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 centers 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.

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 center, 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.

Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis (“steady state”). These changes might be in the level of glucose or calcium in blood or in external temperatures. Homeostasis means to maintain dynamic equilibrium in the body. It is dynamic because it is constantly adjusting to the changes that the body’s systems encounter. It is equilibrium because body functions are kept within specific ranges. Even an animal that is apparently inactive is maintaining this homeostatic equilibrium.

Homeostatic Process

The goal of homeostasis is the maintenance of equilibrium around a point or value called a set point. While there are normal fluctuations from the set point, the body’s systems will usually attempt to go back to this point. A change in the internal or external environment is called a stimulus and is detected by a receptor; the response of the system is to adjust the deviation parameter toward the set point. For instance, if the body becomes too warm, adjustments are made to cool the animal. If the blood’s glucose rises after a meal, adjustments are made to lower the blood glucose level by getting the nutrient into tissues that need it or to store it for later use.

Control of Homeostasis

When a change occurs in an animal’s environment, an adjustment must be made. The receptor senses the change in the environment, then sends a signal to the control center (in most cases, the brain) which in turn generates a response that is signaled to an effector. The effector is a muscle (that contracts or relaxes) or a gland that secretes. Homeostatsis is maintained by negative feedback loops. Positive feedback loops actually push the organism further out of homeostasis, but may be necessary for life to occur. Homeostasis is controlled by the nervous and endocrine system of mammals.

Negative Feedback Mechanisms

Any homeostatic process that changes the direction of the stimulus is a negative feedback loop. It may either increase or decrease the stimulus, but the stimulus is not allowed to continue as it did before the receptor sensed it. In other words, if a level is too high, the body does something to bring it down, and conversely, if a level is too low, the body does something to make it go up. Hence the term negative feedback. An example is animal maintenance of blood glucose levels. When an animal has eaten, blood glucose levels rise. This is sensed by the nervous system. Specialized cells in the pancreas sense this, and the hormone insulin is released by the endocrine system. Insulin causes blood glucose levels to decrease, as would be expected in a negative feedback system, as illustrated in Figure 33.20. However, if an animal has not eaten and blood glucose levels decrease, this is sensed in another group of cells in the pancreas, and the hormone glucagon is released causing glucose levels to increase. This is still a negative feedback loop, but not in the direction expected by the use of the term “negative.” Another example of an increase as a result of the feedback loop is the control of blood calcium. If calcium levels decrease, specialized cells in the parathyroid gland sense this and release parathyroid hormone (PTH), causing an increased absorption of calcium through the intestines and kidneys and, possibly, the breakdown of bone in order to liberate calcium. The effects of PTH are to raise blood levels of the element. Negative feedback loops are the predominant mechanism used in homeostasis.

Figure 33.20 Blood sugar levels are controlled by a negative feedback loop. (credit: modification of work by Jon Sullivan)

Positive Feedback Loop

A positive feedback loop maintains the direction of the stimulus, possibly accelerating it. Few examples of positive feedback loops exist in animal bodies, but one is found in the cascade of chemical reactions that result in blood clotting, or coagulation. As one clotting factor is activated, it activates the next factor in sequence until a fibrin clot is achieved. The direction is maintained, not changed, so this is positive feedback. Another example of positive feedback is uterine contractions during childbirth, as illustrated in Figure 33.21. The hormone oxytocin, made by the endocrine system, stimulates the contraction of the uterus. This produces pain sensed by the nervous system. Instead of lowering the oxytocin and causing the pain to subside, more oxytocin is produced until the contractions are powerful enough to produce childbirth.

Figure 33.21 The birth of a human infant is the result of positive feedback.

State whether each of the following processes is regulated by a positive feedback loop or a negative feedback loop.

1. A person feels satiated after eating a large meal.
2. The blood has plenty of red blood cells. As a result, erythropoietin, a hormone that stimulates the production of new red blood cells, is no longer released from the kidney.

Set Point

It is possible to adjust a system’s set point. When this happens, the feedback loop works to maintain the new setting. An example of this is blood pressure: over time, the normal or set point for blood pressure can increase as a result of continued increases in blood pressure. The body no longer recognizes the elevation as abnormal and no attempt is made to return to the lower set point. The result is the maintenance of an elevated blood pressure that can have harmful effects on the body. Medication can lower blood pressure and lower the set point in the system to a more healthy level. This is called a process of alteration of the set point in a feedback loop.

Changes can be made in a group of body organ systems in order to maintain a set point in another system. This is called acclimatization. This occurs, for instance, when an animal migrates to a higher altitude than that to which it is accustomed. In order to adjust to the lower oxygen levels at the new altitude, the body increases the number of red blood cells circulating in the blood to ensure adequate oxygen delivery to the tissues. Another example of acclimatization is animals that have seasonal changes in their coats: a heavier coat in the winter ensures adequate heat retention, and a light coat in summer assists in keeping body temperature from rising to harmful levels.

Homeostasis: Thermoregulation

Body temperature affects body activities. Generally, as body temperature rises, enzyme activity rises as well. For every ten degree centigrade rise in temperature, enzyme activity doubles, up to a point. Body proteins, including enzymes, begin to denature and lose their function with high heat (around 50^oC for mammals). Enzyme activity will decrease by half for every ten degree centigrade drop in temperature, to the point of freezing, with a few exceptions. Some fish can withstand freezing solid and return to normal with thawing.

Endotherms and Ectotherms

Animals can be divided into two groups: some maintain a constant body temperature in the face of differing environmental temperatures, while others have a body temperature that is the same as their environment and thus varies with the environment. Animals that rely on external temperatures to set their body temperature are ectotherms. This group has been called cold-blooded, but the term may not apply to an animal in the desert with a very warm body temperature. In contrast to ectotherms, poikilotherms are animals with constantly varying internal temperatures. An animal that maintains a constant body temperature in the face of environmental changes is called a homeotherm. Endotherms are animals that rely on internal sources for maintenance of relatively constant body temperature in varying environmental temperatures. These animals are able to maintain a level of metabolic activity at cooler temperature, which an ectotherm cannot due to differing enzyme levels of activity. It is worth mentioning that some ectotherms and poikilotherms have relatively constant body temperatures due to the constant environmental temperatures in their habitats. These animals are so-called ectothermic homeotherms, like some deep sea fish species.

Heat can be exchanged between an animal and its environment through four mechanisms: radiation, evaporation, convection, and conduction (Figure 33.22). Radiation is the emission of electromagnetic “heat” waves. Heat comes from the sun in this manner and radiates from dry skin the same way. Heat can be removed with liquid from a surface during evaporation. This occurs when a mammal sweats. Convection currents of air remove heat from the surface of dry skin as the air passes over it. Heat will be conducted from one surface to another during direct contact with the surfaces, such as an animal resting on a warm rock.

Figure 33.22 Heat can be exchanged by four mechanisms: (a) radiation, (b) evaporation, (c) convection, or (d) conduction. (credit b: modification of work by “Kullez”/Flickr; credit c: modification of work by Chad Rosenthal; credit d: modification of work by “stacey.d”/Flickr)

Heat Conservation and Dissipation

Animals conserve or dissipate heat in a variety of ways. In certain climates, endothermic animals have some form of insulation, such as fur, fat, feathers, or some combination thereof. Animals with thick fur or feathers create an insulating layer of air between their skin and internal organs. Polar bears and seals live and swim in a subfreezing environment and yet maintain a constant, warm, body temperature. The arctic fox, for example, uses its fluffy tail as extra insulation when it curls up to sleep in cold weather. Mammals have a residual effect from shivering and increased muscle activity: arrector pili muscles cause “goose bumps,” causing small hairs to stand up when the individual is cold; this has the intended effect of increasing body temperature. Mammals use layers of fat to achieve the same end. Loss of significant amounts of body fat will compromise an individual’s ability to conserve heat.

Endotherms use their circulatory systems to help maintain body temperature. Vasodilation brings more blood and heat to the body surface, facilitating radiation and evaporative heat loss, which helps to cool the body. Vasoconstriction reduces blood flow in peripheral blood vessels, forcing blood toward the core and the vital organs found there, and conserving heat. Some animals have adaptations to their circulatory system that enable them to transfer heat from arteries to veins, warming blood returning to the heart. This is called a countercurrent heat exchange; it prevents the cold venous blood from cooling the heart and other internal organs. This adaptation can be shut down in some animals to prevent overheating the internal organs. The countercurrent adaptation is found in many animals, including dolphins, sharks, bony fish, bees, and hummingbirds. In contrast, similar adaptations can help cool endotherms when needed, such as dolphin flukes and elephant ears.

Some ectothermic animals use changes in their behavior to help regulate body temperature. For example, a desert ectothermic animal may simply seek cooler areas during the hottest part of the day in the desert to keep from getting too warm. The same animals may climb onto rocks to capture heat during a cold desert night. Some animals seek water to aid evaporation in cooling them, as seen with reptiles. Other ectotherms use group activity such as the activity of bees to warm a hive to survive winter.

Many animals, especially mammals, use metabolic waste heat as a heat source. When muscles are contracted, most of the energy from the ATP used in muscle actions is wasted energy that translates into heat. Severe cold elicits a shivering reflex that generates heat for the body. Many species also have a type of adipose tissue called brown fat that specializes in generating heat.

Neural Control of Thermoregulation

The nervous system is important to thermoregulation, as illustrated in Figure 33.22. The processes of homeostasis and temperature control are centered in the hypothalamus of the advanced animal brain.

Figure 33.23 The body is able to regulate temperature in response to signals from the nervous system.

When bacteria are destroyed by leukocytes, pyrogens are released into the blood. Pyrogens reset the body’s thermostat to a higher temperature, resulting in fever. How might pyrogens cause the body temperature to rise?

The hypothalamus maintains the set point for body temperature through reflexes that cause vasodilation and sweating when the body is too warm, or vasoconstriction and shivering when the body is too cold. It responds to chemicals from the body. When a bacterium is destroyed by phagocytic leukocytes, chemicals called endogenous pyrogens are released into the blood. These pyrogens circulate to the hypothalamus and reset the thermostat. This allows the body’s temperature to increase in what is commonly called a fever. An increase in body temperature causes iron to be conserved, which reduces a nutrient needed by bacteria. An increase in body heat also increases the activity of the animal’s enzymes and protective cells while inhibiting the enzymes and activity of the invading microorganisms. Finally, heat itself may also kill the pathogen. A fever that was once thought to be a complication of an infection is now understood to be a normal defense mechanism.

Negative Feedback

A negative feedback system has three basic components (imagea). 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 center. The control center 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 center 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.

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 releasing the hormone insulin into the bloodstream. The insulin signals skeletal muscle fibers, 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 sugar 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 (imageb). When the brain’s temperature regulation center 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 center.” 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 center 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 epinephrine (adrenaline), 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 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 labor and delivery are the result of a positive feedback system (image).

The first contractions of labor (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 centers 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.

Introduction

Homeostasis is a term that was first coined by physiologist Walter Cannon in 1926, clarifying the 'milieu intérieur' that fellow physiologist Claude Bernard had spoken of ­­in 1865. 'Homeo,' Latinized from the Greek word 'homio,' means 'similar to,' and when combined with the Greek word 'stasis,' meaning 'standing still' gives us the term that is a cornerstone of physiology. Carl Richter proposed that behavioral responses were also responsible for maintaining homeostasis in addition to the previously proposed internal control system, while James Hardy gave us the concept of a setpoint or desired physiological range of values that homeostasis accomplishes.

The body's many functions, beginning at the cellular level, operate as to not deviate from a narrow range of internal balance, a state known as dynamic equilibrium, despite changes in the external environment. Those changes in the external environment alter the composition of the extracellular fluid surrounding the individual cells of the body, but a narrow range must be maintained to stave off the death of cells, tissues, and organs.

Cellular Level

On the cellular level, homeostasis is observable in the biochemical reactions that take place. Regulation of pH, temperature, oxygen, ion concentrations, and blood glucose concentration is necessary for enzymes to function optimally in the environment of the cell, and the formation of waste products must be kept in control as not to disrupt the internal environment of the cells as well. The cell will remain alive as long as the internal environment is favorable and can be a functioning part of the tissue to which it belongs.

Cells respond to changes in volume by activating the metabolic transport of molecules necessary to return to back to normal volume. In both, the cases of hyperosmolar or hypoosmolar external cellular states, the transfer of molecules must result in volume regulation as not to disturb the contents of the cell from their maximum function. All tissues of the body compose organs that comprise organ systems, which do not operate independently and must work together to achieve homeostasis. Each cell benefits from homeostatic control, and contributes to its maintenance as well, providing continuous automaticity to the body.

Development

Homeostasis would not be possible without setpoints, feedback, and regulation. The human body is composed of thousands of control systems to detect change caused by disruptors and employ effectors to mediate that change. The setpoint is invaluable in the development of the homeostatic control system and is the value that the system designs the output to be. Homeostatic regulation involves both local control (paracrine or autocrine responses) as well as reflex control (involving the nervous and endocrine systems).

Although homeostasis is central to understand internal regulation, allostasis, or maintaining stability through change, is worthy of mention, as it is also necessary for organisms to adapt to their environments. Allostasis considers the normal daily variations that exist in the internal system. As such, a difference between homeostasis and allostasis is that, although the goal of homeostasis is to reduce variability and maintain consistency, allostasis favors variability because the internal environment can adapt to various environmental encounters. Although the two concepts may differ, it is important to note the existence of each and their contribution to physiology.

Organ Systems Involved

Homeostasis is involved in every organ system of the body. In a similar vein, no one organ system of the body acts alone; regulation of body temperature cannot occur without the cooperation of the integumentary system, nervous system, musculoskeletal system, and cardiovascular system at a minimum. Chemosensors in the carotid bodies and aortic body measure arterial PCO2 and PO2, send the information to the brainstem (control center), to tell the effectors (the diaphragm and respiratory muscles) to alter breathing rate and tidal volume to return to balance. Altered reabsorption and secretion of inorganic ions are the result of chemosensors in the adrenal cortex (for potassium concentration), parathyroid gland (for calcium concentration), and kidney and carotid and aortic bodies (for sodium concentration) which help to bring these regulated variables back to the normal range.

Function

In short, the purpose of homeostasis is to maintain the established internal environment without being overcome by external stimuli that exist to disrupt the balance.

Mechanism

A proposed mechanism for homeostasis is represented by a regulatory system in which five critical components must work together in a reflex loop: the sensor, setpoint, error detector, controller, and effector. A regulated (sensed) variable has a sensor within the system to measure the change in its value, an example of which is blood glucose concentration. On the other hand, a controlled (nonregulated) variable whose value becomes altered to maintain the regulated variable in the narrow range, an example of which would be the roles of gluconeogenesis, glycolysis, and glycogenolysis in blood glucose concentration.

A controller's role is to interpret an error signal and determine the outputs of the effectors so that homeostasis is once again attainable. Thus, in the body, controllers are usually the endocrine cells and sensory neurons in the autonomic nervous system, medulla, and hypothalamus. The effectors produce the response that forces the variable back to the normal range. Receptors monitor a change in the environment, a stimulus, which is transmitted to the integration center (for example, the brain in the case of the central nervous system, or a gland in the endocrine system). If the determination is that the stimulus differs from the setpoint, it generates a response and sent to the effector organ. A system that utilizes these components is known as a negative feedback system, although the opposite is not true: negative feedback does not mean the system is homeostatic in function.

Negative feedback refers to a response that is opposite to the stress: the compensatory action will increase values if they become too low or decrease if they become too high. Anticipatory (feedforward) controls exist to minimize the disturbance of a predicted change in the environment when anticipating a change. In this type of feedback, controls do not activate when there is a perturbance to the system, but rather before it occurs, as to prepare for the effects that disturbance would have. Lastly, although not as frequently occurring as negative feedback loops, positive feedback, in which the stimulus is reinforced rather than decreased, is necessary in some cases as well. One of the most well-known examples of positive feedback occurs during labor when the release of oxytocin stimulates uterine contractions forcing the baby's head to push against the cervix, which stimulates the release of more oxytocin which cycles until delivery is complete.

Related Testing

A patient's vital signs (blood pressure, core body temperature, heart rate, respiratory rate, and oxygen saturation) are the first measurement indicating if there is a homeostatic imbalance. A basic metabolic panel is a quick blood test to show electrolyte disturbances, if present, to guide diagnosis and treatment. Measurement of the inorganic ions, kidney function (BUN/Creatinine ratio), and glucose enable us to fix those abnormalities as well as the underlying cause.

Pathophysiology

Homeostasis underlies many, if not all, disease processes. Diseases such as diabetes, hypertension, and atherosclerosis, involve both the disturbance of homeostasis, as well as the presence of inflammation.The loss of receptor sensitivity with age increases the risk of illness as an unstable internal environment is allowed to exist. Older individuals are more susceptible to temperature dysregulation and have impaired thirst mechanisms, which contribute to the elevated risk of dehydration seen in this population. Acid-base imbalances underlie acid-base disorders and electrolyte abnormalities that exist from a plethora of medical conditions or medication side effects. Additionally, water balance in terms of fluid maintenance is crucial as not to overload the patient, or underhydrate the patient's cells. Overload would be detrimental to a person with underlying cardiovascular or respiratory conditions. Thus, an individualized approach is necessary to correct a patient's fluid balance, especially in surgical patients.

The setpoint must confine itself to a strict range in certain body functions, but it is not necessarily static in others. For example, deviation of arterial blood gas values from the accepted range would be detrimental to a living system. However, when the body is deprived of food, a 'new normal' must be adjusted to function with less energy and a slower metabolism rate. Without this adaptation, the body's cells would be deprived of the needed nutrients and would die quickly, which is not the case, as a living organism can survive on less intake as long as the energy can be maintained. Disruption in thermoregulation could lead to hypothermia if the body's core temperature falls below the threshold for optimal cellular functioning, or hyperthermia if the body's core temperature exceeds the highest. Fever is another example of how the setpoint can increase without necessarily killing the individual. An increase in core body temperature is necessary to fight off an invader, but in the case of hyperthermia, the adaptive function of temperature has failed, and the setpoint is unable to return to normal.

Clinical Significance

All in all, every medical condition can be traced back to failure at some point in the homeostatic control system, whether it be in the inability to detect the initial external change, failure of initiating a feedback loop, failure to enact a response to return to the setpoint, or failure in the setpoint itself. The goal of the health care provider must be to restabilize the internal milieu of the body without causing further harm and to do so promptly to avoid the death of cells from dysregulation, and irreparable failure of organ systems.