Unit I: Functional Organization and Internal Environment

Organization and Scope of Physiology

Physiology is the science that seeks to explain the physical and chemical mechanisms responsible for the origin, development, and progression of life. It covers a vast range of life forms and their functional characteristics, leading to subdivisions such as viral physiology, bacterial physiology, cellular physiology, plant physiology, invertebrate physiology, vertebrate physiology, mammalian physiology, and human physiology. Human physiology specifically aims to explain the characteristics and mechanisms of the human body that make it a living being. Living beings depend on automatic control systems: hunger drives food seeking, fear drives refuge, sensations of cold drive warmth seeking, and social and reproductive drives promote fellowship and reproduction. These attributes enable life to endure under varying conditions. Human physiology connects basic sciences with medicine and integrates the functions of cells, tissues, and organs into the functioning of the living human being. This integration requires communication and coordination by a broad array of control systems that operate from genes (which program molecular synthesis) to complex nervous and hormonal systems coordinating functions across cells, tissues, and organs. Thus, the coordinated function of the human body is more than the sum of its parts, and life in health and disease relies on complete system function. While the book emphasizes normal human physiology, it also discusses pathophysiology—the study of deranged body function and the basis for clinical medicine.

Cells as the living units of the body

The basic living unit of the body is the cell. Each tissue or organ is an aggregate of many cells held together by intercellular supporting structures. Each cell type is specialized for a particular function. For example, red blood cells (RBCs), numbering about 2.5\times 10^{13} per person, transport oxygen from the lungs to tissues. Although RBCs are the most abundant single cell type, trillions of other cells perform different functions. The total number of human cells is about 3.5\times 10^{13} to 4.0\times 10^{13} (
approximately 35–40 trillion).

Although cells differ markedly, they share fundamental similarities. Oxygen reacts with carbohydrate, fat, and protein to release energy required by all cells. The general chemical mechanisms converting nutrients to energy are essentially the same in all cells, and all cells release products of their chemical reactions into surrounding fluids. Almost all cells can reproduce, generating new cells of their own type. When cells of a type are destroyed, remaining cells of that type can regenerate new cells until the supply is replenished.

In addition to human cells, microorganisms inhabit the body in vast numbers, living on the skin, in the mouth, gut, and nose. The gastrointestinal tract normally contains a complex and dynamic population of 4\times 10^{2} to 10^{3} species of microorganisms that outnumber human cells. These microbial communities, or microbiota, can cause disease but most often live in harmony with the host and provide vital functions essential for survival. The gut microbiota is widely recognized for aiding digestion, but new roles in nutrition, immunity, and other functions are being studied as a major area of biomedical research.

Extracellular Fluid—The “Internal Environment”

About 50\% to 70\% of the adult body is fluid, primarily a water solution of ions and other substances. Most of this fluid is inside cells (intracellular fluid, ICF). About one-third is outside cells (extracellular fluid, ECF), which is in constant motion and transported rapidly in circulating blood. ECF is mixed between blood and tissue fluids by diffusion across capillary walls. In the ECF are the ions and nutrients needed by cells. All cells live in essentially the same environment—the ECF—so the ECF is also called the internal environment or milieu intérieur (a term introduced by Claude Bernard). Cells remain viable and functional as long as appropriate concentrations of oxygen, glucose, ions, amino acids, fatty substances, and other constituents are available in the internal environment.

Differences between Extracellular and Intracellular Fluids

The extracellular fluid contains large amounts of sodium, chloride, and bicarbonate ions, and also nutrients such as oxygen, glucose, fatty acids, and amino acids, plus carbon dioxide and other waste products transported from cells to kidneys for excretion. In contrast, the intracellular fluid contains high levels of potassium, magnesium, and phosphate ions, and relatively lower concentrations of sodium and chloride. Special membrane-transport mechanisms maintain these ion concentration differences; these transport processes are discussed in Chapter 4.

Homeostasis—Maintenance of a Near-Constant Internal Environment

In 1929, Walter Cannon coined the term homeostasis to describe the maintenance of nearly constant internal conditions. Different organs and tissues contribute to homeostasis by performing functions that replenish oxygen, maintain ion concentrations, provide nutrients, and eliminate waste. The internal environment is regulated within a range rather than at fixed values. For some constituents, the range is extremely narrow (e.g., hydrogen ion concentration varies normaly by less than 5\times 10^{-9}\text{ mol/L}). Normal sodium concentration in blood varies only a few millimoles per liter, despite wide changes in intake, illustrating the powerful control systems that maintain cellular and organ function under varying environmental challenges.

The body’s homeostatic mechanisms involve integrated actions of cells, tissues, and organs coupled with nervous, hormonal, and local control systems. When disease occurs, homeostatic mechanisms continue to operate and may compensate, sometimes masking the primary disease. Pathophysiology explains how physiological processes are altered by disease or injury. This chapter outlines the body’s functional systems and the basic theory of control systems that allow these systems to operate in concert.

Extracellular Fluid Transport and Mixing System—The Blood Circulatory System

ECF transport occurs in two stages. First, blood moves through the vasculature; second, fluid exchanges between blood plasma and interstitial fluid across capillary walls. The entire blood volume traverses the circulation about once per minute at rest and up to six times per minute during high activity. As blood passes through capillaries, fluid and dissolved constituents diffuse between plasma and interstitial fluid. Capillary walls are permeable to most plasma constituents; plasma proteins are too large to pass readily, so large amounts of fluid and solutes diffuse back and forth between plasma and tissue spaces. Capillary pores and the kinetic motion of molecules ensure diffusion; most cells are within about 50\,\mu\text{m} of a capillary, enabling rapid diffusion of substances.

Origins of Nutrients in the Extracellular Fluid

• Respiratory system: As blood passes through the lungs, it picks up oxygen through the alveolar membrane, which is extremely thin (about 0.4-2.0\,\mu\text{m}). Oxygen diffuses rapidly into the blood. The alveolar membrane’s thinness and the high diffusion rate facilitate oxygen loading.

• Gastrointestinal tract: Blood flow through the GI tract brings absorbed nutrients (carbohydrates, fatty acids, amino acids) into the extracellular fluid of the blood.

• Liver and other metabolic organs: The liver alters the chemical composition of absorbed substances to more usable forms; other tissues (fat, GI mucosa, kidneys, endocrine glands) modify or store absorbed substances as needed. The liver detoxifies ingested drugs and chemicals by secreting wastes into bile for excretion.

Removal of Metabolic End Products

• Lungs remove carbon dioxide (CO₂) from the blood by exhalation. CO₂ is the most abundant metabolic waste product.

• Kidneys remove other waste products (e.g., urea, uric acid) and excess ions and water by filtration through glomerular capillaries and selective reabsorption in tubules; wastes exit in urine.

• GI tract eliminates undigested material and some metabolic waste in feces.

• Liver detoxifies or eliminates ingested drugs and chemicals, secreting many wastes into bile for fecal elimination.

Regulation of Body Functions

• Nervous System: Composed of sensory input, central nervous system (CNS; brain and spinal cord), and motor output. Sensory receptors detect the body and environment; the CNS stores information, processes it, and generates responses; the motor output executes actions. The autonomic nervous system operates subconsciously to regulate internal organs (heart rate, GI movements, gland secretion).

• Hormone Systems: Endocrine glands secrete hormones into the extracellular fluid; hormones regulate cellular function in distant organs. Examples include:

  • Thyroid hormone increases the rates of most chemical reactions in cells.

  • Insulin controls glucose metabolism.

  • Adrenocortical hormones regulate sodium and potassium balance and protein metabolism.

  • Parathyroid hormone controls bone calcium and phosphate.
    The nervous and hormonal systems coordinate to regulate most organ systems.

Protection of the Body

• Immune System: White blood cells, thymus, lymph nodes, and lymph vessels protect against pathogens (bacteria, viruses, parasites, fungi). The immune system distinguishes self from invaders and eliminates threats via phagocytosis, sensitized lymphocytes, or antibodies.

• Integumentary System: Skin and appendages (hair, nails, glands) protect internal tissues from the external environment, regulate temperature, participate in waste excretion, and provide sensory interfaces. The skin accounts for roughly 12\%\text{-}15\% of body weight.

Reproduction

Reproduction supports the continuity of life and, in a broad sense, contributes to homeostasis by maintaining the population of living beings. Reproductive processes demonstrate how various body structures support lifelong automaticity and species propagation.

Controls and Feedback Systems of the Body

The human body houses thousands of control systems, including genetic control in all cells (discussed in Chapter 3) and organ-wide controls. For instance, the respiratory system, coordinated with the nervous system, regulates extracellular fluid CO₂ concentration; the liver and pancreas regulate glucose; the kidneys regulate hydrogen, sodium, potassium, phosphate, and other ions.

Examples of Control Mechanisms

• Regulation of Oxygen and Carbon Dioxide in the Extracellular Fluid: Oxygen binding by hemoglobin in red blood cells helps maintain tissue oxygen concentration. Hemoglobin binds O₂ in the lungs and releases it to tissues if tissue O₂ is low; if tissue O₂ is adequate, O₂ is not released excessively. This is the oxygen-buffering function of hemoglobin. CO₂ regulation is achieved by respiration: elevated CO₂ stimulates respiration to remove CO₂ via exhalation, restoring normal CO₂ levels.

• Regulation of Arterial Blood Pressure: Baroreceptors in the carotid sinus and aortic arch sense arterial stretch and transmit signals to the brain’s medulla. The vasomotor center modulates sympathetic outflow to the heart and vessels. When arterial pressure rises, baroreceptors reduce sympathetic activity, causing vasodilation and reduced cardiac pumping, lowering blood pressure. When pressure falls, baroreceptors increase sympathetic activity, causing vasoconstriction and increased cardiac output, raising pressure toward normal. This negative feedback maintains arterial pressure within a normal range.

• The gain of a control system determines how effectively it maintains constant conditions. Gain is defined as
  \text{Gain} = \frac{\text{Correction}}{\text{Error}}.
  Example: If a large blood volume transfusion raises arterial pressure from 100 mmHg to 175 mmHg (a +75 mmHg disturbance), and the baroreceptor system returns it toward normal by −50 mmHg, leaving an error of +25 mmHg, then the gain is
  \text{Gain} = \frac{-50}{+25} = -2.
  This means the distance from the normal value is reduced by a factor of 2, so the remaining error is one-half of the initial deviation. Note that other systems have even higher gains (e.g., internal temperature regulation can have a gain around −33 under moderate cold exposure).

• Positive Feedback: In some cases, positive feedback can be useful but is risky because it can produce instability and death if uncontrolled. An example is blood clotting: a clotting cascade accelerates itself to seal a vessel. Another example is childbirth: cervical stretch triggers stronger uterine contractions, which further stretch the cervix, propelling birth. Nerve signal generation can also involve positive feedback via the opening of voltage-gated channels that cause action potentials, though typically positive feedback operates within the broader context of negative feedback control networks.

• Feed-Forward and Adaptive Control: The nervous system uses feed-forward control for rapid movements where reflex signals alone would be too slow. If movement is not performed correctly, the brain adjusts feed-forward signals for subsequent movements (adaptive control). This acts as a delayed negative feedback mechanism.

Physiological Variability

Some physiological variables are tightly regulated (e.g., plasma potassium, calcium, hydrogen ion concentrations), while others vary widely (e.g., body weight, adiposity). Daily activities, posture, diet, age, sex, environment, and genetics influence many variables such as blood pressure, metabolic rate, nervous system activity, and hormones. For simplicity, normal physiology is often described using an average male of about 70\,\text{kg}, though current averages exceed this value in many populations (e.g., many males exceed 70 kg; females often exceed 60 kg). There are sex-, age-, ethnic-, and racial-related differences in physiology that impact normal function and disease pathophysiology. For example, in lean young males, total body water is about 60\% of body weight, but this fraction declines with aging as muscle mass decreases and fat mass increases. Aging can also affect organ function and control systems.

Summary — Automaticity of the Body

The chapter outlines the body as a social order of about 3.5\times 10^{13} to 4.0\times 10^{13} cells organized into functional structures (organs). Each structure contributes to maintaining homeostasis in the extracellular fluid (the internal environment). When normal conditions are maintained, cells live and function; each cell benefits from homeostasis and, in turn, contributes to maintaining it. The reciprocal interplay ensures continuous automaticity of life until one or more functional systems fail, leading to sickness or death.

Notable Constituents and Values (Table 1-1 excerpt)

Key Concepts to Remember

• Physiology explains life-sustaining mechanisms and their integration across cells, tissues, and organs.

• The internal environment (ECF) acts as the milieu intérieur that must be maintained within narrow limits through complex control systems.

• Homeostasis is achieved via negative feedback with variable gains; disruption can occur but is often compensated by other systems; excessive positive feedback can be dangerous but can be advantageous in controlled contexts (e.g., clotting, childbirth).

• The body’s control systems are diverse, including nervous, hormonal, and local feedback mechanisms, with variability arising from age, sex, race, and lifestyle.

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