Conceptual Assessment of Physiology

Conceptual Framework for Homeostasis

Organisms maintain a relatively stable internal environment while living in a changing external environment. Variables that are homeostatically regulated are necessary for the survival of cells and the life of the organism. Homeostasis is a dynamic process that involves a negative feedback system(s) that requires a sensor1, a controller (integrator) and effector(s) (targets).

Although other mechanisms may contribute to homeostasis (including feed-forward processes), this conceptual framework is limited to the concept of homeostasis via negative feedback mechanisms, because these are most often encountered in undergraduate physiology.

This framework specifically addresses homeostasis at the level of the organism (e.g. an animal), and does not address cellular or ecosystem homeostasis.

The organism maintains a stable internal environment in the face of fluctuating external environment.

  1. The organism’s internal environment differs from its external environment.
  2. As the external environment changes, homeostatic processes maintain a more or less stable internal environment.
  3. If homeostatic variables change too much cells cannot function normally and may die.
  4. A limited number of variables (i.e. regulated variables) of the internal environment are maintained stable via homeostatic processes in order to sustain cell function.2
  5. Some variables remain within a normal range over time but are not homeostatically regulated variables (e.g. blood hematocrit, testosterone).
  6. Depending on the particular system, the regulated variable may be kept within a very narrow range or within a much wider range.
  7. Homeostatic (i.e. regulatory) mechanisms operate all the time to determine the value of the regulated variable.
  8. Homeostatic mechanisms depend on resources in the external environment, which may limit the ability of the negative feedback to restore a variable to its normal range.

Any change to a regulated variable (a perturbation) that results in an error signal will result in a physiological response to restore the regulated variable toward to its normal range.

  1. The regulated variable is held stable by a negative feedback system.
  2. Not all negative feedback systems are homeostatic.
  3. The process of responding to a perturbation requires an action by a sensor, a control center and an effector (the components of a negative feedback system).
  4. The sensor, control center, and effectors may be physically far from or near to each other in the body, and can even exist in the same cell.

Homeostatic processes require a sensor inside the body (“what can’t be measured can’t be regulated”)

  1. Sensors detect the regulated variable and respond by transducing that stimulus into a different signal.
  2. Sensors respond within a limited range of stimulus values.
  3. Sensors generate an output whose value is proportional to the magnitude of the input to the sensor (i.e. the stimulus).
  4. Sensors are constantly active (not just active when the regulated variable is not at the set point value or outside of a ‘normal’ range).
  5. An organ system may employ a variety of types of sensors (e.g. chemoreceptors, baroreceptors, mechanoreceptors, etc) to regulate variables associated with that organ system

Homeostatic processes require a control center (which includes an integrator).

  1. The control center is part of the endocrine and/or the nervous system.
  2. The integrator receives a signal from the sensor.
  3. The integrator is a component of the control center.
  4. Physiological systems have a normal range for a regulated variable (a so-called set point).
  5. The integrator continuously determines the difference between the signal from the sensors the set point (i.e. the normal range of the regulated variable).
  6. The value of the difference (between the signal from the sensor and the set point) is used by the control center to calculate a change in the signals going to the effectors (i.e. targets).
  7. It is possible in some circumstances and in some systems for the set point to change.

Homeostatic processes require “effectors” or target organs or tissues.

  1. Physiological targets or effectors are cells, tissues, or organs (unlike “effector molecules” in biochemistry).
  2. The action of the effectors or targets is the physiological response that results in physical or chemical changes in the internal environment.
  3. The response of the effectors determines the value of the regulated variable.
  4. The response of the effectors can result in changes in non-regulated variables that in turn alter the regulated variable.3


1 Refer to Modell et al. 2015, i.e. the “Definitions of Terms for Homeostasis Paper”

2 The following are widely recognized and clearly established as homeostatic regulated variables in humans: the following ions (H+, Ca++, K+) in extracellular fluid (ECF not blood), blood CO2, O2 , blood glucose, blood pressure, blood osmolarity, core body temperature. (refer to “Table. Homeostatic regulated variables typically found in textbooks of undergraduate physiology” in companion paper).

3 For example, blood pressure is a regulated variable that can be changed by altering heart rate (HR) and peripheral resistance (PR), which are not homeostatic regulated.