessels to relax and helps to restore the circulation.

Plasma Anticoagulants

An anticoagulant is any substance that opposes coagulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood. For instance, a cluster of proteins collectively referred to as the protein C system inactivates clotting factors involved in the intrinsic pathway. TFPI (tissue factor pathway inhibitor) inhibits the conversion of the inactive factor VII to the active form in the extrinsic pathway. Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway. And as noted earlier, basophils release heparin, a short-acting anticoagulant that also opposes prothrombin. Heparin is also found on the surfaces of cells lining the blood vessels. A pharmaceutical form of heparin is often administered therapeutically, for example, in surgical patients at risk for blood clots.

Disorders of Clotting

Either an insufficient or an excessive production of platelets can lead to severe bleeding on the hand or excessive platelet plug formation on the other. Both of these situations can be life-threatening. As discussed earlier, an insufficient number of platelets, called thrombocytopenia, typically results in the inability of blood to form clots. This can lead to excessive bleeding, even from minor wounds.

Another reason for failure of the blood to clot is the inadequate production of functional amounts of one or more clotting factors. This is the case in the genetic disorder haemophilia, which is actually a group of related disorders, the most common of which is haemophilia A, accounting for approximately 80 percent of cases. This disorder results in the inability to synthesise enough factor VIII. Haemophilia B is the second most common form, accounting for approximately 20 percent of cases. In this case, there is a deficiency of factor IX. Both of these defects are linked to the X chromosome and are typically passed from a healthy (carrier) mother to her male offspring, since males are XY. Females would need to inherit a defective gene from each parent to manifest the disease, since they are XX. Patients with haemophilia bleed from even minor internal and external wounds, and leak blood into joint spaces after exercise and into urine and stool. Haemophilia C is a rare condition that is triggered by an autosomal (not sex) chromosome defect that renders factor XI non-functional. It is not a true recessive condition, since even individuals with a single copy of the mutant gene show a tendency to bleed. Regular infusions of clotting factors isolated from healthy donors, or manufactured as recombinant proteins, can help prevent bleeding in haemophiliac patients. At some point, genetic therapy will become a viable option.

In contrast to the disorders characterised by thrombocytopenia is thrombocytosis, also mentioned earlier, a condition characterised by excessive numbers of platelets that increases the risk for excessive clot formation, a condition known as thrombosis. Inherited or acquired failures in the control or regulation of coagulation can also result in a tendency towards thrombosis: a condition referred to as thrombophilia or hypercoagulation. Deficiencies of protein C or antithrombin, for example, can predispose an individual to thrombosis. Acquired forms of thrombophilia include the autoimmune disease lupus, immune reactions to heparin, polycythaemia vera, sickle cell disease, pregnancy, and even obesity. A thrombus (plural = thrombi) is an aggregation of platelets, erythrocytes, and even WBCs typically trapped within a mass of fibrin strands. While the formation of a clot is normal following the haemostatic response to blood vessel damage just described, thrombi can form within an intact or only slightly damaged blood vessel. In a large vessel, a thrombus will adhere to the vessel wall and decrease the flow of blood and is referred to as a mural thrombus. In a small vessel, it may totally block the flow of blood and is termed an occlusive thrombus. Thrombi are most caused by vessel damage to the endothelial lining, which activates the clotting mechanism. These may include venous stasis, when blood in the veins, particularly in the legs, remains stationary for long periods. This is one of the dangers of long airplane flights in crowded conditions and may lead to deep vein thrombosis or atherosclerosis, an accumulation of fats, macrophages and cell debris in the walls of arteries. A thrombus can seriously impede blood flow to or from a region and will cause a local increase in blood pressure. If flow is to be maintained, the heart will need to generate a greater pressure to overcome the resistance.

When a portion of a thrombus breaks free from the vessel wall and enters the circulation, it is referred to as an embolus. An embolus that is carried through the bloodstream can be large enough to block a vessel critical to a major organ. When it becomes trapped, an embolus is called an embolism. In the heart, brain, or lungs, an embolism may accordingly cause a heart attack, a stroke, or a pulmonary embolism. These are medical emergencies.

Among the many known biochemical activities of aspirin is its role as an anticoagulant. Aspirin (acetylsalicylic acid) is very effective at inhibiting the aggregation of platelets. Physicians sometimes recommend that patients at risk for cardiovascular disease, which can lead to heart attack or stroke, take a low dose of aspirin on a daily basis as a preventive measure. However, aspirin can also lead to serious side effects, including increasing the risk of gastrointestinal ulcers. A patient is well advised to consult a physician before beginning any aspirin regimen.

A class of drugs collectively known as thrombolytic agents can help speed up the degradation of an abnormal clot. If a thrombolytic agent is administered to a patient within 3 hours following a thrombotic stroke, the patient’s prognosis improves significantly. However, some strokes are not caused by thrombi, but by haemorrhage. Thus, the cause must be determined before treatment begins. Tissue plasminogen activator is an enzyme that catalyses the conversion of plasminogen to plasmin, the primary enzyme that breaks down clots. It is released naturally by endothelial cells but is also used in clinical medicine. New research is progressing using compounds isolated from the venom of some species of snakes, particularly vipers and cobras, which may eventually have therapeutic value as thrombolytic agents. Streptokinase, an enzyme produced by some species of streptococci, has long been used to help degrade the thrombus in heart attack cases.

Section Review

Haemostasis is the physiological process by which bleeding ceases. Haemostasis involves three basic steps: vascular spasm, the formation of a platelet plug, and coagulation, by which clotting factors promote the formation of a fibrin clot. Fibrinolysis is the process in which a clot is degraded in a healing vessel. Anticoagulants are substances that oppose coagulation. They are important in limiting the extent and duration of clotting. Inadequate clotting can result from too few platelets, or inadequate production of clotting factors, for instance, in the genetic disorder haemophilia. Excessive clotting, called thrombosis, can be caused by excessive numbers of platelets or deficiencies in coagulation control factors. A thrombus is a collection of fibrin, platelets, and erythrocytes that has accumulated along the lining of a blood vessel, whereas an embolus is a thrombus that has broken free from the vessel wall and is circulating in the bloodstream.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=432

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=432

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=432

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=432

5.6 Blood Typing

Leanne Dooley

Learning Objectives

By the end of this section, you will be able to:

  • Describe the two basic physiological consequences of transfusion of incompatible blood
  • Compare and contrast ABO and Rh blood groups
  • Identify which blood groups may be safely transfused into patients with different ABO types
  • Discuss the pathophysiology of haemolytic disease of the newborn

Blood transfusions in humans were risky procedures until the discovery of the major human blood groups by Karl Landsteiner, an Austrian biologist and physician, in 1900. Until that point, physicians did not understand why rapid death often followed blood transfusions. They assumed that all human blood was the same. Landsteiner discovered that the plasma of some individuals caused the red blood cells of some other individuals to clump together (agglutinate), and he surmised that fatal transfusion reaction occurred when the type of donor blood infused into the patient was incompatible with the patient’s own blood. Blood groups are determined by the presence or absence of specific marker molecules on the plasma membranes of erythrocytes. With the discovery of these inherited markers, it became possible for the first time to match patient-donor blood types and prevent severe haemolytic transfusion reactions and deaths.

Antigens, Antibodies and Transfusion Reactions

Antigens are substances that the body does not recognise as belonging to the “self” and that therefore trigger a defensive response from the leukocytes of the immune system. (Seek more content for additional information on immunity.) Here, we will focus on the role of antibody-mediated (humoral) immunity in blood transfusion reactions. With RBCs in particular, you may see the antigens referred to as isoantigens or agglutinogens (surface antigens) and the antibodies referred to as isoantibodies or agglutinins. In this chapter, we will use the more common terms antigens and antibodies.

Antigens are generally large proteins, but may include other classes of organic molecules, including carbohydrates, lipids, and nucleic acids. Following an infusion of incompatible blood, erythrocytes with foreign antigens appear in the bloodstream and trigger an immune response. Proteins called antibodies (immunoglobulins), which are produced by certain B lymphocytes called plasma cells, attach to the antigens on the plasma membranes of the infused erythrocytes. Large antibodies, called IgM antibodies, can cause direct destruction of incompatible RBC via activation of group of plasma proteins called complement. This type of RBC destruction is called intravascular haemolysis and the reaction is referred to as an acute haemolytic transfusion reaction, which can be fatal after infusion of as little as 10mL of incompatible RBC. Smaller antibodies, called IgG antibodies, bind to the incompatible RBC and mark them for destruction by macrophages in the spleen. This type of RBC destruction is called extravascular haemolysis and the reaction is called a delayed haemolytic transfusion reaction, which is not often fatal but leads to removal of the transfused RBC, effectively making the transfusion a waste of time.

During an acute haemolytic transfusion reaction haemoglobin is released into the bloodstream as a result of intravascular haemolysis. This haemoglobin travels to the kidneys, which are responsible for filtration of the blood. However, haemoglobin is toxic to endothelial cells in the kidney and the patient can quickly develop kidney failure. In addition, damage to these endothelial cells can trigger coagulation and acute inflammatory response that can lead to shock and death within minutes.

More than 50 antigens have been identified on erythrocyte membranes, but by far the most significant in terms of their potential harm to patients are the A and B antigens of the ABO blood group system discovered by Landsteiner. The next most clinically significant antigen is the D antigen of the Rhesus or Rh blood group system.

The ABO Blood Group

Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are carbohydrate or saccharide antigens and their presence or absence on the RBC membrane is genetically determined. People who have A antigens only on their erythrocyte membrane surfaces are designated blood type A, and those whose erythrocytes have B antigens only are blood type B. People can also have both A and B antigens on their erythrocytes, in which case they are blood type AB. People with neither A nor B antigens are designated blood type O.

Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group. Individuals with type A blood—without any prior exposure to incompatible blood—have pre-formed or naturally occurring antibodies to the B antigen circulating in their blood plasma. These antibodies, referred to as anti-B antibodies, are IgM type antibodies and will cause agglutination and haemolysis if they ever encounter erythrocytes with B antigens. Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have pre-formed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma. Anti-A and anti-B antibodies are not present at birth but develop during the first six months of life in response to A and B-like substances in the environment, especially of the surface of bacteria.

Rh Blood Groups

The Rhesus or Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (It was first discovered in a type of primate known as a rhesus macaque, which is often used in research, because its blood is like that of humans.) Although dozens of Rh antigens have been identified, the antigen, designated D, is the most clinically important. Those who have the Rh D antigen present on their erythrocytes—about 85 percent of Americans—are described as Rh positive (Rh+) and those who lack it are Rh negative (Rh−). Note that the Rh group is distinct from the ABO group, so any individual, no matter their ABO blood type, may or may not have Rh antigen on their RBCs. When identifying a patient’s blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A+) means ABO group A blood with the Rh(D) antigen present, and AB negative (AB−) means ABO group AB blood without the Rh(D) antigen.

Explore ABO and Rh blood type distribution by country and dependency (population averages) by looking at Table 5.6.2.

In contrast to the ABO group antibodies, which are preformed, antibodies to the Rh antigen are produced only in Rh− individuals after exposure to the antigen. This process, called sensitisation, occurs following a transfusion with Rh-incompatible blood or, more commonly, with the birth of an Rh+ baby to an Rh− mother. Problems are rare in a first pregnancy, since the baby’s Rh+ cells rarely cross the placenta (the organ of gas and nutrient exchange between the baby and the mother). However, during or immediately after birth, the Rh− mother can be exposed to the baby’s Rh+ cells (Figure 5.6.1). Research has shown that this occurs in about 13−14 percent of such pregnancies. After exposure, the mother’s immune system begins to generate anti-Rh (anti-D) antibodies. If the mother should then conceive another Rh+ baby, the Rh antibodies she has produced, which are small IgG antibodies, can cross the placenta into the foetal bloodstream and mark the foetal RBCs fir destruction by macrophages in the foetal spleen. This condition, known as haemolytic disease of the foetus and newborn (HDFN) or erythroblastosis foetalis, may cause anaemia in mild cases, but the haemolysis can be so severe that without treatment the foetus may die in the uterus or shortly after birth. An Rh- mother can also produce Rh antibodies after a miscarriage, termination of pregnancy or abdominal trauma during pregnancy with an Rh+ foetus.

Diagram of Erythroblastosis fetalis
Figure 5.6.1. Erythroblastosis foetalis. The first exposure of an Rh− mother to Rh+ erythrocytes during pregnancy induces sensitisation. Anti-Rh antibodies begin to circulate in the mother’s bloodstream. A second exposure occurs with a subsequent pregnancy with an Rh+ foetus in the uterus. Maternal anti-Rh antibodies may cross the placenta and enter the foetal bloodstream, causing agglutination and haemolysis of foetal erythrocytes.

Rh (D) immune globulin (Rh(D)Ig), derived from the plasma of women who have developed Rh antibodies, can temporarily prevent the development of Rh antibodies in the Rh− mother, thereby averting this potentially serious disease for the foetus. The anti-Rh antibodies, injected into the Rh- mother destroy any foetal Rh+ erythrocytes that may cross the placental barrier and enter the mother’s circulation. This effectively prevents sensitisation and the mother’s immune system does not begin to produce Rh antibodies. Rh(D)Ig is normally administered to Rh− mothers during weeks 26−28 of pregnancy, within 72 hours following birth of an Rh+ baby and following any potentially sensitive event. It has proven remarkably effective in decreasing the incidence of HDFN. Earlier we noted that the incidence of HDFN in an Rh+ subsequent pregnancy to an Rh− mother is about 13–14 percent without preventive treatment.

Determining ABO Blood Types

Laboratory technicians and scientists are able to determine a patient’s blood type quickly and easily using commercially prepared antibodies. A drop of the patient’s blood sample is placed into separate wells on a plastic tile or into separate glass test tubes. Into one well a drop of commercially prepared anti-A antibody is added and to another a drop of anti-B antibody is added. If the antigen is present, the antibodies will cause visible agglutination of the cells (Figure 5.6.2). The patient’s blood should also be tested for the Rh(D) antigen using commercially prepared anti-Rh(D) antibodies.

This sample of a commercially produced “bedside” card enables quick typing of both a recipient’s and donor’s blood before transfusion. The card contains three reaction sites or wells. One is coated with an anti-A antibody, one with an anti-B antibody, and one with an anti-D antibody. Mixing a drop of blood and saline into each well enables the blood to interact with a preparation of type-specific antibodies, also called anti-sera. Agglutination of RBCs in a given site indicates a positive identification of the blood antigens, in this case A and Rh(D) antigens for blood type A+. For the purpose of transfusion, the donor’s and recipient’s blood types must be compatible: the donor’s RBC must not express antigens that will react with antibodies in the patient’s plasma.
Figure 5.6.2. Determining blood types. This sample of a commercially produced “bedside” card enables quick typing of both a recipient’s and donor’s blood before transfusion. The card contains three reaction sites or wells. One is coated with an anti-A antibody, one with an anti-B antibody, and one with an anti-D antibody. Mixing a drop of blood and saline into each well enables the blood to interact with a preparation of type-specific antibodies, also called anti-sera. Agglutination of RBCs in a given site indicates a positive identification of the blood antigens, in this case A and Rh(D) antigens for blood type A+. For the purpose of transfusion, the donor’s and recipient’s blood types must be compatible: the donor’s RBC must not express antigens that will react with antibodies in the patient’s plasma.

ABO Transfusion Protocols

To avoid transfusion reactions, it is best to transfuse only matching blood types; that is, a type B+ recipient should ideally receive blood only from a type B+ donor and so on. That said, in emergency situations, when acute haemorrhage threatens the patient’s life, there may not be time for blood typing and cross matching. In these cases, blood from a universal RBC donor—an individual with type O− blood—may be transfused. Recall that type O erythrocytes do not display A or B antigens. Thus, anti-A or anti-B antibodies that might be circulating in the patient’s blood plasma will not encounter any erythrocyte surface antigens on the donated blood and therefore will not be provoked into a response. A patient with blood type AB+ is known as the universal RBC recipient. This patient can theoretically receive RBC of any type of blood, because the patient’s own plasma – having both A and B antigens on the erythrocyte surface – does not contain anti-A or anti-B antibodies. Figure 5.6.3 summarises the ABO blood types and their associated antigen and antibody profiles.

Note that type A RBC can be given to recipients with type A or type AB blood, because both cases, the recipient’s plasma does not contain anti-A antibodies. However, type AB RBC cannot be given to recipients with type A blood because in this case the patient’s plasma will contain anti-B antibodies, which will react with the B antigens on the donor blood.

While most transfusions involve infusion of RBC only, some patients require plasma transfusions. In the case of plasma transfusion, type AB is the universal donor because type AB plasma does not contain either anti-A or anti-B. The Rh(D) antigen also plays a role in blood transfusion. If Rh− individuals receiving blood have had prior exposure to Rh antigen, antibodies for this antigen may be present in the plasma and will trigger delayed haemolytic transfusion reaction and extravascular haemolysis. Although it is always preferable to type and cross match a patient’s blood before transfusing, in a true life-threatening emergency, this is not always possible, and type O- RBC or type AB plasma can be given until the patient’s blood type is established.

At the scene of multiple-vehicle accidents, military engagements, and natural or human-caused disasters, many victims may suffer simultaneously from acute haemorrhage, yet type O blood may not be immediately available. In these circumstances, medics may at least try to replace some of the volume of blood that has been lost. This is done by intravenous administration of a saline solution that provides fluids and electrolytes in proportions equivalent to those of normal blood plasma. Research is ongoing to develop a safe and effective artificial blood that would perform the oxygen-carrying function of blood without the RBCs, enabling transfusions in the field without concern for incompatibility.

ABO blood groups in table
Figure 5.6.3. ABO blood group. This chart summarises the characteristics of the blood types in the ABO blood group system. See the text for more on the concept of a universal donor or recipient.

Section Review

Antigens are non-self molecules, usually large proteins, which provoke an immune response. In transfusion reactions, antibodies attach to antigens on the surfaces of erythrocytes and cause agglutination and haemolysis. ABO blood group antigens are designated A and B. People with type A blood have A antigens on their erythrocytes, whereas those with type B blood have B antigens. Those with AB blood have both A and B antigens, and those with type O blood have neither A nor B antigens. The blood plasma contains preformed antibodies against the antigens not present on a person’s erythrocytes.

A second group of clinically important blood antigens is the Rh group, the most important of which is Rh D. People with Rh− blood do not have this antigen on their erythrocytes, whereas those who are Rh+ do. About 85 percent of Americans are Rh+. When a woman who is Rh− becomes pregnant with an Rh+ foetus, her body may begin to produce anti-Rh antibodies. If she subsequently becomes pregnant with a second Rh+ foetus and has not been treated preventively with Rh(D)Ig, the foetus will be at risk for haemolytic disease of the foetus and newborn.

Agglutination testing to determine blood type is necessary before transfusing blood, unless the patient is experiencing haemorrhage that is an immediate threat to life, in which case type O− red blood cells or type AB plasma may be transfused.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=487

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=487

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=487

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=487

VI

Cardiovascular System

6.1 Heart Anatomy

Learning Objectives

By the end of this section, you will be able to:

  • Describe the location and position of the heart within the body cavity
  • Describe the internal and external anatomy of the heart
  • Identify the tissue layers of the heart
  • Relate the structure of the heart to its function as a pump
  • Compare systemic circulation to pulmonary circulation
  • Identify the veins and arteries of the coronary circulation system
  • Trace the pathway of oxygenated and deoxygenated blood through the chambers of the heart

The vital importance of the heart is obvious. If one assumes an average rate of contraction of 75 contractions per minute, a human heart would contract approximately 108,000 times in one day, more than 39 million times in one year and nearly 3 billion times during a 75-year lifespan! Each of the major pumping chambers of the heart ejects approximately 70 mL blood per contraction in a resting adult. This would be equal to 5.25 litres of fluid per minute and approximately 14,000 litres per day. Over one year, that would equal 10,000,000 litres (2.6 million gallons) of blood sent through roughly 97,000 kilometres (60,000 miles) of vessels. In order to understand how that happens, it is necessary to understand the anatomy and physiology of the heart.

Location of the Heart

The human heart is located within the thoracic cavity, medially between the lungs in the space known as the mediastinum. Figure 6.1.1 shows the position of the heart within the thoracic cavity. Within the mediastinum, the heart is separated from the other mediastinal structures by a tough membrane known as the pericardium, or pericardial sac, and sits in its own space called the pericardial cavity. The dorsal surface of the heart lies near the bodies of the vertebrae, and its anterior surface sits deep to the sternum and costal cartilages. The great veins, the superior and inferior venae cavae, and the great arteries, the aorta and pulmonary trunk, are attached to the superior surface of the heart, called the base. The base of the heart is located at the level of the third costal cartilage, as seen in Figure 6.1.1. The inferior tip of the heart, the apex, lies just to the left of the sternum between the junction of the fourth and fifth ribs near their articulation with the costal cartilages. The right side of the heart is deflected anteriorly, and the left side is deflected posteriorly. It is important to remember the position and orientation of the heart when placing a stethoscope on the chest of a patient and listening for heart sounds, and when looking at images taken from a midsagittal perspective. The slight deviation of the apex to the left is reflected in a depression in the medial surface of the inferior lobe of the left lung, called the cardiac notch.

Diagram that shows position of the heart
Figure 6.1.1. Position of the heart in the thorax. The heart is located within the thoracic cavity, medially between the lungs in the mediastinum. It is about the size of a fist, is broad at the top, and tapers toward the base.

Everyday Connection

CPR
The position of the heart in the torso between the vertebrae and sternum (see Figure 6.1.1 for the position of the heart within the thorax) allows for individuals to apply an emergency technique known as cardiopulmonary resuscitation (CPR) if the heart of a patient should stop. In adults, pressure is applied with the flat portion of one hand on the sternum in the area between the line at T4 and T9 (Figure 6.1.2), it is possible to manually compress the blood within the heart enough to push some of the blood within it into the pulmonary and systemic circuits. This is particularly critical for the brain, as irreversible damage and death of neurons occur within minutes of loss of blood flow. Current standards call for compression of the chest at least 5 cm deep and at a rate of 100-120 compressions per minute, a rate equal to the beat in “Staying Alive,” recorded in 1977 by the Bee Gees. If you are unfamiliar with this song, a version is available on www.youtube.com. At this stage, the emphasis is on performing high-quality chest compressions, rather than providing artificial respiration, but typically compression to ventilation ratio is 30:2. CPR is generally performed until the patient regains spontaneous contraction or is declared dead by an experienced healthcare professional.

When performed by untrained or overzealous individuals, CPR can result in broken ribs or a broken sternum and can inflict additional severe damage on the patient. It is also possible, if the hands are placed too low on the sternum, to manually drive the xiphoid process into the liver, a consequence that may prove fatal for the patient. Proper training is essential. This proven life-sustaining technique is so valuable that virtually all medical personnel as well as concerned members of the public should be certified and routinely recertified in its application. CPR courses are offered at a variety of locations, including colleges, hospitals, the Australian Red Cross and some commercial companies. They normally include practice of the compression technique on a mannequin.

CPR technique
Figure 6.1.2. CPR technique. If the heart should stop, CPR can maintain the flow of blood until the heart resumes beating. By applying pressure to the sternum, the blood within the heart will be squeezed out of the heart and into the circulation. Proper positioning of the hands on the sternum to perform CPR would be between the lines at T4 and T9.

Shape and Size of the Heart

The shape of the heart is similar to a pinecone, rather broad at the superior surface and tapering to the apex (see Figure 6.1.1). A typical heart is approximately the size of your fist: 12 cm (5 in) in length, 8 cm (3.5 in) wide, and 6 cm (2.5 in) in thickness. Given the size difference between most members of the sexes, the weight of a female heart is approximately 250–300 grams (9 to 11 ounces), and the weight of a male heart is approximately 300–350 grams (11 to 12 ounces). The heart of a well-trained athlete, especially one specialising in aerobic sports, can be considerably larger than this. Cardiac muscle responds to exercise in a manner like that of skeletal muscle. That is, exercise results in the addition of protein myofilaments that increase the size of the individual cells without increasing their numbers, a concept called hypertrophy. Hearts of athletes can pump blood more effectively at lower rates than those of nonathletes. Enlarged hearts are not always a result of exercise; they can result from pathologies, such as hypertrophic cardiomyopathy. The cause of an abnormally enlarged heart muscle is unknown, but the condition is often undiagnosed and can cause sudden death in apparently otherwise healthy young people.

Chambers and Circulation Through the Heart

The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle. Each of the upper chambers, the right atrium (plural = atria) and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body.

There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. The systemic circuit transports oxygenated blood to virtually all the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation.

The right ventricle pumps deoxygenated blood into the pulmonary trunk, which leads toward the lungs and bifurcates into the left and right pulmonary arteries. These vessels in turn branch many times before reaching the pulmonary capillaries, where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins—the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood.

The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava, which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions (Figure 6.1.3).

Dual system of the human blood circulation - diagram
Figure 6.1.3. Dual system of the human blood circulation. Blood flows from the right atrium to the right ventricle, where it is pumped into the pulmonary circuit. The blood in the pulmonary artery branches is low in oxygen but relatively high in carbon dioxide. Gas exchange occurs in the pulmonary capillaries (oxygen into the blood, carbon dioxide out), and blood high in oxygen and low in carbon dioxide is returned to the left atrium. From here, blood enters the left ventricle, which pumps it into the systemic circuit. Following exchange in the systemic capillaries (oxygen and nutrients out of the capillaries and carbon dioxide and wastes in), blood returns to the right atrium and the cycle is repeated.

Membranes, Surface Features and Layers

Our exploration of more in-depth heart structures begins by examining the membrane that surrounds the heart, the prominent surface features of the heart and the layers that form the wall of the heart. Each of these components plays its own unique role in terms of function.

Membranes

The membrane that directly surrounds the heart and defines the pericardial cavity is called the pericardium or pericardial sac. It also surrounds the “roots” of the major vessels, or the areas of closest proximity to the heart. The pericardium, which literally translates as “around the heart,” consists of two distinct sublayers: the sturdy outer fibrous pericardium and the inner serous pericardium. The fibrous pericardium is made of tough, dense connective tissue that protects the heart and maintains its position in the thorax. The more delicate serous pericardium consists of two layers: the parietal pericardium, which is fused to the fibrous pericardium, and an inner visceral pericardium, or epicardium, which is fused to the heart and is part of the heart wall. The pericardial cavity, filled with lubricating serous fluid, lies between the epicardium and the pericardium.

In most organs within the body, visceral serous membranes such as the epicardium are microscopic. However, in the case of the heart, it is not a microscopic layer but rather a macroscopic layer, consisting of a simple squamous epithelium called a mesothelium, reinforced with loose, irregular, or areolar connective tissue that attaches to the pericardium. This mesothelium secretes the lubricating serous fluid that fills the pericardial cavity and reduces friction as the heart contracts. Figure 6.1.4 illustrates the pericardial membranes and the layers of the heart.

Pericardial membranes and layers of the heart wall
Figure 6.1.4. Pericardial membranes and layers of the heart wall. The pericardial membranes that surrounds the heart consists of three layers and the pericardial cavity. The heart wall also consists of three layers. The pericardial membrane and the heart wall share the epicardium.

Disorders of the Heart: Cardiac Tamponade

If excess fluid builds within the pericardial space, it can lead to a condition called cardiac tamponade, or pericardial tamponade. With each contraction of the heart, more fluid—in most instances, blood—accumulates within the pericardial cavity. In order to fill with blood for the next contraction, the heart must relax. However, the excess fluid in the pericardial cavity puts pressure on the heart and prevents full relaxation, so the chambers within the heart contain slightly less blood as they begin each heart cycle. Over time, less and less blood is ejected from the heart. If the fluid builds up slowly, as in hypothyroidism, the pericardial cavity may be able to expand gradually to accommodate this extra volume. Some cases of fluid in excess of one litre within the pericardial cavity have been reported. Rapid accumulation of as little as 100 mL of fluid following trauma may trigger cardiac tamponade. Other common causes include myocardial rupture, pericarditis, cancer, or even cardiac surgery. Removal of this excess fluid requires insertion of drainage tubes into the pericardial cavity. Premature removal of these drainage tubes, for example, following cardiac surgery, or clot formation within these tubes are causes of this condition. Untreated, cardiac tamponade can lead to death.

Surface Features of the Heart

Inside the pericardium, the surface features of the heart are visible, including the four chambers. There is a superficial leaf-like extension of the atria near the superior surface of the heart, one on each side, called an auricle—a name that means “ear like”—because its shape resembles the external ear of a human (Figure 6.1.5). Auricles are relatively thin-walled structures that can fill with blood and empty into the atria or upper chambers of the heart. You may also hear them referred to as atrial appendages. Also prominent is a series of fat-filled grooves, each of which is known as a sulcus (plural = sulci), along the superior surfaces of the heart. Major coronary blood vessels are located in these sulci. The deep coronary sulcus is located between the atria and ventricles. Located between the left and right ventricles are two additional sulci that are not as deep as the coronary sulcus. The anterior interventricular sulcus is visible on the anterior surface of the heart, whereas the posterior interventricular sulcus is visible on the posterior surface of the heart. Figure 6.1.5 illustrates anterior and posterior views of the surface of the heart.

Diagram of external anatomy of heart
Figure 6.1.5. External anatomy of the heart. Inside the pericardium, the surface features of the heart are visible.

Layers

The wall of the heart is composed of three layers of unequal thickness. From superficial to deep, these are the epicardium, the myocardium and the endocardium (see Figure 6.1.4). The outermost layer of the wall of the heart is also the innermost layer of the pericardium, the epicardium, or the visceral pericardium discussed earlier.

The middle and thickest layer is the myocardium, made largely of cardiac muscle cells. It is built upon a framework of collagenous fibres, plus the blood vessels that supply the myocardium and the nerve fibres that help regulate the heart. It is the contraction of the myocardium that pumps blood through the heart and into the major arteries. The muscle pattern is elegant and complex, as the muscle cells swirl and spiral around the chambers of the heart. They form a figure 8 pattern around the atria and around the bases of the great vessels. Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex. More superficial layers of ventricular muscle wrap around both ventricles. This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would. Figure 6.1.6 illustrates the arrangement of muscle cells.

Heart musculature
Figure 6.1.6. Heart musculature. The swirling pattern of cardiac muscle tissue contributes significantly to the heart’s ability to pump blood effectively.

Although the ventricles on the right and left sides pump the same amount of blood per contraction, the muscle of the left ventricle is much thicker and better developed than that of the right ventricle. In order to overcome the high resistance required to pump blood into the long systemic circuit, the left ventricle must generate a great amount of pressure. The right ventricle does not need to generate as much pressure, since the pulmonary circuit is shorter and provides less resistance. Figure 6.1.7 illustrates the differences in muscular thickness needed for each of the ventricles.

Differences in ventricular muscle thickness. between relaxed and contracted heart
Figure 6.1.7. Differences in ventricular muscle thickness. The myocardium in the left ventricle is significantly thicker than that of the right ventricle. Both ventricles pump the same amount of blood, but the left ventricle must generate a much greater pressure to overcome greater resistance in the systemic circuit. The ventricles are shown in both relaxed and contracting states. Note the differences in the relative size of the lumens, the region inside each ventricle where the blood is contained.

The innermost layer of the heart wall, the endocardium, is joined to the myocardium with a thin layer of connective tissue. The endocardium lines the chambers where the blood circulates and covers the heart valves. It is made of simple squamous epithelium called endothelium, which is continuous with the endothelial lining of the blood vessels (see Figure 6.1.4).

Once regarded as a simple lining layer, recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium. The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life, and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility. Endothelins are potent vasoconstrictors and, in a normal individual, establish a homeostatic balance with other vasoconstrictors and vasodilators.

Internal Structure of the Heart

Recall that the heart’s contraction cycle follows a dual pattern of circulation—the pulmonary and systemic circuits—because of the pairs of chambers that pump blood into the circulation. In order to develop a more precise understanding of cardiac function, it is first necessary to explore the internal anatomical structures in more detail.

Septa of the Heart

The word septum is derived from the Latin for “something that encloses;” in this case, a septum (plural = septa) refers to a wall or partition that divides the heart into chambers. The septa are physical extensions of the myocardium lined with endocardium. Located between the two atria is the interatrial septum. Normally in an adult heart, the interatrial septum bears an oval-shaped depression known as the fossa ovalis, a remnant of an opening in the foetal heart known as the foramen ovale. The foramen ovale allowed blood in the foetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the pulmonary circuit. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern.

Between the two ventricles is a second septum known as the interventricular septum. Unlike the interatrial septum, the interventricular septum is normally intact after its formation during foetal development. It is substantially thicker than the interatrial septum, since the ventricles generate far greater pressure when they contract.

The septum between the atria and ventricles is known as the atrioventricular septum. It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta. Located in each of these openings between the atria and ventricles is a valve, a specialised structure that ensures one-way flow of blood. The valves between the atria and ventricles are known generically as atrioventricular valves. The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves. The interventricular septum is visible in Figure 6.1.8. In this figure, the atrioventricular septum has been removed to better show the bicuspid and tricuspid valves; the interatrial septum is not visible, since its location is covered by the aorta and pulmonary trunk. Since these openings and valves structurally weaken the atrioventricular septum, the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton, or skeleton of the heart. It includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta, and serve as the point of attachment for the heart valves. The cardiac skeleton also provides an important boundary in the heart electrical conduction system.

Internal structures of the heart.
Figure 6.1.8. Internal structures of the heart. This anterior view of the heart shows the four chambers, the major vessels and their early branches, as well as the valves. The presence of the pulmonary trunk and aorta covers the interatrial septum, and the atrioventricular septum is cut away to show the atrioventricular valves.

Disorders of the Heart: Heart Defects

One very common form of interatrial septum pathology is patent foramen ovale, which occurs when the septum primum does not close at birth, and the fossa ovalis is unable to fuse. The word patent is from the Latin root patens for “open.” It may be benign or asymptomatic, perhaps never being diagnosed, or in extreme cases, it may require surgical repair to close the opening permanently. As much as 20–25 percent of the general population may have a patent foramen ovale, but fortunately, most have the benign, asymptomatic version. Patent foramen ovale is normally detected by auscultation of a heart murmur (an abnormal heart sound) and confirmed by imaging with an echocardiogram. Despite its prevalence in the general population, the causes of patent ovale are unknown, and there are no known risk factors. In nonlife-threatening cases, it is better to monitor the condition than to risk heart surgery to repair and seal the opening.

Coarctation of the aorta is a congenital abnormal narrowing of the aorta that is normally located at the insertion of the ligamentum arteriosum, the remnant of the foetal shunt called the ductus arteriosus. If severe, this condition drastically restricts blood flow through the primary systemic artery, which is life threatening. In some individuals, the condition may be benign and not detected until later in life. Detectable symptoms in an infant include difficulty breathing, poor appetite, trouble feeding, or failure to thrive. In older individuals, symptoms include dizziness, fainting, shortness of breath, chest pain, fatigue, headache, and nosebleeds. Treatment involves surgery to resect (remove) the affected region or angioplasty to open the abnormally narrow passageway. Studies have shown that the earlier the surgery is performed, the better the chance of survival.

A patent ductus arteriosus is a congenital condition in which the ductus arteriosus fails to close. The condition may range from severe to benign. Failure of the ductus arteriosus to close results in blood flowing from the higher-pressure aorta into the lower pressure pulmonary trunk. This additional fluid moving toward the lungs increases pulmonary pressure and makes respiration difficult. Symptoms include shortness of breath (dyspnoea), tachycardia, enlarged heart, a widened pulse pressure, and poor weight gain in infants. Treatments include surgical closure (ligation), manual closure using platinum coils or specialised mesh inserted via the femoral artery or vein, or nonsteroidal anti-inflammatory drugs to block the synthesis of prostaglandin E2, which maintains the vessel in an open position. If untreated, the condition can result in congestive heart failure.

Septal defects are not uncommon in individuals and may be congenital or caused by various disease processes. Tetralogy of Fallot is a congenital condition that may also occur from exposure to unknown environmental factors; it occurs when there is an opening in the interventricular septum caused by blockage of the pulmonary trunk, normally at the pulmonary semilunar valve. This allows blood that is relatively low in oxygen from the right ventricle to flow into the left ventricle and mix with the blood that is relatively high in oxygen. Symptoms include a distinct heart murmur, low blood oxygen percent saturation, dyspnoea or difficulty in breathing, polycythaemia, broadening (clubbing) of the fingers and toes, and in children, difficulty in feeding or failure to grow and develop. It is the most common cause of cyanosis following birth. The term “tetralogy” is derived from the four components of the condition, although only three may be present in an individual patient: pulmonary infundibular stenosis (rigidity of the pulmonary valve), overriding aorta (the aorta is shifted above both ventricles), ventricular septal defect (opening), and right ventricular hypertrophy (enlargement of the right ventricle). Other heart defects may also accompany this condition, which is typically confirmed by echocardiography imaging. Tetralogy of Fallot occurs in approximately 400 out of one million live births. Normal treatment involves extensive surgical repair, including the use of stents to redirect blood flow and replacement of valves and patches to repair the septal defect, but the condition has a relatively high mortality. Survival rates are currently 75 percent during the first year of life; 60 percent by four years of age; 30 percent by 10 years; and five percent by 40 years.

In the case of severe septal defects, including both tetralogy of Fallot and patent foramen ovale, failure of the heart to develop properly can lead to a condition commonly known as a “blue baby.” Regardless of normal skin pigmentation, individuals with this condition have an insufficient supply of oxygenated blood, which leads to cyanosis, a blue or purple coloration of the skin, especially when active.

Septal defects are commonly first detected through auscultation, listening to the chest using a stethoscope. In this case, instead of hearing normal heart sounds attributed to the flow of blood and closing of heart valves, unusual heart sounds may be detected. This is often followed by medical imaging to confirm or rule out a diagnosis. In many cases, treatment may not be needed. Some common congenital heart defects are illustrated in Figure 6.1.9.

Diagram Congenital heart defects
Figure 6.1.9. Congenital heart defects. (a) A patent foramen ovale defect is an abnormal opening in the interatrial septum, or more commonly, a failure of the foramen ovale to close. (b) Coarctation of the aorta is an abnormal narrowing of the aorta. (c) A patent ductus arteriosus is the failure of the ductus arteriosus to close. (d) Tetralogy of Fallot includes an abnormal opening in the interventricular septum.

Right Atrium

The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation. The two major systemic veins, the superior and inferior venae cavae, and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium. The superior vena cava drains blood from regions superior to the diaphragm: the head, neck, upper limbs, and the thoracic region. It empties into the superior and posterior portions of the right atrium. The inferior vena cava drains blood from areas inferior to the diaphragm: the lower limbs and abdominopelvic region of the body. It, too, empties into the posterior portion of the atria, but inferior to the opening of the superior vena cava. Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus. This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart. The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure 6.1.8.

While the bulk of the internal surface of the right atrium is smooth, the depression of the fossa ovalis is medial, and the anterior surface demonstrates prominent ridges of muscle called the pectinate muscles. The right auricle also has pectinate muscles. The left atrium does not have pectinate muscles except in the auricle.

The atria receive venous blood on a nearly continuous basis, preventing venous flow from stopping while the ventricles are contracting. While most ventricular filling occurs while the atria are relaxed, they do demonstrate a contractile phase and actively pump blood into the ventricles just prior to ventricular contraction. The opening between the atrium and ventricle is guarded by the tricuspid valve.

Right Ventricle

The right ventricle receives blood from the right atrium through the tricuspid valve. Each flap of the valve is attached to strong strands of connective tissue, the chordae tendineae, literally “tendinous cords,” or sometimes more poetically referred to as “heart strings.” There are several chordae tendineae associated with each of the flaps. They are composed of approximately 80 percent collagenous fibres with the remainder consisting of elastic fibres and endothelium. They connect each of the flaps to a papillary muscle that extends from the inferior ventricular surface. There are three papillary muscles in the right ventricle, called the anterior, posterior, and septal muscles, which correspond to the three sections of the valves.

Chordae tendineae and papillary muscles
Figure 6.1.10. Chordae tendineae and papillary muscles. In this frontal section, you can see papillary muscles attached to the tricuspid valve on the right as well as the mitral valve on the left via chordae tendineae. (credit: modification of work by “PV KS”/flickr.com).

When the myocardium of the ventricle contracts, pressure within the ventricular chamber rises. Blood, like any fluid, flows from higher pressure to lower pressure areas, in this case, toward the pulmonary trunk and the atrium. To prevent any potential backflow, the papillary muscles also contract, generating tension on the chordae tendineae. This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction. Figure 6.1.10 shows papillary muscles and chordae tendineae attached to the tricuspid valve.

The walls of the ventricle are lined with trabeculae carneae, ridges of cardiac muscle covered by endocardium. In addition to these muscular ridges, a band of cardiac muscle, also covered by endocardium, known as the moderator band (see Figure 6.1.8) reinforces the thin walls of the right ventricle and plays a crucial role in cardiac conduction. It arises from the inferior portion of the interventricular septum and crosses the interior space of the right ventricle to connect with the inferior papillary muscle.

When the right ventricle contracts, it ejects blood into the pulmonary trunk, which branches into the left and right pulmonary arteries that carry it to each lung. The superior surface of the right ventricle begins to taper as it approaches the pulmonary trunk. At the base of the pulmonary trunk is the pulmonary semilunar valve that prevents backflow from the pulmonary trunk.

Left Atrium

After exchange of gases in the pulmonary capillaries, blood returns to the left atrium high in oxygen via one of the four pulmonary veins. While the left atrium does not contain pectinate muscles, it does have an auricle that includes these pectinate ridges. Blood flows nearly continuously from the pulmonary veins back into the atrium, which acts as the receiving chamber, and from here through an opening into the left ventricle. Most blood flows passively into the heart while both the atria and ventricles are relaxed, but toward the end of the ventricular relaxation period, the left atrium will contract, pumping blood into the ventricle. This atrial contraction accounts for approximately 20 percent of ventricular filling. The opening between the left atrium and ventricle is guarded by the mitral valve.

Left Ventricle

Recall that, although both sides of the heart will pump the same amount of blood, the muscular layer is much thicker in the left ventricle compared to the right (see Figure 6.1.7). Like the right ventricle, the left also has trabeculae carneae, but there is no moderator band. The mitral valve is connected to papillary muscles via chordae tendineae. There are two papillary muscles on the left—the anterior and posterior—as opposed to three on the right.

The left ventricle is the major pumping chamber for the systemic circuit; it ejects blood into the aorta through the aortic semilunar valve.

Heart Valve Structure and Function

A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane (Figure 6.1.11). The valves ensure unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the right atrioventricular valve, or tricuspid valve. It typically consists of three flaps, or leaflets, made of endocardium reinforced with additional connective tissue. The flaps are connected by chordae tendineae to the papillary muscles, which control the opening and closing of the valves.

Diagram that shows valves of heart
Figure 6.1.11. Heart valves. With the atria and major vessels removed, all four valves are clearly visible, although it is difficult to distinguish the three separate cusps of the tricuspid valve.

Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve, or the pulmonary valve; it is also known as the pulmonic valve or the right semilunar valve. The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue. When the ventricle relaxes, the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk. This flow of blood fills the pocket-like flaps of the pulmonary valve, causing the valve to close and producing an audible sound. Unlike the atrioventricular valves, there are no papillary muscles or chordae tendineae associated with the pulmonary valve.

Located at the opening between the left atrium and left ventricle is the mitral valve, also called the bicuspid valve or the left atrioventricular valve. Structurally, this valve consists of two cusps, known as the anterior medial cusp and the posterior medial cusp, compared to the three cusps of the tricuspid valve. In a clinical setting, the valve is referred to as the mitral valve, rather than the bicuspid valve. The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle.

At the base of the aorta is the aortic semilunar valve, or the aortic valve, which prevents backflow from the aorta. It normally is composed of three flaps. When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta, blood will fill the cusps of the valve, causing it to close and producing an audible sound.

In Figure 6.1.12a, the two atrioventricular valves are open and the two semilunar valves are closed. This occurs when both atria and ventricles are relaxed and when the atria contract to pump blood into the ventricles. Figure 6.1.12b shows a frontal view. Although only the left side of the heart is illustrated, the process is virtually identical on the right.

(a) A transverse section through the heart illustrates the four heart valves. The two atrioventricular valves are open; the two semilunar valves are closed. The atria and vessels have been removed. (b) A frontal section through the heart illustrates blood flow through the mitral valve. When the mitral valve is open, it allows blood to move from the left atrium to the left ventricle. The aortic semilunar valve is closed to prevent backflow of blood from the aorta to the left ventricle.
Figure 6.1.12. Blood flow from the left atrium to the left ventricle. (a) A transverse section through the heart illustrates the four heart valves. The two atrioventricular valves are open; the two semilunar valves are closed. The atria and vessels have been removed. (b) A frontal section through the heart illustrates blood flow through the mitral valve. When the mitral valve is open, it allows blood to move from the left atrium to the left ventricle. The aortic semilunar valve is closed to prevent backflow of blood from the aorta to the left ventricle.

Figure 6.1.13a shows the atrioventricular valves closed while the two semilunar valves are open. This occurs when the ventricles contract to eject blood into the pulmonary trunk and aorta. Closure of the two atrioventricular valves prevents blood from being forced back into the atria. This stage can be seen from a frontal view in Figure 6.1.13b.

(a) A transverse section through the heart illustrates the four heart valves during ventricular contraction. The two atrioventricular valves are closed, but the two semilunar valves are open. The atria and vessels have been removed. (b) A frontal view shows the closed mitral (bicuspid) valve that prevents backflow of blood into the left atrium. The aortic semilunar valve is open to allow blood to be ejected into the aorta.
Figure 6.1.13. Blood flow from the left ventricle into the great vessels. (a) A transverse section through the heart illustrates the four heart valves during ventricular contraction. The two atrioventricular valves are closed, but the two semilunar valves are open. The atria and vessels have been removed. (b) A frontal view shows the closed mitral (bicuspid) valve that prevents backflow of blood into the left atrium. The aortic semilunar valve is open to allow blood to be ejected into the aorta.

When the ventricles begin to contract, pressure within the ventricles rises and blood flows toward the area of lowest pressure, which is initially in the atria. This backflow causes the cusps of the tricuspid and mitral (bicuspid) valves to close. These valves are tied down to the papillary muscles by chordae tendineae. During the relaxation phase of the cardiac cycle, the papillary muscles are also relaxed and the tension on the chordae tendineae is slight (see Figure 6.1.12b). However, as the myocardium of the ventricle contracts, so do the papillary muscles. This creates tension on the chordae tendineae (see Figure 6.1.13b), helping to hold the cusps of the atrioventricular valves in place and preventing them from being blown back into the atria.

The aortic and pulmonary semilunar valves lack the chordae tendineae and papillary muscles associated with the atrioventricular valves. Instead, they consist of pocket-like folds of endocardium reinforced with additional connective tissue. When the ventricles relax and the change in pressure forces the blood toward the ventricles, the blood presses against these cusps and seals the openings.

Disorders of the Heart Valves

When heart valves do not function properly, they are often described as incompetent and result in valvular heart disease, which can range from benign to lethal. Some of these conditions are congenital, that is, the individual was born with the defect, whereas others may be attributed to disease processes or trauma. Some malfunctions are treated with medications, others require surgery, and still others may be mild enough that the condition is merely monitored since treatment might trigger more serious consequences.

Valvular disorders are often caused by carditis, or inflammation of the heart. One common trigger for this inflammation is rheumatic fever, or scarlet fever, an autoimmune response to the presence of a bacterium, Streptococcus pyogenes, normally a disease of childhood.

While any of the heart valves may be involved in valve disorders, mitral regurgitation is the most common, detected in approximately 2 percent of the population, and the pulmonary semilunar valve is the least frequently involved. When a valve malfunctions, the flow of blood to a region will often be disrupted. The resulting inadequate flow of blood to this region will be described in general terms as an insufficiency. The specific type of insufficiency is named for the valve involved: aortic insufficiency, mitral insufficiency, tricuspid insufficiency, or pulmonary insufficiency.

If one of the cusps of the valve is forced backward by the force of the blood, the condition is referred to as a prolapsed valve. Prolapse may occur if the chordae tendineae are damaged or broken, causing the closure mechanism to fail. The failure of the valve to close properly disrupts the normal one-way flow of blood and results in regurgitation, when the blood flows backward from its normal path. Using a stethoscope, the disruption to the normal flow of blood produces a heart murmur.

Stenosis is a condition in which the heart valves become rigid and may calcify over time. The loss of flexibility of the valve interferes with normal function and may cause the heart to work harder to propel blood through the valve, which eventually weakens the heart. Aortic stenosis affects approximately two percent of the population over 65 years of age, and the percentage increases to approximately four percent in individuals over 85 years. Occasionally, one or more of the chordae tendineae will tear or the papillary muscle itself may die as a component of a myocardial infarction (heart attack). In this case, the patient’s condition will deteriorate dramatically and rapidly, and immediate surgical intervention may be required.

Auscultation, or listening to a patient’s heart sounds, is one of the most useful diagnostic tools, since it is proven, safe, and inexpensive. The term auscultation is derived from the Latin for “to listen,” and the technique has been used for diagnostic purposes as far back as the ancient Egyptians. Valve and septal disorders will trigger abnormal heart sounds. If a valvular disorder is detected or suspected, a test called an echocardiogram, or simply an “echo,” may be ordered. Echocardiograms are sonograms of the heart and can help in the diagnosis of valve disorders as well as a wide variety of heart pathologies.

Career Connection

Cardiologist

Cardiologists are medical doctors that specialise in the diagnosis and treatment of diseases of the heart. The pathway to become a certified cardiologist in Australia consists of four basic steps. Firstly, a completion of an undergraduate degree (3 years full time) in either a health science or biomedical science field with provisional entry into medicine. Second step is completing either a Bachelor of Medicine/Bachelor of Surgery or a Doctor of Medicine (MD) degree which generally takes four years full time. The third step is to complete an internship/residency in a public hospital system (two years). The final stage requires further vocational training and a Fellowship in a specialised training program (e.g. Fellowship of the Royal Australasian College of Physicians (FRACP) which takes approximately three to five years to complete. The annual salary of a Cardiologist in Australia can range between $60k up to $630k.

Cardiovascular Technologist/Technician

Cardiovascular technologists/technicians are trained professionals who perform a variety of imaging techniques, such as sonograms or echocardiograms, used by physicians to diagnose and treat diseases of the heart. Nearly all of these positions require an associate degree, and include, but are not limited to, Grade 1 Cardiac Technician (~$48k – $80k per annum), radiographer (~$55k – $104k per annum), cardiac sonographer (~$62k – $135k per annum).

Coronary Circulation

You will recall that the heart is a remarkable pump composed largely of cardiac muscle cells that are incredibly active throughout life. Like all other cells, a cardiomyocyte requires a reliable supply of oxygen and nutrients, and a way to remove wastes, so it needs a dedicated, complex, and extensive coronary circulation. And because of the critical and nearly ceaseless activity of the heart throughout life, this need for a blood supply is even greater than for a typical cell. However, coronary circulation is not continuous; rather, it cycles, reaching a peak when the heart muscle is relaxed and nearly ceasing while it is contracting.

Coronary Arteries

Coronary arteries supply blood to the myocardium and other components of the heart. The first portion of the aorta after it arises from the left ventricle gives rise to the coronary arteries. There are three dilations in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the left posterior aortic sinus and anterior aortic sinus, give rise to the left and right coronary arteries, respectively. The third sinus, the right posterior aortic sinus, typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the artery and follow the sulci are called epicardial coronary arteries.

The left coronary artery distributes blood to the left side of the heart, the left atrium and ventricle, and the interventricular septum. The circumflex artery arises from the left coronary artery and follows the coronary sulcus to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger anterior interventricular artery, also known as the left anterior descending artery (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the posterior interventricular artery, forming anastomoses. An anastomosis is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart, so a coronary artery blockage often results in death of the cells (myocardial infarction) supplied by the particular vessel.

The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the heart conduction system. Normally, one or more marginal arteries arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery, also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles. Figure 6.1.14 presents views of the coronary circulation from both the anterior and posterior views.

Diagram of croonary circulation
Figure 6.1.14. Coronary circulation. The anterior view of the heart shows the prominent coronary surface vessels. The posterior view of the heart shows the prominent coronary surface vessels.

Diseases of the Heart: Myocardial Infarction

Myocardial infarction (MI) is the formal term for what is commonly referred to as a heart attack. It normally results from a lack of blood flow (ischaemia) and oxygen (hypoxia) to a region of the heart, resulting in death of the cardiac muscle cells. An MI often occurs when a coronary artery is blocked by the build-up of atherosclerotic plaque consisting of lipids, cholesterol and fatty acids, and white blood cells, primarily macrophages. It can also occur when a portion of an unstable atherosclerotic plaque travels through the coronary arterial system and lodges in one of the smaller vessels. The resulting blockage restricts the flow of blood and oxygen to the myocardium and causes death of the tissue. MIs may be triggered by excessive exercise, in which the partially occluded artery is no longer able to pump sufficient quantities of blood, or severe stress, which may induce spasm of the smooth muscle in the walls of the vessel.

In the case of acute MI, there is often sudden pain beneath the sternum (retrosternal pain) called angina pectoris, often radiating down the left arm in males but not in female patients. Until this anomaly between the sexes was discovered, many female patients suffering MIs were misdiagnosed and sent home. In addition, patients typically present with difficulty breathing and shortness of breath (dyspnoea), irregular heartbeat (palpations), nausea and vomiting, sweating (diaphoresis), anxiety and fainting (syncope), although not all of these symptoms may be present. Many of the symptoms are shared with other medical conditions, including anxiety attacks and simple indigestion, so differential diagnosis is critical. It is estimated that between 22 and 64 percent of MIs present without any symptoms.

An MI can be confirmed by examining the patient’s ECG, which frequently reveals alterations in the ST and Q components. Some classification schemes of MI are referred to as ST-elevated MI (STEMI) and non-elevated MI (non-STEMI). In addition, echocardiography or cardiac magnetic resonance imaging may be employed. Common blood tests indicating an MI include elevated levels of creatine kinase MB (an enzyme that catalyses the conversion of creatine to phosphocreatine, consuming ATP) and cardiac troponin (the regulatory protein for muscle contraction), both of which are released by damaged cardiac muscle cells.

Immediate treatments for MI are essential and include administering supplemental oxygen, aspirin that helps to break up clots, and nitroglycerine administered sublingually (under the tongue) to facilitate its absorption. Despite its unquestioned success in treatments and use since the 1880s, the mechanism of nitroglycerine is still incompletely understood but is believed to involve the release of nitric oxide, a known vasodilator, and endothelium-derived releasing factor, which also relaxes the smooth muscle in the tunica media of coronary vessels. Longer-term treatments include injections of thrombolytic agents such as streptokinase that dissolve the clot, the anticoagulant heparin, balloon angioplasty and stents to open blocked vessels, and bypass surgery to allow blood to pass around the site of blockage. If the damage is extensive, coronary replacement with a donor heart or coronary assist device, a sophisticated mechanical device that supplements the pumping activity of the heart, may be employed. Despite the attention, development of artificial hearts to augment the severely limited supply of heart donors has proven less than satisfactory but will likely improve in the future.

MIs may trigger cardiac arrest, but the two are not synonymous. Important risk factors for MI include cardiovascular disease, age, smoking, high blood levels of the low-density lipoprotein (LDL, often referred to as “bad” cholesterol), low levels of high-density lipoprotein (HDL, or “good” cholesterol), hypertension, diabetes mellitus, obesity, lack of physical exercise, chronic kidney disease, excessive alcohol consumption, and use of illegal drugs.

Coronary Veins

Coronary veins drain the heart and generally parallel the large surface arteries (see Figure 6.1.14). The great cardiac vein can be seen initially on the surface of the heart following the interventricular sulcus, but it eventually flows along the coronary sulcus into the coronary sinus on the posterior surface. The great cardiac vein initially parallels the anterior interventricular artery and drains the areas supplied by this vessel. It receives several major branches, including the posterior cardiac vein, the middle cardiac vein, and the small cardiac vein. The posterior cardiac vein parallels and drains the areas supplied by the marginal artery branch of the circumflex artery. The middle cardiac vein parallels and drains the areas supplied by the posterior interventricular artery. The small cardiac vein parallels the right coronary artery and drains the blood from the posterior surfaces of the right atrium and ventricle. The coronary sinus is a large, thin-walled vein on the posterior surface of the heart lying within the atrioventricular sulcus and emptying directly into the right atrium. The anterior cardiac veins parallel the small cardiac arteries and drain the anterior surface of the right ventricle. Unlike these other cardiac veins, it bypasses the coronary sinus and drains directly into the right atrium.

Diseases of the Heart: Coronary Artery Disease

black and white image of Atherosclerotic coronary arteries
Figure 6.1.15. Atherosclerotic coronary arteries. In this coronary angiogram (X-ray), the dye makes visible two occluded coronary arteries. Such blockages can lead to decreased blood flow (ischaemia) and insufficient oxygen (hypoxia) delivered to the cardiac tissues. If uncorrected, this can lead to cardiac muscle death (myocardial infarction).

Coronary artery disease is the leading cause of death worldwide. It occurs when the build-up of plaque—a fatty material including cholesterol, connective tissue, white blood cells, and some smooth muscle cells—within the walls of the arteries obstructs the flow of blood and decreases the flexibility or compliance of the vessels. This condition is called atherosclerosis, a hardening of the arteries that involves the accumulation of plaque. As the coronary blood vessels become occluded, the flow of blood to the tissues will be restricted, a condition called ischaemia that causes the cells to receive insufficient amounts of oxygen, called hypoxia. Figure 6.1.15 shows the blockage of coronary arteries highlighted by the injection of dye. Some individuals with coronary artery disease report pain radiating from the chest called angina pectoris, but others remain asymptomatic. If untreated, coronary artery disease can lead to MI or a heart attack.

The disease progresses slowly and often begins in children and can be seen as fatty “streaks” in the vessels. It then gradually progresses throughout life. Well-documented risk factors include smoking, family history, hypertension, obesity, diabetes, high alcohol consumption, lack of exercise, stress, and hyperlipidaemia or high circulating levels of lipids in the blood. Treatments may include medication, changes to diet and exercise, angioplasty with a balloon catheter, insertion of a stent, or coronary bypass procedure.

Angioplasty is a procedure in which the occlusion is mechanically widened with a balloon. A specialised catheter with an expandable tip is inserted into a superficial vessel, normally in the leg, and then directed to the site of the occlusion. At this point, the balloon is inflated to compress the plaque material and to open the vessel to increase blood flow. Then, the balloon is deflated and retracted. A stent consisting of a specialised mesh is typically inserted at the site of occlusion to reinforce the weakened and damaged walls. Stent insertions have been routine in cardiology for more than 40 years.

Coronary bypass surgery may also be performed. This surgical procedure grafts a replacement vessel obtained from another, less vital portion of the body to bypass the occluded area. This procedure is clearly effective in treating patients experiencing a MI, but overall does not increase longevity. Nor does it seem advisable in patients with stable although diminished cardiac capacity since frequently loss of mental acuity occurs following the procedure. Long-term changes to behaviour, emphasising diet and exercise plus a medicine regime tailored to lower blood pressure, lower cholesterol and lipids, and reduce clotting are equally as effective.

Section Review

The heart resides within the pericardial sac and is located in the mediastinal space within the thoracic cavity. The pericardial sac consists of two fused layers: an outer fibrous capsule and an inner parietal pericardium lined with a serous membrane. Between the pericardial sac and the heart is the pericardial cavity, which is filled with lubricating serous fluid. The walls of the heart are composed of an outer epicardium, a thick myocardium, and an inner lining layer of endocardium. The human heart consists of a pair of atria, which receive blood and pump it into a pair of ventricles, which pump blood into the vessels. The right atrium receives systemic blood relatively low in oxygen and pumps it into the right ventricle, which pumps it into the pulmonary circuit. Exchange of oxygen and carbon dioxide occurs in the lungs, and blood high in oxygen returns to the left atrium, which pumps blood into the left ventricle, which in turn pumps blood into the aorta and the remainder of the systemic circuit. The septa are the partitions that separate the chambers of the heart. They include the interatrial septum, the interventricular septum, and the atrioventricular septum. Two of these openings are guarded by the atrioventricular valves, the right tricuspid valve and the left mitral valve, which prevent the backflow of blood. Each is attached to chordae tendineae that extend to the papillary muscles, which are extensions of the myocardium, to prevent the valves from being blown back into the atria. The pulmonary valve is located at the base of the pulmonary trunk, and the left semilunar valve is located at the base of the aorta. The right and left coronary arteries are the first to branch off the aorta and arise from two of the three sinuses located near the base of the aorta and are generally located in the sulci. Cardiac veins parallel the small cardiac arteries and generally drain into the coronary sinus.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=506

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=506

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=506

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=506

6.2 Cardiac Muscle and Electrical Activity

Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure of cardiac muscle
  • Identify and describe the components of the conducting system that distributes electrical impulses through the heart
  • Compare the effect of ion movement on membrane potential of cardiac conductive and contractile cells
  • Relate characteristics of an electrocardiogram (ECG) to events in the cardiac cycle
  • Identify blocks that can interrupt the cardiac cycle

 

Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle, but it has some unique properties of its own. Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism. This property is known as autorhythmicity. Neither smooth nor skeletal muscle can do this. Even though cardiac muscle has autorhythmicity, heart rate is modulated by the endocrine and nervous systems.

There are two major types of cardiac muscle cells: myocardial contractile cells and myocardial conducting cells. The myocardial contractile cells constitute the bulk (99 percent) of the cells in the atria and ventricles. Contractile cells conduct impulses and are responsible for contractions that pump blood through the body. The myocardial conducting cells (1 percent of the cells) form the conduction system of the heart. Except for Purkinje cells, they are generally much smaller than the contractile cells and have few of the myofibrils or filaments needed for contraction. Their function is similar in many respects to neurons, although they are specialised muscle cells. Myocardial conduction cells initiate and propagate the action potential (the electrical impulse) that travels throughout the heart and triggers the contractions that propel the blood.

Structure of Cardiac Muscle

Compared to the giant cylinders of skeletal muscle, cardiac muscle cells, or cardiomyocytes, are considerably shorter with much smaller diameters. Cardiac muscle also demonstrates striations, the alternating pattern of dark A bands and light I bands attributed to the precise arrangement of the myofilaments and fibrils that are organised in sarcomeres along the length of the cell (Figure 6.2.1a). These contractile elements are virtually identical to skeletal muscle. T (transverse) tubules penetrate from the surface plasma membrane, the sarcolemma, to the interior of the cell, allowing the electrical impulse to reach the interior. The T tubules are only found at the Z discs, whereas in skeletal muscle, they are found at the junction of the A and I bands. Therefore, there are one-half as many T tubules in cardiac muscle as in skeletal muscle. In addition, the sarcoplasmic reticulum stores few calcium ions, so most of the calcium ions must come from outside the cells. The result is a slower onset of contraction. Mitochondria are plentiful, providing energy for the contractions of the heart. Typically, cardiomyocytes have a single, central nucleus, but two or more nuclei may be found in some cells.

Cardiac muscle cells branch freely. A junction between two adjoining cells is marked by a critical structure called an intercalated disc, which helps support the synchronised contraction of the muscle (Figure 6.2.1b). The sarcolemmas from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialised linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronise the contraction (Figure 6.2.1c). Intercellular connective tissue also helps to bind the cells together. The importance of strongly binding these cells together is necessitated by the forces exerted by contraction.

(a) Cardiac muscle cells have myofibrils composed of myofilaments arranged in sarcomeres, T tubules to transmit the impulse from the sarcolemma to the interior of the cell, numerous mitochondria for energy, and intercalated discs that are found at the junction of different cardiac muscle cells. (b) A photomicrograph of cardiac muscle cells shows the nuclei and intercalated discs. (c) An intercalated disc connects cardiac muscle cells and consists of desmosomes and gap junctions.
Figure 6.2.1. Cardiac muscle. (a) Cardiac muscle cells have myofibrils composed of myofilaments arranged in sarcomeres, T tubules to transmit the impulse from the sarcolemma to the interior of the cell, numerous mitochondria for energy, and intercalated discs that are found at the junction of different cardiac muscle cells. (b) A photomicrograph of cardiac muscle cells shows the nuclei and intercalated discs. (c) An intercalated disc connects cardiac muscle cells and consists of desmosomes and gap junctions. LM × 1600. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012).

Cardiac muscle undergoes aerobic respiration patterns, primarily metabolising lipids and carbohydrates. Myoglobin, lipids, and glycogen are all stored within the cytoplasm. Cardiac muscle cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods. The relaxation is essential so the heart can fill with blood for the next cycle. The refractory period is very long to prevent the possibility of tetany, a condition in which muscle remains involuntarily contracted. In the heart, tetany is not compatible with life, since it would prevent the heart from pumping blood.

Everyday Connection

Repair and Replacement

Damaged cardiac muscle cells have extremely limited abilities to repair themselves or to replace dead cells via mitosis. Recent evidence indicates that at least some stem cells remain within the heart that continue to divide and at least potentially replace these dead cells. However, newly formed or repaired cells are rarely as functional as the original cells, and cardiac function is reduced. In the event of a heart attack or MI, dead cells are often replaced by patches of scar tissue. Autopsies performed on individuals who had successfully received heart transplants show some proliferation of original cells. If researchers can unlock the mechanism that generates new cells and restore full mitotic capabilities to heart muscle, the prognosis for heart attack survivors will be greatly enhanced. To date, myocardial cells produced within the patient (in situ) by cardiac stem cells seem to be non-functional, although those grown in Petri dishes (in vitro) do beat. Perhaps soon this mystery will be solved, and new advances in treatment will be commonplace.

Conduction System of the Heart

If embryonic heart cells are separated into a Petri dish and kept alive, each can generate its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the sinoatrial node, the atrioventricular node, the atrioventricular bundle, the atrioventricular bundle branches, and the Purkinje cells (Figure 6.2.2).

Conduction system of the heart
Figure 6.2.2. Conduction system of the heart. Specialised conducting components of the heart include the sinoatrial node, the internodal pathways, the atrioventricular node, the atrioventricular bundle, the right and left bundle branches, and the Purkinje fibres.

Sinoatrial (SA) Node

Normal cardiac rhythm is established by the sinoatrial (SA) node, a specialised clump of myocardial conducting cells located in the superior and posterior walls of the right atrium in close proximity to the orifice of the superior vena cava. The SA node has the highest inherent rate of depolarisation and is known as the pacemaker of the heart. It initiates the sinus rhythm, or normal electrical pattern followed by contraction of the heart.

This impulse spreads from its initiation in the SA node throughout the atria through specialised internodal pathways, to the atrial myocardial contractile cells and the atrioventricular node. The internodal pathways consist of three bands (anterior, middle, and posterior) that lead directly from the SA node to the next node in the conduction system, the atrioventricular node (see Figure 6.2.2). The impulse takes approximately 50 ms (milliseconds) to travel between these two nodes. The relative importance of this pathway has been debated since the impulse would reach the atrioventricular node simply following the cell-by-cell pathway through the contractile cells of the myocardium in the atria. In addition, there is a specialised pathway called Bachmann’s bundle or the interatrial band that conducts the impulse directly from the right atrium to the left atrium. Regardless of the pathway, as the impulse reaches the atrioventricular septum, the connective tissue of the cardiac skeleton prevents the impulse from spreading into the myocardial cells in the ventricles except at the atrioventricular node. Figure 6.2.3 illustrates the initiation of the impulse in the SA node that then spreads the impulse throughout the atria to the atrioventricular node.

Figure 6.2.3. Cardiac conduction. (1) The sinoatrial (SA) node and the remainder of the conduction system are at rest. (2) The SA node initiates the action potential, which sweeps across the atria. (3) After reaching the atrioventricular node, there is a delay of approximately 100 ms that allows the atria to complete pumping blood before the impulse is transmitted to the atrioventricular bundle. (4) Following the delay, the impulse travels through the atrioventricular bundle and bundle branches to the Purkinje fibres, and reaches the right papillary muscle via the moderator band. (5) The impulse spreads to the contractile fibres of the ventricle. (6) Ventricular contraction begins.
Figure 6.2.3. Cardiac conduction. (1) The sinoatrial (SA) node and the remainder of the conduction system are at rest. (2) The SA node initiates the action potential, which sweeps across the atria. (3) After reaching the atrioventricular node, there is a delay of approximately 100 ms that allows the atria to complete pumping blood before the impulse is transmitted to the atrioventricular bundle. (4) Following the delay, the impulse travels through the atrioventricular bundle and bundle branches to the Purkinje fibres, and reaches the right papillary muscle via the moderator band. (5) The impulse spreads to the contractile fibres of the ventricle. (6) Ventricular contraction begins.

The electrical event, the wave of depolarisation, is the trigger for muscular contraction. The wave of depolarisation begins in the right atrium, and the impulse spreads across the superior portions of both atria and then down through the contractile cells. The contractile cells then begin contraction from the superior to the inferior portions of the atria, efficiently pumping blood into the ventricles.

Atrioventricular (AV) Node

The atrioventricular (AV) node is a second clump of specialised myocardial conductive cells, located in the inferior portion of the right atrium within the atrioventricular septum. The septum prevents the impulse from spreading directly to the ventricles without passing through the AV node. There is a critical pause before the AV node depolarises and transmits the impulse to the atrioventricular bundle (see Figure 6.2.3, step 3). This delay in transmission is partially attributable to the small diameter of the cells of the node, which slow the impulse. Also, conduction between nodal cells is less efficient than between conducting cells. These factors mean that it takes the impulse approximately 100 ms to pass through the node. This pause is critical to heart function, as it allows the atrial cardiomyocytes to complete their contraction that pumps blood into the ventricles before the impulse is transmitted to the cells of the ventricle itself. With extreme stimulation by the SA node, the AV node can transmit impulses maximally at 220 per minute. This establishes the typical maximum heart rate in a healthy young individual. Damaged hearts or those stimulated by drugs can contract at higher rates, but at these rates, the heart can no longer effectively pump blood.

Atrioventricular Bundle (Bundle of His), Bundle Branches and Purkinje fibres

Arising from the AV node, the atrioventricular bundle, or bundle of His, proceeds through the interventricular septum before dividing into two atrioventricular bundle branches, commonly called the left and right bundle branches. The left bundle branch has two fascicles. The left bundle branch supplies the left ventricle, and the right bundle branch the right ventricle. Since the left ventricle is much larger than the right, the left bundle branch is also considerably larger than the right. Portions of the right bundle branch are found in the moderator band and supply the right papillary muscles. Because of this connection, each papillary muscle receives the impulse at approximately the same time, so they begin to contract simultaneously just prior to the remainder of the myocardial contractile cells of the ventricles. This is believed to allow tension to develop on the chordae tendineae prior to right ventricular contraction. There is no corresponding moderator band on the left. Both bundle branches descend and reach the apex of the heart where they connect with the Purkinje fibres (see Figure 6.2.3, step 4). This passage takes approximately 25 ms.

The Purkinje fibres are additional myocardial conductive fibres that spread the impulse to the myocardial contractile cells in the ventricles. They extend throughout the myocardium from the apex of the heart toward the atrioventricular septum and the base of the heart. The Purkinje fibres have a fast inherent conduction rate, and the electrical impulse reaches all the ventricular muscle cells in about 75 ms (see Figure 6.2.3, step 5). Since the electrical stimulus begins at the apex, the contraction also begins at the apex and travels toward the base of the heart, like squeezing a tube of toothpaste from the bottom. This allows the blood to be pumped out of the ventricles and into the aorta and pulmonary trunk. The total time elapsed from the initiation of the impulse in the SA node until depolarisation of the ventricles is approximately 225 ms.

Membrane Potentials and Ion Movement in Cardiac Conductive Cells

Action potentials are considerably different between cardiac conductive cells and cardiac contractive cells. While Naand K+ play essential roles, Ca2+ is also critical for both types of cells. Unlike skeletal muscles and neurons, cardiac conductive cells do not have a stable resting potential. Conductive cells contain a series of sodium ion channels that allow a normal and slow influx of sodium ions that causes the membrane potential to rise slowly from an initial value of −60 mV up to about –40 mV. The resulting movement of sodium ions creates spontaneous depolarisation (or prepotential depolarisation). At this point, calcium ion channels open and Ca2+ enters the cell, further depolarising it at a more rapid rate until it reaches a value of approximately +5 mV. At this point, the calcium ion channels close and Kchannels open, allowing outflux of K+ and resulting in repolarisation. When the membrane potential reaches approximately −60 mV, the Kchannels close and Na+ channels open, and the prepotential phase begins again. This phenomenon explains the autorhythmicity properties of cardiac muscle (Figure 6.2.4).

Graph of action potential at the SA mode
Figure 6.2.4. Action potential at the SA node. The prepotential is due to a slow influx of sodium ions until the threshold is reached followed by a rapid depolarisation and repolarisation. The prepotential accounts for the membrane reaching threshold and initiates the spontaneous depolarisation and contraction of the cell. Note the lack of a resting potential.

Membrane Potentials and Ion Movement in Cardiac Contractile Cells

There is a distinctly different electrical pattern involving the contractile cells. In this case, there is a rapid depolarisation, followed by a plateau phase and then repolarisation. This phenomenon accounts for the long refractory periods required for the cardiac muscle cells to pump blood effectively before they are capable of firing for a second time. These cardiac myocytes normally do not initiate their own electrical potential, although they can do so, but rather wait for an impulse to reach them.

Contractile cells demonstrate a much more stable resting phase than conductive cells at approximately −80 mV for cells in the atria and −90 mV for cells in the ventricles. Despite this initial difference, the other components of their action potentials are virtually identical. In both cases, when stimulated by an action potential, voltage-gated channels rapidly open, beginning the positive-feedback mechanism of depolarisation. This rapid influx of positively charged ions raises the membrane potential to approximately +30 mV, at which point the sodium channels close. The rapid depolarisation period typically lasts 3–5 ms. Depolarisation is followed by the plateau phase, in which membrane potential declines relatively slowly. This is due in large part to the opening of the slow Ca2+ channels, allowing Ca2+ to enter the cell while few K+ channels are open, allowing K+ to exit the cell. The relatively long plateau phase lasts approximately 175 ms. Once the membrane potential reaches approximately zero, the Ca2+ channels close and K+ channels open, allowing K+ to exit the cell. The repolarisation lasts approximately 75 ms. At this point, membrane potential drops until it reaches resting levels once more and the cycle repeats. The entire event lasts between 250 and 300 ms (Figure 6.2.5).

The absolute refractory period for cardiac contractile muscle lasts approximately 200 ms, and the relative refractory period lasts approximately 50 ms, for a total of 250 ms. This extended period is critical, since the heart muscle must contract to pump blood effectively and the contraction must follow the electrical events. Without extended refractory periods, premature contractions would occur in the heart and would not be compatible with life.

Figure 6.2.5. Action potential in cardiac contractile cells. (a) Note the long plateau phase due to the influx of calcium ions. The extended refractory period allows the cell to fully contract before another electrical event can occur. (b) The action potential for heart muscle is compared to that of skeletal muscle.
Figure 6.2.5. Action potential in cardiac contractile cells. (a) Note the long plateau phase due to the influx of calcium ions. The extended refractory period allows the cell to fully contract before another electrical event can occur. (b) The action potential for heart muscle is compared to that of skeletal muscle.

Calcium Ions

Calcium ions play two critical roles in the physiology of cardiac muscle. Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly. Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction. This mechanism is virtually identical to that of skeletal muscle. Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca2+ during the plateau phase. The remaining Ca2+ for contraction is released from storage in the sarcoplasmic reticulum.

Comparative Rates of Conduction System Firing

The pattern of prepotential or spontaneous depolarisation, followed by rapid depolarisation and repolarisation just described, are seen in the SA node and a few other conductive cells in the heart. Since the SA node is the pacemaker, it reaches threshold faster than any other component of the conduction system. It will initiate the impulses spreading to the other conducting cells. The SA node, without nervous or endocrine control, would initiate a heart impulse approximately 80–100 times per minute. Although each component of the conduction system can generate its own impulse, the rate progressively slows as you proceed from the SA node to the Purkinje fibres. Without the SA node, the AV node would generate a heart rate of 40–60 beats per minute. If the AV node were blocked, the atrioventricular bundle would fire at a rate of approximately 30–40 impulses per minute. The bundle branches would have an inherent rate of 20–30 impulses per minute, and the Purkinje fibres would fire at 15–20 impulses per minute. While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30–40 beats per minute (the lowest recorded figure is 28 beats per minute for Miguel Indurain, a cyclist), for most individuals, rates lower than 50 beats per minute would indicate a condition called bradycardia. Depending upon the specific individual, as rates fall much below this level, the heart would be unable to maintain adequate flow of blood to vital tissues, initially resulting in decreasing loss of function across the systems, unconsciousness, and ultimately death.

Electrocardiogram

By careful placement of surface electrodes on the body, it is possible to record the complex, compound electrical signal of the heart. This tracing of the electrical signal is the electrocardiogram (ECG), also commonly abbreviated EKG (K coming kardiology, from the German term for cardiology). Careful analysis of the ECG reveals a detailed picture of both normal and abnormal heart function and is an indispensable clinical diagnostic tool. The standard electrocardiograph (the instrument that generates an ECG) uses 3, 5, or 12 leads. The greater the number of leads an electrocardiograph uses, the more information the ECG provides. The term “lead” may be used to refer to the cable from the electrode to the electrical recorder, but it typically describes the voltage difference between two of the electrodes. The 12-lead electrocardiograph uses 10 electrodes placed in standard locations on the patient’s skin (Figure 6.2.6). In continuous ambulatory electrocardiographs, the patient wears a small, portable, battery-operated device known as a Holter monitor, or simply a Holter, that continuously monitors heart electrical activity, typically for a period of 24 hours during the patient’s normal routine.

Standard placement of ECG leads.
Figure 6.2.6. Standard placement of ECG leads. In a 12-lead ECG, six electrodes are placed on the chest, and four electrodes are placed on the limbs.

 

A normal ECG tracing is presented in Figure 6.2.7. Each component, segment and interval is labelled and corresponds to important electrical events, demonstrating the relationship between these events and contraction in the heart.

There are five prominent points on the ECG: the P wave, the QRS complex and the T wave. The small P wave represents the depolarisation of the atria. The atria begin contracting approximately 25 ms after the start of the P wave. The large QRS complex represents the depolarisation of the ventricles, which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle. The ventricles begin to contract as the QRS reaches the peak of the R wave. Lastly, the T wave represents the repolarisation of the ventricles. The repolarisation of the atria occurs during the QRS complex, which masks it on an ECG.

The major segments and intervals of an ECG tracing are indicated in Figure 6.2.7. Segments are defined as the regions between two waves. Intervals include one segment plus one or more waves. For example, the PR segment begins at the end of the P wave and ends at the beginning of the QRS complex. The PR interval starts at the beginning of the P wave and ends with the beginning of the QRS complex. The PR interval is more clinically relevant, as it measures the duration from the beginning of atrial depolarisation (the P wave) to the initiation of the QRS complex. Since the Q wave may be difficult to view in some tracings, the measurement is often extended to the R that is more easily visible. Should there be a delay in passage of the impulse from the SA node to the AV node, it would be visible in the PR interval. Figure 6.2.8 correlates events of heart contraction to the corresponding segments and intervals of an ECG.

Electrocardiogram
Figure 6.2.7. Electrocardiogram. A normal tracing shows the P wave, QRS complex, and T wave. Also indicated are the PR, QT, QRS and ST intervals, plus the P-R and S-T segments.
Figure 6.2.8. ECG tracing correlated to the cardiac cycle. This diagram correlates an ECG tracing with the electrical and mechanical events of a heart contraction. Each segment of an ECG tracing corresponds to one event in the cardiac cycle.
Figure 6.2.8. ECG tracing correlated to the cardiac cycle. This diagram correlates an ECG tracing with the electrical and mechanical events of a heart contraction. Each segment of an ECG tracing corresponds to one event in the cardiac cycle.

Everyday Connection

ECG Abnormalities

Occasionally, an area of the heart other than the SA node will initiate an impulse that will be followed by a premature contraction. Such an area, which may be a component of the conduction system or some other contractile cells, is known as an ectopic focus or ectopic pacemaker. An ectopic focus may be stimulated by localised ischaemia; exposure to certain drugs, including caffeine, digitalis, or acetylcholine; elevated stimulation by both sympathetic or parasympathetic divisions of the autonomic nervous system; or several disease or pathological conditions. Occasional occurrences are generally transitory and nonlife threatening, but if the condition becomes chronic, it may lead to either an arrhythmia, a deviation from the normal pattern of impulse conduction and contraction, or to fibrillation, an uncoordinated beating of the heart.

While interpretation of an ECG is possible and extremely valuable after some training, a full understanding of the complexities and intricacies generally requires several years of experience. In general, the size of the electrical variations, the duration of the events, and detailed vector analysis provide the most comprehensive picture of cardiac function. For example, an amplified P wave may indicate enlargement of the atria, an enlarged Q wave may indicate a MI, and an enlarged suppressed or inverted Q wave often indicates enlarged ventricles. T waves often appear flatter when insufficient oxygen is being delivered to the myocardium. An elevation of the ST segment above baseline is often seen in patients with an acute MI and may appear depressed below the baseline when hypoxia is occurring.

As useful as analysing these electrical recordings may be, there are limitations. For example, not all areas suffering a MI may be obvious on the ECG. Additionally, it will not reveal the effectiveness of the pumping, which requires further testing, such as an ultrasound test called an echocardiogram or nuclear medicine imaging. It is also possible for there to be pulseless electrical activity, which will show up on an ECG tracing, although there is no corresponding pumping action. Common abnormalities that may be detected by the ECGs are shown in Figure 6.2.9.

Figure 6.2.9. Common ECG abnormalities. (a) In a second-degree or partial block, one-half of the P waves are not followed by the QRS complex and T waves while the other half are. (b) In atrial fibrillation, the electrical pattern is abnormal prior to the QRS complex, and the frequency between the QRS complexes has increased. (c) In ventricular tachycardia, the shape of the QRS complex is abnormal. (d) In ventricular fibrillation, there is no normal electrical activity. (e) In a third-degree block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex).
Figure 6.2.9. Common ECG abnormalities. (a) In a second-degree or partial block, one-half of the P waves are not followed by the QRS complex and T waves while the other half are. (b) In atrial fibrillation, the electrical pattern is abnormal prior to the QRS complex, and the frequency between the QRS complexes has increased. (c) In ventricular tachycardia, the shape of the QRS complex is abnormal. (d) In ventricular fibrillation, there is no normal electrical activity. (e) In a third-degree block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex).

Everyday Connection

External Automated Defibrillators

If the electrical activity of the heart is severely disrupted, cessation of electrical activity or fibrillation may occur. In fibrillation, the heart beats in a wild, uncontrolled manner, which prevents it from being able to pump effectively. Atrial fibrillation (see Figure 6.2.9b) is a serious condition, but as long as the ventricles continue to pump blood, the patient’s life may not be in immediate danger. Ventricular fibrillation (see Figure 6.2.9d) is a medical emergency that requires life support, because the ventricles are not effectively pumping blood. In a hospital setting, it is often described as “code blue.” If untreated for as little as a few minutes, ventricular fibrillation may lead to brain death. The most common treatment is defibrillation, which uses special paddles to apply a charge to the heart from an external electrical source in an attempt to establish a normal sinus rhythm (Figure 6.2.10). A defibrillator effectively stops the heart so that the SA node can trigger a normal conduction cycle. Because of their effectiveness in re-establishing a normal sinus rhythm, external automated defibrillators (EADs) are being placed in areas frequented by large numbers of people, such as schools, restaurants, and airports. These devices contain simple and direct verbal instructions that can be followed by nonmedical personnel to save a life.

Photos of Defibrillators
Figure 6.2.10. Defibrillators. (a) An external automatic defibrillator can be used by nonmedical personnel to re-establish a normal sinus rhythm in a person with fibrillation. (b) Defibrillator paddles are more commonly used in hospital settings. (credit b: “widerider107”/flickr.com).

heart block refers to an interruption in the normal conduction pathway. The nomenclature for these is very straightforward. SA nodal blocks occur within the SA node. AV nodal blocks occur within the AV node. Infra-Hisian blocks involve the bundle of His. Bundle branch blocks occur within either the left or right atrioventricular bundle branches. Hemiblocks are partial and occur within one or more fascicles of the atrioventricular bundle branch. Clinically, the most common types are the AV nodal and infra-Hisian blocks.

AV blocks are often described by degrees. A first-degree or partial block indicates a delay in conduction between the SA and AV nodes. This can be recognised on the ECG as an abnormally long PR interval. A second-degree or incomplete block occurs when some impulses from the SA node reach the AV node and continue, while others do not. In this instance, the ECG would reveal some P waves not followed by a QRS complex, while others would appear normal. In the third-degree or complete block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex). Even in the event of a total SA block, the AV node will assume the role of pacemaker and continue initiating contractions at 40–60 contractions per minute, which is adequate to maintain consciousness.

When arrhythmias become a chronic problem, the heart maintains a junctional rhythm, which originates in the AV node. In order to speed up the heart rate and restore full sinus rhythm, a cardiologist can implant an artificial pacemaker, which delivers electrical impulses to the heart muscle to ensure that the heart continues to contract and pump blood effectively. These artificial pacemakers are programmable by the cardiologists and can either provide stimulation temporarily upon demand or on a continuous basis. Some devices also contain built-in defibrillators.

Cardiac Muscle Metabolism

Normally, cardiac muscle metabolism is entirely aerobic. Oxygen from the lungs is brought to the heart, and every other organ, attached to the haemoglobin molecules within the erythrocytes. Heart cells also store appreciable amounts of oxygen in myoglobin. Normally, these two mechanisms, circulating oxygen and oxygen attached to myoglobin, can supply sufficient oxygen to the heart, even during peak performance.

Fatty acids and glucose from the circulation are broken down within the mitochondria to release energy in the form of ATP. Both fatty acid droplets and glycogen are stored within the sarcoplasm and provide additional nutrient supply.

Section Review

The heart is regulated by both neural and endocrine control, yet it can initiate its own action potential followed by muscular contraction. The conductive cells within the heart establish the heart rate and transmit it through the myocardium. The contractile cells contract and propel the blood. The normal path of transmission for the conductive cells is the sinoatrial (SA) node, internodal pathways, atrioventricular (AV) node, atrioventricular (AV) bundle of His, bundle branches, and Purkinje fibres. The action potential for the conductive cells consists of a prepotential phase with a slow influx of Na+ followed by a rapid influx of Ca2+ and outflux of K+. Contractile cells have an action potential with an extended plateau phase that results in an extended refractory period to allow complete contraction for the heart to pump blood effectively. Recognisable points on the ECG include the P wave that corresponds to atrial depolarisation, the QRS complex that corresponds to ventricular depolarisation and the T wave that corresponds to ventricular repolarisation.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=508

6.3 Cardiac Cycle

Learning Objectives

By the end of this section, you will be able to:

  • Describe the relationship between blood pressure and blood flow
  • Summarise the events of the cardiac cycle
  • Compare atrial and ventricular systole and diastole
  • Relate heart sounds detected by auscultation to action of heart’s valves

The period of time that begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle (Figure 6.3.1). The period of contraction that the heart undergoes while it pumps blood into circulation is called systole. The period of relaxation that occurs as the chambers fill with blood is called diastole. Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body.

Overview of the cardiac cycle. The cardiac cycle begins with atrial systole and progresses to ventricular systole, atrial diastole, and ventricular diastole, when the cycle begins again. Correlations to the ECG are highlighted.
Figure 6.3.1. Overview of the cardiac cycle. The cardiac cycle begins with atrial systole and progresses to ventricular systole, atrial diastole, and ventricular diastole, when the cycle begins again. Correlations to the ECG are highlighted.

Pressures and Flow

Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent.

Phases of the Cardiac Cycle

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left.

Atrial Systole and Diastole

Contraction of the atria follows depolarisation, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70–80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the “atrial kick,” contributes the remaining 20–30 percent of filling (see Figure 6.3.1). Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole.

Ventricular Systole

Ventricular systole (see Figure 6.3.1) follows the depolarisation of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to atrial contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload.

Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction (see Figure 6.3.1).

In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV).

Ventricular Diastole

Ventricular relaxation, or diastole, follows repolarisation of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms.

During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase (see Figure 6.3.1).

In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed (see Figure 6.3.1). The cardiac cycle is complete.

Figure 6.3.2 illustrates the relationship between the cardiac cycle and the ECG.

Relationship between the cardiac cycle and ECG
Figure 6.3.2. Relationship between the cardiac cycle and ECG. Initially, both the atria and ventricles are relaxed (diastole). The P wave represents depolarisation of the atria and is followed by atrial contraction (systole). Atrial systole extends until the QRS complex, at which point, the atria relax. The QRS complex represents depolarisation of the ventricles and is followed by ventricular contraction. The T wave represents the repolarisation of the ventricles and marks the beginning of ventricular relaxation.

Heart Sounds

One of the simplest, yet effective, diagnostic techniques applied to assess the state of a patient’s heart is auscultation using a stethoscope.

In a normal, healthy heart, there are only two audible heart sounds: S1 and S2. S1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “lub,” or first heart sound. The second heart sound, S2, is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “dub” (Figure 6.3.3). In both cases, as the valves close, the openings within the atrioventricular septum guarded by the valves will become reduced, and blood flow through the opening will become more turbulent until the valves are fully closed. There is a third heart sound, S3, but it is rarely heard in healthy individuals. It may be the sound of blood flowing into the atria, or blood sloshing back and forth in the ventricle, or even tensing of the chordae tendineae. S3 may be heard in youth, some athletes, and pregnant women. If the sound is heard later in life, it may indicate congestive heart failure, warranting further tests. Some cardiologists refer to the collective S1, S2, and S3 sounds as the “Kentucky gallop,” because they mimic those produced by a galloping horse. The fourth heart sound, S4, results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle, indicating failure of the left ventricle. S4 occurs prior to S1 and the collective sounds S4, S1, and S2 are referred to by some cardiologists as the “Tennessee gallop,” because of their similarity to the sound produced by a galloping horse with a different gait. A few individuals may have both S3 and S4, and this combined sound is referred to as S7.

Graph of heart sounds
Figure 6.3.3. Heart sounds and the cardiac cycle. In this illustration, the x-axis reflects time with a recording of the heart sounds. The y-axis represents pressure.

The term murmur is used to describe an unusual sound coming from the heart that is caused by the turbulent flow of blood. Murmurs are graded on a scale of 1 to 6, with 1 being the most common, the most difficult sound to detect, and the least serious. The most severe is a 6. Phonocardiograms or auscultograms can be used to record both normal and abnormal sounds using specialised electronic stethoscopes.

During auscultation, it is common practice for the clinician to ask the patient to breathe deeply. This procedure not only allows for listening to airflow, but it may also amplify heart murmurs. Inhalation increases blood flow into the right side of the heart and may increase the amplitude of right-sided heart murmurs. Expiration partially restricts blood flow into the left side of the heart and may amplify left-sided heart murmurs. Figure 6.3.4 indicates proper placement of the bell of the stethoscope to facilitate auscultation.

Image of human body highlightung heart valves
Figure 6.3.4. Stethoscope placement for auscultation. Proper placement of the bell of the stethoscope facilitates auscultation. At each of the four locations on the chest, a different valve can be heard.

Section Review

The cardiac cycle comprises a complete relaxation and contraction of both the atria and ventricles and lasts approximately 0.8 seconds. Beginning with all chambers in diastole, blood flows passively from the veins into the atria and past the atrioventricular valves into the ventricles. The atria begin to contract (atrial systole), following depolarisation of the atria, and pump blood into the ventricles. The ventricles begin to contract (ventricular systole), raising pressure within the ventricles. When ventricular pressure rises above the pressure in the atria, blood flows toward the atria, producing the first heart sound, S1 or lub. As pressure in the ventricles rises above two major arteries, blood pushes open the two semilunar valves and moves into the pulmonary trunk and aorta in the ventricular ejection phase. Following ventricular repolarisation, the ventricles begin to relax (ventricular diastole), and pressure within the ventricles drops. As ventricular pressure drops, there is a tendency for blood to flow back into the atria from the major arteries, producing the dicrotic notch in the ECG and closing the two semilunar valves. The second heart sound, S2 or dub, occurs when the semilunar valves close. When the pressure falls below that of the atria, blood moves from the atria into the ventricles, opening the atrioventricular valves and marking one complete heart cycle. The valves prevent backflow of blood. Failure of the valves to operate properly produces turbulent blood flow within the heart; the resulting heart murmur can often be heard with a stethoscope.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=510

Critical Thinking Question

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=510

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=510

6.4 Cardiac Physiology

Learning Objectives

By the end of this section, you will be able to:

  • Relate heart rate to cardiac output
  • Describe the effect of exercise on heart rate
  • Identify cardiovascular centres and cardiac reflexes that regulate heart function
  • Describe factors affecting heart rate
  • Distinguish between positive and negative factors that affect heart contractility
  • Summarise factors affecting stroke volume and cardiac output
  • Describe the cardiac response to variations in blood flow and pressure

The autorhythmicity inherent in cardiac cells keeps the heart beating at a regular pace; however, the heart is regulated by and responds to outside influences as well. Neural and endocrine controls are vital to the regulation of cardiac function. In addition, the heart is sensitive to several environmental factors, including electrolytes.

Resting Cardiac Output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value, multiply stroke volume (SV), the amount of blood pumped by each ventricle, by heart rate (HR), in contractions per minute (or beats per minute, bpm). It can be represented mathematically by the following equation:

CO = HR × SV

SV is normally measured using an echocardiogram to record EDV and ESV and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialised catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60–100 in some individuals.

Using these numbers, the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. Remember, however, that these numbers refer to CO from each ventricle separately, not the total for the heart. Factors influencing CO are summarised in Figure 6.4.1.

Major factors influencing cardiac output. Cardiac output is influenced by heart rate and stroke volume, both of which are also variable.
Figure 6.4.1. Major factors influencing cardiac output. Cardiac output is influenced by heart rate and stroke volume, both of which are also variable.

SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent, with a mean of 58 percent.

Exercise and Maximum Cardiac Output

In healthy young individuals, HR may increase to 150 bpm during exercise. SV can also increase from 70 to approximately 130 mL due to increased strength of contraction. This would increase CO to approximately 19.5 L/min, 4–5 times the resting rate. Top cardiovascular athletes can achieve even higher levels. At their peak performance, they may increase resting CO by 7–8 times.

Since the heart is a muscle, exercising it increases its efficiency. The difference between maximum and resting CO is known as the cardiac reserve. It measures the residual capacity of the heart to pump blood.

Heart Rates

HRs vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually decreases until young adulthood and then gradually increases again with age.

Maximum HRs are normally in the range of 200–220 bpm, although there are some extreme cases in which they may reach higher levels. As one ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the individual’s age. So, a 40-year-old individual would be expected to hit a maximum rate of approximately 180, and a 60-year-old person would achieve a HR of 160.

Disorders of the Heart: Abnormal Heart Rates

For an adult, normal resting HR will be in the range of 60–100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic if the HR remains above 50 bpm.

Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be required. Other causes include ischaemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen.

Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases, tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness, shortness of breath, light-headedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above 100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anaemia, hypoxia, hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation. Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise. Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation or surgery.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However, as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilise as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual. Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO decreases as SV falls faster than HR increases. So, although aerobic exercises are critical to maintain the health of the heart, individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm, so CO is maintained. The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age.

Cardiovascular Centres

Nervous control over HR is centralised within the two paired cardiovascular centres of the medulla oblongata (Figure 6.4.2). The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centres decrease heart activity via parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centres provide slight stimulation to the heart, contributing to autonomic tone. This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm.

Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibres known as the cardiac plexus near the base of the heart. The cardioaccelerator centres also sends additional fibres, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia T1–T4) to both the SA and AV nodes, plus additional fibres to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibres than parasympathetic fibres. Sympathetic stimulation causes the release of the neurotransmitter noradrenaline (NA) at the neuromuscular junction of the cardiac nerves. NA shortens the repolarisation period, thus speeding the rate of depolarisation and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions.

NA binds to the beta-1 receptor. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR and are one possible treatment for hypertension. Over prescription of these drugs may lead to bradycardia and even stoppage of the heart.

Autonomic innervation of the heart.
Figure 6.4.2. Autonomic innervation of the heart. Cardioaccelerator and cardioinhibitory areas are components of the paired cardiac centres located in the medulla oblongata of the brain. They innervate the heart via sympathetic cardiac nerves that increase cardiac activity and vagus (parasympathetic) nerves that slow cardiac activity.

Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus nerve sends branches to both the SA and AV nodes, and to portions of both the atria and ventricles. Parasympathetic stimulation releases the neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening chemical- or ligand-gated potassium ion channels to slow the rate of spontaneous depolarisation, which extends repolarisation and increases the time before the next spontaneous depolarisation occurs. Without any nervous stimulation, the SA node would establish a sinus rhythm of approximately 100 bpm. Since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. This is like an individual driving a car with one foot on the brake pedal. To speed up, one need merely remove one’s foot from the break and let the engine increase speed. In the case of the heart, decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase up to approximately 100 bpm. Any increases beyond this rate would require sympathetic stimulation. Figure 6.4.3 illustrates the effects of parasympathetic and sympathetic stimulation on the normal sinus rhythm.

Graph on Effects of parasympathetic and sympathetic stimulation on normal sinus rhythm.
Figure 6.4.3. Effects of parasympathetic and sympathetic stimulation on normal sinus rhythm. The wave of depolarisation in a normal sinus rhythm shows a stable resting HR. Following parasympathetic stimulation, HR slows. Following sympathetic stimulation, HR increases.

Input to the Cardiovascular Centre

The cardiovascular centre receives input from a series of visceral receptors with impulses traveling through visceral sensory fibres within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centre to regulate heart function precisely, a process known as cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centre monitor these increased rates of firing and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase blood flow.

Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centre monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centre decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centre increase sympathetic stimulation and decrease parasympathetic stimulation.

There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialised baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac centre responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true.

Increased metabolic by-products associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback to the cardiovascular centre about the need for increased or decreased blood flow, based on the relative levels of these substances.

The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than normal HRs, often accompanied by a surge in the stress hormone cortisol. Individuals experiencing extreme anxiety may manifest panic attacks with symptoms that resemble those of heart attacks. These events are typically transient and treatable. Meditation techniques have been developed to ease anxiety and have been shown to lower HR effectively. Doing simple deep and slow breathing exercises with one’s eyes closed can also significantly reduce this anxiety and HR.

Disorders of the Heart: Broken Heart Syndrome

Extreme stress from such life events as the death of a loved one, an emotional break up, loss of income, or foreclosure of a home may lead to a condition commonly referred to as broken heart syndrome. This condition may also be called Takotsubo cardiomyopathy, transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz syndrome, and stress cardiomyopathy. The recognised effects on the heart include congestive heart failure due to a profound weakening of the myocardium not related to lack of oxygen. This may lead to acute heart failure, lethal arrhythmias, or even the rupture of a ventricle. The exact aetiology is not known, but several factors have been suggested, including transient vasospasm, dysfunction of the cardiac capillaries, or thickening of the myocardium—particularly in the left ventricle—that may lead to the critical circulation of blood to this region. While many patients survive the initial acute event with treatment to restore normal function, there is a strong correlation with death. Careful statistical analysis by the Cass Business School, a prestigious institution located in London, published in 2008, revealed that within one year of the death of a loved one, women are more than twice as likely to die and males are six times as likely to die as would otherwise be expected.

Other Factors Influencing Heart Rate

Using a combination of autorhythmicity and innervation, the cardiovascular centre can provide relatively precise control over HR. However, there are a number of other factors that have an impact on HR as well, including adrenaline, noradrenaline and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance (Table 6.4.1 and Table 6.4.2). After reading this section, the importance of maintaining homeostasis should become even more apparent.

Table 6.4.1. Major factors increasing heart rate and force of contraction

Factor Effect
Cardioaccelerator nerves Release of noradrenaline (NA)
Proprioceptors Increased rates of firing during exercise
Chemoreceptors Decreased levels of O2, increased levels of H+, CO2 and lactic acid
Baroreceptors Decreased rates of firing, indicating falling blood volume/pressure
Limbic system Anticipation of physical exercise or strong emotions
Catecholamines Increased adrenaline and noradrenaline
Thyroid hormones Increased T3 and T4
Calcium Increased Ca2+
Potassium Decreased K+
Sodium Decreased Na+
Body temperature Increased body temperature
Nicotine and caffeine Stimulants, increased heart rate

 

Table 6.4.2. Factors decreasing heart rate and force of contraction

Factor Effect
Cardioinhibitory nerves (vagus) Release of acetylcholine
Proprioceptors Decreased rates of firing following exercise
Chemoreceptors Increased levels of O2; decreased levels of H+ and CO2
Baroreceptors Increased rates of firing, indicating higher blood volume/pressure
Limbic System Anticipation of relaxation
Catecholamines Decreased adrenaline and noradrenaline
Thyroid hormones Decreased T3 and T4
Calcium Decreased Ca2+
Potassium Increased K+
Sodium Increased Na+
Body temperature Decrease in body temperature

Adrenaline (A) and Noradrenaline (NA)

The catecholamines, adrenaline and noradrenaline, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Adrenaline and NA have similar effects: binding to the beta-1 receptors, and opening sodium and calcium ion chemical- or ligand-gated channels. The rate of depolarisation is increased by this additional influx of positively charged ions, so the threshold is reached more quickly and the period of repolarisation is shortened. However, massive releases of these hormones coupled with sympathetic stimulation may actually lead to arrhythmias. There is no parasympathetic stimulation to the adrenal medulla.

Thyroid Hormones

In general, increased levels of thyroid hormone, or thyroxine, increase cardiac rate and contractility. The impact of thyroid hormone is typically of a much longer duration than that of the catecholamines. The physiologically active form of thyroid hormone, T3 or triiodothyronine, has been shown to directly enter cardiomyocytes and alter activity at the level of the genome. It also impacts the beta adrenergic response similar to adrenaline and NA described above. Excessive levels of thyroxine may trigger tachycardia.

Calcium

Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High levels of calcium ions (hypercalcaemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents the time from the start of depolarisation to repolarisation of the ventricles and includes the period of ventricular systole. Extremely high levels of calcium may induce cardiac arrest. Drugs known as calcium channel blockers slow HR by binding to these channels and blocking or slowing the inward movement of calcium ions.

Caffeine and Nicotine

Caffeine and nicotine are not found naturally within the body. Both of these nonregulated drugs have an excitatory effect on membranes of neurons in general and have a stimulatory effect on the cardiac centres specifically, causing an increase in HR. Caffeine works by increasing the rates of depolarisation at the SA node, whereas nicotine stimulates the activity of the sympathetic neurons that deliver impulses to the heart.

Although it is the world’s most widely consumed psychoactive drug, caffeine is legal and not regulated. While precise quantities have not been established, “normal” consumption is not considered harmful to most people, although it may cause disruptions to sleep and acts as a diuretic. Its consumption by pregnant women is cautioned against, although no evidence of negative effects has been confirmed. Tolerance and even physical and mental addiction to the drug result in individuals who routinely consume the substance.

Nicotine, too, is a stimulant and produces addiction. While legal and nonregulated, concerns about nicotine’s safety and documented links to respiratory and cardiac disease and cancer have resulted in warning labels on cigarette packages.

Factors Decreasing Heart Rate

HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis and hypothermia (see Table 6.4.2). The relationship between electrolytes and HR is complex but maintaining electrolyte balance is critical to the normal wave of depolarisation. Of the two ions, potassium has the greater clinical significance. Initially, both hyponatraemia (low sodium levels) and hypernatraemia (high sodium levels) may lead to tachycardia. Severely high hypernatraemia may lead to fibrillation, which may cause CO to cease. Severe hyponatraemia leads to both bradycardia and other arrhythmias. Hypokalaemia (low potassium levels) also leads to arrhythmias, whereas hyperkalaemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail.

Heart muscle relies exclusively on aerobic metabolism for energy. Hypoxia (an insufficient supply of oxygen) leads to decreasing HRs, since metabolic reactions fuelling heart contraction are restricted.

Acidosis is a condition in which excess hydrogen ions are present, and the patient’s blood expresses a low pH value. Alkalosis is a condition in which there are too few hydrogen ions, and the patient’s blood has an elevated pH. Normal blood pH falls in the range of 7.35–7.45, so a number lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex, subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to denaturation of the enzyme.

The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the patient’s blood is normally diverted to an artificial heart-lung machine to maintain the body’s blood supply and gas exchange until the surgery is complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body systems to cease normal function, beginning with the central nervous system.

Stroke Volume

Many of the same factors that regulate HR also impact cardiac function by altering SV. While several variables are involved, SV is ultimately dependent upon the difference between EDV and ESV. The three primary factors to consider are preload, or the stretch on the ventricles prior to contraction; the contractility, or the force or strength of the contraction itself; and afterload, the force the ventricles must generate to pump blood against the resistance in the vessels. These factors are summarised in Table 6.4.1 and Table 6.4.2.

Preload

Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider is filling time, or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases.

With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to the physical constraints of the location of the heart, this excessive stretch is not a concern.

The relationship between ventricular stretch and contraction has been stated in the well-known Frank-Starling mechanism or simply Starling’s Law of the Heart. This principle states that, within physiological limits, the force of heart contraction is directly proportional to the initial length of the muscle fibre. This means that the greater the stretch of the ventricular muscle (within limits), the more powerful the contraction is, which in turn increases SV. Therefore, by increasing preload, you increase the second variable, contractility.

Otto Frank (1865–1944) was a German physiologist; among his many published works are detailed studies of this important heart relationship. Ernest Starling (1866–1927) was an important English physiologist who also studied the heart. Although they worked largely independently, their combined efforts and similar conclusions have been recognised in the name “Frank-Starling mechanism.”

Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick, plays a crucial role by providing the last 20–30 percent of ventricular filling.

Contractility

It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors, and those that decrease contractility are described as negative inotropic factors (ino- = “fibre;” -tropic = “turning toward”).

Not surprisingly, sympathetic stimulation is a positive inotrope, whereas parasympathetic stimulation is a negative inotrope. Sympathetic stimulation triggers the release of NE at the neuromuscular junction from the cardiac nerves and stimulates the adrenal cortex to secrete adrenaline and NE. In addition to their stimulatory effects on HR, they also bind to both alpha and beta receptors on the cardiac muscle cell membrane to increase metabolic rate and the force of contraction. This combination of actions has the net effect of increasing SV and leaving a smaller residual ESV in the ventricles. In comparison, parasympathetic stimulation releases ACh at the neuromuscular junction from the vagus nerve. The membrane hyperpolarises and inhibits contraction to decrease the strength of contraction and SV, and to raise ESV. Since parasympathetic fibres are more widespread in the atria than in the ventricles, the primary site of action is in the upper chambers. Parasympathetic stimulation in the atria decreases the atrial kick and reduces EDV, which decreases ventricular stretch and preload, thereby further limiting the force of ventricular contraction. Stronger parasympathetic stimulation also directly decreases the force of contraction of the ventricles.

Several synthetic drugs, including dopamine and isoproterenol, have been developed that mimic the effects of adrenaline and NE by stimulating the influx of calcium ions from the extracellular fluid. Higher concentrations of intracellular calcium ions increase the strength of contraction. Excess calcium (hypercalcaemia) also acts as a positive inotropic agent. The drug digitalis lowers HR and increases the strength of the contraction, acting as a positive inotropic agent by blocking the sequestering of calcium ions into the sarcoplasmic reticulum. This leads to higher intracellular calcium levels and greater strength of contraction. In addition to the catecholamines from the adrenal medulla, other hormones also demonstrate positive inotropic effects. These include thyroid hormones and glucagon from the pancreas.

Negative inotropic agents include hypoxia, acidosis, hyperkalaemia, and a variety of synthetic drugs. These include numerous beta blockers and calcium channel blockers. Early beta blocker drugs include propranolol and pronethalol and are credited with revolutionising treatment of cardiac patients experiencing angina pectoris. There is also a large class of dihydropyridine, phenylalkylamine, and benzothiazepine calcium channel blockers that may be administered decreasing the strength of contraction and SV.

Afterload

Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves, such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure 6.4.4 summarises the major factors influencing SV, Figure 6.4.5 summarises the major factors influencing CO, and Table 6.4.3 and Table 6.4.4 summarise cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis.

Major factors influencing stroke volume. Multiple factors impact preload, afterload, and contractility, and are the major considerations influencing SV.
Figure 6.4.4. Major factors influencing stroke volume. Multiple factors impact preload, afterload, and contractility, and are the major considerations influencing SV.
Flowchart that simarise major factors influencing cardiac output
Figure 6.4.5. Summary of major factors influencing cardiac output. The primary factors influencing HR include autonomic innervation plus endocrine control. Not shown are environmental factors, such as electrolytes, metabolic products, and temperature. The primary factors controlling SV include preload, contractility, and afterload. Other factors such as electrolytes may be classified as either positive or negative inotropic agents.

Table 6.4.3. Cardiac response to decreasing blood flow and pressure due to decreasing cardiac output

  Baroreceptors (aorta, carotid arteries, venae cavae, and atria) Chemoreceptors (both central nervous system and in proximity to baroreceptors)
Sensitive to Decreasing stretch Decreasing O2 and increasing CO2, H+ and lactic acid
Target Parasympathetic stimulation suppressed Sympathetic stimulation increased
Response of heart Increasing heart rate and increasing stroke volume Increasing heart rate and increasing stroke volume
Overall effect Increasing blood flow and pressure due to increasing cardiac output; haemostasis restored Increased blood flow and pressure due to increasing cardiac output; haemostasis restored

 

Table 6.4.4. Cardiac response to increasing blood flow and pressure due to increasing cardiac output

  Baroreceptors (aorta, carotid arteries, venae cavae, and atria) Chemoreceptors (both central nervous system and in proximity to baroreceptors)
Sensitive to Increasing stretch Increasing O2 and increasing CO2, H+ and lactic acid
Target Parasympathetic stimulation increased Sympathetic stimulation suppressed
Response of heart Decreasing heart rate and decreasing stroke volume Decreasing heart rate and decreasing stroke volume
Overall effect Decreasing blood flow and pressure due to decreasing cardiac output; haemostasis restored Decreasing blood flow and pressure due to decreasing cardiac output; haemostasis restored

Section Review

Many factors affect HR and SV, and together, they contribute to cardiac function. HR is largely determined and regulated by autonomic stimulation and hormones. There are several feedback loops that contribute to maintaining homeostasis dependent upon activity levels, such as the atrial reflex, which is determined by venous return.

SV is regulated by autonomic innervation and hormones, but also by filling time and venous return. Venous return is determined by activity of the skeletal muscles, blood volume, and changes in peripheral circulation. Venous return determines preload and the atrial reflex. Filling time directly related to HR also determines preload. Preload then impacts both EDV and ESV. Autonomic innervation and hormones largely regulate contractility. Contractility impacts EDV as does afterload. CO is the product of HR multiplied by SV. SV is the difference between EDV and ESV.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=512

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=512

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=512

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=512

6.5 Development of the Heart

Learning Objectives

By the end of this section, you will be able to:

  • Describe the embryological development of heart structures
  • Identify five regions of the foetal heart
  • Relate foetal heart structures to adult counterparts

The human heart is the first functional organ to develop. It begins beating and pumping blood around day 21 or 22, a mere three weeks after fertilisation. This emphasises the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes both to and from the developing baby. The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo.

The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilisation. Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs. The heart begins to develop near the head of the embryo in a region known as the cardiogenic area. Following chemical signals called factors from the underlying endoderm (another of the three primary germ layers), the cardiogenic area begins to form two strands called the cardiogenic cords (Figure 6.5.1). As the cardiogenic cords develop, a lumen rapidly develops within them. At this point, they are referred to as endocardial tubes. The two tubes migrate together and fuse to form a single primitive heart tube. The primitive heart tube quickly forms five distinct regions. From head to tail, these include the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus. This is a very different pattern from that of an adult.

 

This diagram outlines the embryological development of the human heart during the first eight weeks and the subsequent formation of the four heart chambers.
Figure 6.5.1. Development of the human heart. This diagram outlines the embryological development of the human heart during the first eight weeks and the subsequent formation of the four heart chambers.

The five regions of the primitive heart tube develop into recognisable structures in a fully developed heart. The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk. The bulbus cordis develops into the right ventricle. The primitive ventricle forms the left ventricle. The primitive atrium becomes the anterior portions of both the right and left atria, and the two auricles. The sinus venosus develops into the posterior portion of the right atrium, the SA node, and the coronary sinus.

As the primitive heart tube elongates, it begins to fold within the pericardium, eventually forming an S shape, which places the chambers and major vessels into an alignment like the adult heart. This process occurs between days 23 and 28. The remainder of the heart development pattern includes development of septa and valves and remodelling of the actual chambers. Partitioning of the atria and ventricles by the interatrial septum, interventricular septum, and atrioventricular septum is complete by the end of the fifth week, although the foetal blood shunts remain until birth or shortly after. The atrioventricular valves form between weeks five and eight, and the semilunar valves form between weeks five and nine.

Section Review

The heart is the first organ to form and become functional, emphasising the importance of transport of material to and from the developing infant. It originates about day 18 or 19 from the mesoderm and begins beating and pumping blood about day 21 or 22. It forms from the cardiogenic region near the head and is visible as a prominent heart bulge on the surface of the embryo. Originally, it consists of a pair of strands called cardiogenic cords that quickly form a hollow lumen and are referred to as endocardial tubes. These then fuse into a single heart tube and differentiate into the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and sinus venosus, starting about day 22. The primitive heart begins to form an S shape within the pericardium between days 23 and 28. The internal septa begin to form about day 28, separating the heart into the atria and ventricles, although the foramen ovale persists until shortly after birth. Between weeks five and eight, the atrioventricular valves form. The semilunar valves form between weeks five and nine.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=514

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=514

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=514

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=514

6.6 Structure and Function of Blood Vessels

Learning Objectives

By the end of this section, you will be able to:

  • Compare and contrast the three tunics that make up the walls of most blood vessels
  • Distinguish between elastic arteries, muscular arteries, and arterioles on the basis of structure, location, and function
  • Describe the basic structure of a capillary bed, from the supplying metarteriole to the venule into which it drains
  • Explain the structure and function of venous valves in the large veins of the extremities

Blood is carried through the body via blood vessels. An artery is a blood vessel that carries blood away from the heart, where it branches into ever-smaller vessels. Eventually, the smallest arteries, vessels called arterioles, further branch into tiny capillaries, where nutrients and wastes are exchanged, and then combine with other vessels that exit capillaries to form venules, small blood vessels that carry blood to a vein, a larger blood vessel that returns blood to the heart.

Arteries and veins transport blood in two distinct circuits: the systemic circuit and the pulmonary circuit (Figure 6.6.1). Systemic arteries provide blood rich in oxygen to the body’s tissues. The blood returned to the heart through systemic veins has less oxygen, since much of the oxygen carried by the arteries has been delivered to the cells. In contrast, in the pulmonary circuit, arteries carry blood low in oxygen exclusively to the lungs for gas exchange. Pulmonary veins then return freshly oxygenated blood from the lungs to the heart to be pumped back out into systemic circulation. Although arteries and veins differ structurally and functionally, they share certain features.

. Cardiovascular circulation. The pulmonary circuit moves blood from the right side of the heart to the lungs and back to the heart. The systemic circuit moves blood from the left side of the heart to the head and body and returns it to the right side of the heart to repeat the cycle. The arrows indicate the direction of blood flow, and the colours show the relative levels of oxygen concentration.
Figure 6.6.1. Cardiovascular circulation. The pulmonary circuit moves blood from the right side of the heart to the lungs and back to the heart. The systemic circuit moves blood from the left side of the heart to the head and body and returns it to the right side of the heart to repeat the cycle. The arrows indicate the direction of blood flow, and the colours show the relative levels of oxygen concentration.

Shared Structures

Different types of blood vessels vary slightly in their structures, but they share the same general features. Arteries and arterioles have thicker walls than veins and venules because they are closer to the heart and receive blood that is surging at a far greater pressure (Figure 6.6.2). Each type of vessel has a lumen—a hollow passageway through which blood flows. Arteries have smaller lumens than veins, a characteristic that helps to maintain the pressure of blood moving through the system. Together, their thicker walls and smaller diameters give arterial lumens a more rounded appearance in cross section than the lumens of veins.

Structure of blood vessels. (a) Arteries and (b) veins share the same general features, but the walls of arteries are much thicker because of the higher pressure of the blood that flows through them. (c) A micrograph shows the relative differences in thickness.
Figure 6.6.2. Structure of blood vessels. (a) Arteries and (b) veins share the same general features, but the walls of arteries are much thicker because of the higher pressure of the blood that flows through them. (c) A micrograph shows the relative differences in thickness. LM × 160. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012).

By the time blood has passed through capillaries and entered venules, the pressure initially exerted upon it by heart contractions has diminished. In other words, in comparison to arteries, venules and veins withstand a much lower pressure from the blood that flows through them. Their walls are considerably thinner and their lumens are correspondingly larger in diameter, allowing more blood to flow with less vessel resistance. In addition, many veins of the body, particularly those of the limbs, contain valves that assist the unidirectional flow of blood toward the heart. This is critical because blood flow becomes sluggish in the extremities, as a result of the lower pressure and the effects of gravity.

The walls of arteries and veins are largely composed of living cells and their products (including collagenous and elastic fibres); the cells require nourishment and produce waste. Since blood passes through the larger vessels relatively quickly, there is limited opportunity for blood in the lumen of the vessel to provide nourishment to or remove waste from the vessel’s cells. Further, the walls of the larger vessels are too thick for nutrients to diffuse through to all of the cells. Larger arteries and veins contain small blood vessels within their walls known as the vasa vasorum—literally “vessels of the vessel”—to provide them with this critical exchange. Since the pressure within arteries is relatively high, the vasa vasorum must function in the outer layers of the vessel (see Figure 6.2.2) or the pressure exerted by the blood passing through the vessel would collapse it, preventing any exchange from occurring. The lower pressure within veins allows the vasa vasorum to be located closer to the lumen. The restriction of the vasa vasorum to the outer layers of arteries is thought to be one reason that arterial diseases are more common than venous diseases, since its location makes it more difficult to nourish the cells of the arteries and remove waste products. There are also minute nerves within the walls of both types of vessels that control the contraction and dilation of smooth muscle. These minute nerves are known as the nervi vasorum.

Both arteries and veins have the same three distinct tissue layers, called tunics (from the Latin term tunica), for the garments first worn by ancient Romans; the term tunic is also used for some modern garments. From the most interior layer to the outer, these tunics are the tunica intima, the tunica media, and the tunica externa (see Figure 6.6.2). Table 6.6.1 compares and contrasts the tunics of the arteries and veins.

Table 6.6.1. Comparison of tunics in arteries and veins

  Arteries Veins
General appearance Thick walls with small lumens Thin walls with large lumens
Generally appear rounded Generally appear flattened
Tunica intima Endothelium usually appears wavy due to constriction of smooth muscle Endothelium appears smooth
Internal elastic membrane present in larger vessels Internal elastic membrane absent
Tunica media Normally the thickest layer in arteries Normally thinner than the tunica externa
Smooth muscle cells and elastic fibres predominate (the proportions of these vary with distance from the heart) Smooth muscle cells and collagenous fibres predominate
External elastic membrane present in larger vessels Nervi vasorum and vasa vasorum present
External elastic membrane absent
Tunica externa Normally thinner than the tunica media in all but the largest arteries Normally the thicket layer in veins
Collagenous and elastic fibres Some smooth muscle fibres
Nervi vasorum and vasa vasorum present Nervi vasorum and vasa vasorum present

Tunica Intima

The tunica intima (also called the tunica interna) is composed of epithelial and connective tissue layers. Lining the tunica intima is the specialised simple squamous epithelium called the endothelium, which is continuous throughout the entire vascular system, including the lining of the chambers of the heart. Damage to this endothelial lining and exposure of blood to the collagenous fibres beneath is one of the primary causes of clot formation. Until recently, the endothelium was viewed simply as the boundary between the blood in the lumen and the walls of the vessels. Recent studies, however, have shown that it is physiologically critical to such activities as helping to regulate capillary exchange and altering blood flow. The endothelium releases local chemicals called endothelins that can constrict the smooth muscle within the walls of the vessel to increase blood pressure. Uncompensated overproduction of endothelins may contribute to hypertension (high blood pressure) and cardiovascular disease.

Next to the endothelium is the basement membrane, or basal lamina, that effectively binds the endothelium to the connective tissue. The basement membrane provides strength while maintaining flexibility, and it is permeable, allowing materials to pass through it. The thin outer layer of the tunica intima contains a small amount of areolar connective tissue that consists primarily of elastic fibres to provide the vessel with additional flexibility; it also contains some collagenous fibres to provide additional strength.

In larger arteries, there is also a thick, distinct layer of elastic fibres known as the internal elastic membrane (also called the internal elastic lamina) at the boundary with the tunica media. Like the other components of the tunica intima, the internal elastic membrane provides structure while allowing the vessel to stretch. It is permeated with small openings that allow exchange of materials between the tunics. The internal elastic membrane is not apparent in veins. In addition, many veins, particularly in the lower limbs, contain valves formed by sections of thickened endothelium that are reinforced with connective tissue, extending into the lumen.

Under the microscope, the lumen and the entire tunica intima of a vein will appear smooth, whereas those of an artery will normally appear wavy because of the partial constriction of the smooth muscle in the tunica media, the next layer of blood vessel walls.

Tunica Media

The tunica media is the substantial middle layer of the vessel wall (see Figure 6.6.2). It is generally the thickest layer in arteries, and it is much thicker in arteries than it is in veins. The tunica media consists of layers of smooth muscle supported by connective tissue that is primarily made up of elastic fibres, most of which are arranged in circular sheets. Toward the outer portion of the tunic, there are also layers of longitudinal muscle. Contraction and relaxation of the circular muscles decrease and increase the diameter of the vessel lumen, respectively. Specifically, in arteries vasoconstriction decreases blood flow as the smooth muscle in the walls of the tunica media contracts, making the lumen narrower and increasing blood pressure. Similarly, vasodilation increases blood flow as the smooth muscle relaxes, allowing the lumen to widen and blood pressure to drop. Both vasoconstriction and vasodilation are regulated in part by small vascular nerves, known as nervi vasorum, or “nerves of the vessel,” that run within the walls of blood vessels. These are generally all sympathetic fibres, although some trigger vasodilation and others induce vasoconstriction, depending upon the nature of the neurotransmitter and receptors located on the target cell. Parasympathetic stimulation does trigger vasodilation as well as erection during sexual arousal in the external genitalia of both sexes. Nervous control over vessels tends to be more generalised than the specific targeting of individual blood vessels. Local controls, discussed later, account for this phenomenon. (Seek additional content for more information on these dynamic aspects of the autonomic nervous system.) Hormones and local chemicals also control blood vessels. Together, these neural and chemical mechanisms reduce or increase blood flow in response to changing body conditions, from exercise to hydration. Regulation of both blood flow and blood pressure is discussed in detail later in this chapter.

The smooth muscle layers of the tunica media are supported by a framework of collagenous fibres that also binds the tunica media to the inner and outer tunics. Along with the collagenous fibres are large numbers of elastic fibres that appear as wavy lines in prepared slides. Separating the tunica media from the outer tunica externa in larger arteries is the external elastic membrane (also called the external elastic lamina), which also appears wavy in slides. This structure is not usually seen in smaller arteries, nor is it seen in veins.

Tunica Externa

The outer tunic, the tunica externa (also called the tunica adventitia), is a substantial sheath of connective tissue composed primarily of collagenous fibres. Some bands of elastic fibres are found here as well. The tunica externa in veins also contains groups of smooth muscle fibres. This is normally the thickest tunic in veins and may be thicker than the tunica media in some larger arteries. The outer layers of the tunica externa are not distinct but rather blend with the surrounding connective tissue outside the vessel, helping to hold the vessel in relative position. If you are able to palpate some of the superficial veins on your upper limbs and try to move them, you will find that the tunica externa prevents this. If the tunica externa did not hold the vessel in place, any movement would likely result in disruption of blood flow.

Arteries

An artery is a blood vessel that conducts blood away from the heart. All arteries have relatively thick walls that can withstand the high pressure of blood ejected from the heart. However, those close to the heart have the thickest walls, containing a high percentage of elastic fibres in all three of their tunics. This type of artery is known as an elastic artery (Figure 6.6.3). Vessels larger than 10 mm in diameter are typically elastic. Their abundant elastic fibres allow them to expand, as blood pumped from the ventricles passes through them, and then to recoil after the surge has passed. If artery walls were rigid and unable to expand and recoil, their resistance to blood flow would greatly increase and blood pressure would rise to even higher levels, which would in turn require the heart to pump harder to increase the volume of blood expelled by each pump (the stroke volume) and maintain adequate pressure and flow. Artery walls would have to become even thicker in response to this increased pressure. The elastic recoil of the vascular wall helps to maintain the pressure gradient that drives the blood through the arterial system. An elastic artery is also known as a conducting artery, because the large diameter of the lumen enables it to accept a large volume of blood from the heart and conduct it to smaller branches.

Types of arteries and arterioles. a) Comparison of the walls of an elastic artery, a muscular artery, and an arteriole is shown. In terms of scale, the diameter of an arteriole is measured in micrometres compared to millimetres for elastic and muscular arteries; b) hyoid artery, human, 40x, transverse.
Figure 6.6.3. Types of arteries and arterioles. a) Comparison of the walls of an elastic artery, a muscular artery, and an arteriole is shown. In terms of scale, the diameter of an arteriole is measured in micrometres compared to millimetres for elastic and muscular arteries; b) hyoid artery, human, 40x, transverse. Image from AnatomyTool used under CC-BY.

Farther from the heart, where the surge of blood has dampened, the percentage of elastic fibres in an artery’s tunica intima decreases and the amount of smooth muscle in its tunica media increases. The artery at this point is described as a muscular artery. The diameter of muscular arteries typically ranges from 0.1 mm to 10 mm. Their thick tunica media allows muscular arteries to play a leading role in vasoconstriction. In contrast, their decreased quantity of elastic fibres limits their ability to expand. Fortunately, because the blood pressure has eased by the time it reaches these more distant vessels, elasticity has become less important.

Notice that although the distinctions between elastic and muscular arteries are important, there is no “line of demarcation” where an elastic artery suddenly becomes muscular. Rather, there is a gradual transition as the vascular tree repeatedly branches. In turn, muscular arteries branch to distribute blood to the vast network of arterioles. For this reason, a muscular artery is also known as a distributing artery.

Arterioles

An arteriole is a very small artery that leads to a capillary. Arterioles have the same three tunics as the larger vessels, but the thickness of each is greatly diminished. The critical endothelial lining of the tunica intima is intact. The tunica media is restricted to one or two smooth muscle cell layers in thickness. The tunica externa remains but is very thin (see Figure 6.6.3).

With a lumen averaging 30 micrometres or less in diameter, arterioles are critical in slowing down—or resisting—blood flow and, thus, causing a substantial drop in blood pressure. Because of this, you may see them referred to as resistance vessels. The muscle fibres in arterioles are normally slightly contracted, causing arterioles to maintain a consistent muscle tone—in this case referred to as vascular tone—in a similar manner to the muscular tone of skeletal muscle. In reality, all blood vessels exhibit vascular tone due to the partial contraction of smooth muscle. The importance of the arterioles is that they will be the primary site of both resistance and regulation of blood pressure. The precise diameter of the lumen of an arteriole at any given moment is determined by neural and chemical controls, and vasoconstriction and vasodilation in the arterioles are the primary mechanisms for distribution of blood flow.

Capillaries

capillary is a microscopic channel that supplies blood to the tissues themselves, a process called perfusion. Exchange of gases and other substances occurs in the capillaries between the blood and the surrounding cells and their tissue fluid (interstitial fluid). The diameter of a capillary lumen ranges from 5–10 micrometres; the smallest are just barely wide enough for an erythrocyte to squeeze through. Flow through capillaries is often described as microcirculation.

The wall of a capillary consists of the endothelial layer surrounded by a basement membrane with occasional smooth muscle fibres. There is some variation in wall structure: In a large capillary, several endothelial cells bordering each other may line the lumen; in a small capillary, there may be only a single cell layer that wraps around to contact itself.

For capillaries to function, their walls must be leaky, allowing substances to pass through. There are three major types of capillaries, which differ according to their degree of “leakiness:” continuous, fenestrated, and sinusoid capillaries (Figure 6.6.4).

Continuous Capillaries

The most common type of capillary, the continuous capillary, is found in almost all vascularised tissues. Continuous capillaries are characterised by a complete endothelial lining with tight junctions between endothelial cells. Although a tight junction is usually impermeable and only allows for the passage of water and ions, they are often incomplete in capillaries, leaving intercellular clefts that allow for exchange of water and other very small molecules between the blood plasma and the interstitial fluid. Substances that can pass between cells include metabolic products, such as glucose, water, and small hydrophobic molecules like gases and hormones, as well as various leukocytes. Continuous capillaries not associated with the brain are rich in transport vesicles, contributing to either endocytosis or exocytosis. Those in the brain are part of the blood-brain barrier. Here, there are tight junctions and no intercellular clefts, plus a thick basement membrane and astrocyte extensions called end feet; these structures combine to prevent the movement of nearly all substances.

Diagram of types cpillaries
Figure 6.6.4. Types of capillaries. The three major types of capillaries: continuous, fenestrated and sinusoid.

Fenestrated Capillaries

fenestrated capillary is one that has pores (or fenestrations) in addition to tight junctions in the endothelial lining. These make the capillary permeable to larger molecules. The number of fenestrations and their degree of permeability vary, however, according to their location. Fenestrated capillaries are common in the small intestine, which is the primary site of nutrient absorption, as well as in the kidneys, which filter the blood. They are also found in the choroid plexus of the brain and many endocrine structures, including the hypothalamus, pituitary, pineal and thyroid glands.

Sinusoid Capillaries

sinusoid capillary (or sinusoid) is the least common type of capillary. Sinusoid capillaries are flattened, and they have extensive intercellular gaps and incomplete basement membranes, in addition to intercellular clefts and fenestrations. This gives them an appearance not unlike Swiss cheese. These very large openings allow for the passage of the largest molecules, including plasma proteins and even cells. Blood flow through sinusoids is very slow, allowing more time for exchange of gases, nutrients, and wastes. Sinusoids are found in the liver and spleen, bone marrow, lymph nodes (where they carry lymph, not blood), and many endocrine glands including the pituitary and adrenal glands. Without these specialised capillaries, these organs would not be able to provide their myriad of functions. For example, when bone marrow forms new blood cells, the cells must enter the blood supply and can only do so through the large openings of a sinusoid capillary; they cannot pass through the small openings of continuous or fenestrated capillaries. The liver also requires extensive specialised sinusoid capillaries in order to process the materials brought to it by the hepatic portal vein from both the digestive tract and spleen, and to release plasma proteins into circulation.

Metarterioles and Capillary Beds

metarteriole is a type of vessel that has structural characteristics of both an arteriole and a capillary. Slightly larger than the typical capillary, the smooth muscle of the tunica media of the metarteriole is not continuous but forms rings of smooth muscle (sphincters) prior to the entrance to the capillaries. Each metarteriole arises from a terminal arteriole and branches to supply blood to a capillary bed that may consist of 10–100 capillaries.

The precapillary sphincters, circular smooth muscle cells that surround the capillary at its origin with the metarteriole, tightly regulate the flow of blood from a metarteriole to the capillaries it supplies. Their function is critical: If all of the capillary beds in the body were to open simultaneously, they would collectively hold every drop of blood in the body and there would be none in the arteries, arterioles, venules, veins, or the heart itself. Normally, the precapillary sphincters are closed. When the surrounding tissues need oxygen and have excess waste products, the precapillary sphincters open, allowing blood to flow through and exchange to occur before closing once more (Figure 6.6.5). If all of the precapillary sphincters in a capillary bed are closed, blood will flow from the metarteriole directly into a thoroughfare channel and then into the venous circulation, bypassing the capillary bed entirely. This creates what is known as a vascular shunt. In addition, an arteriovenous anastomosis may bypass the capillary bed and lead directly to the venous system.

Although you might expect blood flow through a capillary bed to be smooth, in reality, it moves with an irregular, pulsating flow. This pattern is called vasomotion and is regulated by chemical signals that are triggered in response to changes in internal conditions, such as oxygen, carbon dioxide, hydrogen ion, and lactic acid levels. For example, during strenuous exercise when oxygen levels decrease and carbon dioxide, hydrogen ion, and lactic acid levels all increase, the capillary beds in skeletal muscle are open, as they would be in the digestive system when nutrients are present in the digestive tract. During sleep or rest periods, vessels in both areas are largely closed; they open only occasionally to allow oxygen and nutrient supplies to travel to the tissues to maintain basic life processes.

Diagram of cappilary bed
Figure 6.6.5. Capillary bed. In a capillary bed, arterioles give rise to metarterioles. Precapillary sphincters located at the junction of a metarteriole with a capillary regulate blood flow. A thoroughfare channel connects the metarteriole to a venule. An arteriovenous anastomosis, which directly connects the arteriole with the venule, is shown at the bottom.

Venules

venule is an extremely small vein, generally 8–100 micrometres in diameter. Postcapillary venules join multiple capillaries exiting from a capillary bed. Multiple venules join to form veins. The walls of venules consist of endothelium, a thin middle layer with a few muscle cells and elastic fibres, plus an outer layer of connective tissue fibres that constitute a very thin tunica externa (Figure 6.6.6). Venules as well as capillaries are the primary sites of emigration or diapedesis, in which the white blood cells adhere to the endothelial lining of the vessels and then squeeze through adjacent cells to enter the tissue fluid.

Veins

vein is a blood vessel that conducts blood toward the heart. Compared to arteries, veins are thin-walled vessels with large and irregular lumens (see Figure 6.6.6). Because they are low-pressure vessels, larger veins are commonly equipped with valves that promote the unidirectional flow of blood toward the heart and prevent backflow toward the capillaries caused by the inherent low blood pressure in veins as well as the pull of gravity. Table 2 compares the features of arteries and veins.

Diagram of veins and venules
Figure 6.6.6. Comparison of veins and venules. Many veins have valves to prevent back flow of blood, whereas venules do not. In terms of scale, the diameter of a venule is measured in micrometres compared to millimetres for veins.

Table 6.6.2. Comparison of arteries and veins

  Arteries Veins
Direction of blood flow Conducts blood away from heart Conducts blood toward the heart
General appearance Rounded Irregular, often collapsed
Pressure High Low
Wall thickness Thick Thin
Relative oxygen concentration Higher in systemic arteries

Lower in pulmonary arteries

Lower in systemic veins

Higher in pulmonary veins

Valves Not present Present most commonly in limbs and in veins inferior to the heart

Disorders of the Cardiovascular System: Oedema and Varicose Veins

Photo of varicose veins on legs
Figure 6.6.7. Varicose veins. Varicose veins are commonly found in the lower limbs. (credit: Thomas Kriese).

Despite the presence of valves and the contributions of other anatomical and physiological adaptations we will cover shortly, over the course of a day, some blood will inevitably pool, especially in the lower limbs, due to the pull of gravity. Any blood that accumulates in a vein will increase the pressure within it, which can then be reflected back into the smaller veins, venules, and eventually even the capillaries. Increased pressure will promote the flow of fluids out of the capillaries and into the interstitial fluid. The presence of excess tissue fluid around the cells leads to a condition called oedema.

Most people experience a daily accumulation of tissue fluid, especially if they spend much of their work life on their feet (like most health professionals). However, clinical oedema goes beyond normal swelling and requires medical treatment. Oedema has many potential causes, including hypertension and heart failure, severe protein deficiency, renal failure, and many others. In order to treat oedema, which is a sign rather than a discrete disorder, the underlying cause must be diagnosed and alleviated.

Oedema may be accompanied by varicose veins, especially in the superficial veins of the legs (Figure 6.6.7). This disorder arises when defective valves allow blood to accumulate within the veins, causing them to distend, twist, and become visible on the surface of the integument. Varicose veins may occur in both sexes but are more common in women and are often related to pregnancy. More than simple cosmetic blemishes, varicose veins are often painful and sometimes itchy or throbbing. Without treatment, they tend to grow worse over time. The use of support hose, as well as elevating the feet and legs whenever possible, may be helpful in alleviating this condition. Laser surgery and interventional radiologic procedures can reduce the size and severity of varicose veins. Severe cases may require conventional surgery to remove the damaged vessels. As there are typically redundant circulation patterns, that is, anastomoses, for the smaller and more superficial veins, removal does not typically impair the circulation. There is evidence that patients with varicose veins suffer a greater risk of developing a thrombus or clot.

Veins as Blood Reservoirs

In addition to their primary function of returning blood to the heart, veins may be considered blood reservoirs, since systemic veins contain approximately 64 percent of the blood volume at any given time (Figure 6.6.8). Their ability to hold this much blood is due to their high capacitance, that is, their capacity to distend (expand) readily to store a high volume of blood, even at a low pressure. The large lumens and relatively thin walls of veins make them far more distensible than arteries; thus, they are said to be capacitance vessels.

Tabl e of distribution of blood flow- systemic circulation 84, pulmonary circulation 9% and heart 7%
Figure 6.6.8. Distribution of Blood Flow.

When blood flow needs to be redistributed to other portions of the body, the vasomotor centre located in the medulla oblongata sends sympathetic stimulation to the smooth muscles in the walls of the veins, causing constriction—or in this case, venoconstriction. Less dramatic than the vasoconstriction seen in smaller arteries and arterioles, venoconstriction may be likened to a “stiffening” of the vessel wall. This increases pressure on the blood within the veins, speeding its return to the heart. As you will note in Figure 6.6.8, approximately 21 percent of the venous blood is located in venous networks within the liver, bone marrow, and integument. This volume of blood is referred to as venous reserve. Through venoconstriction, this “reserve” volume of blood can get back to the heart more quickly for redistribution to other parts of the circulation.

Career Connection

Vascular Surgeons and Technicians

Vascular surgery is a specialty in which the physician deals primarily with diseases of the vascular portion of the cardiovascular system. This includes repair and replacement of diseased or damaged vessels, removal of plaque from vessels, minimally invasive procedures including the insertion of venous catheters, and traditional surgery. Following completion of medical school, the physician generally completes a five-year surgical residency followed by an additional one to two years of vascular specialty training. In Australia, most vascular surgeons are a member of the Vascular Surgeons in Australia and New Zealand (ANZSVS) which is the principal body for the education and training of vascular surgeons in Australia and New Zealand. This is similar to the Society of Vascular Surgery in the United States.

Vascular technicians are specialists in imaging technologies that provide information on the health of the vascular system. They may also assist physicians in treating disorders involving the arteries and veins. This profession often overlaps with cardiovascular technology, which would also include treatments involving the heart. In Australia, a cardiac surgeon may earn between $99k – $509k per annum.

Section Review

Blood pumped by the heart flows through a series of vessels known as arteries, arterioles, capillaries, venules, and veins before returning to the heart. Arteries transport blood away from the heart and branch into smaller vessels, forming arterioles. Arterioles distribute blood to capillary beds, the sites of exchange with the body tissues. Capillaries lead back to small vessels known as venules that flow into the larger veins and eventually back to the heart.

The arterial system is a relatively high-pressure system, so arteries have thick walls that appear round in cross section. The venous system is a lower-pressure system, containing veins that have larger lumens and thinner walls. They often appear flattened. Arteries, arterioles, venules, and veins are composed of three tunics known as the tunica intima, tunica media, and tunica externa. Capillaries have only a tunica intima layer. The tunica intima is a thin layer composed of a simple squamous epithelium known as endothelium and a small amount of connective tissue. The tunica media is a thicker area composed of variable amounts of smooth muscle and connective tissue. It is the thickest layer in all but the largest arteries. The tunica externa is primarily a layer of connective tissue, although in veins, it also contains some smooth muscle. Blood flow through vessels can be dramatically influenced by vasoconstriction and vasodilation in their walls.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=516

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=516

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=516

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=516

6.7 Blood Flow, Blood Pressure and Resistance

Learning Objectives

By the end of this section, you will be able to:

  • Distinguish between systolic pressure, diastolic pressure, pulse pressure, and mean arterial pressure
  • Describe the clinical measurement of pulse and blood pressure
  • Identify and discuss five variables affecting arterial blood flow and blood pressure
  • Discuss several factors affecting blood flow in the venous system

Blood flow refers to the movement of blood through a vessel, tissue, or organ, and is usually expressed in terms of volume of blood per unit of time. It is initiated by the contraction of the ventricles of the heart. Ventricular contraction ejects blood into the major arteries, resulting in flow from regions of higher pressure to regions of lower pressure, as blood encounters smaller arteries and arterioles, then capillaries, then the venules and veins of the venous system. This section discusses a number of critical variables that contribute to blood flow throughout the body. It also discusses the factors that impede or slow blood flow, a phenomenon known as resistance.

As noted earlier, hydrostatic pressure is the force exerted by a fluid due to gravitational pull, usually against the wall of the container in which it is located. One form of hydrostatic pressure is blood pressure, the force exerted by blood upon the walls of the blood vessels or the chambers of the heart. Blood pressure may be measured in capillaries and veins, as well as the vessels of the pulmonary circulation; however, the term blood pressure without any specific descriptors typically refers to systemic arterial blood pressure—that is, the pressure of blood flowing in the arteries of the systemic circulation. In clinical practice, this pressure is measured in mm Hg and is usually obtained using the brachial artery of the arm.

Components of Arterial Blood Pressure

Arterial blood pressure in the larger vessels consists of several distinct components (Figure 6.7.1): systolic and diastolic pressures, pulse pressure, and mean arterial pressure.

Systolic and Diastolic Pressure

When systemic arterial blood pressure is measured, it is recorded as a ratio of two numbers (e.g., 120/80 is a normal adult blood pressure), expressed as systolic pressure over diastolic pressure. The systolic pressure is the higher value (typically around 120 mm Hg) and reflects the arterial pressure resulting from the ejection of blood during ventricular contraction, or systole. The diastolic pressure is the lower value (usually about 80 mm Hg) and represents the arterial pressure of blood during ventricular relaxation, or diastole.

The graph shows the components of blood pressure throughout the blood vessels, including systolic, diastolic, mean arterial, and pulse pressures.
Figure 6.7.1. Systemic blood pressure. The graph shows the components of blood pressure throughout the blood vessels, including systolic, diastolic, mean arterial, and pulse pressures.

Pulse Pressure

As shown in Figure 6.7.1, the difference between the systolic pressure and the diastolic pressure is the pulse pressure. For example, an individual with a systolic pressure of 120 mm Hg and a diastolic pressure of 80 mm Hg would have a pulse pressure of 40 mmHg.

Generally, a pulse pressure should be at least 25 percent of the systolic pressure. A pulse pressure below this level is described as low or narrow. This may occur, for example, in patients with a low stroke volume, which may be seen in congestive heart failure, stenosis of the aortic valve, or significant blood loss following trauma. In contrast, a high or wide pulse pressure is common in healthy people following strenuous exercise, when their resting pulse pressure of 30–40 mm Hg may increase temporarily to 100 mm Hg as stroke volume increases. A persistently high pulse pressure at or above 100 mm Hg may indicate excessive resistance in the arteries and can be caused by a variety of disorders. Chronic high resting pulse pressures can degrade the heart, brain, and kidneys, and warrant medical treatment.

Mean Arterial Pressure

Mean arterial pressure (MAP) represents the “average” pressure of blood in the arteries, that is, the average force driving blood into vessels that serve the tissues. Mean is a statistical concept and is calculated by taking the sum of the values divided by the number of values. Although complicated to measure directly and complicated to calculate, MAP can be approximated by adding the diastolic pressure to one-third of the pulse pressure or systolic pressure minus the diastolic pressure:

MAP = diastolic BP + ((systolic-diastolic BP) / 3)

In Figure 6.7.1, this value is approximately 80 + (120 − 80) / 3, or 93.33. Normally, the MAP falls within the range of 70–110 mm Hg. If the value falls below 60 mm Hg for an extended time, blood pressure will not be high enough to ensure circulation to and through the tissues, which results in ischaemia, or insufficient blood flow. A condition called hypoxia, inadequate oxygenation of tissues, commonly accompanies ischaemia. The term hypoxaemia refers to low levels of oxygen in systemic arterial blood. Neurons are especially sensitive to hypoxia and may die or be damaged if blood flow and oxygen supplies are not quickly restored.

Pulse

After blood is ejected from the heart, elastic fibres in the arteries help maintain a high-pressure gradient as they expand to accommodate the blood, then recoil. This expansion and recoiling effect, known as the pulse, can be palpated manually or measured electronically. Although the effect diminishes over distance from the heart, elements of the systolic and diastolic components of the pulse are still evident down to the level of the arterioles.

Because pulse indicates heart rate, it is measured clinically to provide clues to a patient’s state of health. It is recorded as beats per minute. Both the rate and the strength of the pulse are important clinically. A high or irregular pulse rate can be caused by physical activity or other temporary factors, but it may also indicate a heart condition. The pulse strength indicates the strength of ventricular contraction and cardiac output. If the pulse is strong, then systolic pressure is high. If it is weak, systolic pressure has fallen, and medical intervention may be warranted.

Pulse can be palpated manually by placing the tips of the fingers across an artery that runs close to the body surface and pressing lightly. While this procedure is normally performed using the radial artery in the wrist or the common carotid artery in the neck, any superficial artery that can be palpated may be used (Figure 6.7.2). Common sites to find a pulse include temporal and facial arteries in the head, brachial arteries in the upper arm, femoral arteries in the thigh, popliteal arteries behind the knees, posterior tibial arteries near the medial tarsal regions, and dorsalis pedis arteries in the feet. A variety of commercial electronic devices are also available to measure pulse.

Pulse sites on the body
Figure 6.7.2. Pulse sites. The pulse is most readily measured at the radial artery but can be measured at any of the pulse points shown.

Measurement of Blood Pressure

Blood pressure is one of the critical parameters measured on virtually every patient in every healthcare setting. The technique used today was developed more than 100 years ago by a pioneering Russian physician, Dr. Nikolai Korotkoff. Turbulent blood flow through the vessels can be heard as a soft ticking while measuring blood pressure; these sounds are known as Korotkoff sounds. The technique of measuring blood pressure requires the use of a sphygmomanometer (a blood pressure cuff attached to a measuring device) and a stethoscope. The technique is as follows:

  1. The clinician wraps an inflatable cuff tightly around the patient’s arm at about the level of the heart.
  2. The clinician squeezes a rubber pump to inject air into the cuff, raising pressure around the artery and temporarily cutting off blood flow into the patient’s arm.
  3. The clinician places the stethoscope on the patient’s antecubital region and, while gradually allowing air within the cuff to escape, listens for the Korotkoff sounds.

Although there are five recognised Korotkoff sounds, only two are normally recorded. Initially, no sounds are heard since there is no blood flow through the vessels, but as air pressure drops, the cuff relaxes, and blood flow returns to the arm. As shown in Figure 6.7.3, the first sound heard through the stethoscope—the first Korotkoff sound—indicates systolic pressure. As more air is released from the cuff, blood is able to flow freely through the brachial artery and all sounds disappear. The point at which the last sound is heard is recorded as the patient’s diastolic pressure.

Blood pressure measurement
Figure 6.7.3. Blood pressure measurement. When pressure in a sphygmomanometer cuff is released, a clinician can hear the Korotkoff sounds. In this graph, a blood pressure tracing is aligned to a measurement of systolic and diastolic pressures.

The majority of hospitals and clinics have automated equipment for measuring blood pressure that work on the same principles. An even more recent innovation is a small instrument that wraps around a patient’s wrist. The patient then holds the wrist over the heart while the device measures blood flow and records pressure.

Variables Affecting Blood Flow and Blood Pressure

Five variables influence blood flow and blood pressure:

Recall that blood moves from higher pressure to lower pressure. It is pumped from the heart into the arteries at high pressure. If you increase pressure in the arteries (afterload), and cardiac function does not compensate, blood flow will actually decrease. In the venous system, the opposite relationship is true. Increased pressure in the veins does not decrease flow as it does in arteries, but actually increases flow. Since pressure in the veins is normally relatively low, for blood to flow back into the heart, the pressure in the atria during atrial diastole must be even lower. It normally approaches zero, except when the atria contract (see Figure 6.7.1).

Cardiac Output

Cardiac output is the measurement of blood flow from the heart through the ventricles and is usually measured in litres per minute. Any factor that causes cardiac output to increase, by elevating heart rate or stroke volume or both, will elevate blood pressure and promote blood flow. These factors include sympathetic stimulation, the catecholamines adrenaline and noradrenaline, thyroid hormones, and increased calcium ion levels. Conversely, any factor that decreases cardiac output, by decreasing heart rate or stroke volume or both, will decrease arterial pressure and blood flow. These factors include parasympathetic stimulation, elevated or decreased potassium ion levels, decreased calcium levels, anoxia, and acidosis.

Compliance

Compliance is the ability of any compartment to expand to accommodate increased content. A metal pipe, for example, is not compliant, whereas a balloon is. The greater the compliance of an artery, the more effectively it is able to expand to accommodate surges in blood flow without increased resistance or blood pressure. Veins are more compliant than arteries and can expand to hold more blood. When vascular disease causes stiffening of arteries, compliance is reduced and resistance to blood flow is increased. The result is more turbulence, higher pressure within the vessel, and reduced blood flow. This increases the work of the heart.

A Mathematical Approach to Factors Affecting Blood Flow

Jean Louis Marie Poiseuille was a French physician and physiologist who devised a mathematical equation describing blood flow and its relationship to known parameters. The same equation also applies to engineering studies of the flow of fluids. Although understanding the math behind the relationships among the factors affecting blood flow is not necessary to understand blood flow, it can help solidify an understanding of their relationships. Please note that even if the equation looks intimidating, breaking it down into its components and following the relationships will make these relationships clearer, even if you are weak in math. Focus on the three critical variables: radius (r), vessel length (λ), and viscosity (η).

Poiseuille’s equation:

Blood flow = π ΔP r48ηλ

π is the Greek letter pi, used to represent the mathematical constant that is the ratio of a circle’s circumference to its diameter. It may commonly be represented as 3.14, although the actual number extends to infinity.

One of several things this equation allows us to do is calculate the resistance in the vascular system. Normally this value is extremely difficult to measure, but it can be calculated from this known relationship:

If we rearrange this slightly,

Then by substituting Poiseuille’s equation for blood flow:

By examining this equation, you can see that there are only three variables: viscosity, vessel length, and radius, since 8 and π are both constants. The important thing to remember is this: Two of these variables, viscosity and vessel length, will change slowly in the body. Only one of these factors, the radius, can be changed rapidly by vasoconstriction and vasodilation, thus dramatically impacting resistance and flow. Further, small changes in the radius will greatly affect flow, since it is raised to the fourth power in the equation.

We have briefly considered how cardiac output and blood volume impact blood flow and pressure; the next step is to see how the other variables (contraction, vessel length, and viscosity) articulate with Poiseuille’s equation and what they can teach us about the impact on blood flow.

Blood Volume

The relationship between blood volume, blood pressure, and blood flow is intuitively obvious. Water may merely trickle along a creek bed in a dry season but rush quickly and under great pressure after a heavy rain. Similarly, as blood volume decreases, pressure and flow decrease. As blood volume increases, pressure and flow increase.

Under normal circumstances, blood volume varies little. Low blood volume, called hypovolaemia, may be caused by bleeding, dehydration, vomiting, severe burns, or some medications used to treat hypertension. It is important to recognise that other regulatory mechanisms in the body are so effective at maintaining blood pressure that an individual may be asymptomatic until 10–20 percent of the blood volume has been lost. Treatment typically includes intravenous fluid replacement.

Hypervolaemia, excessive fluid volume, may be caused by retention of water and sodium, as seen in patients with heart failure, liver cirrhosis, some forms of kidney disease, hyperaldosteronism, and some glucocorticoid steroid treatments. Restoring homeostasis in these patients depends upon reversing the condition that triggered the hypervolaemia.

Blood Viscosity

Viscosity is the thickness of fluids that affects their ability to flow. Clean water, for example, is less viscous than mud. The viscosity of blood is directly proportional to resistance and inversely proportional to flow; therefore, any condition that causes viscosity to increase will also increase resistance and decrease flow. For example, imagine sipping milk, then a milkshake, through the same size straw. You experience more resistance and therefore less flow from the milkshake. Conversely, any condition that causes viscosity to decrease (such as when the milkshake melts) will decrease resistance and increase flow.

Normally the viscosity of blood does not change over short periods of time. The two primary determinants of blood viscosity are the formed elements and plasma proteins. Since most formed elements are erythrocytes, any condition affecting erythropoiesis, such as polycythaemia or anaemia, can alter viscosity. Since most plasma proteins are produced by the liver, any condition affecting liver function can also change the viscosity slightly and therefore decrease blood flow. Liver abnormalities include hepatitis, cirrhosis, alcohol damage, and drug toxicities. While leukocytes and platelets are normally a small component of the formed elements, there are some rare conditions in which severe overproduction can impact viscosity as well.

Vessel Length and Diameter

The length of a vessel is directly proportional to its resistance: the longer the vessel, the greater the resistance and the lower the flow. As with blood volume, this makes intuitive sense, since the increased surface area of the vessel will impede the flow of blood. Likewise, if the vessel is shortened, the resistance will decrease and flow will increase.

The length of our blood vessels increases throughout childhood as we grow, of course, but is unchanging in adults under normal physiological circumstances. Further, the distribution of vessels is not the same in all tissues. Adipose tissue does not have an extensive vascular supply. One pound of adipose tissue contains approximately 200 miles of vessels, whereas skeletal muscle contains more than twice that. Overall, vessels decrease in length only during loss of mass or amputation. An individual weighing 68kg has approximately 96,560km of vessels in the body. Gaining about 4.5km adds from 3218 to 6437 kilometres of vessels, depending upon the nature of the gained tissue. One of the great benefits of weight reduction is the reduced stress to the heart, which does not have to overcome the resistance of as many miles of vessels.

In contrast to length, the diameter of blood vessels changes throughout the body, according to the type of vessel, as we discussed earlier. The diameter of any given vessel may also change frequently throughout the day in response to neural and chemical signals that trigger vasodilation and vasoconstriction. The vascular tone of the vessel is the contractile state of the smooth muscle and the primary determinant of diameter, and thus of resistance and flow. The effect of vessel diameter on resistance is inverse: Given the same volume of blood, an increased diameter means there is less blood contacting the vessel wall, thus lower friction and lower resistance, subsequently increasing flow. A decreased diameter means more of the blood contacts the vessel wall, and resistance increases, subsequently decreasing flow.

The influence of lumen diameter on resistance is dramatic: A slight increase or decrease in diameter causes a huge decrease or increase in resistance. This is because resistance is inversely proportional to the radius of the blood vessel (one-half of the vessel’s diameter) raised to the fourth power (R = 1/r4). This means, for example, that if an artery or arteriole constricts to one-half of its original radius, the resistance to flow will increase 16 times. And if an artery or arteriole dilates to twice its initial radius, then resistance in the vessel will decrease to 1/16 of its original value and flow will increase 16 times.

The Roles of Vessel Diameter and Total Area in Blood Flow and Blood Pressure

Recall that we classified arterioles as resistance vessels, because given their small lumen, they dramatically slow the flow of blood from arteries. In fact, arterioles are the site of greatest resistance in the entire vascular network. This may seem surprising, given that capillaries have a smaller size. How can this phenomenon be explained?

Figure 6.7.4 compares vessel diameter, total cross-sectional area, average blood pressure, and blood velocity through the systemic vessels. Notice in parts (a) and (b) that the total cross-sectional area of the body’s capillary beds is far greater than any other type of vessel. Although the diameter of an individual capillary is significantly smaller than the diameter of an arteriole, there are vastly more capillaries in the body than there are other types of blood vessels. Part (c) shows that blood pressure drops unevenly as blood travels from arteries to arterioles, capillaries, venules, and veins, and encounters greater resistance. However, the site of the most precipitous drop, and the site of greatest resistance, is the arterioles. This explains why vasodilation and vasoconstriction of arterioles play more significant roles in regulating blood pressure than do the vasodilation and vasoconstriction of other vessels.

Part (d) shows that the velocity (speed) of blood flow decreases dramatically as the blood moves from arteries to arterioles to capillaries. This slow flow rate allows more time for exchange processes to occur. As blood flows through the veins, the rate of velocity increases, as blood is returned to the heart.

Relationships among vessels in the systemic circuit.
Figure 6.7.4. Relationships among vessels in the systemic circuit. The relationships among blood vessels that can be compared include (a) vessel diameter, (b) total cross-sectional area, (c) average blood pressure, and (d) velocity of blood flow.

Disorders of the Cardiovascular System: Arteriosclerosis

Compliance allows an artery to expand when blood is pumped through it from the heart, and then to recoil after the surge has passed. This helps promote blood flow. In arteriosclerosis, compliance is reduced, and pressure and resistance within the vessel increase. This is a leading cause of hypertension and coronary heart disease, as it causes the heart to work harder to generate a pressure great enough to overcome the resistance.

Arteriosclerosis begins with injury to the endothelium of an artery, which may be caused by irritation from high blood glucose, infection, tobacco use, excessive blood lipids, and other factors. Artery walls that are constantly stressed by blood flowing at high pressure are also more likely to be injured—which means that hypertension can promote arteriosclerosis, as well as result from it.

Recall that tissue injury causes inflammation. As inflammation spreads into the artery wall, it weakens and scars it, leaving it stiff (sclerotic). As a result, compliance is reduced. Moreover, circulating triglycerides and cholesterol can seep between the damaged lining cells and become trapped within the artery wall, where they are frequently joined by leukocytes, calcium, and cellular debris. Eventually, this build-up, called plaque, can narrow arteries enough to impair blood flow. The term for this condition, atherosclerosis (athero- = “porridge”) describes the mealy deposits (Figure 6.7.5).

Diagram and image of Atherosclerosis
Figure 6.7.5. Atherosclerosis. (a) Atherosclerosis can result from plaques formed by the build-up of fatty, calcified deposits in an artery. (b) Plaques can also take other forms, as shown in this micrograph of a coronary artery that has a build-up of connective tissue within the artery wall. LM × 40. (Micrograph provided by the Regents of University of Michigan Medical School © 2012).

Sometimes a plaque can rupture, causing microscopic tears in the artery wall that allow blood to leak into the tissue on the other side. When this happens, platelets rush to the site to clot the blood. This clot can further obstruct the artery and—if it occurs in a coronary or cerebral artery—cause a sudden heart attack or stroke. Alternatively, plaque can break off and travel through the bloodstream as an embolus until it blocks a more distant, smaller artery.

Even without total blockage, vessel narrowing leads to ischaemia—reduced blood flow—to the tissue region “downstream” of the narrowed vessel. Ischaemia in turn leads to hypoxia—decreased supply of oxygen to the tissues. Hypoxia involving cardiac muscle or brain tissue can lead to cell death and severe impairment of brain or heart function.

A major risk factor for both arteriosclerosis and atherosclerosis is advanced age, as the conditions tend to progress over time. Arteriosclerosis is normally defined as the more generalised loss of compliance, “hardening of the arteries,” whereas atherosclerosis is a more specific term for the build-up of plaque in the walls of the vessel and is a specific type of arteriosclerosis. There is also a distinct genetic component, and pre-existing hypertension and/or diabetes also greatly increase the risk. However, obesity, poor nutrition, lack of physical activity, and tobacco use all are major risk factors.

Treatment includes lifestyle changes, such as weight loss, smoking cessation, regular exercise, and adoption of a diet low in sodium and saturated fats. Medications to reduce cholesterol and blood pressure may be prescribed. For blocked coronary arteries, surgery is warranted. In angioplasty, a catheter is inserted into the vessel at the point of narrowing, and a second catheter with a balloon-like tip is inflated to widen the opening. To prevent subsequent collapse of the vessel, a small mesh tube called a stent is often inserted. In an endarterectomy, plaque is surgically removed from the walls of a vessel. This operation is typically performed on the carotid arteries of the neck, which are a prime source of oxygenated blood for the brain. In a coronary bypass procedure, a non-vital superficial vessel from another part of the body (often the great saphenous vein) or a synthetic vessel is inserted to create a path around the blocked area of a coronary artery.

Venous System

The pumping action of the heart propels the blood into the arteries, from an area of higher pressure toward an area of lower pressure. If blood is to flow from the veins back into the heart, the pressure in the veins must be greater than the pressure in the atria of the heart. Two factors help maintain this pressure gradient between the veins and the heart. First, the pressure in the atria during diastole is very low, often approaching zero when the atria are relaxed (atrial diastole). Second, two physiologic “pumps” increase pressure in the venous system. The use of the term “pump” implies a physical device that speeds flow. These physiological pumps are less obvious.

Skeletal Muscle Pump

In many body regions, the pressure within the veins can be increased by the contraction of the surrounding skeletal muscle. This mechanism, known as the skeletal muscle pump (Figure 6.7.6), helps the lower-pressure veins counteract the force of gravity, increasing pressure to move blood back to the heart. As leg muscles contract, for example during walking or running, they exert pressure on nearby veins with their numerous one-way valves. This increased pressure causes blood to flow upward, opening valves superior to the contracting muscles so blood flows through. Simultaneously, valves inferior to the contracting muscles close; thus, blood should not seep back downward toward the feet. Military recruits are trained to flex their legs slightly while standing at attention for prolonged periods. Failure to do so may allow blood to pool in the lower limbs rather than returning to the heart. Consequently, the brain will not receive enough oxygenated blood, and the individual may lose consciousness.

Skeletal muscle pump
Figure 6.7.6. Skeletal muscle pump. The contraction of skeletal muscles surrounding a vein compresses the blood and increases the pressure in that area. This action forces blood closer to the heart where venous pressure is lower. Note the importance of the one-way valves to assure that blood flows only in the proper direction.

Respiratory Pump

The respiratory pump aids blood flow through the veins of the thorax and abdomen. During inhalation, the volume of the thorax increases, largely through the contraction of the diaphragm, which moves downward and compresses the abdominal cavity. The elevation of the chest caused by the contraction of the external intercostal muscles also contributes to the increased volume of the thorax. The volume increase causes air pressure within the thorax to decrease, allowing us to inhale. Additionally, as air pressure within the thorax drops, blood pressure in the thoracic veins also decreases, falling below the pressure in the abdominal veins. This causes blood to flow along its pressure gradient from veins outside the thorax, where pressure is higher, into the thoracic region, where pressure is now lower. This in turn promotes the return of blood from the thoracic veins to the atria. During exhalation, when air pressure increases within the thoracic cavity, pressure in the thoracic veins increases, speeding blood flow into the heart while valves in the veins prevent blood from flowing backward from the thoracic and abdominal veins.

Pressure Relationship in the Venous System

Although vessel diameter increases from the smaller venules to the larger veins and eventually to the venae cavae (singular = vena cava), the total cross-sectional area actually decreases (see Figure 6.7.4a and 6.7.4b). The individual veins are larger in diameter than the venules, but their total number is much lower, so their total cross-sectional area is also lower.

Also notice that, as blood moves from venules to veins, the average blood pressure drops (see Figure 6.7.4c), but the blood velocity actually increases (see Figure 6.7.4d). This pressure gradient drives blood back toward the heart. Again, the presence of one-way valves and the skeletal muscle and respiratory pumps contribute to this increased flow. Since approximately 64 percent of the total blood volume resides in systemic veins, any action that increases the flow of blood through the veins will increase venous return to the heart. Maintaining vascular tone within the veins prevents the veins from merely distending, dampening the flow of blood, and as you will see, vasoconstriction actually enhances the flow.

The Role of Venoconstriction in Resistance, Blood Pressure and Flow

As previously discussed, vasoconstriction of an artery or arteriole decreases the radius, increasing resistance and pressure, but decreasing flow. Venoconstriction, on the other hand, has a very different outcome. The walls of veins are thin but irregular; thus, when the smooth muscle in those walls constricts, the lumen becomes more rounded. The more rounded the lumen, the less surface area the blood encounters, and the less resistance the vessel offers. Vasoconstriction increases pressure within a vein as it does in an artery, but in veins, the increased pressure increases flow. Recall that the pressure in the atria, into which the venous blood will flow, is very low, approaching zero for at least part of the relaxation phase of the cardiac cycle. Thus, venoconstriction increases the return of blood to the heart. Another way of stating this is that venoconstriction increases the preload or stretch of the cardiac muscle and increases contraction.

Section Review

Blood flow is the movement of blood through a vessel, tissue, or organ. The slowing or blocking of blood flow is called resistance. Blood pressure is the force that blood exerts upon the walls of the blood vessels or chambers of the heart. The components of blood pressure include systolic pressure, which results from ventricular contraction, and diastolic pressure, which results from ventricular relaxation. Pulse pressure is the difference between systolic and diastolic measures, and mean arterial pressure is the “average” pressure of blood in the arterial system, driving blood into the tissues. Pulse, the expansion and recoiling of an artery, reflects the heartbeat. The variables affecting blood flow and blood pressure in the systemic circulation are cardiac output, compliance, blood volume, blood viscosity, and the length and diameter of the blood vessels. In the arterial system, vasodilation and vasoconstriction of the arterioles is a significant factor in systemic blood pressure: Slight vasodilation greatly decreases resistance and increases flow, whereas slight vasoconstriction greatly increases resistance and decreases flow. In the arterial system, as resistance increases, blood pressure increases and flow decreases. In the venous system, constriction increases blood pressure as it does in arteries; the increasing pressure helps to return blood to the heart. In addition, constriction causes the vessel lumen to become more rounded, decreasing resistance and increasing blood flow. Venoconstriction, while less important than arterial vasoconstriction, works with the skeletal muscle pump, the respiratory pump, and their valves to promote venous return to the heart.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=518

Critical Thinking Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=518

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=518

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=518

6.8 Capillary Exchange

Learning Objectives

By the end of this section, you will be able to:

  • Identify the primary mechanisms of capillary exchange
  • Distinguish between capillary hydrostatic pressure and blood colloid osmotic pressure, explaining the contribution of each to net filtration pressure
  • Compare filtration and reabsorption
  • Explain the fate of fluid that is not reabsorbed from the tissues into the vascular capillaries

The primary purpose of the cardiovascular system is to circulate gases, nutrients, wastes, and other substances to and from the cells of the body. Small molecules, such as gases, lipids, and lipid-soluble molecules, can diffuse directly through the membranes of the endothelial cells of the capillary wall. Glucose, amino acids, and ions—including sodium, potassium, calcium, and chloride—use transporters to move through specific channels in the membrane by facilitated diffusion. Glucose, ions, and larger molecules may also leave the blood through intercellular clefts. Larger molecules can pass through the pores of fenestrated capillaries, and even large plasma proteins can pass through the great gaps in the sinusoids. Some large proteins in blood plasma can move into and out of the endothelial cells packaged within vesicles by endocytosis and exocytosis. Water moves by osmosis.

Bulk Flow

The mass movement of fluids into and out of capillary beds requires a transport mechanism far more efficient than mere diffusion. This movement, often referred to as bulk flow, involves two pressure-driven mechanisms: Volumes of fluid move from an area of higher pressure in a capillary bed to an area of lower pressure in the tissues via filtration. In contrast, the movement of fluid from an area of higher pressure in the tissues into an area of lower pressure in the capillaries is reabsorption. Two types of pressure interact to drive each of these movements: hydrostatic pressure and osmotic pressure.

Hydrostatic Pressure

The primary force driving fluid transport between the capillaries and tissues is hydrostatic pressure, which can be defined as the pressure of any fluid enclosed in a space. Blood hydrostatic pressure is the force exerted by the blood confined within blood vessels or heart chambers. Even more specifically, the pressure exerted by blood against the wall of a capillary is called capillary hydrostatic pressure (CHP), and is the same as capillary blood pressure. CHP is the force that drives fluid out of capillaries and into the tissues.

As fluid exits a capillary and moves into tissues, the hydrostatic pressure in the interstitial fluid correspondingly rises. This opposing hydrostatic pressure is called the interstitial fluid hydrostatic pressure (IFHP). Generally, the CHP originating from the arterial pathways is considerably higher than the IFHP, because lymphatic vessels are continually absorbing excess fluid from the tissues. Thus, fluid generally moves out of the capillary and into the interstitial fluid. This process is called filtration.

Osmotic Pressure

The net pressure that drives reabsorption—the movement of fluid from the interstitial fluid back into the capillaries—is called osmotic pressure (sometimes referred to as oncotic pressure). Whereas hydrostatic pressure forces fluid out of the capillary, osmotic pressure draws fluid back in. Osmotic pressure is determined by osmotic concentration gradients, that is, the difference in the solute-to-water concentrations in the blood and tissue fluid. A region higher in solute concentration (and lower in water concentration) draws water across a semipermeable membrane from a region higher in water concentration (and lower in solute concentration).

As we discuss osmotic pressure in blood and tissue fluid, it is important to recognise that the formed elements of blood do not contribute to osmotic concentration gradients. Rather, it is the plasma proteins that play the key role. Solutes also move across the capillary wall according to their concentration gradient, but overall, the concentrations should be similar and not have a significant impact on osmosis. Because of their large size and chemical structure, plasma proteins are not truly solutes, that is, they do not dissolve but are dispersed or suspended in their fluid medium, forming a colloid rather than a solution.

The pressure created by the concentration of colloidal proteins in the blood is called the blood colloidal osmotic pressure (BCOP). Its effect on capillary exchange accounts for the reabsorption of water. The plasma proteins suspended in blood cannot move across the semipermeable capillary cell membrane, and so they remain in the plasma. As a result, blood has a higher colloidal concentration and lower water concentration than tissue fluid. It therefore attracts water. We can also say that the BCOP is higher than the interstitial fluid colloidal osmotic pressure (IFCOP), which is always very low because interstitial fluid contains few proteins. Thus, water is drawn from the tissue fluid back into the capillary, carrying dissolved molecules with it. This difference in colloidal osmotic pressure accounts for reabsorption.

Interaction of Hydrostatic and Osmotic Pressures

The normal unit used to express pressures within the cardiovascular system is millimetres of mercury (mm Hg). When blood leaving an arteriole first enters a capillary bed, the CHP is quite high—about 35 mm Hg. Gradually, this initial CHP declines as the blood moves through the capillary so that by the time the blood has reached the venous end, the CHP has dropped to approximately 18 mm Hg. In comparison, the plasma proteins remain suspended in the blood, so the BCOP remains fairly constant at about 25 mm Hg throughout the length of the capillary and considerably below the osmotic pressure in the interstitial fluid.

The net filtration pressure (NFP) represents the interaction of the hydrostatic and osmotic pressures, driving fluid out of the capillary. It is equal to the difference between the CHP and the BCOP. Since filtration is, by definition, the movement of fluid out of the capillary, when reabsorption is occurring, the NFP is a negative number.

NFP changes at different points in a capillary bed (Figure 6.8.1). Close to the arterial end of the capillary, it is approximately 10 mm Hg, because the CHP of 35 mm Hg minus the BCOP of 25 mm Hg equals 10 mm Hg. Recall that the hydrostatic and osmotic pressures of the interstitial fluid are essentially negligible. Thus, the NFP of 10 mm Hg drives a net movement of fluid out of the capillary at the arterial end. At approximately the middle of the capillary, the CHP is about the same as the BCOP of 25 mm Hg, so the NFP drops to zero. At this point, there is no net change of volume: Fluid moves out of the capillary at the same rate as it moves into the capillary. Near the venous end of the capillary, the CHP has dwindled to about 18 mm Hg due to loss of fluid. Because the BCOP remains steady at 25 mm Hg, water is drawn into the capillary, that is, reabsorption occurs. Another way of expressing this is to say that at the venous end of the capillary, there is an NFP of −7 mm Hg.

 

diagram of Capillary exchange. Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint since CHP = BCOP. Net reabsorption occurs near the venous end since BCOP is greater than CHP.
Figure 6.8.1. Capillary exchange. Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint since CHP = BCOP. Net reabsorption occurs near the venous end since BCOP is greater than CHP.

The Role of Lymphatic Capillaries

Since overall CHP is higher than BCOP, it is inevitable that more net fluid will exit the capillary through filtration at the arterial end than enters through reabsorption at the venous end. Considering all capillaries over the course of a day, this can be quite a substantial amount of fluid: Approximately 24 litres per day are filtered, whereas 20.4 litres are reabsorbed. This excess fluid is picked up by capillaries of the lymphatic system. These extremely thin-walled vessels have copious numbers of valves that ensure unidirectional flow through ever-larger lymphatic vessels that eventually drain into the subclavian veins in the neck. An important function of the lymphatic system is to return the fluid (lymph) to the blood. Lymph may be thought of as recycled blood plasma.

Section Review

Small molecules can cross into and out of capillaries via simple or facilitated diffusion. Some large molecules can cross in vesicles or through clefts, fenestrations, or gaps between cells in capillary walls. However, the bulk flow of capillary and tissue fluid occurs via filtration and reabsorption. Filtration, the movement of fluid out of the capillaries, is driven by the CHP. Reabsorption, the influx of tissue fluid into the capillaries, is driven by the BCOP. Filtration predominates in the arterial end of the capillary; in the middle section, the opposing pressures are virtually identical so there is no net exchange, whereas reabsorption predominates at the venule end of the capillary. The hydrostatic and colloid osmotic pressures in the interstitial fluid are negligible in healthy circumstances.

Review Questions

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=520

Critical Thinking Question

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=520

Click the drop down below to review the terms learned from this chapter.

An interactive or media element has been excluded from this version of the text. You can view it online here:
https://usq.pressbooks.pub/anatomy/?p=520

6.9 Homeostatic Regulation of the Vascular System

Learning Objectives

By the end of this section, you will be able to:

  • Discuss the mechanisms involved in the neural regulation of vascular homeostasis
  • Describe the contribution of a variety of hormones to the renal regulation of blood pressure
  • Identify the effects of exercise on vascular homeostasis
  • Discuss how hypertension, haemorrhage, and circulatory shock affect vascular health

In order to maintain homeostasis in the cardiovascular system and provide adequate blood to the tissues, blood flow must be redirected continually to the tissues as they become more active. In a very real sense, the cardiovascular system engages in resource allocation, because there is not enough blood flow to distribute blood equally to all tissues simultaneously. For example, when an individual is exercising, more blood will be directed to skeletal muscles, the heart, and the lungs. Following a meal, more blood is directed to the digestive system. Only the brain receives a more or less constant supply of blood whether you are active, resting, thinking, or engaged in any other activity.

Table 6.9.1 provides the distribution of systemic blood at rest and during exercise. Although most of the data appears logical, the values for the distribution of blood to the integument may seem surprising. During exercise, the body distributes more blood to the body surface where it can dissipate the excess heat generated by increased activity into the environment.

Table 6.9.1 Systemic blood flow during rest, mild exercise, and maximal exercise in a healthy young individual.

Organ Resting (mL/min) Mild exercise (mL/min) Maximal exercise (mL/min)
Skeletal muscle 1200 4500 12,500
Heart 250 350 750
Brain 750 750 750
Integument 500 1500 1900
Kidney 1100 900 600
Gastrointestinal 1400 1100 600
Others

(i.e., liver, spleen)

600 400 400
Total 5800 9500 17,500

Three homeostatic mechanisms ensure adequate blood flow, blood pressure, distribution, and ultimately perfusion: neural, endocrine, and autoregulatory mechanisms. They are summarised in Figure 6.9.1.

Flowchart Summary of factors maintaining vascular homeostasis. Adequate blood flow, blood pressure, distribution, and perfusion involve autoregulatory, neural, and endocrine mechanisms.
Figure 6.9.1. Summary of factors maintaining vascular homeostasis. Adequate blood flow, blood pressure, distribution, and perfusion involve autoregulatory, neural, and endocrine mechanisms.

Neural Regulation

The nervous system plays a critical role in the regulation of vascular homeostasis. The primary regulatory sites include the cardiovascular centres in the brain that control both cardiac and vascular functions. In addition, more generalised neural responses from the limbic system and the autonomic nervous system are factors.

The Cardiovascular Centres in the Brain

Neurological regulation of blood pressure and flow depends on the cardiovascular centres located in the medulla oblongata. This cluster of neurons responds to changes in blood pressure as well as blood concentrations of oxygen, carbon dioxide, and hydrogen ions. The cardiovascular centre contains three distinct paired components:

  1. The cardioaccelerator centres stimulate cardiac function by regulating heart rate and stroke volume via sympathetic stimulation from the cardiac accelerator nerve.
  2. The cardioinhibitor centre slow cardiac function by decreasing heart rate and stroke volume via parasympathetic stimulation from the vagus nerve.
  3. The vasomotor centre control vessel tone or contraction of the smooth muscle in the tunica media. Changes in diameter affect peripheral resistance, pressure, and flow, which affect cardiac output. The majority of these neurons act via the release of the neurotransmitter noradrenaline from sympathetic neurons.

Although each centre functions independently, they are not anatomically distinct.

There is also a small population of neurons that control vasodilation in the vessels of the brain and skeletal muscles by relaxing the smooth muscle fibres in the vessel tunics. Many of these are cholinergic neurons, that is, they release acetylcholine, which in turn stimulates the vessels’ endothelial cells to release nitric oxide (NO), which causes vasodilation. Others release noradrenaline that binds to β2 receptors. A few neurons release NO directly as a neurotransmitter.

Recall that mild stimulation of the skeletal muscles maintains muscle tone. A similar phenomenon occurs with vascular tone in vessels. As noted earlier, arterioles are normally partially constricted: With maximal stimulation, their radius may be reduced to one-half of the resting state. Full dilation of most arterioles requires that this sympathetic stimulation be suppressed. When it is, an arteriole can expand by as much as 150 percent. Such a significant increase can dramatically affect resistance, pressure, and flow.

Baroreceptor Reflexes

Baroreceptors are specialised stretch receptors located within thin areas of blood vessels and heart chambers that respond to the degree of stretch caused by the presence of blood. They send impulses to the cardiovascular centre to regulate blood pressure. Vascular baroreceptors are found primarily in sinuses (small cavities) within the aorta and carotid arteries: The aortic sinuses are found in the walls of the ascending aorta just superior to the aortic valve, whereas the carotid sinuses are in the base of the internal carotid arteries. There are also low-pressure baroreceptors located in the walls of the venae cavae and right atrium.

When blood pressure increases, the baroreceptors are stretched more tightly and initiate action potentials at a higher rate. At lower blood pressures, the degree of stretch is lower and the rate of firing is slower. When the cardiovascular centre in the medulla oblongata receives this input, it triggers a reflex that maintains homeostasis (Figure 6.9.2).

When blood pressure rises too high, the baroreceptors fire at a higher rate and trigger parasympathetic stimulation of the heart. As a result, cardiac output falls. Sympathetic stimulation of the peripheral arterioles will also decrease, resulting in vasodilation. Combined, these activities cause blood p