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.[1] '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.[2] 

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.[3] 

Cells respond to changes in volume by activating the metabolic transport of molecules necessary to return to back to normal volume.[4] 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.[5] 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.[6] 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.[7] 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.[5] 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.[2] 

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.[5] 

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.[8] 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.[2] The loss of receptor sensitivity with age increases the risk of illness as an unstable internal environment is allowed to exist.[9] 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.[10] 

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.[9] 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.[2] 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.