01

Leave Feedbai

HOMEOSTASIS

Introduction 00:01:22

It is concept o? constancy (inspite o? changes in external

environment, body tries to maintain all its parameters near
to a constant value)
Claude Bernard said despite o? changes in the external
environment, the body will always try to maintain a stable
internal environment (milieu interior).
blotter Cannon • Coined the term homeostasis.
To maintain constancy, body uses 3 control systems :

• Positive VeedbacK process.

• Feed forward control system.
Megative VeedbacK process i
During exercise, there is an increase in BP. Once the purpose
is achieved there is an opposite eWect i.e decrease in BP.

Positive Veedbach process :

BP is usually under the nervous control (CMS) Via action
potential.
During action potential, Ma* channels open leading to Ma*
in^ux. This is depolarization. It opens more Ma* channels, more
Ma* in^ux and further depolarization.
This cycle is Known as HodgK'n’s cycle.
In positive VeedbacK, the initial stimulus <s ampl&ed further.

Feed forward control system »

Mo stimulus required Anticipatory thinKing produces response.
It is also called as anticipatory control system. space
The process oV thinKing o? doing exercise itsel? can rise heart
rate and respiratory rate. Applicable to all events in li?e. Active

Physiology • v4.0 • Marrow 6.0 • 2022

 Q-j Homeostasis
Leave Feedba,

Inftnite Veedbacb yain :

I? error is zero, yain is inanity.
example Bole o? Kidneys in the control o? &P.
Kidneys bring bach 6P to laomm hy by excretiny urine
containiny water and sodium but it tabes a longer time.

Positive feedback control system 00:22:41

The initiating stimulus is amplifted Further,

mnemonic CLAPS =
C : Clotting is an ampliftcation cascade, Forming a stable clot.
L : LH
ovulation).
—
surge (increase in estroyen » increase in LH to briny

A : Action potential (Hodybin’s cycle).

P ; Parturition (delivery oF Fetus).
Ferguson’s reftex :
/ > Fetal head presses on uterine cervix
4/
Release oF oxytocin
Uterine contraction
4,
Facilitates Further descent oF Fetal head

Delivery oF Fetus
S : Shocb (decrease in 6P decreased blood ftow to
heart > weabening oF heart muscles
decrease in contraction > decrease in 6P >
Shocb worsens). It is a vicious cycle. So, positive Feedbacb
is not always beneftcial.

Feed forward control system 00:30:57

Mo stimulus is required
It is also called as anticipatory control system.
examples = space
• Thinbiny o? perVorminy exercise leads to anticipatory Active
tachycardia and tachypnea.
• Body temperature regulation u)hen an individual is
exposed to cold, sbin temperature (shell temperature)
Falls.

Physiology • v4.0 • Marrow 6.0 • 2022

 02
Leave Feedbai

CELL MEMBRANE

Ports o? ot cell :
Intermediate mitochondria
^lament Plasma
Pibosomes membrane

I2ough endoplasmic microtubule

reticulum
Nucleus Centrosome

Mucleolus microftlament
Chromatin
Lysosome
Gtolyi Smooth endoplasmic
apparatus reticulum

€tolgi vesicle Secretory vesicle

Peroxisome
cytoplasm vacuole

Cell membrane components OO:O2:13

The 3 macromolecules present are :

-
Proteins (SS%) major component o¥ cell membrane.
Lipids : 40%.
Carbohydrates : 5%.

space
Active

Physiology • v4.0 • Marrow 6.0 • 2022

 02 Cell
Membra Leave Feedbal
Lecithin is usually expressed
Outer
only on the outer sur Vace oV
lipid bilayer
Inner surface

-> Phosphatidyl serine is usually

expressed only on the inner
Surface oV lipid bilayer

4. Phosphatidyl inositol :
• Also called as inositol triphosphate (iP^.
• Rets as a second messenger. Causes influx of Ca‘
ion which also acts as a second messenger.
• Forms IP^- DR^ Caa’ system.

S. Cardiol ipin :
• Exclusively abundant in mitochondria of cardiac cells.
• if anti cardiolipin antibodies develop in body, indicates
infection by Treponema pallidum (syphilis).
• Detected on voer test.

glycolipids »
exclusively abundant in CMS and QIT.
Types of glycolipids :
I. gangliosides s
Opn I ganglioside present in GOT, is recognised by

microorganisms and used as a receptor for entry.

Vibrio cholerae toxin enters through eon I
ganglioside and causes diarrhoea.
a. Cerebrosides.

Cholesterol : Present in shin as a precursor form.

1 - dehydrocholesterol
Sunlight
Vitamin D. I
Fluidity of lipids ’
• Cell membrane needs to be in a fluid lihe state for
optimum functioning.

Physiology • v4.0 • Marrow 6.0 • 2022

 Cell a
02
Leave Feedbai

Transmembrane proteins
• Hormonereceptors : e<PCRs (e< - protein coupled
receptors), Insulin receptors etc.,
• Pumps Ma*- VS* pumps.
$

• Ion channels : Chloride ion channel.

CFTR (Cystic Fibrosis Transmembrane Regulator) gene
regulates the opening o? Cl' channels.
CFTR gene mutation leads to cystic ^brosis disease.

Peripheral proteins s

Function :
Supportive in nature. They
support the structure o?
R6CS and skeletal muscle.
• RCCs (biconcaved disc
shaped cells) structural
proteins =
Spectrin.
PnKyrin. macr<
• Skeletal muscle structural proteins »
Dystrophm.
• Certain cell Surface receptors.

Hereditary elliptocytosis Charge in shape

o? 26Cs to elliptical due to mutation in spectr in protein.
Hereditary spherocytosis : mutation in anKyrin protein alters
shape o? RSCs, causing extensive destruction by splenic
macrophages leading to hemolytic anemias.

Dystrophin (anchor protein) : mutation o? dystrophin leads to

Duchenne muscular Dystrophy (Dmo).
• Skeletal muscle weakness.
• power’s sign positive Climbing on own body to stand.
• muscle weakness progressing to diaphragm, leads to
respiratory muscle paralysis and causes death.

Physiology • v4.0 • Marrow 6.0 • 2022

 02 Cel1
Membra >a

Membrane carbohydrates 00:50:56

Function in RBCs '• For blood grouping (ABO).

-
• A blood group : M acetyl galactosamine (MAE)
sugar present on RBC
• 6 blood group : Gialactose sugar on RBC.
• AB blood group Both sugars Vound on RBC
• O blood group ‘ Mo sugar on RBC .

Highest protein content is seen in inner mitochondrial

membrane (10%).

Exception *•
In -
myelin (nerve cell membrane) lipid protein ratio is
reversed. Lpids « 80% proteins s £0%.

Qi. ft cell
membrane is damaged by insertion oV microneedle,
repair shall occur by which oV the Vollowing processes ?
A. Lateral movement oV proteins.
6. Resealing by lipid bilayer.
C Enzymatic reaction.
O. Hydrophobic interaction.

Small gap : Lipid bilayer rescaling, Big gap : CaJ‘ dependent

Q£. ulhich oVthe Vollowing membrane has the hghest protein

content per gram tissue ?
A. Inner mitochondrial membrane.
6. Outer mitochondrial membrane.
C Plasma membrane.
O. myelin sheath.

8
I

Physiology • v4.0 • Marrow 6.0 •2022

 03
Leave Feedbac

CELL ORGANELLES

Cell organelles are parts of the cell

Two important cell parts are Endoplasmic Reticulum (er) and
Qolgi Apparatus (SiA). They are similar structurally
functionally. Hence, they are called twin organelles.
Endoplasmic reticulum 00:01:54

TWO types •
• granularendoplasmic reticulum • Surface appears
rough due to the presence of granules, granules contain
ribosomes. Also Known as Rough Endoplasmic Reticulum
(rer).
• Agranular endoplasmic reticulum = Surface appears
smooth due to absence of granules/ribosomes. Also
Known as smooth endoplasmic reticulum.

Sough endoplasmic reticulum :

Functions :
Synthesis of proteins called translation.
Folding of proteins with the help of chaperones (neat
shocK proteins or HSPs). For proper functioning.
Endoplasmic Reticulum Assisted Degradation (ERAD) •
Accumulation of misfolded proteins can lead to cell
death. To prevent cell death, endoplasmic reticulum
destroys misfolded proteins. Endoplasmic reticulum
combines the misfolded protein with ubiquitin
—
(process Known as tagging) > This complex moves to
—
proteasomes > undergoes degradation.
Hence, rough endoplasmic reticulum is associated with
quality control of proteins.
space
Diseases due to misfolded proteins : Active
l. Prion diseases :
CMS expresses a normal protein called PrPc. misfolding
of this protein forms PrPsc. PrPsc is toxic and its
accumulation leads toCreutzfeldt jaKob Disease (CJD)

Physiology • v4.0 • Marrow 6.0 • 2022

 03 Cell
Organelles Leave Feedba*

3 Parts :

=
Cis end Close -to rough endoplasmic reticulum, receiving end.
e<olgi apparatus proper : Functions o? golgi apparatus are
performed lihe PTm Sorting o? proteins in the Vorm o?
vescicles.
Trans end : Away Vrom rough endoplasmic reticulum, vescicles
are released Vrom trans end

Lysosomes 00:23:53

On a general note, it is the recycle bin o? cells.

Concerned with acid mediated destruction =
—
• Has H* ATPase proton pump > Influx o? H* ions > —
Acidic pH inside lysosome —
> Acid mediated destruction.
• Also called as suicidal bags as they are prone Vor acidic
damage. Other names are residual bodies and recycle
bins.
• Has many enzymes Vor destruction such as acid
hydrolases, acid proteases etc.
Autophagy (sei? destruction) $ €\iven nobel prize.
Starvation —
> Lysosomes engul? mitochondria »
mitochondria is destroyed —
> Release o? proteins flrom the
—
inner mitochondr ial membrane —
» Proteins undergo
metabolism to release energy.
This process is exclusively important Vor survival especially
in the later stages o? starvation.

Peroxisomes 00:31:21

Peroxisomes are concerned with generation and destruction

o? hydrogen peroxide (h^O :
• Hydrogen peroxide is a Vree radical. Its destruction is
mediated by the enzyme catalase in peroxisomes.
• Catalase is also available in drug Vorm s Pseudocatalase.
It is useful in diseases with excessive Vree radicals such 8
as Vitiligo (Vree radical mediated shin pigmentation). I
Oxidation o? long chain and very lorg chain Vatty acids :
• Occurs in peroxisomes. Phytanic acid oxidase enzyme is
involved in this process.

Physiology • v4.0 • Marrow 6.0 • 2022

 03 0611
Leave Feedbac

• mutations in mitochondrial genome are IO times greater

compared to nuclear genome and DMA repair is
ineffective compared to nuclear genome.
• mitochondrial genome cannot function on its own. It
worhs with nuclear genome to produce proteins that are
enzymes concerned with oxidative phosphorylation.
mitochondrial diseases :
• Affects organs with high metabolic rate —> defective
energy production.
—
• Involvement of skeletal muscle > altered muscle
contraction and relaxation (Is* to be involved).
Always accompanied by lactic acidosis.
—
• Involvement of QI tract > QI disturbances.
—
• Involvement of CMS > Seizures, developmental delays.
• Altered growth.
• Hgh susceptibility to infections.

Nucleus 00:45:44

Present in all dividing cells.

Contains chromosomes which has the blueprint for all
genetic expressions.
Chromosomes are made of DMA wrapped by histones.
DMA + Histones = Chromatin.
Chromatin contains a repeating structural unit called
nucleosomes.
Mucleoli contain granules with CMA and ribosomes — —»
eiive r ise to proteins.
Part of DMA contains genes (units of heredity).
Mucleus is surrounded by outer nuclear membrane and
inner nuclear membrane. Substances can move bach
and Sorth through nuclear pore complex that spans the
nuclear membrane.
Muclear pore complexes express two proteins « 8
&
8
exportins (tahe substances outside) and importins (tahe I
substances in).
Substances should express nuclear localization
sequences (MLS) to move through nuclear pore

Physiology • v4.0 • Marrow 6.0 • 2022

 IQ
04
Leave Feedbac

CYTOSKELETAL FILAMENTS AND

CELLULAR JUNCTIONS

Cytoskeletal filaments 00:00:17

Considered -to be the bone/skeletal structure of cells, It

provides strength and support to the cell.
It also helps in cellular movements.
It is classified based on the size into 3 types :
• microtubules Cig size ftlaments.
• microftlaments : Small size ftlaments.
• Intermediate ftlaments : most abundant cytosheletal
ftlaments.

Microtubules 00:02:53

Three structural proteins play a role in three vital functions.

The structural proteins are ’
• binesin.
• Dynein.
• Tubulin.
The three vital functions are :
• Axonal transport in neurons. Forward axonal (substances
move from cell body to synapse) and reverse axonal
(synapse to cell body) transport.
hinesin mediates forward axonal movement.
Dynein mediates reverse axonal movement.
Certain microorganisms and toxins invade the cell body
via reverse axonal movement. Some examples include $
I. Rabies virus.
a. Herpesvirus.
3. Tetanus toxin. space
Dynein is exclusively involved in the movement eft 3
structures :
Active
I. Cilia in lungs. It is capable of bending type of
movement and is involved in collecting and

Physiology • v4.0 • Marrow 6.0 • 2022

 Q4 Cytoskeletal 21
Filameni Leave Feedbac
Cellular
• Cellular movement (actir). Actin polymerization leads to
movement.
Listeria monocytogenes is capable o? inducing actin
plymerization to develop a poly-A tail.
It is involved in the characteristic tumbling motility seen
in the microorganism.

Intermediate filaments 00:20:43

They ore specie to each cell type and are hence

considered as tumor markers. examples are :
• heratin • Seen exclusively in epithelia) cells. It is used as
tumor markers (cytoheratir) Vor squamous cell
carcinoma
Cytoheratin can be accumulated in alcoholic liver
disease forming the mallory Deris bodies.
• Desmin • It is exclusively expressed in muscles and is
hence considered a tumor marher Vor sarcomas
(rhabdomyosarcoma).
• Vimentin • Commonly expressed in connective tissue
cells liKe Vibroblasts.
majority o? these connective tissue are mesenchymal
derivates and they are tumor markers Vor
cancers oV mesenchymal origin.
• e^lial ^brillary acidic protein (€^FAP) They are the
intermediate ^laments seen in glial cells lihe astrocytes.
They are tumor markers Vor gliomas lihe astrocytoma
• Lamin : exclusively expressed in cell nucleus, mutations
can cause uJerner syndrome (progeria) leading to
premature ageing.

Cellular junctions 00:28:22

Cell-cell junctions ;
• Cell adhesive junctions (cells touch each other). 8
• Tight junctions. I
• Qap junctions (cells communicate to each other).

Physiology • v4.0 • Marrow 6.0 • 2022

 04 Cytoske
Filaments and
Cellular
Tight junctions regulate the sideward movement of
substances called paracellular pathway (sidewards).
Claudin l(o mutations exclusively affects tight junctions in the
Kidney. It causes familial hypomagnesemia hypercalciuria
Affected patients are prone to develop calcium stones or
nephrocalcinosis.
Gap junctions »
Cells communicate via gap of 3 - 4 nm gap called gap
junctions. These are exclusively abundant in the heart,
smooth muscles (vascular and GilT) and neurons.
Comexin is the protein which forms the gap junctions. They
are seen in locations where rapid communications between
cells are important.
In an x-lmKed disease called Charcot mare tooth disease,
Comexin 3a is mutated and it affects neurons and nerve
^bers.
I? connexin 40 (seen in heart) is mutated, it leads to
idiopathic atrial fibrillation.
Comexin 31 is present in vascular smooth muscles and its
mutation can lead to arteriosclerosis.

Cell-basal lamina junctions 00:48:34

uJhen these junctions are disrupted, the cells start to move

which is seen in metastasis.
They are of two types =
• =
Hemidesmosomes Connects to intermediate filaments.
• Focal adhesions : Connects to actin.
Identifications of cell parts :
Each part cam be identified by certain enzymes specific to
that cell part called marKer enzymes.
Cell part marker enzyme
Cell membrane MaW ATPase and Adenylyl cyclase.
endoplasmic reticulum ejucose (o phosphatase.

eolgi apparatus galactosyl transferase.

Lysosomes Acid phosphatase and cathepsins.

Physiology • v4.0 • Marrow 6.0 • 2022

 05 OK
Leave Feedba<

CELL MESSENGERS AND

RECEPTORS

Hormones 00:01:03

There are 4 classes o? hormones

l. Single amino acid derivatives :
• Tyrosine Thyroid hormones (T3 and T4) and
catecholamines.
(Epinephr ine, norepinephrine, and dopamine).
• Tryptophan : Serotonin.
• Arginine : Mitric oxide.
A. Protein hormones (multiple amino acid) :
• Insulin : si amino acids.
• Parathormone • 84 amino acids.
Any hormone with a protein structure cannot cross the cell
membrane and hence, act on the membrane receptors.

3. Cholesterol derivatives :
• Steroids^
Sex steroids ViKe estrogen, progesterone and testosterone,
adrenal cortex steroids liKe aldosterone and cortisol.
Steroid hormones can cross cell membrane and act via.
intracellular receptors.
4. Vitamins » A and O.
They are Vat soluble Vitamins and can cross the cell
membrane. They have intracellular receptors as well.

Receptors 00:07:22

membrane receptors or extracellular receptors can be oV

diWerent types : space
• Q-protein coupled receptor (6jPCC). Active
• Tyrosine Kinase receptor.
• Janus Kinase receptor/JAK.
• Ser ine Kinase receptor.

Physiology • v4.0 • Marrow 6.0 • 2022

 05 Cell M<
and Re >tors ]
€iPC£s can use any oV the three secondary messengers.
There are di^rent subunits ¥or a »
• (Stimulatory) Stimulates adenylyl cyclase which
increases the cyclic AmP levels.
• Gn (inhibitory) $ Inhibits adenylyl cyclase which decreases
the cyclic AmP levels.

QPCRs using Caa* as second messengers :

• Q ; when activated increases calcium levels.
Cyclic G^mP :
• G^ (Transducir) : It is seen in rods and cons.
When G^ is activated, the Transducin activates
phosphodiesterase enzyme which causes hydrolysis o?
cyclic <qmP levels.
G^ a when stimulated increase cyclic AmP (cAmP). There is a
pathologically hgh levels o? cAmP i? there is again o? function
mutation.
People with such a mutation are prone Vor :
• Precocious puberty.
• Skeletal abnormalities.
• SKin pgmentations: Ca?e au lart spots.
This clinical disorder is called mcCune Albright syndrome.

Hormones and their 2nd messengers 00:24:24

cAmP :
• Hormones concerned with metabolism requires cAmP :
glucagon in liver causes glycogenolysis uses cAmP as
the second messenger.
cAmP is the ^rst ever second messenger to be
discovered
• Hormones concerned with water reabsorption :
Vasopressin (antidiuretic hormone) in the collecting duct
cells acts on the V, receptor fe\PCR). S
It increases the production o¥ channel protein called I
aquaporins concerned with water resorption.
• Hormones concerned with electrolyte secretion :
Secretin is the $rst hormone discovered

Physiology • v4.0 • Marrow 6.0 •2022

 • Erythropoietin (EPO) through its JAK action increases
26C production.

4. Serine Kinase receptors are exclusively concerned with

hormones concerned with hormone reproduction.
• ActiVm : Increases Vollicular stimulating hormone(FSH).
• Anti mullerian hormone (Amu).

Intracellular receptors 00:40:54

Cytoplasmic receptors :
• Aldosterone 5 mineralocorticoid receptor (m2).
• Cortisol glucocorticoid receptor (Q2).
$

• Testosterone Androgen receptor (A2).

• vitamin D receptor.
Muclearreceptors :
• Thyroid hormones.
• Vitamin A.
• Estrogen receptor (E2).
• Progesterone receptor (P2).
Aldosterone crosses the cell membrane and binds to the m2.
m2 when inactive are combined to certain proteins called
heat shocK proteins <HSPs).
m2 is activated when aldosterone binds to it and the complex
is called hormone receptor complex (H2C).
H2.C eventually move into the nucleus to exert its action.
Each steroid hormone has a specie binding site. The H2C
formed aVter binding moves into the nucleus to bind to the
hormone responsive elements (H2.E).
The H2.E activates transcription activators which leads to an
increase in transcription (m2MA and proteins).

An increase in hormone levels leads to overactivity. There are

safety mechanisms to prevent overactivity.
Downregulation o? receptors by :
• Internalization o? receptors.
• Desensitization o? receptors by mod&cations maKirg it
less responsive.
• Inactivation.

Physiology • v4.0 • Marrow 6.0 • 2022

 06
Leave Feedba*

MEMBRANE TRANSPORT

Closs&cotion o? membrane transport processes :

It is based on energy usage.
ATP is -the universal energy currency o? the cell.

Passive transport processes : ATP is not required.

Active transport processes : PTP is required

Passive transport processes oo:12:26

I. Simple diV^ruSiOn «
Substances move Vrom hgh concentration to low
concentration. Mo ATP required.
Example DiV^rusion o? gases in lung alveoli.

Simple dt?\usion
Oi^usion depends on concentration gradient, area o? the
membrane and thicKness o? the membrane.

Ack’s law :
• DiV^uSion o? a substance is directly proportional to
concentration gradient.
• Di^rusion is directly proportional to area o? the
membrane.
• Oi^rusion is inversely proportional to thichness o? the
membrane. space
lipid SOlubilituJ Cone, qradient x Area
DiWuSion a ——
size
DiWuSion «
ThicKness Active
CnV^usion is directly proportional to lipid solubility and inversely
proportional to size o? the partide/molecule.
Emphysema :

Physiology • v4.0 • Marrow 6.0 • 2022

 06 Membrane
Transport Leave Feedbai

Semipermeable
> membrane
HO HO Dilute
zf Ma.'
Concentrated 4/JzMa'
xLTzwq
osmosis

=
unit o? osmolarity mosm/litre o¥ solvent.
unit o? osmolality • mosm/hy oV solvent.
most commonly used in clinical practice is osmolarity.

Active transport 00:22:06

Hydrolysis oV ATP is required.

a types : Primary active transport and secondary active
transport.
Primary active transport :
Have ATPase enzyme activity.
Example : Ma"- ts" ATPase, Caa* ATPase, H" ATPase
(proton pump).
Ma" h" ATPase :
• Transmembrane protein.
• a subunits (heterodimer and heterogenous) • Alpha and
beta. Alpha may be a I, a a and a 3.
Beta may be I, /J a and ft 3.
• Ma" ions are transported outside and h" ions are
transported inside.
• For every 3 Ma" ions that move outside,
a h" ions come inside (Coupling ratio = 3 : a).
• It is called as electrogenic pump as movement o?
charges are unequal. 3 Ma'
It is Vound in all body cells
(universal/ubiquitous in
expression).
Alpha Subunit has binding sites.
One part is extracellular, and the &
2
other part is intracellular. I
Intracellular part has binding sites Ma' b' RTPase
Vor Ma" and ATP.
Extracellular part has h" binding site.

Physiology • v4.0 • Marrow 6.0 • 2022

 06 Membrane
Transport Leave Feedbai

Exchongers/ontiports »
CT H003' exchanger (anion exchanger).

Ma* glucose cotransporter :

• Also called as S64-T channel protein.
• Ma* h* ATPase pump is expressed on basolateral
membrane. It transports 3 Ma* outside and a h* ions
inside -* intracellular Ma* becomes low.
PTP hydrolysis occurs during this process. This is called
primary active transport.
Os intracellular Ma* is low, Ma* moves inside the cell
Vrom the apical end and glucose follows Ma* ion. This
transport occurs through S€\LT channel protein. It is an
example Vor secondary active transport as it utilizes
the gradient established by pr imary active transport.
ATP is not directly used in ths process.

S6J.T has two isoVorms 5

• SQLT I : Located in intestines (basis oV ORS solution ?or
the treatment o¥ diarrhea).
• S^LT a : Located in proximal convoluted tubules o?
Kidneys.
Vesicular transport processes 00:41:08

Substances are transported in the Vorm oV vesicles.

They are energy dependent -* active transport.
Requires calcium.
Types5
Exocytosis 5 vesicles move ?rom inside to outside.
Endocytosis s vesicles move Vrom outside to inside.
Special proteins are required 5 SMARE proteins Vor
exocytosis and clathrin, megalin Vor endocytosis.
Mo role Vor concentration gradient.

Endocytosis :
Types o? endocytosis 5 I
• Phagocytosis -* microorganism is engulVed inside Vor
destruction.
• Pinocytosis -* fluid billed vesicle is pinched oW inside.

Physiology • v4.0 • Marrow 6.0 • 2022

 06 Membra
Transpol Leave Feedbai

Examples • Facilitated diffusion (carrier mediated) and active

transport processes (channel protein mediated).
Simple diffusion does not show saturation Kinetics.
mCQS :
I. A a9 year old patient was presented with diplopia,
vertigo and gait abnormality for the previous 4 days
preceded by nausea and stomach ache. Meurological
examination revealed mild divergent strabismus of the left
eye, bilateral ptosis and flaccid paralysis. This toxin degrades
which of the followirg ?
A. dathrin.
6. megalin.
C~ Cubulin.
D. Synaptobrevin.
-
Answer D. Synaptobrevin.

a. A 19 year old male patient presenting with features

suggestive of congestive cardiac failure and prescribed
furosemide. This drug inhibits which transport mechanism ?
A. Simple diffusion.
6. Monionic diffusion.
C. Primary active transport.
D. Secondary active transport.

Answer : D. Secondary active transport.

Furosemide blocKs Ma* VS* ad' cotransporter found in thicK
ascending limb of loop of Henle.
3. A SB year old white male presented with shortness of
breath, dry cough, fatigue and we'ght loss for a months
and diagnosed with idiopathic pulmonary flbrosis. He will
have decrease in diffusion of gases because of ?
A. Increase in membrane surface area.
8
6. Increase in membrane thickness.
C. Decrease in pCoa. I
D. Decrease in membrane thicKness.

Answer : 6. Increase in membrane thicKness.

Diffusion is inversely proportional to membrane thicKness.

Physiology • v4.0 • Marrow 6.0 • 2022

 07 Membrane 39
Potentials' Leave Feedbai

QmP is aVflected only by K ions.

Hyperkalemia ; Hypokalemia :
Increase in X in tCF K is Iouj in &CF (concentration gradient
favorable to movement o¥ ion)
OiWusion o? k’ outside is hampered
I
♦V tends to stay inside
elusion o? k‘ outside is enhanced

Inside o? cell becomes more negative

i (hyper polarized) * Less excitable
inside o? cell is positive
(depolarized) » more
excitable

I? QmP is unstable ue. PmP oscillating between -(oO mV to

-40 mV is binown as restless membrane potential. Seen in all
pacemakers :
• SA node o? heart.
• Interstitial cells o? Cajal in QIT.
• Pre botzinger complex neuron in medulla :
Pacemaker Vor respiration.

Equilibrium potential oo:14:25

At isoelectric potential, there is no net ion movement across

the cell (no current flow).

-> Concentration
gradient ECP
intracellular positivity intracellular negativity

Electrical gradient

Intracellular positivity
Concentration gradient : k’ moves Vrom inside to outside

Electrical gradient : h" outside is attracted inside by the

negative charge

At one point, concentration gradient is equal opposite to

electric gradient

Physiology • v4.0 • Marrow 6.0 • 2022

 07 Mer
Pot< Leave Feedbal

potential ¥or multiple ions.

It tahes into consideration both concentration and
permeability o? ions.
Rapid changes in permeability o? Ma*, h*, Cl ions needed Vor
'

action potential generation is understood with the help o? this

equation.

Driving force 00:32:02

-
Driving Vorce = membrane potential Equilibrium potential.
(OF)
e.g : For Ma*, OF = (-10 mv) - (+ GO mv).
OF = - ISO mv.
Ma

I? driving Vorce is negative, a positively charged ion tends to

move inside cell i.e. there is a driving Vorce Vor a cation to
enter the cell and anions will be moved out Vrom the cell.

Gibbs-Donnan effect 00:35.33

ts* and Cl' are permeant ions (easily diV^usible through the
permeable membrane).
However, proteins are anions that cannot move across the
membrane (non-permeable, non-diWusible).
Presence o? non-permeant anions (proteins) on the inside
aV^rect the distribution o? permeant ions (h* and Cl").
Qibbs-Oonnan eVflect is exclusively because o? protein
anions.
emP Megativity inside the cell is because o? protein anions.
The plasma proteins (albumin) are also responsible Vor colloid
oncotic pressure. It is also a starling Vorce helping in fluid
reabsorption.
Q. Extracellular concentration o? positive ion is lOOml/L, and its
intracellular concentration is 10 mmol/u Equilibrium space
potential across the membrane using nemst potential is
A) -GO mV C) GO mV
Active
6) -IO mV o) IO mV

Q. (Zesting membrane potential o? nerve is equal to equilibrium

Physiology • v4.0 • Marrow 6.0 • 2022

 08
Leave Feedbac

CELLULAR FLUIDS

LOoter is the major contributor oV body weight.

In an adult male weighing 10 hg total body water is
-
around 43 L (oO% o? body weight.
18% oV body weght is contributed by proteins.
15% oV body weght is contributed by lipids.
7% o¥ body weght is contributed by minerals.

Total body water = Intracellular fluid + Extracellular fluid

LOater present inside the cell Intracellular fluid (1CF).
uJater present outside the cell : Extracellular fluid (ECF).
a/3rd oV total body water is intracellular.
Remaining i/srd oV total body water is extracellular.
iV total body water is 43 L, 38 L is intracellular and 14 L
is extracellular.

Extracellular fluid (ECF) 00:04:52

Components oV ECF :
• Interstitial fluid
• Plasma
Transcellular fluid is a special subtype oV ECF. It is around
1-3 L and is Vound as pleural fluid, pericardial fluid, synovial
fluid, intraocular fluid
• Total body water in male = (oO% oV body weght.
• Total body water in Vemale = 50% oV body weight.
• Total body water in children = 75% oV body weight.
males have more total body water due to lower Vat
content. (Cater content is inversely proportional to Vat
content. Females have more adipose tissue and lower water space
content compared to males.
Active
Lean body mass Body mass - (Adipose tissue Vat + Mon
adipose tissue Vat + Bone mass).
ulater content is around 70 ml / lOOg oV lean body mass.

Physiology • v4.0 • Marrow 6.0 •2022

 08 Cellular Fluids
Leave Feedba

uJater loss •
• Sweating is around loo ml / day.
• Insensible water loss is usually through evaporation Vrom
shin and lungs.
l-t amounts -to GOO-lOO ml / day.

UJater movement :
• uJater is the solvent and Ma* is the solute.
• UJater follows Ma* movement.
• Ma* is osmotically active -* Drags water along with it.

Osmolarity 00:29:02

Plasma osmolarity = 300 mOsm/L.

Concentration o? osmotically active substances are quantised
using moles and equivalents.
I mole = Qram molecular uoeght oV the substance,
example : I mole oV Mad = £3 + 35.S = S8.S.
equivalents = e^ram molecular weight/valency.
I equivalent o? calcium = 4o/j = £0.

Cell shape changes

• Cell placed in a solution containing 0.9% Mad ( ISO
mmol/L ) = Mo change as the fluid is isotonic.
• Cell placed in a solution containing 300 mmol /l o? urea
( hypotonic solution ) = Cell swells and bursts.
• Cell placed in a solution containing 300 mmol /l o?
mannitol (hypertonic solution) = Cell shrinks.

Plasma osmolarity = 300 mOsm / L.

major contributor Vor plasma osmolarity = Ma* (contributes to
£10 mOsm / l).
Proteins contribute to 0.1S mOsm / L as concentration is low.
Fluid accumulation in interstitial space is edema. In healthy
individuals, there is no accumulation o? fluid in interstitial space
space due to Vollowing safety factors :
I. low Interstitial space compliance Less
Active
distensibilrty -* Mo edema.
Contributes to a safety factor o? around 3mmHg.

Physiology • v4.0 • Marrow 6.0 • 2022

 08 Cellular Fluids 47
Leave Feedbai

Loss o? isotonic Modi Example • Diarrhoea.

ECF volume ICF volume ECF osmolarity

decreases Mo change Mo change

ICF osmolar ity

Mo change

Addition o? hypertonic solution / Excess intahe o? Mad

(Pathogenesis o? hypertension) :

EOF volume ICF volume EOF osmolarity

increases decrease increases

ICF osmolarity
space
increases Active

Physiology • v4.0 • Marrow 6.0 • 2022

 08 Cellular Fluids 49
Leave Feedba,

3. Volume o¥ ICF in body :

O. 0.J X body uoeiyht
&. 0.4 x body coeyht.
F. O.G x body uoeiyht
Gj. 0.8 x body uueyht.

Ansuuer : 6. 0.4 x body uueiyht.

Physiology • v4.0 • Marrow 6.0 • 2022

 09 Characteristics of 51
Leave Feedbac

Bipolar : One end is a dendrite -to receive information and the

other end is an axon to conduct information. Seen in
retina, nose (olfactory epithelium).
multipolar (most common) • Seen in spinal alpha motor neuron.
Dendrites
-> Cell body/soma
0 - MiSSl bodies
Mucleus
> Axon hilioch
Initial segment
*
: myelin sheath
Axon

J
’Mode of Ranvier
/-
> Meurotransmitters
Synapse
Synthesis of proteins • Missl bodies (R&R).
Dendrites ’
• Receiving end
Axon hilloch :
• Part of cell body from where axon originates.
Initial segment :
• Initial First proper part of axon.
• Initiation of action potential in motor neurons
(axon hilloch + initial segment).
Axon terminal/ Synaptic terminal
• Axon ends by forming synapse.
myelm :
• Conduction in axon can be fast /slow based on
presence or absence of myelin.
• if myelin absent, conduction = Slow.
• if myelin present, conduction • Fast.
Modes of Ranvier :
• It is the area of axon devoid of myelin.
• maximum number of Ma’ channels are present,
(aooo - laooo/sq m).
• Initiation of action potential occurs at the Is* node of
Ranvier in sensory neurons.
Axon is for conduction.

Physiology • v4.0 • Marrow 6.0 • 2022

 09 Characteristics Qf
Nerve Fi Leave Feedbai

Action potential 00:37:03

Resting membrane potential oV neuron • - lOmv

X axis : Time in ms.

V axis : membrane potential changes,can be measured with
micro electrodes.
S : Stimulus.
R Response.
;

Latent period is the gap between the stimulus (s) and

response (R).
Local potential change • Tabes membrane potential Vrom
- -
10 mv to 55 mv (threshold or flring (eve). Occurs due
to influx oV Ma* (less slow).
Depolarisation = Because oV Ma* influx (more Vast)
through voltage gated Ma* channels, goes up to a
value oV + 35 mv (close to equilibrium potential oV Ma*
(bMa*) : GO mv), and the inside becomes less negative.
3. Repolar isation : Regains its own polarity. Occurs due to
eWlux oV K*.
4. Hyperpolarisation = Polarity inside the neuron becomes
more negative Vollowing repolarisation up to 90 mv, -
occurs due to
• K eWlux, slow closure oV K channels. I
• CT influx.

Physiology • v4.0 • Marrow 6.0 • 2022

 Q9 Characterigti^gf S5
Leave Feedbai

• In open state m gate is open, H gate is open. Ma+ in$ux

occurs.
• m gate is open, H gate is closed
In inactivation state s
Ma* influx does not occur.

Biphasic action potential ulhen electrodes placed on surface

on neurons. Positive phase -* Isoelectric phase -* Megative

Compound action potential = varying peahsj seen in mixed

nerves. They have lot o? nerve fibres with varying conduction

Graded potential vs Action potential O1:O2:18

Graded potential Action potential

Amplitude charges with Amplitude is always
intensity o? stimulus. constant} independent o?
stimulus strength.

Mo all or none law. All or none law.

Summation possible. Mo summation.
Threshold not needed Threshold is required
mop:
1
Question I : A 3S year old Vemale abrupty developed a right
hemisensor y deceit aVter several days o¥ worK a months
ago, the patient was worKing hard and was under a lot o?
stress.

Physiology • v4.0 • Marrow 6.0 • 2022

 10 57
Leave Feedbai

CLASSIFICATION OF NERVE FIBERS

two »
Edonger-Qasser clossiVcotion.
Lloyd-Hunt classification (sensory classification)

Erlanger- Gasser classification oo:Q1:15

ftosed on presence or absence oV myelin.

3 types oV nerve fibers : 0, 6 and C groups.
• myelin content, size oV nerve fibers and nerve
conduction velocity decrease Vrom A to C.
• myelin content is maximum in A group.
C. group is unmyelinated.
• A group oV nerve fibers are thickest. C yroup oV nerve
fibers are small, slender and thin.
• A yroup oV nerve fibers have Vastest nerve
conduction velocity. C yroup oV nerve fibers have
slowest nerve conduction velocity.
• A yroup oV nerve fibers are Vurther classified into ACK,
Ay and Ad.
• ACK is the thickest nerve fiber, has maximum myelin
content and Vastest nerve conduction velocity.
• Merve conduction velocity oV ACK nerve fibers is
lAOm/sec. Spihe duration oV action potential is less.
• Merve conduction velocity oV C yroup oV fibers is
3lm/sec. SpiKe duration oV action potential is maximum
(around A ms).

‘A’ nerve fibers 00:07:49

ACK nerve fiber :

Has both sensory and motor components.
Has Vastest nerve conduction velocity (because oV maximum
myelin) Vor the sensory Vunction '• Proprioception (joint position
sense).
Proprioception helps in maintaininy balance.
motor Vunction : Alpha motor neuron in spinal cord

Physiology • v4.0 • Marrow 6.0 • 2022

 10 Classifi
Nerve
Lloyd-Hunt classification (sensory
classification) 00:19:09

Mo motor component.
4 types o¥ nerve fibers each corresponding to a type in
&rlarger-e\asser classification :
Type l corresponds to Pa. Has a components la
(muscle spindles) and lb Ce^olgi tendon organs).
Type a corresponds to
Type 3 corresponds to Ad.
Type 4 corresponds to C nerve fibers (unmyelinated).
Strength duration curve :
Threshold stimulus for action potential depends on strength of
stimuli and duration of stimuli Relationship between strength
and duration of stimuli is studied using strength-duration
graph.

Chronaxie = I ms
Strength of current is denoted on V-axis.
Duration of stimuli is denoted on X- axis.
Rheobase : minimum strength of current required to produce
a response (denoted on V-axis).
Chronaxie : Time required for twice the strength of rheobase
to produce a response (denoted on x-axis).
Chronaxie is inversely related to excitability of the tissue
(less chronaxie -* more excitable). space
Chronaxie of nerve fibers is less compared to chronaxie of Active
muscles (nerve fibers are more excitable than muscles).

Threshold stimulus is required to generate action potential.

Accommodation Repeated subthreshold stimuli does not
produce action potential.
Physiology • v4.0 • Marrow 6.0 • 2022
 10 Classific
Nerve Fl

Tinel’s sign • On -tapping the injured nerve, tingling sensation

is Veit along the course of the nerve. Positive sign indicates
nerve regeneration.

Classification of nerve injuries 00:40:18

each individual axon is surrounded by a covering layer called

endoneurium.
groups o? axons are found in a bundle which is covered by a
covering layer called perineurium.
groups of bundles are surrounded by a covering layer called

Seddon’s classification (to determine prognosis) $

3 grades :
• Meuropraxia '• Physiological prolongation of nerve
conduction velocity.
Seen in nerve compression. Has good prognosis
(spontaneoud recovery is seen).
Example $ Saturday night palsy.
• Axonotmes’is » Axonal injury. Intermediate prognosis.
• Meurotmesis : Complete transection of nerve ftber
(nerve fiber is split into a halves)
Has the worst prognosis.
&
Sunderland classification (to determine prognosis) 8
S grades s I
• indegree -* Meuropraxia.
• aM degree -* Axonotmesis (Axonal injury).
• 3rd degree -* Axon + Endoneurium disruption.

Physiology • v4.0 • Marrow 6.0 • 2022

 11
Leave Feedbai

SKELETAL MUSCLE

Skeletal muscle 00:00:48

Parts :
Cell membrane • Sarcolemma.
Connective tissue layers :
• Endomysium surrounds each muscle ftber.
• groups o? muscle ftbers are collected inside a. bundle
called Vascicles
Perimysium surrounds each Vascide.
• Entire muscle is surrounded by epimysium.
Functional units -* Sarcomere.
Contains A primary proteins • Actin and myosin.
Sarcomere ;
• Area, between two z lines is one sarcomere.
• Thin ^lament • Actin
• I band : Contains actin.

space
Active
(non overlapping
Part o¥ myosin)

Physiology • v4.0 • Marrow 6.0 • 2022

 -
Dystrophin glycoprotein complex »
Dystrophin attaches actin to dystroglycan in the cell
membrane which in turn attaches to a dystroglycan.
a dystroglycan is attached to laminin in the extracellular
matrix.
Dystrophin requires syntrophins to attach actin to fl
dystroglycan.
fl dystroglycan also attaches to sarcoglycan and
sarcospan in the cell membrane.
-
Dystrophin glycoprotein complex
- Laminin

-
a dystroglycan

Sarcoglycan <
fl - dystroglycan

Actin

-
Dystrophin glycoprotein complex involves the Vollowing :
Dystrophin, syntrophins, beta dystroglycan, alpha
dystroglycan, sarcoglycan and sarcospan.
Dystrophin is also called as anchor protein.
Absence oV dystrophin causes Duchenne muscular dystrophy
(omo). SKeletal muscle weakness is the predominant Venture.
u)eahness oV diaphragm causes respiratory muscle
paralysis and death in Dmo.
Titin !
• muscle spring.
• e^ives elastic support.
• Largest protein in humans (word ‘titus’ means giant).
• extends Vrom Z. line to m line. space
•
•
Attaches myosin head to 2. line.
beeps actin and myosin in place (side by side
Active

Physiology •v4.0 • Marrow 6.0 • 2022

 1j Skeletal Muscle 67
Leave Feedbac

Depolarization Ma' influx -through voltage gated Ma+ channel.

Resting membrane potential changes to - 40 mV Vrom -10
mV.
voltage gated Caa' channels open at -40 mv -* Calcium
influx.
Calcium causes release o¥ acetylcholine (exocytosis).
Acetylcholine (Ach) acts on muscle causing contraction.
• Pu¥fler flsh contains tetrodotoxin uhich is a blocher o?
voltage gated Ma' channel. It causes muscle paralysis
and death.
• Lambert baton myasthenia syndrome :
Autoantibodies cause destruction o? voltage gated Caa*
channel -* Mo release oV Ach -* muscle paralysis.
• Release o? Ach requires synaptobreVm which is degraded
by botulinum toxin flaccid paralysis.
Ach acts on nicotinic acetylcholine receptor in the skeletal
muscle -* influx o? Ma' -* end plate potential (&PP), a type o?
local potential.
&PP summates and crosses threshold -* flring o? action
potential muscle contraction.
Spontaneous release o? Ach vesicles can induce miniature end
plate potential (mePP).

Calcium channels in skeletal muscles 00:45:38

Dihydropyridine receptor Caa' channel (dhPR) : Found in ‘t’

tubules, ‘t’ tubules are invaginations o? skeletal muscle cell

membrane resembling the alphabet ‘t’.

DHPR receptors are located close to sarcoplasmic reticulum,
bnd part o? sarcoplasmic reticulum is called terminal cistern.
Calcium is stored in terminal cisterns.

Ryanodine receptor Caa' channel (RVR) : Found in space

sarcoplasmic reticulum.
Active
DHPR and RVR calcium channels interact mechanically.
Action potential travels through ‘t’ tubules and activates DHPR
receptors.

Physiology • v4.0 • Marrow 6.0 • 2022

 1-| Skeletal Mijscle 69
Leave Feedbai

• myosin head detachment requires a new ATP molecule.

uJith new ATP molecule, the above cycle repeats.
• AVter death, no ATP available -* muscles in sustained
contraction -» r igor mortis.

Relaxation of skeletal muscle 00:59:23

Calcium is stored in terminal cisterns o? sarcoplasmic

reticulum. Ryanodine receptor helps in release o¥ calcium Vor
muscle contraction. Following muscle contraction, calcium is
tahen bach inside through S8I2.CA pump.
S&2.CA pump helps in storage oV calcium and muscle relaxation.

Ryanodine receptor overactivity -* enhanced release o?

calcium -* increased muscle contraction increased release
o? heat -* malignant hyperthermia.
Treatment : Blochade o? ryanodine receptor by dantrolene
sodium

moqs =
l. A 8 year old boy presents with muscle weakness,
diWiculty climbirg stairs and Vailing down more oVten
when playing with his Vriends. This disorder is because
o? absence oV :
A. Troponin.
6. Tropomyosin.
C. Calmodulin.
Dystrophin.
D.
Answer : D. Dystrophin.
A.Spontaneous release o¥ acetylcholine at the
neuromuscular junction produces *
-
A. miniature end plate potential.
6. Action potential
C. Post - tetanic potential.
§
0. testing membrane potential.
8
Answer : A. miniature end - plate potential. I
3. A 30 year old Vemale presents with little to no pain at
the beginning o? the day but it progressively gets worse
as the day progresses. By the end o? the day, she

Physiology • v4.0 • Marrow 6.0 • 2022

 12 Leave Feedbai

PROPERTIES OF SKELETAL
MUSCLE

Contraction (muscle shortening) : Length changes.

Force of contraction = Tension changes.

Length tension relationship graph 00:01:53

Tension

Tension ; —
Decreases

C p
|m||||

Actin and myosin maximum overlapping between Actin and myosin

are wide apart = myosin = Optimal overlap/ still overlap but
actin and
Mot overlapping. maximum overlap. not optimal.

Tension > minimum Tension = maximum (corresponds to Tension :

a sarcomere length o¥ a/z) Decreases

Types oV -tension :
Skeletal muscle stimulated -* Actin and
l. Active -tension

myosin interacts -> muscle contracts (cross bridge

formation).
Active tension a Cross bridge formation.
Active tension a Diameter o? muscle ^bre.
Active tension a Length o? muscle ^bre.
Active tension a Frequency o? active potential
space
Active tension a Klumber o? motor units recruited. Active
A. Passive tension muscle not stimulated -* elastic stretching
(passive : Titin mediatecD.
3. Total tension : Active tension + Passive tension.

Physiology • v4.0 • Marrow 6.0 • 2022

 j2 Propertii
Skeletal Leave Feedbac

Motor units 00:23:57

• Consists o? a. single alpha motor neuron and the muscle

ftbers it innervates.
• For muscles with $ne precise movements.
=
Example Extraocular muscles 6 motor unit innervates
only around 3-G muscle ftbers).
• In case o? coarse movements. Example : Leg and loach
muscles (l motor unit innervates upto foOO muscle ftbers).

During the process o? muscle contraction relaxation, heat is

generated.
Types o? heat =
In a resting state :
• testing heat = Because muscles undergo basal metabolic
process.
During contraction :
• Activation heat : uJhen actin and rryosin are activated.
• Shortening heat During process o? shortening.
During relaxation =
• Relaxation heat Seen dur ing isotonic contraction
(tension is same but length changes). It is the heat that
is liberated to bring the length bach to its previous length.
• Recovery heat.
Phenomena related to contraction relaxation =
• upon stimulation, there is contraction relaxation :
Simple muscle twitch phenomenon.
• In response to
multiple stimuli, both Contraction and
relaxation are seen but they are not complete. This
phenomenon is called incomplete tetanus.
• Further increase in stimuli, muscle will go into a state oV
sustained contraction. Mo relaxation in
between. This phenomenon is called complete tetanus.
Pathological Spastic paralysis (in tetanus by
Tetanospasmin toxin).

Physiology • v4.0 • Marrow 6.0 • 2022

 13 7S
Leave Feedba

CARDIAC MUSCLE AND SMOOTH

MUSCLES

Introduction 00:00:24

Cardiac muscle is similar to skeletal muscle with few

differences •
• Contractions are involuntary : Meeds pacemaker (SR
node).
• Has actin and myosin. It is a striated muscle.
• myosin heavy chain consists of alpha (mainly in atrium)
and beta subunits (mainly in ventr icles).
• Has tropomyosin and troponin.
• elastic nature (elastic recoil phenomenon) due to titin
protein.
• mutation in titin : Dilated cardiomyopathy (ho recoiling,
only stretches).
• Synchronized contraction happens and is called
functional Syncytium because of gapJunctions.
• Protein that forms gapJunctions » Comexins.
• Histology *• QapJunctions are located in intercalated disc
region.

Unique features of cardiac muscle 00:07:03

I. Length Tension relationship :

• Length is determined by blood volume : end diastolic
blood volume (SDv).
• Tension determined by force of contraction ; Pressure
in left ventricle.

space
Active

(end-diastolic volume)

Physiology • v4.0 • Marrow 6.0 • 2022

 13 Cardiac
Muscle and
Smooth
major part of contraction lies in absolute refractory period
Hence, the second stimuli cannot be summated So, cardiac
muscle cannot be tetanteed (adequate contraction
relaxation are always needed for proper functioning of
heart). This is an evolutionary adaptation.

Smooth muscles 00:21:46

• Mo striations on the surface.

• Involuntary PacemaKer = Cajal cells.
• Has actin and myosin, no Z - lines, but has dense bodies.
• Mo troponin but has calcium binding protein : Calmodulin.
• Mo titin, not elastic (no elastic recoil).

Types of smooth muscles

€\ap junctions present ; Stop junctions absent :

Single unit/unitary multi-unit smooth muscles/
smooth muscles vascular smooth muscles
• InQIT. • In blood vessels.
• uterus.
• urinary bladder.
• ureter.
Contraction and relaxation (both are myosin based regulation) :
• Contraction mLCK (myosin Light Chain Kinase)
activation -* Petin myosin interaction (contraction)
• Relaxation : mLCP (myosin Light Chain Phosphatase)
activation -* inhibits contraction.
mLCP inhibited by Rho Kinases -* Mo relaxation.
Rho Kinase inhibitors (maKes relaxation possible),
example : Fasudil.
Contraction and relaxation (regulation with help of AMS) :
• Parasympathetic -* Excitatory potential Contraction.
• Sympathetic -* Inhibitory potential -* Relaxation.
a receptors for calcium release in smooth muscles :
IP^RVRs

Physiology • v4.0 • Marrow 6.0 • 2022

 14
Leave Feedba,

SYNAPTIC TRANSMISSION AND

NEUROTRANSMITTERS

Synaptic transmission 00:00:47

a types.
Electrical synapses :
Communication through gapJunctions.
Fast process.
Chemical synapses :
Involves the release of neurotransmitters.
Slow process.
Synapse »
• Point of communication between two neurons.
• me type of synapse is axosomatic synapse -* Axon of
one neuron communicates with the cell body of another
neuron.
• Meurotransmitters are released in synapse.
• Meuron above synapse is called as presynaptic neuron.
Meuron below synapse is called as postsynaptic neuron.
• Structure of synapse was first identified by Sir Charles
Sherrington. He is considered as the 'Father of synaptic
transmission’.
• Meurotransmitters act on postsynaptic neuron -*
produce post synaptic potentials -* can be
Excitatory (excitatory post synaptic potential) or
Inhibitory (inhibitory post synaptic potential).
• Excitatory and inhibitory post synaptic potential can be
fast or slow.
• Excitatory post synaptic potential (ePSP) can be brought
about by glutamate.
• Inhibitory post synaptic potential (1PSP) can be brought
space
about by glycine or QA6A. Active
Fast EPSP :
Cell interior becomes less negative due to influx of positive
ion : Either Ma* or Caa*.

Physiology • v4.0 • Marrow 6.0 • 2022

 14 Synaptic, RI
Transmission & Leave Feedbai
Neurotransmittf
A. Lateral inhibition -* Presynaptic neuron is inhibited by
another neuron Vrom the lateral side. It is also called as
presynaptic inhibition. Example • Retina.

3. Feedbacks inhibition -> Alpha motor neuron activates

another neuron called as Renshaw cell neuron which in
turn inhibits the alpha motor neuron.
Renshaw cells utilize glycine ¥or feedbacks inhibition.
They are useful to control firing o? alpha motor neuron.

Alpha motor
neuron

Feedbacks
inhibition

2.enshauj cell

Meuron

Neurotransmitters 00:21:22

Otto Loewi discovered the first neurotransmitter -> ft chemical

that decreases heart rate called vayusstof^. It was later
identified as Acetylcholine.
Criteria Vor neurotransmitters :
• Neurotransmitter should be synthesized and stored in
the presynaptic neuron.
• Release o? neurotransmitter into the synapse should
occur in response to a signal

Physiology • v4.0 • Marrow 6.0 • 2022

 14 Synaptic 83
Transmi! Leave Feedba<
Neurotra
• Nicotinic receptor is an inotropic receptor.
• muscar inic receptor is a metabotropic receptor.

Biogenic amines 00:35:04

Norepinephrine :
• Synthesized from dopamine with the help o? dopamine
beta hydroxylase.
• Norepinephr ine isexclusively distributed in locus coeruleus.
Throuyh locus coeruleus, it has widespread connections
to major parts o? the brain.
• Neurotransmitter o? arousal -* Helps to Keep in awake
state.
Dopamine :
3 pathways :
• Niyrostriatal pathway in basal yanylia -* motor
movement control.
Deficiency leads to development o? parkinsonism.
• mesocortical pathway -* 8 areas •
ventral teymental area (vTP) -* Reward pathway.
Nucleus Accumbens Addiction behavior.
• Tuberoinfundibular pathway Dopamine inhibits the
release o? prolactin Vrom anterior pituitary.
Dopamine receptors :

Di, oa, 03, D4 OS receptors. All are Q protein coupled.

Serotonin •
• major inhibitory neurotransmitter in brain.
• Location Raphe nuclei, QI tract, blood platelets.
• Another name is S-Hydroxy Tryptamine (5HT).
• There are 7 receptors $ SHT to SHT. All are Q protein
coupled except SHTs which is lyandyated (ionotropic).
• Actions are based on receptors :
: Platelets -» Platelet ayyreyation.
SHT^
5HTac : QIT -* Decreases food intake (satiety).
SHT^ : Area postrema “* Vomitiry.
SHT* : QIT -> Peristalsis.
SHT^ and SHT^ -* Limbic system.

Physiology •v4.0 • Marrow 6.0 • 2022

 14 Synaptic 85
Transmis
Neurotrai
^LJLeave Feedbai
sclerosis. Riluzole is a MmDA receptor blocher used in the
treatment o¥ amyotrophic lateral sclerosis.
G^ABA :
• G\ABA is a predominantly inhibitory neurotransmitter.
• Distr ibuted throughout the brain.
• G^ABA produces inhibition through hyperpolar ization (cell
interior is more negative). Hyperpolarization is due to
Cl' ion in^ux.
• G\A&A agonists Benzodiazepines, Barbiturates are used
as sedatives.
• G^ABA ejects • Basal ganglia -» Striatum -» Inhibition o?
involuntary movements.
Loss o? G\ABA along with loss o? cholinergic neurons
containing Ach in the striatum leads to an involuntary
movement disorder Known as Huntington’s chorea

G^BA receptors :
• QABA A, G\ABA 6, and QABA C.
• QA6A A &.ABA C are linKed to ion channels.
• QABA 6 is a protein coupled receptor.
glycine :
• Both excitatory and inhibitory neurotransmitter.
• Inhibitory e^Kect is predominantly seen in Henshaw cell
neurons in spinal cord. Alpha motor neuron activates
Renshaw cell neuron which in turn inhibits alpha motor
neuron through glycine.
• Excitatory e^rVect is seen in hippocampus (activation o?
MmoA receptor).
• Strychnine is an antagonist o? glycine.
Strychnine poisoning causes overactivity o? a motor
neurons -* spastic paralysis.

Tetanospasmin also causes spastic paralysis. Tetanospasmin

&
inhibits inhibitory interneuron (uses QA6A) -* Mo G^ABA release 8
Vrom inhibitory interneuron -* spastic paralysis. I

Physiology • v4.0 • Marrow 6.0 • 2022

 15 R7
Leave Feedba

SENSORY RECEPTORS

Meurophysiology can broadly be classified into ’

• Sensory physiology.
• motor physiology.
• Higher mental Sanctions.
Sensory pathways are aSSerent, ascendirg pathways,
chives input to the central nervous system,
motor pathways are efferent, descending pathways.
Carries output Srom the central nervous system.

Sensory physiology 00:02:38

Two important group o? senses =

I. general senses/somatic senses : Receptors in shin.
• Touch.
• Rain.
• Temperature.
a. Special senses are 5 in number.
Receptors inside the shull.
• Vision.
• Hearing.
• Olfaction.
• Taste.
• balance : maintain erect posture Ooy vestibular
apparatus).
Sensory control is bottom up control system/ascending
pathways »
Lower most control point lies in shin.
Shin receptors (Sensation lihe touch/pain)
| Primary aV^erents/i5* order neurons
Spinal cord space
Thalamus
Active
Thalamus (sensory relay station)
Tertiary a?Serents/3rd order neurons
Sensory cortex

Physiology • v4.0 • Marrow 6.0 • 2022

 Intensity :
Conveyed through action potential that obeys all or
none law (amplitude is always constant, frequency can
change).
more intense stimuli is conveyed through increase in
frequency of action potential.
Less intense stimuli is conveyed through decrease in
frequency of action potential.
Duration • Time interval between starting and stopping
of a response.

General senses receptors 00:24:54

Touch, pain and temperature receptors.

Touch receptors (4 types) :
Superficial : meissner’s corpuscle and merhel cells.
Deep : Pacinian corpuscle and Ruffini’s endings.

meissner’s merKel cells Pacinian corpuscle Ruffini’s endings

corpuscle
I.meissner’s corpuscle :
• Abundant in lips and fingertips.
• Responds to gentle tap, low frequency vibrations
(around 5-40 Hz).

a. merhel cells ;
• Respond to touch, sustained pressure (estimating pulse).
• Sensitive to edges and comers feraille reading in blind
people).
3. Pacinian corpuscle :
• Largest.
• Encapsulated receptor.
• Responds to deep touch (deep pressure), high
frequency vibration ((oO-SOO Hz).
4.Ruffini’s endings •
• Exclusively abundant in joint spaces. Also called as joint
capsule receptors.
Physiology • v4.0 • Marrow 6.0 • 2022
 15 Sensory
ReceptJ Leave Feedba<

Analgesia 00:47:46

Activated Vree nerve endings convey the inVormation using

depolarization. For depolarization, voltage gated Ma* channels
are required
IV voltage gated Ma* channels are blocked, local anaesthesia
is produced (mechanism oV action oV Lignocaine).

IV voltage gated Ma* channels undergo mutation, no pain is

Veit. It is a called Congenital insensitivity to pain syndrome
(CIPS).

endogenous opioid analgesic system (morphine lihe) consist

oV endorphins, dynorphins, enKephalins. It is Vound in PAQ
(per iaqueductal gray matter).
Acupuncture activates per iaqueductal gray matter » Release —
—
oV endogenous opioids » Analgesia.
Stress induced analgesia =
Pain is abolished in stressVul conditions (eg: soldiers in war).
It is due to endogenous cannabinoids : Anandamide.
Anandamide containing neurons are Vound in periaqueductal
gray matter.
Perception oV pain :
Ad and C nerve Vibers
activates
Projection neurons in spinal cord

—
Relays pain to cortex » Pain sensation is Veit.

QAT& control theory proposed by melzach and Ldall explains

how massaging relieves pain.
massaging is a Vorm oV gentle touch.
^activates
nerve $bers 8
I
^activates
Inhibitory interneurons

Inhibition oV projection neurons —> Mo pain.

Physiology • v4.0 • Marrow 6.0 • 2022
 qq
15 Sensory
Leave Feedbai

Slowly adapting receptors (tonic receptors) •

First stimulus produces an action potential Vollowed by no
response. Another action potential is produced because o? a
stimulus some time later.
example : merhel cells, EuWini’s endings, Vree nerve endings.
Phasic receptor
AP
Mo response

I' 'T 'T

First stimulus multiple Stimuli

AP

'T “t 't
First stimulus Another stimuli
Tonic receptor

mops
massage and the application o? liniments to pain?ul
area in the body relieves pain due to !
A. Stimulation o? endogenous analgesic system.
6. (Seiease o? endorphins by the ftrst order neurons in
the brain stem.
C, Eelease o? glutamate and substance P in the spinal

cord.
O. Inhibition by large myelinated aft?erent ftbers.
Answer : D Cerate control theory using touch
receptors).
a. Pain relie? in acupuncture is mediated by:
A.
6. Kinins.
C. Substance P.
D. Prostaglandins.
Answer : A.

3. Phasic receptors is
A. merhel’s disc.
6. Euft?ini’s end organ.
C. Pacinian corpuscle.
D. Pain receptors.
Answer : C.

Physiology • v4.0 • Marrow 6.0 •2022

 jQ Somatosensory. os
Pathways Leave Feedbai

ftroun Sequard syndrome Hemisection o? spinal cord

’
Clinical features :
Ipsilateral loss o? dorsal column sensations
(proprioception, Vine -touch, vibration).
Contralateral loss o? anterolateral pathway sensations
(loss o? opposite side pain and temperature).
Ipsilateral motor paralysis.

Spino-Thalamic pathway 00:13:50

• Third level o? control system : Thalamus.

• Thalamus is considered to be the sensory relay station.
• ventro Postero Lateral nuclei (vPl) r Thalamic nuclei
associated with touch, pain and temperature (general
senses)
I? vPl gets inVarcted in strobe, the patient presents
with excruciating pain : Dejerine Roussy syndrome.
3rd order neurons originate Vrom vPl nuclei.

Sensory cortex oo:17:20

Sensory cortex is located in parietal cortex.

Brodmann areas 3, 1 a Vorms the sensory cortex.
Responsible Vor localization o? sensation.
Alt body parts are represented here by which the brain
recognizes the specific body part.
The representation is Known as sensory homunculus.

I
Pre central
(fronted cortex)

motor cortex

nsory homunculus =
• parietal cortex.
Seen in the
• Plotted by Penfteld : Hence Known as Penfteld
homunculus.
• medial top part represented by legs.

Physiology • v4.0 • Marrow 6.0 • 2022

 16 Somatosensory _ 97
Leave Feedba

present and ft projects the sensation to the lowermost

receptor (phantom thumb).
Cortical plasticity s Any region in the sensory cortex which
becomes unused Vollowing loss oV the body part, gets
encroached upon by nearby regions. Plays a more important
role in explaining phantom limb.

uJeber-Fechner law =
magnitude oV sensation Veit is always directly proportional to
the log intensity oV initial stimulus.

mCQs =
I. fin anterolateral cordotomy relieving pain in the right leg is
elective because ft interrupts the :
A. LeVt Dorsal column.
6. LeVt ventral spinothalamic tract.
C. LeVt lateral spinothalamic tract.
D. £ight lateral spinothalamic tract.
Pain is conducted through contralateral lateral spinothalamic
pathway.
Q. Loss oV Veel oV size and shape oV an object is seen in lesion
o?:
A. Pons. &. midbrain.
C. Thalamus. D. cerebral cortex.
Astereognosis is seen in lesions oV cerebral cortex.
Q. whichoV the Vollowing has small representation in
somatosensory area oV cerebral cortex?
A. Lips. 6. Thumb/Vingers.
C. Tongue. D. TrunK.

Physiology • v4.0 • Marrow 6.0 • 2022

 Vision qq
17
Leave Feedbai

7. fcetinol glial cells (&^c)/rnuller’s cells :

It has no role in vision.
1+ is a simple supporting cell.

Rods 00:10:28

The rods contain a visual pigment called visual purple or

rhodopsin.
fchodopsin is comprised of the protein opsin with an isomer of
vitamin A.
Form of Vitmain A :
In the darts state ll-cis retinal
In I’ght state • All trans retinal

Phototransduction :
It is the process of converting a light stimulus into an action
potential.
Light converts ll-cis retinal > All trans retinal.
Oorts state =
The resting membrane potential of the rods is -GO mV.
There is h* efflux.
Kia" channels open with the help of increased cQmP to bring
about Ma* influx, this is called as darts current.
This leads to depolarisation.
ll-cis retinal is present.

space
Active

Physiology • v4.0 • Marrow 6.0 • 2022