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HOMEOSTASIS

COMMUNICATIO
N

Prof. Hardi Darmawan, MD, MPH&TM.,FRSTM


Department of Physiology & Biophysic

DEFINITION OF PHYSIOLOGY
BASIC PRINCIPLE OF
PHYSIOLOGY
Physiology is the study of how things work
Homeostasis is the basic principle
of physiology
Homeostasis is the maintenance
of a constant environment
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COMPONENT OF A
HOMEOSTASIS SYSTEM
Regulated variable is a variable to be
kept constant.
Set point is the desired value of the
regulated variable.
Sensors assess current status of the
regulated variable.
Feedback controller compares current
conditions with the set point.
Effector brings current status of
regulated variable into line with the set
point.
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CHARACTERISTICS OF
HOMEOSTASIS

Effectors may have opposing


actions.
Negative feedback is the
process that prevent change.
Positive feedback is the process
that perpetuates change.
Feed forward control is outside
stimuli that alter the normal
feedback response.
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COMMUNICATON IS AN
ESSENTIAL ELEMENT OF A
HOMEOSTATIC SYSTEM
Two languages of communication are
chemical and electrical.
Characteristics of communication are
distance, speed, distribution.
The sensor has to communicate with the
feedback controller and the feedback
controller has to communicate with the
effector. There are essentially two
languages of communication. One is
chemical and the other is electrical.
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These will be developed in later chapters.

Communication has several


characteristics :
1. Distance : short vs long
2. Speed : fast vs slow
3. Distribution : focused vs diffuse

Communication occurs over


distance as short as the
environment surrounding a single
cell. Cells can stimulate
themselves, called autocrine
stimulation, or their neighbor,
called paracrine stimulation
through the release of chemical
agents.
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Communication can also occur


over long distance, such as a
nerve cell located in the spinal
cord sending a process out to
the end of the finger to
stimulate a muscle cell.

Communication can be fast, again


like nerve stimulation of a muscle
cell or the electrical communication
between cells during the heartbeat.
And it can be slow. Slow
communication occurs when the
transmission of the chemical is
determined by its distribution in the
blood. The response to a hormone is
intrinsically slower than that to
nerve stimulation.
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Finally, communication can be very


focused, such as the activation of
single muscle cells in the eye in order
to focus on an object. And it can be
diffuse, such as when epinephrine,
released from the adrenal medulla
when blood pressure falls, acts on the
heart and the vasculature throughout
the whole body.

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COMMUNICATION BETWEEN
CELLS figure 1.2
Cells communicate with each other
by mechanisms which include
endocrine, paracrine and neurocrine
actions.
Endocrine communication is through
secretion of chemicals or hormones
into the blood stream which then
circulates to cells of target organs.
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Paracrine is a cell to cell or local


communication by adjacent cells via
secretions which diffuse into the
interstitial fluid. This is mediated by
receptors.
In neurocrine or synaptic communication,
the transmitter released at a nerve
ending passes through a synapse to the
communicating or post-synaptic cell.

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Intercellular Communication
Type

Description`

Autocrin Process by
e
which cell
produces
subtance that
regulates that
cell or
neighboring
cells of same
type

Means of
Message
Transmissi
on

Local or
General

By
Locally
diffusion in diffuse
interstitial
fluid

Examples

Prostaglandin
e released by
uterine tissue
induce
contractions
of uterine
smooth
muscle

Prostaglandin
s released by
bronchiolar
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smooth

Endocri
ne

Process by
which cell
secretes
regulatory
substance
directly into
blood
stream,
which
affects cells
that maybe
some
distance
away

By
Genera Anterior pituitary
circulating l
secretes prolactin,
blood
which travels via
bloodstream to
mammary glands
to stimulate milk
synthesis.
Pancreatic cells in
islets of Langerhans
secrete glucagon,
insulin,
somatostatin, and
pancreatic
polypeptide
(pancreas has both
exocrine and
endocrine function)
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Exocrin
e

Process by
which cell
delivers
regulatory
substances
to an
epithelial
surface

Usually via Local Pancreatic acinar


a duct
cells secrete digestive
enxymes (eg,
carboxypeptidase,
pancreatic lipase,
ribonuclease (trypsin)
into pancreatic duct of
Wirsung which joins
common bile duct to
form ampulla of Vater
Ducts sweat and
salivary glands`

Neural Process by
Across
(Synapt which
sysnaptic
ic)
neurons
cleft
release
neurotransmi
tter across
synaptic cleft
to
postynsaptic

Local At neuromuscular
junction, motor nerve
releases Ach which
increases Na+ and K+
conductance of
muscle membrane
This action causes
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influx
Na + and produces

Neurocri Process by
ne
which neuron
releases
regulatory
substances
into blood
stream to
affect distant
Paracrin Process
by
cells
e
which cell
secretes
regulatory
substance
that diffuses
into ECF to
affect nearby
cells that are
different from

Axonal
transport
to
bloodstrea
m

Gener
al

by diffusion Locall
in
y
interstitial diffuse
fluid)

Hypothalamus
releases
antidiuretic
hormone into
bloodstream

Histamine
released from
cells in wall of
stomach
stimulates HCL
secretion by
parietal cells of
gastric gland.
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Process of Intracellular
Communication
Sequence Action
1

Agonist binds membrane receptor

G protein is activated by binding GTP

Amplification allows one agonist complex to


activate hundreds of effectors
Activated G protein interacts with effector
proteins to alter their activities
Effectors include enzymes, ion channels, and
phospholipases
Effector proteins affect activities of second
messengers (cAMP, cGMP, DAG, IP3)

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6
7

Activity of second messenger alters activity


of second messenger-dependent protein
kinases (cAMP-dependent protein kinases,
cGMP-dependent protein kinases, protein
kinase C, calmodulin-dependent protein
kinase)
ion channels of enzyme or ion
Level of or
phosphorylation
channel is altered
Final cellular response

AGE SPLuRge Agonist, G Protein, Effector proteins, Second messeng


Protein kinases, level of phosphorylation, response
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Intracellular Mediators
Type
Second
Messenger
Cyclic
Nucleotides
(cAMP,
cGMP)

Description / Example

Vision depends on cGMPgated Na+ channels


present in plasma
membranes of rods
When rhodopsin (receptor)
is activated by light
(stimulus), rhodopsin
interacts with the G
protein transducin
Activated transducin

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IP3 and DAG

G protein activates agonist receptor


complex, which then cleaves
phosphatidylinositol 4,5-bisphosphate
into IP3 and DAG
IP3 binds receptors on endoplasmic
reticulum, leading to release of Ca2+
into cytosol, which triggers cellular
response

Ca2+

Immunosuppressant drug
cyclosporine helps prevent transplant
Ca2+ calmodulin complex activates
rejection by blocking this pathway.
myosin light-chain kinase (a
calmodulin-dependent protein kinase),
which phosphorylates myosin, resulting
in smooth muscle contraction.
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Protein Kinases
Protein Kinase

Enzyme activated by second messenger


that
phosphorylates proteins on serine or
threonine
residues (protein phosphatase is enzyme
that
dephosphorylates proteins).
cAMP-dependent protein kinase
phosphorylates
rate-determining enzymes in glycogen
metabolism
Ca2+ stimulates protein kinase C, which
stimulates
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cell division and is involved in growth of

Protein
Tyrosine
Kinase

Membrane receptors that


are themselves
protein kinases
When agonist binds
receptor, protein
tyrosine kinase
phosphorylates protein
substrates on tyrosine
residues
Receptors for insulin and
those for growth
factors (epidermal
growth factor, colony24
stimulating factor,

G Proteins
Heterotrimeri
c

Nucleotide regulatory protein


that aids in
translation of signals between
cells and helps
modulate intracellular
concentrations of second
messengers.
In active state, acts as GTPase,
hydrolyzing GTP
toGDP
Adenylyl cyclase (enzyme that
aids synthesis of
cAMP) and cGMP
phosphodiesterase (enzyme that
breaks down cGMP) are

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Monomeric

Small G protein involved in protein


synthesis, cell
proliferation, neoplastic cell
transformation and
vesicle transport.
Ras like G protein regulate cell growth
and
differentiation
Rab-like G protein help target vesicles to
membranes

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Response to water deprivation

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Response to water intake

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