Biomedicine and Health: Physiology

Introduction

Physiology is the study of the relationship between an organism's form and its function. The best known branch of physiology deals with the mechanical function of limbs and joints. However, the study of physiology also includes the function of organs and tissues, as well as the biochemical systems within and between cells. Physiology is broadly divided into two main branches: plant and animal. Animal physiology developed from the study of human physiology, which was the focus of much early inquiry in the field.

While most ancient societies knew of the existence of the body's organs, they usually lacked a correct or complete understanding of how they worked. Many of these misconceptions can be linked to reliance on philosophy rather than observation. This led physicians to speculate on what an organ should do, rather than determine empirically what its actual function was. Major advances in physiology usually followed advances in anatomy; with a better understanding of a structure's form, its function could be better determined.

Historical Background and Scientific Foundations

The studies of anatomy and physiology have always been linked. Today the discovery of a new structure, organ, cell type, or biochemical quickly leads to speculation on its use. In much of the ancient world, however, study of the human body was limited by philosophical preconceptions and by social and religious restrictions. Many ancient cultures, including the Greeks and Romans, believed that the universe was made up of four elements, and that the body was ruled by four humors, or bodily fluids: yellow bile, blood, phlegm, and black bile. If the four humors were in balance, the body would be healthy. However, if the body had too much of one humor, it would disrupt normal function and cause illness.

Humoral imbalance was also associated with certain personality traits. A patient with too much blood was known as sanguine and would be treated by bleeding. Similarly, a patient with excess yellow bile was called choleric; one with excess phlegm was phlegmatic; and one with excess black bile was melancholy. The humors were deemed so influential because each was thought to give off vapors that rose directly to the brain, altering both health and mental state. This theory of disease persisted until the eighteenth and nineteenth centuries, with bloodletting a popular “cure” for disease.

Other common misconceptions plagued the ancient study of physiology. Many of these errors can be traced to the almost universal prohibition on autopsies. Physicians could not undertake systematic investigations, but had to draw conclusions from animal dissection, treatment and observation of wounds, and from the tenets of various philosophies.

One of the most contentious early questions was the location of the seat of consciousness. Ancient Egyptians believed that it rested in the heart. Interestingly, the Edwin Smith papyrus, a medical text dating from the seventeenth century BC, show that its author understood that the brain controlled the body, but did not connect this idea with the sentient mind. Ancient Greeks argued over this issue as well. Greek physiologist Alcmaeon (fl. sixth c. BC) believed that the brain could perceive the senses, but not think. He did, however, understand that brain injury could cause paralysis or other incapacitation, thereby discovering one of its most important functions.

The Greek anatomist Erasistratus (fl. 250 BC) is considered be one of the first physiologists. More than his contemporaries, he was interested in determining the function of organs, as well as improving understanding of their anatomy. He realized that the chest creates negative pressure to draw in breath, but did not distinguish between the respiratory and circulatory systems, believing both to be filled with air. The air was supposed to push outward into the smallest capillaries within the muscle, allowing them to move by its pressure. He argued that digestion was achieved by the heat and pressure of the stomach, having no knowledge of the enzymes and acids that actually accomplish this.

Erasistratus had a good understanding of renal function, too, knowing that the kidneys produced urine. He was also one of the first to describe the heart as a pump for blood. Erasistratus ignored humoral theory, relying instead on what he observed. His successor Galen of Pergamum (AD 129–c.216), a Greek physician living in the Roman Empire, vigorously disagreed with this omission and went to great lengths to disprove him. Galen was well known for the systematic way in which he undertook his experiments. His most frequent method for experimentation was simply to sever or tie off the structure he was interested in and see how normal processes were disrupted. He famously used this method to prove that urine was produced by the kidneys and flowed through the ureters to the bladder. Galen was also able to show that blood vessels contained blood, not air as Erasistratus asserted. Galen experimented extensively to learn the function of the spinal cord and nerves, showing that they regulate both breathing and movement. It should be noted that Galen performed all of his experiments on animals. Though he learned a great deal, he made some significant errors that were passed on in his teachings, not to be questioned for a thousand years.

During the Renaissance, a new interest in anatomy drove further advancement in physiology. Among the famous physicians and dissectors of the day, Leonardo da Vinci (1452–1519) stands apart. An artist and natural polymath (knowledgeable about many things), he was not trained as a physician, but approached problems from a different point of view. He was also resolutely opposed to the vivisection of animals, a powerful tool for many physiologists. Da Vinci acutely observed his subjects and used the sciences of geometry and physics to determine the way they worked. He considered his study of physiology to be part of his study of physics as a whole. To satisfy his vast curiosity, da Vinci built models and experimented with them. One of the most interesting was his model of the eye, through which he discovered the primitive type of camera known as the camera obscura. He even built a model of the aorta and heart valves to study their function, laboriously casting the vessel in wax, plaster, and finally glass to get a working replica.

Modern Cultural Connections

Modern physiology began in the eighteenth century as the elements necessary for a scientific understanding subject fell into place; a greater understanding of the scientific method and the development of complementary sciences aided its progression. An early milestone occurred when Dutch physician Hermann Boerhaave (1668–1738) unified two competing theories to assert that all physical processes were the result of chemical reactions. Scientists began to conduct more advanced experiments than Galen's basic surgical severings, among them Luigi Galvani's (1737–1798) 1771 discovery that frog leg muscles responded to electrical stimulation.

The dominant figure of nineteenth-century physiology was French physiologist Claude Bernard (1813–1878), the first to popularize the concept of homeostasis, the complex system of processes that sustains life. Through homeostasis, animals regulate body temperature, blood sugar, fluid levels, sleep, and other factors. They also can respond to infection or other threats. Scottish anatomist Charles Bell (1774–1842) undertook more advanced inquiry into brain and nerve function, publishing New Idea of Anatomy of the Brain in 1811 and The Nervous System of the Human Body in 1830.

One of the most significant trends in physiology in the twentieth century has been its gradual dissolution as an independent science. Though there are still scientists who study only physiology, the field was inextricably incorporated into other life sciences as scientists recognized that function is as important as anatomical form; knowledge of one is incomplete without the other.

Technological advances have allowed the study of ever-smaller structures. One of the most interesting areas of development has been the immune system, which coordinates organs, cells, and biochemical reactions to fight infection. Discoveries have included the functions of the spleen, thymus, and bone marrow, all of which process immune cells in different ways. The myriad ways that immune cells act on pathogens is another vast area for scientists to examine. Even the effect of special biochemicals on pathogens can now be studied.

The discovery and understanding of hormones is another physiology research front. Hormones are chemicals that cause cells and tissues to perform a specific action. For example, the hormone insulin causes cells to process glucose in the blood and store it as energy. Different glands, organs, and tissues produce hormones to signal other parts of the body. Even plants produce hormones for the same reasons. Scientists study the

IN CONTEXT: COMPARATIVE PHYSIOLOGY

Comparative physiology examines the physiological adaptations among organisms to diverse and changing environments. Comparative physiology, like comparative anatomy, attempts to uncover evolutionary relationships between organisms or groups of organisms. It seeks to explain the evolution of biological functions by likening physiological characteristics between and among organisms (usually animals). In conjunction with other comparative disciplines, it enables us to trace the evolution of organisms and their unique structures and to view ourselves in a broader light. By comparing the physiology among living things, scientists can gain insights into how groups of organisms have solved the adaptive problems in their natural environments over time.

Comparative physiology compares basic physiological processes like cellular respiration and gas exchange, thermoregulation, circulation, water and ion balance, nerve impulse transmission, and muscle contraction. The form of an organ, or other biological structure, is tied to its function in much the same way a tool is linked to its purpose. For example, the function of an enzyme (a protein molecule that speeds up a chemical reaction) depends heavily upon its three-dimensional shape. If the 3-D conformation of the enzyme molecule is altered (by heat or acid), the function of the enzyme will also be altered. If the shape of an enzyme is changed considerably, its biological activity will be lost.

A major theme dominating the topic of comparative physiology is the concept of homeostasis. The term is derived from two Greek words (homeo, meaning “same,” and stasis, meaning “standing still”) and literally means staying the same. Homeostasis thus refers to the ability of animals to maintain an internal environment that compensates for changes occurring in the external environment. Only the surface cells of the human body, for example, and the lining of the gastrointestinal and respiratory tracts come into direct contact with the outside surroundings (like the atmosphere). The vast majority of cells of the body are enclosed by neighboring cells and the extracellular fluid (fluid found outside of cells) that bathes them. So the body in essence exists in an internal environment that is protected from the wider range of conditions that are found in the external surroundings. Therefore, to maintain homeostasis, the body must have a system for monitoring and adjusting its internal environment when the external environment changes. Comparative physiologists observe physiological similarities and differences in adaptations between organisms in solving identical problems concerning homeostasis.

Some of the problems that animals face in maintaining physiological homeostasis involve basic life processes. Energy acquisition from food (digestion) and its expenditure, the maintenance of body temperature and metabolic rate, the use of oxygen or the ability to live in its absence, and the way body size affects metabolism and heat loss are examples of problems that require homeostatic systems. Comparative physiologists might, for example, compare the efficiency of the relative oxygen capturing abilities of mammalian hemoglobin (in red blood cells) and insect hemolymph. Both groups of animals must maintain homeostasis and regulate the amount of oxygen reaching their tissues, yet each group solves the problem differently.

All reactions of metabolism, however, are part of the overall goal of the organism to maintain its internal orderliness, whether that organism is a single-celled protozoan or a human. Organisms maintain this orderliness by removing energy from nutrients or sunlight and returning to their environment an equal amount of energy in a less useful form, mostly heat. This heat becomes dissipated throughout the rest of the organism's environment.

According to the first law of thermodynamics, in any physical or chemical change, the total amount of energy in the universe remains constant, that is, energy cannot be created or destroyed. Thus, when the energy stored in nutrient molecules is released and captured (often in the form of ATP) some energy is lost as heat. However, the total amount of energy is unchanged.

The second law of thermodynamics states that physical and chemical changes proceed in such a direction that useful energy undergoes irreversible degradation into a randomized form—entropy. The dissipation of energy during metabolism represents an increase in the randomness, or disorder, of the organism's environment. Because this disorder is irreversible, it provides the driving force and direction to all metabolic enzymatic reactions.

Even in the simplest cells, such as bacteria, there are at least a thousand such reactions. Regardless of the number, all cellular reactions can be classified as one of two types of metabolism: anabolism (building reactions) and catabolism (break down reactions).

Comparative physiology makes specific measurements to obtain biologically relevant information from which to make comparisons. The kinds of processes that physiologists measure from anatomical structures to gain insight into their function include: rates (how fast something occurs), changes in rates, gradients (increasing or decreasing concentrations of substances), pressures, rate of flow (of a fluid such as air or blood), diffusion (the act of a substance moving from an area of high concentration to one of low concentration), tension (material stress caused by a pull), elasticity, electrical current, and voltage. For example, a comparative physiologist might measure the rate of diffusion of sugar molecules across intestinal cell membranes, or the pressure exerted on the walls of blood vessels that are close to the heart. In each case, the comparative physiologist is trying to gain information that will help explain how a particular structure functions and how it compares with similar structures in other organisms trying to solve the same homeostatic problem. The conclusions derived, then, tell us all about our evolutionary history.

physiology of hormone production, detection by other cells, and the changes they cause within the organism. Other bodily systems are just as interesting to physiologists as cellular function. Respiratory physiology is the study of the function of the respiratory system, and similar sciences exist for the circulatory, musculoskeletal, gastrointestinal, renal, and reproductive systems.

IN CONTEXT: METABOLIC ENGINEERING

All living bodies, including plants and animals, are made of cells. Each cell in a body is programmed to carry out a number of chemical reactions. Metabolism comprises all of these reactions. There are two different types of metabolic processes. Anabolic reactions take place to form a compound (chemical molecule), while catabolic reactions are responsible for the breakdown of compounds. Enzymes are substances that catalyze (or speed up) metabolic reactions.

Metabolic reactions typically follow set sequences, called metabolic pathways. Scientists study these pathways to understand the functioning of cells, tissues, organs, and eventually the complete body system. Enzymes catalyze each step in a cellular pathway, so determining the specific enzymes participating in a reaction is important. Metabolic engineering involves discovering and analyzing such metabolic pathways.

Metabolic engineering can be used to improve food production for such products as cheese, wine, and beer. It is helpful in finding cures for diseases, for the mass production of antibiotics, to improve agricultural practices, and to enable effective means of energy production. Metabolic engineering can also assist in the development of eco-friendly ways for cleaning up the environment.

One of the newest branches of physiology is the study of adipose tissue. More commonly known as fat tissue, until recently it was considered only a simple way to store energy. As the incidence of obesity grows, however, scientists are interested in learning how the body stores energy as fat, how it decides when to use that energy, and how it goes about putting it to use. Adipose tissue signals to the body via biochemical messengers, many of which have only recently been discovered. Understanding how these messages are communicated may lead to a way to change or disrupt them.

Some branches of modern physiology are not easily contained within the study of one bodily system. This is because organ systems do not act in isolation, but work together to create homeostasis. Scientists can study the specific interactions between these systems, such as the communications between the neurological and endocrine systems. Other new fields within physiology include cell, cell membrane, and exercise physiology.

As more discoveries about humans, plants, and animals are made, the importance of physiology increases. No longer is it enough to understand the appearance of an organism, organ, or cell; understanding its function, often in the minutest detail, is critical to biological knowledge. It's also important to note that even though new frontiers of physiology are possible on a molecular scale, there is still interest in the nuances of the larger body systems.

See Also Biomedicine and Health: The Brain and Nervous System; Biomedicine and Health: Dissection and Vivisection; Biomedicine and Health: Embryology; Biomedicine and Health: Galen and Humoral Theory; Biomedicine and Health: Human Gross Anatomy; Biomedicine and Health: Hormonal Regulation of the Body; Biomedicine and Health: Immunity and the Immune System.

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Web Sites

Journal of Neurosurgery. “Herophilus, Erasistratus, Aretaeus, and Galen: Ancient Roots of the Bell-Magendie Law.” http://thejns.org/doi/pdf/10.3171/FOC-07/07/E12 (accessed February 4, 2008).

Levity.com. The Alchemy Web Site. “Medicine in Old Egypt.” http://www.levity.com/alchemy/islam22.html (accessed February 4, 2008).

PubMed Central. U.S. National Institutes of Health. “Alcmaeon of Croton: His Life, Work, and Fragments.” http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2183733 (accessed February 4, 2008).

PubMed Central. “Three Early Masters of Experimental Medicine: Erasistratus, Galen, and Leonardo da Vinci.” http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1870463 (accessed February 4, 2008).

University of Colorado at Boulder. “Physiology.” http://autocww.colorado.edu/̃toldy2/E64ContentFiles/AnatomyAndPhysiology/Physiology.html (accessed February 4, 2008).

University of Michigan. Center for the Study of Complex Systems. “Claude Bernard: 1813–1878.” http://www.cscs.umich.edu/̃crshalizi/notabene/claudebernard.html (accessed February 4, 2008).

Washington State University. Medieval Themes and Topics: Some Interesting and Essential Stuff. “The Four Humors.” http://www.wsu.edu:8080/̃hanly/chaucer/coursematerials/humours.html (accessed February 4, 2008).

Kenneth T. LaPensee