1. HOMEOSTATIC REGULATION

2. Learning Objectives Explain homeostasis Discuss the relationship between external and internal environments List the main body fluid compartments, their constituents and their relationship to each other Define equilibrium and steady state Give examples of homeostatic mechanisms Explain negative feedback Define controlled variable, sensor, comparator and set point and give examples of each in a negative feedback loop Discuss factors that may change set points Define redundancy and hierarchy with respect to homeostatic control mechanisms Explain positive feedback Explain feed-forward regulation

3. Organ Systems in Review The integration between systems of the body

4. External and Internal Environments “all the vital mechanisms, however varied they may be, have only one object, that of preserving constant the conditions of life in the internal environment.” Claude Bernard (1857) The Basis of Physiological Regulation A Stable Internal Environment Is Essential for Normal Cell Function

5. Environments pH 7.4 40 mm Hg0.23 mm HgPCO 2 PaO 2 95 mm Hg160 mm HgPO 2 37 °C-10 and +40 °CTemperature InsideOutsideVariable stability of the internal environment is the primary condition for a free and independent existence - By controlling its internal environment the organism is no longer at the mercy of the environment pH?/variable

6. Body Fluid Compartments and their Relationship Blood Plasma 3 L Interstitial 11 L Intracellular 28 L Transcellular 1 L most cases substances within the plasma must pass through the interstitial fluid before entering cells. Therefore the interrelationships between these 4 compartments are crucial in underlying whole body homeostasis. Body

7. Body Fluid Constituents [Na + ] = 145 [K + ] = 4.5 [Cl - ] = 116 [Protein] = 0 mM Osmolality 290 mOsm [Na + ] = 142 [K + ] = 4.4 [Cl - ] = 102 [Protein] = 1 Osmolality 290 mOsm [Na+] = 15 [K+] = 120 [Cl-] = 20 [Protein] = 4 Osmolality 290 mOsm PlasmaInterstitial Cellular substances aren’t in equilibrium, but there is a balance  there is a difference between the basic constituents of the body-fluid compartments. This means that homeostasis is not about reaching equilibrium, but about maintaining a steady- state. Since the system is not necessarily in equilibrium energy expenditure is required to maintain a steady state.

8. To summarize: Homeostasis is the maintenance of a steady state of the internal environment of the body.

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10. Homeostatic control mechanisms

11. Feedback( flow of information along a closed loop ) – Negative or Positive Negative – change is sensed and action taken to prevent further change e.g- regulation of secretion of hormones. Positive – change is sensed and action taken to amplify change (usually associated with a discrete end point, e.g. birth, ovulation)

12. Homeostatic Mechanisms Most homeostatic mechanisms are based on negative feedback specific terms that are used to describe the processes involved- Controlled Variable Sensor Comparator, set point Effectors

13. Blood Pressure Regulation Blood Loss Blood Pressure (controlled variable) Baroreceptor (sensor) Brain (comparitor) Vasoconstriction ↑ Cardiac Output (effectors) Cardiovascular control center – compares BP to set point and adjusts vascular tone and cardiac output accordingly

14. Blood Glucose -ve Feedback  -cell Variable Blood Glucose  -cell Glucose Insulin secretion Cells

16. “Gain” of a Control System The degree of effectiveness with which a control system maintains constant, conditions is determined by the gain of the negative feedback.

17. For instance, let us assume that a large volume of blood is transfused into a person whose baroreceptor pressure control system is not functioning, and the arterial pressure rises from the normal level of 100 mm Hg up to 175 mm Hg. Then, let us assume that the same volume of blood is injected into the same person when the baroreceptor system is functioning, and this time the pressure increases only 25 mm Hg. Thus, the feedback control system has caused a “correction” of –50 mm Hg—that is, from 175 mm Hg to 125 mm Hg. There remains an increase in pressure of +25 mm Hg, called the “error,” which means that the control system is not 100 per cent effective in preventing change.

19. Q Assume that excess blood is transfused into a patient whose arterial baroreceptors are nonfunctional and blood pressure increases from 100 to 150 mm Hg. Then, assume that the same volume is blood is infused into the same patient under conditions where his arterial baroreceptors are functioning normally and blood pressure increases from 100 to 125 mm Hg. What is the approximate feedback “gain” of the arterial baroreceptors in this patient when they are functioning normally? A) -1.0 B) -2.0 C) 0.0 D) +1.0 E) +2.0

20. Positive Feedback This is when instead of the comparator causing the controlled variable to come back to normal it potentiates the error signal and the controlled variable moves further away. There are few normal physiological events that are controlled by positive feedback.

21. Positive Feedback Contraction oxytocin All steps in this process produce an increase in the next step leading to a loop of stimulation. The positive feedback loop is broken when the baby is expelled from the uterus and hence the step involving pressure against the cervix has been removed.

23. Feed-forward Control Anticipation of change – gets the body ready for change e.g. heart rate and ventilation can increase even before exercise begins Or salivation and digestive enzyme production begins before a meal is eaten

24. Redundancy Homeostatic mechanisms are important – therefore often there is more than one control mechanism If one mechanism fails – then there is a backup system (e.g. control of cutaneous blood vessels by both cardiovascular control center and temperature control center, or blood pressure)

25. Hypovolemic Shock B.P. falls Kidney Juxtaglomerular cells Aortic arch Carotid sinus Renin Activity drop Hypothalamus Posterior Pituitary Medulla oblongata Angiotensinogen in blood Angiotensin I LUNG Angiotenin II ACE Adrenal Cortex Heart rate contractility Blood Vessels Kidney Salt water conservation Aldosterone ADH Sympathetic output Inc. volume Inc. vasc. resistance Inc. B.P.

26. In response to a bacterial infection my body's thermostat is raised. I start to shiver and produce more body heat. When my body temperature reaches 101 degrees, I stop shivering and my body temperature stops going up. This is an example of: A) Negative feedback B) A malfunctioning control system C) Positive feedback D) A negative impact

28. Which of the following is an example of a positive feedback? A) Shivering to warm up in a cold winter storm B) A cruise control set on your car applies more gas when going up a hill C) You sweat on a hot summer's day and the blood vessels in your skin vasodilate D) You get cut and platelets form a clot. This in turn activates the fibrin clotting system and more blood forms clots

29. Where is the body's "thermostat" found? A) Within the nervous system, in the Hypothalamus B) Within the integumentary system, in the skin C) Within the brain, in the corpus callosum D) Within the Urinary system, in the kidneys What system has little to contribute to the homeostasis of the organism? A) Urinary System B) Reproductive System C) Respiratory System D) Nervous System

30. Summary I Homeostasis – maintenance of a stable internal environment Steady state – unchanging with time Equilibrium – when parameters are maintained in an energetically favorable situation Redundancy – more than 1 system to control a variable (backup systems)

31. Summary II Negative feedback – feedback causes a perturbation to be minimized or reversed with view to keeping parameter at a set point Positive feedback – amplification of a deviation (usually defined end point)