Homeostasis and Responses to the External Environment John M. Connors, Ph.D. 3054A HSN

HOMEOSTASIS homeo -- like or similar stasis -- a standing still Homeostasis conveys the impression that something is stopped or unchanging. From the dictionary: homeostasis ≡ the tendency of a system, especially the physiological system of higher animals, to maintain internal stability, owing to the coordinated response of its parts to any situation or stimulus tending to disturb its normal condition or function. Two essential ideas implied by the term homeostasis: 1)Internal stability, and 2)A coordinated response to variations in the external environment that maintains the constancy of the internal environment.

Some measures are static day after day, year after year. Body temperature Blood pressure Heart rate Respiratory rate Urine output Body weight Blood composition Total body composition Etc. A battery of clinical tests have been developed which measure things. The results of these tests are meaningful because we know that certain values are always obtained in a state of health. We expect these values to be static in a state of health. These values may vary with disease or sickness.

“Without an appreciation of homeostasis and the comprehension of homeostatic mechanisms, medicine is empirical, not rational.” L.L. Langley, Homeostasis: Origins of the Concept, 1973 Over a period of many years, we have come to understand many of the physiological mechanisms that maintain this internal stability. When abnormal values are detected, that fact alone tells us something about the responsible physiological mechanism. Thus, the importance of the concept of homeostasis to physiology and medicine.

Homeostatic Control Systems A functionally interconnected network of body components that operate to maintain a chemical or physical factor in the internal environment relatively constant around an optimal level. That is, the control system must be able to respond to and resist changes in the physiological factor being regulated (i.e., the “regulated variable”). Required capabilities: Detection of deviations of the regulated variable from its normal “operating point” or “set point. Integration of information concerning deviations with other relevant information. A means to effect an appropriate adjustment in the activity of the body components, such that the deviation of the regulated variable is minimized or abolished.

Homeostatic control systems can be grouped into two classes: 1.Intrinsic controls Built into or inherent in a organ Examples vascular autoregulation in exercising skeletal muscle, or Frank-Starling mechanism in the heart 2.Extrinsic controls Regulatory control mechanisms initiated outside of an organ alter the activity of that organ. Extrinsic controls maintain most of the factors in the internal environment. Nervous and endocrine controllers.

Extrinsic control of the organs and body systems permits coordinated control of several organs toward a common goal. Coordinated overall regulatory mechanisms are crucial for maintaining the dynamic steady state of the internal environment as a whole. Feedback control A change in the controlled or regulated variable brings forth a corrective response. Feedforward control Anticipation of a change in the controlled or regulated variable brings forth an anticipatory response.

Feedback Control Systems: Positive feedback control systems Negative feedback control systems

CAUTION: No set of equations, however precise, can indicate whether or not a system contains any feedback loops. Feedback is a particular kind of working relationship, not a particular kind of mathematical relationship.

Feedback Relationships B = f(A) A = g(B) A B Lower arrow: A is a function of B; B is the independent variable and A is the dependent variable. Upper arrow: B is a function of A; A is the independent variable and B is the dependent variable. A and B are interdependent variables.

Feedback Relationships B = f(A) A = g(B) A B External Factor + Positive Feedback: operation of the feedback loop tends to enhance or magnify the primary change in A. + +

Feedback Relationships - - A B + External Factor B = f(A) A = g(B) Positive Feedback: operation of the feedback loop tends to enhance or magnify the primary change in A.

Feedback Relationships Negative Feedback: a primary increase in A will cause a secondary increase in B; the increase in B will decrease A, opposing or minimizing the primary change in A. A B + External Factor + - B = f(A) A = g(B)

Examples of Physiological Positive Feedback Systems Estrogen control of GnRH release at ovulation. Others?

Examples of Physiological Negative Feedback Systems involved in Homeostasis Blood pressure Blood volume Plasma osmolarity Plasma CO 2, pH Endocrine gland secretion Etc.

Error-Actuated Feedback Control Systems Engineered SystemsEngineered Systems Primary aim is to design an apparatus that monitors the performance of a physical system and to automatically adjust the controls of the system so as to reduce its error. Error is the difference between the actual performance and the desired or ideal performance.

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - Generalized Feedback Control System

A “normal” steady-state value for the output variable of interest may be considered to be the standard “operating point” of the system. This operating point may serve as the set point in mathematical analyses of the system. In most biological systems, there is no identifiable reference standard with a value (i.e., the set point) that is to be matched (for errorless performance) by the value of the corresponding output. If this is so, then the term “error” makes no sense.

Negative Feedback Systems Purpose of a negative feedback control system: To keep the output signal (y o ) equal to, or at least close to the command signal (y i ) at all times. In general, there will be other input signals (e.g., F d ) acting on the controlled system. The properties of the controlled system may not remain constant as wear occurs and environmental conditions change.

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - Generalized Feedback Control System Input or Command Signal Output Or Controlled Signal Disturbing or Noise Signal

Error-Actuated Feedback Control Systems Questions about the “working behavior” of the system: Servo-System: With the load (F d ) kept constant at zero, how effectively does the system respond to changes in y i by making the desired changes in the output (y o )? How good is the tracking ability of the system? Regulator: With the input signal (y i ) kept constant, how effectively does the system minimize changes in the output (y o ) when changes in load (F d ) occur? How good is the stabilizing or homeostatic ability of the system?

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - Servo-System Controlled System Hold the “Load” Constant How effectively does the system respond to changes in y i by making the desired changes in the output (y o )? How good is the tracking ability of the system?

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - Regulator Control System Hold Input Signal Constant How effectively does the system minimize changes in the output (y o ) when changes in load (F d ) occur? How good is the stabilizing or homeostatic ability of the system?

Properties of the Controlling System - + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ -

y i = reference input or command signal y o = output of the controlled system y e = actuating error signal k = transfer function F c = controlling signal (“manipulated variable”) Controlling System Input or Command Signal yiyi Controller k Error Detector FcFc Controlling Signal - + yeye Error Signal yoyo Proportional Controller: F c = ky e

Properties of the Controlled System - + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ -

Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - F c = controlling signal (“manipulated variable”) F d = disturbing signal G 1 (s)= transfer function G 2 (s) = transfer function y o = output of the controlled system y o = F c G 1 (s) + F d G 2 (s)

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + y o = F c G 1 (s) + F d G 2 (s) y o = ky e G 1 (s) + F d G 2 (s) y o = k [y i -y o ] G 1 (s) + F d G 2 (s) +/ - A “proportional control system is characterized by steady-state error (y i -y o ).

Types of Negative Feedback Control  On-Off Controller  Proportional Controller  Derivative Controller  Integral Controller On-Off and Integral controllers require a physically real set point, but Proportional and Derivative controllers do not. mechanisms

Types of Negative Feedback Control  On-Off Controller F c = k F c = constant output when y e > 0 F c = zero output when y e < 0.

Types of Negative Feedback Control  Proportional Controller F c = k p y e where k p is a constant of proportionality with appropriate dimensions

- + Controlling System Input or Command Signal yiyi yeye Error Signal Controller k Error Detector yoyo Feedback Loop Controlled System FdFd FcFc Disturbing or Noise Signal Controlling Signal yoyo Output or Controlled Signal G 1 (s) G 2 (s) + +/ - Generalized Feedback Control System

DEVELOPMENT OF THE CONCEPT OF HOMEOSTASIS First, the means had to be developed for accurate measurement. Early investigators and physicians depended upon their own senses. Estimate body heat by virtue of their own temperature receptors Count the pulse rate Smell the breath Detect sugar in the urine by the sense of taste Visual observations Appropriate instrumentation was needed to measure specific body temperature, blood pressure, blood and urine sugar, the chemical makeup of the whole body and its components. For example, the concept of homeostatic regulation of body temperature was dependent on the means of actually measuring temperature.