LECTURE - 4

Continued from Lec- 3

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When faced with unusually heavy demands

Ordinary homeostasis is not enough
because homeostat
is raised beyond its capacity,
perhaps to
a higher level of function
Resetting :
Essential function for Long Term Survival

Hans Selye
1956

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heterostasis
Physiology

homeostasis

reactive

predictive

Anticipatory adaptationReaction to immediate

Anticipates & modulates in
Physiological demands
context of future needs &
Regulation of
Resource allocation

BP, pH, Temp

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PRIOR
KNOWLEDGE

PREDICTION

SET
POINT

EFFECTOR
SENSOR

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CONTROLLED
VARIABLE
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Example
Variations of blood pressure
- Morning when you get out of bed
- Blood pressure rises
- Blood flow to brain maintained when
you stand up to maintain oxygen
tension in brain
Unsatisfactory social interaction
- Neural signals: sustained: Essential
Hypertension, Type II Diabetes
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Allostasis
Stability through change
Goal of regulation is not constancy
It
is fitness under natural selection
Prior information predicts demand
Adjust all parameters to meet that
demand
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ALLOSTASIS
INVOLVES WHOLE BRAIN AND
BODY RATHER THAN SIMPLE
LOCAL FEEDBACK
FAR MORE COMPLEX FORM OF
REGULATION THAN
HOMEOSTASIS

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ADAPTATION

ACCLIMATIZATION

ACCLIMATION
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Acclimatization or acclimation
is the process of an organism adjusting to change in its environment
, allowing it to survive changes in temperature, water and food
availability, other stresses and often relates to seasonal weather
changes.
acclimatization occurs in a short time, (days to weeks) and within
one organism's lifetime (compare adaptation).
this may be a discrete occurrence or may instead represent part of a
periodic cycle, such as a mammal shedding heavy winter fur in favor
of a lighter summer coat.
acclimation is an important characteristic among many organisms
because it allows them to evolve over time while changes are also
simultaneously occurring in their environment.
organisms adjust their morphological, behavioral, physical, and/or
biochemical traits in response to these environmental changes that
they are faced with.

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 HIGH ALTITUDE
naturally acclimatize to new environment by
developing an increase in the number of
red blood cells to increase the oxygen
carrying capacity of the blood, in order to
compensate for lower levels of oxygen in
the air

HEAT- Desert
body make internal adjustments to compensate for
the change in environmental conditions. A heat
acclimatized person will begin to sweat earlier and
more intensely under heat, have a lower heart
rate, and a lower skin temperature. The salt
content of sweat also decreases as people
acclimatize
If people do not acclimatize, then the person is at
higher risk of heat related injuries (heat stroke,
heat cramp).
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Adaptation
the process whereby a population
becomes better suited to its habitat.
this process takes place over many
generations,and is one of the basic
phenomena of biology
The ability to acclimatize is an
adaptation

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pathologic
stimuli

physiological
stress

cell

Adaptation..
Achieves a new steady state
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Preserves
viability
Physiology

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12

hypertrophy

hyperplasia

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hypertrophy

Ventricular hypertrophy
the increase in size of the
ventricles of the heart.

is the increase
in the volume of
an organ or
tissue due to
the
enlargement of
its component
cells.
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1.aerobic or
anaerobic exercise changes can be
beneficial or healthy

Physiology

2.
high blood pressure
or other disease
states pathological
changes14

hyperplasia
Pregnancy Growth and
multiplication of milksecreting glandular cells in
the breast future
breast feeding.

Hyperplasia of the
breast
A focal expansion of the
number of cells in a breast
duct, associated with an
increased risk of developing
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breast cancer.

Normal

Abnormal

15

 Hypertrophy and hyperplasia are two

distinct process, they frequently occur
together,
Example:hormonally-induced proliferation
and enlargement of the cells of the uterus
during pregnancy.

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metaplasia
Some insult or injury
The transformation of one type of
mature differentiated cell type into another
mature differentiated cell type,
as an adaptive response
By such a change in differentiation
(and hence patterns of gene expression)
the cells are more resistant to the effects of the insult.
It is usually a reversible phenomenon.
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Details from Pathology

atrophy
Partial or complete wasting away of a part of the body.
Causes include poor nourishment, poor circulation, loss of
hormonal support, loss of nerve supply to the target organ,
disuse or lack of exercise or disease intrinsic to the tissue
itself.
Physiological process of breakdown of tissues,
involving apoptosis on a cellular level.
Pathological atrophy -- occurs as a result of disease or
loss of trophic support due to other disease,
As part of normal development --- shrinking and
involution of the thymus in early childhood and the
tonsils in adolescence.
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Principal Adaptive Responses

hypertrophy
hyperplasia
metaplasia
atrophy
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Apoptosis is one of the

main types of programmed
cell death which involves a
series of biochemical
events leading to specific
cell morphology
characteristics and
ultimately death of cells.
Genetically controlled mechanisms of cell death involved in the
regulation of tissue homeostasis.
The 2 major pathways of apoptosis
the extrinsic (Fas and other TNFR superfamily members and
ligands) and
the intrinsic (mitochondria-associated) pathways,
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both are

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found in theScytoplasm.

20

Ageing
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Biological clock:
the bodyguard of temporal homeostasis .
the timing of the
bodys biological
functions

CRUCIAL

organism to function
properly

Suprachiasmatic nucleus

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www.glimmerveen.nl/le/biological_clock.html

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Doctors should listen to the rhythm of an

illness
We should better stay in bed in the morning for that is a
dangerous time: most heart attacks happen in the morning
shortly after getting up.
Many diseases show a clear rhythm (rheumatism, migraine,
asthma etc). Also the result of therapy can be very different
depending on the cycle: when a woman with breast cancer is
operated during the second half of her cycle, the chance to get
it back is 25%, when the surgery is done during the first half it
is 37%. But it is still rarely so that the planning of the treatment
is made according to this knowledge.
The effectiveness of drugs can depend on the time of day they
are taken. Both the effect and the side effects can be very
different depending on the moment of taking them. Slowly
some insight in these rhythms is growing, but doctors find it
often difficult to take in consideration.
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TIGHT
JUNCTIONS

cell-cell
connections

DESMOSOMES
NEURAL

GAP
JUNCTIONS

NEURO
ENDOCRINE
ENDOCRINE

cell-cell
communication

AUTOCRINE
PARACRINE
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TIGHT
JUNCTIONS
Tightly stitched seams between cells.
Completely encircles each cell, preventing the
movement of material between the cell.
Characteristic of cells lining the digestive tract,
where materials are required to pass
through cells, rather than intercellular
spaces, to penetrate the bloodstream .

GAP
JUNCTIONS

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Narrow tunnels between cells

that consist of proteins called connexons.
The proteins allow only
the passage of ions and small molecules.
Communication between cells through
the exchange of materials or
the transmission of electrical impulses.
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CELL TO CELL
COMMUNICATION
NEURAL
NEUROENDOCRINE
ENDOCRINE
AUTOCRINE
PARACRINE
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Structure of the Cell Membrane

Outside of cell
Carbohydrate
chains

Proteins

Lipid
Bilayer
Transport
Protein

Phospholipids

Inside of cell
(cytoplasm)
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Physiology

29

Signal transduction how a cell

communicates

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Signal transduction how a cell

communicates and second messengers
There are three basic types of
secondary messenger molecules:
Hydrophobic molecules: waterinsoluble molecules, like
diacylglycerol, and
phosphatidylinositols, regulate
membrane-associated
effector proteins
Hydrophilic molecules: watersoluble molecules, like cAMP, cGMP
, IP3, and Ca2+, that are located
within the cytosol
Gases: nitric oxide (NO) and
carbon monoxide (CO), which can
diffuse both through cytosol and
across cellular membranes.
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Cyclic AMP
Cyclic GMP

BIOLOGICAL
AMPLIFICATION

Calcium ions
Inositol
Triphosphate
[IP3]

1 MOLECULE OF 1ST
MESSENGER

Diacylglycero
l [DAG]

10 6 RESPONSE
importance of second messengers

Sutherland
awarded Nobel
Prize for cAMP
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33

CELLULAR HOMEOSTASIS
Cell membrane is selectively
permeable
Allows for:
OSMOTIC EQUILLIBRIUM
CHEMICAL DISEQUILLIBRIUM
ELECTRICAL DISEQUILLIBRIUM

End Result :

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 Behavior of charged particles near a

semi-permeable membrane to sometimes fail
to distribute evenly across the two sides of the
membrane.
The usual cause is the presence of a different
charged substance that is unable to pass
through the membrane and

thus creates an uneven electrical charge

.

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 For example, the large anionic proteins in

blood plasma are not permeable to
capillary walls.
Because small cations are attracted, but
are not bound to the proteins, small
anions will cross capillary walls more
readily than small cations
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GibbsDonnan effect
Also known as the Donnan
effect, Donnan law, Donnan
equilibrium, or GibbsDonnan
equilibrium)

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IT IS WELL RECOGNIZED THAT the plasma water Na+ and Clconcentrations and interstitial fluid (ISF) Na+ and Cl- concentrations
are different despite the high permeability of Na+ and Cl- ions across
the capillary membrane, which separates these two fluid compartments
This difference in ionic concentrations between the plasma and the ISF
is attributed to the much higher concentration of proteins in the
plasma
compared with the ISF. Proteins are large-molecular-weight substances
and therefore do not cross the capillary membrane easily.
The low protein permeability across capillary membranes is
responsible
for causing ionic concentration differences between the plasma and
ISF
and is known as the Gibbs-Donnan effect or Gibbs-Donnan equilibrium
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Gibbs-Donnan equilibrium is established when the altered distribution

of cations and anions results in electrochemical
equilibrium.
It is also well recognized that another consequence of the GibbsDonnan effect is that there are more osmotically active particles
in the plasma space than in the ISF at equilibrium .

Consequently, the plasma osmolality is slightly

greater than the
osmolality of the ISF and intracellular fluid (ICF).
Indeed, the plasma osmolality is typically 1
mosmol/l H2O greater than that of the ISF and
ICF .
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In addition to the modulating effect of GibbsDonnan equilibrium on the

[Na+]pw and plasma osmolality, alterations
in the osmolality of the ISF
and ICF will also lead to changes in the
[Na+]pw and plasma
osmolality due to intercompartmental H2O
shift since the body
fluid compartments are in osmotic
equilibrium.
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cell volume
relatively constant

maintenance of protein function

Cell Volume
perturbation

wide array of signaling events

protective

adaptive

(e.g., cytoskeletal
rearrangement)
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(e.g., altered expression of

Physiology osmolyte transporters
42
and heat shock proteins)

Membrane Transporters
Channel proteins
Water filled pores

Y
R
T
S
I
M
E
Carrier proteins
H

C
O
I
B
Uniport
Gated : voltage or ligand
Open

Symport
Antiport
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Na+/K+-ATPase
Helps maintain resting potential,
Helps avail transport, and
Helps regulate cellular volume.
It also functions as signal transducer/integrator
to regulate MAPK pathway, ROS, as well as
intracellular calcium.
For most animal cells, the Na+/K+-ATPase is
responsible for 1/3 of the cell's energy
expenditure. For neurons, the Na+/K+-ATPase is
responsible for 2/3 of the cell's energy
expenditure.

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Cell to swell up and lyse.

OSMOSIS

H2O
H2O

H2O

The Na+-K+ pump is a

mechanism to prevent this.

H2O

The pump transports

3 Na+ ions out of the cell

and
in exchange
takes 2 K+ ions into the cell.

Pr-

Pr-

Pr-

Pr2K+

3 Na+
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+
+
+

Membrane is far less permeable to Na+ ions than K+ ions. Sodium ions
have a tendency to stay there.
The opposing osmotic tendency that results operates to drive the water
molecules out of the cells. Furthermore, when the cell begins to swell,
this automatically activates the Na+-K+ pump, which moves still more
ions to the exterior.

K+ ions

Na+ ions

ADP

ATP
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K+

Electrical status of the cells

Resting Membrane Potential
Cell interior is negative as compared to cell
exterior
It is mostly due to K+
40 times more permeable to K+ than to Na+
RMP~ -70 mV

Changes in ion permeability changes the

membrane potential
Mostly one of the four ions Na+, Ca+2 Cl- & K+,
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Excitable tissues
Muscles & Nerves
Can generate electrical signals and also
propagate them through long distances
Like all other cells
Negative RMP
Uneven distribution of ions
Membrane permeability of the ions different

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Nernst Equation
Membrane Potential that would result if the
membrane were permeable to only one ion
Described by Nernst equation
E ion =( 61/z)log [ion]out / [ion]in
Ideally it should have been -90 mV if K+ alone
would have been the ion responsible
But real value is -70mV
other ions must be contributing
Membranes are slightly permeable to Na+
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 Goldman-Hodgkin-Katz equation
Na+, K+, Cl- are the three ions that
influence membrane potential in resting
cells
More of this when you do Biopotential
lectures
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DIRECTED SELF LEARNING

meant for the students to study since these are topics
learnt in earlier days

Questions to be brought up in the

Tutorials
On Friday [2/10] & Monday [5/10]
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Effects of Osmosis on Life

Osmosis- diffusion of water through a
selectively permeable membrane
Water is so small and there is so much
of it the cell cant control its movement
through the cell membrane.

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Hypotonic Solution

Osmosis
Animations for
isotonic, hypertonic,
and hypotonic
solutions

Hypotonic: The solution has a lower concentration of

solutes and a higher concentration of water than
inside the cell. (Low solute; High water)

Result: Water moves from the solution to inside the

cell):
Cell Swells and
bursts
open (cytolysis)!
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Hypertonic Solution

Osmosis
Animations for
isotonic, hypertonic,
and hypotonic
solutions

Hypertonic: The solution has a higher concentration

of solutes and a lower concentration of water than
inside the cell. (High solute; Low water)

shrinks
Result: Water moves from inside the cell into the
solution:
Cell shrinks
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Osmosis
Animations for
isotonic, hypertonic,
and hypotonic
solutions

Isotonic Solution

Isotonic: The concentration of solutes in the solution

is equal to the concentration of solutes inside the cell.

Result: Water moves equally in both directions and

the cell remains same size! (Dynamic Equilibrium)
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What type of solution are these cells in ?

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Hypertonic

Isotonic

Hypotonic

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Cell swelling

Cell shrinkage
Cells accumulate ions

Cells release ions

through activation of K
channels and/or anion
channels, KClcotransport, or parallel
activation
of K+/H+ exchange and
Cl-/HCO3- exchange.

through activation of Na, K, 2Cl

cotransport, Na/H exchange in
parallel to Cl/HCO3 exchange, or
Na channels.
Na taken up is extruded by the

Na/K- ATPase in exchange

They release osmolytes

during cell swelling.
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Physiology

for K.
Accumulation of organic
osmolytes- generate sorbitol and
glycerophosphorylcholine
and monomeric amino acids by
altered metabolism and take up
myoinositol (inositol), betaine,
taurine and amino acids by Na
coupled transport
57

 After acute swelling, cell volume is regulated by

the process of regulatory volume decrease
(RVD), which involves the activation of KCl
cotransport and of channels mediating K(+), Cl(-),
and taurine efflux.
Conversely, after acute shrinkage, cell volume is
regulated by the process of regulatory volume
increase (RVI), which is mediated primarily by
Na(+)/H(+) exchange, Na(+)-K(+)-2Cl(-)
cotransport, and Na(+) channels.

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Osmolarity
is the measure of solute
concentration, defined
as the number of
osmoles of solute per
liter of solution
(osmol/L).
The osmolarity of a
solution is usually
expressed as Osm
(pronounced "osmolar"),
Osmolarity measures
the number of osmoles
of solute particles per
unit volume of
solution.
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Osmol
1 osmole = 1 mole of
osmotically active particles

the amount of osmotically active

particles that when dissolved in
22.4 L of solvent at 0 degrees celsius
exerts an osmotic pressure of 1
atmosphere.
a solution of 1 mol/L NaCl
corresponds to an osmolarity of 2 osmol/L.
NaCl salt particle dissociates fully in water
to become two separate particles:
an Na+ ion and a Cl- ion.
Therefore, each mole of NaCl
in solution.
Physiologybecomes two osmoles
59

Osmolality
is a measure of the
osmoles of solute
per kilogram of
Osmolarity
solvent (osmol/kg).
such as sodium,
is the measure of
chloride, potassium,
solute concentration,
urea, glucose, and
defined as the
other ions in blood.
number of osmoles of
solute per liter of
HUMAN RANGE
275-299 milli-osmoles per kilogram
solution (osmol/L).
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Clinical relevance
Cell membranes in general are freely permeable to
water,
the osmolality of the extracellular fluid (ECF) is
approximately equal to that of the intracellular fluid (ICF).

Therefore, plasma osmolality is a guide to

intracellular osmolality.
This is important, as it shows that changes in
ECF osmolality have a great affect on ICF
osmolality - changes that can cause
problems with normal cell functioning and
volume.
If the ECF was to become too hypotonic,
water would readily fill surrounding cells,
increasing their
volume and potentially
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61
lysing them (cytolysis).

dehydration

overhydration

Osmolality of blood increases

Osmolality of blood decreases

increased

suppressed

secretion of antidiuretic hormone (ADH).

water reabsorption
More
concentrated

urine

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water reabsorption

Less
Con centrated
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Physiology

blood plasma

More concentrated blood plasma

Less concentrated
urine
62

Plasma Osmolality: (280 285 mOsm/Kg)

As cell membranes in general

are freely permeable to water,
the osmolality of the
ECF is approximately equal to that of the ICF

Therefore, plasma osmolality is a guide to

intracellular osmolality

Plasma Osmolality =
(2 x (Na + K)) + (BUN / 2.8) +
(glucose / 18)
Na- Sodium, K Potassium, BUN- Blood Urea Nitrogen
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TONICITY vs OSMOLALITY

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Effect of tonicity on cell integrity

Tonicity is a measure of the osmotic pressure of two solutions

separated by a semipermeable membrane.
It is commonly used when describing
the response of cells immersed in an external solution.
Like osmotic pressure, tonicity
is influenced only by solutes that cannot cross the membrane,
as only these exert an osmotic pressure.
Solutes able to freely cross the membrane do not affect tonicity
because
they will always be in
equal concentrations on both sides
of the membrane.
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 Osmolarity and tonicity are related, but

different, concepts.
The terms ending in -osmotic (isoosmotic,
hyperosmotic, hypoosmotic) are not
synonymous with the terms ending in -tonic
(isotonic, hypertonic, hypotonic).
The terms are related
they both compare the solute concentrations of
two solutions separated by a membrane.

The terms are different because

osmolarity takes into account the total
concentration of penetrating solutes and nonpenetrating solutes, whereas tonicity takes into
account the total concentration of only nonpenetrating solutes.
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 Penetrating solutes
can diffuse through the cell membrane,
causing momentary changes in cell
volume as the solutes "pull" water
molecules with them.
Non-penetrating solutes
cannot cross the cell membrane, and
therefore osmosis of water must occur for
the solutions to reach equilibrium.
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Solution can be
both hyperosmotic and isotonic
The intracellular fluid and extracellular can
be hyperosmotic, but isotonic
if the total concentration of solutes in one
compartment is different than the other,
but one of the ions can cross the
membrane, drawing water with it and thus
causing no net change in solution volume.

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