Porth's Essentials of Pathophysiology, 4e

207

Stress and Adaptation

C h a p t e r 9

rather the local fluid environment that surrounds each cell. Claude Bernard, a 19th-century physiologist, was the first to clearly describe the central importance of a stable internal environment, which he termed the milieu intérieur . 1 Bernard recognized that body fluids surround- ing cells and various organ systems provide a means for exchange between the external and internal environments. It is from this internal environment that body cells receive their nourishment, and it is into this fluid that they secrete their wastes. Even contents of the gastrointestinal tract and lungs do not become part of the internal environment until they have been absorbed into the extracellular fluid. A multicellular organism is able to survive only as long as the composition of the internal environment is compat- ible with the survival needs of the individual cells. For example, even a small change in the pH of body fluids can disrupt metabolic processes of individual cells. The concept of a stable internal environment was supported by Walter B. Cannon, who proposed that this kind of stability, which he called homeostasis, was achieved through a system of carefully coordinated physiologic processes that oppose change. 2 Cannon pro- posed that these processes were largely automatic and emphasized that homeostasis involves resistance to both internal and external disturbances (Box 9-1). In his book The Wisdom of the Body, published in 1939, Cannon presented four tentative propositions to describe general features of homeostasis. 2 Based upon this set of propositions, Cannon emphasized that when a factor is known to shift homeostasis in one direction, it is reasonable to expect mechanisms that have the opposite effect exist. For example, in the homeostatic regulation of 1. Constancy in an open system, such as our bodies represent, requires mechanisms that act to maintain this constancy. Cannon based this proposition on insights into the ways by which steady states such as glucose concentrations, body temperature, and acid- base balance were regulated. 2. Steady-state conditions require that any tendency toward change automatically meets with factors that resist change. An increase in blood sugar results in thirst as the body attempts to dilute the concentration of sugar in the extracellular fluid. 3. The regulating system that determines the homeostatic state consists of a number of cooperating mechanisms acting simultaneously or successively. Blood sugar is regulated by insulin, glucagon, and other hormones that control its release from the liver or its uptake by the tissues. 4. Homeostasis does not occur by chance, but is the result of organized self-government. From THE WISDOM OF THE BODY, Revised Edition by Walter B. Cannon, M. D. Copyright 1932, 1939 by Walter B. Cannon, renewed © 1960, 1967, 1968 by Cornelia J. Cannon. Used by permission of W. W. Norton & Company, Inc. BOX 9-1 Constancy of the Internal Environment

blood sugar, mechanisms that both raise and lower blood glucose play significant roles. As long as the respond- ing mechanism to the initiating disturbance can recover homeostasis, body integrity and normality are retained. Control Systems The ability of the body to function and maintain homeostasis under conditions of change in the internal and external environment depends upon thousands of physiologic control systems that regulate body function. A homeostatic control system consists of a collection of interconnected components that function to keep a physical or chemical parameter of the body relatively constant. The body’s control systems regulate cellular function, control life processes, and integrate functions of different organ systems. Neuroendocrine control systems that influence behav- ior have recently been studied extensively. Biochemical messengers in our brain control nerve activity, informa- tion flow, and, ultimately, behavior. 3–5 These control systems mediate physical, emotional, and behavioral reactions to stressors. When taken together, these reac- tions are known as the stress response . Most control systems in the body operate by nega- tive feedback mechanisms, which function in a manner similar to the thermostat in a heating system. When the monitored function or value decreases below the set point of the system, feedback mechanisms cause the function or value to increase, and when the function or value is increased above the set point, the feedback mechanism causes it to decrease (Fig. 9-1). For example, in the negative feedback mechanism that controls blood glucose levels, an increase in blood glucose stimulates an increase in insulin, which enhances removal of glu- cose from the blood. When glucose has been taken up by cells and blood glucose levels fall, insulin secretion is inhibited and glucagon and other counter-regulatory mechanisms stimulate release of glucose from the liver, which causes blood glucose levels to return to normal. Most physiologic control systems function under neg- ative rather than positive feedback mechanisms because

Decreased insulin release and addition of glucose to the blood

Glucose sensor in beta cells

Decrease in blood glucose

Increase in blood glucose

Increased insulin release and removal of glucose from the blood

Glucose sensor in beta cells

FIGURE 9-1. Illustration of negative feedback control mechanisms using blood glucose as an example.