# Human Physiology/Homeostasis

## Overview

The human organism consists of trillions of cells all working together
for the maintenance of the entire organism. While cells may perform very
different functions, all the cells are quite similar in their metabolic
requirements. Maintaining a constant internal environment with all that
the cells need to survive (oxygen, glucose, mineral ions, waste removal,
and so forth) is necessary for the well-being of individual cells and
the well-being of the entire body. The varied processes by which the
body regulates its internal environment are collectively referred to as
homeostasis.

### What is Homeostasis?

**Homeostasis** in a general sense refers to stability or balance in a
system. It is the body\'s attempt to maintain a constant internal
environment. Maintaining a stable internal environment requires constant
monitoring and adjustments as conditions change. This adjusting of
physiological systems within the body is called *homeostatic
regulation*.

Homeostatic regulation involves three parts or mechanisms: 1) the
***receptor***, 2) the***control center***and 3) the***effector***.

The ***receptor***receives information that something in the environment
is changing. The***control center***or***integration center***receives
and processes information from the***receptor***. And lastly,
the***effector***responds to the commands of the***control center*** by
either opposing or enhancing the stimulus. This is an ongoing process
that continually works to restore and maintain homeostasis. For example,
in regulating body temperature there are temperature *receptors* in the
skin, which communicate information to the brain, which is the *control
center,* and the *effector* is our blood vessels and sweat glands in our
skin.

Because the internal and external environments of the body are
constantly changing and adjustments must be made continuously to stay at
or near the set point, homeostasis can be thought of as a *synthetic
equilibrium.*

Since homeostasis is an attempt to maintain the internal conditions of
an environment by limiting fluctuations, it must involve a series of
negative feedback loops.

### Positive and Negative Feedback

When a change of variable occurs, there are two main types of feedback
to which the system reacts:

-   ***Negative feedback***: a reaction in which the system responds in
    such a way as to reverse the direction of change. Since this tends
    to keep things constant, it allows the maintenance of homeostasis.
    For instance, when the concentration of carbon dioxide in the human
    body increases, the lungs are signaled to increase their activity
    and expel more carbon dioxide. Thermoregulation is another example
    of negative feedback. When body temperature rises, receptors in the
    skin and the hypothalamus sense a change, triggering a command from
    the brain. This command, in turn, effects the correct response, in
    this case a decrease in body temperature.

:   

    :   **Home Heating System Vs. Negative Feedback**\'\'
    :   When you are at home, you set your thermostat to a desired
        temperature. Let\'s say today you set it at 70 degrees. The
        thermometer in the thermostat waits to sense a temperature
        change either too high above or too far below the 70 degree set
        point. When this change happens the thermometer will send a
        message to to the \"Control Center\", or thermostat,which in
        turn will then send a message to the furnace to either shut off
        if the temperature is too high or kick back on if the
        temperature is too low. In the home-heating example the air
        temperature is the \"NEGATIVE FEEDBACK.\" When the Control
        Center receives negative feedback it triggers a chain reaction
        in order to maintain room temperature.

-   ***Positive feedback***: a response is to amplify the change in the
    variable. This has a destabilizing effect, so does not result in
    homeostasis. Positive feedback is less common in naturally occurring
    systems than negative feedback, but it has its applications. For
    example, in nerves, a threshold electric potential triggers the
    generation of a much larger action potential. Blood clotting in
    which the platelets process mechanisms to transform blood liquid to
    solidify is an example of positive feedback loop. Another example is
    the secretion of oxytocin which provides a pathway for the uterus to
    contract, leading to child birth.

:   

    :   **Harmful Positive Feedback**
    :   Although Positive Feedback is needed within Homeostasis it also
        can be harmful at times. When you have a high fever it causes a
        metabolic change that can push the fever higher and higher. In
        rare occurrences the body temperature reaches 113 degrees
        Fahrenheit / 45 degrees Celsius and the cellular proteins stop
        working and the metabolism stops, resulting in death.

**Summary**: Sustainable systems require combinations of both kinds of
feedback. Generally with the recognition of divergence from the
homeostatic condition, positive feedbacks are called into play, whereas
once the homeostatic condition is approached, negative feedback is used
for \"fine tuning\" responses. This creates a situation of
\"metastability,\" in which homeostatic conditions are maintained within
fixed limits, but once these limits are exceeded, the system can shift
wildly to a wholly new (and possibly less desirable) situation of
homeostasis.

***Homeostatic systems have several properties***

-   They are ultra-stable, meaning the system is capable of testing
    which way its variables should be adjusted.
-   Their whole organization (internal, structural, and functional)
    contributes to the maintenance of balance.
-   Physiology is largely a study of processes related to homeostasis.
    Some of the functions you will learn about in this book are not
    specifically about homeostasis (e.g. how muscles contract), but in
    order for all bodily processes to function there must be a suitable
    internal environment. Homeostasis is, therefore, a fitting framework
    for the introductory study of physiology.

***Where did the term \"Homeostasis\" come from?***

The concept of homeostasis was first articulated by the French scientist
Claude Bernard (1813-1878) in his studies of the maintenance of
stability in the \"milieu interior.\" He said, \"All the vital
mechanisms, varied as they are, have only one object, that of preserving
constant the conditions of life in the internal environment\" (from
*Leçons sur les Phénonèmes de la Vie Commune aux Animaux et aux
Végétaux*, 1879). The term itself was coined by American physiologist
Walter Cannon, author of *The Wisdom of the Body* (1932). The word comes
from the Greek *homoios* (same, like, resembling) and *stasis* (to
stand, posture).

### Cruise Control on a car as a simple metaphor for homeostasis

When a car is put on cruise control it has a set speed limit that it
will travel. At times this speed may vary by a few miles per hour but in
general the system will maintain the set speed. If the car starts to go
up a hill, the systems will automatically increase the amount of fuel
given to maintain the set speed. If the car starts to come down a hill,
the car will automatically decrease the amount of fuel given in order to
maintain the set speed. It is the same with homeostasis- the body has a
set limit on each environment. If one of these limits increases or
decreases, the body will sense and automatically try to fix the problem
in order to maintain the pre-set limits. This is a simple metaphor of
how the body operates---constant monitoring of levels, and automatic
small adjustments when those levels fall below (or rise above) a set
point.

## Pathways That Alter Homeostasis

A variety of homeostatic mechanisms maintain the internal environment
within tolerable limits. Either homeostasis is maintained through a
series of control mechanisms, or the body suffers various illnesses or
disease. When the cells in the body begin to malfunction, the
homeostatic balance becomes disrupted. Eventually this leads to disease
or cell malfunction. Disease and cellular malfunction can be caused in
two basic ways: either, *deficiency* (cells not getting all they need)
or *toxicity* (cells being poisoned by too much of the things they need,
or by things they do not need). When homeostasis is interrupted in your
cells, there are *pathways* to correct or worsen the problem. In
addition to the internal control mechanisms, there are external
influences based primarily on lifestyle choices and environmental
exposures that influence our body\'s ability to maintain cellular
health.

-   **Nutrition:** If your diet is lacking in a specific vitamin or
    mineral your cells will function poorly, possibly resulting in a
    disease condition. For example, a menstruating woman with inadequate
    dietary intake of iron will become anemic. Lack of hemoglobin, a
    molecule that requires iron, will result in reduced oxygen-carrying
    capacity. In mild cases symptoms may be vague (e.g. fatigue), but if
    the anemia (British English: *anaemia*) is severe the body will try
    to compensate by increasing cardiac output, leading to palpitations
    and sweatiness, and possibly to heart failure.
-   **Toxins:** Any substance that interferes with cellular function,
    causing cellular malfunction. This is done through a variety of
    ways; chemical, plant, insecticides, and/or bites. A commonly seen
    example of this is drug overdoses. When a person takes too much of a
    drug their vital signs begin to waver; either increasing or
    decreasing, these vital signs can cause problems including coma,
    brain damage and even death.
-   **Psychological:** Your physical health and mental health are
    inseparable. Our thoughts and emotions cause chemical changes to
    take place either for better as with meditation, or worse as with
    stress.
-   **Physical:** Physical maintenance is essential for our cells and
    bodies. Adequate rest, sunlight, and exercise are examples of
    physical mechanisms for influencing homeostasis. Lack of sleep is
    related to a number of ailments such as irregular cardiac rhythms,
    fatigue, anxiety and headaches.
-   **Genetic/Reproductive:** Inheriting strengths and weaknesses is
    part of our genetic makeup. Genes are sometimes turned off or on due
    to external factors which we can have some control over, but at
    other times little can be done to correct or improve genetic
    diseases. Beginning at the cellular level a variety of diseases come
    from mutated genes. For example, cancer can be genetically inherited
    or can be caused due to a mutation from an external source such as
    radiation or genes altered in a fetus when the mother uses drugs.
-   **Medical:** Because of genetic differences some bodies need help in
    gaining or maintaining homeostasis. Through modern medicine our
    bodies can be given different aids, from anti-bodies to help fight
    infections, or chemotherapy to kill harmful cancer cells.
    Traditional and alternative medical practices have many benefits,
    but like any medical practice the potential for harmful effects is
    present. Whether by nosocomial infections, or wrong dosage of
    medication, homeostasis can be altered by that which is trying to
    fix it. Trial and error with medications can cause potential harmful
    reactions and possibly death if not caught soon enough.

The factors listed above all have their effects at the cellular level,
whether harmful or beneficial. Inadequate beneficial pathways
(deficiency) will almost always result in a harmful waver in
homeostasis. Too much toxicity also causes homeostatic imbalance,
resulting in cellular malfunction. By removing negative health
influences, and providing adequate positive health influences, your body
is better able to self-regulate and self-repair, thus maintaining
homeostasis.

## Homeostasis Throughout the Body

Each body system contributes to the homeostasis of other systems and of
the entire organism. No system of the body works in isolation, and the
well-being of the person depends upon the well-being of all the
interacting body systems. A disruption within one system generally has
consequences for several additional body systems. Here are some brief
explanations of how various body systems contribute to the maintenance
of homeostasis:

### Nervous System

Since the nervous system does not store nutrients, it must receive a
continuous supply from blood. Any interruption to the flow of blood may
bring brain damage or death. The nervous system maintains homeostasis by
controlling and regulating the other parts of the body. A deviation from
a normal set point acts as a stimulus to a receptor, which sends nerve
impulses to a regulating center in the brain. The brain directs an
effector to act in such a way that an adaptive response takes place. If,
for example, the deviation was a lowering of body temperature, the
effector acts to increase body temperature. The adaptive response
returns the body to a state of normalcy and the receptor, the regulating
center, and the effector temporarily cease their activities. Since the
effector is regulated by the very conditions it produced, this process
is called control by negative feedback. This manner of regulating
normalcy results in a fluctuation between two extreme levels. Not until
body temperature drops below normal do receptors stimulate the
regulating center and effectors act to raise body temperature.
Regulating centers are located in the central nervous system, consisting
of the brain and spinal cord. The hypothalamus is a portion of the brain
particularly concerned with homeostasis; it influences the action of the
medulla oblongata, a lower part of the brain, the autonomic nervous
system, and the pituitary gland.

The nervous system has two major portions: the central nervous system
and the peripheral nervous system. The central nervous system consists
of the cranial and spinal nerves. The autonomic nervous system is a part
of peripheral nervous system and contains motor neurons that control
internal organs. It operates at the subconscious level and has two
divisions, the sympathetic and parasympathetic systems. In general, the
sympathetic system brings about those results we associate with
emergency situations, often called fight or flight reactions, and the
parasympathetic system produces those effects necessary to our everyday
existence.

### Endocrine System

The endocrine system consists of glands which secrete hormones into the
bloodstream. Each hormone has an effect on one or more target tissues.
In this way the endocrine system regulates the metabolism and
development of most body cells and body systems. To be more specific,
the Endocrine system has sex hormones that can activate sebaceous
glands, development of mammary glands, alter dermal blood flow and
release lipids from adipocytes. MSH can stimulate melanocytes on our
skin. Our bone growth is regulated by several hormones, and the
endocrine system helps with the mobilization of calcitonin and calcium.
In the muscular system, hormones adjust muscle metabolism, energy
production, and growth. In the nervous system, hormones affect neural
metabolism, regulate fluid/electrolyte balance and help with
reproductive hormones that influence CNS development and behaviors. In
the Cardiovascular system, we need hormones that regulate the production
of RBC\'s (red blood cells), which elevate and lower blood pressure.
Hormones also have anti-inflammatory effects and stimulate the lymphatic
system. In summary, the endocrine system has a regulatory effect on
basically every other body system.

### Integumentary System

The integumentary system (the skin) is involved in protecting the body
from invading microbes (mainly by forming a thick impenetrable layer),
regulating body temperature through sweating and
vasodilation/vasoconstriction, or shivering and piloerection (goose
bumps), and regulating ion balances in the blood. Stimulation of mast
cells also produce changes in blood flow and capillary permeability
which can effect the blood flow in the body and how it is regulated. It
also helps synthesize vitamin D which interacts with calcium and
phosphorus absorption needed for bone growth, maintenance, and repair.
Hair on the skin guards entrance into the nasal cavity or other
orifices, preventing invaders from getting further into our bodies. Our
skin also helps maintain balance by excretion of water and other solutes
(i.e. the keratinized epidermis limits fluid loss through skin). It also
provides mechanical protection against environmental hazards. We need to
remember that our skin is integumentary; it is our first line of
defense.

### Skeletal System

As the structural framework for the human body, the skeletal system
consists mainly of the 206 or so bones of the skeletal system but also
includes cartilages, ligaments, and other connective tissues that
stabilize and interconnect them. Bones work in conjunction with the
muscular system to aid in posture and locomotion. Many bones of the
skeleton function as levers, which change the magnitude and direction of
forces generated by skeletal muscle. Protection is a pivotal role
occupied by the skeletal system, as many vital organs are encased within
the skeletal cavities (e.g. cranial and spinal), and bones form much of
the structural basis for other body cavities (ex: thoracic and pelvic
cavities). The skeletal system also serves as an important mineral
reserve. For example, if blood levels of calcium or magnesium are low
and the minerals are not available in the diet, they will be taken from
the bones. Also, the skeletal system provides calcium needed for all
muscular contraction. Finally, red blood cells, lymphocytes and other
cells relating to the immune response are produced and stored in the
bone marrow.

### Muscular System

The muscular system is one of the most versatile systems in the body.
The muscular system contains the heart, which constantly pumps blood
through the body. The muscular system is also responsible for actions
both involuntary (e.g. goose bumps, digestion, breathing) and voluntary
(e.g. walking, picking up objects). Muscles also help protect organs in
the body\'s cavities. The muscles in your body use energy, which
increases your body heat when you\'re cold. The act of shivering occurs
when the internal temperature drops. Muscles around vital organs move,
breaking down ATP and thereby releasing heat, which is then distributed
to the rest of the body.

### Cardiovascular System

The cardiovascular system, in addition to needing to maintain itself
within certain levels, plays a role in maintenance of other body systems
by transporting hormones (heart secretes Atrial Natriuretic Peptide and
Brain Natriuretic Peptide, or ANP and BNP, respectively) and nutrients
(oxygen, EPO to bones, etc.), taking away waste products, and providing
all living body cells with a fresh supply of oxygen and removing carbon
dioxide. Homeostasis is disturbed if the cardiovascular or lymphatic
systems are not functioning correctly. Our skin, bones, muscles, lungs,
digestive tract, and nervous, endocrine, lymphatic, urinary and
reproductive systems use the cardiovascular system as its \"road\" or
\"highway\" as far as distribution of things such as nutrients, oxygen,
waste products, hormones, drugs, etc. There are many risk factors for an
unhealthy cardiovascular system. Some diseases associated are typically
labeled \"uncontrollable\" or \"controllable.\" The main uncontrollable
risk factors are age, gender, and a family history of heart disease,
especially at an early age.

The cardiovascular system also contains sensors to monitor blood
pressure, called baroreceptors, that work by detecting how stretched a
blood vessel is. This information is relayed to the Medulla Oblongata in
the brain where action is taken to raise or lower blood pressure via the
autonomic nervous system.

### Lymphatic System

The lymphatic system has three principal roles. First is the maintenance
of blood and tissue volume. Excess fluid that leaves the capillaries
when under pressure would build up and cause edema. Secondly, the
lymphatic system absorbs fatty acids and triglycerides from fat
digestion so that these components of digestion do not enter directly
into the blood stream. Third, the lymphatic system is involved in
defending the body against invading microbes, and the immune response.
This system assists in maintenance, such as bone and muscle repair after
injuries. Another defense is maintaining the acidic pH of urine to fight
infections in the urinary system. The tonsils are our bodies \"helpers\"
to defend us against infections and toxins absorbed from the digestive
tract. The tonsils also protect against infections entering into our
lungs.

### Respiratory System

The respiratory system works in conjunction with the cardiovascular
system to provide oxygen to cells within every body system for cellular
metabolism. The respiratory system also removes carbon dioxide. Since
CO2 is mainly transported in the plasma as bicarbonate ions, which act
as a chemical buffer, the respiratory system also helps maintain proper
blood pH levels, a fact that is very important for homeostasis. In
hyperventilation, CO2 is decreased in blood levels. This causes the pH
of body fluids to increase. If pH levels rise above 7.45, the result is
respiratory alkalosis and passing out. On the other hand,
hypoventilation may causes pH to fall below 7.35 which results in
respiratory acidosis. This is the mechanism for death by opioid
overdose. The respiratory system also helps the lymphatic system by
trapping pathogens and protecting deeper tissues within. Note that when
you have increased thoracic space it can provide abdominal pressure
through the contraction of respiratory muscles. This can assist in
defecation.

The organs of the respiratory system include the nose, pharynx, larynx,
trachea, bronchi and lungs. Together these organs permit the movement of
air into the tiny, thin walled sacs of the lungs called alveoli. It is
in the alveoli that oxygen from the air is exchanged for the waste
product carbon dioxide, which is carried to lungs by the blood so that
it can be eliminated from the body.

### Digestive System

Without a regular supply of energy and nutrients from the digestive
system, all body systems would soon suffer. The digestive system absorbs
organic substances, vitamins, ions, and water that are needed all over
the body. In the skin, the digestive tract provides lipids for storage
in the subcutaneous layer. Note that food undergoes three types of
processes in the body: digestion, absorption, and elimination. If one of
these is not working, you will have problems that will be extremely
noticeable. Mechanics of digestion can include chemical digestion,
movements, ingestion absorption, and elimination. In order to maintain a
healthy and efficient digestive system, we have to remember the
components involved. If these are disturbed, digestive health may be
compromised.

### Urinary System

Toxic nitrogenous wastes accumulate as proteins and nucleic acids are
broken down and used for other purposes. The urinary system rids the
body of these wastes. The urinary system is also directly involved in
maintaining proper blood volume (and indirectly blood pressure) and ion
concentration within the blood. One other contribution is that the
kidneys produce a hormone (erythropoietin) that stimulates red blood
cell production. The kidneys also play an important role in maintaining
the correct water content of the body and the correct salt composition
of extracellular fluid. External changes that lead to excess fluid loss
trigger feedback mechanisms that act to inhibit fluid loss.

### Reproductive System

The Reproductive System is unique in that it does little to contribute
to the homeostasis of the organism. Rather than being tied to the
maintenance of the organism, the reproductive system relates to the
maintenance of the species. Having said that, the sex hormones do have
an effect on other body systems, and an imbalance can lead to various
disorders (e.g. a woman whose ovaries are removed early in life is at
much higher risk of osteoporosis).

### Excretory System

Excretory System is responsible for removing wastes, excess water and
salt in the urine. Regulates the volume and pH of the internal
environment. The human excretory system maintains homeostasis by
removing metabolic waste such as water, salt and metabolite
concentrations in the blood. The kidneys, which are the primary
excretory organs, are major organs of homeostasis because they excrete
nitrogenous wastes, and regulate water-salt balance and acid base
balance. This section will examine the kidney in details.

## Thermoregulation

The living bodies have been characterized with a number of automated
processes, which make them self-sustainable in the natural environment.
Among these many processes are that of reproduction, adjustment with
external environment, and instinct to live, which are gifted by nature
to living beings.

The survival of living beings greatly depends on their capability to
maintain a stable body temperature irrespective of temperature of
surrounding environment. This capability of maintaining body temperature
is called thermoregulation. Cold blooded animals, such as reptiles, have
somewhat different means of temperature regulation than warm blooded (or
homeothermic) animals, such as humans and other mammals. This section is
most relevant when considering warm blooded organisms.

Body temperature depends on the heat produced minus the heat lost. Heat
is lost by radiation, convection, and conduction, but the net loss by
all three processes depends on a gradient between the body and the
outside. Thus, when the external temperature is low, radiation is the
most important form of heat loss. When there is a high external
temperature, evaporation is the most important form of heat loss. The
balance of heat produced and heat lost maintains a constant body
temperature. However, temperature does vary during the day, and this set
point is controlled by the hypothalamus.

Body temperature is usually about 37.4°C, but does vary during the day
by about 0.8°C. The lowest daily temperature is when the person is
asleep. Temperature receptors are found in the skin, the great veins,
the abdominal organs and the hypothalamus. While the ones in the skin
provide the sensation of coldness, the hypothalamic (central core)
temperature receptors are the most important. The core body temperature
is usually about 0.7-1.0°C higher than axillary or oral temperature.

When body temperature drops due to external cold, an important component
of protection is vaso-constriction of skin and limb blood vessels. This
drops the surface temperature, providing an insulating layer (such as
the fat cell layer) between the core temperature and the external
environment. Likewise, if the temperature rises, blood flow to the skin
increases, maximizing the potential for loss by radiation and
evaporation. Thus, if you dilated the skin blood vessels by alcohol
ingestion this might give a nice warm glow, but it would increase heat
loss (if the external temperature was still low). The major adjustments
in cold are to shiver to increase heat production, and constrict blood
vessels in the periphery and skin. This helps to minimize heat loss
through the skin, and directs blood to the vital internal organs.

Besides the daily variation in body temperature, there are other cyclic
variations. In women, body temperature falls prior to ovulation and
rises by about 1°C at ovulation, largely due to progesterone increasing
the set point. Thyroid hormone and pyrogens also increase the set point.
The basal metabolic rate (BMR) is about 30 calories/sq m/h. It is higher
in children than in adults, partly as a result of different surface area
to body mass ratio. Due to this relationship, young children are more
likely to drop their temperature rapidly; there is greater temperature
variation in children than in adults. It is increased by thyroid hormone
and decreased by thyroid hormone lack. Different foods can affect BMR
and the Respiratory Quotient of foods differ. Carbohydrate 1.0; Protein
= 1.0; Fats = 0.7

## Body Composition

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Extracellular Fluid

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Cellular Fluid

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Volume

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plasma -- 3 litres

interstitial -- 10 litres

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30 litres

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290

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290

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140

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2.2

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110

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30

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4

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150

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1.5

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15

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2

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40

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pH

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7.4

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7.1

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Potential Difference (mV)

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\

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-70

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```
Blood pressure is expressed as two different numbers. The first number
is called the \"systolic\" blood pressure, and the second is the
\"diastolic\" blood pressure. Systolic blood pressure is the pressure at
the time of the cardiac cycle when the heart contracts, forcing blood
out(called systole). This is the time of greatest pressure. The
Diastolic number comes from the time in the cardiac cycle when pressure
is at its lowest, while the heart is refilling with blood. This phase is
called Diastole. The blood pressure in large arteries is about 120/80
mmHg. By the time this comes to the capillaries it has partly lost its
pulsatile nature and has a pressure of about 35 mmHg. The pressure falls
rapidly along the capillary to 15 mmHg at the venous end. This
hydrostatic pressure tends to force fluid out of the capillary into the
interstitium (the fluid between cells) but balance is maintained by the
colloid osmotic pressure (due to protein, principally albumin) of 26
mmHg. Net water movement is small (about 2%) and thus colloid osmotic
pressure is the same at the arterial and venous end of the capillary.

At the arterial end of the capillary there is a net outward force of
about 11 mmHg while at the venous end the net inward force is about 9
mmHg (ie. -9). There is an imbalance between water movement out and
movement back in which leads to an imbalance of about 3 litres/day,
which is removed as lymph. There is some albumin in the interstitial
tissue and it varies in different organs but the concentration may be up
to 10 or 20% of plasma. This gives an interstitial oncotic pressure
which causes movement of fluid into the interstitium. However the bulk
movement of water is not the way nutrients get to cells. Nutrients
diffuse down their concentration gradient as the capillary is very
permeable to all small molecules.

The extracellular volume is approximately thirteen litres in a seventy
kg person. Ten litres are in the interstitial space and three litres in
plasma. The capillaries are the interface between the two compartments
and are permeable to most substances with a molecular weight less than
20,000. Thus nutrients can readily diffuse across the wall and go from
blood to cell. Despite the high permeability of the capillary water is
maintained inside due to the oncotic pressure and only about 2% of the
plasma flowing through the capillary moves across the wall.

The blood volume is about 5 litres of which about 3 litres are plasma
and about 2 litres red blood cells. The red blood cell volume
(haematocrit) is about 43% and the relationship between plasma and blood
volume and haematocrit is Blood Volume = Plasma Volume 100/(100 - Ht).
Most of the blood is usually in the veins (70%).

Capillaries differ in their permeability throughout the body. Brain
capillaries are relatively impermeable due to tight junctions between
endothelial cells lining the blood vessels. This is known as the blood
brain barrier, or BBB, and helps prevent toxins from entering the brain.

In order of less permeability:

Brain \< Muscle \< Glomerulus \< Liver sinusoids.

The capillaries, while having a large surface area, only contain about
7% of the blood volume. The arteries and arterioles contain about 15%.
Most of the blood is in the veins.

## Body Fluid Distribution

The cell membrane is a bilipid layer that is permeable to water and
lipid soluble particles. However, it is impermeable to charged
particles. It is the osmolality controlling factor. Osmolality in the
cell and interstitial fluid are the same but the anionic and cationic
compositions differ. Made of albumin, the capillary membrane is
permeable to everything except proteins. The membranes in different
tissues differ. There are fenestrae (or pores) to promote better flow of
fluids. Particles weighing over 40,000 Daltons have low permeability. It
is the oncotic pressure controlling factor. Capillaries in the brain are
relatively impermeable while capillaries in liver sinusoids and
glomeruli are extremely permeable.

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```
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\

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Water (litres)

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Sodium (mmol)

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Potassium (mmol)

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Total

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43

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3700

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4000

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Intracellular

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30

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400

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\

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Bone

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\-

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1500

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300

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Extracellular

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13

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1820

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52

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Plasma

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3

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420

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12

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```
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Interstitial

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10

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1400

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40

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Usual Intake

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1.5

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180

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70

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Range

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0.7-5

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5-400

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50-400

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```
## Dehydration and Volume Depletion

Plasma osmolality is about 290 mosmol/l contributed mainly by sodium
(140 mmol/l) and it\'s accompanying anions. In dehydration water is lost
from the body. The rise in osmolality that occurs in the plasma (also
sodium rises) causes water to initially move out of the cells along the
osmotic gradient. Thus cell volume is initially reduced but cell
homeostatic processes subsequently return it towards normal by taking up
solute.

In dehydration water is removed from the plasma and thus haematocrit and
albumin which have not been lost will have a higher concentration. In
volume depletion water and electrolytes are both lost and thus there
will be little effect on either sodium concentration or osmolality. As
osmolality is not altered there will be no force to pull water out of
the cells and cell volume is not affected.

In volume depletion due to blood loss the haematocrit acutely is the
same but the resultant fall in blood pressure causes fluid to come out
of the interstitium into the vascular compartment and albumin and
haematocrit both decrease. When there is volume depletion due to
electrolyte and water loss by vomiting or diarrhoea there will be little
or no effect on plasma osmolality or sodium concentration. However there
will be a small increase in haematocrit and plasma albumin because the
volume is lost from the extracellular space and as blood cells and
albumin are not lost this increases the concentration.

In volume depletion forces are activated that retain sodium and water in
the body. The sodium retention works to a major extent by the
renin-angiotensin-aldosterone system which is activated by a fall in
blood pressure caused by volume depletion. In dehydration, the high
osmolality activates ADH secretion which causes water retention. As
there is also volume depletion, this activates the
renin-angiotensin-aldosterone system which causes sodium to be retained.
This retention would tend to cause a rise in sodium concentration which
is already high but the water retention would correct this. There is no
effective receptor that monitors and controls Na concentration by
altering sodium excretion. Sodium retaining hormones are predominantly
regulated by the volume and blood pressure. Initially in blood loss the
haematocrit is not altered but falls as fluid comes in from the
interstitial space.

## Water Balance

Vasopressin, also called Antidiuretic Hormone (ADH), is the principal
compound controlling water balance by decreasing water output by the
kidney, and thus decreased urination. It perceives the need by
monitoring plasma osmolality and if this is high, vasopressin is
secreted. Vasopressin is formed in the hypothalamus and travels down
axons to the posterior pituitary where it is stored.

Plasma osmolality is the usual factor regulating vasopressin release but
other factors alter the release. Pain and emotion release vasopressin
together with the other posterior pituitary hormone oxytocin. Alcohol
inhibits the release of vasopressin and thus causes a diuresis. A low
plasma volume also releases vasopressin which in high concentration can
cause vasoconstriction. These different factors can overcome the usual
physiological control of osmolality.

Osmoreceptors in the hypothalamus monitor the plasma osmolality and send
a signal down the axon that releases vasopressin from the posterior
pituitary gland. Vasopressin travels by the blood to the kidney and
binds to a receptor on the basolateral membrane and by a series of
cellular events alters the permeability of the luminal membrane to
water, thereby increasing the water permeability of the collecting duct
and due to osmotic gradients created in the kidney causes water to be
retained by the body (ie. an antidiuresis) which provides the other name
for vasopressin of antidiuretic hormone.

Vasopressin released by the pituitary binds to a receptor on the
basolateral membrane and activates adenyl cyclase which increases cyclic
AMP levels in the kidney. This by a series of reactions, some of which
involve calcium, cause microfilaments to contract and insert preformed
water channels (aquaporins) into the luminal membrane increasing water
permeability.

A high plasma osmolality is the important physiological stimulus causing
vasopressin release. Urea in plasma in a normal person only has a
concentration of 6 mmol/l and thus contributes to only a small part of
plasma osmolality. Even if plasma urea is elevated to 30 mmol/l it would
not have a significant effect on vasopressin release as membranes
(including those of the osmoreceptor cells) are permeable to urea. If
there is excessive ADH water is retained and the osmolality and sodium
concentration would fall (hyponatraemia). If there is no ADH water is
lost and osmolality and sodium concentration would rise
(hypernatraemia). While ADH is released if the plasma volume falls the
most important factor to restore volume is retention of sodium by the
renin-angiotensin-aldosterone and other salt retaining systems.

## Sodium Balance

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Amount

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Concentration

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Amount in body

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3700 mmol

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\

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Intracellular

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400 mmol

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15 mmol/l

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Extracellular

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1800 mmol

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140 mmol/l

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Plasma

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420 mmol

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140 mmol/l

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Interstitial

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1400 mmol

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```{=html}
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140 mmol/l

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Bone

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1500 mmol

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\

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Amount in diet

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\

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Hunter Gatherer

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20 mmol/day

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\

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Western

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180 mmol/day

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\

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Japanese

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```
300 mmol/day

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\

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Obligatory Need

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\< 5 mmol/day

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\

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```
Sodium is an important cation distributed primarily outside the cell.
The cell sodium concentration is about 15 mmol/l but varies in different
organs and with an intracellular volume of 30 litres about 400 mmol are
inside the cell. The plasma and interstitial sodium is about 140 mmol/l
with an extracellular volume of about 13 litres, 1800 mmol are in the
extracellular space. The total body sodium, however, is about 3700 mmol
as there is about 1500 mmol stored in bones.

The usual sodium intake of an Australian diet is about 180 mmol/d but
varies widely (50-400 mmol/day) depending on habit and cultural
influences. The body has potent sodium retaining mechanisms and even if
a person is on 5 mmol Na+/day they can maintain sodium balance. Extra
sodium is lost from the body by reducing the activity of the renin
angiotensin aldosterone system which leads to increased sodium loss from
the body. Sodium is lost through the kidney, sweat and faeces. In states
of sodium depletion aldosterone levels increase and in states of sodium
excess aldosterone levels decrease. The major physiological controller
of aldosterone secretion is the plasma angiotensin II level which
increases aldosterone secretion. A high plasma potassium also increases
aldosterone secretion because besides retaining Na+ high plasma
aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little
effect on aldosterone secretion.

A low renal perfusion pressure stimulates the release of renin, which
forms angiotensin I which is converted to angiotensin II. Angiotensin II
will correct the low perfusion pressure by causing constriction of blood
vessels and by increasing sodium retention by a direct effect on the
proximal renal tubule and by an effect operated through aldosterone. The
perfusion pressure to the adrenal gland has little direct effect on
aldosterone secretion and the low blood pressure operates to control
aldosterone via the renin angiotensin system.

In addition to aldosterone and angiotensin II other factors influence
sodium excretion. Thus in high sodium states due either to excess intake
or cardiac disease (+ others) atrial peptide is secreted from the heart
and by a series of actions causes loss of sodium by the kidney. Elevated
blood pressure will also tend to cause Na+ loss and a low blood pressure
usually leads to sodium retention. Aldosterone also acts on the sweat
ducts and colonic epithelium to conserve sodium. When aldosterone has
been activated to retain sodium the plasma sodium tends to rise. This
immediately causes release of ADH which causes water to be retained,
thus retaining Na+ and H2O in the right proportion to restore plasma
volume.

## Potassium Balance

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Amount

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Concentration

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Amount in body

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4000 mmol

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\

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```{=html}
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Intracellular

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3000 + mmol

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110 mmol/l

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Extracellular

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53 mmol

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4 mmol/l

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Plasma

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12 mmol

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4 mmol/l

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Interstitial

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40 mmol

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4 mmol/l

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Bone

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300 mmol

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\

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Amount in diet

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\

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\

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Hunter Gatherer

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200 -- 400 mmol/day

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\

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Western

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50 -- 100 mmol/day

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\

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30 -- 50 mmol/day

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Potassium is predominantly an intracellular ion and most of the total
body potassium of about 4000 mmol is inside the cells and the next
largest proportion (300-500 mmol) is in the bones. Cell K+ concentration
is about 150 mmol/l but varies in different organs. Extracellular
potassium is about 4.0 mmol/l and with an extracellular value of about
13 litres, 52 mmol (ie. less than 1.5%) is present here and only 12 mmol
in the plasma.

In an unprocessed diet potassium is much more plentiful than sodium and
is present as an organic salt while sodium is added as NaCl. In a hunter
gatherer K+ intake may be as much as 400 mmol/d while in the Western
diet it is 70 mmol/d or less if a person has a minimal amount of fresh
fruit and vegetables. Processing of foods replaces K+ with NaCl. While
the body can excrete a large K+ load it is unable to conserve K+. On a
zero K+ intake or in a person with K+ depletion there will still be a
loss of K+ of 30-50 mmol/d in the urine and faeces.

If there is a high potassium intake, e.g. 100 mmol, this would
potentially increase the extracellular K+ level 2 times before the
kidney could excrete the extra potassium. The body buffers the extra
potassium by equilibrating it within the cells. The acid base status
controls the distribution between plasma and cells. A high pH (ie.
alkalosis \>7.4) favours movement of K+ into the cells whilst a low pH
(ie. acidosis) causes movement out of the cell. A high plasma potassium
increases aldosterone secretion and this increases the potassium loss
from the body, restoring balance. This change of distribution with the
acid base status means that the plasma K+ may not reflect the total body
content. Thus a person with an acidosis (pH 7.1) and a plasma K+ of 6.5
mmol/l could be depleted of total body potassium. This occurs in
diabetic acidosis. Conversely a person who is alkalotic with a plasma K+
of 3.4 mmol/l may have normal total body potassium.

## Calcium and Phosphate Balance

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Interstitial (0.9%)

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270 mmol

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Cytoplasm

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\<1 mmol

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Cell organelles

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270 mmol

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Extracellular (0.1%)

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30 mmol

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2.2 mmol/l

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Plasma

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7 mmol

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2.2 mmol/l

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Interstitial

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23 mmol

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Bone (99%)

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27.5 mol (1.1 kg)

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1200 mg/day

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40 mmol/day

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300 mg/day

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300 mg/day

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100 mg/day

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3 mmol/day

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Calcium is a very important electrolyte. 99% or more is deposited in
bone but the remainder is importantly associated with nerve conduction,
muscle contraction, hormone release and cell signalling. The plasma
concentration of Ca++ is 2.2 mmol/l and phosphate 1.0 mmol/l. The
solubility product of Ca and P is close to saturation in plasma. The
concentration of Ca++ in the cytoplasm is \< 10-6 mmol/l but the
concentration of Ca++ in the cell is much higher as calcium is taken up
(and is able to be released from) cell organelles.

In the Australian diet there is about 1200 mg/d of calcium. Even if it
was all soluble it is not all absorbed as it combines with phosphates in
the intestinal secretions. In addition absorption is regulated by active
Vitamin D and increased amounts increase Ca++ absorption. Absorption is
controlled by Vitamin D while excretion is controlled by parathyroid
hormones. However, the distribution from bone to plasma is controlled by
both the parathyroid hormones and vitamin D. There is a constant loss of
calcium by the kidney even if there was none in the diet. The excretion
of calcium by the kidney and its distribution between bone and the rest
of the body is primarily controlled by parathyroid hormone.

Calcium in plasma exists in 3 forms. Ionized, non ionized and protein
bound. It is the ionized calcium concentration that is monitored by the
parathyroid gland and if low, parathyroid hormone secretion is
increased. This acts to increase ionized calcium levels by increasing
bone re-absorption, decreasing renal excretion and acting on the kidney
to increase the rate of formation of active Vitamin D, and thereby
increase gut absorption of calcium.

The usual amount of phosphate in the diet is about 1 g/d but not all is
absorbed. Any excess is excreted by the kidney and this excretion is
increased by parathyroid hormone. Parathyroid hormone also causes
phosphate to come out of bone. Plasma phosphate has no direct effect on
parathyroid hormone secretion. However if it is elevated it combines
with Ca++ decreasing the ionized Ca++ in plasma, thereby increasing
parathyroid hormone secretion.

## Case Study

**Heat stroke and Heat exhaustion**

If you have ever performed heavy manual labor or competed in an athletic
event on a very hot day, you may have experienced symptoms of heat
exhaustion. Typically these include an elevated core body temperature
(above 104F or 40C), profuse sweating, pale color, muscle cramps,
dizziness, and in some extreme circumstances, fainting or loss of
consciousness.

Heat exhaustion occurs as a consequence of disruption of the body\'s own
system of thermoregulation, the means by which it adjusts temperature.
Sweating is the principal means through which the body cools itself
down, but diverting blood from other regions toward the skin also serves
this purpose. Although sweat allows excess heat to dissipate as the
moisture reaches the skin surface, it can also have dangerous
implications for blood pressure and volume. As sweating increases, blood
volume can drop precipitously, meaning that the brain and other body
systems are at risk for insufficient oxygen and nutrient supplies.
Furthermore, diverting blood away from other systems and towards the
skin compounds the changes in blood volume and blood pressure induced
through sweating.

Heat stroke is a far more serious condition. This happens when the
body\'s temperature rises out of control due to the failure of the
thermoregulating system. If the body is unable to reduce its temperature
due to outside or physical influences, the brain will start to
malfunction. Delirium and loss of consciousness set in. The center of
the brain controlling the sweat glands will stop functioning, halting
the production of sweat. This causes the body\'s temperature to rise
even faster. Furthermore, with the increase of the body\'s temperature,
the metabolic process will speed up causing even more heat in the body.
If left untreated this will result in death. One of the easiest ways to
spot heat stroke is the skin. If it is flushed due to the increase of
blood flow but dry because the sweat glands have stopped secreting, the
individual will need prompt medical attention.

## Other Examples

-   Thermoregulation
    -   The skeletal muscles can shiver to produce heat if the body
        temperature is too low.
    -   Non-shivering thermogenesis involves the decomposition of fat to
        produce heat.
    -   Sweating cools the body with the use of evaporation.
-   Chemical regulation
    -   The pancreas produces insulin and glucagon to control
        blood-sugar concentration.
    -   The lungs take in oxygen and give off carbon dioxide, which
        regulates pH in the blood.
    -   The kidneys remove urea, and adjust the concentrations of water
        and a wide variety of ions.

Main examples of homeostasis in mammals are as follows:

-   The regulation of the amounts of water and minerals in the body.
    This is known as osmoregulation. This happens primarily in the
    kidneys.
-   The removal of metabolic waste. This is known as excretion. This is
    done by the excretory organs such as the kidneys and lungs.
-   The regulation of body temperature. This is mainly done by the skin.
-   The regulation of blood glucose level. This is mainly done by the
    liver and the insulin and glucagon secreted by the pancreas in the
    body.

Most of these organs are controlled by hormones secreted from the
pituitary gland, which in turn is directed by the hypothalamus.

## Review Questions I

Answers for these questions can be found here

1\. Meaning of Homeostasis:

A\) contributor and provider

B\) expand

C\) same or constant

D\) receiver

2\. What is the normal pH value for body fluid?

A\) 7.15-7.25

B\) 7.35-7.45

C\) 7.55- 7.65

D\) 7.00-7.35

E\) 6.5-7.5

3\. An example of the urinary system working with the respiratory system
to regulate blood pH would be

A\) When you hold your breath the kidneys will remove CO~2~ from your
blood

B\) If you exercise a lot your urine will become more acidic

C\) If you have emphysema the kidneys will remove fewer bicarbonate ions
from circulation

D\) If you hyperventilate the kidneys will counteract the alkalinity by
adding hydrogen ions into the blood stream

E\) None of the above-the urinary system never works with the
respiratory system

4\. The urge to breathe comes in direct response to:

A\) How long it has been since you last took a breath

B\) The oxygen concentration of your surrounding environment

C\) The build-up of nitrogen within your blood stream

D\) The pH of your blood

E\) The build-up of blood pressure that occurs when you don\'t breathe

5\. 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

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

7\. 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

9\. Select the *phrase(s)* below that best describe(s) homeostasis.

A\) Fluctuating within a homeostatic range

B\) Maintaining a constant internal environment

C\) Dynamic equilibrium

D\) Deviating

10\. In which part of the nephron does ADH act?

A)PCT

B)DCT

C)Loop of Henle

D)None

### Review Answers

-   1=C
-   2=B
-   3=C
-   4=D
-   5=A
-   6=D
-   7=A
-   8=B
-   9=B
-   10=B

## Glossary

-   **Control Center or Integration Center:** receives and processes
    information from the receptor
-   **Effector:** responds to the commands of the control center by
    either opposing or enhancing the stimulus
-   **Homeostasis:** refers to stability, balance or equilibrium
-   **Negative Feedback:** a reaction in which the system responds in
    such a way as to reverse the direction of change
-   **Positive Feedback:** a response is to amplify the change in the
    variable
-   **Receptor:** receives information that something in the environment
    is changing

fr:Cours de physiologie/Contrôle, régulation et
homéostasie
