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 hemoestatic control mechanisms
Explain positive feedback
Explain feed-forward regulation

3. Organ Systems in Review
The integration between systems of the body
schematic diagram showing the interrelationships of most of the 10 physiological organ systems in the human body .The integumentary system [integumentum, covering], composed of the skin, forms a protective boundary that separates the body's internal environment from the external environment (the outside world). The musculoskeletal system provides support and body movement.
Four systems exchange materials between the internal and external environments. The respiratory system exchanges gases, the digestive system takes up nutrients and water and eliminates wastes, the urinary system removes excess water and waste material, and the reproductive system produces eggs or sperm.
The remaining four systems extend throughout the body. The circulatory system distributes materials by pumping blood through vessels. The nervous and endocrine systems coordinate body functions. Note that the figure shows them as a continuum rather than as two distinct systems. Because as we have learned more about the integrative nature of physiological function, the lines between these two systems have blurred. The one system not shown in Figure is the diffuse immune system. Immune cells are positioned to intercept material that may enter through the exchange surfaces or through a break in the skin, and they protect the internal environment from foreign invaders. In addition, immune tissues are closely associated with the circulatory system.

4. Body Fluid Compartments
20%
Body-fluid compartments
The diagram shows the body-fluid compartments of the average 70kg male. It is usual to call the fluid water as the major constituent of the fluid is water.
the total amount of water in a man of average weight (70 kilograms) is approximately 40 liters, averaging 57 percent of his total body weight.
body water is broken down into the following compartments:
Intracellular fluid (2/3 of body water).- in a body containing 40 liters of fluid, about 25 liters is intracellular, which amounts to 62.5% (5/8), close enough to the 2/3 rule of thumb.
Extracellular fluid (1/3 of body water). for a 40 litre body, about 15 litres is extracellular,[5] which amounts to 37.5% Again, this is close to the 1/3 rule of thumb cited here.
Plasma (1/5 of extracellular fluid). of the 15 litres of extracellular fluid, plasma volume averages 3 litres.[5] This amounts to 20%.
Interstitial fluid (4/5 of extracellular fluid)
Transcellular fluid (a.k.a. "third space,”)
Contained inside organs, such as the gastrointestinal, cerebrospinal, peritoneal, and ocular fluids.
The simplest calculation is the rule.
Total Body Water = 60% of body weight
Intracellular fluid = 40% of body weight
Extracellular fluid = 20% of body weight

5. Compartments and their Relationship
Blood Plasma
3 L
Interstitial
11 L
Intracellular
28 L
Transcellular
1 L
This diagram shows that the major constituent of body fluid is found within the cells. It is important to understand that in 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.
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.

6. 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
The Basis of Physiological Regulation
Our bodies are made up of incredibly complex and delicate materials, and we are constantly subjected to all kinds of disturbances, yet we keep going for a lifetime. It is clear that conditions and processes in the body must be closely controlled and regulated, i.e., kept within appropriate values.
A Stable Internal Environment Is Essential for Normal Cell Function
The nineteenth-century French physiologist Claude Bernard was the first to formulate the concept of the internal environment . He pointed out that an external environment surrounds multicellular organisms (air or water), but also a liquid internal environment (extracellular fluid) surrounds the cells that make up the organism. These cells are not directly exposed to the external world but, rather, interact with it through their surrounding environment, which is continuously renewed by the circulating blood.
FIG--The living cells of our body, surrounded
by an internal environment (extracellular
fluid), communicate with the external world through this
medium. Exchanges of matter and energy between the body and
the external environment (indicated by arrows) occur via the gastrointestinal
tract, kidneys, lungs, and skin (including the specialized
sensory organs).

7. Environments pH 7.4 40 mm Hg 0.23 mm Hg PCO2 PaO2 95 mm Hg 160 mm Hg
PO2
37 °C
-10 and +40 °C
Temperature
Inside
Outside
Variable pH
?/variable
For optimal cell, tissue, and organ function in animals, several facets of the internal environment must be maintained within narrow limits. These include but are not limited to (1) oxygen and carbon dioxide tensions, (2) concentrations of glucose and other metabolites, (3) osmotic pressure, (4) concentrations of hydrogen, potassium, calcium, and magnesium ions, and (5) temperature.
Departures from optimal conditions may result in dysfunction, disease, or death. Bernard stated that stability of the internal environment is the primary condition for a free and independent existence. He recognized that an animal's independence from changing external conditions is related to its capacity to maintain a relatively constant internal environment. A good example is the ability of warm-blooded animals to live in different climates. Over a wide range of external temperatures, core temperature in mammals is maintained constant by both physiological and behavioral mechanisms. This stability offers great flexibility and has an obvious survival value. .
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 .

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

9. Body Fluid Constituents
[Na+] = 142
[K+] = 4.4
[Cl-] = 102
[Protein] = 1
Osmolality
290 mOsm
[Na+] = 145
[K+] = 4.5
[Cl-] = 116
[Protein] = 0 mM
Osmolality
290 mOsm
[Na+] = 15
[K+] = 120
[Cl-] = 20
[Protein] = 4
Osmolality
290 mOsm
Plasma
Interstitial
Cellular
substances aren’t in equilibrium, but there is a balance
This table shows that even though the osmolarity (Osmolarity is the measure of solute concentration,) of the three compartments is equal there are significant differences in the constituents. You need to know these values. It is important to note the differences in intracellular and extracellular concentrations of Na+ and K+. Therefore substances aren’t in equilibrium, but there is a balance. This is an important concept.
Under normal conditions 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.
Important concept: Equilibrium and steady state are not the same thing. Steady-state means the maintenance of a state that does not change with time, and energy expenditure may be necessary. While equilibrium there is also no change in state over time but it is energetically favorable.
Whole body homeostasis involves more than the maintenance of the steady state of the substances of the above table. In order to survive we must control temperature, pH, oxygen and carbon dioxide levels, blood pressure and many more.
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.

11. Homeostasis & Controls
Successful compensation
Homeostasis reestablished
Failure to compensate
Pathophysiology
Illness
Death
Homeostasis Is the Maintenance of Steady States in the Body by Coordinated Physiological Mechanisms
The key to maintaining the stability of the body's internal environment is the masterful coordination of important regulatory mechanisms in the body. The renowned physiologist Walter B. Cannon captured the spirit of the body's capacity for self-regulation by defining the term homeostasis as the maintenance of steady states in the body by coordinated physiological mechanisms.
Understanding the concept of homeostasis is important for understanding and analyzing normal and pathological conditions in the body. To function optimally under a variety of conditions, the body must sense departures from normal and then be able to activate mechanisms for restoring physiological conditions to normal. Deviations from normal conditions may vary between too high or too low, so mechanisms exist for opposing changes in either direction. For example, if blood glucose concentration is too low, the hormone glucagon is released from the alpha cells of the pancreas and epinephrine is released from the adrenal medulla, to increase it. If blood glucose concentration is too high, insulin is released from the beta cells of the pancreas to lower it by enhancing the cellular uptake, storage, and metabolism of glucose. Behavioral responses also contribute to the maintenance of homeostasis. For example, a low blood glucose concentration stimulates feeding centers in the brain, driving the animal to seek food.
Homeostatic regulation of a physiological variable often involves several cooperating mechanisms activated at the same time or in succession. The more important a variable, the more numerous and complicated are the mechanisms that operate to keep it at the desired value. When the body is unable to restore physiological variables, then disease or death can result.

12. 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)

13. Homeostatic Mechanisms
Most homeostatic mechanisms are based on negative feedback
specific terms that are used to describe the processes involved-
Controlled Variable
Sensor
Controlled Variable: This is the physiological parameter being controlled (e.g. blood pressure).
Sensor: This is usually a type of receptor that detects changes in the controlled variable (e.g. baroreceptors)
Comparator: This is the integration center of the negative feedback response (e.g. cardiovascular control center of the brain). It analyzes the data from the sensor and compares it to a set point. The set point is influenced by inheritance and by adaptations to the environment (See later). If the data is different from the set point it sends out an error signal.
Effectors: These are the nerve pathways and cells or tissues that carry out the response. For example, in response to a lowered blood pressure, the sympathetic nervous system is activated to cause constriction of blood vessels. Such an action then increases the blood pressure back towards normal, thus restoring homeostasis.
Comparator, set point
Effectors

14. Blood Pressure Regulation
Blood Loss
Baroreceptor
(sensor)
Brain
(comparitor)
Cardiovascular control
center – compares BP to
set point and adjusts
vascular tone and
cardiac output
accordingly
Diagram showing the various roles of the processes involved in the maintenance of blood pressure after a hemorrhage.
For example an increase in the controlled variable will be noted by the sensor which will send this information to the Comparator.
The Comparator will compare this with the set point and if it is different will send out an error signal via the effector which will attempt to bring the control variable back to normal (or under control). 3
Vasoconstriction
↑ Cardiac Output
(effectors)
Blood Pressure
(controlled variable)

15. Blood Glucose -ve Feedback
b-cell
Variable
Blood Glucose
Insulin
secretion
A diagram showing a basic negative feedback system. An increase in blood glucose concentration will lead to the pancreas secreting more insulin to decrease blood glucose levels. Whilst a drop in glucose leads to decreased insulin secretion and maintenance of a higher blood glucose concentration
Glucose
b-cell
Cells

17. Cutaneous Blood Vessels
Anticipation of exercise and during exercise
Sympathetic outflow increases
to maintain blood pressure

18. Cutaneous Blood Vessels
Anticipation of strenous exercise
Sympathetic outflow increases
to maintain blood pressure
Hypothalamus detects heat increase
And inhibits sympathetic outflow
Vasodilation helps to divert blood flow to the skin
For heat loss

19. Cutaneous Blood Vessels
With extreme exercise the need to control
Blood pressure takes priority and the
Vessels constrict
Hypothalamus detects heat increase
And inhibits sympathetic outflow
Vasodilation helps to divert blood flow to the skin
For heat loss

20. 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.
Positive Feedback
This is when instead of the comparitor 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. One example is childbirth.
Figure 7. 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.
Feed-Forward
Contraction
oxytocin

21. Feed-forward Control
Anticipation of change – gets 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
Feed-Forward Regulation
This is when your body anticipates a change of a controlled-variable before it happens and prepares the body for it. For example temperature sensitive receptors in the skin will send information to the brain if a person moves outside in the cold from a warm room. This will lead to the stimulation of heat production and heat conservation to prevent internal body temperature to fall, even though internal body temperature hasn’t begun to fall.
Figure

22. Redundancy
Homeostatic mechanisms are important – therefore often there is more than 1 control mechanism
If 1 mechanism fails – then there is a backup system (e.g. ATP/adenosine in airway surface liquid secretion or control of cutaneous blood vessels by both cardiovascular control center and temperature control center)
Or blood pressure (next slide)

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

24. What is the normal pH value for body fluid?C) D) E)
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

25. 6. 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

26. 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
8. What system has little to contribute to the homeostasis of the organism?
A) Urinary System
B) Reproductive System
C) Respiratory System
D) Nervous System

27. 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)

28. 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)

35. Positive feed back