Respiratory system 3 l1

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Essentials of Clinical Medicine
Session 17 Lecture 1 Homeostasis Peter Stanfield
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The concept of homeostasis and the internal
environment
The concept of homeostasis is the central dogma
of physiology.
Most physiological quantities components of the
internal environment - are controlled between
relatively strict limits.
Loss or alteration - of this homeostatic
control occurs in disease. In normal physiology,
loss of homeostatic control occurs only in
extreme (external) environments.
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Origins of the concept of the internal
environment and its homeostasis
Claude Bernard
The constancy of the internal environment is the
condition for a free and independent life.
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Origins of the concept of the internal
environment and its homeostasis
The term homeostasis was introduced by WB Cannon
in 1932
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Origins of the concept of the internal
environment and its homeostasis
The coordinated physiological processes which
maintain most of the steady states in the
organism are so complex and so peculiar to living
beings that I have suggested a special
designation for these states homeostasis. The
word does not imply something set and immobile, a
stagnation. It means a condition a condition
which may vary, but which is relatively constant.
WB Cannon The Wisdom of the Body (1932)
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The concept of homeostasis and the internal
environment

• If control of the internal environment exists
  there must be mechanisms capable of exerting it.
• The physiological quantity must be sensed
• while the external environment is sensed by
  exteroceptors (including the special senses),
  the internal environment is sensed by
  interoceptors.
• Means must exist for correcting errors in this
  quantity
• involving an inbuilt notion of the correct value
  a set point
• action through the nervous and endocrine
  systems to correct errors.
• There must be balance between input and output.

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The concept of homeostasis and the internal
environment
Comparator
Set point
Often the nervous system
Often the nervous or endocrine systems
Sensor
Effector
Controlled quantity
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The reflex arc is one building block for
homeostatic control
Integrates multiple inputs
afferents carry information to the CNS
reflex centre within the CNS
efferents carry information from the CNS to
effector organs
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The reflex arc is one building block for
homeostatic control
Usually in homeostatic control the efferent limb
of a reflex arc belongs to the autonomic nervous
system

• The autonomic nervous system has two divisions
• sympathetic
• parasympathetic

See Mike Stansbies lecture in session 14 more
later in semester 2
The sympathetic division has the wider
distribution and is the more important in
homeostasis.
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The endocrine system also underlies homeostatic
control
Endocrine glands release hormones into the blood
stream
The pituitary gland links nervous action and
control of the output of hormones
cell of an endocrine gland
Capillary of the blood supply of the gland
( related terms are paracrine, where released
agents act on neighbouring cells, and autocrine,
where agents acts on the cell that secretes the
agent.)
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The concept of homeostasis and the internal
environment
Take as an example control of body fluid levels
volume and composition are vital for normal
physiological activity, including normal
excitability of nerve and muscle as well as for
the maintenance of the output of an appropriate
volume of blood by the heart.
Later this session deal with control mechanisms
controlled quantities are osmolality and volume
This lecture expands concepts of the
compartmentalisation of body fluids and the
equilibrium between these compartments
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Water and saline are distributed differently and
dealt with by different mechanisms
changes osmolality
changes volume of ECF and Na balance
From G Pocock CD Richards Human Physiology
The Basis of Medicine 3rd Edition 2006 Fig 28.1
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The concept of homeostasis and the internal
environment
Comparator
Set point
Often the nervous system
Often the nervous or endocrine systems
Sensor
Effector
Controlled quantity
Different sensors and effectors involved in
handling water and saline loads
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Water compartments in health

• 60 body weight is water 42 litres
•   Divided into two major elements
• ICF 40 of body weight 28 litres
• ECF 20 of body weight 14 litres
• ECF is divided into
• Interstitial 10 litres
• Intravascular/plasma 3 litres
• Transcellular Secretions, eg CSF 1 litre

Figures are for a 70kg (154lb) male women
typically have 50 of body weight as water, with
intracellular water at 30 of total body weight.
CSF cerebrospinal fluid
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Water compartments in health
Extracellular fluid (ECF) 14
Plasma
Interstitial fluid
Secretions
Intracellular fluid (ICF)
1
3
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10
Total body water 42
Equilibrium exists between the fluid
compartments cells do work to produce secretions
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The concept of balance of body water
We take in and give out variable amount of water
during the day. But these variable amounts must
balance each other.
IN (ml.day-1) Drink 1600 Food
500 Metabolism 500 Total 2600
OUT (ml.day-1) Urine 1500 Faeces 100 Skin
500 Lungs 500 Total 2600
Through saturation of expired air with water
vapour
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Intake of fluid and output of urine are the
controlled quantities
But the threat to homeostasis may come from other
elements.
For example In a hot, dry environment,
evaporative losses through sweating and through
adding water vapour to expired air may become
severe. In diarrhoea, faecal losses become
severe. In cholera may lose several litres of
fluid each day, leading to circulatory collapse
and rapid death.
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The balance of body sodium
Similarly with sodium as Na - there is a need
to balance intake and output. However this can
be more difficult to achieve
OUT 10 15 g.day-1 Urine controlled
physiologically Faeces Sweat
IN (in diet) 10 15 g.day-1
Intake of Na is greater than required as the
minimum (0.5g.day-1), and greater than what is
recommended (lt6g of NaCl.day-1)
Equivalent to 2.4g Na
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The concept of osmolality

• The osmotic pressure of a solution is measured
  clinically as its osmolality
• It gives a measure of the number of osmotically
  active particles dissolved in one kg of solvent
  (water).
• Extracellular fluid plasma, interstitial fluid
  typically has an osmolality of 300mOsm.kg-1
  (per kg of H2O).
• Contributed principally by electrolytes (NaCl
  etc), which dissociate in solution (NaCl to Na
  and Cl-), but also by non electrolytes such as
  glucose, protein etc.
• In cytoplasm, a higher fraction of the
  osmolality (300mOsm.kg-1) is contributed by non
  electrolytes.
• A solution of osmolality 1 Osm.kg-1 exerts an
  osmotic pressure equivalent to 22.4 atmospheres
  (2300kPa or 17000 mm Hg).

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The equilibrium between compartments
The equilibrium between the cellular and
interstitial fluid is principally osmotic. If
the osmolality of extracellular fluid is lowered
by absorbing water from the gastrointestinal
tract water will move into cells to maintain
osmotic equilibrium The equilibrium between
interstitial fluid and plasma is determined by
osmotic pressure and hydrostatic pressure
differences. Gravity can contribute to
considerations of hydrostatic pressure
differences, increasing these pressures eg in
dependent limbs.
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In osmotic terms, cells are in equilibrium with
the interstitial fluid that surrounds them
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The equilibrium between interstitial and
intracellular fluid
Three principles to bear in mind 1. There will
be osmotic equilibrium between the
compartments. 2. The total number of positive
charges on cations will be balanced by the
total number of negative charges on anions
both in the intracellular and the interstitial
fluid. 3. If an ionic species can permeate the
cell membrane, these permeant ions will move
towards equilibrium.
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How is an equilibrium established between
interstitial and intracellular fluid?
Consider a condition where the first two of these
conditions are met
cell
extracellular
K
K
Organic anions A-
Cl-
Is this situation stable?
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How is an equilibrium established between
interstitial and intracellular fluid?
Not stable if K and Cl- are able to permeate the
cell membrane
cell
extracellular
K
K
2. K will follow
Impermeant organic anions A-
1. Cl- will move in
Cl-
3. H2O will also move to maintain osmotic
equilibrium
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How is cellular swelling avoided?
Cell volume is stabilised with Na as the
principal cation of the extracellular space
held there by its relative impermeance and by
active transport
cell
extracellular
K
K
Na
Na
Cl-
Cl-
Organic anions A-
Stable if A- cannot permeate Na is kept out of
the cell by the Na-K ATPase.
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How is an equilibrium established between
interstitial and intracellular fluid?
Tendency for Cl- to move in is balanced by the
tendency for K to move out
cell
extracellular
K
K
Na
Na
Cl-
Cl-
Organic anions A-
Donnan equilibrium
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How is an equilibrium established between
interstitial and intracellular fluid?
Are there situations where this equilibrium is
upset?
Physiologically, cells of the kidney are exposed
to considerable variations in osmolality and
electroyte composition. If Na-K ATPase is
blocked - by cooling or by cardiac glycoside a
drug that blocks the ATPase In open heart
surgery, the heart may be paralysed by perfusing
it with a cardioplegic solution containing high
KCl. (What effect will cardioplegic solutions
have on cell volume?)
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What are the actual ionic concentrations?
Concentration in mmol.l-1
cell
extracellular
K
4
160
K
10
Na
Na
150
3
Cl-
Organic anions A-
Cl-
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Other ions, including HCO3-, Ca2 and Mg2 , make
up the balance of charges and the osmotic
pressure of solutions
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Equilibrium between plasma and interstitial fluid
is determined by osmotic forces and by
hydrostatic pressure differences. Equilibrium is
established in capillary beds.
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Capillary beds are the site of exchange between
blood and metabolising tissues
From JB Kerr Atlas of Functional Histology Fig.
7.10b
Capillaries are thin-walled and permit
electrolytes and water to move downhill between
blood and tissues. Most capillaries are
impermeable to plasma proteins.
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The osmolality of plasma is contributed by two
components
Overall osmolality is 300mOsm.kg-1
Most (gt99) is contributed by electrolytes -
crystalloid osmotic pressure
A small amount (0.3) is contributed by plasma
protein - colloid osmotic pressure or oncotic
pressure. In units of mm Hg, used in cardiology,
this equates to 25mm Hg.
But the blood in capillaries is also under
pressure owing to the pumping action of the
heart.
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Impermeance of plasma proteins generates a
colloid osmotic pressure
Colloid osmotic pressure draws fluid into
capillaries from interstitial space
arteriolar
venular
Colloid osmotic pressure 25mm Hg
This simplifies there is some protein in
interstitial fluid
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However, hydrostatic pressure tends to force
fluid out of the plasma across capillary walls
arteriolar
venular
hydrostatic pressure 35mm Hg
capillary
hydrostatic pressure 15mm Hg
filtration of plasma
This also simplifies there are effects of
gravity increasing hydrostatic pressures in
organs below the heart
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Equilibrium between plasma and interstitial fluid
Filtration pressure hydrostatic pressure
colloid osmotic pressure
arteriolar
venular
 
filtration at arteriolar end
colloid osmotic pressure 25mm Hg
hydrostatic pressure 15mm Hg
hydrostatic pressure 35mm Hg
reabsorption at venular end
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Errors in this equilibrium may result in oedema.

• Loss of oncotic pressure gradient
• Loss of plasma protein in
• starvation,
• liver disease,
• kidney disease.
• Alterations of capillary permeability for
  example in anaphylaxis

Alterations of hydrostatic pressures Cardiovascula
r disease especially in heart failure, where
venous pressures rise
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Pitting oedema interstitial fluid is a gel
From G Pocock CD Richards Human Physiology
The Basis of Medicine 3rd Edition 2006 Fig 28.10
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Pitting oedema interstitial fluid is a gel
Interstitial space contains collagen, salts of
hyaluronic acid, and proteoglycans. Hydrated
hyaluronates and proteoglycans form a
gel. Interstitial fluid does not trickle through
the body under the influence of gravity. Indeed
oedema for example associated with heart
failure is described as pitting oedema.
From G Pocock CD Richards Human Physiology
The Basis of Medicine 3rd Edition 2006 Fig 28.10
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Secretion and secretion pressure

• Note that movements between interstitial fluid
  are downhill, so that the electrolyte composition
  of the compartments will be similar.
• Transcellular fluids are usually secretions
  CSF, aqueous humour etc. These are formed by
  cells doing work.
• The electrolyte composition will in general not
  be the same as that of interstitial fluid.
• Further, a secretion pressure can be developed.
• Failure of normal drainage leads to an increase
  in pressure. Eg
• CSF hydrocephalus
• Aqueous humour - glaucoma

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To summarise

• Homeostasis central to understanding
  physiology consider systemic regulation of
  body fluids in lecture 2.
• Body fluids are compartmentalised.
• These compartments are in equilibrium with
  each other, particularly in terms of their
  osmotic pressure.
• Impermeant cellular anions and active
  transport of Na affect the distribution of
  other, permeant ions (K and Cl-).
• Interstitial fluid and plasma are in
  equilibrium because of the balance of
  hydrostatic and osmotic pressure gradients.
• Secretion involves cells doing work, altering
  ionic composition and generating a secretion
  pressure.