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HOMEOSTASIS

COMMUNICATION

Dr. Hardi Darmawan,MPH&TM.,FRSTM


FK UNSRI
DEFINITION OF PHYSIOLOGY

• Physiology is the study of how things work


BASIC PRINCIPLE OF
PHYSIOLOGY
• Homeostasis is the basic principle of
physiology
• Homeostasis is the maintenance of a
constant environment
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.
CHARACTERISTICS OF
HOMEOSTASIS
• Effectors may have opposing actions.
• Negative feedback is the process that
prevent change.
• Positive feedback is the process that
perpetuates change.
• Feedforward control is outside stimuli that
alter the normal feedback response.
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.
These will be developed in later chapters.
Communication has several characteristics :
2. Distance : short vs long
3. Speed : fast vs slow
4. 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. 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.
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.
COMMUNICATION BETWEEN
CELLS – figure 1.2
Cells communicate with each other by
mechanisms which include endocrine,
paracrine and neurocrine actions.

Endrocrine communication is through


secretion of chemicals or hormones into
the blood stream which then circulates to
cells of target organs.
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.
Intercellular Communication
Type Description` Means of Local or Examples
Message General
Transmission
Autocrine Process by which By diffusion in Locally diffese • Prostaglandine
cell produces interstitial fluid released by uterine
subtance that tissue induce
regulates that cell contractions of
or neighboting uterine smooth
cells of same type muscle
• Prostaglandins
released by
bronchiolar
smooth muscle
induce
vasodilation
Endocrine Process by By General •Anterior pituitary
which cell circulating secretes prolactin, which
secretes blood travels via bloodstream
regulatory to mammary glands to
substance stimulate milk synthesis.
directly into •Pancreatic cells in islets
blood stream, of Langerhans secrete
which affects glucagon, insulin,
cells that maybe somatostatin, and
some distance pancreatic polypeptide
away (pancreas has both
exocrine and endocrine
function)
Exocrine Process by Usually via a Local •Pancreatic acinar cells
which cell duct secrete digestive enxymes
delivers (eg, carboxypeptidase,
regulatory pancreatic lipase,
substances to ribonuclease (trypsin) into
an epithelial pancreatic duct of Wirsung
surface whish koins common bile
duct to form ampulla of
Vatex
•Ducts sweat and salivary
glands`
Neurl Process by Across Local •At neuromuscular juntiong,
(Synaptic which neurons sysnaptic nerve release AH which
) release cleft increases Na and K
neuthansmitters comtructor of musble
across synaptic membrane
cleft to •This action causes info
postynsaptic Na2 and produces
cells depolarixing.
Nurocrine Process by which Axonal General • Hypotalamus
neuron releases transport to releases hormone into
regulatory bloodstream bloodstream
substances into
blood stream to
affect distant cells

Paracrine Process by which 3y diffusin in Locally Histamin released


cell secretes intertitialan diffuse cells in wall aor thamh
regulatory hukum) stimulates HL sectayn
subtance that dengan pariental
diffuses inttto cellsof gastric glan.
ECG to affact
cells that are
different from
itselh`
Process of Intracellular Communication
Sequence Action
1 Agonist binds membrane receptor
2 • G protein is activated by binding GTP
• Amplification allows one agonist complex to activate hundreds
of effectors
3 • Activated G protein interacts with effector proteins to alter their
activities
•Effectors include enzymes, ion channels, and phospholipases

4 Effector proteins affect activities of second messengers (cAMP,


cGMP, DAG, IP3)
5 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) or ion channels
6 Level of phosphorylation of enzyme or ion channel is
altered
7 Final cellular response

AGE SPLuRge – Agonist, G Protein, Effector proteins, Second messengers,


Protein kinases, level of phosphorylation, response
Intracellular Mediators
Type Description / Example

Second Messenger
Cyclic Nucleotides • Vision depends on cGMP-gated Na+ channels
(cAMP, cGMP) present in plasma membranes of rods
• When rhodopsin (receptor) is activated by light
(stimulus), rhodopsin interacts with the G
protein transducin
• Activated transdusin interacts with cGMP
phosphodiesterase, which increases eGMP and
causes closing of cGMP- activated Na+
channels and hyperpolarization of
photoreceptor cell
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 cyctosol, which
triggers cellular response
• Immunosuppressant drug cyclosporine helps
prevent transplant rejection by blocking this
pathway.
Ca2+ Ca2+ calmodulin complex activates myosin light-
chain kinase (a calmodulin-dependent protein
kinase), which phosphorylates myosin, resulting in
smooth muscle contraction.
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
cell division and is involved in growth of tumor
cells.
Protein Tyrosine Kinase • Membrane receptors that are themselves
protein kinases
• When agonist binds receptor, protein
tyrosine kinase ohosphorylates protein
substrates on tyrosine residues
• Receptors for insulin and those for growth
factors (epidermal growth factor, colony-
stimulating factor, fibrolast growth factor)
are protein tyrosine kinases.
• Uncontrolled protein-tyrosine kinases play
major role in cell transformation and
malignancy
G Proteins
Heterotrimeric • 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 modulated by G proteins.
• Activation of phospholopase A2 by G protein leads
to production of arachidonic acid
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
Intercellular Communication
By Chemical Mediators

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