Physiology Points

By
Dr. S. Krishna Kumar MD PHY (AIIMS, New Delhi)
Table of contents
Topic Page No.
General physiology 2
Nerve muscle physiology 12
Neurophysiology 22
Cardiovascular physiology 38
Respiratory physiology 59
Gastro intestinal physiology 69
Renal physiology 80
Endocrine physiology 92
Reproductive physiology 110

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 General physiology-High yield topics

Homeostasis The foundation of physiology

 Normal cell function depends on the
constancy of intestitial component of
the ECF
 To describe “the various physiologic
arrangements which serve to restore the
normal state, once it has been
disturbed,” W.B. Cannon coined the
term homeostasis.
 Claude Bernard-concept of milieu
intérieur
 Steady state and equilibrium are both
stable conditions, but energy is required
to maintain a steady state

Control systems and feedback

 Basically designed to maintain a controlled variable at a setpoint

 Effectiveness of a control system assessed using Gain
 Gain=Correction/Error
 Higher the gain, higher the accuracy of regulation.
 For body temperature control system,gain is -33
Negative feedback
 A pathway in which response opposes or removes the signal
 Stabilize the variable being regulated
 Examples-ACTH secretion,Aldosterone-potassium,Glucose regulation,Growth hormone
secretion,BP regulation
Positive feedback
 Response reinforces rather than decrease or removes it.Leads to vicious cycle.
 Examples-Clotting,Calcium entry into sarcoplasmic reticulum,LH surge during
ovulation,Action potential(Hodgkin’s cycle),Parturition(Ferguson reflex),Shock(Menmonic:
CLAPS)
Feedforward control
 Allows the body to anticipate change and maintain stability
 Example-Salivation reflex-sight,smell,thought of food leads to salivation-anticipation of food

The Body As Organised “SOLUTIONS”

TOTAL BODY WATER (60% of body weight),42 liters

INTRACELLULAR FLUID EXTRACELLULAR FLUID
2/3rd of TBW i.e., 40% 1/3rd of TBW .i.e., 20% body weight (14 liters)
body weight (28 liters) INTERSTITIAL FLUID PLASMA
75% or 3/4 of ECF or 15% of 25% or 1/4th of ECF Or 5%of
th

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 body weight (10.5 litres) body weight (3.5 litres)

 In the average young adult male, 18% of the body weight is protein and related substances,
7% is mineral, and 15% is fat
 Daily intake of water-2300ml
 Output: Insensible—skin 350ml,Insensible—lungs 350ml,Sweat 100ml,Feces 100ml,Urine
1400ml
 ECF: Most abundant cation-Na+
 Most abundant anion-Cl-
 ICF: Most abundant cation-K+
 Most abundant anion-Phosphates > Proteins
 Transcellular fluid(1-2L)- synovial, peritoneal, pericardial,intraocular spaces,cerebrospinal
fluid

Measurement of Body Fluid Volumes:

 Measurement of Fluid Volumes in the Different Body Fluid Compartments is by The

Indicator-Dilution Principle:Volume=Amount/concentration
 Total body water: 2H2O(Deutrium oxide), 3H2O(Tritium Oxide),Antipyrine(Mn:TAD)
 Extracellular fluid : 22Na,125I-iothalamate, Thiosulfate,Inulin,Sucrose(Mn:NITIS)
 Intracellular fluid : (Calculated as Total body water – Extracellular fluid volume)
 Plasma volume: 125I-Albumin, Evans blue dye (T-1824)(Mn:PIE)
 Blood volume: 51Cr-labeled red blood cells, or calculated as Blood volume = Plasma volume/
(1 - Hematocrit)
 Interstitial fluid: (Calculated as Extracellular fluid volume - Plasma volume)

Osmosis
 The diffusion of solvent molecules into a region in which there is a higher concentration of a
soluteto which the membrane is impermeable
 The pressure necessary to prevent solvent migration to the more concentrated solution is
the osmotic pressure of the solution
 Osmotic pressure depends on the number rather than the type of particles in a
solution(colligative property)
 Other examples of colligative property-Freezing point depression,Vapour pressure
lowering,boiling point elevation
 The concentration of osmotically active particles is usually expressed in osmoles and
milliosmoles

Osmolarity and osmolality

 OsmolaRity-number of osmoles per litRe of solution

 Osmolality-number of osmoles per kg of solvent.Serum osmolality-285-295mOsm/kg H2O
 Osmolality is not affected by changes in volume of solution or by temperature.
 Most accurate way of finding out osmolality is by Freezing point depression
 Approximate formula is Osmolality (mOsm/L) = 2[Na+] (mEq/L) +0.055[Glucose] (mg/dL) +
0.36[BUN](mg/dL)

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  Vant Hoff Law-used to calculate osmotic pressure-
Π = σ(nCRT)
σ – Reflection coefficient
Π – osmotic pressure
N = number of dissociable particles
R = Gas constant
T = Temperature (K)

Tonicity

 Used to describe the osmolality of a solution relative to plasma

 Same osmolality as plasma-isotonic(0.9% Nacl)

Plasma Protein Molecular Weight Concentration Contribution to osmotic

pressure

ALBUMIN 69,000 3.5-5g% 80%

GLOBULIN 1,40,000 2g% 20%

FIBRINOGEN 4,00,000 0.3g% 0%

Non-ionic diffusion-
 Substances cannot cross the membrane in charged form but cross in undissociated form
 Example-Ammonia transport in GIT/Kidney

Cellular Physiology-High yield topics

Electrophysiology of the cell

Resting Membrane Potential

 Every cell shows a potential difference with the inside being negative.
 Due to diffusion of K+ and sodium potassium ATPase(5-10%)
Some important resting membrane potentials

Structure RMP(mv)

Neuron -70

Skeletal Muscle -90

SA node -30 to -40

Ventricle -90

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Smooth Muscle -30 to -40

RBC -10

Equilibrium Potential
 Membrane potential at which there is no net flux of that ion

Ion Equilibrium Potential(mv)

Sodium +60

Potassium -90

Chloride -70

Ecl- is close to RMP

 To calculate equilibrium potential of a single ion: Nernst Equation

Goldman-Hodgkin-Katz Equation:
 Involves multiple ions
 Depends on concentration gradient and permeability of ions
Gibbs Donnan Effect:
 The presence of non-diffusible ions across the cell membrane affects the concentration of
diffusible ions. The negatively charged proteins and phosphates which are present inside the
cell cannot diffuse across the membrane. This results in a greater permeability of chloride (a
diffusible anion).

Cell Membrane  Current concepts of membrane physiology

is based on Fluid and Mosaic model
proposed by Singer & Nicolson,1972

Membrane Lipids  Has both hydrophilic and hydrophobic

properties(Amphipathic)
 Phospholipids-
Phosphatidylcholine,Phosphatidylethanola
mine ,Phosphatidylserine
Phosphatidylinositol,Sphingomyelin
 Glycolipids-Cerebrosides,Gangliosides
 Sterols-Cholestrol
 Membrane fluidity changes with
temperature: Temperature at which the
membrane undergoes ordered to
disordered(melts) is the transition
temperature(Tm)
 Saturated FA- Increase in Tm, decrease in
fluidity

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Membrane proteins
 Unsaturated FA- Decrease in Tm, Increase
in fluidity
 Cholesterol modifies fluidity:Below Tm-
Increases fluidity,Above Tm-Limits fluidity
and that’s why is called as FLUIDITY
BUFFER
 Membrane lipids are asymmetrically
distributed: Outer Membrane-Lecithin and
sphingomyelin
 Inner leaflet- Phosphotidyl
serine,phosphotidylethanolamine
 Integral proteins (Glycophorins in RBC):
distributed asymmetrically.has a
transmembrane region (Having a stretch of
hydrophobic aminoacids and hydrophilic
regions at the ends.
 Peripheral proteins(Spectrin in
RBC):attaches by
glycosylphosphatidylinositol (GPI) anchors
 Examples of GPI anchored proteins:Alkaline
Phosphatase,CAMs,proteins that Combat
Cell lysis by complement
 Proteins may be
myristoylated,palmitoylated or prenylated
 Functions as 1.CAMs 2.Pumps 3.Carriers
4.Receptors 5.Enzymes(Mn:PCR-E.Coli)

Composition of cell membrane

Component Percentage

Protein 55

Phospholipids 25

Cholesterol 13

Glycolipid 4

Carbohydrate 3

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Ratio of protein to lipids in different membranes

Inner mitochondrial membrane 3.2

Sarcoplasmic Reticulum 2.0

Outer mitochondrial membrane 1.1

Myelin 0.23

Transport across cell membrane

Passive processes Diffusion:

 No energy is expended directly to
mediate the transport process
 Net flux of solute particles from areas of
high to areas of low concentration
 The time required for equilibrium by
diffusion is proportional to the square of
the diffusion distance
 Fick’s law of diffusion: J= -DA ΔC/ΔX,
where J is the net rate of diffusion, D is
the diffusion coefficient, A is the area,
and Δc/Δx is the concentration
gradient
Facilitated Diffusion:
 Carrier proteins move substances in the
direction of their chemical or electrical
gradients, no energy input is required.
 Has a transport maximum (it is
saturable),can be inhibited competitively
and non competitively
 Example-glucose transport by GLUT

Active Processes Primary active transport:

 Energy is used and substances
transported against gradient.
 Energy derived directly by hydrolysis of
ATP(Na+ K+ ATPase)
Sodium potassium ATPase pump
 discovered by Jens Skou-1997 nobel
prize in chemistry
 Accounts for about 24% of the energy
utilized by cells, and in neurons it
accounts for 70%
 Has an alpha and beta subunit

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  Alpha subunit:
 Intracellular-Na+ binding
site,Phosphorylation site,ATP binding
site
 Extracellular-K+ binding site,ouabain
binding site
 Beta subunit:
 Extra cellular glycosylation site
 Extrude three Na+ from the cell and take
two K+ into the cell for each molecule of
ATP hydrolyzed (electrogenic)
 Activity is inhibited by ouabain,digitalis
REGULATION OF Na, K ATPase:
 Agents Increasing pump activity-Throid
hormones,Aldosterone,Insulin(MN:ThAI)
 Agents Decreasing Pump activity-
Dopamine.causes natriuresis
 Secondary active transport:
 Active transport of Na+ is coupled to the
transport of other substances
 Examples:Na+K+Cl-,Na-Glucose,Na-
aminoacids.Na-bile salts,Na-choline
uptake
Secondary active transport:
 Active transport of Na+ is coupled to the
transport of other substances
 Examples:Na+K+Cl-,Na-Glucose,Na-
aminoacids.Na-bile salts,Na-choline
uptake
Exocytosis  For vesicles containing material for
export,mediated through v-SNARE and t-
SNARE
 Non constitutive(regulated) pathway-
extensive processing occurs before
exocytosis.Ex-insulin release
 Constitutive pathway-little or no
processing,no storage.Ex-mucus release
into GI lumen

Endocytosis  Various types namely phagocytosis,

pinocytosis, clathrin-mediated
endocytosis, caveolae-dependent
uptake, and nonclathrin/noncaveolae
endocytosis
 Pinocytosis-cell drinking and
phagocytosis-cell eating
 Clathrin mediated endocytosis:
 Involves clathrin(triskelion),GTP binding
protein Dynamin
 Examples-internalisation of receptors for

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 nerve growth factor,low density
lipoprotein receptor, Transferrin(Iron)
 Caveolae mediated endocytosis:
 Involves Rafts-rich in cholesterol and
sphingolipids and caveolae (flask-shaped
membrane depression) and caveolin.
 Examples-Folate receptor (Folate)
 Emeiocytosis-Insulin release from stored
granules, requires calcium
Transcytosis  Combines both exocytosis and
endocytosis.
 Otherwise called as cytopempsis
Coats and vesicle proteins
 Assembly protein 1 (AP-1)-Vesicles from Trans golgi to lysosomes
 Assembly protein 2-Endocytic vesicles to endosomes
 COP I and COP II-Vesicles that transport between the endoplasmic reticulum and the Golgi

Ion channels
 Specific for K + , Na + , Ca 2+ , and Cl as well as nonselective
 Examples-Amiloride sensitive epithelial sodium channels (ENaC),
 Cl- channels-GABAA, Glycine receptors,Cystic fibrosis transmembrane conductance
regulator(CFTR)

Cytoskeleton

 Maintains structure,allows the cells to change shape and move

 Made up of microtubules, intermediate filaments, and microfilaments
Microtubules (25nm)  Dynamic portion of cytoskeleton, provide
the tracks that moves transport vesicles,
organelles
 made up of alpha,beta and gamma
tubulins
 γ-tubulin-production of microtubules by
centrosomes(Microtubule Organising
centres(MTOCs)
 Microtubule assembly is prevented by
colchicine and vinblastine
 Paclitaxel (Taxol) binds to microtubules
and makes them so stable that organelles
cannot move
Intermediate filaments (8–14 nm)  Form a flexible scaff olding for the cell and
help it resist external pressure
 Keratin(epithelia),Vimentin(fibroblasts)
,Desmin(muscle) ,GFAP,Peripherin
,Neurofilaments ,Nestin ,Lamin(Mn:DVL-
GP-KPN)

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Microfilaments (4–6 nm)  Made up of ACTIN-most abundant protein
in mammalian cells
 Found in microvilli(GIT) and
lamellipodia(Crwaling)
 Involves in cytokinesis during cell division

MOLECULAR MOTORS

 There are three super families of molecular motors: kinesin, dynein, and myosin.
 Kinesin-move its cargo toward the “+” ends of microtubules
 Dyneins-move particles and membranes to the “–”end of the microtubules.
 Myosin- for contraction of muscle and cell migration

Axonal transport

Transport type Speed Material transported Mechanism

(mm/day)

Fast 200- 400 Golgi-derived vesicles containing peptides, Kinesin

anterograde enzyme, neurotransmitter
(ATP
dependent)

Fast 200-400 Endosomes, lysosomes Dynein

retrograde
(Endocytic pathway –membrane receptor, (ATP
absorbed exogenous material) dependent)

Slow ~0.2-8 Neurofilaments, microtubule subunits (actin, Not clear

anterograde tubulin, dynein, tau protein etc)

Bidirectional 50-100 Mitochondria Kinesin,

dynein

Cell Adhesion Molecules (CAMs)

 Cells are attached to the basal lamina and to each other by CAMs
 Four broad families: (1) integrins; (2) IgG superfamily of immunoglobulins; (3) cadherins, Ca
2+ -dependent molecules (4) selectins-lectin-like domains-bind carbohydrates.
 Transmit signals into and out of the cell

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INTERCELLULAR CONNECTIONS:

 Hold cells together:tight junctions (zonula occludens), gap junction, desmosome and zonula
adherens
 Attach cells to their basal lamina-hemidesmosome and focal adhesions

Tight junctions Gap junctions

Intestinal mucosa, the walls of the renal tubules,
and the choroid plexus
Proteins-occludin, junctional adhesion molecules
(JAMs), and claudins
Helps maintain cell polarity-prevent the
movement of proteins in the plane of the
membrane
Determines the degree of leakiness(paracellular
pathway
3 nm gaps lined up with CONNEXONS (Cx).
6 subunits of connexins=1 connexon
permit the rapid propagation of electrical activity
from cell to cell
Diseases: X-linked Charcot-Marie-Tooth disease
(Cx32), cataract (Cx46 and Cx50), Clouston
Syndrome(Cx 30), myoclonic epilepsy (Cx36),
arteriosclerosis (Cx37), idiopathic atrial fi
brillation (Cx40)

 Zonula adherens-major site of attachment for intracellular microfilaments,contains

cadherins
 Hemidesmosomes-connected to intermediate filaments. Contains cadherins

Aging (Senescence)

 Progressive deteriorative changes,during the adult period of life,which underlie an

increasing vulnerability to challenges and thereby decrease the ability of the organism to
survive
 Cellular and molecular mechanisms of aging:
1.oxidative stress(Free radical theory)-widely accepted theory of aging.Damage to the
macromolecules by H202,0H,superoxide anion radical
2.Glycation hypothesis of aging-due to formation of advanced glycation end products from
Amadori product
3.Mitochondrial theory of aging-damage to mitochondria leads to reduced synthesis of ATP
4.DNA damage theory of aging-accumulated DNA damage interferes with DNA replication
and transcription
5.DNA repair theory of aging-DNA repair declines with advancing age
6.Hayflick limit-cells could divide only a limited number of times

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 Nerve Muscle physiology-High yield topics

GLIAL CELLS

 Meaning-Glue, continue to undergo cell division in adulthood

 Two types- microglia and microglia
 Microglia-Derived from macrophages, physiologically and embryologically unrelated to other
neural cell types
 Macroglia: oligodendrocytes,Schwann cells, and astrocytes
 Oligodendrocytes-myelin formation around axons in the CNS
 Schwann cells are involved in myelin formation around Axons in peripheral nervous system
 Astrocytes-two types namely fibrous and protoplasmic.
Functions of astrocytes:
1. Formation of blood brain barrier
2. Produce substances that are tropic to neurons
3. Help maintain the appropriate concentration of ions and neurotransmitters by taking up K +
and the neurotransmitters glutamate and γ-aminobutyrate (GABA).

Neurons

 The human central nervous system (CNS) contains about 1011(100 billion) neurons
 Site of action potentials generation-the initial segment in spinal motor neurons, the initial
node of Ranvier in cutaneous sensory neurons
 Location of cell body:Dendritic zone end of the axon(most common).Within the axon (eg,
auditory neurons),Attached to the side of the axon (eg, cutaneous neurons)
 The number of Na+ channels per square micrometer of membrane in myelinated
mammalian neurons is 50-75 in the cell body, 350-500 in the initial segment, less than 25 on
the surface of the myelin, 2000-12,000 at the nodes of Ranvier, and 20-75 at the axon
terminals.
 Along the axons of unmyelinated neurons, the number is about 110.
 Action potentials can be recorded in dendrites
 Dendritic spines-dynamic structures,produce proteins, which alters the effects of input from
individual synapses.Implicated in motivation, learning, and long-term memory

Myelin:

 Protein-lipid complex formed by Schwann cells in PNS and oligodendrocytes in CNS

 Sphingomyelin-excellent electrical insulator
 Formed by Protein Zero (Po)-mutations in Po causes peripheral neuropathies
 Envelops the axon except at nodes of Ranvier(periodic 1-μm constrictions about 1 mm apart)
 Schwann cell forms the myelin between two nodes of Ranvier but oligodendrocytes emit
multiple processes that form myelin on many neighboring axons
 Loss of myelin-Multiple sclerosis caused due to the autoimmune attack of myelin leads to
leakage of K + through voltage-gated channels, hyperpolarization, and failure to conduct
action potentials

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Treatment of multiple sclerosis:

1. Corticosteroids
2. Beta interferons
3. Glatiramer acetate
4. Natalizumab
5. Rituximab, an anti-CD20 monoclonal antibody
6. Fingolimod- acts by sequestering lymphocytes in the lymph nodes

EXCITATION & CONDUCTION

 Nonpropagated potentials- synaptic, generator or electrotonic potentials

 Propogated-Action potentials
 resting membrane potential in nerve is usually about –70 mV, which is close to the
equilibrium potential for K+
 intracellular and extracellular K + concentrations are the prime determinants of the resting
membrane potential

Nerve action potential:

Action potential Feature

Depolarization Na+ influx
Firing level After initial 15mV of depolarization (the threshold) the rate
increases. This is firing level
Upstroke phase Rapid depolarization phase caused by rapid Na+ influx
Overshoot Part of action potential in which the membrane potential is
positive (above o mV)
Repolarization or down Rapid return of membrane towards RMP. It is due to
stroke phase a. Closing of Na+ channels; b. Opening of K+ channels
Hyperpolarization Membrane potential becomes more-ve than its initial RMP
due to late closure of K channels.
After hyperpolarization Result of K+ channels remaining open, allowing the continued
efflux of K+ ions

 Hyperkalemia-resting potential moves closer to the threshold for eliciting an action

potential(more excitable)
 Hypokalemia-membrane potential is reduced,neuron hyperpolarised
 Hypocalcemia-increases the excitability by decreasing the amount of depolarization
necessary to initiate action potential
 Hypercalcemia-stabilize the membrane by decreasing excitability

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All or None character of action potential

 increases in the intensity of a stimulus produce no increment or other change in the action
potential as long as the other experimental conditions remain constant
 constant amplitude and form regardless of the strength of the stimulus if the stimulus is at
or above threshold intensity

Saltatory conduction

 “jumping” of depolarization from node to node in myelinated axons for rapid conduction

Erlanger and Gasser classification of nerve fibre types

Fiber Type Function Fiber Conduction

Diameter (μm) Velocity (m/s)
Aα Proprioception; 12–20 70–120
somatic motor
Aβ Touch, pressure 5–12 30–70
Aγ Motor to muscle 3–6 5–30
spindles
Aδ Pain, temperature 2–5 12–30
B Preganglionic <3 3–15
autonomic
C , Dorsal root Pain, temperature 0.4–1.2 0.5–2
C , Sympathetic Postganglionic 0.3–1.3 0.7–2.3
sympathetic
 In general, the greater the diameter of a given nerve fiber, the greater is its speed of
conduction

Numerical classification of sensory nerve fibers:

Number Origin Fiber Type

Ia Muscle spindle, annulo-spiral Aα
ending
Ib Golgi tendon organ Aα
II Muscle spindle, flower-spray Aβ
ending; touch, pressure
III Pain and cold receptors; some Aδ
touch receptors
IV Pain, temperature, and other Dorsal root C
receptors

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Relative susceptibility of mammalian A, B, and C nerve fibers to conduction block produced by
various agents (Mn.HPL is BACk)

Susceptibility To: Most Intermediate Least

Susceptible Susceptible
Hypoxia B A C
Pressure A B C
Local anesthetics C B A

Neurotrophins:

 Produced by astrocytes and transported both anterogradely and retrogradely

 Produce proteins associated with neuronal development, growth, and survival
 The first neurotrophin to be characterized was NGF- growth and maintenance of cholinergic
neurons in the basal forebrain and the striatum
 NGF reduce apoptosis of neurons thereby enhancing survival

Neurotrophin Receptor
Nerve growth factor (NGF) Trk A
Brain-derived neurotrophic factor (BDNF) Trk B
Neurotrophin 3 (NT-3) Trk C, less on Trk A and Trk B
Neurotrophin 4/5 (NT-4/5) Trk B
 p75 NTR- binds all four neurotrophins with equal affinity.Has a role in apoptosis

Other Growth factors trophic to neurons

 Ciliary neurotrophic factor (CNTF)

 Glial cell line-derived neurotrophic factor (GDNF)
 leukemia inhibitory factor (LIF)
 insulin-like growth factor I (IGF-I)
 transforming growth factor (TGF)
 fibroblast growth factor (FGF)
 platelet-derived growth factor (PDGF)

Skeletal muscle

 Have two types of filaments (thick & thin).

 Thick-made of Myosin-II proteins (Two heads & single long tail).The head contains ATP ase
activity). Each myosin filament is surrounded by six actin filaments.
 Thin-made of ACTIN, TROPONIN & TROPOMYOSIN
 TROPONIN: has 3 sub units-I, T, C.
 TROP-I: inhibits the interaction of myosin with actin
 TROP-C: contains the binding sites for the Ca 2+ that helps to initiate contraction
 TROP-T: binds troponin components to Tropomyosin
 Z line: divides each myofibril into compartments. The protion of myofibril between two Z
line is a sarcomere

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  I band: formed by thin filament mainly actin
 A band: overlapping of actin & myosin
 H zone: narrow lighter area at the middle of A band, no actin in this zone
 M line: transverse line in the middle of H zone. site of the reversal of polarity of the myosin
molecules

Other structural proteins

 Actinin, titin and desmin

 Actinin binds actin to the Z lines
 Titin-largest known protein,provides scaf olding for the sarcomere and also provide muscle
with its elasticity
 Desmin-binds Z line to the plasma membrane
 Mutations in Titin leads to dilated cardiomyopath, hypertrophic cardiomyopathy, tibialis
muscular dystrophy

Dystrophin-Glycoprotein complex

 adds strength to the muscle by providing a scaf olding for the i brils and connecting them
to the extracellular environment
 comprises of dystrophin,beta-dystroglycan,syntrophins,merosin,alpha-dystroglycan and
sarcoglycan
 Absent Dystrophin-Duchenne muscular dystrophy
 Altered Dystrophin-Becker muscular dystrophy

SARCOTUBULAR SYSTEM

 made up of a T system and a sarcoplasmic reticulum

 Triads- arrangement of the central T system with a cistern of the sarcoplasmic reticulum on
either side
 “I” (transverse) tubules: penetrate the muscle & opens to the ECF: responsible for rapid
transmission of AP
 ‘L’ (longitudinal) tubules: extends throughout the sarcoplasm, no connection to exterior:
storage house of Ca2+

ELECTRICAL CHARACTERISTICS OF SKELETAL MUSCLE

 The resting membrane potential of skeletal muscle is about –90 mV

 action potential lasts 2–4 ms
 conduction velocity-5 m/s
 Absolute refractory period is 1–3 ms

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Skeletal muscle contraction

 Sliding filament theory/walk along theory/ratchet theory , proposed by A.F. HUXLEY &
H.E.HUXLEY
 Discharge of motor neuron---Release of transmitter (acetylcholine) at motor end-plate---
Binding of acetylcholine to nicotinic acetylcholine receptors---Increased Na+ and K+
conductance in end-plate membrane---Generation of end-plate potential---Generation of
action potential in muscle fibers---Inward spread of depolarization along T tubules---Release
of Ca2+ from terminal cisterns of sarcoplasmic reticulum and diffusion to thick and thin
filaments---Binding of Ca2+ to troponin C,uncovering myosin-binding sites on actin---
Formation of cross-linkages between actin and myosin and sliding of thin on thick filaments
 Relaxation---rapid uptake of calcium into sarcoplasmic or endoplasmic reticulum Ca 2+
ATPase (SERCA). uses energy from ATP hydrolysis

Thus, main source of Ca2+ for contraction in:

 Skeletal muscle-SR
 Cardiac & Smooth muscle-ECF

Classification of fiber types in skeletal muscles:

Type I Type IIA Type IIB

Other names Slow, Fast, Fast,
Oxidative Oxidative, Glycolytic
(SO) Glycolytic (FG)
(FOG)
Color Red Red White
Myosin ATPase Slow Fast Fast
activity
Ca 2+ -pumping Moderate High High
capacity of
sarcoplasmic
reticulum
Diameter Small Large Large
Glycolytic capacity Moderate High High
Associated Motor Slow (S) Fast Fast
Unit Type Resistant to Fatigable
Fatigue (FR) (FF)
Oxidative capacity High Moderate Low

CARDIAC MUSCLE

 Has numerous mitochondria, and a high content of myoglobin

 35% of the caloric needs of the human heart are provided by carbohydrate, 5% by ketones
and amino acids, and 60% by fat
 Intercalated disks(occur at Z lines)-helps in effective transfer of contractile force along the
axis
 Presence of Gap junctions(Functional syncytium)
 The T system in cardiac muscle is located at the Z lines (skeletal muscle at A–I junction)

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  The resting membrane potential of individual mammalian cardiac muscle cells is about –80
mV
 Action potential of a typical ventricular cardiomyocyte: Initial rapid depolarization and the
overshoot (phase 0)-opening of voltage-gated Na + channels .The initial rapid repolarization
(phase 1)-closure of Na+ channels and opening of one type of K+ channel. Prolonged plateau
(phase 2)-slower but prolonged opening of voltage-gated Ca 2+ channels. Final repolarization
(phase 3) to the resting membrane potential (phase 4)-closure of the Ca2+ channels and a
slow, delayed increase of K+ efflux through various types of K+ channels.
 Cardiac myocytes-two types of Ca2+ channels (T- and L-types), mostly due to opening of the
slower L-type Ca2+ channels.
 Influx of extracellular Ca2+ through the voltage-sensitive DHPR-triggers calcium-induced
calcium release through the RyR
 Absolute refractory period- phases 0 to 2 and about half of phase 3 and relatively refractory
until phase 4.Thus cardiac muscle cannot be TETANIZED
 Isoforms- Cardiac muscle contains both the α and the β isoforms of the myosin heavy chain
(α MHC and β MHC). β MHC-lower myosin ATPase activity compared to α MHC.ATRIA-has
both isoforms but α MHC.VENTRICLES-has β MHC
 Long QT syndrome-due to mutations in voltage gated K + channel genes (KCNQ1 or KCNH2),
voltage-gated Na + channels (eg, SCN5A), Ca 2+ channels (eg, CACNA1C). K+ or Mg2+
deficiencies should be corrected in these patients.Therapy with β-blockers-to reduce the risk
of cardiac arrhythmias

Smooth muscles

 Lacks cross striations.Contains dense bodies(Attaches α-actinin to actin)in place of Z lines

 Contains tropomyosin, but lacks troponin
 Has different isoforms of actin and myosin
 Has less extensive sarcoplasmic reticulum and few mitochondria
 Two types-Unitary and Multi unit smooth muscles
 Unitary type-has many gap junctions(Syncytium).Present in intestine, the uterus, and the
ureters
 Multiunit type-few or no gap junctions.Present in iris of the eye.Able to display fine and
discrete contraction patterns
 Blood vessels has both types of smooth muscles
 No true RMP.varies between -20 to -65mV
 Main source of calcium-Extracellular
 Ca2+ binds to calmodulin-activates calmodulin-dependent myosin light chain kinase-
phosphorylates myosin on serine at position 19, increasing its ATPase activity(Myosin based)
 Regulation is through myosin light chain phosphatase-dephosphorylates myosin(relaxation)
 Relaxation also occurs through Endothelium derived relaxating factor(NITRIC OXIDE)
 Latch bridge mechanism- myosin cross-bridges remain attached to actin for some time after
the cytoplasmic Ca2+ concentration falls leading to sustained contraction with little
expenditure of energy
 Plasticity-if an unitary smooth muscle is stretched-at first there is increase in tension but the
tension gradually decreases if the muscle is held at the greater length after stretching
 Norepinephrine-decreases the spikes and acetyl choline-increases the spikes in unitary
smooth muscles

18
SYNAPTIC TRANSMISSION

 Synapse- the junctions where the axon or some other portion of one cell (the presynaptic
cell) terminates on the dendrites, soma, or axon of another neuron,muscle or gland
 There are about 2 × 1014 synapses
 Synaptic cleft-space between presynaptic and post synaptic neuron. 20–40 nm wide
 postsynaptic density- ordered complex of specific receptors, binding proteins, and enzymes
induced by postsynaptic effects
 synaptic vesicles-Three types: small, clear vesicles-acetylcholine, glycine, GABA, or
glutamate; small vesicles with a dense core-catecholamines; and large vesicles with a dense
core-neuropeptides
 Active zones-site of discharge of small vesicles. Calcium channels arranged in rows
 Proteins that hold synapses together- Neurexins
 Proteins involved in Exocytosis of vesicles: v-snare protein synaptobrevin and t-snare
protein syntaxin
 Toxins blocking neurotransmitter release:Tetanus toxin and botulinum toxin
 Tetanus toxin- attaches to gangliosides and blocks release of inhibitory transmitters glycine
and GABA leading to spastic paralysis
 Botulinum toxin- Toxins A, B, and E-toxic to humans. Toxins A and E cleave synaptosome-
associated protein (SNAP-25)-a presynaptic membrane protein needed for fusion of synaptic
vesicles containing acetylcholine to the terminal membrane.Toxin B- cleaves synaptobrevin
ultimately leading to flaccid paralysis.BOTOX(botulinum toxin) clinically useful in achalasia
and to remove wrinkles in face

EPSP(Extitatory post synaptic potential) IPSP(Inhibitory post synaptic potential)

 Transient partial depolarization
 The excitability of the neuron to other
stimuli is increased
 Due to opens Na + or Ca2+ channels
 Transient hyperpolarisation
 The excitability of the neuron to other
stimuli is decreased
 Due to opening of Cl-channels,opening of
K + channels

 Slow EPSP-due to decreases in K+ conductance. Latency is 100-500 ms

 Slow IPSPs are due to increases in K+ conductance. Latency is 100-500 ms
 Presynaptic inhibition-Mediated by GABA acting through GABA A- increases Cl– conductance
and GABA B- increases K+ conductance
 Renshaw cell inhibition-Neurons inhibiting themselves through negative feedback
mechanisms. Neurotransmitter involved is Glycine

19
Neuromuscular transmission

 Impulse arriving in the end of the motor neuron--- increases the permeability of its endings
to Ca2+---Exocytosis of acetylcholine-containing synaptic vesicles--- acetylcholine binds to
nicotinic cholinergic (NM) receptors---Increases Na+ and K+ conductance---End plate potential
 Average human end plate contains about 15–40 million acetylcholine receptors.
 On arrival of nerve impulse---Ach released from 60 synaptic vesicles.Each vesicle contains
10,000 molecules of Ach. This amount is enough to activate about 10 times the number of
NM recep-tors needed to produce a full end plate potential(10-fold safety factor)
 Miniature end plate potential (MEEP)-At rest, small quanta (packets) of acetylcholine are
released randomly---produces MEEP of 0.5mV amplitude. size of the quanta of acetylcholine
released varies directly with the Ca2+ concentration and inversely with the Mg2+
concentration

Myasthenia Gravis

 Caused by the formation of circulating anti-bodies to the muscle type of nicotinic cholinergic
receptors.
 Affected muscles have 70–90% decrease in the number of receptors per end plate. In most
patients, the thymus is hyperplastic; and 10–15% has a thymoma.
 Treatment is with acetylcholinesterase inhibitor such as neostigmine or pyridostigmine and
immunosuppressive drugs like prednisone, azathioprine, or cyclosporine.Thymectomy is
indicated in patients with thymoma

Lambert Eaton syndrome

 Due to autoimmune attack of the voltage-gated Ca 2+ channels.

 Repetitive stimulation of the motor nerve facilitates accumulation of Ca2+ in the nerve
terminal and increases acetylcholine release, leading to an increase in muscle strength. This
is in contrast to myasthenia gravis in which symptoms are exacerbated by repetitive
stimulation.
 Associated with small cell cancer of the lung, lymphosarcoma, malignant thymoma, and
cancer of the breast, stomach, colon, prostate, bladder, kidney, or gall bladder.
 Use of aminoglycoside antibiotics also produces a similar syndrome
 Treatment-. Prednisone,plasmapheresis,intravenous immunoglobulin,aminopyridines

Synapse en passant

 Neuron forms a synapse on the surface of another neuron or a smooth muscle cell and then
passes on to make similar contacts with other cells
 Characteristic of smooth muscles
 No recognizable end plates or other postsynaptic specializations

20
  Multiple branches of the neurons are beaded with enlargements (varicosities) and contain
synaptic vesicles
 This arrangement permits one neuron to innervate many effector cells

Neuromuscular transmission Blockers

 Neuronal sodium channel blockers-Tetrodotoxin,saxitoxin

 Calcium channel blocker-ω-Conotoxin
 Potassium channel blocker-Dendrotoxin
 Agents preventing Ach release-Tetanus toxin,Botulinum toxin
 Muscle sodium channel blocker- Tetrodotoxin,saxitoxin,μ-Conotoxin
 AchReceptor blocker-Tubocurarine(competitive,non-depolarising),Succinyl
choline(depolarising,non-competitive)
 Acetylcholine esterase inhibitors-Physostigmine,Neostigmine,disopropylfluro-
phsophate(DFP)

21
 Neurophysiology-High yield topics

Neurotransmitters:

Acetylcholine  transmitter at -neuromuscular junction,

Drugs that alter cholinergic transmission:
Norepinephrine and epinephrine
in autonomic ganglia, and in
postganglionic parasympathetic, basal
forebrain complex, pontomesen-cephalic
cholinergic complex
 Involved in regulation of sleep-wake
states, learning, and memory
 from choline and acetyl-CoA by the
enzyme choline acetyltransferase
(ChAT)
 synthesis and release involves- Na+-
dependent choline transporter, vesicle-
associated trans-porter (VAT)
 Removal-by acetylcholinesterase in the
synaptic cleft
 Receptors:2 types
1. Muscarinic: (M1, M4, and M5-CNS),( M2-
Heart),( M3-glands and smooth muscles)
2. Nicotinic: (NM- neuromuscular junction),
(N N- CNS and autonomic ganglia)
 Hemicholinium- blocks the choline
transporter
 Vesamicol- blocks the VAT
 botulinum toxin- prevents the release
of acetylcholine
 Location- locus coeruleus, spinal cord,
cerebellum, paraventricular, supraoptic,
and periventricular nuclei of the
hypothalamus, the thalamus, the basal
telencephalon, neocortex
 Synthesised from TYROSINE
 Rate limiting enzyme- tyrosine
hydroxylase(subject to feedback
inhibition by dopamine and
norepinephrine)
 Nor-epinephrine-only small-molecule
transmitter that is syn-thesized in
synaptic vesicles instead of being
transported into the vesicle after its
synthesis
 phenylethanolamine-N-
methyltransferase (PNMT)-Converts Nor
epinephrine to epinephrine
 Catabolism-Enzymes involved are
monoamine oxidase (MAO), catechol-O-

22
 methyltransferase (COMT)
 MAO isoenzyme form locations:
– MAO-A in: Adrenergic peripheral
structures, Alimentary mucosa
– MAO-B in: Brain,Blood platelets
 Urinary metabolites- vanil-lylmandelic
acid (VMA), 3-methoxy-4-
hydroxyphenylglycol (MHPG)
 drugs that alter noradrenergic
transmission:
1. metyrosine- blocks the action of tyrosine
hydroxylase
2. Reserpine- blocks the VMAT that moves
dopamine into the synaptic vesicle
3. bretylium and guanethidine-prevents
release
4. Cocaine and tricyclic antidepressants-
blocks reputake
Dopamine  Location- Nigrostriatal system(midbrain
substantia nigra to the striatum in the
basal ganglia) and mesocortical
system(ventral tegmental area to
nucleus accumbens and limbic
subcortical areas
 involved in reward behavior and
addiction
 Receptors:D1,D2,D3,D4,D5(All are
metabotropic).D4 blocker-Clozapine
Serotonin  present in highest concentration in
blood platelets and in the gastrointesti-
nal tract
 Also in midline raphé nuclei
 synthesized from tryptophan
 Rate limiting enzyme- tryptophan
hydroxylase
 Reuptake- serotonin transporter (SERT)
 urinary metabolite-5-
hydroxyindoleacetic acid (5-HIAA)
 Receptors-7 types(5-HT1 to 5-HT7)
 5-HT2A- platelet aggregation and smooth
muscle contraction
 5-HT 3- gastrointestinal tract and the
area postrema-related to vomiting
 5-HT4- facilitate secretion and peristalsis
 5-HT6 and 5-HT7-limbic system
 Selective serotonin uptake inhibitors
(SSRIs)- fluoxetine
Histamine  Location- gastric mucosa,mast cells,
tubero-mammillary nucleus of the
posterior hypothalamus

23
  formed by decarboxylation of the amino
acid histidine
 Receptors- H 1, H2, and H3, H4
 Involved in- arousal, sexual behavior,
blood pres-sure, drinking, pain
thresholds,regulation of anterior
pituitary hormone secretion
 H4- regulating cells of the immune
system
ATP  Colocalised in nora-drenergic
postganglionic sympathetic neurons
 Neurotransmitter in autonomic nervous
system and habenula
Substance P  Location- primary afferent neurons in
the spinal cord, nigrostriatal system,
hypothalamus
 Responsible for axon
reflex,peristalsis,pain transmission
 Receptors- neurokinin receptors (NK1-
NK3)
Glutamate  responsible for 75% of the excitatory
transmission in the CNS
 Synthesis:
1. Conversion of α-ketoglutarate to
glutamate by GABA transaminase
2. Conversion of Glutamine to glutamate
by glutaminase
 Excitotoxicity- exces-sive levels of
glutamate during ischemia, anoxia,
hypoglycemia, or trauma-Death of
neurons(massive Ca2+ influx)
 Involved in learning and memory-
synaptic plasticity, long-term
potentiation
 Receptors-AMPA,Kainate,NMDA,mGLUR
GABA  formed by decarboxylation of glutamate
by the enzyme glutamate decarboxylase
(GAD)
 vesicu-lar GABA transporter (VGAT)-
transports GABA and glycine into
secretory vesicles
 Receptors- GABAA, GABAB, and GABAC
 GABA agonists- benzodiazepines,
Barbiturates
Glycine  facilitate pain transmission by NMDA
receptors in the dorsal horn
 acts by increasing Cl – conductance(Like
GABA)
 Antagonist- strychnine

24
Sensory Physiology

Modality Stimulus Energy Receptor Cell Types

Touch Tap, flutter 5–40 Hz Meissner corpuscles
Touch Motion Hair follicle receptors
Deep pressure, vibration
Touch 60–300 Hz Pacinian corpuscles
Touch Touch, pressure Merkel cells
Touch Sustained pressure Ruffini corpuscles
Proprioception Stretch Muscle spindles
Proprioception Tension Golgi tendon organ
Temperature Thermal Cold and warm receptors
Chemical, thermal, and Polymodal receptors or chemical, thermal,
Pain mechanical and mechanical nociceptors
Vision Light Rods, cones
Hearing Sound Hair cells (cochlea)
Balance Angular acceleration Hair cells (semicircular canals)
Linear acceleration,
Balance gravity Hair cells (otolith organs)
Smell Chemical Olfactory sensory neuron
Taste Chemical Taste buds

Pain Physiology:

Pain  First pain (epicritic pain)- ability to

localize the site and intensity of the
noxious stimulus. Activation of Aδ fibers,
which release glutamate, is responsible
for this
 Slow pain (protopathic pain)- dull,
intense, diffuse, and unpleasant feeling.
Activation of C fibers, which release a
combination of glutamate and substance
P, is responsible for this
 Receptor channels:
1. Transient receptor potential (TRP)
channels. TRPV1- activated by intense
heat, acids, and chemicals such as
capsaicin. TRPA1 receptors-activated by
Noxious mechanical, cold, and chemical
stimuli
2. acid sensing ion channel (ASIC)
receptors- activated by pH changes
3. purinergic receptors-ATP acts on it
4. Tyrosine receptor kinase A (TrkA)-
activated by nerve growth factor (NGF)
 Hyperalgesia- exaggerated response to a
noxious stimulus
 Allodynia- sensation of pain in response
to a normally innocuous stimulus

25

Modulation of pain transmission
Stress induced analgesia
 Two components of pain pathways:
1. From VPL nuclei in the thalamus, fibers
project to SI and SII. (Pathway
responsible for the discriminative aspect
of pain-the neospinothalamic tract
2. Paleospinothalamic tract-the pathway
that includes synapses in the brain stem
reticular formation and centrolateral
thalamic nucleus projects to the frontal
lobe, limbic system, and insula. This
pathway mediates the motivational-
affect component of pain.
1. gate-control mechanism
 Proposed by Melzack&Wall.
 simultaneous activation of innocuous
cutaneous mechanoreceptors
 simultaneous activation of innocuous
cutaneous mechanoreceptors- reduce
the responsiveness of dorsal horn
neurons to their input from nociceptive
afferent terminals
 This is the rationale behind the use of
transcutaneous electrical nerve
stimulation (TENS)
2. Opiod peptides:
 endogenous opioid peptides-enkephalin
and dynorphin
 Action on postsynaptic opioid receptors-
increase in K + conductance
 Action on Presynaptic opioid receptors-
decrease in Ca 2+ influx, resulting in a
decrease in release of glutamate and
substance P
3. Endogenous analgesic system:
 periaqueductal gray (PAG)-projects to
nucleus raphé magnus and rostral
ventromedial medulla
 Neurons in both of these regions project
to the dorsal horn of the spinal cord-
release serotonin and norepinephrine
which inhibits the activity of dorsal horn
neurons that receive input from
nociceptive afferent fibres
 Locus coeruleus-Releases
norepinephrine which modulates pain
transmission
 release of endogenous cannabinoids
such as 2-arachidonoylglycerol (2AG)
and anandamide
 acts on CB1 and CB 2 receptors
26
  CB1- accounts for the euphoric actions of
cannabinoids
 CB 2- expressed in activated
microglia.Resposible for analgesia

Vision:

Characteristics of rods and cones:

Rods(RoD: Dim light) Cones(Cones-Colour)

Outer segment-slender,cylindrical Long conical
Invaginated cell membrane separated from cell Invaginated cell membrane continues cell
surface surface
Photopigment-Rhodopsin(vision in dim light) Photopsin(vision in bright light)
Disks slowly toward the tip of rods Disks don’t move
Smaller nucleus Larger nucleus
Terminal part-Narrower Terminal part-Expanded

Phototransduction in rods and cones:

Incident lightStructural change in the retinal of photopigmentConformational change

of photopigmentActivation of transducinActivation of phosphodiesteraseDecreased
intracellular cGMPClosure of Na+ channelsHyperpolarisationDecreased release of
synaptic transmitter(Glutamate) Response in bipolar cells and other neural elements

Melanopsin:

 few retinal ganglion cells contain melanopsin rather than rhodopsin or cone pigments
 project to the suprachiasmatic nuclei of the hypothalamus
 involved in circardian rhythms

Lateral geniculate body  Fibres from ipsilateral hemiretina-ends

From lateral geniculate nucleus to visual cortex
Blobs and the visual pathway
in lamina 2,3,5
 Fibres from contralateral nasal retina-
ends in lamina 1,4,6
 Two pathways
1. Magnocellular pathway-From layer
1&2.Carries signal for detection of
movement,depth and flickers
2. Parvocellular pathway-From layers
3,4,5,6.Carries signals for color
vision,texture,shape and fine details
 Layers 2 and 3 contain a high
concentration of ‘cytochrome oxidase’
called as blobs and are concerned with
color processing

27
Cone type color Peak(nm) Range(nm)
Short wave/blue Blue violet 440 440-500
sensitive
Medium wave/green Green 535 450-545
sensitive
Long wave/red Yellow,red 565 564-580
sensitive

Sense of hearing:

External ear  Pinna,external auditory meatus,

tympanic membrane
Middle ear  Auditory ossicles- malleus, incus, and
stapes
 communicates with the nasopharynx by
the eustachian tube, allowing air
pressure to be equalized on both sides of
the tympanic membrane
Inner ear  comprises of the
“Outer cells are Out of the brain. Inner cells utricle,saccule,semicircular canals and
are Into the Brain” the cochlear duct
Outer hair cells are motor efferents to amplify  Endolymph-fluid inside he vestibular
signal labyrinth.Rich in K+
Inner hair cells are sensory afferents that  Perilymph- fluid outside the vestibular
actually pick up the sound labyrinth.Rich in Na+
 organ of Corti- located in the basilar
membrane and contains inner and outer
hair cells
 Prestin-motor protein of outer hair cells.
 Spiral ganglion- contains cell bodies of
the auditory nerve whose pe-ripheral
axons innervate hair cells on the organ
of Corti
 High-frequency sound waves cause
maximum displacement of the basilar
membrane and stimulation of hair cells
at the base of the cochlea
 Low-frequency sound waves maximally
stimulate hair cells at the apex of the
cochlea
Auditory transduction  E-Eighth nerve
 C-cochlear nuclei
 O-olivary complex
 L-lateral lemniscus
 I-Inferior colliculi
 M-medial geniculate body
 A-auditory cortex
– Auditory cortex -located on the superior
temporal gyrus of the temporal lobe
– Planum temporal-located between

28
 Heschl’s gyrus (transverse temporal
gyrus) and the sylvian fissure.This area is
larger in the left than in the right.
involved in language-related auditory
processing

Smell:

Olfactory epithelium  comprises of

1. bipolar olfactory sensory neurons
2. supporting (sustentacular) cells
3. basal stem cells
4. Bowman glands(mucus secreting)
5. odorant-binding proteins (OBP):
concentrate the odorants and transfer
them to the receptors, sequester
odorants-for clearance
Olfactory sensory neuron  contains 6–12 cilia
 contains odorant receptors
Olfactory bulb  Contains excitatory neurons:mitral and
tufted cells(glutamate
 Inhibitory neurons(periglomerular cells
and granule cells(GABA)
 anatomically discrete synaptic units
called as Olfactory glomeruli
Olfactory cortex  anterior olfactory nucleus, olfactory
tubercle, piriform cortex,amygdala(for
emotional response), entorhinal
cortex(for olfactory memory)
 cortical representation of olfaction is
asymmetric(greater on right)

Taste:

Taste Buds  Contains 4 types of cells:

1. basal cells
2. dark cells(type I)
3. light cells(type II)
4. intermediate cells(type III)
 has between 50 and 100 taste cells
 receptors couple to the heterotrimeric G
protein, gustducin
 fungiform papillae- most numerous near
the tip of the tongue
 circumvallate papillae- arranged in a V
on the back of the tongue
 foliate papillae-Back of tongue
Taste modalities 1. Sweet- T1R3 family of GPCR

29
 2. Salt-ENac Channels
3. Sour-Enac channels, HCN, a
hyperpolarization-activated cyclic
nucleotide-gated cation channel
4. Bitter- T2R family
5. Umami- mGluR4
Taste pathways  Anterior 2/3rd of tongue-chorda
tympanic branch of facial nerve
 Posterior third-Glossopharyngeal nerve
 Pharynx-Vagus nerve
 unite in the gustatory portion of the
nucleus of the tractus solitarius (NTS)
Thalamus anterior insula and the
frontal operculum in the ipsilateral
cerebral cortex

Motor system:

Muscle spindles  Intrafusal muscle fibers-pure sensory

function
 Extra fusal fibres-the regular contractile
units of the muscle
 Two types of intrafusal fibers- nuclear
bag fiber(dynamic and static) and
nuclear chain fiber
Sensory endings in spindle  A single primary (group Ia) ending and
up to eight secondary (group II) endings
 dynamic response- Ia afferents are very
sensitive to the velocity of the change in
muscle length during a stretch
 static response- activity of group Ia and II
afferents provide information on steady-
state length of the muscle
Motor nerve supply  γ-motor neurons(constitute about 30%
of the fibers
 two types of γ-motor neurons: dynamic-
supplies the dynamic nuclear bag fibers
and static- supply the static nuclear bag
fibers and the nuclear chain fibers
 Activation of dynamic -motor neurons
increases the dynamic sensitivity of the
group Ia endings
 Activation of the static -motor neurons
increases the tonic level of activity in
both group Ia and II endings, decreases
the dynamic sensitivity of group Ia
afferents, and can prevent silencing of Ia
afferents during muscle stretch

30
α–γ coactivation  both α- and γ-motor neurons are
activated- In response to descending
excitatory input
 intrafusal and extrafusal fibers shorten
together, and spindle afferent activity
can occur throughout the period of
muscle contraction
 Responsible for reflexively adjustment of
α-motor neuron discharge

Inverse stretch reflex

 Receptor- Golgi tendon organ(netlike collection of knobby nerve end-ings among the
fascicles of a tendon)
 3–25 muscle fibers per tendon organ
 Regulates muscle force(or tension(

Postural reflexes

REFLEX STIMULUS RECEPTOR CENTRE

Stretch reflex Stretch Muscle spindle Spinal cord,

medulla

Positive supporting Contact with palm or sole Proprioceptors in Spinal cord

reaction extensors

Negative supporting Stretch Proprioceptors in Spinal cord

reacting extensors

Tonic labyrinthine Gravity Otolith organs Medulla

reflex

Tonic neck reflex Head turned to Neck proprioceptors Medulla

side/up/down

Labyrinthine righting Gravity Otolitth organs Midbrain

reflex

Neck righting reflex Stretch of neck muscles Muscle spindle Midbrain

Body on head Pressure on side of body Exteroceptors Midbrain

righting reflex

Body on body Pressure on side of body Exteroceptors Midbrain

righting reflex

Optical righting Visual cues Eyes Cortex

31
 reflex

Vestibular Placing Linear acceleration Receptors in utricle and Cortex

reactions saccule

Visual placing Visual cues Eyes Cortex

reactions
Hopping reactions Lateral displacement Muscle spindle Cerebral
while standing cortex

 All righting reflexes are integrated at midbrain except optical righting reflex, which is
integrated at cortex

Motor cortex:

Primary motor cortex  In precentral gyrus of the frontal lobe

 Cortical representation of body parts-
motor homunculus
 executes the movements
 representation of each body part is
proportional in size to the skill with
which the part is used in fine, voluntary
movement
 The areas involved in speech and hand
movements are especially large
Supplementary motor area  In superior bank of the cingulate sulcus
 projects to the primary motor cortex
 involved primarily in organizing or
planning motor sequences
Premotor cortex  located anterior to the precentral gyrus
 receives input from sensory regions of
the parietal cortex and projects to M1,
the spinal cord, and the brain stem
reticular formation
 concerned with setting posture at the
start of a planned movement and with
getting the individual prepared to move
 involved in control of proximal limb
muscles needed to orient the body for
movement
Cerebellum:

Structure  weighs only 10% as much as the cerebral

cortex, but its surface area is about 75% of
that of the cerebral cortex
 superior cerebellar peduncle-fibers
from deep cerebellar nuclei--project to the
brain stem, red nucleus, and thalamus
 middle cerebellar peduncle-afferent fibers

32

Organisation
Divisions of cerebellum
Histology
Input to the cerebellar cortex
from the contralateral pontine nuclei
 inferior cerebellar peduncle-afferent fibers
from the brain stem and spinal cord and
efferent fibers to the vestibular nuclei
 comprises of cerebellar cortex and deep
nuclei
 four deep nuclei:
Dendate,Globose,Emdoliform,Fatigial(Mn.D
EFG)
 Anatomical division
1.Flocculo-nodular lobe
2.Anterior lobe
3.Posterior lobe
 Phylogenetic division
1.Archicerebellum
2.Paleocerebellum
3.Neocerebellum
 Functional division
1.Vestibulocerebellum
2.Spinocerebellum
3.Cerebrocerebellum (Neocerebellum)
 Layers
– External molecular layer
– Middle Purkinje cell layer
– Internal granule cell layer
 Cell types(Mn.SPB-G2)
– Purkinje cell
– Granule cell
– Basket cell
– Stellate cell
– Golgi cell
 Climbing fibres:
– arise from the region of inferior olivary
nucleus in medulla.
– They make synaptic connections with
Purkinje cells.
– Climbing fibres produce high frequency
bursts or complex spikes.
– They play a major role in motor learning.
– Carry proprioceptive impulses from all over
the body
 Mossy fibres:
– Arise from different centres in brainstem
and spinal cord.
– They make synaptic connection with
Purkinje cells.
– They produce simple spikes.
– They also synapse with granule cells.
– Axons of granule cells bifurcate. They excite
the Purkinje cells through parallel fibres.
33

Output from cerebellar cortex
Functions
Effects of cerebellar lesions
– Carry proprioceptive input from all parts of
the body and cerebral cortex
 Output of the cerebellar cortex is from
Purkinje cells. These outputs are always
inhibitory.
 The output projects to deeper cerebellar
nuclei and vestibular nucleus.
 The inhibitory inputs influence the output
from the cerebellum to regulate range,
direction and rate of movement.
 Gamma aminobutyric acid (GABA) is the
neurotransmitter
Vestibulo cerebellum (Archi cerebellum)
• It is concerned with maintenance of balance
and equilibrium.
• It is responsible for regulating the stability
of head and body in space.
• It adjusts the tone of the trunk muscle.
• Controls the ocular movements and other
postural reflexes.
Spino cerebellum (Paleocerebellum)
• Maintains the posture and helps in
execution of gross movements.
• It controls the interplay between the
agonist and antagonist group of muscles
• It is essential for the control of rapid
muscular activities like running and talking
Cerebro cerebellum (Neocerebellum)
• Controls fine, highly precise and
coordinated movements.
• It is involved in programming of voluntary
and skilled movements.
• It plays a major role in the timing of the
motor activities and rapid progression from
one movement to the next
– Ataxia
– Hypotonia or atonia
– Dysmetria
– Dysdiadokokinesia
– Decomposition of movement
– Staccato speech or slurring speech.
– Pendular knee jerk
– Intention tremors
– Nystagmus
34
Basal Ganglia:

Structure Deep telecephalic nuclei (noncortical gray

matter):
(i) Caudate and putamen = “
striatum”
(ii) Globus pallidus
Associated nuclei:
(i) Diencephalon: ventral
anterior thalamic nucleus,
ventral lateral, thalamic nuc,
central median nuc,
subthalamic nuc
(ii) Mesencephalon: substantia
nigra
Connections Caudate and putamen
– Caudate= projections mostly from
prefrontal, temporal, parietal assoc
areas
– Putamen= from motor, somatosensory
cortices
– Inhibitory to Globus pallidus (GABAergic)
Globus pallidus
– External segment (GPe)- inhibitory
(GABA) to subthalamic nucleus
– Interanal segment (GPi)- inhibitory
(GABA) to VL/VA, CM of thalamus
(balances excitatory input from dentate
nucleus to cerebellum)
Subthalamic nucleus
– (i) Excitatory to internal globus pallidus
(GPi) ( inhibits thalamus cortex)
– Receives strong excitatory projection
from motor cx (net inhibition of cortex)
Substantia nigra pars compacta- Dopaminergic
efferents to caudate/putamen
– D1 = excitatory, D2 =inhibitory
– Projects to pallidum
Pathways Direct pathway:
 Net excitatory effect on cortex
Indirect pathway:
 Net inhibitory effect on cortex

Applied aspects Damage to basal ganglia — classical symptoms:

– Increased motor tone — rigidity
– Dyskinesias-tremors, other involuntary
movement
– Bradykinesia/Akinesia-slowing/ almost
absent voluntary movement
Hemiballismus

35
 – Damage to subthalamic nucleus or its
connections to GPi (unilateral)
– Involuntary, irregular flinging of
contralateral extremity (usually upper)
Huntington’s disease
– Early degeneration of the striatum
– Involuntary movements “choreiform”-
writhing
Parkinson’s disease
– Damage to SNpc (depletion of DA in
striatum)
– Rigidity and tremor, brady/akinesia
– Reflects disruption of cortical-basal
ganglia-cortical loop:
1. Direct pathway: loss of DA1 decrease
inhibition of GPi ...less net
excitation of cortex
2. Indirect pathway: loss of DA2 more
inhibition less net excitation of cortex
3. Result is akinesia
– Imbalance of excitatory (D1) and
inhibitory (D2) effects of pathway
treat by restoring balance:
(i) Increasing efficacy of
dopamine release
(administer L- DOPA)
(ii) lesions to block GPi/STN
activity
(iii) transplant dopaminergic
neurons

CEREBRAL DOMINANCE

Also called categorical hemisphere Also called representational hemisphere

Functions: Functions:

 Understanding & Expression  spatio-temporal relations

of speech and ideas.  identification of form of objects
 Categorization  recognition of faces
 symbolization  recognition of musical themes
Lesions: Language disorders Lesions: Asterognosis & Agnosia

Hypothalamus

Functions Integrating area of hypothalamus

36
 Increased ECF osmolarity (Thirst) Osmoreceptors-Anterior hypothalamus

Response to heat Anterior hypothalamus

Response to cold Posterior hypothalamus

Emotion Dorsal and posterior lhypothalamus

Circadian rhythm Suprachiasmatic nucleus

Gn RH secretion Arcuate nucleus

TSH (vai TRH secrection) Paraventricular &neighboring nuclei

Prolactin via PRH & PIH Arcuate nucleus

Oxytocin release Paraventricular nucleus (mainly)

ADH release Supra optic nucleus (mainly)

Satiety centre Ventro medial nucleus

Feeding centre Lateral nucleus

Sexual behavior Anterior ventral hypothalamus plus, in the

male, piriform cortex

Circumventricular Organs (Mn-SOAP-M)

 Posterior pituitary
 Median eminence
 Area postrema
 Organum vasculosum of the lamina terminalis
 Subfornical organ

37
 Cardiovascular Physiology-High yield topics
Location of SA node
Location of AV node
Fibres connecting SA node to AV node
Cardiac output
Stroke volume
Cardiac index
end-diastolic ventricular volume
end-systolic ventricular volume
Ejection fraction
Total electromechanical systole (QS2)
left ventricular ejection time (LVET)
preejection period (PEP)
PEP/LVET ratio
Normal arm to tongue circulation time
Properties of ventricular myocyte
 resting membrane potential is –90 mV
 Action potential phases:
1. rapid depolarization (phase 0)- rapidly
opening Na+ channels
2. rapid repolarization (phase 1)-
inactivation of Na+ channels
3. plateau (phase 2)- Ca2+ influx through
more slowly opening Ca2+ channels
4. return to the resting membrane
potential (phase 4)- net K+ efflux
junction of the superior vena cava with the
right atrium
right posterior portion of the interatrial
septum
anterior, middle (tract of Wenckebach), and
poste-rior (tract of Thorel) tracts
Bachmann’s bundle- connects the right and
left atria
5L/min
70 ml
3.2L/min/m2
130 ml
50 ml
percentage of the end-diastolic
ventricular volume that is ejected with each
stroke, is about 65%
QS2 is the period from the onset of the QRS
complex to the closure of the aortic valves
period from the beginning of the carotid
pressure rise to the dicrotic notch
difference between QS2 and LVET and
represents the time for the electrical as well as
the mechanical events that precede systolic
ejection
0.35
15 s
Pacemaker potentials
 resting membrane potential fluctuates
between -60 and -40mV
 Initial part of pacemaker potential-due
to the channel activated following
hyperpolarization(h channel),also
called as “funny current”(permeable to
both Na+ and K+)
 Later part-(ICa) due to opening of T
channels completes the prepotential,
and ICa due to opening of L channels
produces the impulse
 Repolarisation-K+channels
 Th e action potentials in the SA and AV
nodes are largely due to Ca2+, with no
contribution by Na+ influx
 reduced slope of the prepotential-
after vagal stimulation via M2
38
 muscarinic receptors which increases
the K+ conductance
 Increased spontaneous discharge- after
sympathetic stimulation.
Norepinephrine via β 1 receptors
resulting in the increase in intracellular
cAMP which facilitates the opening of L
channels

Conduction speeds in cardiac tissue:

Tissue Conduction Rate

(m/s)

SA node 0.05

Atrial pathways 1

AV node 0.05

Bundle of His 1

Purkinje system 4

Ventricular muscle 1

Tissue Rate of impulse generation

S.A. Node 70-80/min

A.V. Node 40-60/min

Bundle of His 40/min

Purkinje fibres 24/min

First of the heart to be depolarized: left endocardial surface of the inter ventricular septum

Last part of the heart to be depolarized:

 Postero basal portion of left ventricle

 Pulmonary conus

 Upper most portion of the septum

39
 Depolarization Repolarisation

Single From endocardium to From endocardium to

ventricular epicardium epicardium
muscle fiber

Whole heart From endocardium to From epicardium to

epicardium edocardium

Electrocardiogram (ECG):

Intervals Normal duration in secs Events in the heart

Average Range

P wave Atrial depolarization

PR interval 0.18 0.12- Atrial depolarization &

0.20 conduction through AV
node

QRS interval 0.08 0.08- Ventricular

0.10 depolarization & atrial
repolarisation

QT interval 0.40 0.40- Ventricular

0.43 depolarization &
ventricular
repolarisation

AT interval 0.32 Ventricular

repolarisation

Einthoven’s law: lead II=lead I+ lead III

Kirchoff’s law lead I + lead II+ lead III=0
Normal cardiac axis between-30 degress to +110 degress
Standard limb leads Lead I, II & III
Augmented limb leads aVR, aVL, aVF

Generalizations for leads in normal ECG:

aVR All the deflections are negative

aVL/aVF Predominantly positive or biphasic

40
V1, V2 No Q wave, deep S wave

V3, V4 Biphasic

V5, V6 Small Q wave, Tall R wave

Lead I, II, III All positive deflection, largest in lead II

HIS BUNDLE ECG:

 Studying the electrical events of AV node, Bundle of His & Purkinje system in a patient
with heart block by placing catheter with electrode through a vein

Wave Significance Interval Significance Duration

A wave AV node PA Conduction time from the 27ms

activation SA node to the AV node

H spike His bundle AH AV nodal conduction time 92ms

transmission

V Ventricular HV Conduction in the bundle 43ms

deflection depolarization of his and the bundle
branches

Heart Block:

Incomplete heart block  first-degree heart block- all the atrial

impulses reach the ventricles but the
PR interval is abnormally long
 second-degree heart block- not all
atrial impulses are conducted to the
ventricles. PR interval lengthens
progressively until a ventricular beat is
dropped (Wenckebach phenomenon).
Complete heart block  Third degree heart block- conduction
from the atria to the ventricles is com-
pletely interrupted
 ventricles beat at a low rate
(idioventricular rhythm)-as low as 15
beats/min leads to Stokes–Adams
syndrome- cerebral ischemia causes
dizziness and fainting

Electrolyte abnormalities:

41
Hyponatremia  low-voltage electrocardiographic
complexes
Hyperkalemia  the appearance of tall peaked T waves,
prolongation of the QRS complexes,
heart stops in diastole
Hypokalemia  prolongation of the PR interval,
prominent U waves, T wave inversion
Hypercalcemia  plasma calcium level is rarely high
enough to affect the heart
 heart stops in systole (calcium rigor)
Hypocalcemia  prolongation of the ST segment and QT
interval

Cardiac Cycle:

 The cardiac events that occur from the beginning of one heartbeat to the beginning of
the next are called the cardiac cycle

Phase Ventricle Atrium Total duration of

Systole 0.27sec 0.1sec cardiac cycle 0.8sec
Diastole 0.53 sec 0.7 sec

Atrial systole  Duration-0.1 s

 Follows impulse generation in the S.A.
Node
 Proples 30% of additional blood into
the ventricles
Ventricular systole  Duration-0.27 s
1. Isometric contraction: 0.05sec:
 Ventricles contract and the
pressure exceeds the arterial
pressure
 Closure of AV Valves  first heart
sound
 Bulging of AV valves into the atrium
2. Ventricular systole proper: (0.25sec)
 Rapid ejection phase: (0.1 sec)-
2/3rd of the stroke volume is
ejected, Intra ventricular pressure
rises to the maximum, AV valves
come back to original position & a
sharp fall in atrial pressure occurs
 Slow ejection phase (0.15sec)
Ventricular diastole  Duration-0.5 s

42
 1. Proto diastole: (0.04sec): Ventricular
pressure drops more rapidly. Closure
of Semilunar valves sound heart
sound
2. Isometric relaxation: (0.08sec): Initial
part of ventricular diastole. Intra
ventricular pressure drops, ventricular
muscle continues to relax without
change in the ventricular volume
3. Ventricular diastole proper: passive
filling of ventricles (70%)
4. Initial rapid filling phase: opening of AV
Valves and continued relaxation of
ventricles
5. Slow filling phase (Diastasis):
continuous venous return filling both
atrium & ventricles
Atrial Diastole  Duration-0.7 S
 Atrial muscle relaxes and the pressure
gradually increases due to venous
return

Valvular events Cardiac events ECG JVP

Opening of AV End of isometric relaxation End of T wave V-Y descent

valve phase

Closure of AV valve End of diastole Later half of R End of x

wave descent

Opening of End of isometric contraction ST segment Peak of C

semilunar Valve wave

Closure of Beginning of diastole Later half of T

semilunar valve wave

Arterial Pulse Rate of travel:

 Aorta: 4m/s
 Large arteries: 8m/s
 Small arteries: 16 m/s

43
WAVES IN ARTERIAL PULSE

Ascending limb/Anacrotic or primary limb rise in pressure during systole

Descending limb/Catacrotic limb Fall in pressure during diastole

Percussion wave (P wave) Ejection pase of ventricular systole

Tidal wave (T wave) Falling blood column during slow ejection

phase

Dicrotic notch (N) Closure of Aortic valve, marks the end of

ventricular systole

Dicrotic wave (D) Rebound of blood column from closed aortic

valve

WAVES IN JVP

A wave Atrial systole

C wave Bulging of tricuspid valve into the right atrium during isovolumic ventricular
contration

V wave Filling of the right atrium by venous return

X decent Atrial relaxation and downward displacement of closed tricuspid valve during
ventricular contraction

Y descent Blood flow from RA to RV

Various pressures:

Diastole Systole

Right Atrium 0 5mm Hg

Right Ventricle 0-5 mm Hg 15-30 mm Hg

Pulmonary Artery 10 mm Hg 15-30 mm Hg

Left Atrium 4 mm Hg 12mm Hg

Left Venticle 4-12mm Hg 90-140 mm Hg

Aorta 60-90 mm Hg 90-140 Hg

44
 Variation in length of action potential and associated phenomena with cardiac rate:

Heart Heart
Rate Rate
75/min 200/min
Duration, each 0.80 0.30
cardiac cycle
Duration of systole 0.27 0.16
Duration of action 0.25 0.15
potential
Duration of 0.20 0.13
absolute
refractory period
Duration of relative 0.05 0.02
refractory period
Duration of diastole 0.53 0.14

Hear sounds:

First Heart Sound Sound Heart Sound Third Heart Sound Fourth Heart Sound
Due to closure of AV Due to closure of Due to vibration of the Produced by atrial
valves Semilunar valves ventricle & turbulence of systole
blood flow
Marks the onset of Marks the onset of rapid filling phase of Due to vaentricular
ventricular systole ventricular diastole ventricle filling
 Continuous  Split Sound  Low Pitched  Also called
sound  Last 0.1 to Sound atrial sound
 Lasts 0.14- 0.14sec  Lasts<0.1sec  Low-
0.17sec  Audible  Audible In pitched
 Audible better better at  -30% of normal Sound
at tricuspid Aortic and population  Audible in
&Mitral areas Pulmonary  -MI & -Heart filure  -MI
 Coincides with areas  -Cardiomyopathy  -Heart
‘R’ wave of  Coincides  -Ventricular failure
ECG with end of hypertrophy
 Dull, ‘T’ wave of
Prolonged, ECG
Soft, Low, low-  Short, Sharp,
pitched sound high-pitched
(LUB) sound (DUB

Cardiac output:

 output of the heart per unit time which equals 5L/min

Methods of measuring cardiac output

Direct method Indirect method
Electromagnetic Flow meter Fick’s principle

45
 Indicator dilution principle/Thermo dilution t echnique
Doppler echo cardiogram

 Fick’s Principle- amount of a substance taken up by an organ (or by the whole body) per
unit of time is equal to the arterial level of the substance minus the venous level (A-V
difference) times the blood flow
 Factors controlling cardiac output:
1. Changes in heart rate(controlled primarily by the autonomic nerves, with sym-
pathetic stimulation increasing the rate and parasympathetic stimulation
decreasing it)
2. Changes in stroke volume

preload  the degree to which the myocardium is

stretched before it contracts
afterload  resistance against which blood is
expelled
Frank–Starling law  “energy of contraction is proportional to
the initial length of the cardiac muscle
fiber”
 For the heart, the length of the muscle
fibers (ie, the extent of the preload) is
proportional to the end-diastolic volume
Frank–Starling curve  The relation between ventricular stroke
volume and end-diastolic volume
heterometric regulation  When cardiac output is regulated by
changes in cardiac muscle fiber lengt
homometric regulation  regulation due to changes in contractility
indepen-dent of length
pericardial sac  contains 5–30 mL of clear fluid

Effect of various conditions on cardiac output:

No change Increase in CO Decrease in CO

Sleep Anxiety, Eating, Exercise Rapid cardiac arrhythmias
Moderate change in Hyperthermia Heart disease
temperature Pregnancy, Epinephrine Sitting/standing from lying
posture

Factors that depress myocardial contractility:

Hypercapnia
Hypoxia
Acidosis
Drugs such as quinidine, procainamide, and barbiturates
Acute heart failure(“myocardial hibernation”)

46
Oxygen consumption by the heart:

 Basal O2 consumption-2 mL/100 g/min

 O 2 consumption by the beating heart-9 mL/100 g/min
 Determined by
1. intramyocardial tension
2. contractile state of the myo-cardium
3. heart rate
 “increase in afterload causes a greater increase in cardiac O2 consump-tion than does an
increase in preload”

Normal values for the cellular elements in human blood:

Approximate Percentage
Cells/μL Normal of Total
Cell (average) Range White Cells
9000 4000-11,000
Total white blood cells
Granulocytes
Neutrophils 5400 3000–6000 50–70
Eosinophils 275 150–300 1–4
Basophils 35 0–100 0.4
Lymphocytes 2750 1500–4000 20–40
Monocytes 540 300–600 2–8
Erythrocytes
Females 4.8 × 106
Males 5.4 × 106
Platelets 300,000 200,000–500,000
Characteristics of human red cells:

Male Female
Hematocrit (Hct) (%) 47 42
Red blood cells (RBC)
(106/μL) 5.4 4.8
Hemoglobin (Hb)
(g/dL) 16 14
Mean corpuscular Hct × 10/
volume (MCV) (fL) RBC (106/μL) 87 87

Mean corpuscular
hemoglobin (MCH) Hb × 10/
(pg) RBC (106/μL) 29 29

Mean corpuscular
hemoglobin
concentration Hb × 100/
(MCHC) (g/dL) Hct 34 34

Mean cell diameter

(MCD) μm) Mean diameter of 500 cells in smear 7.5 7.5

47
 RBC Indices Normal value

Mean corpuscular corpuscular (MCV) 80-94 Cubic microns (3)

=Hematocrit /Number of red cells

Mean Corpuscular Hemoglobin (MCH) 27-32 Pico grams (pg)

=MCH Blood hemoglobin (g/L) Red ell count

(Cells/L)

Mean Corpuscular Hb Concentration (MCHC) 33%

=Hb (g/L)/hematocrit

Colour Index (CI)=%of b 0.9-1.1%

% of RBC

Hemoglobin:

Adult human haemoglobin: Fetal hemoglobins:

 Hemoglobin A(α 2β2)  Hemoglobin F(α2γ2)
 Gower 1 hemoglobin (ζ2ε2)
 Gower 2 hemoglobin (α2ε2)

ABO system:

Blood Agglutini Frequency in Plasma

Type ns India % Agglutinates Red
in Plasma Cells of Type:

O Anti-A, 40 A, B, AB
anti-B
A Anti-B 22 B, AB

B Anti-A 33 A, AB

AB None 5 None

Blood-clotting factors:

Factora Names
I Fibrinogen
II Prothrombin
III Thromboplastin
IV Calcium

48
 V Proaccelerin, labile factor, accelerator
globulin
VII Proconvertin, SPCA, stable factor
VIII Antihemophilic factor (AHF), antihemophilic
factor A,antihemophilic globulin (AHG)
IX Plasma thromboplastic component (PTC),
Christmas factor, antihemophilic factor B
X Stuart–Prower factor
XI Plasma thromboplastin antecedent (PTA),
antihemophilic factor C
XII Hageman factor, glass factor
XIII Fibrin-stabilizing factor, Laki–Lorand factor
HMW-K High-molecular-weight kininogen, Fitzgerald
factor
Pre-Ka Prekallikrein, Fletcher factor
Ka Kallikrein
PL Platelet phospholipid
a
Factor VI is not a separate entity and has been dropped.

Diseases due to deficiency of clotting factors:

Deficiency Clinical Syndrome Cause

of Factor:

I Afibrinogenemia Depletion during

pregnancy with
premature separation
of placenta; also
congenital (rare)
II Hypoprothrombinemia Decreased hepatic
(hemorrhagic synthesis, usually
tendency in liver secondary to vitamin K
disease) deficiency
V Parahemophilia Congenital
VII Hypoconvertinemia Congenital
VIII Hemophilia A (classic Congenital defect
hemophilia) due to various
abnormalities of
the gene on X
chromosome that
codes for factor VIII;
disease is therefore
inherited as a sex-
linked characteristic
IX Hemophilia B Congenital
(Christmas disease)

49
 X Stuart–Prower factor Congenital
deficiency
XI PTA deficiency Congenital
XII Hageman trait Congenital

Proteins synthesised by liver:

Name Principal Function Binding Characteristics Serum or Plasma Concentration

Albumin Binding and carrier protein; Hormones, amino acids, steroids, 4500–5000 mg/dL
osmotic regulator vitamins, fatty acids
Orosomucoid Uncertain; may have a role in Trace; rises in inflammation
inflammation

α1-Antiprotease Trypsin and general protease Proteases in serum and tissue 1.3–1.4 mg/dL
inhibitor secretions
α-Fetoprotein Osmotic regulation; binding Hormones, amino acids Found normally in fetal blood
and carrier proteina

α2-Macroglobulin Inhibitor of serum endoproteases Proteases 150–420 mg/dL

Antithrombin-III Protease inhibitor of intrinsic 1:1 binding to proteases 17–30 mg/dL
coagulation system
Ceruloplasmin Transport of copper Six atoms copper/molecule 15–60 mg/dL

C-reactive protein Uncertain; has role in tissue Complement C1q < 1 mg/dL; rises in inflammation
inflammation
Fibrinogen Precursor to fibrin in hemostasis 200–450 mg/dL
Haptoglobin Binding, transport of cell-free Hemoglobin 1:1 binding 40–180 mg/dL
hemoglobin
Hemopexin Binds to porphyrins, particularly 1:1 with heme 50–100 mg/dL
heme for heme recycling
Transferrin Transport of iron Two atoms iron/molecule 3.0–6.5 mg/dL

Apolipoprotein B Assembly of lipoprotein particles Lipid carrier

Angiotensinogen Precursor to pressor peptide
angiotensin II
Proteins, coagulation factors Blood clotting 20 mg/dL
II, VII, IX, X
Antithrombin C, protein C Inhibition of blood clotting

Insulinlike growth factor I Mediator of anabolic effects of IGF-I receptor

Steroid hormone-binding
globulin
Thyroxine-binding globulin
Transthyretin (thyroid-
binding prealbumin)
growth hormone
Carrier protein for steroids in Steroid hormones 3.3 mg/dL
bloodstream
Carrier protein for thyroid Thyroid hormones 1.5 mg/dL
hormone in bloodstream
Carrier protein for thyroid Thyroid hormones 25 mg/dL
hormone in bloodstream

Protein content of lymph in humans:

Source of Lymph Protein Content

(g/dL)

50
 Choroid plexus 0
Ciliary body 0
Skeletal muscle 2
Skin 2
Lung 4
Gastrointestinal tract 4.1
Heart 4.4
Liver 6.2(Max)

Characteristics of various types of blood vessels:

Vessel Cross sectional area(m2) % of blood contained

Aorta 4.5 2
Artery 20 8
Arteriole 400 1
Capillary 4500 5
Venule 4000
Vein 40 54
Vena cava 18

Arteries 1. Large Elastic Arteries:

 Windkessel VesselEg. Aorta & its main
branches
 Smooth muscles arranged Spirally
 More elastic
2. Large muscular Arteries:
 Smooth muscle content is high
 Few elastic fibres are present
3. arterioles (stop cocks of circulation):
 seat of maximum peripheral resistance
 Lacks elastic fibres
 Rich in smooth muscle-arranged in
circular fashion
Veins 1. Large Veins:
 Thin walled
 Large than largest arteries
 Elastin Content is less
 Capacitance Vessels (hold maximum
blood)
2. Venules:
 Thin-walled but larger than arterioles
 Less elastin content than arterioles
Capillaries  Small vessels guarded by Precapillary

51
 Sphincter
 Modified smooth musles (Pericytes) are
present
 Has Single layer of endothelium
 Types:
1. Continuous
– Seen in heart, lung, brain & skeletal
muscle
2. Fenestrated
– Seen in the endocrinal glands and renal
glomeruli
3. Discontinuous (Sinusoids)
– Seen in red bone marrow & liver
– Highly permeable

BLOOD FLOW:

LAMINAR TURBULENT

Silent Noisy

Flow is maximum in the centre of the flow & No such flow

decreases towards the wall (paraboloid
velocity profile)

The probability of turbulence is given by Reynolds’s number:

Re=DV

 is the density of the fluid; D is the diameter of the tube

V is the velocity of the flow;  is the viscosity of the fluid

 The higher the value of Re, the greater the probability of turbulence

 Flow is usually not turbulent is Re is less than 2000

 When Re is more than 3000, turbulence is almost always present

Critical closing pressure: The pressure at which flow ceases.Value is not zero but above zero

Poiseuille–Hagen formula  8ήL/πr4

 flow varies directly and resistance
inversely with the fourth power of the
radius, blood flow
Law of Laplace  tension in the wall of a cylinder (T) is
equal to the product of the transmural

52
 pressure (P) and the radius (r) divided by
the wall thickness (w):T = Pr/w
Bernoulli’s principle  the sum of the kinetic energy of low and
the potential energy—is constant
Newtonian fluid  viscosity is independent of the rate of
shear.Examples-Plasma,saline
Non Newtonian fluid  Viscosity changes with changes in shear
rate.Example-Blood

Blood pressure:

 cardiac output x peripheral resistance

 S.I. unit: PASCAL
 1 mmHg=0.133kPa

Regulation of blood pressure:

• Short Term Regulation of BP

– Baroreflex

– Chemoreflex

– CNS Ischaemic Response

– Hormonal Mechanisms

• Catecholamine Release

• Renin-Angiotensin Mechanism

– Intrinsic Vascular Mechanism

• Capillary Fluid Shift

• Stress Relaxation

• Long Term Regulation of BP

– Blood Volume (Fluid Balance)

– ADH, Renin-Angiotensin System, Atrial Natriuretic Peptide

Cardiovascular Regulation:

Medulla Vasomotor area(rostral ventrolateral medulla):

 Neurotransmitter-Glutamate
 Direct stimulation of RVLM:
1. CO2
2. Hypoxia
 Excitatory inputs to RVLM:

53

Baroreceptors
(carotid SinuS: measures pressure
carotid bO2dy measures O2)
Increased blood pressure buffer nerves
nucleus tractus solitaries
Baroreflex:
1. Cortex via hypothalamus
2. Mesencephalic periaqueductal gray
3. Brain stem reticular formation
4. Pain pathways
5. Somatic afferents (somatosympathetic
reflex)
6. Carotid and aortic chemoreceptors
 Inhibitory inputs to RVLM:
1. Cortex via hypothalamus
2. Caudal ventrolateral medulla
3. Caudal medullary raphé nuclei
4. Lung inflation afferents
5. Carotid, aortic, and cardiopulmonary
baroreceptors
 carotid sinus & Aortic arch
receptor(Buffer Nerves)
 Afferent from carotid sinus-
Glossopharyngeal nerve
 Afferent from Aortic arch-Vagus
 Tract 1: NTSexcitatory
glutaminergic neurons caudal &
intermediate ventrolateral medulla
stimulate GABA ergic neurons 
rostal ventro lateral medulla (RVLM),
the VMCinhibition of
VMCdecreased sympathetic
activity
 Tract 2: NTSdorsal motor nucleus
& Nucleus ambiguous vagal
neurons
 Increased BPStimulation of baro
receptors vagal stimulation +
inhibition of VMC ( sympathetic
activity)  Vasodilatation, ven
dilatation, BP, bradycardia,
cardiac output

Chemoreflex  When MAP falls below 80mm

Hgfall in blood flow to
chemoreceptors  corresponding
reduction in oxygen delivery
(hypoxia) and an accumulation of
CO2 and H+detected by
chemoreceptors located in the
carotid and aortic bodiesexcites
the vasomotor centre
 Not a powerful arterial pressure

54
 controller until pressure falls below 80
mm Hg
Atrial stretch receptors  Type-A: discharge primarily in atrial
systole
 Type-B: discharge primarily in late atrial
diastole
 The response is vasodilatation, fall in BP
& increase in heart rate
Cushing’s Reflex(CNS ISCHEMIC RESPONSE/LAST  INCREASE IN INTRA CRANIAL tension
DITCH STAND) hypoxia & hypercapnia of
VMCdirect simiulation of
VMCincreased sympathetic
activityintense vaso constriction
increase in BP
 Doesn’t become significant until
pressure falls below 60 mm Hg
 Greatest degree of stimulation at 15 to
20 mm Hg
 Elevate mean arterial pressure for as
long as 10 minutes and as high as 250
mm Hg
Bainbridge reflex:  Rapid perfusion of blood saline
stimulates the atrial stretch receptors &
results in increased heart rate if the
initial HR is low
Bezold-Jarisch reflex: (coronary chemoreflex)  Serotonin & Chemicals like nicotine in
the coronary or pulmonary arteries can
stimulate the receptors of the left
ventricle resulting in profound
bradycardia, hypotension, and a brief
period of apnea followed by rapid
shallow breathing
 Activation of chemosensitive vagal C
fibers

AUTO REGULATION

 Ability of an organ to regulate its blood flow with changes in perfusion pressure. Seen in
brain, kidney, skeletal muscle, heart, liver etc… (Not in skin)

 Theories of auto regulation:

 Myogenic theory: Pacemaker cells in the smooth muscles of lblood vessels possess basal
myogenic tone, which responds to change in blood pressure

55
  Metabolic theory: accumulation of metabolites increases the blood flow by
vasodilatation
 Nutrient lack theory: lack of oxygen vasodilatation
Factors affecting the caliber of the arterioles:
Vasoconstriction
Local factors
 Decreased local temperature
 Autoregulation
Endothelial products
 Endothelin-1
 Locally released platelet
 serotonin
 Thromboxane A2
Circulating neurohumoral agents
 Epinephrine (except in
 skeletal muscle and liver)
 Norepinephrine
 Arginine vasopressin
 Angiotensin II
 Endogenous digitalis-like
substance
 Neuropeptide Y
 Urotensin-II
Neural factors
 Increased discharge of
sympathetic nerves
Coronary circulation
Vasodilation
 Increased CO2 and decreased O2
+
 Increased K , adenosine, lactate
 Decreased local pH
 Increased local temperature
 Nitric oxide
 Kinins
 Prostacyclin
 Epinephrine in skeletal muscle
 and liver
 Calcitonin G-related protein
 Substance P
 Histamine
 Atrial natriuretic peptide
 Vasoactive intestinal polypeptide
 Decreased discharge of sympathetic nerves
 Activation of sympathetic cholinergic vasodilator nerves to
vasculature of skeletal muscles ofthe limbs
 Metabolic factors (hypoxia) are more
potent regulators than neural factors
 Only organ in which the blood flow is
decreased during systole
 The coronary arterioles contain -
adrenergic receptors, which mediate
vasoconstriction, and -adrenergic
receptors, which mediate
vasodilation
 However, norepinephrine increases
the heart rate and the force of
cardiac contraction, and the
vasodilation is due to production of
vasodilator metabolites in the
myocardium secondary to the
56
 increase in its activity

Regulation of coronary blood flow:

Physical Factors Metabolic Factors Neural Factors

Arterial BP: Hypoxia (most Sympathetic

potent)
Diastolic BP Vasodilatation (-
+ +
influences the CO 2, H , K , lactate, receptors)
rate of coronary prosta-glandins,
Blood flow adenine Vasoconstriction
nucleotides and (receptors)
Coronary adenosine
Vascular
resistances

Extra-coronary
vascular pressure

Cerebral circulation  Exhibits autoregulation

 Most important vasodilator-Co2
 Sympathetic nerves play a minor role
Cutaneous circulation  Temperature regulation is the principal
function
 Has extensive sympathetic innervations
 Triple response:
1. Redness- due to capillary dilation
2. Wheal-increased permeability of the
capillaries and postcapillary venules
3. Flare-due to arteriolar dilation
 When the skin needs to CONServe heat,
the blood vessels of the skin CONStrict

Ciruculation through special regions:

Blood flow arteriovenous Oxygen Resistanc Percentage of Total

e (Runits)
Oxygen Consumption

Difference

57
Region Mas mL/mi mL/100g (mL/L) mL/min mL/100 Absolute Per Cardiac Oxygen
(kg) n /min g/min kg output consum
ption

Liver 2.6 1500 57.7 34 51 2.0 3.6 9.4 27.8 20.4

Kidneys 0.3 1260 420.0 14 18 6.0 4.3 1.3 23.3 7.2

Brain 1.4 750 54.0 62 46 3.3 7.2 10.1 13.9 18.4

Skin 3.6 462 12.8 25 12 0.3 11.7 42.1 8.6 4.8

Skeletal 31.0 840 2.7 60 50 0.2 6.4 198.4 15.6 20.0

muscle

Heart 0.3 250 84.0 114 29 9.7 21.4 6.4 4.7 11.6
muscle

Rest of 23.8 336 1.4 129 44 0.2 16.1 383.2 6.2 17.6
body

Whole 63.0 5400 8.6 46 250 0.4 1.0 63.0 100.0 100.0
body

Overall(ml/min)
Blood flow O2 consumption
Liver>Kidney>Skeletal muscle>Brain>skin>heart Liver>Skeletal muscle>Brain>heart

Per unit mass(ml/100g/min)

Blood flow O2 consumption

Kidney> heart> Liver Heart>kidney>brain

Resistance

Absolute Per Kg

Heart-Max Skeletal muscle-Max

Liver-Min Kidney-Min

Av o2 difference
Heart-Max
Kidney-Min

58
 Respiratory Physiology-High yield topics

Conducting Zone  First 16 generations

 Comprises of
trachea,bronchi,bronchioles and
terminal bronchioles
Respiratory Zone  Last 7 generations
 Comprises of Respiratory
bronchioles,alveolar ducts and alveolar
sacs

Conduction zone to respiratory zone transition events

 Secretory glands are absent from the epithelium of the bronchioles and terminal bronchioles
 smooth muscle-more prominent
 cartilage-absent
 Clara cells,Basal cells- serve as progenitor cells after injury

Epithelial cells in the conducting airway secrete  Secretory immuno-globulins (IgA)

 collectins (including surfactant protein
(SP) -A and SP-D)
 reactive oxygen species
 reactive nitrogen species
 chemokines,cytokines

Respiratory cilia  beat at rates of 10–15 Hz

 is capable of moving particles 16
mm/min

Alveolar airways  Humans have 300 million alveoli

 Total area-70 m2.
 two types of epithelial cells- Type I
cells(primary lining cells of the
alveoli,Covers 95% of area) and Type II
cells (granular pneumocytes)
 type II cell- production of surfactant
- lamellar bodies- membrane-
bound organelles containing
phospholipids
- Surfactant-reduces surface
tension
 Other cells- Pulmonary alveolar
macrophages,lymphocytes, plasma cells,
neuroendocrine cells, and mast cells

59
 RESPIRATORY VOLUMES

MEASUREMENT TYPICAL DEFINITION

VALUE

Tidal volume (TV) 500ML Amount of air that enters or leaves lungs during
one inspiration or expiration (respiratory cycle)

Inspiratory reserve 3000ML Maximum volume of air that can be inspired

volume (IRV) over the normal TV

Expiratory reserve 1200ML Extra volume of air expired by forceful expiration

volume (ERV) after the end of normal tidal expiration

Residual volume (RV) 1200ML Amount of air left in lungs after forced
exhalation

Closing volume lung volume above the residual volume at which

the alveoli of lung bases begin to close off

RESPIRATORY CAPACITIES

Vital capacity (VC) 4700ML IRV+TV+ERV, maximum amount of air that can
be exhaled after a maximum inspiration

Inspiratory capacity (IC) 3500ML TV+IRV, maximum amount of air that can be
inhaled after a normal expiration

Functional residual 2400 ML RC+ERV, amount of air remaining in the lungs

capacity (FRC) after a normal tidal expiration

Total lung capacity 5900ML RV+VC, maximum volume to which the lungs can
ITLC) be expanded

Closing capacity RV+ the volume expired between the beginning

of airway closure and
the RV

 Spirometer: measures all volumes & capacities except RV, FRC and TLC
 Methods to measure RV & FRC:
Helium dilution technique
Plethysmography
Nitrogen washout method
 Obstructive disordes-marked decrease in both FVC and FEV 1/FVC
 Restrictive disorders result in a loss of FVC without loss in FEV 1 /FVC

60
Surfactant  Mixture of
dipalmitoylphosphatidylcholine(DPPC),
other lipids, and proteins
 Proteins- surfactant protein (SP)-A, SP-B,
SP-C, and SP-D
 SP-A and SP-D-belongs to collectin
family, involved in innate immunity
 SP-B and SP-C- members of the
monomolecular film of surfactant
 Surfactant deficiency- infant respiratory
distress syndrome(Prolonged
immaturity of the epithelial Na+
channels (ENaCs)
 Overproduction/dysregulation of
surfactant proteins- Pulmonary Alveolar
Proteinosis (PAP)

Dead space  Anatomical- Volume of air occupying

the conducting zone (not
participating in gaseous exchange).
(150ml), measured by Bohr’s
method
 Roughly equal to body weight in
pounds or twice the body wt. in kgs
 Alveolar dead space-volume of gas
not equilibrating with blood,
“WASTED VENTILATION”,
PHYSIOLOGICAL DEAD SPACE=
ANATOMICAL DEAD
SPACE+ALVEOLAR DEAD SPACE
 Under normal conditions, alveolar
dead space is zero. Hence both
anatomical & physiological DS are
equal

Diffusion across alveolocapillary membrane

 substances passing from the alveoli to the capillary blood reach equilibrium in the 0.75 s
 N2O- not limited by diffusion but by the amount of blood flowing through the pulmonary
capillaries(Perfusion-limited)
 Carbonmonoxide- taken up by hemoglobin in the red blood cells at such a high rate,
equilibrium is not reached in the 0.75 s(not limited by perfusion at rest -diffusion-limited)
 Oxygen-Intermediate. Taken up by hemoglobin, but much less avidly than CO, reaches

61
 equilibrium with capillary blood in about 0.3 s(Perfusion limited)
 Diffusing capacity- directly proportional to the surface area of the alveolocapillary mem-
brane and inversely proportional to its thickness
 diffusing capacity for CO (Dlco)- measured as an index of diffusing capacity because its
uptake is diffusion-limited
VCO/
DLCO = PACO
 Normal value of Dlco at rest-25 mL/min/mm Hg
 Normal value of diffusing capacity for O 2 at rest-25 mL/min/mm Hg

Ventilation-Perfusion ratio

 For the whole lung at rest is about 0.8

 ventilation, as well as perfusion in the upright position, declines in a linear fashion
from the bases to the apices of the lungs
 Gravity affects perfusion much more than it affects ventilation
 ventilation/perfusion ratios are high in the upper portions of the lungs
 At apex-Intrapleural pressure more negative, Greater transmural pressure, Large
alveoli(More underperfused than underventilated)

Agents affecting smooth muscle in pulmonary arteries and veins:

Constriction Relaxation
1. Adrenergic (α1) 1. Adrenergic(α1, β 2)
2. Purinergic (P2x) 2. Muscarinic (M3)
3. Tachykinin(NK2) 3. Purinergic(P2Y)
4. Adenosine( A1) 4. Tachykinin(NK1)
5. Angiotensin II( AT 1) 5. VIP
6. Endothelin (ETA) 6. CGRP
7. Serotonin (5-HT1) 7. Adenosine( A2)
8. Thromboxane (TP) 8. ANP
9. Bradykinin
10. Endothelin (ETB)
11. Histamine(H1,H2)
9. Serotonin (5-HTC)
12. Vasopressin (V1)

Biologically active substances metabolized by the lungs

Synthesized and used in the lungs

Surfactant
Synthesized or stored and released into the blood
Prostaglandins
Histamine
Kallikrein
Partially removed from the blood

62
 Prostaglandins
Bradykinin
Adenine nucleotides
Serotonin
Norepinephrine
Acetylcholine
Activated in the lungs
Angiotensin I → angiotensin II

Oxygen Hemoglobin Dissociation curve

 relates percentage saturation of the O 2 carrying power of hemoglobin (SaO2) to the Po2
 Hemoglobin-tense (T) configuration- reduced the affinity for O 2
 Relaxed(R) configuration- exposes more O2 binding sites
 When fully saturated, each gram of normal hemoglobin contains 1.34 mL of O 2
 1 dL of blood contains 20.1 mL (1.34 mL × 15) of O2 bound to hemoglobin when the hemo-
globin is 100% saturated

Gas content of blood:

mL/dL of Blood Containing 15 g of Hemoglobin

Arterial Blood Venous Blood
PO2 95 mm Hg; PCO2 40 mm (PO2 40 mm Hg; PCO2 46 mm
Hg; Hb 97% Saturated) Hg; Hb 75% Saturated)
Gas Dissolved Combined Dissolved Combined
O2 0.29 19.5 0.12 15.1
CO2 2.62 46.4 2.98 49.7
N2 0.98 0 0.98 0

 The point where 50% of Hb is satured with O2 is called the P5027mmHg

FACTORS AFFECTING THE AFFINITY OF HEMOGLOBIN FOR OXYGEN:

Shift to the Right (Release/tissues) Shift to the left (Lungs/binding)

 Increased PCO2  Decreased PCO2
 Increased temperature  Decreased temperature
 Increased 2,3-DPG  Decreased 2,3-DPG
 Growth hormone  Alkalosis (increased pH)
 Exercise  Fetal Hb(poor binding of 2,3-DPG by
 Hypoxia the γ polypeptide chains)
 High altitude  stored blood(2,3-DPG level falls)

63
  anemia
 Acidosis (decreased pH)
 Sickle cell anemia
 Adult Hb

 HbF binds Forcefully to oxygen

 Stored blood is SOS: Stored blood Hb binds to Oxygen Strongly because of decrease in 2,3
BPG
 2,3 BPG binding site is BBC: BPG binds to Beta Chain of Hb

Bohr Effect:

 The decrease in O 2 affinity of hemoglobin when the pH of blood falls

 Curve shifts to the right

Haldane effect:

 increased capacity of deoxygenated hemo-globin to bind and carry CO2

Myoglobin

 Iron-containing pigment found in skeletal muscle.

 binds 1 mol of O2 per mole protein(Hb binds 4)
 Dissociation curve- a rectangular hyperbola
 higher affinity for O 2(Leftward shift in curve)
 Its utmost purpose is utilised during exercise(O2 is released only at low Po2 values)
 During exercise- it continuos to provide O2 under reduced blood flow and/or reduced Po2 in
the blood
 Myoglobin binding strength is MOM: Myoglobin binds Oxygen More strongly than Hb

Acid Base Balance:

Plasma pH, HCO3–, and PCO2 values in various typical disturbances of acid–base balance:

Arterial Plasma
−
HCO3 PCO2
Condition pH (mEq/L) (mm Hg) Cause

Normal 7.40 24.1 40

Metabolic 7.28 18.1 40 NH4Cl ingestion

acidosis 6.96 5.0 Diabetic acidosis
23

Metabolic 7.50 30.1 40 NaHCO3 ingestion

alkalosis 7.56 49.8 58 Prolonged
vomiting

Respiratory 7.34 25.0 48 Breathing 7% CO2

acidosis 7.34 33.5 64 Emphysema
Respiratory 7.53 22.0 27 Voluntary hyper-
alkalosis ventilation
7.48 18.7 26 Three-week
residence at 4000-

64
 m altitude

Anion gap

 the difference between the concentration of cations other than Na+ and the concentration
of anions other than Cl– and HCO3– in the plasma
 comprises of proteins in anionic form, HPO42–, SO42–, and organic acids
 normal value-12 mEq/L
 Increased:
1. when the plasma concentration of K+, Ca2+, or Mg+ is decreased
2. when the concentration of plasma proteins is increased
3. when organic anions such as lactate or foreign anions accumulate in blood
4. in metabolic acidosis due to ketoacidosis, lactic acidosis
 Decreased:
1. when cations are increased
2. when plasma albumin is decreased

Graphic analysis of pH disturbances can be done using

 The Davenport Diagram

 The Siggard-Anderson nomogram

Hypoxia: O2 deficiency at the tissue level

Type Causes Mechanism PAO2 PaO2 O 2 A-V

content difference
Hypoxic/Anoxic High altitude -Poor availability of O2 for    
& diffusion
Pneumonia _Decreased Partial Pressure
of O2 in arterial blood
Anemic Anemia CO -Decreased O2 carrying    
Poisoning capacity
Stagnant/ Cardiogenic O2 content of the blood is    
Ischemic/ shock exhausted due to reduction
Hypoperfusion in blood velocity
Histotoxic Beriberi Tissue cannot make use of    
HNC available O2
Poisoning

Best test for hypoxia

 Hypoxic hypoxia (Anoxic/Arterial): partial pressure of arterial O2, treated by oxygen

therapy

65
  Anemic hypoxia-oxygen content (Hb%)
 Stagnant hypoxia- A-V difference (increased)
 Histotoxic hypoxia- A-V difference(decreased) or PO 2 of venous blood (increased)

Neural control of respiration:

 Voluntary system-located in the cerebral cortex and sends impulses to the respiratory motor
neurons via the corticospinal tracts
 Automatic system-pacemaker cells in the medulla-activate motor neurons in the cervical and
thoracic spinal cord that innervate inspiratory muscles

Medullary system: Pontine & vagal influences:

Pre-Botzinger Complex:
 rhythm of respiration (pace maker of
respiration)
 has NK1 receptors,μ-opioid receptors
and 5HT 4 receptors
 substance P stimulates and opioids
inhibit respiration
 5HT 4 agonists blocks the inhibitory ef
ect of opiates
Dorsal respiratory group (DRG):
 Nucleus Tractus solitaries (NTS)
 Site of origin of rhythmic inspiratory
discharge. (Inspiratory ramp signals)
Ventral respiratory group (VRG):
 Nucleus Retro Ambigualis (NRA)
 Both inspiratory & expiratory control
Switching between inspiration & expiration
Pneumotaxic centre:
 medial parabrachial and Kölliker–Fuse
nuclei
 inhibitory effect on apneustic centre
Apneustic centre:
 lower pons
 has an intrinsic rhythm, promotes
prolonged inspirations when active
Vagus:
Stretching of lungs during inspiration

Stimulates afferent pulmonary vagal fibres

Inhibit inspiratory discharge

Chemical control of respiration:

Peripheral chemoreceptors: Central chemoreceptors:

Carotid and aortic bodies:
 two types of cells, type I and type II
cells
 Type-I (glomus) cells
1. are closely assoivated with cup
like endings of the afferent
nerves
2. resemble adrenal chromai n
cells and have dense-core gran-
ules containing catecholamines
that are released upon expo-
sure to hypoxia and cyanide
3. excited by hypoxia-
Neurotransmitter-Dopamine(D2
receptor)
 Location: ventral surface of the
medulla, solitary tract nuclei, the
locus ceruleus, and the hypothalamus
 CSF (H+) is the potent stimulus to
central chemo receptor.
 Effects of Co2- mainly due to its
movement into the CSF and brain
interstitial fluid and increases the H +
concentration
 The magnitude of the stimulation is
proportional to the rise in H +
concentration.

66
 4. have O 2 sensitive K + channels-
conductance is reduced in
proportion to the degree of
hypoxia
 Type II-Glia like cells, surrounds four to
six type I cells
 Blood flow per unit of tissue is so
enormous- 2000 mL/100 g of
tissue/min
 Af ferents from the carotid bodies
ascend to the medulla via the carotid
sinus and glossopharyngeal nerves, and
fibers from the aortic bodies ascend in
the vagi
 respond to PO2PCO2&H+ of arterial
blood
 Hypoxia is the potent stimulus
 carotid bodies more effective than
aortic bodies

Airway and lung receptors:

Vagal Location in
Innervation Type Interstitium Stimulus Response

Myelinated Slowly Among airway smooth Lung inflation Inspiratory time shortening
adapting muscle cells (?) Hering–Breuer inflation
and deflation reflexes
Bronchodilation
Tachycardia
Hyperpnea
Rapidly Among airway Lung hyperinflation Cough
adapting epithelial cells Exogenous and endogenous substances Bronchoconstriction
(eg, histamine, prostaglandins) Mucus secretion
Unmyelinated Pulmonary C Close to blood vessels Lung hyperinflation Apnea followed by rapid breathing
C fibers fibers Exogenous and endogenous substances Bronchoconstriction
Bronchial C (eg, capsaicin, bradykinin, serotonin) Bradycardia
fibers
Hypotension
Mucus secretion

Abnormal respiratory patterns:

Pattern Cause Mechanics

Cheyne-stokes -Opium Periodic breathing due to Rhythmic alteration of

respiration poisoning apnea & hyperpnea

-Uremia & Waxing & waning tidal volume

CCF

67
 -hypoxia

Biot’s breathing Meningitis Periodic breathing with one or more large tidal
(Irregularly volumes separated by apnea
irregular
breathing)

Kussmaul’s -DKA Rapid & deep breathing

respiration
hunger) -Uremia

Ondine’s curse Loss of spontaneous breathing with only voluntary

control

68
 Gastro Intestinal Physiology

Specializations of GI epithelium

 Villi (fingerlike projections)- maximizes the surface area available for nutrient absorption.
 Crypts-Infoldings between villi.Base of the crypts contains STEM CELLS that give rise to both
crypt and villus epithelial cells
 Microvilli- dense glycocalyx (the brush border) that protects the cells from digestive
enzymes.contains brush border enzymes

Salivary Secretion

 Saliva-Produced from three pairs of salivary glands (the parotid, submandibular, and
sublingual glands
 1000–1500 mL of saliva per day is secreted
 Hypotonic and alkaline
 Parasympathetic-increases the secretion
 Sympathetic-increase protein content of saliva,has little effect on volume
 Antibacterial agents in saliva- immunoglobulin A and lysozyme

Source Enzyme Activator Substrate Catalytic Function or

Products

Salivary glands Salivary α- Cl− Starch Hydrolyzes 1:4α

amylase linkages, producing
α-limit
dextrins,maltotriose,
and maltose

Gastric Secretion

 About 2.5 L per day

 Parietal (oxyntic) cells- secrete hydrochloric acid and intrinsic factor(absorption of vitamin
B12)
 Chief (zymogen, peptic) cells- pepsinogens and gastric lipase("Chief of Pepsi":Chief cells of
stomach produce Pepsin.
 Trefoil peptides- stabilize the mucus-bicarbonate layer

Contents of normal gastric juice (fasting stating)

Cations: Na+, K+, Mg2+, H+ (pH approximately 3.0)

Anions: Cl−, HPO42−, SO42−

Pepsins

Lipase
69
Mucus

Intrinsic factor
Three primary stimuli of gastric secretion

1. Gastrin
 comes from G cells in antrum.Releasing factors- gastrin releasing peptide (GRP) or bombesin,
oligopeptides
 binds to receptors in parietal cells- to activate secretion and also enterochromaffin-like cells
(ECL cells)-release histamine
2. Histamine- H2 histamine receptors(triggers secretion)
3. Acetylcholine

“Gastrin and acetylcholine promote secretion by elevating cytosolic free calcium concentrations,
whereas histamine increases intracellular cyclic adenosine 3΄,5΄-monophosphate (cAMP)”

 Synergistic- greater than additive effect on secretion rates when histamine plus gastrin or
acetylcholine, or all three, are present simultaneously

Somatostatin: inhibits gastric secretion by inhibiting both G and ECL cells

Source Enzyme Activator Substrate Catalytic

Function or
Products

Stomach Pepsins HCl Proteins and Cleave peptide

(pepsinogens) polypeptides bonds adjacent to
aromatic amino
acids

Gastric lipase Triglycerides Fatty acids and

glycerol

Pancreatic secretion

 Exocrine cells(secrete enzymes) and duct cells(secrete bicarbonate)

 Composition-Cations: Na + , K + , Ca 2+ , Mg2+ (pH approximately 8.0), Anions: HCO3− , Cl− ,
SO42− , HPO42−,Digestive enzymes and other proteins
 About 1.5 L per day

Source Enzyme Activator Substrate Catalytic Function or Products

Exocrine pancreas Trypsin Enteropeptidase Proteins and Cleave peptide bonds on carboxyl
polypeptides side of basic amino acids (arginine
or lysine)

Chymotrypsins Trypsin Proteins and Cleave peptide bonds on carboxyl

polypeptides side of aromatic amino acids

70
 Elastase Trypsin Elastin Cleaves bonds on carboxyl side of
aliphatic amino acids
Cleave carboxyl terminal amino
Carboxypeptidase A Trypsin Proteins and acids that have aromatic or
polypeptides branched aliphatic side chains
Proteins and Cleave carboxyl terminal amino
Carboxypeptidase B Trypsin polypeptides acids that have basic side chains
Binds pancreatic lipase to oil
Colipase Trypsin Fat droplets droplet in the presence of bile acids

Pancreatic lipase Triglycerides Monoglycerides and fatty acids

Cholesteryl ester hydrolase Cholesteryl esters Cholesterol

Pancreatic α-amylase Cl− Starch Hydrolyzes 1:4α linkages, producing

α-limit dextrins,maltotriose, and
maltose

Ribonuclease RNA Nucleotides

Deoxyribonuclease DNA Nucleotides

Phospholipase A Trypsin Phospholipids Fatty acids, lysophospholipids

Regulation of pancreatic secretion:

SECRETIN CCK

Acts on the pancreatic ducts to cause copious Acts on the acinar cells to cause the release of
secretion of a very alkaline pancreatic juice that zymogen granules and production of pancreatic
is rich in HCO3− and poor in enzymes juice rich in enzymes but low in volume

Acts by increase in intracellular cAMP mediated by phospholipase C

BILE

 About 500 mL is secreted per day

 Only route by which the body can dispose of cholesterol
 alkaline electrolyte solution that resembles pancreatic juice

Bile acids  Primary- cholic acid and chenodeoxycholic acid

 Secondary- deoxycholic, lithocholic, and ursodeoxycholic acids
 synthesized from cholesterol
 reduce surface tension,emulsification of fat
 Amphipathic
 form cylindrical disks called micelles
 absorbed from terminal ileum by Na+ –bile salt cotransport system (ABST)
 normal rate of bile acid synthesis-0.2–0.4 g/d
 total bile acid pool- 3.5 g

71
  recycles- 6–8 times per day via enterohepatic circulation

Daily water turnover (mL) in the gastrointestinal tract:

A. Ingested-2000
B. Endogenous secretions-7000
 Salivary glands-1500
 Stomach-2500
 Bile-500
 Pancreas-1500
 Intestine-1000

Total input (A + B)-9000

Reabsorbed-8800(98%)

 Jejunum-5500
 Ileum-2000
 Colon-1300

Balance in stool-200

 Secretion-largely driven by the active transport of chloride ions into the lumen
 Colon-has ENaC channels for sodium absorption(expression increased by ALDOSTERONE)
 Cl – enters enterocytes through Na + –K + –2Cl− cotransporters and secreted into lumen
through the cystic fibrosis transmembrane conductance regulator (CFTR) channel which is
activated by protein kinase A and cAMP
 Cholera toxin((A1 peptide)- binds to GM-1 ganglioside receptors-inhibits GTPase activity of α
subunits leading to increase in the intracellular cAMP concentration.Function of NHE
transporter for Na+ is reduced leading to increased sodium chloride excretion

Gastrointestinal hormones:

Gastrin  Produced by G cells in the antral portion

of the gastric mucosa
 Three forms- G 34, G 17, and G 14
gastrins
 G 17 is the principal form
 Stimuli that increase gastrin secretion:
Peptides,amino
acids(Phenylalanine,tryptophan),
Distention,Gastrin releasing peptide,
Calcium,Epinephrine

 Stimuli that decrease gastrin secretion:

Acid,somatostatin, Secretin, GIP, VIP,

72
 glucagon, calcitonin

 acts via CCK-B receptor

 Actions- stimulation of gastric acid and

pepsin secretion and stimulation of the
growth of the mucosa of the stomach
and small and large intestines (trophic
action)

Cholecystokinin  secreted by I cells in the mucosa of the

upper small intestine
 Also found in nerves in the distal
ileum,colon and brain
 acts via CCK-A receptor
 Functions in gut- stimulation of
pancreatic enzyme secretion, con-
traction of the gallbladder and relaxation
of the sphincter of Oddi
 Functions in brain- regulation of food
intake, the production of anxiety and
analgesia
 Other actions- augments the action of
secretin, inhibits gastric emptying, exerts
a trophic effect on the pancreas,
increases the synthesis of enterokinase
 Releasing factors that activate CCK
secretion- CCK-releasing
peptide(intestinal mucosa) and monitor
peptide(pancreas)
 Stimuli that increase CCK secretion:
peptides and amino acids, fatty acids
(more than 10 carbon atoms)

Secretin  first hormone identified by Bayliss and

Starling
 secreted by S cells(mucosa of the upper
portion of the small intestine)
 increases the secretion of bicarbonate
by the duct cells of the pancreas and
biliary tract(Watery,alkaline juice)
 augments the action of CCK,decreases

73
 gastric acid secretion
 Stimuli that increase secretin secretion:
Products of protein digestion,acid

GIP

 produced by K cells in the mucosa of the duodenum and jejunum

 secretion is stimulated by glucose and fat in the duodenum
 stimulates insulin secretion -called as glucose-dependent insulinotropic peptide

VIP

 stimulates intestinal secretion of electrolytes, water

 relaxes intestinal smooth muscle, including sphincters; dilation of peripheral blood vessels;
and inhibits of gastric acid secretion
 potentiates the action of ace-tylcholine in salivary glands

Motilin

 secreted by enterochromaffin cells and Mo cells in the stomach, small intestine, and colon
 contracts smooth muscle in the stomach and intestines in between meals

Somatostatin

 Produced by D cells in the pancreatic islets and intestinal mucosa

 inhibits the secretion of gastrin, VIP, GIP, secretin, and motilin
 inhibits-pancreatic exocrine secretion,gastric acid secretion and motility and gallbladder
contraction
 inhibits the absorption of glucose, amino acids, and triglycerides
 ACID in lumen-main stimulus for somatostatin secretion

Ghrelin

 Produced in stomach
 Has a role in central control of food intake
 stimulates growth hormone secretion

Gastrin releasing peptide (Bombesin)

 neurotransmitter producing vagally mediated increases in gastrin secretion

Guanylin

 Binds guanylyl cyclise leading to increase in cGMP- causes increased secretion of Cl − into the

74
 intestinal lumen
 E. coli has a structure very similar to guanylin and activates guanylin receptors in the
intestine(Molecular Mimickry)

Peptide YY

 Stimulated by presence of fat. inhibits gastric acid secretion and motility

 Choleretics-stimulate bile secretion. Bile salts are most potent. Others are secretin & vagal
stimulation
 Cholagogues- increases bile flow by GB contraction. Mainly CCK.others are fatty acids &
amino acids

Enteric nervous system

 Myenteric plexus (Auerbach‘s plexus)-present between the outer longitudinal and middle
circular muscle layers. concerned primarily with motor control(Myenteric: Motility)
 Sub mucous plexus (Meissner‘s plexus)-present between the middle circular layer and the
mucosa. primarily involved in the control of intestinal secretion.Innervates the glan-dular
epithelium, intestinal endocrine cells, and submucosal blood vessels(Submucosal: Secretion
and blood flow)
 contains about 100 million sensory neurons, inter-neurons, and motor neurons in humans-
little brain”
 Parasympathetic-increases intestinal smooth muscle activity
 Sympathetic- decreases intestinal smooth muscle activity.sphincters constrict
 Intestinal blood vessels-Dual innervations.Extrinsic-noradrenergic and intrinsic-NO and
VIP(responsible for the increase in local blood flow (hyper-emia) that accompanies digestion
of food)
 Sphlanchnic circulation-receives about 30% of the cardiac output
Neurotransmitters:
 Norepinephrine,serotonin,GABA,ATP,nitric oxide,carbon monoxide

Digestion and absorption:

Source Enzyme Substrate Catalytic Function or Products

Intestinal mucosa Enteropeptidase Trypsinogen Trypsin

Aminopeptidases polypeptides Cleave amino terminal amino

acid from peptide

75
 Carboxypeptidases polypeptides Cleave carboxy terminal amino
acid from peptide

Endopeptidases Proteins and Cleave between residues in

polypeptides midportion of peptide

Dipeptidases dipeptides Two amino acids

Maltase Maltose,
maltotriose Glucose

Lactase Lactose Glucose and galactose

Sucrase Sucrose; also Glucose and fructose

maltotriose and
maltose

Isomaltase α-limit dextrins, Glucose

maltose
maltotriose

Nuclease Nucleic acids Pentoses and purine

and pyrimidine bases

Absorption or secretion of substances by the intestine:

Absorption of Small intestine colon

Upper(Jejunum) mid Lower
Sugars (glucose, ++ +++ ++
galactose, etc)
Amino acids ++ ++ ++
Water-soluble and fat- +++ ++
soluble vitamins except
vitamin B 12

Antibodies in newborns + ++ +++

Long-chain fatty acid +++ ++ +
absorption and
conversion to
triglyceride
Bile acids + + +++
Vitamin B 12 + +++

Na + +++ ++ +++ +++

Ca 2+ +++ ++ +
Fe2+ +++ + +
Cl – +++ ++ + +

K+ + + + secreted

Absorption of iron

 Regulated by three factors-1. Dietary intake of iron, 2. State of the iron stores in the body, 3.
state of erythropoiesis in the bone marrow
 amount of iron absorbed is normally about 3–6% of the amount ingested
 Dietary form- ferric (Fe3+) and absorption form is ferrous (Fe2+)
 Role of stomach in iron absorption: Gastric secre-tions dissolve the iron and permit it to
form soluble complexes with ascorbic acid and other substances that aid its reduction to the
Fe2+ form
 Maximum absorption occurs in duodenum

76
  Transport of Fe 2+ into the enterocytes-divalent metal transporter 1 (DMT1) and basolateral
transporter named ferroportin 1
 hephaestin (Hp)- facilitates basolateral transport(not a transporter by itself)
 Transport form- Transferrin. Has two iron-binding sites. Normally 35% saturated with iron
 HFE gene- normally inhibits expression of the duo-denal transporters that participate in iron
uptake. HFE mutations(short arm of chromosome 6) leads to hereditary forms of
hemochromatosis

Neurotransmitters and Hormones That Influence Feeding and Satiety Centers in the
Hypothalamus:

Decrease Feeding (Anorexigenic) Increase Feeding (Orexigenic)

 Melanocyte-stimulating hormone (a-MSH)  Neuropeptide Y (NPY)

 Leptin  Agouti-related protein (AGRP)
 Serotonin  Melanin-concentrating hormone (MCH)
 Norepinephrine  Orexins A and B
 Corticotropin-releasing hormone  Endorphins
 Insulin  Galanin (GAL)
 Cholecystokinin (CCK)  Amino acids (glutamate and g-aminobutyric
 Glucagon-like peptide (GLP) acid)
 Cocaine- and amphetamine-regulated  Cortisol
transcript (CART)  Ghrelin
 Peptide YY (PYY)

Lengths of various segments of the gastrointestinal tract:

Segment Length (cm)

Pharynx,esophagus, and stomach 65

Duodenum 25
Jejunum and ileum 260
Colon 110

Gastrointestinal motility

 Smooth muscle of the GIT- membrane potential fluctuates between about –65 and –45 mV
 Interstitial cells of Cajal:
- stellate mesenchymal pacemaker cells
- Location: stomach and the small intestine-the outer circular muscle layer near the
myenteric plexus.In colon-submucosal border of the circular muscle layer
- Initiates the Basic electrical rhythm (BER)
- Rate of BER: 4/min in the stomach, 12/min in the duodenum, 8/min in the distal
ileum, 2/min at the cecum, 6/min at the sigmoid

77
Migrating motor complex (MMC)

 Has 3 phases

phase I quiescent period

phase II period of irregular electrical and mechanical
activity
phase III burst of regular activity

 Initiated by motilin.circulating level of this hormone increases at intervals of

approximately 100 min in the interdigestive state.
 migrate aborally at a rate of about 5 cm/ min
 Aids in clearing the stomach and small intestine of luminal contents in preparation for
the next meal
 Erythromycin-binds to motilin receptors.useful in treating patients with reduced GI
motility

Lower esophageal sphincter

 tonically active but relaxes on swallowing

 tone of the LES-under neural control: acetylcholine(Contracts the sphincter) and NO and
VIP(Relaxation of sphincter)
 Achalasia cardia- myenteric plexus of the esophagus is deficient at the LES and release of NO
and VIP is defective

Gastric motility

 Receptive relaxation- fundus and upper portion of the body relax and accommodate the
food with little if any increase in pressure
 Antral systole- contraction of the distal stomach, last up to 10 s
 Fastest emptying-meal rich in carbohydrates
 Slowest emptying-meal rich in fats
 Hyperosmolality of the duodenal contents-sensed by duodenal osmoreceptors and decrease
gastric emptying

Transit time in the intestine and colon:

Segment Time
cecum 4hrs
First third of the colon 6hrs
Second third of the colon 9hrs
Sigmoid colon 12hrs

78
Hirschsprung disease

 Also called aganglionic megacolon

 Due to congenital absence of the ganglion cells in both the myenteric and submucous plexus
in colon(failure of the normal cranial-to-caudal migration of neural crest cells)
 Endothelins-acts on endothelin B receptor necessary for normal migration of certain neural
crest cells
 Mutations in endothelin B receptor is one cause of congenital aganglionic mega colon

79
 Renal Physiology-High Yield Topics

Parameters Dimension
No.of nephrons in each kidney 1 million
Glomerulus 200 μm in diameter
filtration slits 25 nm wide
Free passage of neutral substances across Up to 4nm
glomerulus
total area of glomerular capillary endothelium 0.8m2
for filtration
Length of proximal convoluted tubule 15mm
Distal convoluted tubule 5mm long
collecting ducts 20mm long
total length of the nephrons 45 to 65mm
volume of blood in the renal capillaries 30–40 mL
Renal blood flow 1.2–1.3 per minute
Effective renal plasma flow (ERPF) 625 mL/min
glomerular capillary pressure 45 mm Hg
peritubular capillary pressure 8 mm Hg
pressure in the renal vein 4 mm Hg
Cortical blood flow 5 mL/g of kidney tissue/min
Medullary blood flow outer medulla(2.5 mL/g/min)
inner medulla(0.6 mL/g/min)
arteriovenous oxygen difference for the whole 14 mL/L of blood
kidney
Po2 of the cortex 50 mm Hg
PO2 of the medulla 15 mm Hg
GFR 125 mL/min is 7.5 L/h, or 180 L/d,
amount of protein in the urine <100mg/day
filtration fraction 0.16–0.20
Filtration coefficient(Kf) 4.2 ml/min/mm Hg
peristaltic contractions in ureter 1-5 times/min
Half life of vasopressin 18 min

Renal medullary interstitial cells (RMICs)- major site of cyclooxygenase 2 (COX-2) and prostaglandin
synthase (PGES) expression.Synthesize PGE2

Regulation of renal blood flow:

 Vasoconstrictors- Norepinephrine, Angiotensin II

 Vasodilators-Dopamine,Acetylcholine
 Prostaglandins- increase blood flow in the renal cortex and decrease blood flow in the renal
medulla
 Norepinephrine-acting through β 1-adrenergic receptors increases renin secretion and
increases Na+ reabsorption
 Mediator for tubuloglomerular feedback-Adenosine

80
Normal clearance values of different solutes:

Substance Clearance (mL/min)

Glucose 0
Sodium 0.9
Chloride 1.3
Potassium 12
Phosphate 25
Urea 75
Inulin 125
Creatinine 140
PAH 560

Glomerular Filtration Rate:

Parameters Afferent end(mm Hg) Efferent end((mm Hg)

mean hydrostatic pressure in 45 45
the glomerular capillaries
the mean hydrostatic pressure 10 10
in the tubule (Bowman’s space)
oncotic pressure of the plasma 20 35
in the glomerular capil-laries
Net filtration pressure 15 0

Juxta Glomerular apparatus:

 Comprises of JG cells,Macula Densa and Lacis cells

JG cells  Also known as Granular cells

 Secrete RENIN
 Located in media of afferent arterioles
as they enter glomeruli
Macula densa  Morphologically distict region of thick
ascending limb
 Senses sodium chloride concentration
via Na+-K+-Cl- cotransporter
Lacis cells  Also known as extraglomerular
mesangial cells
 Located at the junction between
afferent and efferent arterioles

 Counter-current multipliers- loops of Henle

 Counter-current exchangers- vasa recta

81
Mesangial cells

 Support the entire glomerular tuft

 Secrete mesangial matrix
 Are contractile
 Are phagocytic
 Capable of proliferation

Agents causing contraction or relaxation of mesangial cells:

Contraction Relaxation

 Endothelins  ANP
 Angiotensin II  Dopamine
 Vasopressin  PGE2
 Norepinephrine  cAMP
 Platelet-activating
factor
 Platelet-derived
growth factor
 Thromboxane A2
 PGF2
 Leukotrienes C 4
and D4
 Histamine

Transport proteins involved in the movement of Na+ and Cl– across the apical membranes of renal
tubular cells:

Site Apical Function

Transporter
Proximal tubule Na/glucose CT Na+ uptake, glucose uptake
Na+/Pi CT Na+ uptake, Pi uptake
Na+ amino acid Na + uptake, amino acid
CT uptake
Na/lactate CT Na+ uptake, lactate uptake
Na/H exchanger Na+ uptake, H+ extrusion
Cl/base Cl– uptake
exchanger
Thick ascending Na–K–2Cl CT Na + uptake, Cl– uptake, K +
limb uptake
Na/H exchanger Na+ uptake, H+ extrusion
K+ channels K + extrusion (recycling)
Distal NaCl CT Na+ uptake, Cl– uptake
convoluted
tubule

82
Collecting duct Na+ channel Na + uptake
(ENaC)

Transport maximum (Tm):

 renal active transport systems have a maximal rate at which they can transport a particular
solute

Tm for substances that are actively transported:

Substance Transport Maximum

Glucose 375 mg/min

Phosphate 0.10 mM/min
Sulfate 0.06 mM/min
Amino acids 1.5 mM/min
Urate 15 mg/min
Lactate 75 mg/min

Plasma protein 30 mg/min

Creatinine 16 mg/min
Para-aminohippuric acid 80 mg/min

Proximal convoluted tubule:

Reabsorption:
 Water-67% of filtered load
 NaCl-67% of filtered load
 K+-67% of filtered load
 Ca2+-70% of filtered load
 Pi-80% of filtered load
 Hco3--80% of filtered load
 Protein-100% of filtered load
 Urea-67% of filtered load
Henle’s loop:
Reabsorption:
 Water-15% of filtered load(thin descending limb only)
 NaCl-25% of filtered load
 K+-20% of filtered load
 Ca2+-20% of filtered load
 Hco3--10% of filtered load
Secretion:
 Urea-thin descending limb only
Distal tubule:
Reabsorption:
 NaCl-5% of filtered load
 Ca2+-9% of filtered load
 Hco3--6% of filtered load

83
  Pi-10% of filtered load
 Water-variable depending on presence of ADH,ANP
Collecting Duct:
Reabsorption:
 Water- variable depending on presence of ADH,ANP
 NaCl-3% of filtered load
 K+-normally zero
 Hco3--4% of filtered load
 Urea- variable depending on presence of ADH
Secretion:
 K+-0% to 70% of the filtered load

Monogenic renal diseases involving transport proteins:

Diseases Mode of Gene Transport protein Nephron Phenotype

inheritance segment
Cystinuria type I AR SLC3A1 Basic amino acid Proximal Increased
transporter (rBAT) tubule excretion of basic
amino acids ,
nephrolithiasis
(kidney stones)
Proximal renaltubular AR SLC4A4 Na+ -HCO3- Proximal Hyperchloremic
acidosis cotransporter tubule metabolic acidosis

Bartter syndrome AR SLC12A1 Na+-K+-2Cl- TAL Hypokalemia,

(type I) transporter metabolic
(furosemide alkalosis, hyperal-
sensitive) dosteronism
KCNJ1 Potassium channel
(type II)
CLCNKB Chloride channel
(type III)
X-linked XLR CLC5 Chloride channel Distal Hypercalciuria,
nephrolithiasis (Dents (C1C-5) tubule nephrolithiasis
disease) (kidney stones)
Hypomagnesemia- AR PCCLN-1 Paracellin-1 TAL Hypomagnesemia,
Hypercalciuria hypercalciuria,
syndrome nephrolithiasis
Gitelman syndrome AR SLC12A3 Thiazide-sensitive Distal Hypomagnesemia,
cotransporter tubule hypokalemic
metabolic
alkalosis,
hypocalciuria,
hypotension
Liddle syndrome AD SCNN1B, α, β, and γsubunit Collecting Decreased
SCNN1G of amiloride- duct excretionof Na+,
sensitive Na+ hypertension
channel

84
Hormones that regulate NaCl and water absorption:

Hormone Major stimulus Nephron site of Effect on transport

action

Angiotensin II ↑Renin PT ↑NaCl and H2O reabsorption

Aldosterone ↑Angiotensin II, ↑*K+]p TAL, DT/CD ↑NaCl and H2O reabsorption
ANP ↑ECV CD ↓H2O and NaCl reabsorption
Urodilatin ↑ECV CD ↓H2O and NaCl reabsorption
Sympathetic nerves ↓ECV PT, TAL, DT/CD ↑NaCl and H2O reabsorption
Dopamine ↑ECV PT ↓H2O and NaCl reabsorption
ADH ↑Posm, ↓ECV DT/CD ↑H2O reabsorption

Major functions of the various collecting-duct cells:

Principal cells

 Reabsorb sodium (stimulated by aldosterone)

 Secrete potassium (stimulated by several signals, including aldosterone)
 Reabsorb water (stimulated by antidiuretic hormone)

Type A intercalated cells

 Secrete hydrogen ions, which effect reabsorption of bicarbonate and excretion of titratable
acid (stimulated by increased Pc o2and decreased extracellular pH)
 Reabsorb potassium

Type B intercalated cells

 Reabsorb chloride (stimulated by chloride depletion)

 Secrete bicarbonate (stimulated by increased extracellular pH)

Aquaporins:

 In 2003,Dr.Peter Agre received Nobel prize in chemistry for its discovery

 To date,13 aquaporins have been identified

Aquaporin subtype Location

AQP-1 Apical and basolateral membranes of proximal
tubule and distal thin limb of Henle
AQP-2 Apical side of principal cells in collecting
tubule(Levels regulated by ADH)
AQP-3 and AQP-4 Basolateral side of principal cells in collecting
tubule
AQP-4 Blood Brain barrier

Mechanism of action of various diuretics:

Agent Mechanism of Action

85
Water
Ethanol
Antagonists of V2 vasopressin receptors such as
astolvaptan
Large quantities of osmotically active substances
such as mannitol and glucose
Xanthines such as caffeine and theophylline
Inhibits vasopressin secretion
Inhibits vasopressin secretion
Inhibit action of vasopressin on collecting duct
Produce osmotic diuresis
Decrease tubular reabsorption of Na+ and
increase GFR

Acidifying salts such as CaCl2 and NH4Cl Supply acid load; H+ is buffered, but an anion is
excreted with Na+ when the ability of the kidneys
to replace Na+ with H+ is exceeded

Carbonic anhydrase inhibitors such as Decrease H+ secretion, with resultant increase in

acetazolamide Na+ and K+ excretion

Metolazone,thiazides such as chlorothiazide Inhibit the Na–Cl cotransporter in the early

portion of the distal tubule
Loop diuretics such as furosemide,ethacrynic Inhibit the Na–K–2Cl cotransporter in the
acid and bumetanide medullary thick ascending limb of the loop of
Henle

K+-retaining natriuretics such as Inhibit Na+–K+ “exchange” in the collecting ducts

spironolactone,triamterene and amiloride by inhibiting the action of aldosterone
(spironolactone) or by inhibiting the ENaCs
(amiloride)

“Free water clearance” (CH2O)

 to quantitate the gain or loss of water by excretion of a concentrated or dilute urine

 difference between the urine volume and the clearance of osmoles
UOsm V
CH2O = V• –
P
Osm

(V is the urine flow rate and UOsm and POsm ,the urine and plasma
osmolality respectively)

 CH2O is negative when the urine is hypertonic and positive when the urine is hypotonic

Vasopressin:

Receptor Characteristics
V1A  Acts by increasing the intracellular Ca2+
concentration
 mediate the vasoconstrictor effect
 also found in the liver and the brain
 decrease in cardiac output(area
postrema)

86
  glycogenolysis in the liver
V1B (also called V 3 receptors)  unique to the anterior pituitary
 Acts by increasing the intracellular Ca2+
concentration
 increase secretion of
adrenocorticotropic hormone (ACTH)
from the corticotropes
V2 receptors  Acts through cAMP
 insertion of aquaporin 2 into the apical
membranes of the principal cells of the
collecting ducts

Stimuli affecting vasopressin secretion:

Vasopressin Vasopressin Secretion

Secretion Decreased
Increased
Increased effective Decreased effective
osmotic osmotic
pressure of plasma pressure of plasma
Decreased ECF Increased ECF volume
volume
Pain, emotion, Alcohol
“stress,” exercise
Nausea and vomiting
Standing
Clofibrate,
carbamazepine
Angiotensin II

Vasopressin escape

 prolonged exposure to elevated levels of va-sopressin can lead eventually to down-

regulation of the production of aquaporin-2
 to limit the degree of hyponatremia in SIADH

Angiotensin-II:

Receptor Characteristics
AT1  Acts by increasing the cytosolic free Ca 2+
level
 subtypes, AT1A and AT1B
 AT1A- mediates most of the known
effects of angiotensin II
 AT1B- anterior pituitary and the adrenal

87
 cortex
 excess of angiotensin II down-regulates
the vascular receptors, but up-regulates
the adrenocortical receptors
 increases production of caveolin-1
AT 2  Coded in X chromosome
 open K+ channels
 increases the production of Nitric oxide
 more plentiful in fetal and neonatal life

Actions of Angiotensin II

 one of the most potent vasoconstrictors known

 arteriolar constriction-rise in systolic and diastolic blood pressure
 increase the secretion of aldosterone
 facilitation of the release of norepinephrine
 contraction of mesangial cells
 increase Na+ reabsorption
 Actions in brain- decrease the sensitivity of the baroreflex(area postrema), increase the
secretion of vasopressin and ACTH(subfornical organ (SFO) and the OVLT)

Angiotensin III

 40% of the pressor activity of angiotensin II

 100% of the aldosterone-stimulating activity

Tissue Renin Angiotensin Systems  blood vessels

 uterus
 the placenta
 fetal membranes
 eyes
 exocrine portion of the pancreas
 heart
 fat
 adrenal cortex
 testis
 ovary
 anterior and intermediate lobes of the
pituitary
 pineal
 brain

Conditions that increase renin secretion:

 Na+ depletion
 Diuretics

88
  Hypotension
 Hemorrhage
 Upright posture
 Dehydration
 Cardiac failure
 Cirrhosis
 Constriction of renal artery or aorta
 Various psychologic stimuli

Natriuretic Peptides:

 Three types-Atrial Natriuretic Peptide(ANP), brain natriuretic peptide (BNP), C-type

natriuretic peptide (CNP)
 Actions:
1. dilating afferent arterioles and relaxing mesangial cells- increase Na+ excretion, inhibit Na+
reabsorption
2. increase in capillary permeability
3. relax vascular smooth muscle in arte-rioles and venules(CNP has a greater dilator effect on
veins)
4. inhibit renin secretion
5. in the brain-effects are opposite to those of angiotensin II, involved in lowering blood
pressure and promoting natriuresis
 Receptors:
1. Three types- NPR-A, NPR-B, NPR-C
2. ANP has the greatest affinity for the NPR-A receptor, and CNP has the greatest affinity for
the NPR-B receptor
3. NPR-C, binds all three natriuretic peptides. clearance receptor- removes natriuretic peptides
from the bloodstream, releases them later thereby maintain a steady blood level of the
hormones

Na, K ATPase INHIBITING FACTOR:

 Probably OUABAIN-comes from adrenal gland
 produces natriuresis

Erythropoietin:
 glycoprotein-165 amino acid residues and 4 oligosaccharide chains
 increases the number of erythropoietin-sensitive committed stem cells in the bone marrow-
converted to red blood cell precursors
 Receptor-has tyrosine kinase activity, inhibits apoptosis of red cells
 Source-85% from kidney(interstitial cells in the peri-tubular capillary bed) and 15% from
Liver(perivenous hepatocytes)
 also produced in the brain- protective effect against excitotoxic damage triggered by hypoxia

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 Stimulators of erythropoietin secretion 1. hypoxia
2. cobalt salts
3. androgens
4. alkalosis at high altitude
5. catecholamines via a β-adrenergic
mechanism

Micturition:

Innervation of bladder • Degree of stretch – parasympathetic

afferents (S2, S3 and S4)
• Micturition reflex - parasympathetic
efferents (S2,S3 and S4)
• Relaxation of external sphincter –
pudendal Nerve.
• Sense of fullness, pain – sympathetic
hypogastric plexus
Micturition centers  Sacral micturition center(S2-S4)
 Pontine micturition centre(Barrington’s
center)-Facilitatory
 Posterior hypothalamus- Facilitatory
 Mid brain-inhibitory
 Cerebral cortex-Detrusor motor area
located in medial frontal lobe(superior
frontal gyrus)
Micturition abnormalities Sensory denervated bladder (Atonic bladder):
 occurs due to lesions of sacral posterior
nerve roots
 stretch impulses are not transmitted to
the center, leading to over distension
and overflow dribbling(overflow
incontinence)
 bladder is thin walled, flaccid, distended
& hypotonic
Denervated bladder (Autonomous bladder):
 Both afferent & efferent fibers are
interrupted & the bladder is isolated
from the spinal cord
 Initially the bladder is flaccid &
distended. Later becomes active and
partially expel its contents
 Bladder gets shrunken & atrophied
 Eg. Cauda equina lesion or section of
pelvic nerves
Uninhibited neurogenic bladder:
 In lesions in which the cortico-spinal
inhibitory fibres are damaged, leaving

90
 the facilitatory fibres intact
 There is increased frequency with
voiding of small quantities

91
 Endocrine Physiology and Reproductive Physiology-High yield topics

 The term endocrine was coined by Starling

 The term hormone, derived from a Greek phrase meaning "to set in motion"

Five major classes of hormones

1. Amino acid derivatives---dopamine, catecholamine

2. Small neuropeptides ---GnRH,TRH
3. Large proteins---insulin,PTH
4. Steroid hormones ---Cortisol,estrogen
5. Vitamin derivatives---Vit-A,Vit-D

Receptors for hormones

Membrane Receptors Nuclear Receptors

1) Seven transmembrane GPCRs Has various domains:
2) Tyrosine kinase receptors(Insulin,IGF-1)  AF1-also known as modulator region and
3) Cytokine receptors(Growth involved in activating transcription
hormone,prolactin)  DBD-C domain.binds to hormone
4) Serine kinase receptors (Activin.TGF- responsive elements(DNA sequences)
beta)  LBD-Ligand binding domain which binds
ligand
 Hinge region-permits flexibility
 AF2-interacts with coactivators and
facilitates transactivation
Receptors for
1. Glucocorticoids
2. Mineralocorticoids
3. Androgen
4. Estrogen
5. Progestin
6. Thyroid hormones
7. Vitamin D
Receptors are dynamic structures Down regulation through
Can be down regulated or up regulated 1. Receptor mediated endocytosis
2. Internalization
3. Desensitization
First messenger Extracellular ligands
Second messenger intracellular mediators

G proteins(activated after binding GTP):

1. Small G proteins
 Rab-vesicle traffic
 Rho/Rac -cytoskeleton and cell membrane

92
  Ras-regulates growth
2. Large heterotrimeric G proteins
- G proteins--Rodbell,Gilman(1994) awarded noble prize for its characterization
- GPCR-Kobilka,Lefkowitz(2012) awarded noble prize in Chemistry
- Binding of ligand to G-protein coupled receptor facilitates exchange of GTP for GDP, a
and bg dissociate

Three major families of G-proteins

Gs  couples to Adenylate Cyclase

Examples:  stimulates AC activity
 b-adrenergic receptor  increases cAMP
 ACTH receptor  activates Protein Kinase A
 FSH receptor
Gi  couples to Adenylate Cyclase
 a2-adrenergic receptor  inhibits AC activity
 M2 muscarinic receptor  decreases cAMP
 inhibits Protein Kinase A

Gq  couples to Phospholipase C
 a1-adrenergic receptor  increases diacylgyclerol (DAG)
 M1, M3 muscarinic receptors  increases IP3
 Angiotensin receptor  increases intracellular Ca2+
 activates Protein Kinase C

G proteins and their receptor abnormalities:

Site Type of Disease

Mutation
Receptor
Cone opsins Loss Color blindness
Rhodopsin Loss Congenital night
blindness; two
forms of retinitis
pigmentosa
V2 Loss X-linked
vasopressin nephrogenic
diabetes insipidus
ACTH Loss Familial
glucocorticoid
deficiency
LH Gain Familial male
precocious
puberty
TSH Gain Familial
nonautoimmune
hyperthyroidism
TSH Loss Familial
hypothyroidism

93
 2+
Ca Gain Familial
hypercalciuric
hypocalcemia
Thromboxan Loss Congenital
e A2 bleeding
Endothelin B Loss Hirschsprung
disease
G protein
Gs α Loss Pseudohypothyroi
dism
type 1a
Gs α Gain/loss Testotoxicosis
Gs α Gain (mosaic) McCune–Albright
syndrome
Gs α Gain Somatotroph
adenomas with
acromegaly
Gi α Gain Ovarian and
adrenocortical
tumors

Hormones That Use the Adenylyl Cyclase–cAMP Second Messenger System (Mn-FLAGSHiP-CCTV2-
CASh)

 Adrenocorticotropic hormone (ACTH)

 Angiotensin II (epithelial cells)
 Calcitonin
 Catecholamines (b receptors)
 Corticotropin-releasing hormone (CRH)
 Follicle-stimulating hormone (FSH)
 Glucagon
 Human chorionic gonadotropin (HCG)
 Luteinizing hormone (LH)
 Parathyroid hormone (PTH)
 Secretin
 Somatostatin
 Thyroid-stimulating hormone (TSH)
 Vasopressin (V2 receptor, epithelial cells)

 cAMP is constantly inactivated by phosphodiesterase

 Theophylline blocks the phosphodiesterase

Hormones That Use the Phospholipase C Second Messenger System(V1 GOT AC)

 Angiotensin II (vascular smooth muscle)

 Catecholamines (a receptors)
 Gonadotropin-releasing hormone (GnRH)
 Growth hormone–releasing hormone (GHRH)

94
  Oxytocin
 Thyroid-releasing hormone (TRH)
 Vasopressin (V1 receptor, vascular smooth muscle)

Calcium-Calmodulin dependent protein kinases(Mn-MCG)

 Myosin Light Chain Kinase
 Glycogen Phosphorylase Kinase

Guanylate Cyclase Receptors(Mn.NAG)

Transmembrane Guanylate Cyclase Receptor activated by peptide hormones(Atrial natriuretic

peptide/factor ANP)
Soluble Guanylate Cyclase Receptor activated by Nitric Oxide (NO)

Pituitary Gland

 The pituitary gland weighs approx.600 mg

 Contains Pituicytes-modified astrocytes
 Folliculostellate cells- release paracrine factors
 pluripotent stem cells-responsible for Plasticity in pituitary
 Cell types-
Somatotrope(GH),Lactotrope(prolactin),Corticotroph(ACTH),Thyrotroph(TSH),Gonadotrophs
(FSH,LH)
 Maximum percentage of secretory cells-Somatotrope
 Minimum percentage of secretory cells-Thyrotroph
 Acidophilic cells-Prolactin,Growth hormone(Mn.Parle-G)

Proopiomelanocortin (POMC):

 In corticotrophs- POMC hydrolysed to ACTH and beta endorphins

 Intermediate lobe cells, POMC is hydrolyzed to corticotropin-like intermediate-lobe peptide
(CLIP),γ -LPH,β-endorphin,α and β-MSH
 α and β-MSH do not circulate in adult humans
 ACTH binds to melanotropin-1 receptors (pigmentation in addison’s disease)

Human Growth Hormone:

1. Present in long arm of human chromosome 17

2. Half life is 6-20 min
3. Daily growth hormone output-0.5 – 1 mg/day
4. 50% bound to protein—provides reservoir
5. Receptor--cytokine receptor superfamily
6. Acts through JAK2-STAT pathway
7. Ghrelin-marked growth hormone-stimulating activity

95
Factors That Stimulate or Inhibit Secretion of Growth Hormone:

Stimulate Growth Hormone Inhibit Growth Inhibit Growth Hormone Secretion

Hormone Secretion
 Decreased blood glucose  Increased blood glucose
 Decreased blood free fatty acids  Increased blood free fatty
 Starvation or fasting, protein deficiency  acids
 Trauma, stress, excitement  Obesity
 Exercise  Aging
 Testosterone, estrogen  Growth hormone inhibitory hormone
 Deep sleep ( stages II and IV) (somatostatin)
 Growth hormone–releasing hormone  Growth hormone (exogenous)
 Somatomedins (insulin-like growth
factors)

Effects of Growth hormone

Effect on growth  Epiphyses not yet closed---

Chondrogenesis is
accelerated,Cartilaginous epiphysial
plates widen,lay down more bone matrix
 Epiphyses closed---linear growth is no
longer possible

Effects on protein Metabolism  protein anabolic hormone

 positive nitrogen and phosphorus
balance
 fall in blood urea nitrogen
Effect on electrolytes  GI absorption of Ca2+ increased
 Na+ and K+ excretion is reduced
 excretion of the amino acid 4-
hydroxyproline is increased
Effect on carbohydrate metabolism  Anti insulin effect in muscles
 Diabetogenic-increase hepatic glucose
output
Effect on Fat metabolism  ketogenic
 increases circulating free fatty acid (FFA)
 provides a ready source of energy during
hypoglycemia

Somatomedins:

 Somatomedin C-otherwise known as IGF-1

 IGF-2-otherwise known as Multiplication stimulating activity
 IGF-1:Mediates the insulin like activity,antilypolytic activity,protein synthesis,epiphyseal
growth actions of growth hormone

96
Growth hormone disorders:

In children Gigantism
In adults Acromegaly:
 greatly enlarged hands and feet
 vertebral changes attributable to
osteoarthritis
 soft tissue swelling, hirsutism
 protrusion of the brow and jaw.
 Abnormal growth of internal organs
Laron Dwarfism(Growth Hormone insensitivity)  Reduced plasma IGF-1
 GH levels normal
 Hypersecretion of growth hormone is accompanied by hypersecretion of prolactin in 20–
40% of patients with acromegaly
 About 25% of patients have abnormal glucose tolerance tests, and 4% develop lactation in
the absence of pregnancy

Prolactin:

1. Weakly homologous to GH and human placental lactogen (hPL)

2. Normal levels--10–25 g/L in women and 10–20 g/L in men
3. Secretion is pulsatile
4. Highest peaks occurring during rapid eye movement sleep
5. Half life is 50 min
6. Inhibited by Dopamine(D2),Glucocorticoids,Thyroid hormones
7. Stimulated by Thyrotrophin Releasing Hormone Vasoactive Intestinal Peptide
8. Serum PRL levels rise transiently after
 exercise, meals
 sexual intercourse
 minor surgical procedures
 general anesthesia
 chest wall injury
 acute myocardial infarction
Prolactin Levels increase markedly during pregnancy and lactation, In the breast, the lobuloalveolar
epithelium proliferates
 Functions of prolactin:
1. Decrease reproductive function
2. Suppress sexual drive
3. In females---hypoestrogenism and anovulation
4. In males---decreased spermatogenesis,low testosterone

Thyroid Gland:

 one of the larger endocrine glands

 Blood flow—160ml/100g/min
 maintain the level of metabolism in the tissues
 stimulate O2 consumption by most of the cells
 Secretes T3,T4 and Calcitonin
 Thyrocytes express receptors for

97
 TSH
IGF-I
EGF
IGF-I and EGF promote growth
interferon γ and tumor necrosis factor inhibit growth
 Whwn the Gland is inactive—colloid abundant,large follicles,and flat cells
 Whwn the Gland is active,small follicles,cuboid or columnar cells
 Site of active Colloid resorption--- "reabsorption lacunae"
 Iodine-the raw material for thyroid hormone synthesis
Dietary Iodide-absorbed from intestine
Minimal daily requirement-150µg in adults
20% enters thyroid gland
80% excreted by kidney
Salivaryglands,mammaryglands,placenta-Extrathyroidal
 Free T4 0.7–1.24 ng/dL
 Total T4 5.4–11.7 μg/dL
 Free T3 2.4–4.2 pg/mL
 Total T3 77–135 ng/dL
 Binding proteins
Albumin
Transthyretin
Thyroxine-binding globulin (TBG)
 Albumin--largest capacity to bind T4
 TBG--largest affinity to bind T4

T4 Vs T3

Characteristics T4 T3

Half life Long(6 days) Short(2 days)

Max binding TBG Albumin

In colloid More (25%) Less (7%)

potency less More(3-5 times)

Action slower Much rapid

Binding to nuclear receptors less more

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Thyroid Stimulating Hormone (TSH):

1. Glycoprotein
2. Alpha chain-Chromosome 6 ,beta chain-chromosome 1
3. Half life 60 min
4. Secretion is pulsatile,peaks at midnight
5. Average plasma level-2μg/ml
6. Increases iodine trapping,synthesis of t3,t4,secretion of thyroglobulin,endocytosis of colloid
7. Inhibited by stress,dopamine,somatostatin,thyroid hormones

Physiologic effects of thyroid hormones:

Heart Chronotropic and Inotropic  Increased number of β-

adrenergic receptors
 Enhanced responses to
circulating
catecholamines
 Increased proportion of
α-myosin heavy chain
(with higher ATPase
activity)
Adipose tissue Catabolic  Stimulates lipolysis
Muscle Catabolic  Increased protein
breakdown
Bone Developmental  Promote normal
growth and skeletal
development
Nervous system Developmental  Promote normal brain
development
Gut Metabolic  Increased rate of
carbohydrate
absorption
Lipoprotein Metabolic  Formation of LDL
receptors
Other Calorigenic  Stimulated oxygen
consumption by
metabolically active
tissues (exceptions:
testes,uterus, lymph
nodes, spleen, anterior
pituitary(Mn.LUSTAN)
 Increased metabolic
rate

Wolf-Chaikoff Effect Intake of iodide exceeds 2 mg/day --Iodide

suppressesNADPHoxidase activity
and the NIS and TPO genes --Inhibits hormone
biosynthesis
Jod-Basedow Phenomenon Iodine-induced hyperthyroidism, typically

99
 presenting in a
patient with endemic goiter
Endocrine Pancreas:

 The islet of Langerhans are ovoid, 76- x 175-μm collection of cells

 Scattered throughout the pancreas, but they are more plentiful in the tail than the body
and head
The cells in the islets can be divided into types on the basis of their staining properties and
morphology-
 A cell- make up 20% of the total, surrounds the B cells & secrete glucagon
 B cell- most common, 60% of the total, located in the centre of each islet & secrete
insulin
 D cell- less common, secrete & secrete somatostatin & gastrin
 F cell- less important in humans, secrete pancreatic polypeptide

Insulin:

 Has an alpha and beta chain

 Transcription factors-hepatocyte nuclear factor-4 and pancreatic and intestinal homeobox-1
 Zinc bound crystals
 Equimolar amounts of C-peptide secreted
 Measurements of C peptide in the Blood--quantify endogenous insulin production in
patients receiving exogenous insulin
 Glucokinase-Rate Limiting Step in insulin secretion
 Biphasic insulin release-Early phase-preformed insulin,Late phase-newly formed
 Half life-5 min
 Degraded by Insulinase in liver
 Otherwise called” Hormone of abundance”
Principal Actions:
 Rapid-Increases transport of glucose amino acids and potassium into insulin sensitive cells.
 Intermediate-Stimulates protein synthesis. Inhibits protein breakdown,Activation of
glycolytic and inhibition of gluconeogenic enzymes
 Delayed-Increases formation of mRNA for lipogenic action
Effects of insulin on various tissues:
Adipose tissue
 Increased glucose entry
 Increased fatty acid synthesis
 Increased glycerol phosphate synthesis
 Increased triglyceride deposition
 Activation of lipoprotein lipase
 Inhibition of hormone-sensitive lipase
 Increased K+ uptake
Muscle
 Increased glucose entry
 Increased glycogen synthesis
 Increased amino acid uptake
 Increased protein synthesis in ribosomes
 Decreased protein catabolism
 Decreased release of gluconeogenic amino acids

100
  Increased ketone uptake
 Increased K + uptake
Liver
 Decreased ketogenesis
 Increased protein synthesis
 Increased lipid synthesis
 Decreased glucose output due to decreased gluconeogenesis,
 increased glycogen synthesis, and increased glycolysis
General
 Increased cell growth

Glucagon:

• A cells in pancreatic islets

• In L cells—Glicentin,GLP-1,GLP-2,Oxyntomodulin
• Glicentin has some glucagon activity
• GLP-1 (7–36), is a potent stimulator of insulin secretion
• GLP-2 lowers food intake
Actions of glucagon:
• glycogenolytic, gluconeogenic, lipolytic, and ketogenic
• does not cause glycogenolysis in muscle
• positively inotropic effect on the heart
• stimulates the secretion of growth hormone, insulin and pancreatic somatostatin
• Half life-5-10 min

Somatostatin:

• Somatostatin 14, Somatostatin 28-D cells

• inhibit the secretion of insulin, glucagon, and pancreatic polypeptide—paracrine
• decreased gastric acid secretion
• Inhibition of CCK secretion.
• increased by several of the same stimuli that increase insulin secretion

Pancreatic polypeptide:

• F cells in the islets

• secretion is under cholinergic control
• increased by a meal containing protein and by fasting, exercise, and acute hypoglycemia
• slows the absorption of food in humans

Other factors affecting carbohydrate metabolism:

• Exercise-insulin independent increase in the number of GLUT 4

• Epinephrine-glycogenolysis,increase hepatic glucose output,decrease peripheral use
• Thyroid hormones-Hyperglycemia,metathyroid diabetes,enhances GI glucose absorption
• Cortisol-Gluconeogenic(Permissive)
• GH-Anti insulin effect, increase hepatic glucose output

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Glucose transporters:

Function Major sites of expression

SGLT 1 Absorption of glucose Small intestine, renal tubules
SGLT 2 Absorption of glucose Renal tubules
GLUT 1 Basal glucose uptake Placenta, blood-brain barrier,
brain, red cells,kidneys, colon,
many other organs
GLUT 2 B-cell glucose sensor; transport B cells of islets, liver, epithelial
out of intestinal and renal cells of small intestine, kidneys
epithelial cells
GLUT 3 Basal glucose uptake Brain, placenta, kidneys, many
other organs
GLUT 4 Insulin-stimulated glucose Skeletal and cardiac muscle,
uptake adipose tissue,other tissues
GLUT 5 Fructose transport Jejunum, sperm
GLUT 6 Unknown Brain, spleen and leukocytes
GLUT 7 Glucose 6-phosphate Liver
transporter in endoplasmic
reticulum

Adrenal gland:

• Adrenal cortex
– Zona glomerulosa-Mineralocorticoid(15%).Also involved in Formation of new cortical
cells
– Zona fasciculata-Glucocorticoids (50%)
– Zona reticularis-Adrenal androgens (7%)
– Adrenal Medulla (18%)
• Epinephrine(90% cells,larger,less dense granules)
• Nor epinehrine(10% cells,smaller dense granules)
• Dopamine
Effects of Epinephrine & Norepinephrine:
1. glycogenolysis in liver and skeletal muscle
2. mobilization of free fatty acids (FFA),
3. increased plasma lactate
4. stimulation of the metabolic rate
5. Increases secretion of insulin and glucagon(Beta) and decreases the same(Alpha)
6. Intial increase in K+,then prolonged fall(beta2)
Effects of Dopamine:
1. Renal and mesentric vasodilation
2. Elsewhere-Vasoconstriction
3. Positive inotropic effect-use in cardiogenic,traumatic shock
4. Natriuresis by inhibiting renal sodium potassium ATPase
Adrenal cortical hormones :
 derivatives of cholesterol
 has cyclopentanoperhydrophenanthrene nucleus

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Aldosterone:

 Increase the reabsorption of Na+ from the urine, sweat,saliva, and the contents of the colon.
 principal cells (P cells)-K+ diuresis and urinary acidity
 Genomic action—through serum- and glucocorticoid-regulated kinase (sgk)
 Non genomic action---increases the activity of membrane Na+–K+ exchangers
Aldosterone Escape:
• Whenever aldosterone is increased, Na+ ions are retained in the body.
• This causes osmotic absorption of water. Therefore ECF volume increases.
• Increase in ECF leads to increase in arterial pressure causing excretion of salt and water by
pressure diuresis,natriuresis(ANP)
• This secondary increase in water and salt excretion by the kidneys is called aldosterone
escape.
Aldosterone Excess:
• Primary Hyper aldosteronism
Conn’s syndrome-adenoma,carcinoma
Low renin
• Secondary Hyper aldosteronism
cirrhosis, heart failure, and nephrosis
High renin
Apparent Mineralocorticoid Excess (AME)
1. 11 -hydroxysteroid dehydrogenase type 2 deficiency
2. Due to intake of licorice containing glycyrrhetinic acid
3. Hyperaldosteronism,hypertension
Glucocorticoid-Remediable Aldosteronism (GRA):
1. autosomal dominant disorder
2. ACTH-sensitive aldosterone synthase
3. Suppressed by administrating cortisol
Deficiency of aldosterone(Addison’s disease):
• Loss of sodium and chloride ions
• Excess of potassium ions
• Fluid and blood volume decreases
• Diminished cardiac output
• Shock like state
• Death in 3 days to 2 weeks
• Highly susceptible to stress and infections.
• Pigmentation of skin and mucus membrane
• Mineralocorticoid is life saving hormone of adrenal gland
Addisonian crisis:
• A person with Addison’s disease succumbs to stress. This condition is called addisonian crisis.
They need extra amounts of glucocorticoids

Glucocorticoids-Cortisol:

• This is a C21 steroid produced mainly from zona fasciculata.

• It combines with cortisol binding globulin.
• 96 % of the cortisol is transported in bound form. Only 4 % is transported in free form.
• It stays in circulation for 1 to 2 hours
• It is degraded in the liver and conjugated to form glucuronides. It is excreted in urine

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Functions of cortisol:
On carbohydrate metabolism
On protein metabolism
On fat metabolism
Water and Mineral metabolism
Anti inflammatory effect
Effect on blood cells
 It stimulates gluconeogenesis by the
liver by increasing glucose-6-
phosphatase.
 It decreases rate of glucose utilization by
the peripheral tissues by inhibiting
phosphorylation (anti-insulin action)—
ADRENAL DIABETES
 Increases glycogen synthesis in liver by
increasing activity of glycogen synthase.
 It causes protein breakdown in skeletal
muscles.
 Cortisol enhances amino acid uptake by
the liver cells & enhances
transamination - (AA synthesis),
deamination – (glucose formation)
 Hence proteins like plasma proteins
produced by liver are increased
• It causes fatty acid mobilization from
adipose tissue increasing free fatty acids
in plasma.
• It stimulates absorption of lipids from
the intestine.
• It causes redistribution of fats in the
body
• Mild mineralocorticoid activity – retains
Na & excretes K
• Increases angiotensinogen synthesis in
liver leading to Na retention via
aldosterone
• Provides adequate GFR via anti-ADH
activity
• Cortisol inhibits all aspects of
inflammation.
• It reduces leucocyte margination,
chemotaxis, phagocytosis of bacteria.
• Aggregation of monocytes is also
inhibited.
• Cortisol inhibits the synthesis and
release of chemical mediators of
inflammation like prostaglandins &
arachidonic acid
• Causes eosinopenia- sequestration of it
in lungs and spleen, increased
destruction
• lymphopenia – due to reduced
formation and increased destruction
• basopenia
• neutrophilia -increased release from
104
 bone marrow, decreased margination
and escape to the tissues
• Polycythemia by stimulation of
erythropoiesis.

Permissive action • On glucagon & catecholamines to exert

calorigenic action
• On catecholamines to exert lipolytic
effect & glycogenolytic effect.
• On catecholamines to exert pressor
response & bronchodilation
On bone • It causes demineralization of bone
• Retards development of cartilage
• Thinning of epiphyseal plate
• Breaks down bone matrix
• Decreases calcium deposition
• Increases calcium excretion
• Decreases calcium absorption from GIT
• Results in osteoporosis and tetany

Abnormalities of the adrenal cortex:

Cushing’s Syndrome • Excess secretion of glucocorticoids.

Causes
• Adrenocortical tumours
• Anterior pituitary tumours
• Ectopic ACTH producing tumour
• Prolonged glucocorticoid therapy.
– Cushing’s syndrome caused due
to tumours of anterior pituitary
is called Cushing’s disease.

21-Hydroxylase deficiency • Adrenal and gonads

• Most common form of congenital
adrenal hyperplasia (80-90%)
• Signs and symptoms:
– Dehydration, Hyperkalemia,
Hyponatremia
– Genital ambiguity (XX)
– advanced somatic development
– short adult stature

11β-Hydroxylase deficiency • Adrenals

• 10 – 20% cases of congenital adrenal
hyperplasia
• 11-Deoxycorticosterone accumulation
• Signs and symptoms:
– Hypertension
– Genital ambiguity (XX)
– advanced somatic development

105
 short adult stature
3β-Hydroxysteroid dehydrogenase deficiency • Adrenals and gonads
• Signs and symptoms:
– Dehydration
– Hyperkalemia, Hyponatremia
– Ambiguous genitalia
(Hypospadia, Undescended
testis, Cliteromegaly)

Lipoid adrenal hyperplasia • Steroidogenic Acute Response Protein

(StAR) mutation
• Adrenal and gonads
• Signs and symptoms:
– Dehydration
– Alkalosis, Hyperkalemia, Hyponatremia
– Female external genitalia regardless of
genetic sex (Male
pseudohermaphroditism in XY
individuals)
– Undescended testis

17α-Hydroxylase deficiency • Adrenal and gonads

• Increased Corticosterone,
Deoxycorticosterone
• Decreased sex hormones, Cortisol
• Signs and symptoms:
• Hypertension
• Episodic vomiting, headache
• Female external genitalia
• Undescended testis
Adrenogenital syndrome • An adrenocortical tumour secretes
excess amounts of androgens causing
intense masculanizing effects.
• Females develop virile characteristics
like growth of beard, deep voice,
baldness, masculine distribution of hair
& growth of clitoris.
• Prepubertal male has rapid development
of sexual organs (precocious puberty).
• In an adult male, it is difficult to diagnose
the condition because the signs are
obscured by normal virilizing
characteristics of testosterone

Hormones involved in calcium homeostasis:

 1,25 Dihydrocholecalciferol
 Parathyroid hormone
 Calcitonoin
 Parathyroid hormone related protein { PTHrP}

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  Miscellaneous hormones :
Glucocorticoids, Growth hormone, Estrogen

Parathormone:

• FOUR parathyroid glands located behind the thyroid gland

• 6 x 3 x 2 mm
• Two types of cells
1. Chief cells
2. Oxyphil cells
 Normal plasma PTH-10 -55 pg / mL
 Half life – 10 mins
Actions of PTH:
I. Increases calcium and phosphate absorption from the bones
II. Decreases excretion of calcium by the kidneys
III. Increases the excretion of phosphate by the kidneys(inhibits NaPi cotransporter)(Phosphate
Terminating Hormone)
IV. Increases intestinal absorption of calcium and phosphate.
All these actions leads to increased plasma calcium

Abnormalities of PTH secretion:

Primary Hyperparatyroidism • Tumors – adenoma of parathyroid

glands
• Extreme osteolytic resorption
• Increase in calcium and decrease in
phosphate levels.

Secondary Hyperparathyroidism • Increased levels of PTH is the result of

compensatory mechanism to
hypocalcemia
• Due to chronic renal disease or
deficiency of Vitamin D 3
Familial benign hypocalciuric hypercalcemia • Inactivating mutation in Calcium
receptor(CaR)
Familial hypercalciuric hypocalcemia • Gain of function mutation(CaR)
Pseudohypoparathyroidism • 50% reduction of the activity of Gs
occurs

Parathormone related peptide (PTHrP):

As a paracrine signal • In Cell differentiation and survival

Physiological endocrine role • In pregnancy-increases placental calcium
transport
• During lactation-maintains adequate
calcium levels for lactation
Pathological • Hypercalcemia of malignancy

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Vitamin D:

Promotes intestinal calcium absorption

BY
1. Formation of calcium binding protein
(calbindin)
2. Formation of calcium stimulated ATPase
3. Formation of alkaline phosphatase
Decreases renal excretion of calcium & phosphate
Increases both bone resorption and bone mineralization
1. BONE RESORPTION – by stimulating PTH.
Calcitriol receptors are present in osteoblasts
Receptor – calcitriol complex – stimulate osteoblasts --- activation & differentiation of osteoclasts.
2. BONE MINERALIZATION – by stimulation osteoblasts and alkaline phosphatase secretion

Abnormalities of vitamin D secretion:

Vitamin D deficiency in children and adults

- defective bone mineralization and calcification
- failure to deliver adequate Ca and PO4
Features:
Weakness and bowing of weight bearing bones, dental defects and hypocalcemia.
Responsive to Vitamin D therapy.
Vitamin D Resistant Rickets:
mutations in the gene coding for the enzyme
1 α HYDROXYLASE
1,25-dihydroxycholecalciferol receptor (type II vitamin D-resistant rickets)

Calcitonin and its actions:

• Secreted by C cells of thyroid

• Helps in Calcium absorption during pregnancy and lactation
• Decreases osteoclasts number and activity

Fibroblast Growth Factor 23(FGF 23):

• Secreted by osteoblasts
• Inhibits Vitamin D
• Inhibits PTH
• Promotes calcium and phosphate excretion
• Mutation in PHEX-X-linked hypophosphatemia , FGF23 levels increase

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Role of other hormones in calcium homeostasis:

Glucocorticoids • Lowers plasma calcium by inhibiting

osteoclasts.
• Over Long periods – osteoporosis
• Inhibit protein synthesis in
osteoblasts,thereby synthesis of organic
matrix
• Inhibit absorption of Ca and Po4 from the
gut and facilitate its excretion in the
kidneys.

Growth hormone • Increases intestinal absorption of

Calcium “Positive calcium balance”
IGF – I • Stimulates protein synthesis in bone
Thyroid hormone • Hypercalcemia, Hypercalciuria and
Osteoporosis
Estrogens • Prevents osteoporosis by inhibiting
certain cytokines
Insulin • Increases bone formation

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 Reproductive physiology

Genetic Sex 44XY and 44XX…presence or absence of Y

chromosome
Gonadal Sex Testis in male and Ovary in female
Phenotypic Sex Based on internal and external genital organs

The SRY Gene:

 located on the Y chromosome, is the primary determinant of sexual development
 If a developing embryo has a functional SRY gene in its cells, it will develop as a male(Testis).
And, if there is no functional SRY, the embryo develops as female

Female Bipotential structure Male

Clitoris Genital tubercle Glans penis
Labia minora Urethral folds and groove Shaft of penis
Labia majora Labioscrotal swellings Scrotum
Forms ovary Gonad(cortex) Regresses
Regresses Gonad(medulla) Forms testis

Functions of Sertoli cells:

1. Forms a Blood-Testes barrier.
2. Mechanical support for maturing gametes.
3. Provides nutrition to developing spermatozoa.
4. Helps in maturation of sperms.
5. Phagocytes damaged germ cells.
6. Participates in Spermiation.
7. Provides driving force for conveying sperm from testes to epididymis
8. Produces various substances:
• H-Y antigen.
• Anti Mullerian Hormone/MIS.
• Androgen Binding Protein (ABP).
• Inhibins.
• Aromatase  Testosterone to Estrogen.
Peritubular Myoid cells:
• Have contractile effects on tubules and vasculature
• Secretes paracrine regulatory products

Reflex pathway for erection • Afferent Pudendal nerve

(Parasympathetic-Points) • Efferent  Pelvic splanchnic neve/nervi
erigenti (Parasympathetic)
• NeurotransmitterAch, VIP, and Nitric
Oxide
Emission • Movement of semen into urethra, by
(Sympathetic-Shoots) contraction of vas deferens, epididymis,
ejaculatory ducts and seminal vesicles.
• Sympathetic response (T12-L2)
Ejaculation • Expulsion of semen out of urethra by

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 contraction of bulbocavernous muscle
and smooth muscles at the base of penis
• It is also a spinal reflex

Seminiferous tubules Interstitials cells of

Leyding

Primitive germ cells: Sertoli cells: Secretes testosterone

Mature into Secrete: Inhibin & Activin, Androgen binding

spermatocytes Protein, Mullerian Inhibiting Substance
(MIS)/Mullerian

Regression Factor (MRF)

Acts as Blood Testes barrier

Spermatogensesis Oogenesis

Spermatogonium (2n) Oogonia(2n),

 Mitosis  Ist meiotic division in embryonic ovary,

arrested in the stage of late prophase
Primary spermatocyte (2n)
Primary Oocyte(2n)
Meiosis
 completion of Ist meiotic division, Just
Two Secondary spermatocytes (n) before ovulation
 Secondary Oocyte (n)+Ist polar body
Two Spermatids (n) from each
IInd meiotic division, arrested At
 Metaphase
Spermatozoa (n)
Oozoa (n) +IInd polar body
*1primary spermatocyte gives rise to 4
The second meiotic division is completed
spermatids
only after the entry of sperm in to ovum
*1 Spermatogonium gives rise to 512
1 primary Oocyte gives rise to one ovum
spermatids

*It takes 74 days for the spermatogonium to

become spermatozoa

 The arrest in metaphase is due, at least in some species, to formation in the ovum of

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 the protein PP39mos, which is encoded by the C-mos protooncogene. When
fertilization occurs, the PP39mos is destroyed within 30 min by calpain, a calcium-
dependent cysteine cysteine protease
 Matured spermatozoa are released from Sertoli cells and stored, matured & gains
motility in epididymis
 Capacitation occurs in female genital tract

COMPOSITION OF SEMEN:

• Color  white, opalescent.

• Specific gravity  1028
• pH 7.35-7.5
• Composition :
• Sperms  5%
• Prostate 20%
• Seminal vesicle60%
• Sperm count  about 50- 100million/ml.
• Volume  2.5-3.5ml/ejaculate.
• Sperm movement3mm/min in female tract
• Maximal duration of fertilising capacity in female tract is 24-48hours, motility persists for 48-
60hours
• Reaction of semen is alkaline
Prostate gland constituents:
• Citrate, Calcium, Zinc, Spermine, Cholesterol, Phospholipids, Fibrinolysins, Fibrinogenase,
Acid Phosphatase.
Seminal vesicle constituents:
• Fructose, Phosphoryl choline, Ergothioneine, Ascorbic acid, Flavins, Prostaglandins
Capacitation:
• Continuation of sperm differentiation in female genital tract.
• Function: Prepares the sperm plasma membrane for acrosome reaction.
• Time taken1-4hours
Changes :
• Changes in motility pattern.
• Loss of adsorbed surface proteins, decapacitation factors.
• Loss of lipid and sterol components and redistribution of surface proteins.
• Increased permeability to calcium.
• Ca++ influx into headacrosome reaction.
• Ca++ influx into mitochondria changes in motility.
Acrosome reaction:
• Involves distinct structural changes in plasma membrane and outer acrosomal membrane.
++
Ca dependent
Changes in sperm after acrosome reaction:
• Conversion of inactive enzymes into active enzymes.
• A new surface, inner acrosomal membrane which contains proteins is exposed.
• Activation of sperm enzymes.
• Increased membrane fluidity

Actions of testosterone:

On foetal life :

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  Foetal differentiation.
 Development of male brain.
 Development of external & internal
genitalia.
 Descent of testes
At Puberty :
 Initiation of Spermatogenesis.
 Growth of external & internal genitalia.
Secondary sexual characterstics :
 Deepening of voice.
 Moustache, beard,pubic hair,body hair& acne.
 Masculine pattern of fat distribution.
 Male body contour broad thoracic cage & shoulders, narrow pelvis.
 Mental changesaggressive behaviour
In Adult Life :
 Maintenance of Spermatogenesis.
 Maintenance of accessory sex organs.
 Maintenance of Libido
Other actions
 Hyperglycemic.
 Increases levels of LDL’s & decreases levels of HDL’s.
 Accumulation of upper body, abdominal & visceral fat.
 Increases protein synthesis.
 Reabsorption of Na+ from kidneys
 Promotes bone growth
 Causes enlargement of muscle mass.
 Stimulates synthesis of Erythropoietin , so increase in RBC mass

Ovarian Hormones:

Oestrogen Oestrone: more in post menopause

Oestradiol: Most potent; Oestriol: least potent, ed during pregnancy

Synthesized by Theca interna, granulose cells, corpus luteum

Progesterone Synthesized in Corpus luteum

- Suppresses ovulation & menstruction in pregnancy

- Thermogenic effect

Inhibin Secreted by sertoli cells in males & granulose cells in females. Inhibits
FSH secretion

Relaxin Secreted by corpus luteum & placenta

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 Relaxes the pelvis during pregnancy & helps in cervical ripening

Activin Secreted by sertoli cells in males & granulose cells in females

Stimulates FSH secretion

Estrous Cycle:

 Mammals other than primates do not menstruate & their sexual cycle is called an
estrous cycle

 No episodic vaginal bleeding occurs but the underlying endocrinal mechanisms are
essentially the same as those in the menstrual cycle

 In other species ovulation is induced by copulation. (reflex ovulation)

Ovarian cycle: Follicular enlargement dominant follicle (6th day)secreted oestrogengraafian

folliclematuration of ovumfollicular rupture & release of ovum into the peritoneal cavity
(ovulation)remnants of graafian follicle forms corpus luteum  secretes progesterone >
oestrogen  lysis of corpus luteum 2 days before menstruation leaving a fibrous scar called corpus
albicans

Menstrual cycle:

Phase Other names Period Endometrial changes

Proliferative Preovulatory / Post menstrual 6th day-14th Endometrial glands enlarge &
phase / follicular phase day proliferates
(oestrogen)
Increased vascularity & coiled
arteries

Thickness: 2-3 mm

Secretory Post ovulatory / premenstrual 15th day - Endometrial glands

phase / luteal/pro gestational phase 27th day hypertrophies & distended with
(progesterone) mucus

 in no. of coiled arteries, 

blood flow

*Thickness: 5-6mm

Menstrual Destructive phase / blooding 1-5th day Vasoconstriction of spiral arteries

phase phase  ischemic changes  necrosis
of endometrium  sheddin g;

114

Endometrial cycle:
Endometrium
Characteristics Proliferative Phase
Thickness Increases due to cell division & Cell growth.
0.5mm to3.5-5mm.
Stromal cells Proliferate & increase in size thus increasing
thickness.
Glands Straight tubular glands form lined with
columnar epithelial cell. Produce and store large
amount of glycogen.
Spiral Arteries Increasingly vascularised and spiral arteries
elongate
Myometrium Increase in excitability & Contractility and
increase sensitivity to oxytocin.
Fallopian Increase ciliary activity and motility and
tubes secretory activity of cells.
Cervix Cervical mucus is thin and become crystalline,
forming channels that facilitate the passage of
sperm into uterus, Alkaline in nature.
Shows ferning like effect i.e. arborisation on
drying.
Hormonal influence of menstrual cycle
 FSH-early development of G. Follicle
 Final maturation of ovum-FSH&LH
 LH-ovulation, formation & maintenance of C. Luteum
 A surge in LH secretion triggers ovulation, and ovulation normally occurs about 9 h after
the peak of the LH surge at midcycle
 The LH surge begins about 24-36 hours before ovulation and reaches its peak about 8-10
hours before ovulation. It is this surge that acts to trigger ovulation
Bleeding: 75% arterial
Secretory Phase
Slightly increases and becomes
edematous.
Stromal proliferation and cell
growth continues.
Becomes increasingly tortous
and spiralised, produce great
amount of mucus.
Becomes increasingly tortous
and spiralised
Decrease in excitability and
decreases contractility.
Increases ciliary activity and
sensitivity and decreases
motility
Cervical mucus is thick and
sticky, tenacious and cellular.
Does not show ferning effect.
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Indicators of Ovulation
1. Basal Body Temparature
2. Fern Test
3. Endometrial Biopsy
4. Estimation of hormonal levels
5. Ultra sound examination of follicle

Actions of estrogen:

On Ovary
 Increases size of ovary & stromal cells.
 Initiates oogenesis & development & maintainence of follicles.
 Brings cyclical changes in ovary
On Uterus
 Increases size of uterus, fallopian tubes, cervix.
 Increases excitability of smooth muscle.
 Increases blood supply to myometrium.
 Causes changes in endometrium& onset of menarche.
 Increases no. of oxytocin receptors on myometrium in pregnant
On fallopian tubes :
 Increase ciliary activity and motility and secretory activity of cells.
On Cervix :
 Cervical mucus is thin and become crystalline, forming channels that facilitate the passage
of sperm into uterus, Alkaline in nature.
 Shows ferning like effect i.e. arborisation on drying.
On Vagina :
 lined with stratified squamous epithelium
 Vaginal secretions are increased.
6. On Breast :
 Promotes ductal growth.
 Causes pigmentation of areola.
 Promotes deposition of fat.
On Metabolisms
 Carbohydrate  Hyperglycemic
 Protein  Anabolic & Protein synthesis
 Fat  Plasma Cholesterol
 Mineral & H2O  Reabsorption of Na+
Water retention& Wt.gain
On bone:
 The epiphyseal growth centers are more sensitive to Estradiol than Testosterone, they close
sooner
Actions of progesterone:

Principal target organs :

 Uterus
 Breast
 Brain
Endometrium:

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  Thickness slightly increases
 Makes edematous
 Promotes stromal cell growth &proliferation
 Glands – Tortous& Spiralised,mucus secretion increases
 Spiral arteries - Tortous& Spiralised
Myometrium
 Decrease excitability
 Decreases Contractility
On Cervix
 Cervical mucus becomes thick & sticky,tenacious and cellular
 No Ferning effect
Calorigenic action
 Thermogenic
 Responsible for rise in basal body temperature at time of ovulation
On Respiration
 Stimulates Respiration
 Decreases Alveolar Pco2
On Kidneys
 Large doses – Natriuresis by blocking the action of Aldosterone

Lactation

 Oestrogen-proliferation of mammary ducts

 Progesterone-Lobulo-alveolar development
 Prolactin-Initiation of milk secretion & maintenance(PROlactin-PROduce milk)
 Oxytocin-Milk ejection(Ooze milk)
 Breast feeding stimulates prolactin secretion
 Prolactin- inhibits the action of GnRH on the pituitary, and antagonizes the action of
gonadotropins on the ovaries
Oxytocin (Paraventricular nucleus-Parturition)

 Acts primarily on the breasts and uterus & involved in luteolysis

 It triggers increase in intracellular Ca2+ levels
 The milk ejection Reflex
a) Contraction of the myoepithelial cells in the ducts of breast resulting in milk
ejection
b) Milk ejection is a neuroendocrine reflex. The receptors involved are the touch
receptors, Impulses generated are relayed from the somatic touch pathways to
the supraoptic and paraventricular nuclei
c) In lactating women, genital stimulation and emotional stimuli also produce
oxytocin secretion
 The sensitivity of the uterine musculature to oxytocin is enhanced by estrogen and
inhibited by progesterone
 Act on the non pregnant uterus to facilitate sperm transport
 Circulating oxytocin increases at the time of ejaculation in males, and it causes increased
contraction of the smooth muscle of the vas deferens, propelling sperm toward the
urethra

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 PHYSIOLOGY-MCQs
Dr.S.Krishna Kumar MD Physiology (AIIMS)

INDEX
Topic Page No.
General & Nerve muscle physiology 119
Neurophysiology 141
Cardiovascular physiology 166
Endocrine physiology 183
Reproductive physiology 205
Respiratory physiology 218
Renal physiology 233
Gastrointestinal physiology 248

118
General Physiology
“Father of Physiology” is
A. Erasistratus
B. Sir Charles Sherrington
C. Claude Bernard
D. Walter Cannon
Ans-a
Father of neurophysiology Sir Charles Sherrington
Father of Experimental physiology William Harvey
Father of Gastric physiology William Beaumont
Father of Renal physiology Homer Smith
Father of stress physiology Hans Selye
Father of pulmonary medicine Rene Laennec

MCQ
Nobel prize in Physiology/Medicine for the year 2014 awarded for
A. Innate immunity & dendritic cells
B. Reprogramming mature cells
C. Internal map of the environment
D. Vesicular traffic
Ans-C

Dr. John M. O’Keefe :

discovered PLACE CELLS-signal position and
provide the brain with spatial memory
Capacity
Dr. Moser &Moser :
GRID CELLS - internal coordinate system
essential for navigation

HOMEOSTASIS
The term “Homeostasis” coined by
a. Erasistratus
b. Sir Charles Sherrington
c. Claude Bernard
d. Walter Cannon
Ans-d
Positive feedback is seen in
A. LH surge
B. Entry of calcium into Sarcoplasmic reticulum
C. Formation of thrombin
D. Parturition
Ans-abcd
Feed forward control system is employed during
A. LH surge
B. Anticipatory increase in heart rate before exercise
C. Formation of thrombin
D. Parturition
Ans-b

Homeostasis The foundation of physiology

 Normal cell function depends on the
constancy of intestitial component of
the ECF

119
  To describe “the various physiologic
arrangements which serve to restore the
normal state, once it has been
disturbed,” W.B. Cannon coined the
term homeostasis.
 Claude Bernard-concept of milieu
intérieur
 Steady state and equilibrium are both
stable conditions, but energy is required
to maintain a steady state

Positive feedback examples:

Clotting
Calcium entry into SR
LH surge
Action potential
Shock
Parturition
Negative feedback:
Endocrine hormone regulation
BP regulation
Feed forward(Anticipatory control):
Anticipatory increase in heart rate &breathing
before exercise
Co-ordination of movements-cerebellum

Body fluids & its measurement

Sucrose space is
A. Intracellular space
B. Extracellular space
C. Plasma volume
D. Transcellular space
Ans-b
The term
a. Erasistratus
b. Sir Charles Sherrington
c. Claude Bernard
d. Walter Cannon
Ans-c
The term
A. Intracellular fluid
B. Extracellular fluid
C. Plasma volume
D. Transcellular fluid
Ans-b

MCQ
An adult male has a hematocrit of 40% and plasma volume 3L. His total blood volume will be
A. 4L B. 5L C. 6L D. 7L
Ans-b
In average young adult male,18% of the body weight is proteins,7% is minerals,15% is fat and 60% is
water
TOTAL BODY WATER (60% of body weight),42 liters
INTRACELLULAR FLUID EXTRACELLULAR FLUID
2/3rd of TBW i.e., 40% 1/3rd of TBW .i.e., 20% body weight (14 liters)

120
body weight (28 liters) INTERSTITIAL FLUID PLASMA
75% or 3/4th of ECF or 15% of 25% or 1/4th of ECF Or 5%of body
body weight (10.5 litres) weight (3.5 litres)

Measurement of body fluid volumes

Volume Indicator
Total body water 2H2O, Antipyrine
Extracellular fluid (ECF) 22Na, 125I-iodothalamate, thiosulphate, inulin, Radioactive chloride,
Sucrose
Intracellular fluid (ICF) Calculated as total body water-ECF volume
Plasma volume 125I albumin, Evans blue dye (T-1824)
Blood volume 51Cr-labelled red blood cells, or calculated as plasma volume/(1-
hematocrit)
Interstitial volume Calculated as ECF volume-Plasma volume

Percentage of body water depends on

 Age
 Gender(less in women)
 % body fat
Transcellular fluid – 1 to 2 L.
synovial, peritoneal, pericardial, intraocular spaces,cerebrospinal fluid
ECF
Most abundant cation - Na+
Most abundant anion - Cl-
ICF
Most abundant cation - K+
Most abundant anion - Phosphates > Proteins

MCQ
Ideal characteristic of simple and facilitated diffusion
A. They need a carrier protein for transport
B. Blocked by specific inhibitors
C. ATP is not needed for their functioning
D. Shows saturation kinetics
Ans-c

MCQ
Regarding active transport true-A/E
A. Requires energy
B. Energy is provided by the hydrolysis of ATPs
C. Transport against concentration or electrical gradients
D. Glucose transporter is an example
Ans-d

Exocytosis of synaptic vesicles containing neurotransmitters involves the following proteins

A. Syntaxin
B. Clathrin
C. SNAP-25
D. Synaptobrevin
E. Synaptotagmin
Ans-b
Exocytosis-SNARE complex
(Noble Prize medicine 2013-Rothman,Schekman,
Sudhof)
Synaptotagmin-Ca2+ sensor
vSNARE- Synaptobrevin

121
tSNARE- SNAP-25,Syntaxin
Botulinum Toxins:
A & E-cleave SNAP-25
C- cleave syntaxin

Transport across cell membrane

Passive Diffusion:
processes No energy is expended directly to mediate the transport process
Net flux of solute particles from areas of high to areas of low concentration
The time required for equilibrium by diffusion is proportional to the square of the
diffusion distance
Fick’s law of diffusion: J= -DA ΔC/ΔX, where J is the net rate of diffusion, D isthe diffusion
coefficient, A is the area, and Δc/Δx is the concentration gradient
Facilitated Diffusion:
Carrier proteins move substances in the direction of their chemical or electrical
gradients, no energy input is required.
Has a transport maximum (it is saturable),can be inhibited competitively and non
competitively
Example-glucose transport by GLUT
Non-ionic diffusion-
 Substances cannot cross the membrane in charged form but cross in
undissociated form
Example-Ammonia transport in GIT/Kidney
Active Primary active transport:
Processes Energy is used and substances transported against gradient.
Energy derived directly by hydrolysis of ATP(Na+ K+ ATPase)
Sodium potassium ATPase pump
discovered by Jens Skou-1997 nobel prize in chemistry
Accounts for about 24% of the energy utilized by cells, and in neurons it accounts for
70%
Has an alpha and beta subunit
Alpha subunit:
Intracellular-Na+ binding
site,Phosphorylation site, ATP binding site
Extracellular-K+ binding site,ouabainbinding site
Beta subunit:
Extra cellular glycosylation site
Extrude three Na+ from the cell and take two K+ into the cell for each molecule of
ATP hydrolyzed (electrogenic)
Activity is inhibited by ouabain,digitalis
REGULATION OF Na, K ATPase:
Agents Increasing pump activity-Throid
hormones,Aldosterone,Insulin(MN:ThAI)
Agents Decreasing Pump activity146 Dopamine.causes natriuresis
Secondary active transport:
Active transport of Na+ is coupled to the transport of other substances
Examples:Na+K+Cl-,Na-Glucose,Naaminoacids.
Na-bile salts,Na-choline uptake
Secondary active transport:
Active transport of Na+ is coupled to the transport of other substances
Examples:Na+K+Cl-,Na-Glucose,Naaminoacids.
Na-bile salts, Na-choline uptake
Exocytosis For vesicles containing material for
export,mediated through v-SNARE and t-

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 SNARE
Non constitutive (regulated) pathwayextensive processing occurs before exocytosis.Ex-
insulin release
Constitutive pathway-little or no
processing,no storage.Ex-mucus release into GI lumen
Endocytosis Various types namely phagocytosis, pinocytosis, clathrin-mediated endocytosis,
caveolae-dependent uptake, and nonclathrin/noncaveolae endocytosis
Pinocytosis-cell drinking and phagocytosis-cell eating
Clathrin mediated endocytosis:
Involves clathrin(triskelion), GTP binding protein Dynamin
Examples-internalisation of receptors for nerve growth factor,low density lipoprotein
receptor, Transferrin(Iron)
Caveolae mediated endocytosis:
Involves Rafts-rich in cholesterol and sphingolipids and caveolae (flask-shaped
membrane depression) and caveolin.
Examples-Folate receptor (Folate)
Emeiocytosis-Insulin release from stored
granules, requires calcium
Transcytosis Combines both exocytosis and endocytosis.
Otherwise called as cytopempsis
Coats and vesicle proteins
Assembly protein 1 (AP-1)-Vesicles from Trans golgi to lysosomes
Assembly protein 2-Endocytic vesicles to endosomes
COP I and COP II-Vesicles that transport between the endoplasmic reticulum and the Golgi 

Osmolarity and osmolality

OsmolaRity-number of osmoles per litRe of solution
Osmolality-number of osmoles per kg of solvent.Serum osmolality-285-295mOsm/kg H2O
Osmolality is not affected by changes in volume of solution or by temperature.
Most accurate way of finding out osmolality is by Freezing point depression
Approximate formula is Osmolality (mOsm/L) = 2[Na+] (mEq/L) +0.055[Glucose] (mg/dL) +
0.36[BUN](mg/dL)
Vant Hoff Law-used to calculate osmotic pressure-
Π = σ(nCRT)
σ – Reflection coefficient
Π – osmotic pressure
N = number of dissociable particles
R = Gas constant
T = Temperature (K)

Cell Membrane
Eukaryotic plasma membrane is made up of all except
A. Carbohydrates
B. Triglycerides
C. Lecithin
D. Cholesterol
Ans-b
Plasma membrane is mainly composed of
A. Cholesterol
B. Carbohydrates
C. Proteins
D. Phospholipid
Ans-C
Membrane fluidity is increased by
A. Stearic acid

123
 B. Palmitic acid
C. Cholesterol
D. Linoleic acid
Ans-D
Transition temperature of membrane is increased by
A. Cholesterol
B. Saturated fatty acids
C. Hydrocarbons
D. Unsaturated fatty acids
Ans-B
Cell Membrane  Current concepts of membrane physiology
is based on Fluid and Mosaic model
proposed by Singer & Nicolson,1972

Membrane Lipids  Has both hydrophilic and hydrophobic

properties(Amphipathic)
 Phospholipids-
Phosphatidylcholine,Phosphatidylethanola
mine ,Phosphatidylserine
Phosphatidylinositol,Sphingomyelin
 Glycolipids-Cerebrosides,Gangliosides
 Sterols-Cholestrol
 Membrane fluidity changes with
temperature: Temperature at which the
membrane undergoes ordered to
disordered(melts) is the transition
temperature(Tm)
 Saturated FA- Increase in Tm, decrease in
fluidity
 Unsaturated FA- Decrease in Tm, Increase
in fluidity
 Cholesterol modifies fluidity:Below Tm-
Increases fluidity,Above Tm-Limits fluidity
and that’s why is called as FLUIDITY
BUFFER
 Membrane lipids are asymmetrically
distributed: Outer Membrane-Lecithin and
sphingomyelin
 Inner leaflet- Phosphotidyl
serine,phosphotidylethanolamine
Membrane proteins  Integral proteins (Glycophorins in RBC):
distributed asymmetrically.has a
transmembrane region (Having a stretch of
hydrophobic aminoacids and hydrophilic
regions at the ends.
 Peripheral proteins(Spectrin in
RBC):attaches by
glycosylphosphatidylinositol (GPI) anchors
 Examples of GPI anchored
proteins:Alkaline
Phosphatase,CAMs,proteins that Combat
Cell lysis by complement
 Proteins may be
myristoylated,palmitoylated or prenylated
 Functions as 1.CAMs 2.Pumps 3.Carriers
4.Receptors 5.Enzymes(Mn:PCR-E.Coli)

Cell organelles

124
Studies completed on a 5-year-old boy show an accumulation of cholesteryl esters and
triglycerides in his liver, spleen, and intestines and calcification of both adrenal glands. Additional
studies indicate the cause to be a deficiency in acid lipase A activity.This enzyme is located in
A. Peroxisome
B. Lysosome
C. Liposome
D. Dyctyosome
Ans-B
Characteristics of Lysosomes
1. Discovered by Christian de Duve
2. Contains acid hydrolases,acid lipases,collagenase
3. ATP-dependent proton pumps in the membrane maintain an acidic environment (pH 4.0–5.0)

Generation and degradation of H2O2 occurs in

A. Peroxisome
B. Lysosome
C. Liposome
D. Dyctyosome
Ans-A
Characteristics of Peroxisomes
 Mammalian kidney and liver cells
 Generation and degradation of H2O2occur within the same organelle
 Detoxification of Harmful Compounds
 Oxidation of Fatty Acids-long-chain (16–22 carbons), very long-chain (24–26 carbons), and
branched fatty acids

The abnormal cleavage of mannose residues during the post-translational processing of

glycoproteins results in the development of a lupus-like autoimmune disease in mice. The
abnormal cleavage is due to a mutation of the enzyme α-mannosidase II.
This enzyme is located in
A. Peroxisome
B. Lysozyme
C. Nucleus
D. Golgi apparatus
Ans-d
Golgi apparatus
Post translational modifications of proteins(Glycosylation)
Rough ER
Biosynthesis of proteins
Protein folding
ER-associated degradation
Smooth ER
Drug Detoxification
Carbohydrate Metabolism
Glucose-6-phosphatase
Liver, kidney, intestinal cells
Calcium Storage
Steroid Biosynthesis
Adrenal gland,Liver,Testis,Ovary

Type of cell junction which attaches cells to the basal lamina is

A. Desmosomes
B. Tight junctions
C. Gap junctions
D. Hemidesmosomes
Ans-D
The effect of diffusible ions on the resting membrane potential in the presence of non diffusible
ions is best explained by
E. Nernst potential

125
F. Gibbs Donnan
G. Goldman equation
H. Hesselbach equation
Ans-b
MCQ
Connexin is an important component of
A. Desmosomes
B. Tight junctions
C. Gap junctions
D. Hemidesmosomes
Ans-c
INTERCELLULAR CONNECTIONS:

 Hold cells together:tight junctions (zonula occludens), gap junction, desmosome and zonula
adherens
 Attach cells to their basal lamina-hemidesmosome and focal adhesions

Tight junctions Gap junctions

Intestinal mucosa, the walls of the renal tubules,
and the choroid plexus
Proteins-occludin, junctional adhesion molecules
(JAMs), and claudins
Helps maintain cell polarity-prevent the
movement of proteins in the plane of the
membrane
Determines the degree of leakiness(paracellular
pathway
3 nm gaps lined up with CONNEXONS (Cx).
6 subunits of connexins=1 connexon
permit the rapid propagation of electrical activity
from cell to cell
Diseases: X-linked Charcot-Marie-Tooth disease
(Cx32), cataract (Cx46 and Cx50), Clouston
Syndrome(Cx 30), myoclonic epilepsy (Cx36),
arteriosclerosis (Cx37), idiopathic atrial fi
brillation (Cx40)

 Zonula adherens-major site of attachment for intracellular microfilaments,contains

cadherins
 Hemidesmosomes-connected to intermediate filaments. Contains cadherins

MCQ
The magnitude of equilibrium potential is calculated from
A. Nernst equation
B. Goldman equation
C. Gibbs Donnan equation
D. Avogadro’s equation
Ans-a
Electrophysiology of the cell
Resting Membrane Potential:
Every cell shows a potential difference with the inside being negative.
Due to diffusion of K+ and sodium potassium ATPase(5-10%)

Some important resting membrane potentials

Structure RMP (mv)
Neuron -70
Skeletal Muscle -90
SA node -30 to -40
Ventricle -90
Smooth Muscle -30 to -40
RBC -10

126
Equilibrium Potential
Membrane potential at which there is no net flux of that ion
Ion Equilibrium potential (mv)
Sodium +60
Potassium -90
Chloride -70

Goldman-Hodgkin-Katz Equation:
Involves multiple ions
Depends on concentration gradient and permeability of ions

Gibbs-Donnan Equilibrium:
•Presence of impermeant ion on the distribution of permeant ions
•Asymmetric distribution of permeantion

Side 1 Side 2
K+ =9 K+ =6
Cl- =4 Cl- =6
A- =5

Patch clamp technique - To study ion channels in membrane

Last 6 years Nobel prize winners
Year Winner
2013 Rothman, Schekman, Sudhof (vesicle traffic)
2012 Gurdon, Yammanaka (Reprogramming mature cells)
2011 Beutler, Hofmann, Steinmann (innate immunity and Dedritic cells)
2010 Robert Edwards (IVF)
2009 Blackburn, Grieder, Szostak (Telomerase)
2008 Zure Hausen (HPV, Sinoussi, L Montagnier (HIV

MCQ
The microfilament in cytoskeleton is
a. Actin b. Calcineurin
c. Desmin d. Vimentin
Ans-a

MCQ
Mallory body is a
A. Vimentin B. Keratin
C. Neurofilament D. Lipid
Ans-b
Cytoskeleton
Maintains structure,allows the cells to change shape and move
Made up of microtubules, intermediate filaments, and microfilaments
Microtubules Dynamic portion of cytoskeleton, provide the tracks that moves transport vesicles,
(25nm) organelles
made up of alpha, beta and gamma tubulins
γ-tubulin-production of microtubules by centrosomes(Microtubule Organising
centres(MTOCs)
Microtubule assembly is prevented by colchicine and vinblastine
Paclitaxel (Taxol) binds to microtubules and makes them so stable that organelles cannot
move
Intermediate Form a flexible scaff olding for the cell and help it resist external pressure
filaments (8– Keratin(epithelia),Vimentin(fibroblasts),Desmin(muscle),GFAP,Peripherin
14 nm) ,Neurofilaments ,Nestin,Lamin (Mn:DVLGP- KPN)

127
Microfilamen Made up of ACTIN-most abundant protein in mammalian cells
ts (4–6 nm) Found in microvilli(GIT) andLamellipodia(Crwaling)
Involves in cytokinesis during cell division

MOLECULAR MOTORS
There are three super families of molecular motors: kinesin, dynein, and myosin.
Kinesin-move its cargo toward the “+” ends of microtubules
Dyneins-move particles and membranes to the “–”end of the microtubules.
Myosin- for contraction of muscle and cell migration

MCQ
Widely accepted theory of ageing is
A. Cross linkage theory
B. Free radical theory
C. Collagen theory
D. Random mutation theory
Ans-b
Best documented longevity related signaling pathway is
A. mTOR signaling
B. IGF-Insulin signaling
C. Sirtuins
D. Ras pathway
Ans-b

Free Radical(Oxidative stress theory)

1. Imbalance between the production and removal of ROS
2. Free Radical-Unpaired electron in outer orbital
3. Antioxidants- Catalase, Glutathione peroxidase,Vit-C,E
Physiological roles of free radicals:
 Thyroid peroxidase
 Oxidative burst

Signalling pathways & longevity:

• Insulin-IGF pathway:
Decreased signaling up regulates FOXO family transcription factors which protects soma from damage
• mTOR pathway:
Targets of rapamycin
“Conductor of cell signaling symphony”
• Sirtuins:
Histone deacetylase
Metabolizes NAD
Activated by RESVERATROL(red wines)

Recent advances in ageing research

Food restriction extends life by decreasing oxidative stress
Decreasing insulin signaling(Insulin & IGF-1) extends life
Genes involved:
1. age-1 gene
2. prop-1 gene
3. Sirtuin gene sir-2
4. Klotho gene

MCQ
At constant temperature, the volume of a given mass of gas varies inversely with its absolute
pressure.
This law is
A. Bernoulli’s principle
B. Boyle’s law

128
C. Charles law
D. Laplace law
Ans-b

Nerve & Muscle Physiology

MCQ
In most of excitable cells repolarisation is due to
A. Sodium influx
B. Potassium influx
C. Sodium efflux
D. Potassium efflux
Ans-D

Nerve action potential:

Action potential Feature

Depolarization Na+ influx
Firing level After initial 15mV of depolarization (the threshold) the rate
increases. This is firing level
Upstroke phase Rapid depolarization phase caused by rapid Na+ influx
Overshoot Part of action potential in which the membrane potential is
positive (above o mV)
Repolarization or down Rapid return of membrane towards RMP. It is due to
stroke phase b. Closing of Na+ channels; b. Opening of K+ channels
Hyperpolarization Membrane potential becomes more-ve than its initial RMP
due to late closure of K channels.
After hyperpolarization Result of K+ channels remaining open, allowing the continued
efflux of K+ ions
 Hyperkalemia-resting potential moves closer to the threshold for eliciting an action
potential(more excitable)
 Hypokalemia-membrane potential is reduced,neuron hyperpolarised
 Hypocalcemia-increases the excitability by decreasing the amount of depolarization
necessary to initiate action potential
 Hypercalcemia-stabilize the membrane by decreasing excitability

MCQ
In a nerve fibre, the maximum concentration of sodium channels per unit area is in
A. Initial segment
B. Axon under myelin sheath
C. Dendrites
D. Cell body near dendrites
Ans-a
Neurons

 The human central nervous system (CNS) contains about 1011(100 billion) neurons
 Site of action potentials generation-the initial segment in spinal motor neurons, the initial
node of Ranvier in cutaneous sensory neurons
 Location of cell body:Dendritic zone end of the axon(most common).Within the axon (eg,
auditory neurons),Attached to the side of the axon (eg, cutaneous neurons)
 The number of Na+ channels per square micrometer of membrane in myelinated
mammalian neurons is 50-75 in the cell body, 350-500 in the initial segment, less than 25 on
the surface of the myelin, 2000-12,000 at the nodes of Ranvier, and 20-75 at the axon

129
 terminals.
 Along the axons of unmyelinated neurons, the number is about 110.
 Action potentials can be recorded in dendrites
 Dendritic spines-dynamic structures,produce proteins, which alters the effects of input from
individual synapses.Implicated in motivation, learning, and long-term memory

Part of a myelinated neuron No. of sodium channels

Cell body 50-75
Initial segment 350-500
Nodes of Ranvier 2000-12,000
Axonterminals 20-75

Unmyelinated neurons, the number is 110

Saltatory conduction- “jumping” of depolarization from node to node
Myelin:
Protein-lipid complex formed by Schwann cells in PNS and oligodendrocytes in CNS
Sphingomyelin-excellent electrical insulator
Formed by Protein Zero (Po)-mutations in Po causes peripheral neuropathies
Envelops the axon except at nodes of Ranvier(periodic 1-μm constrictions about 1 mm apart)
Schwann cell forms the myelin between two nodes of Ranvier but oligodendrocytes emit multiple
processes that form myelin on many neighboring axons
Loss of myelin-Multiple sclerosis caused due to the autoimmune attack of myelin leads toleakage of K +
through voltage-gated channels, hyperpolarization, and failure to conduct action potentials
GLIAL CELLS

 Meaning-Glue, continue to undergo cell division in adulthood

 Two types- microglia and microglia
 Microglia-Derived from macrophages, physiologically and embryologically unrelated to other
neural cell types
 Macroglia: oligodendrocytes,Schwann cells, and astrocytes
 Oligodendrocytes-myelin formation around axons in the CNS
 Schwann cells are involved in myelin formation around Axons in peripheral nervous system
 Astrocytes-two types namely fibrous and protoplasmic.
Functions of astrocytes:
4. Formation of blood brain barrier
5. Produce substances that are tropic to neurons
6. Help maintain the appropriate concentration of ions and neurotransmitters by taking up K +
and the neurotransmitters glutamate and γ-aminobutyrate (GABA).

MCQ
Fast retrograde axonal transport involves
A. Kinesin
B. dynein
C. keratin
D. Vimentin
Ans-b
Types of axonal transport
Transport type Speed Material transported Mechanism
(mm/day)
Fast anterograde 200-400 Golgi-derived vesicles containing Kinesin (ATP dependent)
peptides, enzyme, neurotransmitter

130
Fast retrograde 200-400 Endosomes, lysosomes Dynein (ATP dependent)
(Endocytic pathway – membrane
receptor, absorbed exogenous material)
Slow anterograde 0.2-8 Neur4ofilaments, microtubule subunits Not clear
(actin, tubulin, dynein, tau protein etc)
Bidirectional 50-100 Mitochondria Kinesin, dynein

Nerve fiber most susceptible to hypoxia is

A. A
B. B
C. C
D. All of the above
Ans-b
Erlanger and Gasser classification
Fiber Type Function Fiber Diameter (μm)
Aα Proprioception; somatic motor 12-20
Aβ Touch, pressure 5-12
Aϒ Motor to muscle spindles 3-6
Aδ Pain, temperature 2-5
B Preganglionic autonomic <3
C, Dorsal root Pain, temperature 0.4-1.2
C, Sympathetic Postganglionic sympathetic 0.3-1.3

Numerical classification of sensory nerve fibers:

Number Origin Fiber Type

Ia Muscle spindle, annulo-spiral Aα
ending
Ib Golgi tendon organ Aα
II Muscle spindle, flower-spray Aβ
ending; touch, pressure
III Pain and cold receptors; some Aδ
touch receptors
IV Pain, temperature, and other Dorsal root C
receptors

Susceptibility To: Most Susceptible Intermediate Lest Susceptible

Hypoxia B A C
Pressure A B C
Local anesthetics C B A

MCQ
Substances that promote the growth and survival of neurons are called as
A. Neuropeptides
B. Neurotransmitters
C. Neuromodulators
D. Neurotrophins
Ans-d
Neurotrophins:
Produced by astrocytes and transported both anterogradely and retrogradely
Produce proteins associated with neuronal development, growth, and survival
 The first neurotrophin to be characterized was NGF- growth and maintenance of cholinergic neurons in
the basal forebrain and the striatum
NGF reduce apoptosis of neurons thereby enhancing survival

131
Neurotrophin Receptor
Nerve growth factor (NGF) Trk A
Brain-derived neurotrophic factor (BDNF) Trk B
Neurotrophin3 (NT-3) Trk C, less on Trk A and Trk B
Neurotrophin 4/5 (NT-4/5) Trk B
p75 NTR- binds all four neurotrophins with equal affinity.Has a role in apoptosis

Other Growth factors trophic to neurons

 Ciliary neurotrophic factor (CNTF)
 Glial cell line-derived neurotrophic factor (GDNF)
 leukemia inhibitory factor (LIF)
 insulin-like growth factor I (IGF-I)
 transforming growth factor (TGF)
 fibroblast growth factor (FGF)
 platelet-derived growth factor (PDGF)

MCQ
Myosin is involved in
A. Skeletal muscle contraction
B. Active transport of sodium
C. Synaptic transmission
D. Cell membrane permeability
Ans-a

MCQ
The protein that binds with Ca2+&shifts the tropomyosin molecule from the active site of actin in
a skeletal muscle is
A. Troponin-C B. Troponin-T
C. Myosin D. Calmodulin
Ans-a

MCQ
True regarding sarcotubular system?
A. T system is continuous with the membrane of the muscle fibre, forms a grid perforated by the
individual muscle fibrils
B. Involved in rapid transmission of potential from cell membrane to all the muscle fibrils
C. The sarcoplasmic reticulum plays an important role in Ca2+ movement
D. All of the above
Ans-d
Skeletal muscle physiology

Dark band – ‘A’ a (ANISOTROPIC) highly refractile

light band - less refractile – ‘I’ a - ISOTROPIC
Z’ – line- highly refractile….

132
substance between two adjacent Z lines is called
sarcomere

Troponin T Binds Tropomyosin

Troponin I inhibits the interaction of myosin with actin
Troponin C Calcium

Other Structural Proteins:

 Actinin
 Titin- Largest known protein
 Desmin
Sarcotubular system

T tubule membrane- Dihydropyridine receptors (DHPR)

Sarcoplasmic reticulum- Ryanodine receptor (RyR)
Physical interaction between the two allows calcium influx

Relaxation Factors:
sarcoplasmic or endoplasmic reticulum Ca 2+ATPase (SERCA)
Sodium Calcium Exchanger Calsequestrin Calreticulin(Smooth Muscle)

133
Classification of muscle fibres:
TYPE 1 TYPE IIA TYPE IIB
Other names Slow, Oxidative (SO) Fast, Qxidative, Fst, Glycolytic (FG)
Glycolytic (FOG)
Color Red Red White
Myosin ATPase Slow Fast Fast
activity
Ca2+-pumping Moderate High High
capacity of
sarcoplasmic
reticulum
Diameter Small Large Large
Glycolytic capacity Moderate High High
Oxidative capacity High Moderate Low
Associated Motor Slow (S) Fast Resistant to Fast Fatigable (FF)
Unit Fatigue (FR)
Type
Membrane potential
=-90 mV
Oxidative capacity High Moderate Low

MCQ
Multiunit smooth muscle is found in
A. Uterus B. Ureter
C. Intestines D. Iris of the eye
Ans-d

MCQ
Latch bridge mechanism is seen in
A. Fast skeletal muscle
B. Slow skeletal muscle
C. Cardiac muscle
D. Smooth muscle
Ans-d

MCQ
The smooth muscle protein which functionally resembles Troponin-C in its action is
A. Calbindin B. Calsequestrin
C. Calcineurin D. Calmodulin
Ans-d

MCQ
Absence of striations and presence of plasticity is the characteristic feature of
A. Fast skeletal muscle
B. Slow skeletal muscle
C. Cardiac muscle
D. Smooth muscle
Ans-d
Smooth muscles
 Lacks cross striations.Containsdense bodies(Attaches α-actinin to actin)in place of Z lines
 Contains tropomyosin, but lacks troponin
 Has different isoforms of actin and myosin
 Has less extensive sarcoplasmic reticulum and few mitochondria
 Two types-Unitary and Multi unit smooth muscles
 Unitary type-has many gap junctions(Syncytium).Present in intestine, the uterus, and theureters
 Multiunit type-few or no gap junctions.Present in iris of the eye.Able to display fine anddiscrete
contraction patterns

134
 Blood vessels has both types of smooth muscles
 No true RMP.varies between -20 to -65mV
 Main source of calcium-Extracellular
 Ca2+ binds to calmodulin-activates calmodulin-dependent myosin light chain
kinasephosphorylates
 myosin on serine at position 19, increasing its ATPase activity(Myosin based)
 Regulation is through myosin light chain phosphatase-dephosphorylates myosin(relaxation)
 Relaxation also occurs through Endothelium derived relaxating factor(NITRIC OXIDE)
 Latch bridge mechanism- myosin cross-bridges remain attached to actin for some time after
 the cytoplasmic Ca2+ concentration falls leading to sustained contraction with littleexpenditure of
energy
 Plasticity-if an unitary smooth muscle is stretched-at first there is increase in tension but the
 tension gradually decreases if the muscle is held at the greater length after stretching
 Norepinephrine-decreases the spikes and acetyl choline-increases the spikes in unitarysmooth
muscles

TYPES OF SMOOTH MUSCLE

 SINGLE UNIT smooth muscle a/c VISCERAL SMOOTH MUSCLES
 Sites-walls of hollow viscera e.g.
GIT,ureters,bronchi,utreus,urinary bladder
 MULTI UNIT smooth muscle
 Sites -most blood vessels, epididymis, vasdeferens, iris, ciliary body, piloerector muscle.

MCQ
Calcium induced calcium release is more prominent in
A. Skeletal muscle B. smooth muscle
C. cardiac muscle D. All of the above
Ans-C

CARDIAC MUSCLE
 Has numerous mitochondria, and a high content of myoglobin
 35% of the caloric needs of the human heart are provided by carbohydrate, 5% by ketones and amino
acids, and 60% by fat
 Intercalated disks(occur at Z lines)-helps in effective transfer of contractile force along the axis
 Presence of Gap junctions(Functional syncytium)
 The T system in cardiac muscle is located at the Z lines (skeletal muscle at A–I junction)
 The resting membrane potential of individual mammalian cardiac muscle cells is about –80 mV
 Action potential of a typical ventricular cardiomyocyte: Initial rapid depolarization and the overshoot
(phase 0)-opening of voltage-gated Na + channels .The initial rapid repolarization
(phase 1)-closure of Na+ channels and opening of one type of K+ channel. Prolonged plateau
(phase 2)-slower but prolonged opening of voltage-gated Ca 2+ channels. Final repolarization
(phase 3) to the resting membrane potential (phase 4)-closure of the Ca2+ channels and a
slow, delayed increase of K+ efflux through various types of K+ channels.
 Cardiac myocytes-two types of Ca2+ channels (T- and L-types), mostly due to opening of the slower
L-type Ca2+ channels.
 Influx of extracellular Ca2+ through the voltage-sensitive DHPR-triggers calcium-induced calcium
release through the RyR
 Absolute refractory period- phases 0 to 2 and about half of phase 3 and relatively refractory until
phase 4.Thus cardiac muscle cannot be TETANIZED
 Isoforms- Cardiac muscle contains both the α and the β isoforms of the myosin heavy chain (α MHC
and β MHC). β MHC-lower myosin ATPase activity compared to α MHC.ATRIA-has both isoforms but
α MHC.VENTRICLES-has β MHC
 Long QT syndrome-due to mutations in voltage gated K + channel genes (KCNQ1 or KCNH2), voltage-
gated Na + channels (eg, SCN5A), Ca 2+ channels (eg, CACNA1C). K+ or Mg2+ deficiencies should be
corrected in these patients.Therapy with β-blockers-to reduce the risk of cardiac arrhythmias

The activity of the calcium pump on the sarcoplasmic reticulum of cardiac muscle is regulated
by A. IP3 B. DAG

135
 C. Phospholamban D. Calsequestrin
Ans-C
Phospholamban:
 inhibits the activity of the SR calcium pump
 Inhibition is relieved upon phosphorylation by cAMP
 Norepinephrine increases cAMP
 Norepinephrine increases calcium availability in SR for subsequent contractions

Neurotransmitters:
Incorrect match regarding the neurotransmitter and its central area is
A. Norepinephrine-locus coeruleus
B. Dopamine-nigrostriatum
C. Serotonin-tubero mamillary nucleus
D. Acetylcholine-Nucleus basalis
Ans-C
Neurotransmitter Central area
Norepinephrine Locus coeruleus
Dopamine Substansia nigra
Nucleus accumbens
Ventral tegmentum
Serotonin Raphe nuclei
Acetyl choline Nucleus basalis
Septal nuclei
Ponto mesencephalo tegmental complex
Histamine Tubero mamillary nucleus
Posterior hypothalamus

Regarding Glutamate all are false except

A. main inhibitory transmitter in the brain and spinal cord
B. Transported into glia and converted to glutamine by glutaminase
C. Acts only on NMDA receptors
D. Is the neurotransmitter responsible for excitotoxicity in stroke
Ans-D
Glutamate responsible for 75% of the excitatory transmission in the CNS
Synthesis:
1. Conversion of α-ketoglutarate toglutamate by GABA transaminase
2. Conversion of Glutamine to glutamate by glutaminase
Excitotoxicity- exces-sive levels of glutamate during ischemia, anoxia, hypoglycemia, or
trauma-Death of
Neurons(massive Ca2+ influx)
Involved in learning and memorysynaptic plasticity, long-term potentiation
Receptors-AMPA,Kainate,NMDA,mGLUR

Major inhibitory mediator in the brain is

A. Glutamate
B. Glycine
C. Gamma amino butyrate(GABA)
D. Acetylcholine
Ans-C
GABA formed by decarboxylation of glutamate by the enzyme glutamate decarboxylase(GAD)
vesicu-lar GABA transporter (VGAT)- transports GABA and glycine intosecretory vesicles
Receptors- GABAA, GABAB, and GABAC
GABA agonists- benzodiazepines, Barbiturates

All are correct matches regarding neurotransmitters and their enzymes responsible for synthesis
except
A. Dopamine-DOPA decarboxylase

136
B. Norepinephrine-Dopamine hydroxylase
C. Epinephrine-Phenylethanoalmine-N methyltransferase
D. Acetlylcholine-acetlycholine esterase
Ans-D
Dopamine-From Tyrosine. DOPA decarboxylase
Norepinephrine-Dopamine hydroxylase
Epinephrine-Phenylethanoalmine-N methyltransferase
Acetylcholine-Choline Acetyl Transferase
Serotonin- From tryptophan.5HT decarboxylase
Histamine-From Histidine. Histidine decarboxylase

Urinary metabolites of norepinephrine metabolism are all except

A. Normetanephrine
B. dihydroxymandelic acid
C. vanillylmandelic acid
D. homovanillic acid
Ans-D

Neurotransmitters and their urinary metabolites:

Norepinephrine- Normetanephrine, dihydroxymandelic acid, vanillylmandelic acid
Mainly by monoamine oxidase (MAO)and the latter by catechol- O-methyltransferase (COMT)
Dopamine- homovanillic acid,DOPAC
Serotonin-hydroxyindoleacetic acid (5-HIAA)

Modulators of norepinephrine transmission are all except

A. Metyrosine- blocks tyrosine hydroxylase
B. Cocaine- blocks Norepinephrine transport
C. Amphetamine-sympathomimetic
D. Guanethidine-enhances norepinephrine release
Ans-D
Modulators of norepinephrine transmission:
Metyrosine-Blocks tyrosine hydroxylase
Bretylium and guanethidine-prevent the release of norepinephrine
Cocaine and tricyclic antidepressants-block the NE transporter
Sympathomimetics-amphetamines and ephedrine

Transmitter at the neuromuscular junction and in autonomic ganglia is

A. Glutamate
B. Acetylcholine
C. GABA
D. Glycine
Ans-B
Acetyl transmitter at -neuromuscular junction, in autonomic ganglia, and in postganglionic
choline parasympathetic, basal forebrain complex, pontomesen-cephalic cholinergic complex
Involved in regulation of sleep-wake states, learning, and memory
from choline and acetyl-CoA by the enzyme choline acetyltransferase(ChAT)
synthesis and release involves- Na+- dependent choline transporter,
vesicleassociatedtrans-porter (VAT)
Removal-by acetylcholinesterase in the synaptic cleft
Receptors:2 types
1. Muscarinic: (M1, M4, and M5-CNS),( M2-
Heart),( M3-glands and smooth muscles)
2. Nicotinic: (NM- neuromuscular junction),
(N N- CNS and autonomic ganglia)
Drugs that alter cholinergic transmission:
Hemicholinium- blocks the choline transporter
 Vesamicol- blocks the VAT
botulinum toxin- prevents the release of acetylcholine

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Substance P is released in response to pain from which of the following
A. Mast cells
B. Endothelium
C. Plasma
D. Nerve terminals
Ans-D
Substance P Location- primary afferent neurons in the spinal cord, nigrostriatal system,
hypothalamus
Responsible for axon reflex,peristalsis,pain transmission
Receptors- neurokinin receptors (NK1- NK3)

Neuromuscular transmission:
Botulinum toxin acts by
A. Post synaptic inhibition
B. Inhibiting acetyl choline esterase
C. Inhibiting release of acetylcholine
D. Activating acetyl choline esterase
Ans-C

SYNAPTIC TRANSMISSION

 Synapse- the junctions where the axon or some other portion of one cell (the presynaptic
cell) terminates on the dendrites, soma, or axon of another neuron,muscle or gland
 There are about 2 × 1014 synapses
 Synaptic cleft-space between presynaptic and post synaptic neuron. 20–40 nm wide
 postsynaptic density- ordered complex of specific receptors, binding proteins, and enzymes
induced by postsynaptic effects
 synaptic vesicles-Three types: small, clear vesicles-acetylcholine, glycine, GABA, or
glutamate; small vesicles with a dense core-catecholamines; and large vesicles with a dense
core-neuropeptides
 Active zones-site of discharge of small vesicles. Calcium channels arranged in rows
 Proteins that hold synapses together- Neurexins
 Proteins involved in Exocytosis of vesicles: v-snare protein synaptobrevin and t-snare
protein syntaxin
 Toxins blocking neurotransmitter release:Tetanus toxin and botulinum toxin
 Tetanus toxin- attaches to gangliosides and blocks release of inhibitory transmitters glycine
and GABA leading to spastic paralysis
 Botulinum toxin- Toxins A, B, and E-toxic to humans. Toxins A and E cleave synaptosome-
associated protein (SNAP-25)-a presynaptic membrane protein needed for fusion of synaptic
vesicles containing acetylcholine to the terminal membrane.Toxin B- cleaves synaptobrevin
ultimately leading to flaccid paralysis.BOTOX(botulinum toxin) clinically useful in achalasia
and to remove wrinkles in face

EPSP(Extitatory post synaptic potential) IPSP(Inhibitory post synaptic potential)

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 Transient partial depolarization
 The excitability of the neuron to other
stimuli is increased
 Due to opens Na + or Ca2+ channels
 Transient hyperpolarisation
 The excitability of the neuron to other
stimuli is decreased
 Due to opening of Cl-channels,opening of
K + channels

 Slow EPSP-due to decreases in K+ conductance. Latency is 100-500 ms

 Slow IPSPs are due to increases in K+ conductance. Latency is 100-500 ms
 Presynaptic inhibition-Mediated by GABA acting through GABA A- increases Cl– conductance
and GABA B- increases K+ conductance
 Renshaw cell inhibition-Neurons inhibiting themselves through negative feedback
mechanisms. Neurotransmitter involved is Glycine

Neuromuscular transmission
 Impulse arriving in the end of the motor neuron--- increases the permeability of its endings to Ca2+---
Exocytosis of acetylcholine-containing synaptic vesicles--- acetylcholine binds to nicotinic cholinergic
(NM) receptors---Increases Na+ and K+ conductance---End plate potential
 Average human end plate contains about 15–40 million acetylcholine receptors.
 On arrival of nerve impulse---Ach released from 60 synapticvesicles.Each vesicle contains 10,000
molecules of Ach. This amount is enough to activate about 10 times the number of NM recep-tors
needed to produce a full end plate potential(10-fold safety factor)
 Miniature end plate potential (MEEP)-At rest, small quanta (packets) of acetylcholine are released
randomly---produces MEEP of 0.5mV amplitude. size of the quanta of acetylcholinereleased varies
directly with the Ca2+ concentration and inversely with the Mg2+concentration

Myasthenia Gravis
 Caused by the formation of circulating anti-bodies to the muscle type of nicotinic cholinergic
receptors.
 Affected muscles have 70–90% decrease in the number of receptors per end plate. In most patients,
the thymus is hyperplastic; and 10–15% has a thymoma.
 Treatment is with acetylcholinesterase inhibitor such as neostigmine or pyridostigmine and
immunosuppressive drugs like prednisone, azathioprine, or cyclosporine.Thymectomy isindicated
in patients with thymoma

Lambert Eaton syndrome

 Due to autoimmune attack of the voltage-gated Ca 2+ channels.
 Repetitive stimulation of the motor nerve facilitates accumulation of Ca2+ in the nerveterminal and
increases acetylcholine release, leading to an increase in muscle strength. Thisis in contrast to
myasthenia gravis in which symptoms are exacerbated by repetitivestimulation.
 Associated with small cell cancer of the lung, lymphosarcoma, malignant thymoma, andcancer of the
breast, stomach, colon, prostate, bladder, kidney, or gall bladder.
 Use of aminoglycoside antibiotics also produces a similar syndrome
 Treatment-. Prednisone,plasmapheresis,intravenous immunoglobulin,aminopyridines

Synapse en passant
 Neuron forms a synapse on the surface of another neuron or a smooth muscle cell and then passes on
to make similar contacts with other cells
 Characteristic of smooth muscles
 No recognizable end plates or other postsynaptic specializations

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 Multiple branches of the neurons are beaded with enlargements (varicosities) and contain synaptic
vesicles
 This arrangement permits one neuron to innervate many effector cells

Neuromuscular transmission Blockers

 Neuronal sodium channel blockers-Tetrodotoxin,saxitoxin
 Calcium channel blocker-ω-Conotoxin
 Potassium channel blocker-Dendrotoxin
 Agents preventing Ach release-Tetanus toxin,Botulinum toxin
 Muscle sodium channel blocker- Tetrodotoxin,saxitoxin,μ-Conotoxin
 AchReceptor blocker-Tubocurarine(competitive,non-depolarising),Succinylcholine(depolarising,non-
competitive)
 Acetylcholine esterase inhibitors-Physostigmine,Neostigmine,disopropylflurophsophate(DFP)

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Neurophysiology

Sensory Physiology

MCQ
Following are touch receptors except
A. Meissner corpuscles
B. Pacinian corpuscles
C. Merkel cells
D. Free nerve endings
Ans-D
Modality Stimulus Energy Receptor Cell Types
Touch Tap, flutter 5–40 Hz Meissner corpuscles
Touch Motion Hair follicle receptors
Deep pressure, vibration
Touch 60–300 Hz Pacinian corpuscles
Touch Touch, pressure Merkel cells
Touch Sustained pressure Ruffini corpuscles
Proprioception Stretch Muscle spindles
Proprioception Tension Golgi tendon organ
Temperature Thermal Cold and warm receptors
Chemical, thermal, and Polymodal receptors or chemical, thermal,
Pain mechanical and mechanical nociceptors
Vision Light Rods, cones
Hearing Sound Hair cells (cochlea)
Balance Angular acceleration Hair cells (semicircular canals)
Linear acceleration,
Balance gravity Hair cells (otolith organs)
Smell Chemical Olfactory sensory neuron
Taste Chemical Taste buds

Elongated, encapsulated receptor found in the dermal pegs of glabrous skin and is especially
abundant on lips and fingertips?
A. Merkel’s disc
B. Free nerve endings
C. Meissner’s corpuscle
D. Ruffini’s endings
Ans-C
Found in the dermis of hairy skin that is specialized to detect continuously applied touch
sensation?
A. Free nerve endings
B. Merkel’s disc
C. Pacinian corpuscle
D. Ruffini’s endings
Ans-B

MCQ
“No matter how or where along the nerve the activity is initiated, the sensation evoked is that for
which the receptor is specialized”This is
A. Munro Kellie Doctrine

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B. Bell Megendie law
C. Law of specific nerve energies(Muller)
D. Weber Fechner Principle
Ans-C

Physiology of pain:
MCQ
Pain is transmitted through which group of nerve fibres
A. Aα and Aβ fibres
B. Aα and Aδ fibres
C. Aδ and Aβ fibres
D. Aδ and C fibres
Ans-D
Which of the following is an important functional parameter of pain receptors?
A. Exhibit little or no adaptation
B. Not affected by muscle tension
C. Signal only flexion at joint capsules
D. Can voluntarily be inhibited
Ans-A
Stimulation by touching or pulling on which of the following structures is least likely to cause a
painful sensation?
A. The postcentral gyrus
B. The dura overlying the postcentral gyrus
C. Branches of the middle meningeal artery that lie superficial to the dura over the postcentralgyrus
D. Branches of the middle cerebral artery that supply the postcentral gyrus
Ans-A
All of the following are pain receptors except
A. Transient Receptor Potential Channels
B. Purinergic receptors
C. Tyrosine receptor kinase
D. protease-activated receptor-2
E. B1 and B2 receptors
F. Prostanoid receptors
Ans-D
protease-activated receptor-2(PAR-2)- for itch

Regarding thermo receptors false statement is

A. warmth receptors activate at 30°C and maximum firing occurs at 46°C
B. Cold receptors activate at 24°C and maximum firing occurs at 10°C
C. There are 4–10 times as many hot-sensitive as cold-sensitive spots
D. TRPV M8 is a cold receptor
E. TRPV 3 and 4 are warm receptors
Ans-C

Pallesthesia is
A. Ability to perceive two caliper points as separate points
B. perception of the form and nature of an object without looking at it
C. inability to identify an object by touch
D. ability to feel mechanical vibrations
Ans-D
Allodynia is
A. exaggerated response to a noxious stimulus
B. Inability to perceive touch sensation
C. Inability to perceive pain sensation
D. sensation of pain in response to a normally innocuous stimulus
Ans-D

All of the following are characteristics of visceral pain except

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A. relative predominance of Aδ nerve fibers in viscera
B. poorly localized
C. Accompanied with autonomic symptoms
D. Pain is referred to other structures
Ans-A
Pain Physiology:
Pain  First pain (epicritic pain)- ability to localize the site and intensity of the noxious stimulus.
Activation of Aδ fibers, which release glutamate, is responsible for this
 Slow pain (protopathic pain)- dull, intense, diffuse, and unpleasant feeling.
Activation of C fibers, which release a combination of glutamate and substance
P, is responsible for this
 Receptor channels:
1.Transient receptor potential (TRP) channels. TRPV1- activated by intense heat, acids, and
chemicals such as capsaicin. TRPA1 receptors-activated by
Noxious mechanical, cold, and chemical stimuli
2. acid sensing ion channel (ASIC)
receptors- activated by pH changes
3. purinergic receptors-ATP acts on it
4. Tyrosine receptor kinase A (TrkA)-
activated by nerve growth factor (NGF)
Hyperalgesia- exaggerated response to a noxious stimulus
Allodynia- sensation of pain in response to a normally innocuous stimulus
Two components of pain pathways:
1. From VPL nuclei in the thalamus, fibers project to SI and SII. (Pathway responsible for the
discriminative aspect of pain-the neospinothalamic tract
2. Paleospinothalamic tract-the pathway that includes synapses in the brain stem reticular
formation and centrolateral thalamic nucleus projects to the frontal lobe, limbic system, and
insula. This pathway mediates the motivationalaffectcomponent of pain.

All of the following are useful in treatment of pain except

A. Capsaicin transdermal patches
B. Lidocaine
C. Ralfinamide
D. NMDA receptor agonists
E. Ziconotide
F. Gabapentin
G. Topiramate
Ans-D
Therapy for chronic pain
Drugs targeting sodium channel Nav 1.8:
1. Capsaicin transdermal patches
2. Lidocaine
3. Ralfinamide
4. Topiramate

Voltage gated N type calcium channel blocker: ZicoNotide

Modulation of pain transmission
Gate control theory is proposed by
A. Melzack & Wall
B. Baltimore
C. Sherrington
D. William carpenter
Ans-A
Stimulation of which brain area can modulate the sensation of pain?
A. Superior olivary complex
B. Locus ceruleus
C. Periaquaductal gray
D. Amygdala

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Ans-C
Which of the following is a type of interneuron in this region utilizes enkephalin to inhibit pain
transmission?
A. Nucleus raphe magnus
B. Postcentral gyrus
C. Dorsal horn of spinal cord
D. Type C sensory fiber
Ans-C

Counter irritants resolves pain by

A. Spatial summation
B. Adaptation of receptors
C. Inhibiting the pain pathway at dorsal horn gate
D. Inhibiting the release of pain mediators
Ans-C
Pain producing substance is
A. Histamine
B. Bradykinin
C. Serotonin
D. All of the above
Ans-D

False statement regarding endogenous analgesia system is

A. periaqueductal gray is an important component
B. Serotonin and norepinephrine are the neurotransmitters involved
C. Endogenous cannabinoids do play a role
D. Opiods inhibits pain by acting postsynaptically
Ans-D
Modulation of 1. gate-control mechanism
pain Proposed by Melzack&Wall.
transmission simultaneous activation of innocuous
cutaneous mechanoreceptors
simultaneous activation of innocuous cutaneous mechanoreceptors- reduce the
responsiveness of dorsal horn neurons to their input from nociceptive afferent terminals
This is the rationale behind the use of transcutaneous electrical nerve stimulation
(TENS)
2. Opiod peptides:
endogenous opioid peptides-enkephalin and dynorphin
Action on postsynaptic opioid receptorsincrease in K + conductance
Action on Presynaptic opioid receptorsdecrease in Ca 2+ influx, resulting in a decrease in
release of glutamate and substance P
3. Endogenous analgesic system:
periaqueductal gray (PAG)-projects to nucleus raphé magnus and rostral ventromedial
medulla
Neurons in both of these regions project to the dorsal horn of the spinal cordrelease
serotonin and norepinephrine which inhibits the activity of dorsal horn neurons that
receive input from nociceptive afferent fibres
Locus coeruleus-Releases norepinephrine which modulates pain transmission
Stress induced release of endogenous cannabinoids such as 2-arachidonoylglycerol (2AG) and
analgesia anandamide
acts on CB1 and CB 2 receptors
CB1- accounts for the euphoric actions of cannabinoids
CB 2- expressed in activated microglia.Responsible for analgesia

Which disorder is characterized by excessive pain in a skin dermatomal distribution

resulting from a viral infection of a dorsal root ganglion?
A. Tic douloureux

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 B. Thalamic pain syndrome
C. Brown-Séquard syndrome
D. Herpes zoster
Ans-D
Which disorder is characterized by the loss of pain sensation throughout one entire side of the
body
and the opposite side of the face?
A. Brown-Séquard syndrome
B. Thalamic pain syndrome
C. Herpes zoster
D. Lateral medullary syndrome
Ans-D

Somato sensory pathways:

MCQ
Characteristic features of dorsal column pathways are all except
A. ascend ipsilaterally in the dorsal columns of the spinal cord to the medulla
B. synapse in the gracilus and cuneate nuclei
C. Ends in ventral posterior lateral thalamic nuclei
D. principal pathways for pain and temperature sensations
Ans-D
Dorasal column:
For Touch, vibratory sense, and proprioception
Sacral cord- represented medially
Cervical cord-represented laterally
Venterolateral tracts:
For Pain & temperature
Crosses midline at spinal level
Synapse in VPL thalamic nuclei

MCQ
Regarding somatosensory cortical pathways false statement is
A. post central gyrus of the parietal lobe
B. size of the cortical receiving area for impulses from a particular part of the body is
proportional
to the size of the part
C. Sylvian fissure is an important component
D. Cells are arranged in vertical columns

Ans-B
Which of the following body parts is represented superiorly and medially within the postcentral
gyrus?
A. Upper limb
B. Lower limb
C. Abdomen
D. Genitalia
Ans-B
Somatosensory cortical areas:
Primary- Post central gyrus
Association area- parietal lobe
Secondary area- sylvian fissure
“size of the cortical receiving area for impulses from a particular part of the body is proportional to the
use of the part”
Thumb and lips-maximum representation

Special Senses
Vision
The cell which doesn’t play a role in visual processing in retina is

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A. Bipolar cells
B. Amacrine cells
C. Muller’s cells
D. Horizontal cells
Ans-C
Cells in the retina:
Rods
Cones
Ganglion cells- Only output cell,Only cell produce action potential
Horizontal cells-connects rods and cones
Amacrine cells-connects bipolar and ganglion cells
Muller’s cells- Glial cells. Supporting cells

MCQ
Important function of pigment epithelium is
A. Synthesis of visual pigments
B. Provides nourishment to retina
C. Phagocytosis of old pigments
D. Reflects light rays back into the retina
Ans-C

Characteristic features of rods and cones are all except

A. Has outer segment, inner segment and synaptic terminal
B. Outer segment synthesizes the photo pigments
C. Inner segment is rich in mitochondria
D. Outer segments are modified cilia with membranous disks
Ans-B
Characteristics of rods and cones:
Rods(RoD: Dim light) Cones(Cones-Colour)
Outer segment-slender,cylindrical Long conical
Invaginated cell membrane separated from Invaginated cell membrane continues cell surface
cell surface
Photopigment-Rhodopsin(vision in dim light) Photopsin(vision in bright light)
Disks slowly toward the tip of rods Disks don’t move
Smaller nucleus Larger nucleus
Terminal part-Narrower Terminal part-Expanded

Cone type color Peak(nm) Range(nm)

Short wave/blue Blue violet 440 440-500
sensitive
Medium wave/green Green 535 450-545
sensitive
Long wave/red Yellow,red 565 564-580
sensitive

MCQ
Relative color and luminosity under changing light conditions are maintained by
A. Bipolar cells
B. Ganglion cells
C. Muller cells
D. Amacrine cells
Ans-D
Horizontal cells and Amacrine cells:
Responsible for Contrast enhancement by the phenomenon of lateral inhibition
Which one of the reactions in the retinal rods is caused directly by the absorption of light
A. Dissociation of scotopsin and metarhodopsin
B. Decomposition of scotopsin

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 C. Transformation of 11-cis retinal to all-trans retinal
D. Transformation of metarhodopsin to lumirhodopsin
Ans-C
Activation of transducin by light activates an enzyme which
A. Hydrolyzes cGMP
B. Increases the dark current
C. Activates adenylyl cyclase
D. Releases calcium from intracellular stores
Ans-A
In which one of the following sensory systems does stimulation cause the receptor cell to
hyperpolarize?
A. Smell
B. Taste
C. Hearing
D. Vision
Ans-D
Phototransduction in rods and cones:

Incident lightStructural change in the retinal of photopigmentConformational change

of photopigmentActivation of transducinActivation of phosphodiesteraseDecreased
intracellular cGMPClosure of Na+ channelsHyperpolarisationDecreased release of
synaptic transmitter(Glutamate) Response in bipolar cells and other neural elements
MCQ
Fibers from contra lateral nasal hemi retina project to the following layers in lateral geniculate
nucleus
A. Layers 2,3 and 5
B. Layers 1,2 and 6
C. Layers 1,4 and 6
D. Layers 4,5 and 6
Ans-C

Lateral geniculate body terminates in which layer of visual cortex

A. Layer 1
B. Layer 2
C. Layer 3
D. Layer 4
Ans-D

Blobs in visual cortex are associated with

A. Ocular dominance
B. Orientation
C. Color processing
D. Saccades
Ans-C
Parvocellular pathway to visual cortex is concerned with
A. Color contrast
B. Luminance contrast
C. Temporal frequency
D. Movement and depth
Ans-A
Lateral geniculate body Fibres from ipsilateral hemiretina-ends in lamina 2,3,5
Fibres from contralateral nasal retinaends in lamina 1,4,6
From lateral geniculate nucleus to Two pathways
visual cortex 1. Magnocellular pathway-From layer 1&2. Carries signal for
detection of movement,depth and flickers
2. Parvocellular pathway-From layers 3,4,5,6. Carries signals

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 for color vision,texture,shape and fine details
Blobs and the visual pathway Layers 2 and 3 contain a high concentration of ‘cytochrome
oxidase’ called as blobs and are concerned withcolor
processing

MCQ
Visual area 8 (V8) is concerned with
A. Detection of movement
B. Detection of faces
C. Color vision
D. None of the above
Ans-C
Visual areas
Area Function
V1-primary visual Shape, form
Dorsal-parietal Motion
Ventral-temporal Recognition of faces
V8-lesion causes Achromatopsia Color vision

MCQ
Simple cells and complex cells are present in
A. Retina
B. Visual cortex
C. Lateral geniculate body
D. Medial geniculate body
Ans-B
Types of cortical cells:
Simple cells:
Respond to bar of light, line or edge and have a particular orientation
Complex cells:
They respond particularly to movement of stimuli
Simple and complex cells are called as “Feature Detectors”

MCQ
Tracking movements of the eyes as they follow moving objects are called as
A. Saccades
B. Smooth pursuit movements
C. convergence
D. accomodation
Ans-B
Which lobe of the cerebral cortex contains the small bilateral cortical area that controls voluntary
fixation movements?
A. Frontal
B. Temporal
C. Occipital
D. Parietal
Ans-A

Eye movements:
Saccades-sudden jerky movements
Centre-frontal cortex and the superior colliculi
2. Smooth pursuit-cerebellum
Superior colliculi:
 constantly active positioning the eyes
 highest rates of blood flow

Hearing:

148
MCQ
By attenuation reflex the sounds are attenuated to lower frequency with decibels of
A. 30-40
B. 10-20
C. 200-220
D. 100-120
Ans-a
Reaction time for tympanic reflex is
A. 20-30ms
B. 40-160 ms
C. 30-60 ms
D. 5-10 ms
Ans-b

MCQ
Stereocilia and kinocilium are seen in
A. Tip of the tongue
B. Nasal mucosa
C. Auditory cortex
D. Inner ear
Ans-d
Stereocilia and kinocilium are seen in
A. Basilar
B. Reissner’s
C. Tectorial
D. Tympanic
Ans-c
Characteristics of inner and outer hair cells are all except
A. There are 20,000 outer hair cells and 3500 inner hair cells in each human cochlea
B. 5% of the sensory neurons innervate inner hair cells and 90 to 95% innervates outer hair cells
C. The resting membrane potential of the hair cells is about –60 mV
D. Prestin is the motor protein of outer hair cells
Ans-b

Attenuation Reflex
 To protect the cochlea from damaging vibrations
 To mask low-frequency sounds
Reduce the intensity of lower-frequency sound transmission by 30 to 40 decibels
Contraction of the Tensor Tympani and Stapedius Muscles
Also called Tympanic reflex(40–160 ms)
Sensory receptors in inner ear
 A Large non-motile cilium-Kinocilium is at one end of hair cells
 Remaining-the stereocilia increase progressively in height
 Bending toward the tallest cilium opens cation channels (inward K+ current)—graded depolarization
 Bending Away-- graded hyperpolarization

External ear  Pinna,external auditory meatus,

tympanic membrane
Middle ear  Auditory ossicles- malleus, incus, and
stapes
 communicates with the nasopharynx by
the eustachian tube, allowing air
pressure to be equalized on both sides of
the tympanic membrane
Inner ear  comprises of the
“Outer cells are Out of the brain. Inner cells utricle,saccule,semicircular canals and
are Into the Brain” the cochlear duct

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Outer hair cells are motor efferents to amplify
signal
Inner hair cells are sensory afferents that
actually pick up the sound
Auditory transduction
 Endolymph-fluid inside he vestibular
labyrinth.Rich in K+
 Perilymph- fluid outside the vestibular
labyrinth.Rich in Na+
 organ of Corti- located in the basilar
membrane and contains inner and outer
hair cells
 Prestin-motor protein of outer hair cells.
 Spiral ganglion- contains cell bodies of
the auditory nerve whose pe-ripheral
axons innervate hair cells on the organ
of Corti
 High-frequency sound waves cause
maximum displacement of the basilar
membrane and stimulation of hair cells
at the base of the cochlea
 Low-frequency sound waves maximally
stimulate hair cells at the apex of the
cochlea
 E-Eighth nerve
 C-cochlear nuclei
 O-olivary complex
 L-lateral lemniscus
 I-Inferior colliculi
 M-medial geniculate body
 A-auditory cortex
– Auditory cortex -located on the superior
temporal gyrus of the temporal lobe
– Planum temporal-located between
Heschl’s gyrus (transverse temporal
gyrus) and the sylvian fissure.This area is
larger in the left than in the right.
involved in language-related auditory
processing

MCQ
Regarding central auditory pathways false statement is
A. Auditory cortex is located on the superior temporal gyrus of the temporal lobe
B. low tones are represented anterolaterally and high tones posteromedially in auditory cortex
C. Musicians have larger planum temporale and cerebellum in the right hemisphere
D. Sound localization is markedly disrupted by lesions of the auditory cortex
Ans-C
Which of the following molecules moves from the endolymph into the stereocilia and depolarizes
the hair cell?
A. Calcium ions
B. Sodium ions
C. Hydrogen ions
D. Potassium ions
Ans-D
Which brainstem structure plays a major role in determining the direction from which a
sound originates?
A. Cochlear nucleus

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 B. Inferior colliculus
C. Lateral lemniscus
D. Superior olivary nucleus
Ans-D

MCQ
The most common mutation leading to congenital hearing loss is that of the protein
A. connexin 26
B. α-tectin
C. myosin-VIIa
D. barttin
Ans-A
Congenital hearing loss:
 Most common cause-mutation in connexin 26
 Mutations in three nonmuscle myosins myosin-VIIa, myosin-Ib, myosin-VI
 α-tectin
 K +channel proteins, KVLQT1-mutated in long QT syndrome
 Pendred syndrome-goitre and deafness
 Barttin-Bartter’s syndrome. Renal manifestations and deafness

Olfaction:
MCQ
Regarding olfactory epithelium, false statement is
A. Each olfactory sensory neuron has a dendrite with 6-12 unmyelinated cilia
B. New olfactory sensory neurons are generated by basal stem cells
C. Bowman glands secrete mucus where Odorant molecules dissolve
D. Free endings of many CN VII pain fibers are found in the olfactory epithelium
Ans-D
Olfactory receptor cells belong to which of the following groups of cells?
A. Bipolar neurons
B. Fibroblasts
C. Modified epithelial cells
D. Multipolar neurons
Ans-A

Characteristics of olfactory bulb are all except

A. mitral cells and tufted cells are the excitatory cells
B. periglomerular cells and granule cells are the inhibitory cells
C. form anatomically discrete synaptic units called olfactory glomeruli
D. Granule cells releases glutamate as neurotransmitter
Ans-D
Central areas concerned with olfaction are all except
A. Anterior olfactory nucleus
B. Olfactory tubercle
C. Anterior cingulate cortex
D. Piriform cortex
E. Amygdala
F. Entorhinal cortex
G. Orbit frontal cortex
Ans-C

Smell:
Olfactory comprises of
epithelium 1. bipolar olfactory sensory neurons
2. supporting (sustentacular) cells
3. basal stem cells
4. Bowman glands(mucus secreting)
5. odorant-binding proteins (OBP): concentrate the odorants and transfer them to the
receptors, sequester odorants-for clearance

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Olfactory contains 6–12 cilia
sensory contains odorant receptors
neuron
Olfactory bulb Contains excitatory neurons: mitral and tufted cells(glutamate)
Inhibitory neurons(periglomerular cellsand granule cells(GABA)
anatomically discrete synaptic units called as Olfactory glomeruli
Olfactory anterior olfactory nucleus, olfactory tubercle, piriform cortex,amygdala(for emotional
cortex response), entorhinal cortex(for olfactory memory)
cortical representation of olfaction is asymmetric(greater on right)

Taste:
MCQ
Taste buds are absent in
A. Fungiform papillae
B. Filiform papillae
C. Foliate papillae
D. Circumvallate papillae
Ans-B
Which of the following substances will elicit the sensation of bitter taste?
A. Aldehydes
B. Alkaloids
C. Amino acids
D. Hydrogen ions
Ans-B
Which of the following taste sensations is the most sensitive (i.e., has the lowest stimulation
threshold)?
A. Acid
B. Bitter
C. Salty
D. Sour
Ans-B
Which of the following substances is responsible for the umami taste sensation?
A. Acetic acid
B. Potassium tartrate
C. Fructose
D. Glutamate
Ans-D

Taste:
Taste Buds Contains 4 types of cells:
1. basal cells
2. dark cells(type I)
3. light cells(type II)
4. intermediate cells(type III)
has between 50 and 100 taste cells
receptors couple to the heterotrimeric G protein, gustducin
fungiform papillae- most numerous near the tip of the tongue
circumvallate papillae- arranged in a V on the back of the tongue
foliate papillae-Back of tongue
Taste 1. Sweet- T1R3 family of GPCR
modalities 2. Salt-ENac Channels
3. Sour-Enac channels, HCN, a hyperpolarization-activated cyclic nucleotide-gated cation
channel
4. Bitter- T2R family

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 5. Umami- mGluR4
Taste Anterior 2/3rd of tongue-chorda tympanic branch of facial nerve
pathways Posterior third-Glossopharyngeal nerve
Pharynx-Vagus nerve
unite in the gustatory portion of the nucleus of the tractus solitarius (NTS)
Thalamus→anterior insula and the frontal operculum in the ipsilateral cerebral cortex

Motor Physiology:
Regarding structure of muscle spindles false statement is
A. each muscle spindle contains 2 or 3 nuclear bag fibers and 5 nuclear chain fibers
B. intrafusal muscle fibers has contractile polar ends and a noncontractile center
C. There are two subtypes of nuclear bag fibers, dynamic and static
D. Intrafusal fibers contributes to the overall contractile force of the muscle
Ans-D

Regarding innervation of muscle spindles false statement is

A. The Ia afferent fiber innervates dynamic, static nuclear bag fibers and nuclear chain fibers
B. Group II sensory fibers don't innervate dynamic nuclear bag fibers
C. γ-motor neurons constitute about 30% of the fibers in the ventral roots
D. Activation of dynamic γ-motor neurons decreases the dynamic sensitivity of the group Iaendings
Ans-D

Inverse stretch reflex is mediated by

A. Muscle spindles
B. Golgi tendon organs
C. Renshaw cells
D. Deiter cells
Ans-B
Muscle Intrafusal muscle fibers-pure sensory function
spindles Extra fusal fibres-the regular contractile units of the muscle
Two types of intrafusal fibers- nuclear bag fiber (dynamic and static) and nuclear
chain fiber
Sensory A single primary (group Ia) ending and up to eight secondary (group II) endings
endings in dynamic response- Ia afferents are very sensitive to the velocity of the change in
spindle muscle length during a stretch
static response- activity of group Ia and II afferents provide information on
steadystate length of the muscle
Motor nerve γ-motor neurons (constitute about 30% of the fibers
supply two types of γ-motor neurons: dynamicsupplies the dynamic nuclear bag fibers and
static- supply the static nuclear bagfibers and the nuclear chain fibers
Activation of dynamic -motor neurons increases the dynamic sensitivity of the group
Ia endings
Activation of the static -motor neurons increases the tonic level of activity in both
group Ia and II endings, decreases the dynamic sensitivity of group Ia afferents, and can
prevent silencing of Ia afferents during muscle stretch

Inverse stretch reflex

Receptor- Golgi tendon organ(netlike collection of knobby nerve end-ings among the fascicles of a
tendon)
3–25 muscle fibers per tendon organ
Regulates muscle force(or tension)

MCQ
The earliest reflex to recover following spinal shock is

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A. Inverse stretch reflex
B. Withdrawl reflex
C. Mass reflex
D. Lengthening reaction
Ans-B

Spinal shock:
 in humans it usually lasts for a minimum of 2 weeks
 Withdrawl reflex and knee jerk appears first
 Mass reflex-associated with defecation, urination elicited by stroking thigh in spinal shockpatients
 Can produce walking movements. Spinal centers- locomotor pattern generators in cervical &lumbar
regions and mesencephalic locomotor region in midbrain
Postural reflexes

REFLEX STIMULUS RECEPTOR CENTRE

Stretch reflex Stretch Muscle spindle Spinal cord,

medulla

Positive supporting Contact with palm or sole Proprioceptors in Spinal cord

reaction extensors

Negative supporting Stretch Proprioceptors in Spinal cord

reacting extensors

Tonic labyrinthine Gravity Otolith organs Medulla

reflex

Tonic neck reflex Head turned to Neck proprioceptors Medulla

side/up/down

Labyrinthine righting Gravity Otolitth organs Midbrain

reflex

Neck righting reflex Stretch of neck muscles Muscle spindle Midbrain

Body on head Pressure on side of body Exteroceptors Midbrain

righting reflex

Body on body Pressure on side of body Exteroceptors Midbrain

righting reflex

Optical righting Visual cues Eyes Cortex

reflex

Vestibular Placing Linear acceleration Receptors in utricle and Cortex

reactions saccule

Visual placing Visual cues Eyes Cortex

reactions
Hopping reactions Lateral displacement Muscle spindle Cerebral

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 while standing cortex

Cerebellum
MCQ
Golgi cells of cerebellum-true are A/E
A. They are inhibitory
B. GABAergic interneurons
C. Their somata are located in the granular layer
D. Golgi cell dendritic trees are flattened
Ans-D
Cerebellum:
Structure weighs only 10% as much as the cerebral cortex, but its surface area is about 75% of
that of the cerebral cortex
superior cerebellar peduncle-fibersfrom deep cerebellar nuclei--project to thebrain
stem, red nucleus, and thalamus
middle cerebellar peduncle-afferent fibersfrom the contralateral pontine nuclei
inferior cerebellar peduncle-afferent fibersfrom the brain stem and spinal cord
andefferent fibers to the vestibular nuclei
Organisation comprises of cerebellar cortex and deep nuclei
four deep nuclei: Dendate,Globose,Emdoliform,Fatigial(Mn.DEFG)
Divisions of Anatomical division
cerebellum 1.Flocculo-nodular lobe
2.Anterior lobe
3.Posterior lobe
Phylogenetic division
1.Archicerebellum
2.Paleocerebellum
3.Neocerebellum
Functional division
1.Vestibulocerebellum
2.Spinocerebellum
3.Cerebrocerebellum (Neocerebellum)
Histology Layers
– External molecular layer
– Middle Purkinje cell layer
– Internal granule cell layer
Cell types(Mn.SPB-G2)
– Purkinje cell
– Granule cell
– Basket cell
– Stellate cell
– Golgi cell
Input to the Climbing fibres:
cerebellar – arise from the region of inferior olivary nucleus in medulla.
cortex – They make synaptic connections with Purkinje cells.
– Climbing fibres produce high frequency bursts or complex spikes.
– They play a major role in motor learning.
– Carry proprioceptive impulses from all over the body
Mossy fibres:
– Arise from different centres in brainstem and spinal cord.
– They make synaptic connection with Purkinje cells.
– They produce simple spikes.
– They also synapse with granule cells.
– Axons of granule cells bifurcate. They excite the Purkinje cells through parallel fibres.

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 – Carry proprioceptive input from all parts of the body and cerebral cortex
Output from Output of the cerebellar cortex is from
cerebellar Purkinje cells. These outputs are always
cortex inhibitory.
The output projects to deeper cerebellar
nuclei and vestibular nucleus.
The inhibitory inputs influence the output
from the cerebellum to regulate range,
direction and rate of movement.
Gamma aminobutyric acid (GABA) is the
neurotransmitter
Functions Vestibulo cerebellum (Archi cerebellum)
•It is concerned with maintenance of balance and equilibrium.
•It is responsible for regulating the stability of head and body in space.
•It adjusts the tone of the trunk muscle.
•Controls the ocular movements and other postural reflexes.
Spino cerebellum (Paleocerebellum)
•Maintains the posture and helps in execution of gross movements.
•It controls the interplay between theagonist and antagonist group of muscles
•It is essential for the control of rapidmuscular activities like running and talking
Cerebro cerebellum (Neocerebellum)
•Controls fine, highly precise andcoordinated movements.
•It is involved in programming of voluntaryand skilled movements.
•It plays a major role in the timing of themotor activities and rapid progression fromone
movement to the next
Effects of – Ataxia
cerebellar – Hypotonia or atonia
lesions – Dysmetria
– Dysdiadokokinesia
– Decomposition of movement
– Staccato speech or slurring speech.
– Pendular knee jerk
– Intention tremors
– Nystagmus

Basal Ganglia:
MCQ
Major function of basal ganglia in motor control is
A. Execution of the movement
B. Generates idea for movement
C. Planning and programming
D. None of the above
Ans-C
Brain areas Motor function
Primary motor cortex Execution
(precentral gyrus)
Cortical association areas Idea generation
Basal ganglia & lateral Planning & programming
cerebellum
Premotor area Proximal limb muscle control
Supplementary motor area Bimanual coordination
Area for LAUGHTER
Posterior parietal(sensory) eating with a knife and fork

Primary motor cortex  In precentral gyrus of the frontal lobe

 Cortical representation of body parts-
motor homunculus

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  executes the movements
 representation of each body part is
proportional in size to the skill with
which the part is used in fine, voluntary
movement
 The areas involved in speech and hand
movements are especially large
Supplementary motor area  In superior bank of the cingulate sulcus
 projects to the primary motor cortex
 involved primarily in organizing or
planning motor sequences
Premotor cortex  located anterior to the precentral gyrus
 receives input from sensory regions of
the parietal cortex and projects to M1,
the spinal cord, and the brain stem
reticular formation
 concerned with setting posture at the
start of a planned movement and with
getting the individual prepared to move
 involved in control of proximal limb
muscles needed to orient the body for
movement

MCQ
Medium spiny neurons in basal ganglia employs which neurotransmitter?
A. Glutamate
B. Acetylcholine
C. Dopamine
D. GABA
Ans-D
Basal ganglia subparts Neurotransmitter
Medium spiny neurons GABA
Large aspiny Acetylcholine
Medium aspiny Somatostatin
Small aspiny GABA
Nigrostriatum Dopamine
D1-excitatory,D2-inhibitory
Striatum to globus pallidus GABA
Within striatum Acetylcholine

MCQ
Following are true regarding parkinsonism except
A. first disease identified as being due to a deficiency in a specific neurotransmitter
B. degeneration of dopaminergic neurons in the substantia nigra pars reticulata
C. can be produced in rapid and dramatic form by injection of 1-methyl-4-phenyl-1,2,5, 6
tetrahydropyridine (MPTP)
D. Recent treatment modalities include fetal striatal tissue transplant, adrenal medullary tissue
orcarotid body transplant
Ans-B
Basal Ganglia:

Structure Deep telecephalic nuclei (noncortical gray

matter):
(iii) Caudate and putamen = “

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 striatum”
(iv) Globus pallidus
Associated nuclei:
(iii) Diencephalon: ventral
anterior thalamic nucleus,
ventral lateral, thalamic nuc,
central median nuc,
subthalamic nuc
(iv) Mesencephalon: substantia
nigra
Connections Caudate and putamen
– Caudate= projections mostly from
prefrontal, temporal, parietal assoc
areas
– Putamen= from motor, somatosensory
cortices
– Inhibitory to Globus pallidus (GABAergic)
Globus pallidus
– External segment (GPe)- inhibitory
(GABA) to subthalamic nucleus
– Interanal segment (GPi)- inhibitory
(GABA) to VL/VA, CM of thalamus
(balances excitatory input from dentate
nucleus to cerebellum)
Subthalamic nucleus
– (i) Excitatory to internal globus pallidus
(GPi) ( inhibits thalamus cortex)
– Receives strong excitatory projection
from motor cx (net inhibition of cortex)
Substantia nigra pars compacta- Dopaminergic
efferents to caudate/putamen
– D1 = excitatory, D2 =inhibitory
– Projects to pallidum
Pathways Direct pathway:
 Net excitatory effect on cortex
Indirect pathway:
 Net inhibitory effect on cortex

Applied aspects Damage to basal ganglia — classical symptoms:

– Increased motor tone — rigidity
– Dyskinesias-tremors, other involuntary
movement
– Bradykinesia/Akinesia-slowing/ almost
absent voluntary movement
Hemiballismus
– Damage to subthalamic nucleus or its
connections to GPi (unilateral)
– Involuntary, irregular flinging of
contralateral extremity (usually upper)
Huntington’s disease

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 – Early degeneration of the striatum
– Involuntary movements “choreiform”-
writhing
Parkinson’s disease
– Damage to SNpc (depletion of DA in
striatum)
– Rigidity and tremor, brady/akinesia
– Reflects disruption of cortical-basal
ganglia-cortical loop:
1. Direct pathway: loss of DA1 decrease
inhibition of GPi ...less net
excitation of cortex
2. Indirect pathway: loss of DA2 more
inhibition less net excitation of cortex
3. Result is akinesia
– Imbalance of excitatory (D1) and
inhibitory (D2) effects of pathway
treat by restoring balance:
(iv) Increasing efficacy of
dopamine release
(administer L- DOPA)
(v) lesions to block GPi/STN
activity
(vi) transplant dopaminergic
neurons

MCQ
Following are trinucleotide repeat disorders except
A. Huntington’s disease
B. Fragile X syndrome
C. Friedreich ataxia
D. Parkinsonism
E. Wilson’s disease
Ans-DE

Thalamus and Hypothalamus

MCQ
All of the thalamic nuclei release excitatory neurotransmitters except
A. Ventral posterior lateral nuclei
B. Ventral postero medial nuclei
C. Anterior nuclei
D. Thalamic reticular nuclei
Ans-D
Thalamic nuclei Function
Lateral geniculate body Vision
Medial geniculate body Hearing
Ventro posterolateral & medial Somatosensory
Ventral anterior & lateral Motor
Anterior nuclei Memory & emotions
Midline & Intralaminar Widespread,nonspecific, reticular activating system
Thalamic reticular nuclei-thalamic interneurons (GABA)

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MCQ
Satiety centre is located in
A. Lateral hypothalamic area
B. Perifornical nucleus
C. Dorsomedial nucleus of the hypothalamus
D. Ventromedial nucleus of the hypothalamus
Ans-D
Period(PER) proteins are involved in
A. Regulation of menstrual cycle
B. Regulation of cortisol secretion
C. Regulation of IGF signaling
D. Regulation of circadian rhythm
Ans-D
Functions Integrating area of hypothalamus

Increased ECF osmolarity (Thirst) Osmoreceptors-Anterior hypothalamus

Response to heat Anterior hypothalamus

Response to cold Posterior hypothalamus

Emotion Dorsal and posterior lhypothalamus
Circadian rhythm Suprachiasmatic nucleus
Gn RH secretion Arcuate nucleus
TSH (via TRH secretion) Paraventricular &neighboring nuclei
Prolactin via PRH & PIH Arcuate nucleus
Oxytocin release Paraventricular nucleus (mainly)
ADH release Supra optic nucleus (mainly)
Satiety centre Ventro medial nucleus
Feeding centre Lateral nucleus
Sexual behavior Anterior ventral hypothalamus plus, in the male, piriform cortex

Circumventricular Organs:
 Posterior pituitary
 Median eminence
 Area postrema(Angiotensin II increases BP)
 Organum vasculosum of the lamina terminalis(Osmoreceptor for vasopressin,IL-1 producesfever)
 Subfornical organ postrema(Angiotensin II increases water intake)

Cerebro Spinal Fluid & Blood Brain Barrier

MCQ
Normal CSF pressure is
A. 10-20 mm H2o
B. 20-40 mm H2o
C. 180-200 mm H2o
D. 70-180 mm H2o
Ans-D
Cerebrospinal fluid:
 volume of CSF is about 150 mL
 rate of CSF production is about 550 mL/d. Turns over about 3.7 times a day
 formed in the choroid plexuses
 absorbed through the arachnoid villi
 CSF pressure is normally 70–180 mm H2O
 Average pressure= 112 mm H2O(filtration and absorption are equal)

160
 At 68 mm H2O, absorption stops

MCQ
pH of CSF is
A. 7.12
B. 7.40
C. 7.33
D. 7.21
Ans-C

Following constituents are more in CSF than plasma except

A. Bicarbonate
B. Chloride
C. Glucose
D. Mg2+
Ans-C
Substance CSF Plasma
HCO3–(meq) 25.1 24.8
Chloride(meq) 113.0 99.0
Glucose(mg/dl) 64.0 100.0
Proteins(mg/dl) 20 6000
Cholesteroll(mg/dl) 0.2 175
pH 7.33 7.40

MCQ
Auto regulation of cerebral blood flow effective at pressures of
A. 20-50 mmHg
B. 150-190 mmHg
C. 64-140 mmHg
D. 200-250mmHg
Ans-C

Cerebral Blood Flow:

 Estimation- Kety’s method(Inhaled N2O)
 Blood flow-750 ml/min or 54 ml/100g of the tissue
 Auto regulation- effective at 65–140 mm Hg
 20% of the total body resting O2consumption(basal ganglia)
 Glucose uptake by GLUT-1
 Regulators-Metabolic rate, arterial Pco2, hypothermia (1˚C---Decreases CBF 5-7%)

MCQ
Blood brain barrier-crossed by all except
A. Water
B. Dopamine
C. Glucose
D. Choline
Ans-B
Blood Brain barrier:
 barrier in the choroid epithelium between blood and CSF
 allows Water, CO 2, and O 2, lipid-soluble free forms of steroid hormones
 P-glycoprotein-Transports drugs back into blood
 If P-glycoprotein blocked-drugs can be concentrated in blood
 The lack of a barrier helps in identifying the location of tumors
Higher Mental functions:
MCQ
In humans continuous development of neurons from the stem cells occurs in
A. Amygdala and entorhinal cortex
B. Thalamus and hypothalamus

161
C. Hippocampus and olfactory bulb
D. Cerebellum and basal ganglia
Ans-C
Postulated CNS areas for stem cells:
1. Sub ventricular zone (SVZ) of the lateral Ventricle
2. Hippocampal subgranular zone(learning and memory)
3. Olfactory bulb
4. Plasticity in pituitary gland

Functions allocated to left hemisphere are all except

A. Left hand control
B. Spoken language
C. Written language
D. Mathematical skills
Ans-A
Left Hemisphere:
 Categorical,sequential,analytical
 Language,mathematical,scientific skills
 96% of right handers and 70% of left handers-dominant
 Planum temporale larger
 Concentration of dopamine higher
 Disorders-Dyslexia,Aphasia,Dyscalculia
Right hemisphere:
 Representational
 Visuo-spatial relations
 Identification of objects form,music
 Art awareness
 Right frontal lobe thicker
 Disorders-Asterognosis,Agnosias,Dysgraphia,neglect

MCQ
Neurotransmitter released by Chandelier cells are
A. Glutamate
B. ATP
C. Somatostatin
D. GABA
Ans-D
Layers & cells of cerebral cortex:
 Six layers
 Pyramidal cells found in all except layer 1
 Chandelier cells-most powerful inhibitory cell(GABA) to pyramidal cells
 Afferents from thalamus-Layer 1v in Spiny stellate cells(Glutamate)
 General theme-COLUMNAR organization- similar response properties

Electroencephalography(EEG) & Sleep:

MCQ
Frequency of alpha waves in EEG decreased in all except
A. Hypoglycemia
B. Hypothermia
C. Reduced partial pressure of co2
D. Reduced glucocoriticoid levels
Ans-C

Highest frequency EEG wave is

A. Alpha
B. Beta
C. Delta
D. Gamma

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Ans-D
Electroencephalography(EEG) Waves:
First recorded by Hans Berger
Waves with decreasing frequency and increasing Amplitude:
Gamma,Beta,Alpha,Theta,Delta(G BAT Dance)
Alpha waves:
8-13 Hz, awake but eyes closed seen in parieto occipital region
Decreased frequency-hypothermia, hypoglycemia and increased partial pressure of co2
Drugs: alcohol, amphetamines, barbiturates,phenytoin and antipsychotics
Propofol-waves like alpha
Beta waves:
During attention, rest with eyes open seen in Parieto frontal region
Delta waves:
NREM sleep
Theta waves:
Seen in hippocampus
Gamma waves:
“bind” together diverse sensory information into a single percept and action

MCQ
Pontogeniculo-occipital (PGO) spikes are characteristic of which sleep stage
A. NREM sleep
B. REM sleep
C. Both of the above
D. None of the above
Ans-B
Sleep stages
Non Rapid Eye Movement(NREM):
Stage 1- theta rhythm(4–7 Hz)
Stage 2- sleep spindles(12–14 Hz) & K complexes
Stage 3 & 4- delta rhythm(0.5–4 Hz)
Rapid Eye Movement(REM) sleep:
Paradoxical sleep(resembles waking)
Pontogeniculo-occipital (PGO) spikes for rapid eye movement
Dreaming occurs in this stage

MCQ
Neurotransmitter promotes wakefulness in an individual are all except
A. Serotonin
B. Nor epinephrine
C. Histamine
D. GABA
Ans-D
Neurotransmitters for sleep & wakefulness:
Wakefulness areas:
midbrain reticular formation (the RAS)
posterior hypothalamus
NTs Promotes wakefulness:
1. Serotonin
2. Norepinephrine
3. Histamine
4. Orexin
Areas promote sleep:
2. preoptic neurons
3. anterior hypothalamus
4. basal forebrain
NTs Promotes sleep:
1. Acetylcholine
2. GABA

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3. Melatonin

MCQ
Regarding melatonin false statement is
A. Synthesized from serotonin
B. Enzyme responsible is N-acetyltransferase
C. Regulates sleep wake cycle
D. Norepinephrine decreases N-acetyltransferase activity
Ans-D
Melatonin receptors:
 MT 1 receptor-sleepiness
 MT 2 receptor-diurnal rhythms
 RAMELTEON-melatonin agonist at both MT 1 and MT 2 receptor. Use in jet lag & insomnia

Learning & Memory:

MCQ
Conversion of short term to long term memory occurs at
A. Cerebellum
B. Amygdala
C. Striatum
D. Hippocampus
Ans-D
Memory types and brain areas:
Explicit memory:
Medial temporal lobe
Hippocampus(CA1 neurons)
Implicit memory:
Priming-neocortex
Procedural-striatum
Conditioning:amygdala,cerebellum
Mamillary bodies:
Alcoholism related brain damage where impairment of recent memory occurs
Storage of long term memory-Neocortex
Nucleus basalis of Meynert-Acetylcholine.Selective loss in Alzhiemer’s disease
Intracortical transfer of memory-occurs in corpus callosum

MCQ
Which of the following is most likely not involved in production of Long term potentiation?
A. Nitric oxide
B. Calcium ions
C. NMDA receptors
D. Membrane hyperpolarisation
Ans-D
Long Term Potentiation(LTP)
 Well characterized in hippocampus
 Glutamate is the neurotransmitter
 Glutamate acts on AMPA and NMDA receptors and increases Calcium levels
 Nitric oxide-enhances glutamate release presynaptically
Long-term depression:
 Opposite of LTP
 Occurs in cerebellum for motor learning

MCQ
Risk factors for Alzheimer’s disease are all except
A. Presenilin 1 mutations
B. Presenilin 2 mutations
C. Amyloid precursor protein gene mutations
D. apoE alleles
E. Trisomy 18

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Ans-E
Risk factors for Alzheimer’s disease:
 Age
 Presenilin 1 mutations (chromosome 14)
 Presenilin 2 mutations (chromosome 1)
 Amyloid precursor protein gene mutations (chromosome 21)
 apoE alleles (chromosome 19)
 Trisomy 21
 α-2 macroglobulin gene

Language & Speech:

MCQ
Speech articulation area lies in
A. Broca’s area
B. Wernicke’s area
C. Insula
D. Angular gyrus
Ans-C
Speech areas
Broca’s area:
 Frontal lobe, motor speech area
 Lesion-Nonfluent aphasia
Insula:
 Speech articulation area
Wernicke’s area:
 posterior end of the superior temporal Gyrus(area 22)
 Sensory speech area
 Lesion-Nonfluent aphasia

MCQ
Prosopagnosia means
A. inability to recognize music
B. inability to recognize pain
C. inability to recognize faces
D. inability to recognize touch
Ans-C

Prosopagnosia:
inability to recognize faces
seen in Right inferior temporal lobe damage
Arithmetic calculations-Left frontal lobe
Lesions-Acalculia
Navigation skills:
right hippocampus and right caudate nucleus
Motivation & Addiction:
Ventral tegmental area and nucleus acumbens:
Reward centres
Neurotransmitter-Dopamine(D3 receptor)

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Cardiovascular Physiology
Conducting system of heart
MCQ
Slow depolarizing pre potentials are characteristic of
A. SA node
B. Atrial muscle fibres
C. Purkinje fibres
D. Bundle of His
Ans-A

Conduction velocity is maximum in

A. Purkinje fibres
B. Ventricle
C. A.V.Node
D. S.A.Node
Ans-A
In which phase of the ventricular muscle action potential is the potassium permeability the
highest?

A. 0
B. 1
C. 2
D. 3
E. 4
Ans-D
If the S-A node discharges at 0.00 seconds, when will the action potential normally arrive at the
epicardial surface at the base of the left ventricle?
A. 0.22 sec
B. 0.18 sec
C. 0.16 sec
D. 0.12 sec
Ans-A

Properties of ventricular myocyte Pacemaker potentials

 resting membrane potential is –90 mV
 Action potential phases:
5. rapid depolarization (phase 0)- rapidly
opening Na+ channels
6. rapid repolarization (phase 1)-
inactivation of Na+ channels
7. plateau (phase 2)- Ca2+ influx through
more slowly opening Ca2+ channels
8. return to the resting membrane
potential (phase 4)- net K+ efflux
 resting membrane potential fluctuates
between -60 and -40mV
 Initial part of pacemaker potential-due
to the channel activated following
hyperpolarization(h channel),also
called as “funny current”(permeable to
both Na+ and K+)
 Later part-(ICa) due to opening of T
channels completes the prepotential,
and ICa due to opening of L channels
produces the impulse
 Repolarisation-K+channels
 Th e action potentials in the SA and AV
nodes are largely due to Ca2+, with no
contribution by Na+ influx
 reduced slope of the prepotential-
after vagal stimulation via M2
muscarinic receptors which increases
the K+ conductance
 Increased spontaneous discharge- after
sympathetic stimulation.

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 Norepinephrine via β 1 receptors
resulting in the increase in intracellular
cAMP which facilitates the opening of L
channels

Funny currents
 Named because the channel activates during hyperpolarisation
 Non specific channel-allows both Na and K
 Responsible for early part of prepotential
 IVABRADINE-funny current channel blocker. Use to reduce heart rate

CONDUCTIVITY
Ability to conduct an action potential by sequential depolarization of adjacent cells.

167
Conduction velocity in cardiac tissues:
 SA node – 0.05 m/sec
 AV node – 0.05 m/sec
 Purkinje fibers – 4 m/sec
 Atrium – 1.o m/sec
 Ventricle – 1.0 m/sec
 Bundle of His – 1.0 m/sec
First of the heart to be depolarized: left endocardial surface of the inter ventricular septum

Last part of the heart to be depolarized:

 Postero basal portion of left ventricle

 Pulmonary conus

 Upper most portion of the septum

Depolarization Repolarisation

Single From endocardium to From endocardium to

ventricular epicardium epicardium
muscle fiber

Whole heart From endocardium to From epicardium to

epicardium edocardium

MCQ
Following are true regarding His Bundle ECG except
A. Useful in patients with heart block
B. Has three waves-A,H and V
C. V deflection indicated ventricular repolarisation
D. HV interval represents the conduction in Bundle of His
Ans-C

168
Waves:
 A wave-AV node
 H wave-Bundle of His
 V wave-Ventricular depolarisation
Intervals:
 PA- SA node to AV node(27 ms)
 AH- AV nodal conduction(92 ms)
 HV- Bundle of His conduction(43 ms)

Electrocardiogram (ECG):

Intervals Normal duration in secs Events in the heart

Average Range

P wave Atrial depolarization

PR interval 0.18 0.12- Atrial depolarization &

0.20 conduction through AV
node

QRS interval 0.08 0.08- Ventricular

0.10 depolarization & atrial
repolarisation

QT interval 0.40 0.40- Ventricular

0.43 depolarization &
ventricular
repolarisation

AT interval 0.32 Ventricular

repolarisation

Einthoven’s law: lead II=lead I+ lead III

Kirchoff’s law lead I + lead II+ lead III=0
Normal cardiac axis between-30 degress to +110 degress
Standard limb leads Lead I, II & III
Augmented limb leads aVR, aVL, aVF

Generalizations for leads in normal ECG:

aVR All the deflections are negative

aVL/aVF Predominantly positive or biphasic

V1, V2 No Q wave, deep S wave

V3, V4 Biphasic

169
 V5, V6 Small Q wave, Tall R wave

Lead I, II, III All positive deflection, largest in lead II

Cardiac cycle & cardiac output

MCQ
During cardiac cycle aortic valve opens at
A. Beginning of diastole
B. End of isovolumic contraction
C. End of diastole
D. End of diastasis
Ans-B
Atrial systole  Duration-0.1 s
 Follows impulse generation in the S.A.
Node
 Proples 30% of additional blood into
the ventricles
Ventricular systole  Duration-0.27 s
3. Isometric contraction: 0.05sec:
 Ventricles contract and the
pressure exceeds the arterial
pressure
 Closure of AV Valves  first heart
sound
 Bulging of AV valves into the atrium
4. Ventricular systole proper: (0.25sec)
 Rapid ejection phase: (0.1 sec)-
2/3rd of the stroke volume is
ejected, Intra ventricular pressure
rises to the maximum, AV valves
come back to original position & a
sharp fall in atrial pressure occurs
 Slow ejection phase (0.15sec)
Ventricular diastole  Duration-0.5 s
6. Proto diastole: (0.04sec): Ventricular
pressure drops more rapidly. Closure
of Semilunar valves sound heart
sound
7. Isometric relaxation: (0.08sec): Initial
part of ventricular diastole. Intra
ventricular pressure drops, ventricular
muscle continues to relax without
change in the ventricular volume
8. Ventricular diastole proper: passive
filling of ventricles (70%)
9. Initial rapid filling phase: opening of AV
Valves and continued relaxation of
ventricles
10. Slow filling phase (Diastasis):
continuous venous return filling both
atrium & ventricles

170
 Atrial Diastole  Duration-0.7 S
 Atrial muscle relaxes and the pressure
gradually increases due to venous
return

Valvular events Cardiac events ECG JVP

Opening of AV End of isometric relaxation End of T wave V-Y descent

valve phase

Closure of AV valve End of diastole Later half of R End of x

wave descent

Opening of End of isometric contraction ST segment Peak of C

semilunar Valve wave

Closure of Beginning of diastole Later half of T

semilunar valve wave

One of the following correlates with isovolumic contraction

A. AV valves open and aortic valve close
B. AV valves close and aortic valve open
C. Both valves are closed
D. Both valves are open
Ans-C

During cardiac cycle, aortic valve closes at the end of

A. isovolumetric systole
B. rapid ejection
C. diastasis
D. protodiastole
Ans-D

The maximum pressure rise in the ventricle occurs during

A. ejection
B. isovolumetric contraction
C. protodiastole
D. diastasis
Ans-B
Ventricular systole(0.27s)
 Isovolumetric ventricular contraction(0.05 s)-ends with opening of aortic valve
 Rapid ejection phase(0.1 s)-2/3rd of ejection
 Slow Ejection phase(0.25 s)
Ventricular diastole(0.53 s)
Sub Phases:
 Protodiastole (0.04 s)-ends with closure of aortic valve
 Isovolumetric relaxation (0.08 s)-Both valves closed
 Rapid filling (0.12 s)
 Diastasis (0.18 s)
 Filling due to atrial contraction (0.1 s)

171
 A 60-year-old woman has a resting heart rate of 70 beats/min, arterial pressure is 130/85 mm
Hg, and body temperature is normal. Her pressure-volume diagram of the left ventricle is
shown. Cardiac output is?

A. 2000 ml/min
B. 5000 ml/min
C. 7000 ml/min
D. 3000 ml/min
Ans-C
When does the second heart sound occur?
A. Point A
B. Point B
C. Point C
D. Point D
Ans-D
When does the 3rd heart sound occur?
A. Between A & B
B. Between B & C
C. Between C & D
D. Point D
Ans-A
Heart sounds:

First Heart Sound Sound Heart Sound Third Heart Sound Fourth Heart Sound
Due to closure of AV Due to closure of Due to vibration of the Produced by atrial
valves Semilunar valves ventricle & turbulence of systole
blood flow
Marks the onset of Marks the onset of rapid filling phase of Due to vaentricular
ventricular systole ventricular diastole ventricle filling
 Continuous  Split Sound  Low Pitched  Also called
sound  Last 0.1 to Sound atrial sound
 Lasts 0.14- 0.14sec  Lasts<0.1sec  Low-
0.17sec  Audible  Audible In pitched
 Audible better better at  -30% of normal Sound
at tricuspid Aortic and population  Audible in
&Mitral areas Pulmonary  -MI & -Heart filure  -MI
 Coincides with areas  -Cardiomyopathy  -Heart
‘R’ wave of  Coincides  -Ventricular failure
ECG with end of hypertrophy
 Dull, ‘T’ wave of
Prolonged, ECG

172
 Soft, Low, low-  Short, Sharp,
pitched sound high-pitched
(LUB) sound (DUB

What is her ejection fraction?

A. 33%
B. 50%
C. 60%
D. 66%
Ans-D
MCQ
Which of the following need to be recorded in order to determine systolic time intervals?
A. ECG, ECHO, Phonocardiogram(PCG)
B. ECG, PCG and carotid artery pulse (CAP)
C. ECHO, CAP and PCG
D. ECG, CAP and Wedge pressure
Ans-B
Total electromechanical systole (QS2) onset of the QRS complex to the closure of aortic
valves
left ventricular ejection time (LVET) beginning of the carotid pressure rise to dicrotic
notch
preejection period (PEP)-Isovolumic contraction difference between QS2 and LVET

MCQ
Cardiac index ratio is defined by
A. Stroke volume & surface area
B. Heart rate & surface area
C. Peripheral resistance
D. Cardiac output & surface area
Ans-D

Cardiac output decreases during

A. Sleep
B. Exercise
C. Pregnancy
D. Standing from lying position
Ans-D
Cardiac output changes:
No change:
 Sleep
Increases during:
 Anxiety and excitement (50–100%)
 Eating (30%)
 Exercise (up to 700%)
 High environmental temperature
 Pregnancy
 Epinephrine
Decreases during:
 Standing from lying
 Heart diseases
The output per minute per square meter of body surface (the cardiac index) averages 3.2 L
Methods to estimate cardiac output:
 Fick’s principle
 Indicator dilution method
 Thermodilution method-cold saline
 Echocardiography

173
 In which type of shock does cardiac output often increase?
A. A. Hemorrhagic shock
B. Anaphylactic shock
C. Septic shock
D. Neurogenic shock
Ans-C
Which one is false when the subject assumes standing position from supine position?
A. Central venous pressure decreases
B. Stroke volume decreases
C. Heart rate decreases
D. Peripheral resistance increases
Ans-C

MCQ
On exposure to positive G which one of the following doesn’t happen
A. Venous pooling in the lower limbs
B. Arterial pressure in the head is reduced
C. Unconsciousness occur
D. Congestion of head & neck vessels occur
Ans-D
Positive G:
• Acts in head to foot
• Venous pooling
• Cerebral pressure decreases
• Unconsciousness
• Vision-Black out
Negative G:
• Acts in foot to head
• Venous return increases
• Cerebral pressure increases
• Congestion of head & neck vessels
• Vision-red out
Blood
MCQ

174
Bone marrow stem cells serve as sources for all except
A. Osteoblasts
B. Kupffer cells
C. Mast cells
D. Dendritic cells
Ans-A
Bone marrow stem cells are the sources of:
 osteoclasts
 Kupffer cells
 mast cells
 dendritic cells
 Langerhans cells
Bone marrow-largest organ. Size and weight like liver

MCQ
Site of RBC formation in 20 year old male is
A. Flat bones
B. Long bones
C. Liver
D. Yolk sac
Ans-A
Age Site of erythropoiesis
3 weeks -3 months Yolk sac
3-5 months Liver, spleen
5-9 months Red bone marrow in long and flat bones
After birth till 20 years of age Red bone marrow in long and flat bones
>20 years Only in flat bones like ilia

MCQ
O blood group individuals have the following antigen
A. H antigen
B. A antigen
C. B antigen
D. None of the above
Ans-A
 H antigen- Present in all blood types
 A Group- Has terminal N-acetylgalactosamine
 B Group- Has terminal galactose

MCQ
Following factor plays the major role in maintaining normal levels of albumin
A. Degradation of albumin
B. Synthesis of albumin
C. Excretion of albumin
D. Reuptake of albumin
Ans-B
Plasma proteins
 Albumin, Globulin and fibrinogen
 Albumin-carrier protein, osmotic regulator
 Synthesized in liver
 Synthesis plays an important role in the maintenance of normal levels
 Synthesis-200–400 mg/kg/d
 45% of albumin is intravascular. Remaining in Skin
 Synthesis decreased during fasting and increased in nephrosis

MCQ
When compared to plasma, serum has higher content of
A. Fibrinogen

175
B. clotting factors II, V, and VIII
C. Serotonin
D. Cholesterol
Ans-C
Serum has essentially the same content of plasma except it doesn’t have
 Fibrinogen
 clotting factors II, V, and VIII
Substance high in serum:
 SEROTONIN-due to platelet breakdown

MCQ
Factor which serves both as procoagulant and anticoagulant is
A. Fibrin
B. Prothrombin
C. Thrombin
D. Plasmin
Ans-C
Thrombin
Procoagulant role of thrombin:
 Activates factors V and VIII
Anticoagulant role of thrombin:
 On binding with THROMBOMODULIN inactivates factors V and VIII
 Increases the formation of plasmin
All circulations have thrombomodulin except CEREBRAL CIRCULATION

MCQ
Which of the following is not involved in intrinsic pathway?
A. Factor 5
B. Factor 8
C. Factor 9
D. Factor 7
Ans-D
Factor 7 & 3-Extrinsic pathway

MCQ
Which factor stabilizes the clot
A. Factor 5
B. Factor 8
C. Factor 9
D. Factor 13
Ans-D
Factor 13- Fibrin stabilizing factor

MCQ
Blood normally doesn’t clot inside vessels because of
A. Vit-K antagonists in plasma
B. Thrombin antagonists in plasma
C. Sodium citrate in plasma
D. Glycocalyx in endothelium
Ans-D
Anticoagulant mechanisms:
 Smoothness of cell surface
 Glycocalyx coating repels clotting factors
 Thrombin binding with thrombomodulin-inactivates factor 5 & 8 through activated protein C& S
 Anti Thrombin III and heparin-inactivates factors 9,10,11,12
 Tissue plasminogen activators & plasmin

MCQ

176
Causes of increased interstitial fluid volume and edema are all except
A. Decreased plasma protein level
B. Increased lymph flow
C. Substance P
D. Increased venous pressure
Ans-B
Starling Forces
 Capillary hydrostatic pressure- arterial 37 mmHg,Venular-17 mmHg
 Capillary oncotic pressure-25 mm Hg(Albumin)
 Interstitial fluid hydrostatic pressure-Negative
 Interstitial fluid oncotic pressure-Negligible
Increased interstitial fluid volume
 Leads to edema
 Causes:
1. Increased venous pressure
2. Decreased albumin levels
3. Substance P, Histamine- increases capillary permeability
4. Decrease in lymph flow

MCQ
Carbonic Anhydrase is found in abundance in
A. Neutrophils
B. RBC’s
C. Platelets
D. Plasma
Ans-B
Carbonic Anhydrase
 Catalyses CO2+ H2O →←H2CO3
 Abundant inside RBCs
 Also in renal tubule cells(I cells) for acid base balance
 Carbonic anhydrase inhibitors:
1. Dorzolamide,Acetazolomide,sulfonamides
2. Useful as diuretics, high altitude illness, glaucoma

MCQ
The protein that contributes maximum for ESR is
A. Albumin
B. Thrombin
C. Fibrinogen
D. Nebulin
Ans-C
Proteins synthesised by liver:
Protein Function
Albumin Binding and carrier protein
Osmotic regulator
Ceruloplasmin Copper(6 atoms/molecule)
Fibrinogen Precursor to fibrin,ESR
Haptoglobin 1:1 binding with heme
Hemoglobin 1:1 binding with heme
Transferrin Two atoms iron/molecule
Hormone binding globulins For steroids,thyroxine
Transthyretin For thyroid hormones

MCQ
The Principal source of serotonin is
A. Basophils
B. Mast cells
C. Platelets

177
D. Macrophages
Ans-C

Coronary circulation
MCQ
Oxygen utilization by ventricular muscles at rest is
A. 10ml/100g/min
B. 100ml/10g/min
C. 10ml/10g/min
D. 10ml/10g/10min
Ans-A
Overall(ml/min)
Blood flow O2 consumption
Liver>Kidney>Skeletal muscle>Brain>skin>heart Liver>Skeletal muscle>Brain>heart

Per unit mass(ml/100g/min)

Blood flow O2 consumption
Kidney> heart> Liver Heart>kidney>brain

MCQ
Most important metabolic factor affecting coronary blood flow is
A. Hyperkalemia
B. Hypercapnia
C. Acidosis
D. Hypoxia
Ans-D

MCQ
Reflex nor adrenergic discharge during fall in blood pressure causes vasodilatation in
A. Splanchnic vessels
B. Renal circulation
C. Coronary vessels
D. Cutaneous vessels
Ans-C
Characteristic features of coronary circulation
 has a very high basal oxygen consumption (8-10 ml O2/min/100g)
 the highest A-V O2 difference of a major organ (10-13 ml/100 ml)
 Normal Coronary blood flow : 60-80ml/100gm/min or 250 ml/min viz, 5% of resting cardiac output
 The peak left coronary flow occurs at the end of isovolumetric relaxation(Diastole)
Autoregulation
 It is the capacity of the tissue to regulate their blood flow – intrinsic basal myogenic tone
 Local Metabolism is the primary controller of coronary flow O2 demand is a major factor
 This mechanism works well even when the nerves are removed
Chemical regulation of CBF
A. Fall in arterial PO2 causes release of vasodilator substances (METABOLIC HYPERAEMIA)
 Adenosine (ATP AMP Adenosine)
 K+ , H+, CO2, bradykinin, Prostaglandin
B. Nitric oxide is also an important regulator of CBF
 continuously produced by the endothelium
 help - maintain basal flow
Neural:
Sympathetic Parasympathetic
Direct Depend on the receptor slight effect – mild vasodilatation
•α – constriction (epicardial vessels)
•β – dilatation (intramuscular vessels)
Indirect ↑ HR, Contractility, metabolic rate Slows HR, ↓ Contractility
↓ ↓
↑ Cardiac O2 ↓Cardiac O2 consumption

178
 consumption ↓
↓ Constrict - coronary artery
Dilate - coronary artery
Arteries,arterioles,capillaries & veins
MCQ
Maximum peripheral vascular resistance is in
A. Aorta
B. Arterioles
C. Veins
D. Capillaries
Ans-B

MCQ
The amount of blood in capillaries
A. 1%
B. 5%
C. 10%
D. 20%
Ans-B

MCQ
Arterioles differ from capillaries by
A. Arterioles are thick walled
B. Arterioles are innervated
C. Arterioles have larger lumen
D. All of the above
Ans-D
Characteristics of various types of blood vessels
Vessel Cross sectional area(m2) % of blood contained
Aorta 4.5 2
Artery 20 8
Arteriole 400 1
Capillary 4500 5
Venule 4000
Vein 40 54
Vena cava 18

Arteries & 1. Windkessel Vessel Eg. Aorta & its main branches
Arterioles 2. Arterioles (stop cocks of circulation):
•seat of maximum peripheral resistance
•Lacks elastic fibres
•Rich in smooth muscle
Veins •Thin walled
•Large than largest arteries
•Capacitance Vessels (hold maximum blood)

Capillaries
 Small vessels guarded by Precapillary Sphincter
 Modified smooth muscles (Pericytes) are present
 Has Single layer of endothelium
Types:
 Continuous --Seen in heart, lung, brain & skeletal muscle
 Fenestrated --Seen in the endocrinal glands and renal glomeruli
 Discontinuous (Sinusoids) --Seen in red bone marrow & liver,Highly permeable

Maximum diameter Vena cava

Maximum thickness Aorta
Maximum cross sectional area capillaries

179
 Maximum blood flow velocity Aorta
Minimum blood flow velocity Capillaries
Shunt vessels AV anastomosis(Temperature regulation)
Maximum blood pressure aorta
Minimum blood pressure Vena cava
Site of gas exchange capillaries

Lymphatic System
MCQ
Lymph is essentially a
A. Interstitial fluid
B. Tissue fluid
C. Plasma enriched with nutrients
D. Plasma minus fibrinogen
Ans-B
 Major functions of Lymph:
1. Returns proteins to circulation
2. Absorption- long chain fatty acids,Cholesterol
Protein content of lymph in humans:
Source of Lymph Protein Content (g/dL)
Choroid plexus 0
Ciliary body 0
Skeletal muscle 2
Skin 2
Lung 4
Gastrointestinal tract 4.1
Heart 4.4
Liver 6.2 (Max)

Regulation of cardiovascular system

MCQ
All of the following agents are vasodilators except
A. Nitric oxide
B. Increased local temperature
C. Urotensin II
D. Histamine
Ans-C
Vasoconstrictors Vasodilators
Decrease local temperature Increase local temperature
Endothelin Nitric oxide, Carbon Monoxide
Nor epinephrine Prostacyclin
Angiotensin II Histamine
Thromboxane A2 CGRP
Vasopressin ANP
Urotensin II Substance P
Epinephrine--Vasodilator in skeletal muscles & liver

MCQ
When noradrenergic and cholinergic systems to heart are blocked, heart rate would be
A. 175 beats/min
B. 70 beats/min
C. 100 beats/min
D. 120 beats/min
Ans-C
 Resting vagal tone- 70 beats/min
 After atropine block- 150-180/min
 When noradrenergic and cholinergic blocked:100/min

180
MCQ
Profound bradycardia, hypotension, and apnea followed by rapid shallow breathing is
A. Bainbridge mass reflex
B. Bezold Jarish reflex
C. Cushing’s reflex
D. None of the above
Ans-B
Bezold Jarish reflex:
 Elicited by a variety of substances like capsaicin, serotonin, phenylbiguanide,veratridine
 Protective reflex-against toxic chemicals and pollutants
 Responsible for hypotension in heart diseases

MCQ
All are known functions of nitric oxide except
A. Vasodilation
B. Vascular remodeling
C. Penile erection
D. Decrease glutamate release
Ans-D
Functions of Nitric oxide:
 Vasodilation
 Penile erection
 Vascular remodeling
 Gaseous transmitter: increase glutamate release

MCQ
Increase in blood flow in salivary glands and exocrine pancreas are due to
A. Histamine
B. Serotonin
C. Nor epinephrine
D. Bradykinin
Ans-D
Actions of Bradykinin:
 Produces pain
 Increases blood flow in salivary glands
 Vasodilation
 Increases capillary permeability

MCQ
Increased baroreceptor discharge
A. Inhibits nucleus ambiguous
B. Inhibits nucleus tractus solitaries
C. Inhibits RVLM
D. Inhibits CVLM
Ans-C
Baroreceptors carotid sinus & Aortic arch receptor(Buffer Nerves)
(carotidSinuS: measures Afferent from carotid sinus-
pressure carotid bO2dy Glossopharyngeal nerve
measures O2)
Afferent from Aortic arch-Vagus
Increased blood pressure → buffer nerves
nucleus tractus solitaries
Tract 1: NTS→ excitatory
glutaminergic neurons → caudal &
intermediate ventrolateral medulla
→stimulate GABA ergic neurons →
rostal ventro lateral medulla (RVLM), the VMC→ inhibition of VMC→
decreased sympathetic activity

181
 Tract 2: NTS→ dorsal motor nucleus & Nucleus ambiguous → vagal
neurons
Baroreflex:
Increased BP→ Stimulation of baro receptors →vagal stimulation +
inhibition of VMC (↓sympathetic activity) →Vasodilatation, ven dilatation,
↓BP, bradycardia, ↓cardiac output

MCQ
C Wave in JVP is due to
A. Atrial contraction
B. Closure of tricuspid valve
C. Isometric contraction
D. Ventricular filling
Ans-C
WAVES IN JVP
A wave Atrial systole
C wave Bulging of tricuspid valve into the right atrium during isovolumic ventricular
Contraction
V wave Filling of the right atrium by Venous return
X decent Atrial relaXation and downward displacement of closed tricuspid valve during
ventricular contraction
Y descent Blood flow from RA to RV

182
Endocrine Physiology
The term endocrine was coined by Starling

The term hormone, derived from a Greek phrase meaning "to set in motion"

Hormones & second messenger systems

Five major classes of hormones
1. Amino acid derivatives---dopamine, catecholamine
2. Small neuropeptides ---GnRH,TRH
3. Large proteins---insulin,PTH,renin
4. Steroid hormones ---Cortisol,estrogen
5. Vitamin derivatives---Vit-A,Vit-D
Receptors for hormones
Membrane Receptors
1) Seven transmembrane GPCRs
2) Tyrosine kinase receptors,
3) Cytokine receptors
4) Serine kinase receptors
Nuclear Receptors
G proteins(activated after binding GTP):
1. Small G proteins
 Rab-vesicle traffic
 Rho/Rac -cytoskeleton and cell membrane
 Ras-regulates growth
2. Large heterotrimeric G proteins
Exchange of GTP for GDP, a and bg dissociate
a subunit- has inherent GTPase activity
- G proteins--Rodbell,Gilman(1994) awarded noble prize for its characterization
GPCR-Kobilka,Lefkowitz(2012) awarded noble prize in Chemistry
- Binding of ligand to G-protein coupled receptor facilitates exchange of GTP for GDP, a and by
dissociate

Gs  couples to Adenylate Cyclase

Examples:  stimulates AC activity
 b-adrenergic receptor  increases cAMP
 ACTH receptor  activates Protein Kinase A
 FSH receptor
Gi  couples to Adenylate Cyclase
 a2-adrenergic receptor  inhibits AC activity
 M2 muscarinic receptor  decreases cAMP
 inhibits Protein Kinase A

Gq
 a1-adrenergic receptor
 M1, M3 muscarinic receptors
 Angiotensin receptor
 couples to Phospholipase C
 increases diacylgyclerol (DAG)
 increases IP3
 increases intracellular Ca2+
 activates Protein Kinase C

Gt-G protein coupled receptor in rods and cones(TRANSDUCIN)

Clinical relevance: bacterial toxins

Cholera toxin interacts with Gs stimulates
Pertussis toxin interacts with Gi inhibits
Both toxins cause excess production of cAMP

183
MCQ
Hormone synthesized as peptide precursor is/are
a) Insulin
b) PTH
c) Renin
d) thyroid hormone
e) Angiotensin II

ANS: abce
Which is not a peptide hormone?
a) a) Somatostatin
b) Serotonin
c) Neuropeptide Y
d) Enkephalin
ANS: b
Not a glycoprotein
A. FSH
B. LH
C. TSH
D. GH
ANS: D

All of the following mediate their action through cAMP except

a) Corticotropin
b) Dopamine
c) Glucagon
d) Oxytocin

ANS: D

cAMP acts through

a) Activation of protein kinase
b) Activation of adenylate cyclase
c) Increased Ca release
d) PIP3 pathway

ANS: a

Cholera toxin
a) Increase the intracellular levels of cyclic GMP
b) Acts through the receptor for opiates
c) Causes continued activation of adenylate cyclase
d) Inhibits the enzyme phosphodiesterase

ANS: C

Action of alpha sub unit of G-protein is

a) Breakdown of GTP to GDP
b) Conversion of GDP to GTP
c) Internalization of receptors
d) Binding of agonist

ANS: A

If there is a Gs alpha subunit gain-of-function mutation, it results in

a) Decreased c-AMP
b) Decreased IP3
c) Increased GTPase activity

184
d) Increased c-AMP

ANS: D

Adrenaline,nor-adrenaline and dopamine acts through

a) Single pass receptors
b) Four pass receptors
c) Seven pass receptors
d) Ligand gated channel

ANS: C
True about second messengers
a) a) Binds first messenger
b) Integral proteins
c) Intracellular receptors
d) Increase or decrease function

ANS: D

Hormones That Use the Adenylyl Cyclase–cAMP Second Messenger System (Mn-FLAGSHiP-CCTV2-
CASh)
 Adrenocorticotropic hormone (ACTH)
 Angiotensin II (epithelial cells)
 Calcitonin
 Catecholamines (b receptors)
 Corticotropin-releasing hormone (CRH)
 Follicle-stimulating hormone (FSH)
 Glucagon
 Human chorionic gonadotropin (HCG)
 Luteinizing hormone (LH)
 Parathyroid hormone (PTH)
 Secretin
 Somatostatin
 Thyroid-stimulating hormone (TSH)
 Vasopressin (V2 receptor, epithelial cells)

MCQ
cGMP is second messenger for which hormone?
a) Somatostatin
b) Atrial natriuretic factor
c) Angiotensin II
d) ADH
e) Nitric oxide

ANS: b, e

Regarding nitric oxide false is

a) Derived from endothelium
b) Acts by increasing c AMP levels
c) Vasodilator
d) Derived from arginine

ANS: B

ANF is mediated by
a) Inositol phosphate
b) DAG

185
c) cAMP
d) cGMP

ANS: D

TRUE about intracellular receptors

a) Mainly on nuclear surface
b) Steroids act on them
c) Estrogen does not act on it
d) GH act on it

ANS: A, B
Hormones That Use the Phospholipase C Second Messenger System(V1 GOT AC)
 Angiotensin II (vascular smooth muscle)
 Catecholamines (a receptors)
 Gonadotropin-releasing hormone (GnRH)
 Growth hormone–releasing hormone (GHRH)
 Oxytocin
 Thyroid-releasing hormone (TRH)
 Vasopressin (V1 receptor, vascular smooth muscle)
Guanylate Cyclase Receptors(Mn.NAG)
Transmembrane Guanylate activated by peptide hormones(Atrial natriuretic peptide/factor ANP)
Cyclase Receptor
Soluble Guanylate Cyclase activated by Nitric Oxide (NO)
Receptor

Nuclear Receptors

Receptors for
 Glucocorticoids
 Mineralocorticoids
 Androgen
 Estrogen
 Progestin
 Thyroid hormones
 Vitamin D

Which set of hormones have nuclear receptor

a) Estrogen,thyroxine,glucagon
b) Estrogen,thyroxine,TSH
c) Estrogen,TSH,GnRH
d) Retinoic acid,thyroxine,leutinizing hormone
e) Testosterone,cortisol,estrogen

ANS: e

C-terminal end of the androgen receptor is concerned with

a) Ligand binding
b) Increasing biological half life
c) Increasing the affinity of receptor to DNA
d) Increasing the level of transcription

186
ANS: A
Aldosterone receptors are present in all except
a) Liver
b) Colon
c) Hippocampus
d) Distal nephron

ANS: A
TRUE about intracellular receptors
a) Mainly on nuclear surface
b) Steroids act on them
c) Estrogen does not act on it
d) GH act on it

ANS: A, B
Pituitary gland,Growth hormone & Prolactin
MCQ
Basophilic cells of pituitary secretes
a) Prolactin
b) GH
c) TSH
d) ACTH
e) LH

ANS: C, D, E

ACTH level is highest during

a) Early morning
b) Afternoon
c) Evening
d) night

ANS: A

Somatomedin mediates
a) Deposition of chondroitin sulfate
b) Lipolysis
c) Gluconeogenesis
d) Decreased rate of glucose uptake by cells

ANS: A

Secretion of prolactin is affected by

a) GnRH analogue
b) Dopamine
c) Serotonin
d) FSH

ANS: B

A/E are caused by accidental transection of pituitary stalk

a) Diabetes mellitus
b) Polyuria
c) Galactorrhea
d) Diabetes inspidus

ANS: A
Pituitary Gland

187
 The pituitary gland weighs approx.600 mg
 Contains Pituicytes-modified astrocytes
 Folliculostellate cells- release paracrine factors
 pluripotent stem cells-responsible for Plasticity in pituitary
 Cell types-
Somatotrope(GH),Lactotrope(prolactin),Corticotroph(ACTH),Thyrotroph(TSH),Gonadotrophs(FSH,L
H)
 Maximum percentage of secretory cells-Somatotrope
 Minimum percentage of secretory cells-Thyrotroph
 Acidophilic cells-Prolactin,Growth hormone(Mn.Parle-G)

Human Growth Hormone:

1. Present in long arm of human chromosome 17
2. Half life is 6-20 min
3. Daily growth hormone output-0.5 – 1 mg/day
4. 50% bound to protein—provides reservoir
5. Receptor--cytokine receptor superfamily
6. Acts through JAK2-STAT pathway
7. Ghrelin-marked growth hormone-stimulating activity

Factors That Stimulate or Inhibit Secretion of Growth Hormone:

Stimulate Growth Hormone Inhibit Inhibit Growth Hormone Secretion
Growth Hormone Secretion
 Decreased blood glucose  Increased blood glucose
 Decreased blood free fatty  Increased blood free fatty
acids  acids
 Starvation or fasting, protein  Obesity
deficiency  Aging
 Trauma, stress, excitement  Growth hormone inhibitory hormone (somatostatin)
 Exercise  Growth hormone (exogenous)
 Testosterone, estrogen  Somatomedins (insulin-like growth factors)
 Deep sleep ( stages II and IV)
 Growth hormone–releasing
hormone
 Ghrelin

Effects of Growth hormone

Effect on growth  Epiphyses not yet closed---

Chondrogenesis is
accelerated,Cartilaginous epiphysial
plates widen,lay down more bone matrix
 Epiphyses closed---linear growth is no
longer possible

Effects on protein Metabolism  protein anabolic hormone

 positive nitrogen and phosphorus
balance
 fall in blood urea nitrogen
Effect on electrolytes  GI absorption of Ca2+ increased
 Na+ and K+ excretion is reduced
 excretion of the amino acid 4-
hydroxyproline is increased
Effect on carbohydrate metabolism  Anti insulin effect in muscles
 Diabetogenic-increase hepatic glucose

188
 output
Effect on Fat metabolism  ketogenic
 increases circulating free fatty acid (FFA)
 provides a ready source of energy during
hypoglycemia

Somatomedins:

 Somatomedin C-otherwise known as IGF-1

 IGF-2-otherwise known as Multiplication stimulating activity
 IGF-1:Mediates the insulin like activity,antilypolytic activity,protein synthesis,epiphyseal
growth actions of growth hormone

Growth hormone disorders:

In children Gigantism
In adults Acromegaly:
 greatly enlarged hands and feet
 vertebral changes attributable to
osteoarthritis
 soft tissue swelling, hirsutism
 protrusion of the brow and jaw.
 Abnormal growth of internal organs
Laron Dwarfism(Growth Hormone insensitivity)  Reduced plasma IGF-1
 GH levels normal
 Hypersecretion of growth hormone is accompanied by hypersecretion of prolactin in 20–
40% of patients with acromegaly
 About 25% of patients have abnormal glucose tolerance tests, and 4% develop lactation in
the absence of pregnancy

Prolactin:
1. Weakly homologous to GH and human placental lactogen (hPL)
2. Normal levels--10–25 g/L in women and 10–20 g/L in men
3. Secretion is pulsatile
4. Highest peaks occurring during rapid eye movement sleep
5. Half life is 50 min
6. Inhibited by Dopamine(D2),Glucocorticoids,Thyroid hormones
7. Stimulated by Thyrotrophin Releasing Hormone Vasoactive Intestinal Peptide
8. Serum PRL levels rise transiently after
 exercise, meals
 sexual intercourse
 minor surgical procedures
 general anesthesia
 chest wall injury
 acute myocardial infarction
Prolactin Levels increase markedly during pregnancy and lactation, In the breast, the lobuloalveolar
epithelium proliferates
 Functions of prolactin:
1. Decrease reproductive function
2. Suppress sexual drive
3. In females-- hypoestrogenism and anovulation

189
4. In males---decreased spermatogenesis,low testosterone

Thyroig gland

MCQ
Thyroid hormones in the blood is transported by
a) Albumin
b) Globulin
c) Pre albumin
d) Transferrin
e) Ceruloplasmin

ANS: A, B, C

Regarding thyroid hormone all are true except

a) T3 is more avidly bound to nuclear receptors than T4
b) T4 has the maximum plasma concentration
c) T3 is more active than T4
d) T4 has shorter half life than T3

ANS: D

Iodine uptake is seen in following organs

a) Ovary
b) Thyroid
c) Parathyroid
d) Salivary gland
e) Mammary gland

ANS: BDE

Thyroxine injected to rat produces A/E

a) Decreased lipolysis
b) Increased oxygen consumption
c) Decrease in BMR
d) Increased myocardial contractility

ANS: AC

TRH stimulation testing is useful for the diagnosis of disorders of following hormones
a) Insulin
b) ACTH
c) Growth hormone
d) PTH

ANS: C
All are actions of T3 except
a) a) Increases heart rate
b) Increases stroke volume
c) Decreases protein breakdown
d) Decreases peripheral resistance
ANS: C

In thyroid follicles for how long the hormones are stored

a) a) 2-3 weeks
b) 2-3 days
c) 2-3 months
d) 4-6 days

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ANS: C

Thyroid Gland:

 one of the larger endocrine glands

 Blood flow—160ml/100g/min
 maintain the level of metabolism in the tissues
 stimulate O2 consumption by most of the cells
 Secretes T3,T4 and Calcitonin
 Thyrocytes express receptors for
TSH
IGF-I
EGF
IGF-I and EGF promote growth
interferon γ and tumor necrosis factor inhibit growth
 Whwn the Gland is inactive—colloid abundant,large follicles,and flat cells
 Whwn the Gland is active,small follicles,cuboid or columnar cells
 Site of active Colloid resorption--- "reabsorption lacunae"
 Iodine-the raw material for thyroid hormone synthesis
Dietary Iodide-absorbed from intestine
Minimal daily requirement-150µg in adults
20% enters thyroid gland
80% excreted by kidney
Salivaryglands,mammaryglands,placenta-Extrathyroidal
 Free T4 0.7–1.24 ng/dL
 Total T4 5.4–11.7 μg/dL
 Free T3 2.4–4.2 pg/mL
 Total T3 77–135 ng/dL
 Binding proteins
Albumin
Transthyretin
Thyroxine-binding globulin (TBG)
 Albumin--largest capacity to bind T4
 TBG--largest affinity to bind T4

T4 Vs T3

Characteristics T4 T3

Half life Long(6 days) Short(2 days)

Max binding TBG Albumin

In colloid More (25%) Less (7%)

potency less More(3-5 times)

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Action slower Much rapid

Binding to nuclear receptors less more

Thyroid Stimulating Hormone (TSH):

8. Glycoprotein
9. Alpha chain-Chromosome 6 ,beta chain-chromosome 1
10. Half life 60 min
11. Secretion is pulsatile,peaks at midnight
12. Average plasma level-2μg/ml
13. Increases iodine trapping,synthesis of t3,t4,secretion of thyroglobulin,endocytosis of colloid
14. Inhibited by stress,dopamine,somatostatin,thyroid hormones

Physiologic effects of thyroid hormones:

Heart Chronotropic and Inotropic  Increased number of β-

adrenergic receptors
 Enhanced responses to
circulating
catecholamines
 Increased proportion of
α-myosin heavy chain
(with higher ATPase
activity)
Adipose tissue Catabolic  Stimulates lipolysis
Muscle Catabolic  Increased protein
breakdown
Bone Developmental  Promote normal
growth and skeletal
development
Nervous system Developmental  Promote normal brain
development
Gut Metabolic  Increased rate of
carbohydrate
absorption
Lipoprotein Metabolic  Formation of LDL
receptors
Other Calorigenic  Stimulated oxygen
consumption by
metabolically active
tissues (exceptions:
testes,uterus, lymph
nodes, spleen, anterior
pituitary(Mn.LUSTAN)
 Increased metabolic
rate

192
Wolf-Chaikoff Effect Intake of iodide exceeds 2 mg/day --Iodide
suppressesNADPHoxidase activity
and the NIS and TPO genes --Inhibits hormone
biosynthesis
Jod-Basedow Phenomenon Iodine-induced hyperthyroidism, typically
presenting in a
patient with endemic goiter

Endocrine Pancreas

MCQ
Delta cells of pancreas secretes
a) Glucagon
b) Insulin
c) Somatostatin
d) Pancreatic polypeptide

ANS: C
Amylin is secreted by
a) a) Alpha cells
b) Delta cells
c) Beta cells
d) F cells

ANS: C
Insulin is essential for glucose entry in
a) RBC
b) Neurons
c) Muscles
d) Nephron
ANS: C

Following hormones are produced by endocrinal part of pancreas

a) Insulin
b) Somatostatin
c) Glucagon
d) Bombesin
e) Pancreatic polypeptide

ANS: A, B, C, E
Half life of insulin is
a) 15 mins
b) 10-12 mins
c) 4-6 mins
d) 20 mins
ANS: C

Which of the following is correctly matched?

a) B cells-somatostatin
b) D cells-glucagon
c) G cells-gastrin
d) A cells-insulin

ANS: C

Insulin is secreted along with the following molecule in a 1:1 ratio

193
a) Pancreatic polypeptide
b) Glucagon
c) GLP- I
d) Somatostatin
e) C-peptide

ANS: E

Glucose mediated insulin release which is true?

a) ATP mediated K channels
b) cAMP
c) Carrier modulators
d) Receptor phosphorylation

ANS: A

Rapid infusion of Insulin causes

a) Hyperkalemia
b) Hypokalemia
c) Hypernatremia
d) Hyponatremia

ANS: B

All of the following causes hyperglycemia except

a) GH
b) Cortisol
c) Catecholamines
d) Insulin
e) Glucagon

ANS: D

Glucose transporter in myocyte

a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

ANS: D

Glucose increases plasma insulin by a process that involves

a) GLUT 1
b) GLUT 2
c) GLUT 3
d) SGLT 1

ANS: B

Insulin mediated glucose uptake occurs through

a) GLUT 1
b) GLUT 2
c) GLUT 3
d) GLUT 4

ANS: D
Stress induced hyperglycaemia is due to
a) Glucocorticoids
b) GH

194
 c) Thyroxine
d) Epinephrine
e) Insulin

ANS: ABD
After a meal rich in carbohydrates, insulin secretion is increased by
a) CCK
b) Serotonin
c) GLP(7-36)
d) VIP

ANS: C
Endocrine Pancreas:
 The islet of Langerhans are ovoid, 76- x 175-μm collection of cells
 Scattered throughout the pancreas, but they are more plentiful in the tail than the body and head
The cells in the islets can be divided into types on the basis of their staining properties and morphology-
 A cell- make up 20% of the total, surrounds the B cells & secrete glucagon
 B cell- most common, 60% of the total, located in the centre of each islet & secrete insulin
 D cell- less common, secrete & secrete somatostatin & gastrin
 F cell- less important in humans, secrete pancreatic polypeptide

Insulin:
 Has an alpha and beta chain
 Transcription factors-hepatocyte nuclear factor-4 and pancreatic and intestinal homeobox-1
 Zinc bound crystals
 Equimolar amounts of C-peptide secreted
 Measurements of C peptide in the Blood--quantify endogenous insulin production in patients
receiving exogenous insulin
 Glucokinase-Rate Limiting Step in insulin secretion
 Biphasic insulin release-Early phase-preformed insulin,Late phase-newly formed
 Half life-5 min
 Degraded by Insulinase in liver
 Otherwise called” Hormone of abundance”
Principal Actions:
 Rapid-Increases transport of glucose amino acids and potassium into insulin sensitive cells.
 Intermediate-Stimulates protein synthesis. Inhibits protein breakdown,Activation of glycolytic and
inhibition of gluconeogenic enzymes
 Delayed-Increases formation of mRNA for lipogenic action
Effects of insulin on various tissues:
Adipose tissue
 Increased glucose entry
 Increased fatty acid synthesis
 Increased glycerol phosphate synthesis
 Increased triglyceride deposition
 Activation of lipoprotein lipase
 Inhibition of hormone-sensitive lipase
 Increased K+ uptake
Muscle
 Increased glucose entry
 Increased glycogen synthesis
 Increased amino acid uptake
 Increased protein synthesis in ribosomes
 Decreased protein catabolism
 Decreased release of gluconeogenic amino acids
 Increased ketone uptake
 Increased K + uptake
Liver

195
 Decreased ketogenesis
 Increased protein synthesis
 Increased lipid synthesis
 Decreased glucose output due to decreased gluconeogenesis,
 increased glycogen synthesis, and increased glycolysis
General
 Increased cell growth
Insulin Induces:
Enzymes of glycolysis- Glucokinase, pyruvate kinase
Enzymes of glycogenesis-glycogen synthase
Enzymes of lipogenesis-Acetyl coA carboxylase
Insulin Inhibits:
Enzymes of glycogenolysis- phosphorylase
Enzymes of neoglucogenesis-pyruvate carboxylase
Enzymes of lipolysis-Hormone sensitive lipase
Stimulators Inhibitors

Glucagon:
 A cells in pancreatic islets
 In L cells—Glicentin,GLP-1,GLP-2,Oxyntomodulin
 Glicentin has some glucagon activity
 GLP-1 (7–36), is a potent stimulator of insulin secretion
 GLP-2 lowers food intake
Actions of glucagon:
 glycogenolytic, gluconeogenic, lipolytic, and ketogenic
 does not cause glycogenolysis in muscle
 positively inotropic effect on the heart
 stimulates the secretion of growth hormone, insulin and pancreatic somatostatin
 Half life-5-10 min

Somatostatin:
 Somatostatin 14, Somatostatin 28-D cells
 inhibit the secretion of insulin, glucagon, and pancreatic polypeptide—paracrine
 decreased gastric acid secretion
 Inhibition of CCK secretion.
 increased by several of the same stimuli that increase insulin secretion

Pancreatic polypeptide:
 F cells in the islets
 secretion is under cholinergic control

196
 increased by a meal containing protein and by fasting, exercise, and acute hypoglycemia
 slows the absorption of food in humans

Other factors affecting carbohydrate metabolism:

• Exercise-insulin independent increase in the number of GLUT 4
• Epinephrine-glycogenolysis,increase hepatic glucose output,decrease peripheral use
• Thyroid hormones-Hyperglycemia,metathyroid diabetes,enhances GI glucose absorption
• Cortisol-Gluconeogenic(Permissive)
• GH-Anti insulin effect, increase hepatic glucose output

Glucose transporters:
Function Major sites of expression
SGLT 1 Absorption of glucose Small intestine, renal tubules
SGLT 2 Absorption of glucose Renal tubules
GLUT 1 Basal glucose uptake Placenta, blood-brain barrier, brain, red cells,kidneys, colon,
many other organs
GLUT 2 B-cell glucose sensor; B cells of islets, liver, epithelial cells of small intestine, kidneys
transport out of intestinal
and renal epithelial cells
GLUT 3 Basal glucose uptake Brain, placenta, kidneys, many other organs
GLUT 4 Insulin-stimulated glucose Skeletal and cardiac muscle, adipose tissue,other tissues
uptake
GLUT 5 Fructose transport Jejunum, sperm
GLUT 6 Unknown Brain, spleen and leukocytes
GLUT 7 Glucose 6-phosphate Liver
transporter in endoplasmic
reticulum

Adrenal Gland

MCQ
Zona glomerulosa secretes
a) Aldosterone
b) Cortisol
c) Testosterone
d) catecholamines

ANS: A
Not an action of cortisol
a) Gluconeogenesis
b) Increases free fatty acids
c) Increases eosinophils
d) Anti inflammatory

ANS: C

Mineralocorticoid receptors are present in all of thefollowing sites,except

a) Hippocampus
b) Kidney
c) Colon
d) Liver

ANS: D

What is the effect of cortisol on metabolism?

a) Increase in neoglucogenesis
b) Increase in lipogenesis

197
c) Increase in proteolysis
d) Increased protein anabolism in liver
e) Increase in glycolysis

ANS: A, C, D

Hyperaldosteronism is associated with all except

a) Hypernatremia
b) Hypokalemia
c) Hypertension
d) Metabolic acidosis

ANS: D

Major adrenal androgen is

a) Testosterone
b) Dihydrotestosterone
c) Dehydroepiandrosterone
d) Norethisterone

ANS: C
Adrenal gland:
 Adrenal cortex
– Zona glomerulosa-Mineralocorticoid(15%).Also involved in Formation of new cortical cells
– Zona fasciculata-Glucocorticoids (50%)
– Zona reticularis-Adrenal androgens (7%)
– Adrenal Medulla (18%)
 Epinephrine(90% cells,larger,less dense granules)
 Nor epinehrine(10% cells,smaller dense granules)
 Dopamine
Effects of Epinephrine & Norepinephrine:
1. glycogenolysis in liver and skeletal muscle
2. mobilization of free fatty acids (FFA),
3. increased plasma lactate
4. stimulation of the metabolic rate
5. Increases secretion of insulin and glucagon(Beta) and decreases the same(Alpha)
6. Intial increase in K+,then prolonged fall(beta2)
Effects of Dopamine:
1. Renal and mesentric vasodilation
2. Elsewhere-Vasoconstriction
3. Positive inotropic effect-use in cardiogenic,traumatic shock
4. Natriuresis by inhibiting renal sodium potassium ATPase
Adrenal cortical hormones:
 derivatives of cholesterol
 has cyclopentanoperhydrophenanthrene nucleus

Aldosterone:
 Increase the reabsorption of Na+ from the urine, sweat,saliva, and the contents of the colon.
 principal cells (P cells)-K+ diuresis and urinary acidity
 Genomic action—through serum- and glucocorticoid-regulated kinase (sgk)
 Non genomic action---increases the activity of membrane Na+–K+ exchangers
Aldosterone Escape:
 Whenever aldosterone is increased, Na+ ions are retained in the body.
 This causes osmotic absorption of water. Therefore ECF volume increases.
 Increase in ECF leads to increase in arterial pressure causing excretion of salt and water by pressure
diuresis,natriuresis(ANP)
 This secondary increase in water and salt excretion by the kidneys is called aldosterone escape.
Aldosterone Excess:

198
• Primary Hyper aldosteronism
Conn’s syndrome-adenoma,carcinoma
Low renin
• Secondary Hyper aldosteronism
cirrhosis, heart failure, and nephrosis
High renin
Apparent Mineralocorticoid Excess (AME)
1. 11 -hydroxysteroid dehydrogenase type 2 deficiency
2. Due to intake of licorice containing glycyrrhetinic acid
3. Hyperaldosteronism,hypertension
Glucocorticoid-Remediable Aldosteronism (GRA):
1. autosomal dominant disorder
2. ACTH-sensitive aldosterone synthase
3. Suppressed by administrating cortisol
Deficiency of aldosterone(Addison’s disease):
• Loss of sodium and chloride ions
• Excess of potassium ions
• Fluid and blood volume decreases
• Diminished cardiac output
• Shock like state
• Death in 3 days to 2 weeks
• Highly susceptible to stress and infections.
• Pigmentation of skin and mucus membrane
• Mineralocorticoid is life saving hormone of adrenal gland
Addisonian crisis:
• A person with Addison’s disease succumbs to stress. This condition is called addisonian crisis. They
need extra amounts of glucocorticoids

Glucocorticoids-Cortisol:
 This is a C21 steroid produced mainly from zona fasciculata.
 It combines with cortisol binding globulin.
 96 % of the cortisol is transported in bound form. Only 4 % is transported in free form.
 It stays in circulation for 1 to 2 hours
 It is degraded in the liver and conjugated to form glucuronides. It is excreted in urine

Functions of cortisol:
On - It stimulates gluconeogenesis by the liver by increasing glucose-6-phosphatase.
carbohydrate - It decreases rate of glucose utilization by the peripheral tissues by inhibiting
metabolism phosphorylation (anti-insulin action)—ADRENAL DIABETES
- Increases glycogen synthesis in liver by increasing activity of glycogen synthase.
On protein - It causes protein breakdown in skeletal muscles.
metabolism -Cortisol enhances amino acid uptake by the liver cells & enhances transamination - (AA
synthesis), deamination – (glucose formation)
- Hence proteins like plasma proteins produced by liver are increased
On fat • It causes fatty acid mobilization from adipose tissue increasing free fatty acids in
metabolism plasma.
• It stimulates absorption of lipids from the intestine.
• It causes redistribution of fats in the body
Water and • Mild mineralocorticoid activity – retains Na & excretes K
Mineral • Increases angiotensinogen synthesis in liver leading to Na retention via aldosterone
metabolism • Provides adequate GFR via anti-ADH activity
Anti • Cortisol inhibits all aspects of inflammation.
inflammatory • It reduces leucocyte margination, chemotaxis, phagocytosis of bacteria.
effect • Aggregation of monocytes is also inhibited.
• Cortisol inhibits the synthesis and release of chemical mediators of inflammation like
prostaglandins & arachidonic acid
Effect on • Causes eosinopenia- sequestration of it in lungs and spleen, increased destruction

199
blood cells • lymphopenia – due to reduced formation and increased destruction
• basopenia
• neutrophilia -increased release from bone marrow, decreased margination and escape
to the tissues
• Polycythemia by stimulation of erythropoiesis.
Permissive • On glucagon & catecholamines to exert calorigenic action
action • On catecholamines to exert lipolytic effect & glycogenolytic effect.
• On catecholamines to exert pressor response & bronchodilation
On bone • It causes demineralization of bone
• Retards development of cartilage
• Thinning of epiphyseal plate
• Breaks down bone matrix
• Decreases calcium deposition
• Increases calcium excretion
• Decreases calcium absorption from GIT
• Results in osteoporosis and tetany

Abnormalities of the adrenal cortex:

Cushing’s • Excess secretion of glucocorticoids. Causes
Syndrome • Adrenocortical tumours
• Anterior pituitary tumours
• Ectopic ACTH producing tumour
• Prolonged glucocorticoid therapy.
– Cushing’s syndrome caused due to tumours of anterior pituitary is called Cushing’s
disease.
21- • Adrenal and gonads
Hydroxylase • Most common form of congenital adrenal hyperplasia (80-90%)
deficiency • Signs and symptoms:
– Dehydration, Hyperkalemia, Hyponatremia
– Genital ambiguity (XX)
– advanced somatic development
– short adult stature
11β- • Adrenals
Hydroxylase • 10 – 20% cases of congenital adrenal hyperplasia
deficiency • 11-Deoxycorticosterone accumulation
• Signs and symptoms:
– Hypertension
– Genital ambiguity (XX)
– advanced somatic development short adult stature
3β- • Adrenals and gonads
Hydroxyster • Signs and symptoms:
oid – Dehydration
dehydrogena – Hyperkalemia, Hyponatremia
se deficiency – Ambiguous genitalia (Hypospadia, Undescended
testis, Cliteromegaly)
Lipoid • Steroidogenic Acute Response Protein (StAR) mutation
adrenal • Adrenal and gonads
hyperplasia • Signs and symptoms:
– Dehydration
– Alkalosis, Hyperkalemia, Hyponatremia
– Female external genitalia regardless of genetic sex (Male pseudohermaphroditism in XY
individuals)
– Undescended testis
17α- • Adrenal and gonads
Hydroxylase • Increased Corticosterone, Deoxycorticosterone
deficiency • Decreased sex hormones, Cortisol
• Signs and symptoms:
• Hypertension
• Episodic vomiting, headache

200
 • Female external genitalia
• Undescended testis
Adrenogenit • An adrenocortical tumour secretes excess amounts of androgens causing intense
al syndrome masculanizing effects.
• Females develop virile characteristics like growth of beard, deep voice, baldness,
masculine distribution of hair & growth of clitoris.
• Prepubertal male has rapid development of sexual organs (precocious puberty).
• In an adult male, it is difficult to diagnose the condition because the signs are obscured by
normal virilizing characteristics of testosterone

Calcium Homeostasis

MCQ
Calcium absorption is facilitaed by
a) Phytates
b) Oxalates
c) Proteins
d) acid
ANS : C
A small Ca binding protein that modifies activity of many enzymes and proteins in response to
changes of Ca concentration is
a) Cycline
b) Calmodulin
c) Collagen
d) Kinesin

ANS: B
Parathyroid hormone is responsible for all except
a) Increased absorption of phosphorus
b) Increase in vit-D
c) Mobilizes Ca from bone
d) Increased intestinal absorption of calcium
ANS : A
Calcium absorption is from
a) Proximal small intestine
b) Distal ileum
c) Middle small intestine
d) Ascending colon
ANS : A

Which of the following is false regarding PTH secretion

a) Non ionic calcium is most important stimulus for PTH secretion
b) Mg stimulates PTH secretion in the same way as calcium
c) Hypercalcemia in cancer patients is due to parathormone related protein
d) Parathyroid senses calcium through calcium sensing receptor
ANS: A
TRUE of the following
a) Calcium reabsorbed in DCT
b) 90 % calcium excreted by glomerulus
c) PTH promotes absorption of Ca from intestine
d) PTH promotes action of calcitonin

ANS: C

Hypocalcemia due to calcitonin is by

a) Increased excretion in kidney
b) Decreased bone resorption
c) Decreased intestinal absorption
d) Decreased renal reabsorption

201
ANS: B

Osteoclasts are inhibited by

a) Parathyroid hormone
b) Calcitonin
c) 1,25-dihydroxycholecalciferol
d) Tumour necrosis factor

ANS: B

Osteoclasts has specific receptor for

a) Parathyroid hormone
b) Calcitonin
c) Thyroxin
d) Vit D3

ANS: B
Sudden decrease in serum calcium is associated with
a) Increased thyroxine and PTH secretion
b) Increased phosphate
c) Increased excitability of muscle and nerve
d) Cardiac conduction abnormalities

ANS: C
Hypocalcemia is characterized by all except
a) Numbness and tingling of circumoral region
b) Hyperactive tendon reflexes and positive chyostek’s sign
c) Shortening of Q-T interval in ECG
d) Carpopedal spasm

ANS: C
In tetany hyperexcitability is due to
a) Low calcium increases permeability to sodium
b) Prevent pottasium release
c) Prevent Na and K release
d) Decreased Ca produce generation of action potential

ANS: A
Which of the following organ is not involved in Ca metabolism
a) Lung
b) Liver
c) Spleen
d) Skin
e) Kidney

ANS: C

Hypercalcaemia associated with malignancy is most oten mediated by

a) Parathyroid hormone
b) PTH related peptide (PTHrP)
c) Interleukin-6
d) Calcium

ANS: B
Which of the following hormones is an example of a peptide hormone
a) Parathormone
b) Adrenaline
c) Cortisol

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 d) Thyroxine
ANS : A
Increased calcium leads to
a) increase in 24,25 vitamin d3
b) Increase in PTH
c) decrease in Calcitonin
d) Increase in vitamin d3
ANS : A

Hormones involved in calcium homeostasis:

 1,25 Dihydrocholecalciferol
 Parathyroid hormone
 Calcitonoin
 Parathyroid hormone related protein ( PTHrP)
 Miscellaneous hormones :
Glucocorticoids, Growth hormone, Estrogen

Parathormone:
 FOUR parathyroid glands located behind the thyroid gland
 6 x 3 x 2 mm
 Two types of cells
1. Chief cells
2. Oxyphil cells
 Normal plasma PTH-10 -55 pg / mL
 Half life – 10 mins
Actions of PTH:
I. Increases calcium and phosphate absorption from the bones
II. Decreases excretion of calcium by the kidneys
III. Increases the excretion of phosphate by the kidneys(inhibits NaPi cotransporter)(Phosphate
Terminating Hormone)
IV. Increases intestinal absorption of calcium and phosphate.
All these actions leads to increased plasma calcium

Abnormalities of PTH secretion:

Primary •Tumors – adenoma of parathyroid glands
Hyperparatyroi • Extreme osteolytic resorption
dism • Increase in calcium and decrease in phosphate levels.

Secondary •Increased levels of PTH is the result of compensatory mechanism tohypocalcemia

Hyperparathyro • Due to chronic renal disease or deficiency of Vitamin D3
idism

Familial benign •Inactivating mutation in Calcium receptor(CaR)

hypocalciuric
hypercalcemia
Pseudohypopar •50% reduction of the activity of Gs occurs
athyroidism

Parathormone related peptide (PTHrP):

As a paracrine In Cell differentiation and survival
signal
Physiological •In pregnancy-increases placental calcium transport
endocrine role • During lactation-maintains adequate
calcium levels for lactation
Pathological •Hypercalcemia of malignancy

Vitamin D:
Promotes intestinal calcium absorption

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BY
1. Formation of calcium binding protein
(calbindin)
2. Formation of calcium stimulated ATPase
3. Formation of alkaline phosphatase
Decreases renal excretion of calcium & phosphate
Increases both bone resorption and bone mineralization
1. BONE RESORPTION– by stimulating PTH.
Calcitriol receptors are present in osteoblasts
Receptor – calcitriol complex – stimulate osteoblasts --activation & differentiation of osteoclasts.
2. BONE MINERALIZATION– by stimulation osteoblasts and alkaline phosphatase secretion

Abnormalities of vitamin D secretion:

Vitamin D deficiency in children and adults
- defective bone mineralization and calcification
- failure to deliver adequate Ca and PO4
Features:
Weakness and bowing of weight bearing bones, dental defects and hypocalcemia.
Responsive to Vitamin D therapy.
Vitamin D Resistant Rickets:
mutations in the gene coding for the enzyme
1 α HYDROXYLASE
1,25-dihydroxycholecalciferol receptor (type II vitamin D-resistant rickets)

Calcitonin and its actions:

•Secreted by C cells of thyroid
• Helps in Calcium absorption during pregnancy and lactation
• Decreases osteoclasts number and activity

Fibroblast Growth Factor 23(FGF 23):

•Secreted by osteoblasts
• Inhibits Vitamin D
• Inhibits PTH
• Promotes calcium and phosphate excretion
• Mutation in PHEX-X-linked hypophosphatemia, FGF23 levels increase

Role of Klotho in calcium homeostasis:

Normal ageing protein
Stabilises membrane receptors:
If it stbilises membrane receptor for FGF-23-decrease calcium levels
If it stbilises membrane receptor for TRPV5-increse calcium levels

Role of other hormones in calcium homeostasis:

Glucocorticoids • Lowers plasma calcium by inhibiting osteoclasts.
• Over Long periods – osteoporosis
• Inhibit protein synthesis in osteoblasts,thereby synthesis of organic matrix
• Inhibit absorption of Ca and Po4 from the gut and facilitate its excretion in the kidneys.
Growth • Increases intestinal absorption of Calcium “Positive calcium balance”
hormone
IGF – I • Stimulates protein synthesis in bone
Thyroid • Hypercalcemia, Hypercalciuria and Osteoporosis
hormone
Estrogens • Prevents osteoporosis by inhibiting certain cytokines

Insulin • Increases bone formation

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Reproductive Physiology
Development of Gonads
MCQ
Sex-determining region of the Y chromosome is
A. RNA-binding regulatory protein
B. Testis-determining gene product
C. Present in long arm of Y chromosome
D. Encodes telomerase
Ans-B

Sex-determining region of the Y chromosome(SRY)

 DNA-binding regulatory protein
 Transcription factor
 testis-determining gene product-for testicular differentiation
 In short arm of Y chromosome
 Enhances production of mullerian inhibiting substance(MIS)
 MIS:
1. Induces apoptosis of mullerian duct
2. testicular descent in boys
Genetic Sex 44XY and 44XX…presence or absence of Y
chromosome
Gonadal Sex Testis in male and Ovary in female
Phenotypic Sex Based on internal and external genital organs

Female Bipotential structure Male

Clitoris Genital tubercle Glans penis
Labia minora Urethral folds and groove Shaft of penis
Labia majora Labioscrotal swellings Scrotum
Forms ovary Gonad(cortex) Regresses
Regresses Gonad(medulla) Forms testis

MCQ
Embryonic ovaries secretes the following hormone
A. Oestradiol
B. Progesterone
C. Inhibin
D. None of the above
Ans-D

 Gonads-Bipotential upto 8 weeks

 Embryonic testis:
1. Leydig cells-testosterone
2. Sertoli cells-MIS
 “Embryonic ovaries doesn’t secrete any hormones”

MCQ
Major excitatory neuromodulator implicated in the onset of puberty is
A. Opiods
B. Melatonin
C. Kisspeptin
D. Neuropeptide Y
Ans-C
Excitatory neuromodulators in puberty:
 Kisspeptin(Receptor-GPR 54)
 Glutamate
 Nor epinephrine

205
Inhibitory neuromodulators:
 GABA
 Opiods
 NPY
 Melatonin
 Gonadal steroids

Reproductive Hormones-Estrogen
MCQ
Which one of the following is the C18 steroid
A. Estradiol
B. Testosterone
C. Progesterone
D. Cortisol
Ans-A

MCQ
Estradiol is secreted by all of the following except
A. Granulosa cells
B. Corpus luteum
C. Placenta
D. Theca interna
Ans-D

Peripheral conversion of testosterone to estradiol occurs in which of the organs

A. Fat
B. Liver
C. Muscle
D. Brain
Ans-A, B, C, D

Granulosa cells have receptors for

A. FSH
B. LH
C. GnRH
D. TSH
Ans-A, B

C 21 steroids Cortisol
Progesterone
C 19 steroids Testosterone
C 18 steroids Estrogen

FSH receptors LH receptors

• Granulosa cells in • Both theca interna & granulosa cells in female
female • Leydig cells in male
• Sertoli cells in male

Secretion of estrogen:
 Sources- granulosa cells, the corpus luteum, and the placenta
 Depends on aromatase-converts testosterone to estradiol
 Peripheral conversion-fat, liver, muscle, and the brain
 Theca interna cells- supply androstenedione to the granulosa cells

MCQ
All of the following are actions of estrogen except
A. Growth of axillary and pubic hair in females

206
B. produce duct growth in the breasts
C. proliferation of dendrites on neurons
D. Makes uterus more sensitive to oxytocin

Ans-A
Actions of estrogen:

On Ovary
 Increases size of ovary & stromal cells.
 Initiates oogenesis & development & maintainence of follicles.
 Brings cyclical changes in ovary
On Uterus
 Increases size of uterus, fallopian tubes, cervix.
 Increases excitability of smooth muscle.
 Increases blood supply to myometrium.
 Causes changes in endometrium& onset of menarche.
 Increases no. of oxytocin receptors on myometrium in pregnant
On fallopian tubes :
 Increase ciliary activity and motility and secretory activity of cells.
On Cervix :
 Cervical mucus is thin and become crystalline, forming channels that facilitate the passage
of sperm into uterus, Alkaline in nature.
 Shows ferning like effect i.e. arborisation on drying.
On Vagina :
 lined with stratified squamous epithelium
 Vaginal secretions are increased.
6. On Breast :
 Promotes ductal growth.
 Causes pigmentation of areola.
 Promotes deposition of fat.
On Metabolisms
 Carbohydrate  Hyperglycemic
 Protein  Anabolic & Protein synthesis
 Fat  Plasma Cholesterol
 Mineral & H2O  Reabsorption of Na+
Water retention& Wt.gain
On bone:
 The epiphyseal growth centers are more sensitive to Estradiol than Testosterone, they close
sooner

MCQ
LH peak occurs - prior to onset of ovulation
A. 8-10 hours
B. 12-24 hours
C. 24-48 hours
D. 48-72 hours
Ans-A

Estrous Cycle:

 Mammals other than primates do not menstruate & their sexual cycle is called an
estrous cycle

207
  No episodic vaginal bleeding occurs but the underlying endocrinal mechanisms are
essentially the same as those in the menstrual cycle

 In other species ovulation is induced by copulation. (reflex ovulation)

Ovarian cycle: Follicular enlargement dominant follicle (6th day)secreted oestrogengraafian

folliclematuration of ovumfollicular rupture & release of ovum into the peritoneal cavity
(ovulation)remnants of graafian follicle forms corpus luteum  secretes progesterone >
oestrogen  lysis of corpus luteum 2 days before menstruation leaving a fibrous scar called corpus
albicans

Menstrual cycle:

Phase Other names Period Endometrial changes

Proliferative Preovulatory / Post menstrual 6th day-14th Endometrial glands enlarge &
phase / follicular phase day proliferates
(oestrogen)
Increased vascularity & coiled
arteries

Thickness: 2-3 mm

Secretory Post ovulatory / premenstrual 15th day - Endometrial glands

phase / luteal/pro gestational phase 27th day hypertrophies & distended with
(progesterone) mucus

 in no. of coiled arteries, 

blood flow

*Thickness: 5-6mm

Menstrual Destructive phase / blooding 1-5th day Vasoconstriction of spiral arteries

phase phase  ischemic changes  necrosis
of endometrium  sheddin g;
Bleeding: 75% arterial

Endometrial cycle:

Endometrium
Characteristics Proliferative Phase Secretory Phase
Thickness Increases due to cell division & Cell growth. Slightly increases and becomes
0.5mm to3.5-5mm. edematous.

Stromal cells Proliferate & increase in size thus increasing Stromal proliferation and cell
thickness. growth continues.

208
Glands Straight tubular glands form lined with Becomes increasingly tortous
columnar epithelial cell. Produce and store large and spiralised, produce great
amount of glycogen. amount of mucus.

Spiral Arteries Increasingly vascularised and spiral arteries Becomes increasingly tortous
elongate and spiralised

Myometrium Increase in excitability & Contractility and Decrease in excitability and

increase sensitivity to oxytocin. decreases contractility.

Fallopian Increase ciliary activity and motility and
tubes secretory activity of cells.
Cervix Cervical mucus is thin and become crystalline,
forming channels that facilitate the passage of
sperm into uterus, Alkaline in nature.
Shows ferning like effect i.e. arborisation on
drying.
Hormonal influence of menstrual cycle
Increases ciliary activity and
sensitivity and decreases
motility
Cervical mucus is thick and
sticky, tenacious and cellular.
Does not show ferning effect.

 FSH-early development of G. Follicle

 Final maturation of ovum-FSH&LH

 LH-ovulation, formation & maintenance of C. Luteum

 A surge in LH secretion triggers ovulation, and ovulation normally occurs about 9 h after
the peak of the LH surge at midcycle

 The LH surge begins about 24-36 hours before ovulation and reaches its peak about 8-10
hours before ovulation. It is this surge that acts to trigger ovulation

Indicators of Ovulation
6. Basal Body Temparature
7. Fern Test
8. Endometrial Biopsy
9. Estimation of hormonal levels
10. Ultra sound examination of follicle

Progesterone
MCQ
Progesterone is metabolized and excreted in urine as
A. Pregnanediol
B. Pregnenolone
C. Etiocholanolone
D. Androsterone
Ans-A

209
C & D-testosterone metabolites in urine
Luteal phase dominant hormone is
A. Estradiol
B. Testosterone
C. Progesterone
D. Cortisol
Ans-C
Corpus luteum in pregnancy is maintained by
A. Estradiol
B. Testosterone
C. Progesterone
D. Cortisol
Ans-C
Progesterone has how many carbons
Estradiol
A. 18
B. 19
C. 20
D. 21
Ans-D

MCQ
All of the following are actions of progesterone except
A. Decreases sensitivity of oxytocin
B. Stimulates respiration
C. stimulates the development of lobules and alveoli in breast
D. Salt & water retention
Ans-D

Actions of progesterone:

Principal target organs :

 Uterus
 Breast
 Brain
Endometrium:
 Thickness slightly increases
 Makes edematous
 Promotes stromal cell growth &proliferation
 Glands – Tortous& Spiralised,mucus secretion increases
 Spiral arteries - Tortous& Spiralised
Myometrium
 Decrease excitability
 Decreases Contractility
On Cervix
 Cervical mucus becomes thick & sticky,tenacious and cellular
 No Ferning effect
Calorigenic action

210
  Thermogenic
 Responsible for rise in basal body temperature at time of ovulation
On Respiration
 Stimulates Respiration
 Decreases Alveolar Pco2
On Kidneys
 Large doses – Natriuresis by blocking the action of Aldosterone

Relaxin
MCQ
One among the following is not a steroid hormone
A. Estrogen
B. Progesterone
C. Relaxin
D. Testosterone
Ans-C

Relaxin
 Polypeptide hormone
 Sources- corpus luteum, uterus, placenta, and mammary glands in women
 prostate gland in men
 relaxes the pubic symphysis,softens cervix
 found in semen
 maintain sperm motility, sperm penetration of the ovum

Inhibins and activins

MCQ
Inhibin inhibits
A. FSH
B. LH
C. Estrogen
D. Progesterone
Ans-A

Inhibins and activins:

 Inhibin B inhibits FSH in male & female
 Activin-Stimulates FSH
 Belongs to TGF β superfamily
 Other actions of Activins:
1. Formation of WBC
2. Formation of Mesoderm
 Inactivator of activin-FOLLISTATIN

Testosterone
MCQ
Testosterone is secreted by
A. Leydig cells
B. Sertoli cells
C. Prostate
D. Cowper’s glands
Ans-A

All of the following are actions of testosterone except

A. Sexual differentiation
B. Wolffian stimulation

211
C. External virilization
D. increase in muscle mass
Ans-C

Testosterone is converted to dihydrotestosterone by 5α-reductase

Type 1 5α-reductase- skin & scalp
Type 2 5α-reductase- Genitals
Actions of testosterone:

On foetal life :
 Foetal differentiation.
 Development of male brain.
 Development of external & internal
genitalia.
 Descent of testes
At Puberty :
 Initiation of Spermatogenesis.
 Growth of external & internal genitalia.
Secondary sexual characterstics :
 Deepening of voice.
 Moustache, beard,pubic hair,body hair& acne.
 Masculine pattern of fat distribution.
 Male body contour broad thoracic cage & shoulders, narrow pelvis.
 Mental changesaggressive behaviour
In Adult Life :
 Maintenance of Spermatogenesis.
 Maintenance of accessory sex organs.
 Maintenance of Libido
Other actions
 Hyperglycemic.
 Increases levels of LDL’s & decreases levels of HDL’s.
 Accumulation of upper body, abdominal & visceral fat.
 Increases protein synthesis.
 Reabsorption of Na+ from kidneys
 Promotes bone growth
 Causes enlargement of muscle mass.
 Stimulates synthesis of Erythropoietin , so increase in RBC mass

Actions of DHT
 External virilization
 Sexual maturation at puberty

Placental hormones
MCQ
After conception HCG can be measured as early as
A. 6 days after conception
B. 10 days after conception
C. 12 days after conception
D. 14 days after conception
Ans-A

212
Human Chorionic Gonadotrophin
 produced by the syncytiotrophoblast
 Has alpha and beta subunits
 hCG-α is identical to the α subunit of LH, FSH, and TSH
 In blood-detected by radioimmunoassay as early as 6 days after conception
 In urine-14 days after conception
 Acts on LH receptor-Leutinizing & Luteotrophic

MCQ
Which hormone is called as “maternal growth hormone of pregnancy”
A. proopiomelanocortin
B. leptin
C. Human Chorionic Somatomammotropin
D. Cortisol
Ans-C

Human Chorionic Somatomammotropin

 Produced by syncytiotrophoblast
 Actions similar to growth hormone
 nitrogen, potassium, and calcium retention
 Promotes lipolysis in mother
 Diverts glucose to fetus
 Low hCS levels-sign of placental insufficiency

Sertoli cells
MCQ
Sertoli cells secrete all except
A. Inhibin
B. Androgen binding protein
C. Mullerian inhibiting substance
D. Testosterone

Ans-D

Mullerian Regression Factor is produced by

A. Leyding cells
B. Sertoli cells
C. Clue cells
D. Peg cells

Ans-B
Functions of Sertoli cells
 Forms a Blood-Testes barrier.
 Mechanical support for maturing gametes.
 Provides nutrition to developing spermatozoa.
 Helps in maturation of sperms.
 Phagocytes damaged germ cells.
 Participates in Spermiation

Substances produced by Sertoli cells

 H-Y antigen.
 Anti Mullerian Hormone/MIS.
 Androgen Binding Protein (ABP).
 Inhibins.
 Aromatase Testosterone to Estrogen.

Spermatogenesis:

213
MCQ
True regarding spermatogensis A/E
A. It takes 74 days for the spermatogonium to become spermatozoa
B. Two spermatids are produced in second meiotic division
C. Androgens are produced by leydig cells
D. Sertoli cells secrete inhibin

Ans-B

Secretions from the prostate are rich in

A. Fructose
B. Fibrinolysins
C. Ascorbic acid
D. Prostaglandins

Ans-B
Sperm acquires motility in
A. Seminal vesicle
B. Testes
C. Epididymis
D. Ejaculatory duct

Ans-C
Maturation of sperm takes place in
A. Epididymis
B. Vas deferens
C. Seminal vesicles
D. Uterus

Ans-A
Prostaglandins in semen comes from
A. Epididymis
B. Vas deferens
C. Seminal vesicles
D. prostate

Ans-C
Haploid number of chromosomes seen in
A. Spermatogonia
B. Primary spermatocyte
C. Secondary spermatocyte
D. none

Ans-C
Velocity of human sperms is
A. 1-3 mm/min
B. 5-6 mm/min
C. 6-9 mm/min
D. 10-12 mm/min

Ans-A
Spermatogenesis is mostly controlled by
A. FSH
B. LH
C. TSH
D. ACTH

Ans-B
Semen is released by

214
 A. Epididymis
B. Vas deferens
C. Seminal vesicles
D. prostate

Ans-B
Seminiferous tubules Interstitials cells of
Leyding

Primitive germ cells: Sertoli cells: Secretes testosterone

Mature into Secrete: Inhibin & Activin, Androgen binding

spermatocytes Protein, Mullerian Inhibiting Substance
(MIS)/Mullerian

Regression Factor (MRF)

Acts as Blood Testes barrier

Spermatogenesis:
 Takes about 64-75days
 Each Spermatogonium 512 spermatids
 Estrogen content of the fluid in the rete testis is high, and the walls of the rete testis contain
numerous α estrogen receptors (ERα)---Concentration of spermatazoa
Spermatogensesis Oogenesis

Spermatogonium (2n) Oogonia(2n),

 Mitosis  Ist meiotic division in embryonic ovary,

arrested in the stage of late prophase
Primary spermatocyte (2n)
Primary Oocyte(2n)
Meiosis
 completion of Ist meiotic division, Just
Two Secondary spermatocytes (n) before ovulation
 Secondary Oocyte (n)+Ist polar body
Two Spermatids (n) from each
IInd meiotic division, arrested At
 Metaphase
Spermatozoa (n)
Oozoa (n) +IInd polar body
*1primary spermatocyte gives rise to 4
The second meiotic division is completed
spermatids
only after the entry of sperm in to ovum
*1 Spermatogonium gives rise to 512
1 primary Oocyte gives rise to one ovum
spermatids

*It takes 74 days for the spermatogonium to

become spermatozoa

215
  The arrest in metaphase is due, at least in some species, to formation in the ovum of
the protein PP39mos, which is encoded by the C-mos protooncogene. When
fertilization occurs, the PP39mos is destroyed within 30 min by calpain, a calcium-
dependent cysteine cysteine protease
 Matured spermatozoa are released from Sertoli cells and stored, matured & gains
motility in epididymis
 Capacitation occurs in female genital tract

COMPOSITION OF SEMEN:

• Color  white, opalescent.

• Specific gravity  1028
• pH 7.35-7.5
• Composition :
• Sperms  5%
• Prostate 20%
• Seminal vesicle60%
• Sperm count  about 50- 100million/ml.
• Volume  2.5-3.5ml/ejaculate.
• Sperm movement3mm/min in female tract
• Maximal duration of fertilising capacity in female tract is 24-48hours, motility persists for 48-
60hours
• Reaction of semen is alkaline
Prostate gland constituents:
• Citrate, Calcium, Zinc, Spermine, Cholesterol, Phospholipids, Fibrinolysins, Fibrinogenase,
Acid Phosphatase.
Seminal vesicle constituents:
• Fructose, Phosphoryl choline, Ergothioneine, Ascorbic acid, Flavins, Prostaglandins
Capacitation:
• Continuation of sperm differentiation in female genital tract.
• Function: Prepares the sperm plasma membrane for acrosome reaction.
• Time taken1-4hours
Changes :
• Changes in motility pattern.
• Loss of adsorbed surface proteins, decapacitation factors.
• Loss of lipid and sterol components and redistribution of surface proteins.
• Increased permeability to calcium.
• Ca++ influx into headacrosome reaction.
• Ca++ influx into mitochondria changes in motility.
Acrosome reaction:
• Involves distinct structural changes in plasma membrane and outer acrosomal membrane.
++
Ca dependent
Changes in sperm after acrosome reaction:
• Conversion of inactive enzymes into active enzymes.
• A new surface, inner acrosomal membrane which contains proteins is exposed.
• Activation of sperm enzymes.
• Increased membrane fluidity

216
Lactation

MCQ
The hormone which causes ejection of milk from the breast is
A. HCG
B. Prolactin
C. Oxytocin
D. Mammotropin

Ans-C
Lactation:
 Oestrogen-proliferation of mammary ducts
 Progesterone-Lobulo-alveolar development
 Prolactin-Initiation of milk secretion &maintenance(PROlactin-PROduce milk)
 Oxytocin-Milk ejection(Ooze milk)
 Breast feeding stimulates prolactin secretion
 Prolactin- inhibits the action of GnRH on the pituitary, and antagonizes the action of gonadotropins
on the ovaries

217
Respiratory Physiology
Structure Function relationship in lung:

MCQ
Following are characteristics of conducting airways except
A. Includes the first 16 generations starting from trachea
B. Smooth muscles and cartilage predominate in this region
C. Membrane bound organelles namely lamellar bodies are present
D. secrete a variety of molecules that aid in lung defense

Ans-C
Conducting Zone  First 16 generations
 Comprises of
trachea,bronchi,bronchioles and
terminal bronchioles
Respiratory Zone  Last 7 generations
 Comprises of Respiratory
bronchioles,alveolar ducts and alveolar
sacs

Conduction zone to respiratory zone transition events

 Secretory glands are absent from the epithelium of the bronchioles and terminal bronchioles
 smooth muscle-more prominent
 cartilage-absent
 Clara cells,Basal cells- serve as progenitor cells after injury

Epithelial cells in the conducting airway secrete  Secretory immuno-globulins (IgA)

 collectins (including surfactant protein
(SP) -A and SP-D)
 reactive oxygen species
 reactive nitrogen species
 chemokines,cytokines

Respiratory cilia  beat at rates of 10–15 Hz

 is capable of moving particles 16
mm/min

Alveolar airways  Humans have 300 million alveoli

 Total area-70 m2.
 two types of epithelial cells- Type I
cells(primary lining cells of the
alveoli,Covers 95% of area) and Type II
cells (granular pneumocytes)
 type II cell- production of surfactant
- lamellar bodies- membrane-
bound organelles containing
phospholipids

218
 - Surfactant-reduces surface
tension
 Other cells- Pulmonary alveolar
macrophages,lymphocytes, plasma cells,
neuroendocrine cells, and mast cells

MCQ
Most common mutation in cystic fibrosis involves lack of following amino acid
A. Cysteine
B. Glycine
C. Methionine
D. Phenylalanine

Ans-D
Cystic fibrosis:
 Cystic fibrosis transmembrane conductance regulator(CFTR)-chloride channel. Long arm
chromosome 7
 5 classes of mutations
 Class 2 mutation most common-loss of the phenylalanine position 508
 infections, particularly with Pseudomonas aeruginosa common
 Defective mucociliary escalator function

MCQ
The type of receptor present in bronchial smooth muscle is
A. Alpha-1
B. Alpha-2
C. Beta-1
D. Beta-2

Ans-D
Airway smooth muscles:
 Trachea and bronchi-mainly smooth muscles
 The walls of the bronchioles are almost entirely smooth muscle
 Beta-2 receptors- Bronchodilation,increase bronchial secretion
 α 1 adrenergic receptors inhibit secretions

Mechanics of ventilation:

MCQ
Following muscles play a role during inspiration except
A. Diaphragm
B. External intercostals
C. Internal intercostals
D. Sternocleidomastoid

Ans-C
Muscles of inspiration Muscles of Expiration
Major muscles: Largely a passive process
Diaphragm Muscles:
External intercostals Internal intercostals
Deep inspiration: Anterior abdominal muscles
Scalene
Sternocleidomastoid

Bucket handle movement:

Increases the transverse diameter
Pump handle movement:
Increases the antero posterior diameter

219
MCQ
Negative intrapleural pressure is basically due to
A. Lymphatic drainage of pleura
B. Uniform distribution of surfactant
C. Negative intraalveolar pressure
D. Presence of cartilage in upper airway

Ans-A
Intrapleural pressure:
 Normally negative in the range of -4 to -5 cm H20
 Also aids in venous return
 Negative pressure created by inward elastic recoil of lung and outward movement of chest wall
 The basic cause of this negative pressure is pumping of fluid from the space by the lymphatics
 Most abundant lymphatics-Lungs

Lung volumes and capacities:

MCQ
The air left in the lungs after a maximal expiratory effort is
A. Tidal volume
B. Inspiratory reserve volume
C. Expiratory reserve volume
D. Residual volume

Ans-D
Normal Vd/Vt ratio is
A. 0.11
B. 0.35
C. 0.76
D. 0.84

Ans-B
Total alveolar ventilation in L/min is
A. 3.3
B. 4.2
C. 5.6
D. 7.4
Ans-B
The air taken in and given out during normal respiration is
A. Tidal volume
B. Inspiratory reserve volume
C. Expiratory reserve volume
D. Residual volume

Ans-A
In which of the following condition respiratory muscles are relaxed
A. Tidal volume
B. Inspiratory reserve volume
C. Expiratory reserve volume
D. Functional residual capacity
Ans-D
MCQ
Inward elastic recoil of lung balances with outward recoil of chest wall at
A. Total lung capacity
B. Vital capacity
C. Functional residual capacity
D. None of the above
Ans-C

220
 RESPIRATORY VOLUMES

MEASUREMENT TYPICAL DEFINITION

VALUE

Tidal volume (TV) 500ML Amount of air that enters or leaves lungs during
one inspiration or expiration (respiratory cycle)

Inspiratory reserve 3000ML Maximum volume of air that can be inspired

volume (IRV) over the normal TV

Expiratory reserve 1200ML Extra volume of air expired by forceful expiration

volume (ERV) after the end of normal tidal expiration

Residual volume (RV) 1200ML Amount of air left in lungs after forced
exhalation

Closing volume lung volume above the residual volume at which

the alveoli of lung bases begin to close off

RESPIRATORY CAPACITIES

Vital capacity (VC) 4700ML IRV+TV+ERV, maximum amount of air that can
be exhaled after a maximum inspiration

Inspiratory capacity (IC) 3500ML TV+IRV, maximum amount of air that can be
inhaled after a normal expiration

Functional residual 2400 ML RC+ERV, amount of air remaining in the lungs

capacity (FRC) after a normal tidal expiration

Total lung capacity 5900ML RV+VC, maximum volume to which the lungs can
ITLC) be expanded

Closing capacity RV+ the volume expired between the beginning

of airway closure and
the RV
MCQ
By spirometry,one can’t measure
A. Residual volume
B. Functional residual capacity
C. Total lung capacity
D. All of the above

Ans-D
Measurement of lung volumes and capacities
Spirometry can’t measure
1. Residual volume
2. Functional residual capacity
3. Total lung capacity
These can be measured using:
1. Helium dilution technique
2. Nitrogen washout method

221
3. Plethysmography

True statement regarding whole body plethysmography during inspiration is

A. Pressure in both lungs and box increase
B. Pressure in both lungs and box decrease
C. Pressure in lung increase but in box decrease
D. Pressure in lung decrease but in box increase

Ans-D
Whole body plethysmography

Boyle’s Law:
PV=constant
Inspiration
In lungs:
V increase & P decrease
In box:
V decrease & P increase
Expiration
In lungs:
V decrease & P increase
In box:
V increase & P decrease
MCQ
Regarding compliance of lung, false statement is
A. Compliance is change in lung volume per unit change in airway pressure
B. normal values are ∼0.2 L/cm H2O
C. Compliance of lung decreases in emphysema
D. Is a measure of elastic property of lung

Ans-C

222
Compliance of lung is a measure of
A. Elasticity
B. Amount of air
C. Blood flow
D. Presence of fluid

Ans-A
Compliance of lung:
Decreases in:
Pulmonary interstitial fibrosis
Pulmonary congestion
Decreased surfactant
Interstitial lung disease
Increases in:
Emphysema
Aging lung

MCQ
Regarding pulmonary circulation false statement is
A. It is a low resistance, low pressure and high compliance system
B. Vasodilation occurs in response to hypoxia
C. Pressure in pulmonary artery is 24/9 mmHg
D. Mean capillary pressure is 10 mmHg which favours reabsorption
Ans-B
Effect of Hypoxia:
Pulmonary Vasoconstriction
Systemic circulation- Vasodilatation
Pulmonary blood flow regulators:
Constriction Relaxation
Adrenergic (alpha) Adrenergic (Beta)
Adenosine Muscarinic
Endothelin Bradykinin
Angiotensin II Histamine
Thromboxane ANP
MCQ
Ventilation perfusion ratio is maximum at
A. Apex of lung
B. Base of lung
C. Middle of lung
D. Posterior lobe of lung

Ans-A
Ventilation perfusion ratio
 Normal VQ ratio is 4/5=0.8
 Highest in apex-favours growth of mycobacterium tuberculosis
 Lower lobes relatively well perfused=gravity effect
 Ventilation without perfusion-Dead space ventilation
 Perfusion without Ventilation –Shunt blood

MCQ
Single breath nitrogen technique is useful to measure
A. Functional residual capacity
B. Vital capacity
C. Anatomic dead space
D. All of the above

Ans-C
Dead spaces

223
A. Anatomic-respiratory system volume exclusive of alveoli. Normal value-150 ml
B. Methods for estimating anatomic dead space:
1. Single-breath N2 curves
2. Bohr’s equation

Physiologic dead space:

volume of gas not equilibrating with blood- wasted ventilation

MCQ
Gas used to measure diffusion capacity of lung is
A. Oxygen
B. Carbon di oxide
C. Carbon monoxide
D. Nitrogen

Ans-C
Diffusion across alveolocapillary membrane

 substances passing from the alveoli to the capillary blood reach equilibrium in the 0.75 s
 N2O- not limited by diffusion but by the amount of blood flowing through the pulmonary
capillaries(Perfusion-limited)
 Carbonmonoxide- taken up by hemoglobin in the red blood cells at such a high rate,
equilibrium is not reached in the 0.75 s(not limited by perfusion at rest -diffusion-limited)
 Oxygen-Intermediate. Taken up by hemoglobin, but much less avidly than CO, reaches
equilibrium with capillary blood in about 0.3 s(Perfusion limited)
 Diffusing capacity- directly proportional to the surface area of the alveolocapillary mem-
brane and inversely proportional to its thickness
 diffusing capacity for CO (Dlco)- measured as an index of diffusing capacity because its
uptake is diffusion-limited
VCO/
DLCO = PACO
 Normal value of Dlco at rest-25 mL/min/mm Hg
 Normal value of diffusing capacity for O 2 at rest-25 mL/min/mm Hg

MCQ
Surfactant is synthesized by
A. Type-I pneumocytes
B. Type-II pneumocytes
C. APUD cells
D. Heart failure cells

Ans-B

Surfactant is synthesized at
A. 5th month of intra-uterine life
B. 7th month of intra-uterine life
C. 36 weeks of fetus
D. After birth

Ans-B
Stability of alveoli is maintained by
A. Compliance of lung
B. Residual air in alveoli
C. Negative intrapleural pressure
D. Reduce surface tension by surfactan
Ans-D
Surfactant production is accelerated by

224
 A. Iodine
B. Carbamazepine
C. Glucocorticoids
D. aldosterone

Ans-C

Surfactant
 Mixture of dipalmitoylphosphatidylcholine(DPPC), other lipids, and proteins
 Proteins- surfactant protein (SP)-A, SP-B, SP-C, and SP-D
 SP-A and D involved in innate immunity
 Production starts at 28th week of gestation
 Produced by Type 2 cells(Granular Pneumocytes)
 Type II cells are important in alveolar repair
 maintains alveolar structure by reducing surface tension
 IRDS,Pulmonary alveolar proteinosis

MCQ
All of the following are non respiratory functions of lung except
A. contain a fibrinolytic system that lyses clots in the pulmonary vessels
B. Inactivates angiotensin ii
C. Removes serotonin and norepinephrine
D. Acts as a blood reservoir

Ans-B

Non respiratory functions of lung

 Stores 500ml of blood-acts as a reservoir
 Prostaglandin metabolism-both synthesizes and metabolises it
 Removes serotonin, norepinephrine, bradykinin
 Fibrinolytic system
 Angiotensin converting enzyme-forms angiotensin ii

MCQ
False regarding J receptor reflex
A. Discovered by A.S.Paintal
B. Sensitive to pulmonary congestion
C. Myelinated endings
D. Stimulated by bradykinin

Ans-C
J Receptors:
 Discovered by A.S.Paintal
 juxtaposition to the pulmonary capillaries
 Stimulated by pulmonary congestion, pulmonary edema
 C fiber endings (unmyelinated)
 Pulmonary chemoreflex-rapid breathing, bradycardia, and hypotension
 Stimulated by Exogenous and endogenous substances (eg, capsaicin, bradykinin, serotonin)

Airway and lung receptors:

Vagal Location in
Innervation Type Interstitium Stimulus Response

Myelinated Slowly Among airway smooth Lung inflation Inspiratory time shortening

225
 adapting muscle cells (?) Hering–Breuer inflation
and deflation reflexes
Bronchodilation
Tachycardia
Hyperpnea
Rapidly Among airway Lung hyperinflation Cough
adapting epithelial cells Exogenous and endogenous substances Bronchoconstriction
(eg, histamine, prostaglandins) Mucus secretion
Unmyelinated Pulmonary C Close to blood vessels Lung hyperinflation Apnea followed by rapid breathing
C fibers fibers Exogenous and endogenous substances Bronchoconstriction
Bronchial C (eg, capsaicin, bradykinin, serotonin) Bradycardia
fibers
Hypotension
Mucus secretion

Which factor is least likely affect turbulence of airflow?

A. Density of gas
B. Viscosity of gas
C. Pressure of gas
D. Diameter of airways

Ans-C
Reynold’s number:
density*velocity*diameter/viscosity

Transport of Gases

MCQ
All the following factors shift the oxygen dissociation curve to the right except
A. Increased pH
B. Increased 2,3-BPCG
C. Increased temperature
D. Increased PCO2

Ans-A

What is the role of 2,3 DPG in Hb

A. Causes osmotic fragility
B. Attains buffering capacity
C. Increases affinity for O2
D. Unloads O2 to the tissue

Ans-D
Oxygen Hemoglobin Dissociation curve

 relates percentage saturation of the O 2 carrying power of hemoglobin (SaO2) to the Po2
 Hemoglobin-tense (T) configuration- reduced the affinity for O 2
 Relaxed(R) configuration- exposes more O2 binding sites
 When fully saturated, each gram of normal hemoglobin contains 1.34 mL of O 2
 1 dL of blood contains 20.1 mL (1.34 mL × 15) of O2 bound to hemoglobin when the hemo-
globin is 100% saturated

Shift to the Right (Release/tissues) Shift to the left (Lungs/binding)

*Increased PCO2 *Decreased PCO2
* Increased temperature * Decreased temperature
* Increased 2,3-DPG * Decreased 2,3-DPG

226
* Growth hormone * Alkalosis (increased pH)
* Exercise * Fetal Hb(poor binding of 2,3-DPG by the γ polypeptide
* Hypoxia chains)
* High altitude * stored blood(2,3-DPG level falls)
* anemia
* Acidosis (decreased pH)
* Sickle cell anemia
* Adult Hb

 HbF binds Forcefully to oxygen

 Stored blood is SOS: Stored blood Hb binds to Oxygen Strongly because of decrease in 2,3
BPG
 2,3 BPG binding site is BBC: BPG binds to Beta Chain of Hb

Bohr Effect:

 The decrease in O 2 affinity of hemoglobin when the pH of blood falls

 Curve shifts to the right

Haldane effect:

 increased capacity of deoxygenated hemo-globin to bind and carry CO2

Myoglobin:
 Iron-containing pigment found in skeletal muscle.
 binds 1 mol of O2 per mole protein (Hb binds 4)
 Dissociation curve- a rectangular hyperbola
 higher affinity for O 2(Leftward shift in curve)
 During exercise- it continues to provide O2 under reduced blood flow and/or reduced Po2 in the
blood
 Neuroglobin-Facilitates O2 transport in brain

MCQ
CO2 is mainly transported in the blood as
A. Bicarbonate
B. Dissolved form
C. Carbamino compound
D. Bound with hemoglobin

Ans-A

MCQ
The normal level of oxygen in the blood when the hemoglobin is fully saturated with O2
A. 15ml/dl
B. 20ml/dl
C. 1.34ml/dl
D. 200ml/dl

Ans-B

Solubility of CO2 is------ times than that of O2

A. 5
B. 10

227
C. 20
D. Same

Ans-C
mL/dL of Blood Containing 15g of Hemoglobin
Arterial Blood (Po2 95 mm Hg; Venous Blood (Po2 40mm Hg; Pco2 46mm Hg; Hb 75%
Pco2 40mm Hg; Hb 97% Saturated)
Saturated)
Gas Dissolved Combined Dissolved Combined
O2 0.29 19.5 0.12 15.1
CO2 2.62 46.4 2.98 49.7
N2 0.98 0 0.98 0

Co2 Transport
A. Solubility 20 times that of oxygen

Method Percentage
• Dissolved in Plasma 7 - 10 %
• Chemically Bound to
Hemoglobin in RBC’s 20 - 30 %
• As Bicarbonate Ion in
Plasma 60 -70 %

MCQ
Function of anion exchanger 1 in RBCs is
A. Maintains hemoglobin in reduced state
B. Maintains pH inside RBCs
C. Exchanges chloride for bicarbonate
D. None of the above

Ans-C
Chloride shift
 anion exchanger 1 also called as band 3 protein
 Chloride is exchanged for Hco3 inside RBCs
 Chloride drags water and RBCs swell in venous blood
 Hematocrit of venous blood is normally 3% greater than that of the arterial blood

Acclimatization to high altitude

MCQ
Acclimatization in high altitude involves all the compensatory changes except 107
A. Polycythemia
B. Shift of ODC to right
C. Hyperventilation
D. Decreased density of systemic capillaries

Ans-D
Acclimatization cause all except
A. Polycythemia
B. Pulmonary hypertension
C. Decreased enzyme activity
D. Increased capillary permeability

Ans-C
Acclimatization to Low PO2
 Increased Pulmonary Ventilation

228
 Increase in Red Blood Cells and Hemoglobin Concentration
 Increased Diffusing Capacity After Acclimatization
 Increased Tissue Capillarity
 Cellular Acclimatization--cell mitochondria and cellular oxidative enzyme systems

MCQ
All of the following are useful for high altitude illness except
A. Acetazolamide
B. Hyperbaric oxygen
C. Nifedipine
D. Propranalol

Ans-D
Treatment for high altitude illness
 Descent to lower altitude
 Hyperbaric oxygen therapy
 Acetazolamide-carbonic anhydrase inhibitor. Stimulates respiration
 Large dose corticosteroids
 Nifedipine-calcium channel blocker to lower pulmonary arterial pressure

Regulation of respiration

MCQ
Pneumotaxic centre is located in
A. Hypothalamus
B. Pons
C. Cerebrum
D. Medulla

Ans-B

Respiratory centre is stimulated by

A. Cyanide
B. Hypoxia
C. Nicotine
D. Hypercarbia

Ans-D

Inhibition of Pneumotaxic centre causes

A. Prolonged inspiratory spasm
B. Prolonged expiratory spasm
C. Decreased inspiration
D. Hyperpnoea

Ans-A
Neural control of respiration:
 Voluntary system-located in the cerebral cortex and sends impulses to the respiratory motor neurons
via the corticospinal tracts
 Automatic system-pacemaker cells in the medulla-activate motor neurons in the cervical and thoracic
spinal cord that innervate inspiratory muscles

Medullary system: Pontine & vagal influences:

Pre-Botzinger Complex:
* rhythm of respiration (pace maker of
respiration)
* has NK1 receptors,μ-opioid receptors
and 5HT 4 receptors
Switching between inspiration & expiration
Pneumotaxic centre:
* medial parabrachial and Kölliker–Fuse nuclei
* inhibitory effect on apneustic centre
Apneustic centre:

229
* substance P stimulates and opioids
inhibit respiration
* 5HT 4 agonists blocks the inhibitory
effect of opiates
Dorsal respiratory group (DRG):
* Nucleus Tractus solitaries (NTS)
* Site of origin of rhythmic inspiratory
discharge. (Inspiratory ramp signals)
Ventral respiratory group (VRG):
* Nucleus Retro Ambigualis (NRA)
* Both inspiratory & expiratory control
* lower pons
* has an intrinsic rhythm, promotes prolonged inspirations
when active
Vagus:
Stretching of lungs during inspiration
Stimulates afferent pulmonary vagal fibres
Inhibit inspiratory discharge

Chemical control of respiration:

Peripheral chemoreceptors: Central chemoreceptors:
Carotid and aortic bodies: * Location: ventral surface of the medulla, solitary tract
* two types of cells, type I and type II cells nuclei, the locus ceruleus, and the hypothalamus
* Type-I (glomus) cells * CSF (H+) is the potent stimulus to central chemo
1. are closely assoivated with cup like endings receptor.
of the afferent nerves * Effects of Co2- mainly due to its movement into the
2. resemble adrenal chromai n cells and have CSF and brain interstitial fluid and increases the H +
dense-core gran-ules containing catecholamines concentration
that are released upon expo-sure to hypoxia * The magnitude of the stimulation is proportional to
and cyanide the rise in H + concentration.
3. excited by hypoxia-Neurotransmitter-
Dopamine(D2 receptor)
4. have O 2 sensitive K + channels- conductance
is reduced in proportion to the degree of
hypoxia
* Type II-Glia like cells, surrounds four to six
type I cells
* Blood flow per unit of tissue is so enormous-
2000 mL/100 g of tissue/min
* Afferents from the carotid bodies ascend to
the medulla via the carotid sinus and
glossopharyngeal nerves, and
fibers from the aortic bodies ascend in the vagi
* respond to PO2+PCO2&H+ of arterial blood
* Hypoxia is the potent stimulus
* carotid bodies more effective than aortic
bodies

Types of Hypoxia:

MCQ
Which is the best parameter for analysis of hypoxic hypoxia
A. Arterial p02
B. Arterial pco2
C. Venous po2
D. AV o2 difference

Ans-A

Anemic hypoxia is due to

A. reduced po2 in arterial blood
B. reduced pco2 in arterial blood
C. reduced po2 in venous blood
D. Reduced o2 content in blood

Ans-D

230
Pao2 levels in venous blood are very high in
A. Anemic hypoxia
B. Hypoxic hypoxia
C. Stagnant hypoxia
D. Histotoxic hypoxia

Ans-D 111

Hyperbaric oxygen therapy is much helpful in

A. Anemic hypoxia
B. Hypoxic hypoxia
C. Stagnant hypoxia
D. Histotoxic hypoxia

Ans-A
Hypoxia: O2 deficiency at the tissue level

Type Causes Mechanism PAO2 PaO2 O 2 A-V

content difference
Hypoxic/ High altitude -Poor availability of O2 for ↓ ↓ ↓ ±
Anoxic & diffusion
Pneumonia _Decreased Partial Pressure of
O2 in arterial blood
Anemic Anemia CO -Decreased O2 carrying ± ± ↓ ±
Poisoning capacity
Stagnant/ Cardiogenic O2 content of the blood is ± ± ± ↑
Ischemic/ shock exhausted due to reduction in
Hypoperf blood velocity
usion
Histotoxic Beriberi Tissue cannot make use of ± ± ± ↓
HNC available O2
Poisoning

Best test for hypoxia

 Hypoxic hypoxia (Anoxic/Arterial): partial pressure of arterial O2, treated by oxygen therapy
 Anemic hypoxia-oxygen content (Hb%)
 Stagnant hypoxia- A-V difference (increased)
 Histotoxic hypoxia- A-V difference(decreased) or PO 2 of venous blood (increased)

MCQ
Regarding Cheyne–Stokes Respiration, false statement is
A. Seen most commonly in patients with congestive heart failure and uremia
B. Follows the sequence of apnea, hyperpnea and apnea
C. Occurs due to reduced sensitivity to Co2
D. Occurrence is not always pathological

Ans-C
Cheyne–Stokes Respiration:
 Called as periodic breathing
 seen most commonly in patients with congestive heart failure and uremia
 Seen also in normal individuals during sleep
 increased sensitivity to CO2
 Follows apnea hyperpnea apnea and the cycle continues

Abnormal respiratory patterns:

231
 Pattern Cause Mechanics

Cheyne-stokes -Opium Periodic breathing due to Rhythmic alteration of

respiration poisoning apnea & hyperpnea

-Uremia & Waxing & waning tidal volume

CCF

-hypoxia

Biot’s breathing Meningitis Periodic breathing with one or more large tidal
(Irregularly volumes separated by apnea
irregular
breathing)

Kussmaul’s -DKA Rapid & deep breathing

respiration
hunger) -Uremia

Ondine’s curse Loss of spontaneous breathing with only voluntary

control

MCQ
Nitrogen narcosis is caused due to
A. Nitrogen inhibits dismutase enzyme
B. Increase production of nitrous oxide
C. Increased solubility of N2 in nerve cell membrane
D. Decrease in oxygen free radicals

Ans-C
Decompression sickness
Other names:
 Caisson’s disease
 Diver’s paralysis
 Bends (knee pain)
 Dysbarism
 Compressed air sickness

Due to sudden return to sea level-nitrogen decompresses-forms air bubbles-air embolism

Potential problems due to increased Barometric pressure:

O2 toxicity Lung damage, convulsions

N2 narcosis Due to increased solubility of N2--Euphoria,
impaired performance
HPNS Tremors, drowsiness
Air embolism Sudden death

232
Renal Physiology
Parameters Dimension
No.of nephrons in each kidney 1 million
Glomerulus 200 μm in diameter
filtration slits 25 nm wide
Free passage of neutral substances across Up to 4nm
glomerulus
total area of glomerular capillary endothelium 0.8m2
for filtration
Length of proximal convoluted tubule 15mm
Distal convoluted tubule 5mm long
collecting ducts 20mm long
total length of the nephrons 45 to 65mm
volume of blood in the renal capillaries 30–40 mL
Renal blood flow 1.2–1.3 per minute
Effective renal plasma flow (ERPF) 625 mL/min
glomerular capillary pressure 45 mm Hg
peritubular capillary pressure 8 mm Hg
pressure in the renal vein 4 mm Hg
Cortical blood flow 5 mL/g of kidney tissue/min
Medullary blood flow outer medulla(2.5 mL/g/min)
inner medulla(0.6 mL/g/min)
arteriovenous oxygen difference for the whole 14 mL/L of blood
kidney
Po2 of the cortex 50 mm Hg
PO2 of the medulla 15 mm Hg
GFR 125 mL/min is 7.5 L/h, or 180 L/d,
amount of protein in the urine <100mg/day
filtration fraction 0.16–0.20
Filtration coefficient(Kf) 4.2 ml/min/mm Hg
peristaltic contractions in ureter 1-5 times/min
Half life of vasopressin 18 min

Parts of nephron

MCQ
Filtration of proteins at the glomerulus is prevented by all except
A. Glomerular polyanion
B. Podocytes
C. Mesangial cells
D. Fenestrated endothelium

Ans-C
Proteins forming filtration slit diaphragm are all except
A. Nephrin
B. Barttin
C. Podocin
D. Alpha actinin-4
Ans-B

Filtration slit diaphragm proteins

 Nephrin
 Podocin

233
 Alpha actinin-4
Mutation in Nephrin:
 Congenital nephrotic syndrome
Mutation in Podocin:
 AR steroid resistant nephrotic syndrome

All causes contraction of mesangial cells except

A. cAMP
B. Endothelin
C. Nor epinephrine
D. Angiotensin II

Ans-A
Mesangial cells
A. Also called stellate cells
B. Major functions:
1. Are contractile-Regulates GFR
Contracting agents- Angiotensin-ii, endothelins, nor epinephrine
Relaxing agents-ANP,PGE2,Dopamine
2. Secretes extracellular matrix
3. Takes up immune complexes

MCQ
Mediator involved in tubulo glomerular feed back is
A. Dopamine
B. Norepinephrine
C. Adenosine
D. PGE2

Ans-C
Tubuloglomerular feedback
 Increase in sodium chloride delivery to distal tubule decreases GFR
 Cell involved-Macula densa
 Transport protein-Na–K–2Cl co transporter
 Mediator-Adenosine
 Response-Adenosine acts on A1 receptors in afferent arteriole----vasoconstriction---reduced GFR

MCQ
Renin is secreted by
A. Juxta glomerular cells
B. Macula densa
C. Podocytes
D. Peritubular capillaries
Ans-A
Following structures lie in renal medulla except
A. Juxta glomerular apparatus
B. Loop of Henle
C. Collecting tubule
D. Vasa recta
Ans-A

MCQ
Specialized cells present at the start of distal convoluted tubule is
A. Lacis cells
B. Juxtaglomerular cells
C. Macula densa
D. Pericytes

Ans-C

234
JG cells * Also known as Granular cells
* Secrete RENIN
* Located in media of afferent arterioles as they enter glomeruli
Macula densa * Morphologically distinct region of thick ascending limb
* Senses sodium chloride concentration via Na+-K+-Cl- co
transporter
Lacis cells * Also known as extraglomerular mesangial cells
* Located at the junction between afferent and efferent
arterioles

MCQ
All of the following cells secrete Prostaglandin E2 in kidney except
A. renal medullary interstitial cells
B. macula densa
C. Afferent arterioles
D. Collecting duct cells

Ans-C

Renal cortical blood flow is increased by

A. Prostaglandin E2
B. Nor epinephrine
C. Angiotensin II
D. Vasopressin

Ans-A
Prostaglandin E2
 important paracrine regulator of salt and water homeostasis

Secreted by:
 renal medullary interstitial cells (RMICs):Contains (COX-2) and prostaglandin synthase
 macula densa, and by cells in the collecting ducts
 Prostacyclin (PGI2)-by arterioles and glomeruli

MCQ
Brush border cells are found in
A. Glomerulus
B. Loop of Henle
C. Collecting tubules
D. Proximal convoluted tubules

Ans-D

Mechanism by which water is reabsorbed in PCT

A. Diffusion
B. Osmosis
C. Active transport
D. Facilitated diffusion

Ans-B
Substance which are secreted and filtered by kidney is
A. Sodium
B. Chloride
C. Uric acid
D. calcium

Ans-C
Potassium, uric acid,creatinine

235
Normal range of urinary osmolality(mosm/L) is
A. 50-1400
B. 300-1200
C. 500-1500
D. 100-300

Ans-A

Salient features of various nephron parts

Glomerular capillaries- only capillaries in the body that drain into arterioles
Proximal convoluted tubule:
 Brush border (microvilli)
 Major site of resorption of water & solutes

Loop of Henle:
 Countercurrent multiplier-for urine concentration
 Countercurrent exchanger- Vasa Recta
 Cortical nephrons-short loop of Henle(85%)
 Juxta medullary nephrons-Long loop(15%)

MCQ
Principal cells and intercalated cells are found in
A. Collecting duct
B. Proximal convoluted tubule
C. Loop of Henle
D. Glomerulus

Ans-A

Artificial Kidney is
A. Hemodialysis
B. Peritoneal dialysis
C. Hemoperitoneum
D. Electrodialysis

Ans-A

Glucose reabsorption occurs in

A. Proximal convoluted tubule
B. Distal convoluted tubule
C. Loop of Henle
D. Collecting duct

Ans-A

Transport maximum for glucose is

A. 180 mg/min
B. 375 mg/dl
C. 120 mg/min
D. 375 mg/min

Ans-D
Transport maximum (Tm):
 renal active transport systems have a maximal rate at which they can transport a particular solute
 Tm for Glucose-375 mg/min
 Renal threshold for glucose:

236
Plasma level at which glucose first appears in Urine---180mg/dl

Proximal convoluted tubule:

Reabsorption:

 Water-67% of filtered load

 NaCl-67% of filtered load
 K+-67% of filtered load
 Ca2+-70% of filtered load
 Pi-80% of filtered load
 Hco3--80% of filtered load
 Protein-100% of filtered load
 Urea-67% of filtered load
Henle’s loop:

Reabsorption:

 Water-15% of filtered load(thin descending limb only)

 NaCl-25% of filtered load
 K+-20% of filtered load
 Ca2+-20% of filtered load
 Hco3--10% of filtered load
Secretion:

 Urea-thin descending limb only

Distal tubule:

Reabsorption:

 NaCl-5% of filtered load

 Ca2+-9% of filtered load
 Hco3--6% of filtered load
 Pi-10% of filtered load
 Water-variable depending on presence of ADH,ANP
Collecting Duct:

Reabsorption:

 Water- variable depending on presence of ADH,ANP

 NaCl-3% of filtered load
 K+-normally zero
 Hco3--4% of filtered load
 Urea- variable depending on presence of ADH
Secretion:

 K+-0% to 70% of the filtered load

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MCQ
Following disorders are correctly matched with their protein defect except
A. Bartter’s syndrome-Na+ K+ Cl- transporter
B. Gitelman syndrome-Na Cl- cotransporter
C. Dent’s disease-K+ channel
D. Liddle’s syndrome-Epithelial sodium channels(ENac)

Ans-C
Monogenic renal diseases involving transport proteins:

Diseases Mode of Gene Transport protein Nephron Phenotype

inheritance segment
Cystinuria type I AR SLC3A1 Basic amino acid Proximal Increased
transporter (rBAT) tubule excretion of basic
amino acids ,
nephrolithiasis
(kidney stones)
Proximal renaltubular AR SLC4A4 Na+ -HCO3- Proximal Hyperchloremic
acidosis cotransporter tubule metabolic acidosis

Bartter syndrome AR SLC12A1 Na+-K+-2Cl- TAL Hypokalemia,

(type I) transporter metabolic
(furosemide alkalosis, hyperal-
sensitive) dosteronism
KCNJ1 Potassium channel
(type II)
CLCNKB Chloride channel
(type III)
X-linked XLR CLC5 Chloride channel Distal Hypercalciuria,
nephrolithiasis (Dents (C1C-5) tubule nephrolithiasis
disease) (kidney stones)
Hypomagnesemia- AR PCCLN-1 Paracellin-1 TAL Hypomagnesemia,
Hypercalciuria hypercalciuria,
syndrome nephrolithiasis
Gitelman syndrome AR SLC12A3 Thiazide-sensitive Distal Hypomagnesemia,
cotransporter tubule hypokalemic
metabolic
alkalosis,
hypocalciuria,
hypotension
Liddle syndrome AD SCNN1B, α, β, and γsubunit Collecting Decreased
SCNN1G of amiloride- duct excretionof Na+,
sensitive Na+ hypertension
channel

Glomerular filtration rate

MCQ
Following factors affect glomerular filtration rate in healthy individuals except
A. Afferent or efferent arteriolar constriction
B. Changes in glomerular capillary hydrostatic pressure
C. Changes in oncotic pressure in Bowman’s capsule

238
D. Changes in effective filtration surface area

Ans-C
Net filtration pressure in kidney is
A. 10 mm Hg
B. 12 mm Hg
C. 15 mm Hg
D. 20 mm Hg

Ans-C

Glomerular Filtration Rate

A. Rate-125ml/min or 180L/day
B. Predominant Regulating factors:
 Hydrostatic pressures in Glomerulus(PGC)and Bowman’s capsule(PT),Oncotic pressure in glomerular
capillaries(πG)
 Oncotic pressure in Bowman’s doesn’t play a role since proteins are not filtered
 Net filtration pressure-15 mm Hg
 Only in glomerular capillaries-Filtration throughout

Glomerular Filtration Rate:

Parameters Afferent end(mm Hg) Efferent end((mm Hg)

mean hydrostatic pressure in 45 45
the glomerular capillaries
the mean hydrostatic pressure 10 10
in the tubule (Bowman’s space)
oncotic pressure of the plasma 20 35
in the glomerular capil-laries
Net filtration pressure 15 0

MCQ
Filtration Fraction normally is
A. 0.10
B. 0.20
C. 0.30
D. 0.40

Ans-B
• Filtration Fraction=GFR/RPF
• Only 20% of the plasma is filtered(1/5th)

Substances used to estimate filtration fraction are

A. Insulin & mannitol
B. Urea & diodrast
C. PAH & phenol red
D. Inulin & PAH

Ans-D

MCQ
The value of Inulin clearance is
A. 1 ml/min
B. 10 ml/min
C. 126 ml/min

239
D. 600 ml/min

Ans-C

Substance with least renal clearance

A. Urea
B. protein
C. Glucose
D. Creatinine

Ans-C
Normal clearance values of different solutes:

Substance Clearance (mL/min)

Glucose 0
Sodium 0.9
Chloride 1.3
Potassium 12
Phosphate 25
Urea 75
Inulin 125
Creatinine 140
PAH 560

The renal plasma flow is determined by

A. Creatine
B. Inulin
C. PAH
D. Evans blue

Ans-C
Para Amino Hippuric Acid
• filtered by the glomeruli and secreted by the tubular cells-High Extraction ratio
• Effective Renal plasma flow- 625 mL/min
• Actual RPF = 700mL/min(Ext.Ratio-0.9)
• Renal blood flow-1273ml/min
• Tm is 80mg/min

Anti diuretic hormone/Vasopressin

MCQ
Vasopressin exerts its antidiuretic activity primarily through
A. V1 receptors
B. V2 receptors
C. V3 receptors
D. V4 receptors

Ans-B

Vasopressin mediates its action through insertion of following channel

A. Epithelial sodium channels
B. Chloride bicarbonate exchanger
C. Urea transporter
D. Aquaporins

240
Ans-D
“Free water clearance” (CH2O)

 to quantitate the gain or loss of water by excretion of a concentrated or dilute urine

 difference between the urine volume and the clearance of osmoles
UOsm V
CH2O = V• –
P
Osm

(V is the urine flow rate and UOsm and POsm ,the urine and plasma
osmolality respectively)

 CH2O is negative when the urine is hypertonic and positive when the urine is hypotonic

ADH Receptors Characteristics

V1A * vasoconstriction
* decrease in cardiac output(area postrema)
* glycogenolysis in the liver
V1B (also called V 3 receptors) * unique to the anterior pituitary
* secretion of adrenocorticotropic hormone (ACTH)
V2 receptors * Acts through cAMP
* insertion of aquaporin 2 into the apical membranes of the
principal cells of the cortical collecting ducts

Aquaporins
• In 2003,Dr.Peter Agre received Nobel prize in chemistry for its discovery

Aquaporin subtype Location

AQP-1 Apical and basolateral membranes of proximal tubule and distal thin limb of
Henle
AQP-2 Apical side of principal cells in collecting tubule(Levels regulated by ADH)
AQP-3 and AQP-4 Basolateral side of principal cells in collecting tubule
AQP-4 Blood Brain barrier

MCQ
In the presence of vasopressin, the greatest fraction of filtered water is absorbed in the
A. proximal tubule
B. loop of Henle
C. distal tubule
D. cortical collecting duct
E. medullary collecting duct

Ans-A- 70% in PCT

For concentration of urine by ADH, absorption of water occurs from

A. Collecting ducts
B. PCT
C. Ascending loop of Henle
D. Descending loop of Henle

Ans-A
Major functions of the various collecting-duct cells:

Principal cells

241
  Reabsorb sodium (stimulated by aldosterone)
 Secrete potassium (stimulated by several signals, including aldosterone)
 Reabsorb water (stimulated by antidiuretic hormone)

Type A intercalated cells

 Secrete hydrogen ions, which effect reabsorption of bicarbonate and excretion of titratable
acid (stimulated by increased Pc o2and decreased extracellular pH)
 Reabsorb potassium

Type B intercalated cells

 Reabsorb chloride (stimulated by chloride depletion)

 Secrete bicarbonate (stimulated by increased extracellular pH)

For concentration of urine, vasopressin also up regulates the following

A. Epithelial sodium channels
B. Chloride bicarbonate exchanger
C. Urea transporters A1 and A3
D. H+ K+ ATPase

Ans-C
Urea transporters in kidney
• Urea-50% contribution to medullary osmolarity
• Urea transporters A1,A2,A3,A4 in kidney
• UT-A1 and UT-A3-regulated by vasopressin
• UT-B is found in erythrocytes and in the descending limbs of the vasa recta

MCQ
All of the following stimuli increase vasopressin secretion except
A. Increased plasma osmolarity
B. Alcohol
C. Nausea
D. Angiotensin II

Ans-B
Vasopressin Secretion Increased
Increased effective osmotic
Pressure of plasma
Decreased ECF volume
Pain, emotion, stress, exercise
Nausea and vomiting
Standing
Clofibrate, carbamazepine
Angiotensim II

Vasopressin Secretion Decreased

Decreased effective osmotic pressure of plasma
Increased ECF volume
Alcohol

MCQ
Osmoreceptors are present in
A. Anterior hypothalamus

242
B. Posterior hypothalamus
C. Pineal gland
D. Hippocampus

Ans-A 124

Renin angiotensin system

MCQ
Which of the following facilitates renin release
A. Vasopressin
B. High Na+ concentration in DCT
C. Sympathetic stimulation
D. Angiotensin-II

Ans-C
Conditions that increase renin secretion:
• Na+ depletion
• Sympathetic stimulation(β1 receptors in JG cells)
• Diuretics
• Hypotension
• Hemorrhage
• Upright posture
• Dehydration

Hormones that regulate NaCl and water absorption:

Hormone Major stimulus Nephron site of Effect on transport

action

Angiotensin II ↑Renin PT ↑NaCl and H2O reabsorption

Aldosterone ↑Angiotensin II, ↑*K+]p TAL, DT/CD ↑NaCl and H2O reabsorption
ANP ↑ECV CD ↓H2O and NaCl reabsorption
Urodilatin ↑ECV CD ↓H2O and NaCl reabsorption
Sympathetic nerves ↓ECV PT, TAL, DT/CD ↑NaCl and H2O reabsorption
Dopamine ↑ECV PT ↓H2O and NaCl reabsorption
ADH ↑Posm, ↓ECV DT/CD ↑H2O reabsorption

All about Angiotensin II-True or false

• It is a much more potent vasopressor compared to nor epinephrine
True
• It inhibits ADH release
False
• It reduces Na reabsorption in PT
False
• It facilitates norepinephrine release from postganglionic sympathetic neurons
True
• It plays an important role in cardiac remodeling after a myocardial infarction
True
• It causes mesangial cells to contract
True

243
• Angiotensin III has 100% aldosterone stimulating activity
True

Angiotensin-II:

Receptor Characteristics
AT1  Acts by increasing the cytosolic free Ca 2+
level
 subtypes, AT1A and AT1B
 AT1A- mediates most of the known
effects of angiotensin II
 AT1B- anterior pituitary and the adrenal
cortex
 excess of angiotensin II down-regulates
the vascular receptors, but up-regulates
the adrenocortical receptors
 increases production of caveolin-1
AT 2  Coded in X chromosome
 open K+ channels
 increases the production of Nitric oxide
 more plentiful in fetal and neonatal life

Actions of Angiotensin II

 one of the most potent vasoconstrictors known

 arteriolar constriction-rise in systolic and diastolic blood pressure
 increase the secretion of aldosterone
 facilitation of the release of norepinephrine
 contraction of mesangial cells
 increase Na+ reabsorption
 Actions in brain- decrease the sensitivity of the baroreflex(area postrema), increase the
secretion of vasopressin and ACTH(subfornical organ (SFO) and the OVLT)

Angiotensin III

 40% of the pressor activity of angiotensin II

 100% of the aldosterone-stimulating activity

Regarding Angiotensin converting enzyme(ACE) false statement is

A. Found in pulmonary endothelium,Kidney and spermatozoa
B. Converts angiotensin I to angiotensin II
C. Activates bradykinin
D. None of the above

Ans-C

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Natriuretic peptides

MCQ
Natriuretic peptides are produced from all the following organs except
A. Atrium
B. Brain
C. Ventricles
D. Vascular smooth muscles

Ans-D

Dehydration increases all the following hormones except

A. Vasopressin
B. angiotensin II
C. atrial natriuretic peptide
D. norepinephrine.

Ans-C
Mediators producing natriuresis
• Atrial natriuretic peptide
• Prostaglandin E2
• Endothelin
• Interleukin 1

Natriuretic peptides
A. Three types- Atrial Natriuretic Peptide(ANP), brain natriuretic peptide (BNP), C-type natriuretic
peptide (CNP)
B. Actions:
• dilating afferent arterioles and relaxing mesangial cells- increase Na+ excretion, inhibit Na+
reabsorption
• relax vascular smooth muscle
• inhibit renin secretion
• in the brain-effects oppose angiotensin II-lowering blood pressure and promoting natriuresis

Receptors of Natriuretic peptides

• Three types- NPR-A, NPR-B, NPR-C
• ANP has the greatest affinity for the NPR-A receptor, and CNP has the greatest affinity for the NPR-B
receptor
• NPR-C, binds all three natriuretic peptides. clearance receptor- removes natriuretic peptides from the
bloodstream, releases them later thereby maintain a steady blood level of the hormones

Erythropoietin

MCQ
Erythropoietin is secreted by
A. Cells in the macula densa
B. cells in the proximal tubules
C. cells in the distal tubules
D. Cells in the peritubular capillary bed

Ans-D
Erythropoietin
• 85% from interstitial cells in the peritubular capillary bed of the kidneys
• 15% from perivenous hepatocytes in the liver
• Produced In brain- prevents excitotoxicity
• In oviducts-Erythropoietin levels increase by estrogen-plays a role in angiogenesis

245
• Increases red cells in 2-3 days
• Epoietin alpha-Rx for anemia due to renal cause

Stimulators of erythropoietin secretion 6. hypoxia

7. cobalt salts
8. androgens
9. alkalosis at high altitude
10. catecholamines via a β-adrenergic
mechanism

Micturition Reflex

MCQ
Atonic bladder occurs in destruction of
A. Afferent impulses from the bladder
B. Efferent impulses from the spinal cord
C. Facilitative impulses from the brain
D. Inhibitory impulses from the brain

Ans-A
Micturition:

Innervation of bladder • Degree of stretch – parasympathetic

afferents (S2, S3 and S4)
• Micturition reflex - parasympathetic
efferents (S2,S3 and S4)
• Relaxation of external sphincter –
pudendal Nerve.
• Sense of fullness, pain – sympathetic
hypogastric plexus
Micturition centers  Sacral micturition center(S2-S4)
 Pontine micturition centre(Barrington’s
center)-Facilitatory
 Posterior hypothalamus- Facilitatory
 Mid brain-inhibitory
 Cerebral cortex-Detrusor motor area
located in medial frontal lobe(superior
frontal gyrus)
Micturition abnormalities Sensory denervated bladder (Atonic bladder):
 occurs due to lesions of sacral posterior
nerve roots
 stretch impulses are not transmitted to
the center, leading to over distension
and overflow dribbling(overflow
incontinence)
 bladder is thin walled, flaccid, distended
& hypotonic
Denervated bladder (Autonomous bladder):
 Both afferent & efferent fibers are
interrupted & the bladder is isolated

246
 from the spinal cord
 Initially the bladder is flaccid &
distended. Later becomes active and
partially expel its contents
 Bladder gets shrunken & atrophied
 Eg. Cauda equina lesion or section of
pelvic nerves
Uninhibited neurogenic bladder:
 In lesions in which the cortico-spinal
inhibitory fibres are damaged, leaving
the facilitatory fibres intact
 There is increased frequency with
voiding of small quantities

247
Gastrointestinal Physiology
Gastrointestinal Secretions

MCQ
Highest potassium ion concentration is in
A. Gastric secretion
B. Pancreatic secretion
C. Biliary secretion
D. Salivary secretion

Ans-C
Maximum potassium ion secretion is seen in
A. Gastric secretion
B. Pancreatic secretion
C. Biliary secretion
D. Salivary secretion

Ans-D

Activator for salivary amylase is

A. Hcl
B. Trypsin
C. Enterokinase
D. Chloride ions

Ans-D
Salivary secretion:
 1000-1500 ml/day
 pH is 7
 Secretion increases by parasympathetic system-Mainly acetylcholine
 Secretion inhibited during sleep,fear,fatigue
 Chloride ions-activator for both salivary & pancreatic amylase

Highest potassium content:

 Colonic secretion(Aldosterone dependent)
 Salivary secretion

MCQ
Following cells in gastric glands are correctly matched except
A. Parietal cells-Acid
B. Chief cells- Pepsinogen
C. Mucous neck cells-stem cells compartment
D. Surface cells-Histamine

Ans-D

248
Intrinsic factor of Castle secreted by
A. Chief cells
B. Parietal cells
C. Enterochromaffin cells
D. B cells

Ans-D
Rennin is present in
A. Liver
B. Lung
C. Kidney
D. Stomach
Ans-C
Also called Chymosin
Coagulate milk in young animals
MCQ
Following agents increase gastric acid output except
A. Gastrin
B. Histamine
C. Somatostatin
D. Acetylcholine

Ans-C
Gastric secretion:
 2.5 L per day. pH is 1-3.5
 Pepsin(protein digestion) and lipase(fat)
 Tubulovesicles-storehouse of H+ K+ ATPase
 Acid secretion increase by Gastrin (CCK-B),Histamine(H2) and Acetylcholine(M3)
 All three have synergistic action
 Inhibited by Somatostatin(activated by acid)

Cephalic phase of gastric secretion contributes what percentage

A. 20
B. 70
C. 10

249
 D. 100
Ans-A
Cephalic phase of gastric secretion
A. On food entering intestine
B. On food entering stomach
C. On thinking food
D. On food entering large intestine

Ans-C
Gastric secretions increased by all except
A. Histamine
B. Acetylcholine
C. Gastrin
D. HCL

Ans-D
Gastric secretions decreased by
1. HCL
2. Somatostatin
3. Secretin
4. CCK
5. GIP
6. VIP
7. PGE2
MCQ
Pancreatic juice rich in enzymes is facilitated by
A. Secretin
B. Gastrin
C. Cholecystokinin
D. Neurotensin

Ans-C

Major stimulus for secretin release is

A. Protein rich diet
B. Fat in the chyme
C. Acidic chyme
D. None of the above

Ans-C
Secretion with very high pH
A. Salivary
B. Gastric
C. Pancreatic
D. Biliary

Ans-C
Trypsinogen is converted to trypsin by
A. Pepsin
B. Enterokinase
C. HCL
D. Secretin

Ans-B
Pancreatic lipase hydrolases ester linkages of triglycerides at position
A. 1 &2
B. 1&3
C. 1&4
D. 1&5

250
Ans-B
Regulation of Pancreatic secretion:
SECRETIN CCK
alkaline pancreatic juice that is rich in Rich in enzymes but low in volume
HCO3− and poor in enzymes(alkaline)
Acts by increase in intracellular cAMP mediated by phospholipase C
Stimulated by acid in duodenum Stimulated by fat in chyme

MCQ
Succus entericus is secreted by
A. Large intestine
B. Small intestine
C. Pancreas
D. Stomach
Ans-B
Secretion of bile into bile canaliculi is by
A. Facilitated diffusion
B. Simple diffusion
C. Osmosis
D. Active transport
Ans-D
BILE

 About 500 mL is secreted per day

 Only route by which the body can dispose of cholesterol
 alkaline electrolyte solution that resembles pancreatic juice

Bile acids  Primary- cholic acid and chenodeoxycholic acid

 Secondary- deoxycholic, lithocholic, and ursodeoxycholic acids
 synthesized from cholesterol
 reduce surface tension,emulsification of fat
 Amphipathic
 form cylindrical disks called micelles
 absorbed from terminal ileum by Na+ –bile salt cotransport system (ABST)
 normal rate of bile acid synthesis-0.2–0.4 g/d
 total bile acid pool- 3.5 g
 recycles- 6–8 times per day via enterohepatic circulation

Which one is not released as proenzyme

A. Trypsin
B. Elastase
C. Chymotrypsin
D. Amylase

Ans-D
Amylase,lipase,cholestryl ester hydrolase,ribo &
deoxyribo nuclease
Enteric Nervous system:

MCQ
The nerve plexus located between the longitudinal & circular fibres of GIT

251
A. Celiac plexus
B. Hypogastric plexus
C. Auerbach’s plexus
D. Meissner’s plexus

Ans-C

Meissner’s plexus is situated in

A. Sub mucous layer
B. Muscular layer
C. Mucosa
D. The omentum

Ans-A

Enteric nervous system

A. Myenteric plexus(Auerbach‘s plexus)-present between the outer longitudinal and middle circular
muscle layers. concerned primarily with motor control(Myenteric: Motility)
B. Sub mucous plexus(Meissner‘s plexus)-present between the middle circular layer and the mucosa
(Submucosal: Secretion and blood flow)
C. Parasympathetic-increases intestinal smooth muscle activity
D. Sympathetic- decreases intestinal smooth muscle activity. Sphincters constrict
E. contains about 100 million sensory neurons, inter-neurons, and motor neurons in humans- little brain”
F. NO and VIP(responsible for the increase in local blood flow (hyperaemia) that accompanies digestion of
food)

Gastrointestinal Hormones:

MCQ
Regarding Cholecystokinin false statement is
A. Increased amylase secretion from pancreas
B. Produced by D cells in small intestine
C. Release is regulated by CCK-releasing peptide and monitor peptide
D. Involved in regulation of food intake, anxiety and analgesia

Ans-B
Enteroendocrine cells in GIT
Enteroendocrine cell Secreting hormone
G cells Gastrin
I cells Cholecystokinin
S cells Secretin
K cells gastric inhibitory peptide or
glucose-dependent insulinotropic
peptide(GIP)
Mo cells Motilin
D cells Somatostatin
Cholecystokinin * secreted by I cells in the mucosa of the upper small intestine,
Brain
* acts via CCK-A receptor
* Functions in gut- stimulation of pancreatic enzyme secretion,
contraction of the gallbladder and relaxation of the sphincter of
Oddi
* Functions in brain- regulation of food intake, production of
anxiety and analgesia
* Stimuli that increase CCK secretion: peptides and amino acids,
fatty acids (more than 10 carbon atoms)

MCQ
Neurotensin is secreted by

252
A. Stomach
B. Ileum
C. Duodenum
D. All parts of intestine

Ans-B
Which causes antral gastrin release
A. Antral distension
B. Acid
C. Secretin
D. CCK
Ans-A

Regarding Gastrin false are A/E

A. It depresses gastric motility
B. Release is stimulated by the presence of acid in the antrum
C. Causes marked secretion of pepsinogen with little acid secretion
D. Is a polypeptide

Ans-D
Gastrin • Produced by G cells in the antrum
• Three forms- G 34, G 17, and G 14 gastrins
• G 17 is the principal form
Stimuli that increase gastrin secretion:
• Peptides,aminoacids( Phenylalanine, tryptophan), Gastrin releasing
peptide( Vagal fibres)
Stimuli that decrease gastrin secretion: Acid,somatostatin, Secretin
• acts via CCK-B receptor
• Actions:
• stimulation of gastric acid and pepsin secretion
• stimulation of the growth of the mucosa of the stomach and small
and large intestines (trophic action)

MCQ
Cholagogues cause
A. Contraction of gall bladder
B. Concentration of bile
C. Acidification of bile
D. Increased production of bile

Ans-A
VIP relaxes intestinal smooth muscle
Stimulates secretions
Ghrelin stimulates growth hormone secretion
Neurotensin Illeum(Increases blood flow)
Guanylin Increases chloride secretion & fluid movement. Similar structure to
heat-stable enterotoxin of E.coli(Molecular mimicry)
Choleretics stimulate bile secretion
Bile salts,secretin,vagal
Cholagogues Gall bladder contraction
CCK,fatty acids, amino acids

MCQ
All of the following agents inhibits food intake except
A. Cholecystokinin
B. Leptin
C. Insulin
D. Ghrelin

253
Ans-D
Decrease Feeding (Anorexigenic satiety factors)
 Melanocyte-stimulating hormone (α-MSH)
 Cocaine- and amphetamine-regulated transcript (CART)
 Leptin
 Norepinephrine
 Corticotropin-releasing hormone
 Insulin
 Cholecystokinin (CCK)

Increase Feeding (Orexigenic)

 Neuropeptide Y (NPY)
 Agouti-related protein (AGRP)
 Ghrelin
 Melanin-concentrating hormone (MCH)
 Orexins A and B
 Endorphins
 Cortisol

Digestion & Absorption

MCQ
Glucose absorption from the intestine predominantly involves
A. Sodium-glucose cotransporter-1(SGLT-1)
B. Sodium-glucose cotransporter-2(SGLT-2)
C. GLUT-1
D. GLUT-5

Ans-A
Intestinal absorption is fastest for
A. Disaccharides
B. Monosaccharides
C. Oligosaccharides
D. Hexoses

Ans-B
Fastest absorbing sugar is
A. Glucose
B. Sucrose
C. Mannose
D. Lactose

Ans-A
Intestinal glucose absorption
 Sodium-glucose cotransporter-1(SGLT-1)
 Basis of oral rehydration solution
 SGLT-1 also transports galactose
 Fructose-doesn’t depend on SGLT-1
 For fructose-GLUT-5
 Doesn’t depend on INSULIN
 SGLT-1 inhibitor-phlorizin
 SGLT-2-glucose transport out of the renal tubules

MCQ
Regarding protein digestion, false statement is
A. Trypsinogen is converted to the active enzyme trypsin by enterokinase
B. Almost all of the protein in the stools is of dietary origin
C. PepT1 transports di and tri peptides and utilizes H+

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D. congenital defect in the transport of basic amino acids causes cystinuria

Ans-B
Protein digestion
 Occurs at 3 locations-the intestinal lumen, the brush border, and the cytoplasm of the mucosal cells
 Almost all of the protein in the stools is NOT of dietary origin but comes from bacteria and cellular
debris
 M cells-Payer’s patches in ileum for absorption of protein antigens
 Defect in neutral amino acid transport-Hartnup disease

MCQ
One of the following statement best describes the role of micelles in fat digestion
A. Prevents degradation of lipids in intestine
B. Micelles are protein aggregates
C. Micelles helps in absorption of both carbohydrates and lipids
D. Micelles keeping lipids in solution and transporting them to the brush border

Ans-D 137
Fat digestion
 Micelles-Bile salts. Essential for transport of digested lipid products
 Critical micellar concentration
 Helps in emulsification of fatty acids
 Lipase and colipase acts better in emulsified fat
 Major site of absorption-Jejunum

MCQ
All of the following are Short Chain Fatty Acids(SCFA) except
A. Acetate
B. Propionate
C. Butyrate
D. Acetoacetate

Ans-D
Short Chain Fatty Acids(SCFA)
 2–5-carbon weak acids
 60% of this total is acetate, 25% propionate, and 15% butyrate
 formed by the action of colonic bacteria
 Functions:
1. trophic effect on the colonic epithelial cells
2. absorbed in exchange for H+(acid base balance)
3. promote the absorption of sodium

Not a function of gut flora

A. Ferments mucin
B. Production of Vit-K
C. Decreased proliferation of epithelial cells
D. Synthesis of SCFA

Ans-C
MCQ
Vitamin B12 is mainly absorbed from
A. Duodenum
B. Jejunum
C. Ileum
D. Colon

Ans-C

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MCQ
All of the following proteins are involved in iron transport except
A. Divalent metal transporter 1 (DMT1)
B. Ferroportin 1
C. Transferrin
D. ATP7B

Ans-D
Iron absorption
 Exclusively from duodenum
 Absorbed in ferrous form
 Apical transporter-Divalent metal transporter 1 (DMT1)
 Basolateral-Ferroportin 1. aided by Haphestin
 Transporter in plasma- Transferrin(35%) saturated with iron
 Hemosiderin-Ferritin molecules in lysosomal membranes(50% iron)
 Ferritin-tracer to study phagocytosis

Vitamins synthesized by intestinal flora are

A. Vitamin A & B
B. Vitamin C
C. Vitamin K & B
D. Vitamin K & C

Ans-C
Vit K,B1,B12,B6,Biotin

Gastrointestinal motility

MCQ
Following neurotransmitters play a role in peristalsis except
A. Serotonin
B. Nitric oxide
C. Substance P
D. Histamine

Ans-D
Peristalsis:
 Initiation-STRETCH of the gut wall. It is independent of extrinsic innervation
 Local stretch-Serotonin which activates myentric plexus
 Moves in oral to caudal direction
 Peristaltic contraction(retrograde)-substance P and acetylcholine
 Peristaltic Relaxation(Antrograde)-Nitric oxide,vasoactive intestinal peptide

MCQ
Basal electrical rhythm is initiated by
A. Mesangial cells
B. Crypts of lieberkuhn
C. Interstitial cells of Cajal
D. Surface mucosal cells

Ans-C
Slow wave BER maximum in
A. Ileum
B. stomach
C. sigmoid
D. Colon

Ans-A

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Gastrointestinal smooth muscles
 Unitary type
 rhythmic fluctuations in membrane potential between about –65 and –45 mV called as basic electrical
rhythm (BER)
 interstitial cells of Cajal-stellate mesenchymal pacemaker cells
 BER itself doesn’t cause muscle contraction
 Acetylcholine increases and norepinephrine decreases BER
Region Basal electrical rhythm
stomach 4/min
duodenum 12/min
distal ileum 8/min
cecum 2/min
sigmoid 6/min

MCQ
Chemical agent responsible for generation of migrating motor complex is
A. Guanylin
B. Substance P
C. Motilin
D. Neurotensin

Ans-C
Migrating Motor Complex (MMC)
 Has three phases
 At intervals of approximately 100 min
 Motilin initiates it
 clear the gut in preparation for the next meal
 Inhibited by intake of food
 Erythromycin-binds to motilin receptors. Useful in treating patients with reduced GI motility

MCQ
Achalasia cardia occurs due to lack of release of the following
A. Norepinephrine
B. Serotonin
C. Acetylcholine
D. Nitric oxide

Ans-D
Motor functions of esophagus
 Lower esophageal sphincter-formed by esophageal smooth muscle(intrinsic) and crural portion of
diaphragm(Extrinsic)
 LES-tonically active
 Achalasia cardia(failure to relax)-Defective myenteric plexus.
 release of NO and VIP is defective and release of acetylcholine is unopposed
 Injection of botulinum toxin-inhibits acetylcholine release is useful as therapy

MCQ
Following factors delay gastric emptying except
A. Meal containing fat
B. Cholecystokinin
C. peptide YY
D. Hypoosmolality of the duodenal contents

Ans-D
Factors delay gastric emptying:
 Meal rich in fat
 Cholecystokinin

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 Peptide YY (Enterogastrone)
 Hyperosmolality of the duodenal contents

Gastric emptying time sequence is

A. Fat>protein>carbohydrates
B. Fat=protein=carbohydrates
C. Protein>fat>carbohydrates
D. carbohydrates>protein>fat

Ans-A
MCQ
Central areas implicated in vomiting are all except
A. reticular formation of medulla
B. vestibular nuclei
C. area postrema
D. Basal ganglia

Ans-D
Vomiting reflex
 The “vomiting center”-reticular formation of the medulla
 Area postrema-circumventricular organ which is outside blood brain barrier
 Vestibular nuclei-motion sickness
 Nucleus tractus solitarius
 Limbic system-“nauseating smells” and “sickening sights”
 Neurotransmitters:
1. Serotonin-5HT3 receptor
2. Dopamine-D2 receptor

MCQ
Hirschsprung Disease occurs due to
A. Defective release of serotonin
B. Overproduction of acetylcholine
C. Defective degradation of norepinephrine
D. Congenital absence of ganglion cells

Ans-D
Hirschsprung Disease
 Aganglionic megacolon
 congenital absence of the ganglion cells in both the myenteric and submucous plexuses of a segment
of the distal colon
 Mutation in the endothelin B receptor gene
 Endothelin- Endothelin B receptor action responsible for normal migration

MCQ
Ingested food reaches the sigmoid colon in
A. 4 hours
B. 8 hours
C. 10 hours
D. 12 hours

Ans-D
Transit time for food in the gut
Segment Time
cecum 4 hours
First 3rd of colon 6 hours
second 3rd of colon 9 hours
Sigmoid colon 12 hours

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MCQ
The urge to defecate first occurs when rectal pressure increases to
A. 10 mm Hg
B. 12 mm Hg
C. 16 mm Hg
D. 18 mm Hg
Ans-D
Defecation reflex:
 Spinal reflex
 Sympathetic-excitatory to internal sphincter
 Parasympathetic-inhibitory to internal sphincter
 Urge to defecate-18mm Hg
 At 55 mmHg-both external & internal sphincters relax

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