Internal environment. Body fluids.

Homeostasis

I. The cell, base of our body

Cells are the basic level of human body. Each cell type is adapted to perform some specific
functions. All the different types of human cells come from the ovum and share
characteristics that are alike and the chemical reactions for transforming nutrients into
energy and structural molecules are the same in all the cells.

 Levels of structural organization

They are different level of organizaton :
Atom, Molecule (or compound), Organelle, Cell, Tissue, Organ, Organ system, Organism
Or even better :
Atom, Molecule (or compound), Organelle, Cell, Tissue, Organ, Organ system, Organism, Population,
Community, Ecosystem
1. Atomic and Molecular level
Studied by the Biochemistry includes glucids, proteins, lipids, nucleic acids… and mostly water
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2. Cellular level
Studied by the Biology. Cells are the basic functional structures of the human body. They are 5 types
3. Tissue level
Specific aggregation of cells with the same function. Includes muscular, epithelial, nervous and connective.
4. Organ level
Structures composed by more than one type of tissue, clearly individualized in the body
5. System level
Group of organs with a common function. Respiratory, renal, reproduction, circulatory, skeletal systems.
6. Organism level
Each human is an organism functioning independently

Types of cells according with transcriptional programs in cells

1. Epithelial 2. Neuronal 3. Endothelial 4. Mesenchymal 5. Blood cells
 II. Internal environment

1. A brief chronology of Life

Life started in water, in the primitive oceans, millions of

years ago
Oxygen was at the beggining not present in the
atmosphere. But was in the oceans in water and as
byproduct of cyanobacterial photosynthesis, but was
sucked up by microbes, iron in ferrous form and other
sinks.
Around 2.330.000 millions of years ago, oxygen
concentration increased suddently in the atmosphere
and the oceans : it was the Great oxygenation event
This initial rise in atmospheric oxygen set off a cascade
of events that would ultimately lead to the advent of
multicellular life.

2. Extracellular fluid
Cell requirements to survive includes being immersed in water with different molecules and atoms. It is
also named the extracellular fluid and represent about 1/3 of the the body fluid (composed of a water
solution of ions and other molecules as glucose, amino acids or vitamins). The rest of the body fluid is
inside of the cells. Globally, the body fluid represents around 60% of the human adult body.
The extracellular fluid is in constant movement. It is divided in four subcompartments :
1. interstitial fluid (represents 16-20% of the body weight)
2. plasmatic fluid (only 4-7% of the body weigth)
3. lymphatic fluid (2% of the body weight) and Internal environment
4. transcellular fluid (enclosed in special compartments or chambers lined by epithelial cells) : cerebro-
spinal fluid and endo and perilymph; peritoneal fluid; intra-ocular fluids.

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 3. Differences between extra and intracellular fluids
The extracellular fluid contains large amounts of sodium, chloride, and bicarbonate ions plus oxygen,
glucose, fatty acids, and amino acids. It also contains carbon dioxide, plus other cellular waste products.
The intracellular fluid contains large amounts of potassium, magnesium, and phosphate ions. Special
mechanisms for transporting ions through the cell membranes maintain the ion concentration differences
between the extracellular and intracellular fluids.

Extracellular compartment : 3+13+1= 17 L of water

Sodium and chloride ++++
Osmolarity : 290 mOsm.L-1
Interstitial fluid : NO PROTEINS (except in the transcellular fluid)

Intracellular compartment : 25 L of water

Potassium ++++
Osmolarity : 290 mOsm.L-1
Thebody
For 70 kg human osmolarity
: on both sides of membranes must be kept constant

- 60% of water : as 1L=1kg in Standard Temperature and Pressure conditions (STP conditions), we can
do this approximation, 0,6x70≈ 42 L of water
- 30% of other coumpounds
N.B : as we are in STP conditions and as the solutes concentrations are very low, we can say that
osmolaLity (Osm.kg-1)≈osmolaRity (Osm.L-1)
Mainly, the sharing of information between organs or between cells takes place at the level of atoms or
molecules. Cell-to-cell or intracellular messengers may be as simple as ions or may also be more complex
chemicals. A cell may release a molecule that acts on a neighboring cell or that enters the bloodstream and
acts on other cells a great distance away.
In other cases, a neuron may send an axon away and rapidly modulate, through a neurotransmitter
molecule, the activity of another cell or another organ. Cells and organs must interact with one another,
and the method of communication is almost always molecular.

III. Homeostasis

1. Definition
Our organism is maintaining a nearly constant conditions in the internal environment which is called
homeostasis since 1929 when Cannon described it. Human body carefully controls a long list of vital
parameters to assure the organism survival and good development.

All organs and tissues of the body perform functions that help maintain these relatively constant conditions. Tightly
regulated parameters include body core temperature and plasma levels of oxygen, glucose, K+, Ca2+, and H+.
Homeostasis also occurs at the level of the single cell

2. How is managed it ?
At the cellular level there are several mechanisms of transport of molecules through the membranes. They include
simple diffusion, facilitated diffusion, active transport, and osmosis.

At the tissue, organ, systemic and organismal levels there are feedback mechanisms responsible of homeostasis.
Most of them are negative-feedback mechanisms.
 3. Properties of Homeostasis

 In mammals the endocrine and the nervous system are essential for regulation
 Level of tonic activity : there is a level of activity of the organism that could be increased or
decreased modulated by part of the nervous system
 Antagonic controls : if there is a molecule that affects the levels of other molecule, could be
another molecule with the opposite effect
 A molecule can have different effects in different tissues
 Homeostasis is a constant and continuous process that implies the record and regulation of multiple
parameters
 The degree of efficiency of the mechanisms of homeostasis changes through the life of the living
beings. Aging is the most disabling process in healthy conditions, but starvation and others can
modify the capacity of recovery
 The failure of Homeostasis produces illness

4. Exemple of dopamine functions

Dopamine as neurotransmitter : 1. activator of the pleasure and reward system (addictions) 2. mood 3.
behaviour and condition activator 4. inhibitor of movement 5. sleep trigger. 6. excitatory effect in learning
Dopamine functions as hormone : 1. vasodilatation (which stimulates the volume of urine excreted)
2.inhibitor of prolactin release 3.reduces the synthesis of insulin 4.induces as paracrine hormone an
increment of urinary sodium excretion due to inhibition of sodium reabsorption in the tubules.

5. Feedback systems 6
a. Negative-feedback system
A negative feedback system requires at least 4 elements :
1. a sensor of the levels of the controlled parameter or receptor
2. have a way to compare the input signal with an internal reference value named set-point
3. the system should be able to multiply the signal to produce a response together with the previous one
constitutes the control center
4. an effector mechanism activated by the control center and able to brings the value closer to the set-
point
 b. Positive feedback system
Sometimes the body controls a parameter by a positivefeedback loop. But this is unusual, because positive
feedback leads to instability, increasing a substance or response and, sometimes, can produce the death of
the subject. It is for that called vicious cycle. Sometimes, as in blood clotting, positive feedback results very
useful: the presence of a clot produced by an injury, causes a positive feedback that stimulates clotting
factors to finish bleeding. Also is useful the positive feedback for the generation of nerve signals triggering
action potentials or intracellular cascades

c. Feedback control
Many times feedback loops operate as part of a larger network of controls. Thus, a complex interplay may exist
among feedback loops within all the levels of the body. Could be proven that two or more feedback loops act either
synergistically or antagonistically. For example, insulin lowers blood glucose levels, whereas epinephrine, glucagon
and cortisol have the opposite effect. Thus, must be determined the relative weights of feedback loops in
competition with one another

d. Glucose loops competition example

e. Important concepts

 Hierarchy : If there are different loops, always one of them is the dominant over the others.
Sometimes the body controls a parameter by a positive-feedback loop.
 Redundancy : As more important for life is a parameter, higher the number of systems or loops to
regulate it. The consequence is an internal environment with a stable composition.
 Equilibrium : Could be consider the state that not involve energy consumption. A well-regulated
parameter is in a steady state. (the value is constant because the actions that raise its
concentration make equal to the ones lower it).
 Each cell plays a specialized role in the overall function of the body. The organisms provides the
internal environment appropriate for the life of each cell. For that, are required:
- priority
 - adaptability through flexible feedback loops
- acclimatization some feedback systems express when the external environment forces the
system
- genome some people have better genes

f. Adaptative control
Includes some simple feedback system and other sophisticated one. The adaptive control uses next trial to
improve the performance and it is, in some way, a delayed negative feedback system. The system is used
for the brain in the perfection of movements (like in dance) through the feed-forward control. The
modification in the features of movement are done next time is performed.

6. Control of Homeostasis in the organism

Normal body functions require the integrated actions of cells, tissues, organs, and the multiple nervous,
hormonal, and local control systems that together contribute to homeostasis
Extracellular fluid is transported through the body in two stages: 1. The movement of blood through the
body in the blood vessels, 2. The movement of fluid between the blood capillaries and the intercellular
spaces between the tissue cells.
The walls of the capillaries are permeable to most molecules in the plasma of the blood, but not to plasma
proteins. Fluid and its dissolved molecules diffuse back and forth between the blood and the tissue spaces,
due to kinetic motion of the molecules in both the plasma and the interstitial fluid. The extracellular fluid
everywhere in the body maintains its homogeneity.
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7. Every organ or tissue contributes to homeostasis

a. Respiratory system
All the blood goes to the lungs where through the alveolar membrane oxygen diffuses to get incorporated
in the hemoglobin and carbon dioxide, the most abundant metabolic product in humans, is release inside
of the alveoli.

b. Digestive system
In the gastrointestinal system are absorbed from the food eaten fatty acids, amino acids and
carbohydrates. Undigested food, fibre, and some waste metabolic products are eliminated by feces.
Growing evidences indicates that the intestinal microbiome has an important product in homeostasis and
immune system

c. Liver, kidneys and other organs with metabolic functions

They take substance from the extracellular fluid and process them, store them or also excreted them. The
liver detoxificats substances to their elimination in the feces and the kidneys excretes them by urine and
controls the electrolytes’ concentration; regulating in a complex team with the lungs the pH and the
concentration of gases

d. Musculoskeletal system
It provides motility to reach the food, facilitates the scape from adverse environments, and form part of a
cycle to generate glucose and reduce the excess of nutrients through exercise.

e. Nervous system
It has 3 portions: the input that receives information; the central system that integrate and processes data;
the output that generates responses. The three of them have a conscious part and a subconscious one
named autonomic nervous system.

f. Hormonal system
There are 8 main endocrine glands that secrete substance to blood called hormones to regulate
homeostasis. Each year new hormones are discovered
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g. Reproduction system
It is maintaining the survival of the species

h. Immune system
Provides the mechanisms for: a) distinction between structures of the organism and external substances
and cells b) capacity of defense against microbiome and molecules through cells or substances secreted by
cells of the system. A growing number of evidences prove that the microbiome have an effect in the
homeostasis of the defensive system.

i. Integumentary system
Several structures (skin, mucous, hair…) cover, cushion, protect internal organs, contributes to the
temperature’s control and excretion of wastes and provides a sensory interface with the exterior. The skins
represents around 15% of body weight

IV. Allostasis

1. Definition
In more developed organisms, to the systems of the cells is added a superior control of homeostasis able
to coordinate a final organic response. This is called allostasis, that is not so dependent of the external
media since all the tissues coordinate a constant internal environment.
Allostasis (proposes by Sterling and Eyer’s in 1988) reflects the process whereby in order to be adaptive,
organisms must be able to change the defended levels of one or more regulated parameters as needed
to adjust to new or changing environments. Allostasis explains the human’s answer in front of the
environment and a big size of the energy’s consumption. The acquisition, utilization, and storage of energy
reserves (and other resources) are critical to lifetime reproductive success. The set points are variable.

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2. Type 1 allostatic overload

Occurs when energy demand exceeds supply, resulting in activation of the emergency life history stage. This serves
to direct the animal away from normal life history stages into a survival mode that decreases allostatic load and
regains positive energy balance.

3. Type 2 allostatic overload

Begins when there is sufficient or even excess energy consumption accompanied by social conflict and
other social dysfunctions. It is the case in human society associated with secretion of glucocorticosteroids
and activity of other mediators of allostasis such as the autonomic nervous system, CNS neurotransmitters,
and inflammatory cytokines wax and wane with allostatic load.
If allostatic load is chronically high, then pathologies develop. Type 2 allostatic overload does not trigger an
escape response, and can only be counteracted through learning and changes in the social structure.

4. Allostasis vs Homeostasis
Control (homeostasis) refers to the process of activating (or deactivating) effector responses that regulate or
stabilize a variable, either by reversing a perturbation that has already occurred and been detected by a sensor 11
(effectors activated via negative feedback control) or by preempting and thus helping circumvent or minimize an
impending perturbation (effectors activated by anticipatory control).

Allostasis in a regulatory system means that deviations (or anticipated deviations) of regulated variables are
detected and trigger effector responses which counter (or mitigate) the deviation, and it is this property that
distinguishes regulation from a passive steady-state.
Allostatic load and overload are terms that refer to the cumulative effects of chronic stress and a lifestyle that is
related to coping with stressful experiences.

V. Reostasis or Homeorheusis in human body

The initial thought was homeostasis as a self-regulating negative feedback system which maintains constancy of the
internal environment. Most contemporary views understand that reliance upon negative feedback systems that do
not get activated until a perturbation of the regulated variable occurs is inefficient and fails to encompass much of
regulation.
Set point is used to indicate that a regulatory system operates ‘as if’ there was an engineering type of set point or
reference signal using behavioral and/or physiological responses. When the regulated variable is at a value where all
effectors are at basal levels of activity, this would be considered the null point or the set point.

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Changes in the level of the variable around which regulation occurs are known as rheostasis, a term proposed by
Mrosovsky in 1990, where there is a higher order of control in which change is regulated rather than maintaining
levels of a substance. Sensory information indicating a challenge to the regulated variable not only provides an
excitatory input that activates corrective effector responses, but also provides inhibitory input to the opposing
effectors.

The coordination of responses in homeostasis are the result of a controller or command center in the central
nervous system that directed the harmonious activation or deactivation of responses subserving the defense of one
or another regulated parameter and coordinates responses with regard to each variable’s set point, and how best to
cope with the magnitude of ongoing or potential perturbations.

And it is controlled through proteins. In the case of weight, the melanocortin 3 receptor (MC3R) maintains "energy
rheostasis,"when the metabolism is challenged, mice without this protein lose more weight when fasting and gain
more weight when eating a high-fat diet, compared with normal mice.

(MC3R) also plays a role in regulating changes in the body's energy balance that occur as part of the normal life cycle.
During both pregnancy and menopause, females experience an increase in the amount of fat reserves stored in the
body.

VI. Summary
Nature tents to repeat structures in order to organize trillions of individuals: atoms in molecules, cells in
organs and tissues, small animals in apparent a whole structure, ants and bees in anthills and hives… all of
them requires specialization.
To maintain the order and hierarchy, cells have to specialize and only express some of the potential
functions and have to be coordinated, regulated by positive and mainly negative feedback systems.
This process assures the right internal environment for the survival and right performance of the organism.
Is the homeostasis
Dysfunctions generates problems: if there are moderate develop sickness and if there are extreme produce
the death of the subject.
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