Physiology Revision E6.5

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Physiology Revision 1 01 1

PHYSIOLOGY REVISION 1 ----- Active space -----

Homeostasis 00:01:55

Maintenance of homeostasis :
Control Systems

Negative feedback Positive feedback Feed-forward

Increase followed by Increase followed Anticipatory changes


decrease by increase Example : Thinking
Example : Examples: (CLAPS) about food increases
Baroreceptor reflex. Clotting. salivary secretions.
Ca entry into
sarcoplasmic
reticulum.
LH surge.
Action potential.
Parturition.
Shock.

Assessment of effectiveness of negative feedback :


Gain = Correction/Error left :
• Correction : The reduction offered by the feedback mechanism.
• Error : The difference of the corrected value from the normal value.
a. If error left : Not a good control system.
b. Zero error : Gain is infinity (Role of kidneys in regulating BP :
Baroreceptors act first → kidney excretes large volumes of urine).
Very high gain : -33 → Regulation of body temperature.

Cellular Physiology 00:13:10

Cell membrane :
Three components : Proteins (55%), lipids (45%) and carbohydrates (5%).
• Based on functional importance : Fluid mosaic model.
• Fluid : lipid ; Mosaic : protein.
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----- Active space -----


1. Lipid bilayer :
The “Fluid” part of the model.
Three types : Phospholipids, glycolipids, and sterols.
a. Phospholipids :
Phosphatidylcholine (Lecithin : Major component of surfactant).
Sphingomyelin (Minor component of surfactant).
Phosphatidylserine : Usually intracellular (Acts as a signal for apoptosis when
presented externally).
Phosphatidylinositol (IP3) : Acts as a second messenger.
Cardiolipin :
• Exclusive to human heart in mitochondria.
• Anticardiolipin Ab seen in Syphilis.

b. Glycolipids :
Cerebrosides : Abundant in CNS.
Gangliosides : Abundant in GIT.
Fragment B of GM1 Ganglioside : Receptor for cholera toxin in GIT.
c. Sterols :
Cholesterol : Maintenance of membrane fluidity (Fluidity buffer).

Increase in fluidity Decrease in fluidity


(unsaturated FAs) (saturated FAs)
• Linoleic acid • Stearic acid
• Linolenic acid • Palmitic acid
• Arachidonic acid
• Omega 3 FAs (Fish)

2. Membrane proteins :
a. Transmembrane proteins (integral membrane proteins) : Present across the
cell membrane.
Can be of multiple types :
• Receptors : G-protein coupled receptor.
• Pumps : Na+ K+ ATPase.
• Channel : Cystic fibrosis transmembrane regulator (CFTR) → Codes for Cl-
channel.
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Physiology Revision 1 01 3

b. Peripheral proteins : Present peripherally on the cell membrane. ----- Active space -----
Exclusively abundant in RBCs and skeletal muscle :
• RBCs : Spectrin and Ankyrin.
• Skeletal muscle : Dystrophin.

c. Lipid anchored proteins :


Require lipids for their attachment.
Exclusively abundant in RBCs.
Prevent RBCs from hemolysis : CD 55, CD 59.

b
a

Cell organelles 00:27:44

1. Endoplasmic reticulum (ER)


They are of two types :
a. Rough ER :
Granulated d/t presence of ribosomes on surface.
Function :
• Aid in the biosynthesis of proteins.
• Along with chaperones (Aid in protein folding) : Heat shock proteins
• ER-associated degradation : Destruction of misfolded proteins (Eg., prion
proteins).

b. Smooth ER :
No granulations.
Functions :
• Drug detoxification in the liver.
• Calcium Storage in muscle : Sarcoplasmic reticulum.
• Steroid biosynthesis in adrenal gland, liver, testis, ovary.

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----- Active space -----


2. Golgi apparatus:
Has 2 ends :
• Cis end receives protein
• Trans end releases vesicles
Function :
• Post translational modification : Glycosylation (Addition of carbohydrate side
chain).
• Sorting of proteins : Adding mannose-6-phosphate (By enzyme phosph
transferase)
Deficiency of phosphotransferase : Inclusion cell disease (I cell disease).
3. Lysosomes:
Responsible for destruction of bacteria by phagolysosome formation.
Acid mediated destruction (Acid lipase, acid hydrolase).
During starvation, can destroy mitochondria to release energy : Autophagy.
4. Peroxisomes :
Function :
• Generation and degradation of hydrogen peroxide (H2O2) by catalase.
• Oxidation of fatty acids : Long chain (16–22 carbons), very long chain (24–26
carbons), and branched chain fatty acids.
Peroxisomal disorders : Zellweger syndrome, Refsum disease.
5. Mitochondria:
Derived from the ovum (i.e., maternal inheritance).
Human mitochondrial DNA : Circular dsDNA (16,500 base pairs).
Mutations in mitochondrial DNA :
• > 10 times the rate for nuclear DNA.
• Affects organs with high metabolic requirements (Skeletal muscle, brain liver,
heart).
6. Nucleus :
The blue prints for DNA : Chromosomes.
DNA + Histones = Chromatin : Has repeating structural unit called nucleosomes
Substances can move to and from the nucleus through nuclear pore complex
(NPC).
Proteins of NPC :
• Exportins : Move substances out of the nucleus.
• Importins : Move substances into the nucleus.

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7. Cytoskeleton : ----- Active space -----


Maintains structural integrity of the cell.
Types :
Intermediate
Microfilaments Microtubules filaments

a. Microtubules :
Kinesin : Forward axonal transport (cell body → synapse).
Dynein :
• Reverse axonal transport (synapse → cell body), used by Rabies, Polio,
C.tetani.
• Motility of Cilia (Lung), sperm, fallopian tubes (Absence : Kartagener’s/
immotile cilia syndrome).
Tubulin : Helps in movement of chromosomes during division.
Microtubule inhibitor drugs : Vincristine, vinblastine, colchicine.
b. Microfilaments :
Exclusive to skeletal muscle.
Actin and myosin.
Function :
• Muscle contraction : Sliding filament theory.
• Cell motility : By actin polymerisation (Eg., L. monocytogens → Tumbling
motility).
C. Intermediate filaments → Act as tumor markers :
Filaments Tissue Marker for
Epithelial tissue Epithelial carcinomas
Keratin Liver (Mallory-Denk
Alcoholic Liver Disease
Bodies)
Desmin Muscle Sarcomas
Connective tissue
Vimentin Mesenchymal tumors
(fibroblasts)
Glial fibrillary acidic
Astrocytes Astrocytomas
protein (GFAP)
Lamin Nucleus Progeria (premature aging)
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----- Active space -----


8. Cell junctions :
They allow for communication
between cells.
They can be classified as :
a. Cell-cell junctions :
• Tight junctions
• Zona adherens
• Desmosomes
• Gap junctions

b. Cell-basement membrane junctions :


• Hemidesmosomes
• Focal adhesions

Cell - cell junction Protein Related disorder


Occludin
Zona occludens
Familial hypomagnesemic hyper-
(Tight junctions) Claudin
calciuria.
Zona adherens Cadherin
Desmosomes Desmoglein Pemphigus
Gap junctions (abundant in
Connexin
heart)

9.Hormone receptors : Types

Extracellular Intracellular

Cell membrane recep- Cytoplasmic receptors : Nuclear receptors :


tors : • Glucocorticoid receptor. • Estrogen Receptor
• G- Protein coupled • Mineralocorticoid • Vitamin A : Retinoic
receptors receptor. acid receptor (RAR)
• Receptor tyrosine • Androgen receptor. • Progesterone
kinase (Insulin) Vitamin D receptor. receptor
• Cytokine receptor • Thyroid hormones.
family (GH, Prolactin,
Leptin, Erythropoietin)

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G-Protein coupled receptors : ----- Active space -----


7 trans-membrane domains.
3 subunits (Alpha, beta, gamma).
The second messenger systems activated through coupling of hormone receptor
complexes :

2nd messenger Hormone Function


Vasopressin (V2) Water reabsorption
cAMP Epinephrine (beta) Metabolism
Secretin Electrolyte secretion
Vasopressin (V1) vasoconstriction
Calcium Oxytocin Uterine contraction
TRH Exocytosis Of TSH
Nitric oxide Dilatation
cGMP
Natriuretic peptides Relaxation
Membrane Transport Processes 01:04:54

1. Simple Diffusion → Fick’s law :


• Directly proportional to concentration, area of membrane, lipid solubility.
• Inversely proportional to membrane thickness, size of particle.
2. Facilitated diffusion : Carrier or channel proteins (GLUT, Aquaporins).
3. Primary active transport : Pumps (ATPases).
4. Secondary active transport :
• Co-transporter : SGLT , Na+ I-- symporter, Na+ K+ 2Cl- Co-transporter.
• Exchanger : Cl- HCO3- exchanger.
• Vesicular transport :
a. Exocytosis (SNARE) , endocytosis (Clathrin)
b. Both require Ca2+.

Passive (no ATP) Active (ATP)


Simple diffusion Facilitated diffusion

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----- Active space ----- Saturation kinetics :

Membrane Potentials 01:14:56

1. Resting Membrane potential (RMP)


The inside of a cell is always negative.
Cause : Passive diffusion of K+ ions out of a cell.
Cell RMP
Neuron -70mV
Skeletal muscle
-90mV
Cardiac ventricle
Sinoatrial node -60 to -40mV
Cajal cell (GIT) (Restless MP : Oscillatory
RMP as they are
Pre- Botzinger complex
pacemakers).
2. Equilibrium potential :
Potential at which there is no ion movement.
Nernst equation :

Equilibrium potential of an ion = ± 61 log Outsise concentration


Inside concentration

Important ions and their equilibrium potentials :


Ion Equilibrium potential
Na+ +60mV
K+ -90mV
Cl- -70mV ( RMP of neuron)
Ca2+ +130mV
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Gibbs-Donnan Effect : ----- Active space -----


The presence of non-diffusible ions affects the distribution of diffusible ions :
Na+, K+, Cl-.
The GD effect is always d/t proteins (Non-diffusible).

Cellular Fluids 01:20:50

1. Classification : Total Body weight (70 kg)

Total body water (60%) Solid Mass (40%)


42 Lts

1/3rd ECF 2/3rd ICF


14 Lts 28 Lts

Interstitial Plasma
fluid 3.5 Lts
10.5 Lts

2. Fluid indicators :

Indicators (Indicator dilution


Volume
principle)
Total Body Water Deuterium, Tritium
Extracellular fluid (ECF) Inulin, Sucrose
Radiolabelled Albumin
Plasma Volume (PV)
Evan’s Blue dye
Blood volume (BV)
Chromium tagged RBCs
= PV/(1 - Hematocrit)
Interstitial fluid
Nil
= ECF - PV
Intracellular fluid
Nil
= TBW - ECF

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----- Active space ----- 3. Darrow - Yannet diagrams :


Normal osmolarity = 300mOsm/L.
Volume → X - axis.
Osmolarity → Y- axis.

Example 1 :
SIADH → gain of water.

Example 2 :
Excessive NaCL intake → Hypertension.

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PHYSIOLOGY REVISION 2 ----- Active space -----

Nerve muscle physiology 00:00:15

Nerve physiology :

Two types of cells in central nervous system :


1. Nerve cells or neurons. 1 neuron : 10 glial cells
2. Glial cells or glia.

Types of neuroglia :
1. Central Nervous System :
i. Ependymal cells : Secrete CSF.
ii. Oligodendrocytes : Myelination in CNS (multiple neurons - 1 : 30).
iii. Astrocytes : Blood Brain barrier.
iv. Microglia : Phagocytosis.
2. Peripheral Nervous System :
i. Satellite cells : Cushioning effect to neurons.
ii. Schwann cells : Myelination in PNS (multiple neurons - 1 : 1).

Structure of neuron :

Myelin :
• Lipid : Sphingomyelin.
• Protein : Myelin basic protein (autoantibody target in multiple sclerosis →
demyelination).
• Use : Fastens conduction velocity, insulation.

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----- Active space ----- Nerve action potential : 00:09:18

Phase 1 : Local potential (slow Na influx)


(-70 → -55 mV).
Phase II : Depolarisation (opening of volt
age gated Na channel, fast
Na influx).
Phase III : Repolarisation (K+ efflux).
Phase IV : Hyperpolarisation (Cl- influx).
ARP : Depolarization & 2/3rd repolarization
RRP : 1/3rd of repolarization to end of
action potential.

Erlanger & Gasser classification Loyd Hunt


classification
Fiber Myelin Diame- Conduction Functions
type ter (um) velocity
(m/s)
Aα Maximum Muscle spindle (Proprioception) 1a
Golgi tendon organ 1b
α motor neurons -
Aβ + Touch, pressure II
Aγ Motor to muscle spindles (γ -
motor neuron)
Aδ Fast pain III
B Pre-ganglionic autonomic -
C - Mini- Slowest Slow pain, Postganglionic 1V
mum sympathetic

Nerve Injury :
Axon : M/C site of nerve injuries.
Wallerian/distal degeneration Retrograde/proximal degeneration
Usually begins within 24-36 hrs after within 48 hours of injury
injury
Axon degeneration → Myelin sheath • Nucleus pushed to periphery.
degeneration → Debris cleared by • Destruction of Nissl bodies → Chromatolysis.
macrophages & Schwann cells
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Nerve regeneration : ----- Active space -----


• Starts within 96 hours of the injury (slow process).
• Tinel sign : Tingling sensation on tapping injuried nerve (positive in regener-
ating nerve).

Skeletal muscle 00:27:58

Sarcomere :
Functional unit of muscle.
Area between two Z lines.

Skeletal muscle proteins :


Contractile Supportive proteins Regulatory Relaxation
proteins proteins protein
• Actin. • Titin (elastic like • Tropomyosin. Calcium channel
• Myosin. spring). • Troponins. protein (SERCA pump
• Calcium channels • Desmin (Intermediate activation →
(Dihydropyridine, filament) : Structural relaxation).
ryanodine support.
receptors). • Dystrophin.
• Alpha actin (attaches
actin to Z line).
• Myomesin (attaches
myosin to M line).
• Nebulin (molecular
ruler).

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----- Active space ----- Neuromuscular junction (NMJ) 00:35:21

Steps of neuromuscular transmission :


Step Disorder
1. Opening of voltage gated Na+ channels → Blocked by tetradotoxin (Puffer fish) →
Na+ influx (Voltage : -70 → -40 mV) Muscle paralysis
2. Opening of voltage gated Ca2+ channels Lambert Eaton syndrome : Antibodies to Ca2+
→ Ca2+ influx channels → Muscle weakness
3. Exocytosis of neurotransmitters (acetyl- Blocked by Botulinium toxin
choline)
4. Attach to nicotinic-ACh receptor Myasthenia gravis : Antibodies to
nicotinic-Ach receptors → Muscle weakness
5. Na+ influx into motor end plate → Depolarization → DHPR receptor activation → Acti-
vates Ryr receptors (mechanical interaction) → Release of Ca2+ → Muscle contraction.

Molecular mechanism of muscle contraction : 00:39:50

Sliding filament theory :

Applied aspect : After death


d/t No ATP → Myosin head
remains attached → Rigor
mortis.

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During this processs, muscle length + tension changes. ----- Active space -----

Between point B & C, actin &


myosin have optimal magnitude
of overlap (sarcomere length :
2.0-2.2 microns) allowing
maximum tension to be
generated.

Fibers of skeletal muscle :


Characteristics Type I fibers Type II fibers
Type II a Type II b
Features Slow, oxidative Fast, oxidative, glycolytic Fast, glycolytic
Myoglobin content Present Present Absent
Color Red Red White
Myosin ATPase activity Slow Fast Fast
Diameter Small Large Large
Glycolytic capacity Moderate High Highest
Oxidative capacity High Moderate Low (glycolysis)
Recruitment order
Function/activities Posture Walking Sprinting/running

Cardiac & smooth muscle 00:52:30

Cardiac muscle :
• Striated, involuntary.
• Intercalated disc with cardiac gap junctions (functional syncytium).
• Proteins : Connexins.
• Calcium Induced calcium release (CICR) : Calcium from extracellular source
→ Induces calcium from intracellular source (sarcoplasmic reticulum).

Smooth muscle :
• Involuntary.
• Single unit (gap junctions present, found in GI tract) &
multi-unit (gap junctions negative, found in blood vessels).
• Dense bodies present, Z lines absent.
• Calmodulin : Calcium binding protein.

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----- Active space -----


• Plasticity : No titin, no elasticity.
• Latch bridge mechanism : Can be maintained in a state of sustained
contraction with a little use of ATP (energy efficient).

Synaptic graded potentials 00:56:30

Excitatory post-synaptic Inhibitory post-synaptic


potential (EPSP) potential (IPSP)
Post- More positive More negative
synaptic neuron
membrane potential
Fast Na+ or Ca2+ influx Cl- influx
Slow K+ efflux reduced K+ efflux increased

Neuronal networks :

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Neurotransmitters (NT) 01:04:28 ----- Active space -----

NT Location Function Other points


Acetylcholine Neuromuscular Muscle contraction, • Botulinium toxin :
junction, nucleus REM sleep. Inhibits release of
basalis of Meynert ACh.
• Receptors : Nicotinic
(NMJ) & muscarinic
(GIT).
Norepinephrine Locus coeruleus Activates reticular
activating system →
awake state
Dopamine 1. Basal ganglia 1. Motor nuclear control.
(Nigrostriatal
pathway).
2. Mesocortical : 2a. Reward centre.
a. Ventral
tegmental area.
b. Nucleus 2b. Addiction.
accumbens.
3. Tuberoinfundib- 3. Inhibits prolactin
ular

Serotonin Raphe nucleus, GI Arousal, peristalsis,


tract, platelets. platelet aggregation.
Histamine Hypothalamus Arousal
Glutamate Hippocampus, sub Learning & memory Major excitatory NT in
thalamic nucleus. brain
GABA Hyperpolarisation (Cl- Major inhibitory NT
Influx)
Glycine Renshaw cells in Inhibit α motor neuron • Both inhibitory and
spinal cord excitatory NT.
• Antagonist :
Strychnine
Nitric oxide Hippocampus Learning & memory Gaseous NT
Carbon Learning, memory, • Produced by
monoxide pain processing & enzymatic
olfaction. degradation of
heme by Heme
oxygenase.
• Gaseous NT.

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----- Active space ----- PHYSIOLOGY REVISION 3

General senses 00:00:30

Touch receptors :
Meissner’s Pacinian corpuscle Merkle’s cell Ruffini
corpuscle endings
• Gentle tapping. • Pressure. • Sustained • Joint capsule
• Low frequency • High frequency pressure. receptor.
vibration. vibration. • Braille reading • Skin stretch.
• Rapidly • Largest by blind people. • Slow adapting.
adapting. receptor. • Slow adapting.
• Rapidly adapting.

Pain receptors :
• Location : Free nerve endings of A-δ & C fibers.
• Slowly adapting.
A-δ fibres C fibers
Responsible for 1st pain (Fast) Responsible for 2nd pain (Slow)
Neospinothalamic tract Paleospinothalamic tract
Release glutamate Release substance P

Gate control theory of pain : .


Normally : A-δ & C fibers → Projection neurons → Thalamus → Sensory cortex.
During massage → A-β fibers activated → Inhibit projection neurons
(substantia gelatinosa) → Inhibit pain.
Somatosensory pathways :
Dorsal column pathway Anterolateral pathway
Myelinated (fast) Unmyelinated (slow)
Carries : Carries :
• Proprioception (A-α fibers). • Pain.
• Touch & Vibration. • Temperature.
Ascends on the same side. Ascends on opposite side.
Crossing over at medulla Crossing over at spinal cord.
Thalamus (Ventroposterolateral nucleus) → Sensory cortex (Post central pari-
etal cortex → Brodmann area 3, 1 & 2).
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Physiology Revision 3 03 19

Brown Sequard syndrome : ----- Active space -----


• Hemisection of spinal cord.
• Ipsilateral (I/L) loss of dorsal column senses.
• Contralateral (C/L) loss of anterolateral
pathway senses.
Sensory homunculus :
• Body parts represented on sensory cortex based
on extent of usage :
a. Max : Lips, thumb.
b. Min : Hip, trunk, back.

Special senses 00:15:48

Vision :
Retina → Thalamus (lateral geniculate body) → Visual cortex.
Retinal cells Characteristics
Rods Max number (120 million)
Receptors for dim vision (night vision).
Cones Around 6 million.
Colour & day light vision.
Bipolar cells Relay b/w rods, cones to ganglion cells.
Ganglion cells Continues as optic nerve (Only output cell).
Horizontal cells Connects rods & cones.
Amacrine cells Connects bipolar & ganglion cells.
Muller cells Retinal glial cells (No role in vision).
Rods : Dark state Rods : Light state
Funny current channels (cGMP 11-cis retinal Light All trans retinal→
dependent Na+ channels) Activates transducin (G protein receptor) →
Activates phosphodiasterase→ Degrades
cGMP → Close Na+ channels.
Depolarisation. Hyperpolarization.
More neurotransmitter release. Decreased neurotranmitter release

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20 03 Physiology

Lateral geniculate body :


----- Active space ----- Magnocellular pathway Parvocellular pathway
Origin Layers 1 & 2 Layers 3, 4, 5, 6
Termination Layer 4 of visual cortex Layer 4 of visual cortex
Movement of eyes, detect
Function Detects colour vision, finer details
depth & flickers
• 2, 3 & 5 : Recieves from I/L eye.
• 1, 4 & 6 : Recieves from C/L eye.

Visual cortex :
Brodmann area 17, 18 & 19 of calcrine cortex of occipital lobe.
Striations due to myelinated fibers (striate cortex or stria of gennari).
Colour vision :
• Red : L cone.
• Green : M cone.
• Blue : S cone.
Cones → LGB (parvocellular pathway)→ Visual cortex (blobs) → Perception.

Hearing :
Cochlea :
Endolymph
• Surrounds scala media.
• K+ rich

Perilymph
• Surrounds scala vestibuli &
tympani.
• Na+ rich
Organ of corti :
• Outer hair cells are numerous, easily prone to damage & ototoxic drugs.
• Tallest hair cell : Kinocilia.
• Progressive small hairs : Stereocilia.
• Hair cells bending to kinocilia : Depolarisation (K+ influx).
• Measured as otoacoustic emissions (kemp waves).

Auditory pathway : (Mnemonic : ECOLIMA)


Eighth nerve → Cochlear nuclei → Olivary nucleus (superior)→ Laternal
lemniscus → Inferior colliculus→ Medial geniculate body → Auditory cortex
(Area 41/Heschl’s gyrus).
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Olfaction : ----- Active space -----

Olfactory receptors :
• Location : Roof of nasal cavity.
• Bipolar neuron.

Olfactory bulb has 4 cells :


• Mitral
Excitatory (releases glutamate)
• Tufted
• Periglomerular
Inhibitory (releases GABA)
• Granule
Olfactory nerve piercing
Cribriform plate
Olfactory receptors → Olfactory bulb→ Thalamus (dorsomedial nucleus) →
Olfactory cortex.
Central area Function
Olfactory cortex (orbitofrontal cortex) Smell perception
Amygdala Interrelation b/w smell & emotion
Entorhinal cortex Interrelation b/w smell & memory
Taste :
5 basic states :
• Sweet.
• Sour.
• Bitter : Alkaloids & poisons.
• Salt.
• Umami : Produced by MSG (Mono Sodium Glutamate).
Pathway :
Anterior 2/3 rd tongue Posterior 1/3 rd tongue Palate, pharynx

Chorda tympani branch of Glossopharyngeal nerve Vagus nerve


facial nerve

Medulla (nucleus tractus solitarius)

Ventral posteromedial nucleus of thalamus

Taste cortex : Anterior insula, frontal operculum


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22 03 Physiology

----- Active space -----


Laws & senses in sensory physiology 00:46:48

1. Doctrine of specific nerve energies (muller’s doctrine ) :


• Receptors are specific for a specific sensation.
• Ex : Pacinian → Touch, Free nerve endings → Pain.
2. Bell Magendie law :
• Dorsal roots : Sensory.
• Ventral roots : Motor.
3. Law of projection :
• Cortex projects sensations to receptor location.
• Ex : Phantom pain.
4. Weber-Fechner law :
• Magnitude felt ∝ Log of intensity of stimulus.

Motor physiology 00:50:35

Neurons & tracts Location


Upper motor neurons Brain : Cortex, brain stem
Lower motor neurons Spinal cord : A-α, A-γ neurons
Pyramidal tract Lateral & anterior component of corticospinal tract
Extrapyramidal tract • Originates from brainstem
• Vestibulospinal, tectospinal, rubrospinal,
reticulospinal tract

Decerebrate rigidity Decorticate rigidity

Fingers flexed, forearms pronated & Upper extremities flexed against


upper extremity extended chest
Extensor rigidity Lesion of CST
CST & rubrospinal tract lesion Intact rubrospinal tract
Overactivity of reticulospinal tract

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Muscle spindles : ----- Active space -----


1. Nuclear bag fibers :
• Dynamic component.
• Static component.
2. Nuclear chain fibers : Static component.

Sensory supply :
Primary (group Ia) endings Secondary (group II) endings
Annulospiral endings Flower spray endings
Innervates all fibers of bag & chain Innervates only static component
Motor supply : γ- motor neuron.

Stretch & Inverse stretch reflex :


Characteristics Stretch reflex Inverse stretch reflex
Receptor Muscle spindle Golgi tendon organ
Detects muscle length Muscle tension
Afferant Group IA & II endings Group Ib
Center Spinal cord Spinal cord
Efferent α-motor neuron α-motor neuron
Effect Contraction Relaxation
Reason for the effect α-motor neuron activated α-motor neuron inhibited
No. of synapses Single : Monosynaptic Two : Disynaptic
involved
Other name Myotatic reflex Lengthening reaction
Regulation of stretch reflex :
• γ- motor neurons stretches periphery of spindle → Activates afferant
central portion of spindle.
• Sensitivity of stretch reflex ↑.

Withdrawal reflex :
• Polysynaptic reflex.
• Flexion of I/L limb away from stressor.
• Extension of C/L limb.
• I/L activation of flexors & inhibition of extensors.
• C/L activation of extensors & inhibition of flexors.
• Reason : Reciprocal innervation.
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24 04 Physiology

----- Active space ----- PHYSIOLOGY REVISION 4

Cerebellum 00:00:21

Motor brain part (efferent).


Function of cerebellum : Start-stop signaling (co-ordination of motor activity).
3 parts of cerebellum 4 cerebellar deep nuclei 5 cells of cerebellum
• Spinocerebellum • Dentate • Purkinje cells
(co-ordination) • Emboliform • Stellate cells Inhibitory
• Vestibulocerebellum • Fastigial Excitatory • Golgi cells
(balance & equilibrium) • Globose • Basket cells
• Neocerebellum • Granule cells (excitatory)
(planning)

Afferents to cerebellum :
Climbing fibers Mossy fibers
Originate in the inferior olivary nucleus Originate from cell bodies in the spinal cord &
(olivocerebellar). brain stem (Spinocerebellar).

+
+ + Granule cells
Deep nuclei Purkinje cells (inhibitory) (excitatory)
+ - +
Thalamus & motor cortex Deep nuclei Stellate, basket,
+ - Golgi cells (inhibitory)
Motor movement Motor movement -
Purkinje cells
NOTE : Granule cells firing can also be +
controlled by its inhibition through Golgi cells . Deep nuclei escapes
+
Features of cerebellar disease : Next motor movement
1. Decomposition of movement
2. Hypotonia 7. Dysdiadochokinesia
3. Pendular knee jerk 8. Rebound phenomenon
4. Ataxia 9. Dysarthria
5. Dysmetria 10. Nystagmus
6. Intention tremor
Note : Resting tremor seen with basal ganglia lesions

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Physiology Revision 4 04 25

Basal ganglia 00:09:11


----- Active space -----

• Always inhibitors (even at rest)


• Inhibits both voluntary + involuntary movements.
• Lesions : Predominantly involuntary movements.
Nuclei :

Input nuclei (use GABA)


output nuclei (use GABA).

major excitatory nuclei :


Use glutamate

Use dopamine

• Lesions in subthalamic nuclei : Sudden violent contractions of one large joint


(hemiballismus).
Pathways :
Direct → Activated → Facilitates movements.
Caudate and putamen (striatum)

- GABA

GPi + Motor nucleus of thalamus (ventral anterior nucleus)


+
Motor cortex
+
+
Movement
Indirect → Activated → Inhibits motors movements
Caudate and putamen (striatum)
-
GPe
+
Subthalamic nucleus
+ +
GPi Motor nucleus of thalamus (ventral anterior nucleus)
-
-
Motor cortex
-
Movement
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26 04 Physiology

----- Active space -----


Thalamus 00:18:39

Olfaction
(dorsal median nucleus)

Memory
(Papez circuit)

Motor nucleus

General senses
(touch, pain, temperature)

Hearing Vision

Hypothalamus 00:20:42

Nuclei Function
Anterior Heat environment
Posterior Cold environment
Lateral Feeding centre (Orexin)
Ventromedial Satiety centre
Suprachiasmatic Regulates circadian rhythm
Supraoptic ADH (mainly)
Paraventricular Oxytocin (mainly)
Ventrolateral Sleep centre
preoptic nucleus
Mamillary bodies Memory
Regulation of body temperature :
Heat Cold
Anterior hypothalamus → Sweating Posterior hypothalamus → Shivering
+ Thirst sensation (osmoreceptors) + frequency of Micturition
+ Vasodilation (to dissipate heat). + Vasoconstriction (conserve heat)
Feed forward control system : Skin temperature → Anticipated by
hypothalamus → Prevents of core temperature

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Learning & Memory : ----- Active space -----


Memory

Declarative/ explicit memory Nondeclarative/ implicit memory

Semantic memory (for facts) Episodic memory (for events) Skills


memory/
procedure
Involves anterior temporal Involves Hippocampus,
memory.
cortex, prefrontal cortex medial temporal lobe, neocortex
Ex : Driving
Hippocampus :
• Short term memory to Long term memory.
• Repetition (revision) → Synaptic strengthening → Long term potentiation
(LTP).
• Lesions : Anterograde amnesia (cannot form long term memories).
• No role in storage of memories.
• Their procedural & skill memories are intact.

Mammillary bodies :
• Memory (part of Papez circuit).
• Lesions : Wernicke Korsakoff psychosis (confabulation - honest lying).
Lesion at Anterior nucleus of thalamus → Loss of recent memories.
Basal Forebrain (Nucleus basalis of Meynert) : Acetylcholine
• Reduced Ach → Alzheimer’s disease.
Amygdala : Emotions & memory.
Entorhinal cortex : Smell & olfactory memory.

Language & Speech :

Supramarginal
gyrus

Angular gyrus
Broca’s area Wernicke’s area

Primary Auditrory
cortex

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28 04 Physiology

----- Active space ----- Broca’s area Wernicke’s area Arcuate Angular gyrus
fasciculus
Located in inferior Located at superior Bundle Area 39
frontal gyrus. temporal gyrus. connecting
Brodmann’s area 44. Brodmann’s area 22. Broca’s &
Motor speech area Word understanding & Wernicke’s Vision & speech
(word formation). comprehension. areas. inter-related.
Sensory speech area.
Lesion : Reduced Lesion : Tremendous Lesion : Lesion : Anomic
speech output problem in understanding Conduction aphasia (can’t
(Broca’s aphasia). + fluent aphasia aphasia say what they
(Wernicke’s aphasia). see).

Fluids in brain 00:36:07

Cerebral blood flow (CBF) :


• For nutrition.
• Around 750 ml/min or 15% of cardiac output.
• O2 consumption : 20% of the total body resting O2 consumption.
• Regulation :
1. Autoregulation → Blood flow constant inspite of changes in pressure
(65-140 mm Hg).
2. Hypercarbia → CBF
3. Hypothermia : of body temperature by 10C → cerebral blood flow
by 7% (therapeutic hypothermia : Useful in neurosurgical procedures to
reduce cerebral blood loss).
Cerebrospinal fluid (CSF) :
• Volume : 150 ml
• Rate of CSF production : 550 mL/day
• CSF turn over per day : 3.7 times.
• Normal CSF pressure : 70-180 mm H20 (elevated pressure → Hydrocephalus)
Chloride, magnesium, sodium CSF > Plasma
Osmolality, Bicarbonate ions CSF = Plasma
Glucose(2/3rd of plasma), proteins CSF < Plasma
CSF marker : β2-Transferrin (useful in CSF otorrhea, CSF rhinorrhea).

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Physiology Revision 4 04 29

Sleep 00:41:26 ----- Active space -----

EEG waves :
EEG wave Frequency Characteristics
Alpha wave 8 – 13 Hz Resting/ relaxed state.
Eyes closed, not sleeping.
Generated from occipital, parietal cortex.
Beta wave 14 – 30 Hz Wide awake, attentive.
Generated from frontal cortex.
Theta wave 4 – 7 Hz NREM sleep (minor).
Generated from hippocampus (memory).
Delta wave/ < 4 Hz NREM sleep (major sleep wave).
slow wave (minimum)
Gamma wave 30–80 Hz (max) Focused attention.
Sleep stages :
NREM (Non rapid eye movement) sleep/ slow-wave sleep :
• Stage 1 : Non-specific theta waves.
• Stage 2 : K-complex & sleep spindles (8-13 hz )
• Stage 3 & 4 : Delta waves (major waves of NREM).
REM Sleep :
• PGO (ponto-geniculo-occipital) spikes → Eye ball movements seen.
• Both in males & females : Genital organ enlargement during sleep.
• Characteristic for REM : Beta wave (wakefulness + REM sleep) →
Paradoxical sleep.
Neurotransmitters in sleep :
Wakefulness Neurotransmitters involved
promoting brain areas Neurotransmitter NREM REM
Cholinergic nuclei of Acetylcholine (REM ON
pons-midbrain junction neurons → ACh
→ Sleep).
Locus coeruleus Norepinephrine
Raphe nuclei Serotonin
Tuberomammillary Histamine
nuclei
Lateral hypothalamus Orexin
(mutation : Narcolepsy).

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30 04 Physiology

----- Active space ----- Parasomnias :

Disorders of NREM Disorders of REM


• Sleep talking. • Nightmares.
• Sleep walking/Somnambulism. • Narcolepsy.
• Teeth grinding/Sleep bruxism (NREM • Meomory of
stage 2 - emotionally deprived children). dream -ve.
• Nocturnal enuresis.
• Nightterrors.

Note : Memory of the dream is present in night mares (REM) but absent in night
terrors (NREM).

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Physiology Revision 5 05 31

PHYSIOLOGY REVISION 5 ----- Active space -----

Respiratory physiology 00:00:15

Airway generations :
Weibel model (23 generations).
Trachea → bronchi → bronchioles → terminal bronchioles
(0) (16)
alveolar sacs alveolar ducts respiratory bronchioles
(23)

Conducting airways (1-16) :


First 16 generations.
Contain cilia → ciliary movement d/t Dynein clears sputum.
• Dynein absent in Kartagener’s syndrome.
• Ciliary immotility : Cystic fibrosis.
Has 2 stem cells : Basal cells & Clara cells (for lung regeneration & repair).
Have smooth muscle.

Agents that modify Bronchial smooth muscle activity:


Bronchoconstriction Bronchodilation
Parasympathetic system : ACh, Methacholine. Sympathetic system : β2 ag-
Histamine. onists.
Leukotriene (most potent). NO(Nitric oxide).

Alveolar airways (17-23) :


2 types of pneumocytes :
• Type I : Large, flat, occupies more surface area, less numerous.
• Type II : Small, more numerous, produce surfactants (stored as lamellar
bodies), act as stem cells.
Composition of surfactants
Surfactant lipids Surfactant proteins
Major : Lecithin/dipalmitoyl phosphatidyl choline (DPPC) SP-A.
Minor : Sphingomyelin. SP-B.
L/S ratio is used to assess fetal lung maturity (normal SP-C.
is ≥ 2). SP-D.

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32 05 Physiology

----- Active space -----


Functions of surfactants :
• Reduce surface tension → prevents alveolar collapse.
• SP-A & SP-D : Role in lung immunity.

Production of surfactant :

Accelerated by Inhibited by
Cortisol (steroids). Insulin (inhibits cortisol) thus Infants of diabetic mothers
T3, T4. are more prone to Hyaline membrane disease.
Long term inhalation of 100% O2.
Occlusion of main bronchus.
Occlusion of one pulmonary artery.
Smoking.

Mechanics of breathing 00:12:15

Boyle’s Law : P ∝ 1/V

1. Intrapleural pressure : 2. Intra alveolar pressure :


+ 1 mm Hg
-2.5 mm Hg -2.5 mm Hg Expiration
Inspiration Expiration

0 mm Hg
Inspiration

-6 mm Hg - 1 mm Hg

3. Transpulmonary pressure = Alveolar pressure - Intrapleural pressure.


(TAP : T = A - P).

Lung compliance:
Hys ation

V
Ins resis
tion
ir
Exp
te
pira

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Physiology Revision 5 05 33

Hysteresis : Difference b/w the pressure volume curves during inspiration & ----- Active space -----
expiration. It happens d/t surface tension forces.

Compliance : Slope of the curve.


= ΔV/ΔP = 200 mL/cm H2O.

Note : For a given change in pressure, change in volume is more during expiration.

Lung Compliance in air filled Vs saline filled lung :


Saline filled Air filled

Volume

Pressure
In saline filled lungs → no air-fluid interface → no surface tension → no
hysteresis.

Equilibrium volume(FRC) : The volume at


which the 2 opposing forces (expanding
force & collapsing force) are at equilibrium.

Minimal volume : The volume of air remaining


in the lungs after complete collapse.

Compliance of chest wall (A), lung (B)


and combined compliance (C).
1

Compliance in various diseases :


• ↑ compliance : Hyperinflation. Seen in COPD.
• ↓ compliance : Stiff lung. Seen in restrictive lung diseases (pulmonary
fibrosis, interstitial lung disease).

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34 05 Physiology

----- Active space -----


Spirometry :

Dynamic measurements : Flow volume curve.


B
A : TLC.
B : Peak expiratory flow rate (PEFR).
C : RV.
A → B : Effort dependent part (air from A C
trachea & bronchi).
6 4 2 0
B → C : Effort independent part (air from
medium & small airways) - affected in COPD.

FEV1, FVC and FEV1/FVC ratio can be measured


from the graph.

Note :
Dog leg pattern/scooped
out pattern : Seen in COPD.

Miniature version of normal


graph : Seen in restrictive
lung diseases.

Flow volume curves


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Physiology Revision 5 05 35

Spirometry cannot measure : These can be measured using : ----- Active space -----
1. RV. 1. Helium dilution technique.
2. FRC. 2. Nitrogen washout technique.
3. TLC. 3. Body plethysmography (most practical).

Ventilation : 00:38:30

Tidal volume (VT) = 500 mL.


Dead space (VD) = 150 mL (air in conducting airways).
Alveolar ventilation (VA) = 350 mL.
VA/min = (VT-VD) x Respiratory rate(12).
= 4.2 L/min.
VD/VT = 30% (% of air which goes unexchanged).

Dead space ventilation : Not used for gas exchange.


3 types :
1. Anatomical dead space (ADS).
2. Alveolar dead space (Alv DS).
3. Total dead space (ADS + Alv DS) : Physiological dead space.

Measurement of ADS : Single breath N2 method/Fowler method.


Measurement of physiological dead space : Bohr’s equation.

PACO2 : Alveolar CO2.


PECO2 : Expired CO2.
VD : Physiological dead space.
VT : Tidal volume. Bohr’s equation

Perfusion :

Pulmonary circulation (~5.5L/min) is unique as its response to hypoxia is pulmo-


nary vasoconstriction.
Mechanism :
Hypoxia → Inhibits outward K+ current → K+ accumulation inside cell

Vasoconstriction Opens Ca2+ channel Depolarisation


causing Ca2+ influx

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36 05 Physiology

----- Active space -----


Lung zones :
PA : Alveolar pressure.
Pa : Arterial pressure.
PV : Venous pressure.
Blood flow distribution in the lung
Blood flow Pressure Driving
blood flow
Minimal (d/t compression of PA ≥ Pa > PV
blood vessels).
Intermittent blood flow Pa > PA > PV
(Waterfall effect).
Middle
Highest(Continuous blood flow) Pa > PV > PA

Ventilation perfusion ratio (V/Q) :

Alveolar ventilation(V) : 4.2 L/min.


Pulmonary blood flow(Q) : 5.5 L/min.
V/Q = 0.8 (in middle). It is more at apex (3.3) & less at base (0.6).

V/Q = 0 (V=0) V/Q = Infinity (Q=0)


Shunt blood (physiological). Anatomical dead space.
Foreign body causing airflow obstruction. Pulmonary embolism.

Diffusion of gases 00:53:32

Fick’s law governs the diffusion of gases in lung.

Vgas : Diffusion of gas.


A : Area.
P1-P2 : Pressure difference.
T : Thickness.
CO : Gas of choice for measuring diffusion capac

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Physiology Revision 5 05 37

Normal value of DLCO (Diffusion Capacity of Lungs for CO2) = 25 mL/min/mm Hg. ----- Active space -----

↓ DLCO ↑ DLCO
• ↓ membrane area : Emphysema. • Polycythemia.
• ↑ thickness : Pulmonary fibrosis. • Exercise.
• Anemia.

Oxygen dissociation curve : X

ift
It is a sigmoid curve.

t sh

al
rm
Lef
P50 : Partial pressure at which %

ift
No

sh
ht
saturation of Hb with O2 is 50%.

Rig
P50 = 27 mm Hg.

P50

Left/upward shift (Haldane effect) Right/downward shift (Bohr effect)


Loading of O2 leading to unloading of Release of O2/ Unloading at
CO2. Causes : tissue. Causes :
• Hypocarbia. • Hypoxia.
• Alkalosis. • Hypercarbia.
• Fetal Hb. • Acidosis.
• CO poisoning. • ↑ 2,3 DPG.
• Stored blood. • High altitude.

CO2 transport :

AE : Anion exchanger.

Chloride shift is aka


Hamburger phenomenon : Buffered
For each HCO3- that exits, a by HCO3-
Cl- enters. Cl- shift

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38 05 Physiology

----- Active space -----


Regulation of respiration 01:07:39

Neural control :

Brain area Function


Pre Botzinger complex Pacemaker : Initiates respiration.
Pneumotaxic center Limits inspiration (inhibits apneustic
center). Controls respiratory rate.
Apneustic center Prolongs inspiration.
Dorsal Respiratory Generates RAMP signal for smooth
Group (DRG) rise in tidal volume during inspiration.
Ventral Respiratory Controls forceful expiration during
Group (VRG) exercise.
(Mnemonic - DIVE : D → Inspiration, V → Expiration)

Chemical control :

Central chemoreceptors Peripheral chemoreceptors


Location Ventral surface of medulla. Carotid & aortic bodies.
Sensitive to pCO2 in blood (As CO2 can ↓ pO2(Hypoxia)
cross BBB & generate H+ Have oxygen sensors
ions) (glomus cells).
Direct stimulation by Rise in H+ ions in CSF. -

Common stimuli to both chemoreceptors : Rise in H+ ions.

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Asphyxia : Rise in pCO2 & H+, fall in pO2. ----- Active space -----

Chemoreceptor activation
Hyperventilation

↓ pCO2 ↓ H+ ↑ pO2

Pulmonary reflexes :

Reflex Stimulus Receptor Afferent Effect


Hering-Breuer Overstretch Pulmonary Large • Inhibits
inflation reflex. of lung. stretch myelinated inspiration.
(Prevent injury) (TV = 1500 receptors (slow vagal fibres. • ↑ duration of
mL) adapting)
expiration.
Hering-Breuer Deflation. Pulmonary Large • Inhibits
deflation stretch myelinated expiration.
reflex.(Prevent receptors (slow vagal fibres. • ↓duration of
collapse) adapting).
expiration
The paradoxical Lung Pulmonary Increase in lung
reflex of head. inflation. stretch inflation.
receptors. Responsible for first
breath of newborn.
J receptor Pulmonary Juxtapulmonary Unmyelinated • Rapid
reflex. edema, receptors vagal C fibres. breathing.
pulmonary • Bradycardia.
congestion. • Hypotension.

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40 05 Physiology

----- Active space ----- Periodic breathing patterns


Cheyne Stokes Biot's breathing Kussmaul's breathing Apneustic spasm
breathing (acidotic breathing)

Seen in : Seen in : Seen in : Seen in :


1. Sleep (normal). 1. Injury to Diabetics. Midpontine lesion
2. CCF. Medulla. with vagus cut.
3. Uremia. 2. Meningitis.

Types of hypoxia 01:24:24

Hypoxic Anemic Stagnant Histotoxic


Features hypoxia hypoxia hypoxia hypoxia
Due to Low arterial Reduced O2 Decreased Decreased ability
pO2 content of blood flow of cells to use
blood to tissues oxygen
Arterial pO2 Decreased Normal Normal Normal
Arterial Hb Normal Decreased Normal Normal
content
Peripheral Stimulated Not stimulated Stimulated Stimulated
chemoreceptor (As dissolved O2
stimulation is normal)
Example High altitude CO poisoning Ischemia Cyanide poisoning

Environmental physiology 01:27:13

High altitude :
Acclimatisation : Physiological compensatory response to high altitude.
High altitude is a low pressure state.
Hypoxia in high altitude

↑ ventilation ↑ EPO → ↑RBC Angiogenesis ↑ diffusion of ↑ O2 utility


(earliest) production (↑ vascularity) gases by cells (cellular
acclimatisation)

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Deep sea : ----- Active space -----


High pressure state → Gases are compressed.
Decompression sickness/Caisson’s disease/Dysbarism/Diver’s palsy :
Seen during rapid ascent to sea level → N2 gets decompressed & released out
as bubbles.
Clinical features :
• N2 narcosis.
• Bends (pain in joints).
• Chokes.
• Air embolism → death.
Rx : Slow ascent → slow decompression → no bubbles.

Space physiology :

It is a state of microgravity.

Positive G Negative G
When an individual is subjected to When an individual is subjected to
positive G, blood is pushed toward the negative G, blood is pushed toward the
lowermost part of the body. head end.
Venous pooling in lower limbs. ↑ Venous return : ↑ CO.
↓ Cerebral pressure : Unconsciousness. Congestion of head & neck vessels.
↓ Blood flow to eye : Black out. Hyperemia of eye : Red out.

Exposure to microgravity on astronauts causes :


• Motion sickness.
• Decrease in blood volume, RBC mass, muscle strength & work capacity.
• Loss of bone mass (d/t loss of calcium & phosphate).

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42 06 Physiology

----- Active space ----- PHYSIOLOGY REVISION 6

Cardiac action potentials 00:00:28

SA (Sino Atrial) nodal potential :


SA node : Pacemaker & responsible for chronotropy.
Ca2+ influx through L type Ca2+
Phase 0 Depolarisation channels.

Phase 3 Repolarization Due to k+ efflux. 0


3
• Decrease in k+ efflux.
Prepotential • Na+ influx through funny
4 4
Phase 4 (Pacemaker channels.
potential) • Ca2+ influx through T type
Ca2+ channels.

Effect of sympathetic & parasympathetic nervous system on SA nodal potential :


Sympathetic nervous system Parasympathetic nervous
(SNS) system (PNS)
Increases Heart rate (HR). Decreases HR.
Increases slope of prepotential Decreases slope of prepotential
phase. phase.

Ventricular action potential :


Ventricles → Responsible for inotropy (contractility).
Phase 0 Early depolarisation Due to Na+ influx.
Phase 1 Early repolarisation Due to k+ efflux. 1 2
Phase 2 Plateau k efflux = Ca influx through
+ 2+

L type Ca2+ channels.


0 3
Phase 3 Late repolarisation Continuation of k+ efflux.
Phase 4 Resting Membrane Na+ - k+ ATPase pump 4
Potential (RMP)

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Physiology Revision 6 06 43

Conducting system of the heart 00:08:26 ----- Active space -----

1. SA node : Dominant pacemaker.


Generates impulse at highest rate (100/min).
2. AV node : AV nodal delay (physiological). SA Node
A-V Node
A-V bundle
Gatekeeper of heart.
Left
Slowest conduction velocity (0.04 m/s). bundle
Inter branch
3. Bundle of His. Nodal Right
pathways
4. Left & Right bundle branch. bundle
branch
5. Purkinje fibres : Max. no. of gap junctions with connexins.
Fastest conduction velocity (4 m/s).
Purkinje fibres

ECG 00:11:02

ECG waveforms :
Wave Cause Duration (sec)
P wave Atrial Depolarisation. 0. 10
QRS Complex Ventricular Depolarisation. 0. 08 to 0. 10
T Wave Ventricular repolarisation. 0. 2
U wave Purkinje fibre repolarisation. -
Papillary muscle repolarisation.

PR ST
segment segment PR interval QT interval
R R
R

T T T
P P P
PR U U U
segment Q S
ST
segment Q S Q S
RR interval

ECG segments :
Segments Extent Denotes
PR segment From to the end of P wave to the Physiological AV nodal delay.
beginning of QRS complex.
ST segment End of QRS complex to the beginning Plateau phase of ventricular action
of T wave. potential.
Isoelectric line (J point).
Note : Physiology : No current flow.
Pathology : Injury current in MI (leads to ST elevation/depression).
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44 06 Physiology

----- Active space -----


ECG intervals :
Intervals Extent Normal value Denotes/ Uses
PR interval From the onset of P wave 0. 12 to 0. 20 S Atrioventricular (AV) conduction
to the beginning of QRS time.
complex.
QT interval From the onset of Q wave 0. 35 to 0. 43 S Ventricular depolarization +
to the end of T wave. repolarization events.

RR interval Interval between two 0. 6 to 1 S HR = 1500/no. of small squares


successive R waves. between two R waves.

If PR interval > 0.20 seconds → Heart block.

Jugular Venous Pressure (JVP) Waveforms 00:19:17

a c v

y
x

JVP waveforms Corresponds to


a wave Right atrial contraction (atrial systole).
Bulging of tricuspid valve into right atrium during right ventricular
c wave
contraction.
x descent Right atrial relaxation.
v wave Venous filling (atrial diastole).
y descent Venous emptying of right atrium into right ventricle.

Cardiac cycle 00:21:21

Cardiac cycle duration → 60/Heart Rate → 0.8 seconds.


Atrial Ventricular
Systole (short) 0. 1 s 0. 3 s
Diastole (long) 0. 7 s 0. 5 s

Ventricular systole :
Isovolumic contraction (IVC)
• Mitral and Aortic valves are closed. Rapid ejection Slow ejection
• Volume remains same & pressure phase (RE) phase (SE)
→ opening of the aortic valve.
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Physiology Revision 6 06 45

End systolic volume (ESV) : Volume of blood remaining in ventricles at the end of ----- Active space -----
systole (50 ml).
Cardiac diastole :
Protodiastole (PD) Isovolumic Filling d/t
Closure of aortic Rapid filling Slow filling atrial contraction
relaxation
valve (RF) (SF) (AC)
(IVR)

80 % filling : Passive process Last 20 % filling :


Active process
End Diastolic volume (EDV) : 120 ml.

Wiggers diagram :
5 components → Pressure changes, volume changes, ECG, phonocardiogram and
JVP wave forms.
Closure of
RE aortic valve
SE
PD
IVC

Pressure
IVR changes
Closure of Opening of
mitral valve mitral valve

IVC
SF AC
RE RF Volume
changes
SE
IVR R
P
T ECG
Q S
a c v a v
c
y
x y
JVP
x
1st 2nd 3rd 4th
Phonocardiogram

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46 06 Physiology

----- Active space ----- Heart sound Correlation


S1 Peak of R wave.
S2 End of T wave.
S3 Rapid filling in cardiac cycle.
S4 P wave/ Atrial contraction.
Pressure volume graph :

Aortic valve SE RE
closes Aortic valve
PD opens
Pressure (mmHg)

IVR Stroke volume IVC

ESV EDV
SF AC
RF

Volume(ml)
• Stroke volume = EDV- ESV = 120- 50 = 70 ml.
• Ejection fraction = Stroke Volume (SV)/EDV x 100

Cardiac output 00:37:24

General features :
• Cardiac output = HR X SV.
• Normal cardiac output values :
Men : 5.6 L/min
Women : 4.9 L/min
• Cardiac index ratio :
Cardiac output expressed per m2 of body surface area (BSA).
Normal cardiac index : 3.2 L/min/m2 of BSA.
• Fick’s Principle :
Cardiac output = O2 consumed in mL/min
Arteriovenous oxygen difference
Regulation of cardiac output :
1. Preload (Volume → Venous return) :
• Preload ∝ cardiac output.
• Best marker : EDV.
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Physiology Revision 6 06 47

2. Myocardial contractility : ----- Active space -----


• Myocardial contractility ∝ cardiac output.
• Best marker : Ejection fraction.
3. Afterload (Pressure → Aortic pressure) :
• Afterload ∝ 1/ Cardiac output.
• Best marker : Aortic pressure or total pressure resistance.
Distribution of cardiac output :
Highest distribution Organ Values
Blood flow Liver 1500 mL/min
Blood flow per 100 g of tissue Kidney 420 ml/100g/min
Arterio-Venous oxygen difference/ O2 extraction Heart 114 ml/L
Oxygen consumption Liver 51 ml/min
Oxygen consumption per 100 g Heart 9.7 ml/100g/min
Percentage of total → Cardiac output Liver 27.8.
Percentage of total → O2 consumption Liver 20.4

Hematopoiesis 00:45:30

Age Site of Hematopoiesis


3 weeks -3 months Yolk sac
3-5 months (hepatic stage) Liver, spleen (<5 m : Extramedullary hematopoiesis)
5-9 months & After birth till 20 yrs Red bone marrow in long & flat bones
>20 years Red bone marrow in flat bones
Erythropoiesis :
Pluripotent Hematopoietic stem cell (PHSC)
GATA Friend Of GATA (FOG)
BFU-E : Burst Forming Unit Erythrocyte (Earliest committed progenitor cells)

CFU-E : Colony Forming Unit Erythrocyte (Highest erythropoietic receptors)

Proerythroblast (Hb synthesis begins)

Basophilic erythroblast

Polychromatophilic erythroblast (Hb appears)

Orthochromatic erythroblast (complete Hb in RBC)

Reticulocyte (Immature RBC)

Erythrocyte (Mature RBC).

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48 06 Physiology

----- Active space -----


Regulation of erythropoiesis :
Increases RBC count : Decreases RBC count :
• Erythropoietin : Act through • Estrogen.
Janus Kinase Receptor.
• Thyroid hormones.
• Testosterone.

Leucopoiesis : Pluripotent hematopoietic stem cell

Lymphoid stem cell Colony forming unit - GM

Lymphoblast Myeloblast

Lymphocyte
Promyelocyte Monoblast

Neutrophil Eosinophil Basophil Promonocyte


myelocyte myelocyte myelocyte
Monocyte

Neutrophil Eosinophil Basophil


metamyelocyte metamyelocyte metamyelocyte

Neutrophil Eosinophil Basophil

Regulation of leucopoiesis :
• Granulocyte colony stimulating factor (G CSF). WBC
• Granulocyte monocyte colony stimulating factor (GM CSF).
• IL 5 : Eosinophil development.
• IL 3 & 4 : Basophil development.

Thrombopoiesis : Pluripotent hematopoietic stem cell


Regulatory factors :
GM CSF thrombo • Thrombopoietin.
• IL 11.
Megakaryocyte • Platelet count.

Platelets
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Physiology Revision 6 06 49

Blood groups : ----- Active space -----

System Important points


ABO system Co dominance pattern of inheritance.
Found in blood, saliva, semen.
Rh system Determined by D antigen :
Rh Incompatibility → Erythroblastosis fetalis.
P system Paroxysmal cold hemoglobinuria : Auto antibodies against p system.
Has receptor for parvo virus entry.
Kell system If Kell system absent : Mcleod phenotype (acanthocytes, cardiac
defects).
Duffy system Receptor for plasmodium vivax

Blood vessel physiology 00:55:43

Blood flow velocity is inversely proportional to cross sectional area.


Vessel with :
• Maximum cross sectional area & min blood flow velocity : Capillaries.
• Minimum cross sectional area & maximum blood flow velocity : Aorta.
• Maximum diameter : Vena cava.
• Maximum % of blood stored : Veins (Storage reservoir→ 54% blood stored).
• Resistance vessels : Arterioles (max smooth muscle content).
• Capacitance vessels : Veins.
• Exchange vessels : Capillaries.
• Windkessel vessel : Aorta (elastic), large blood vessels.
• For temperature regulation : AV shunts.
• Maximum smooth muscle content : Arterioles.
Starling forces at capillary :
Arterial end Venous end

Starling Forces :
Capillaries 1. Capillary hydrostatic pressure (Pc)
2. Capillary oncotic pressure (Πc)
3. Interstitial hydrostatic pressure (Pi)
Interstitial
space 4. Interstitial oncotic pressure (Πi)
Forces directed Forces directed
outwards inwards
(favors filtration) (favors reabsorption)

Net filtration pressure= Forces favouring filtration-Forces favouring reabsorption


= (Pc + Πi ) - (Πc + Pi).
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50 06 Physiology

----- Active space -----


Poiseuille Hagen formula : F (Blood Flow) = (PA- PB) * Πr4 / 8 ηL
• Blood flow ∝ Pressure difference (PA- PB).
• Blood flow ∝ radius4 (r4).
• Blood flow ∝ 1/ Length (L).
Reynolds number (Re) : Reynolds number = pDV/ η
p : Density of the fluid. V : Velocity.
D : Diameter of the tube. η : Viscosity.
Blood flow inside the vessel can be :
1. Laminar flow → Re < 2000.
2. Turbulent flow → Re > 3000.
Significance of Reynolds number (Re) :
• Increase in blood flow velocity across a stenotic valve causes turbulence
(murmur).
• Decrease in viscosity (anemia) causes murmur by increase in Re.

Blood clotting cascade 01:06:20

Blood clotting mechanism → Positive feedback mechanism.


Intrinsic pathway
Kininogen,
XII Kallikrein XII (a)
Extrinsic pathway
XI XI (a)
Tissue Thromboplastin
IX IX (a) (III)

VIII VIII (a) VII (a) VII

X X (a) X
V V (a)

Common pathway Prothrombin (II) Thrombin (IIa)

Fibrinogen Fibrin (Monomer)


Fibrin stabilizing factor (XIII)
Fibrin stabilization
(Definitive clot)

Test Normal value Measures


APTT : Activated Partial
APTT 26-40s Intrinsic & common coagulation pathways Thromboplastin time.
PT 11- 16 s Extrinsic & common coagulation pathways PT : Prothrombin time

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Blood pressure 01:09:56 ----- Active space -----

Arterial Blood Pressure (BP) :


Defined as the lateral pressure exerted by the column of blood on vessel wall.
Pulse pressure (PP) :
Difference between systolic and diastolic blood pressures (SBP – DBP).
Mean Arterial Pressure (MAP) :
• MAP = DBP + 1/3 PP.
• Normal mean arterial pressure is 93 - 100 mm Hg.

Regulation of blood pressure (BP) :


1. Short term regulation of BP (Nervous control) : Baroreflex, Chemoreflex, CNS
Ischemic Response.
2. Intermediate term regulation of BP : Capillary fluid shift, Stress relaxation.
3. Long term regulation of BP (kidney control) :
Renin Angiotensin Aldosterone system (RAAS).
Regulation of blood volume by kidney.

Baroreflex :
• Baroreceptors (high pressure receptors) : Carotid sinus (CN 9), aortic arch
(CN 10) .
• Other Baroreceptors : Atrial and pulmonary artery baroreceptors
Also called low pressure (volume sensing) receptors.
Two types of atrial stretch receptors are,
a. Type A : Activated during atrial systole.
b. Type B : Activated during atrial diastole.
Distension of baroreceptors due to increase in BP

Increased firing in CN 9, 10

Excites nucleus tractus solitarius


Glutamate
Excites �audal ventro-lateral medulla Excites vagal
GABA neurons
Inhibits rostral ventro-lateral medulla
Activation of
Inhibition of sympathetic NS parasympathetic NS

Decrease in BP & HR

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52 06 Physiology

----- Active space -----


Baroreceptors : First line BP control in the range of MAP 70-150 mmHg.
Chemoreceptors : Second line BP control in the range of MAP 40-70 mmHg.
CNS ischemic response : Last ditch stand.
• Last line of control when MAP < 40 mm Hg.
• Activates sympathetic nervous system.

Mayer waves (vasomotor waves) :


Oscillations of nervous control mechanisms of BP.

Cardiac reflexes 01:20:24

Bainbridge reflex :
Venous Return → Atrial Reflex → SA node stimulated → HR.
Bezold Jarisch reflex :
In MI → Profound BP & HR (d/t serotonin).
Cushing’s reflex :
Bradycardia associated with elevated ICT.

Czermak-Hering test :
• Carotid sinus massage → activates parasympathetic NS → decreases HR.
• Rx for paroxysmal supra ventricular tachyarrhythmia.
Marey’s law : HR ∝ 1/BP.

Chemical regulation of cardiovascular system :

Vasoconstrictors ( BP) Vasodilators ( BP)


• Urotensin-II : Most potent. • Calcitonin gene-related peptide
• Endothelin. (CGRP) : Most potent vasodilator.
• Vasopressin. • Nitric oxide.
• Angiotensin II. • Prostacyclin (PGI2).
• Norepinephrine. • Kinins.
• Histamine.

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PHYSIOLOGY REVISION 7 ----- Active space -----

Endocrine Physiology 00:00:15

Forms of cell signalling:

Nearby
cell Autocrine signalling Gap Junctions

Paracrine signalling Endocrine signalling


far away cell
Classification of Hormones :
Class 1 : Amino acid derivatives.
Ex : Tyrosine Epinephrine, Norepinephrine, Dopamine.
Class 2 : Large protein hormones.
Ex : Insulin (51 amino acids), Parathyroid Hormone (84 amino acids).
Class 3 : Cholesterol derivatives.
Ex : Aldosterone, cortisol, testosterone, estrogen, progesterone.
Class 4 : Vitamins.
Ex : Vitamins A and D.

Hypothalamic and Pituitary Hormones 00:03:21

Most of the anterior pituitary hormones will have negative feedback except LH
surge (Increase in estrogen causes increase in LH levels).
Hypothalamic Releasing factors :
Hypothalamic hormones Anterior pituitary hormones
Thyrotropin-releasing hormone (TRH) Thyroid stimulating Hormone (TSH)
Adreno corticotrophin Releasing
Corticotropin-releasing hormone (CRH)
Hormone (ACTH)
Gonadotropin-releasing hormone Follicle Stimulating Hormone (FSH),
(GnRH) Luteinizing Hormone (LH)
Growth hormone-releasing hormone
Growth Hormone
(GHRH)
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----- Active space -----


Hypothalamic Inhibitory Hormones :
• Prolactin Release Inhibiting Hormone Dopamine.
• Growth Hormone Inhibiting Hormone Somatostatin.

Anterior and Posterior Pituitary Hormones :

Cell type Hormone


Anterior pituitary hormones
Acidophilic Somatotrope Growth Hormone
cells Lactotrope Prolactin
Gonadotrope FSH, LH
Basophilic
Thyrotrope TSH
cells
Corticotrope ACTH
Posterior pituitary hormones:
Stores and releases Oxytocin and Vasopressin

Growth Hormone 00:08:01

Regulation of Growth Hormone secretion :

Hypothalamus -

GHRH Somatostatin
+ -
+ Somatotrophs in anterior -
Ghrelin
pituitary
Growth Hormone
Liver

Insulin Like Growth factor -1


(IGF -1) Or Somatomedin-C

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Factors influencing growth hormone secretion : ----- Active space -----

Factors that increase growth Factors that inhibit growth


hormone secretion hormone secretion
• Low blood glucose (GH is a • Somatostatin
diabetogenic hormone) • Increase in blood glucose levels
• Exercise (Eg : glucose infusion)
• Fasting • REM sleep
• Stress
• Starvation
• Deep sleep (NREM stage 3 &4)

Actions of growth hormone :


Direct actions :

Direct actions of growth hormone (Anti insulin like)

Decreased insulin Protein Sodium Lipolysis


sensitivity synthesis retention

Indirect Actions:

Indirect actions of growth hormone

IGF-1 (Insulin like activity)

Anti lipolytic Protein Epiphyseal growth


synthesis

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----- Active space -----


Prolactin 00:13:32

Regulation of prolactin secretion :


Regulation of prolactin secretion

Hypothalamus

Thyrotrophin releasing Prolactin inhibiting factor


hormone (TRH) (Dopamine)
+ -
Lactotrophs in anterior pituitary
+ -
Vasoactive intestinal Glucocorticoids
peptide (VIP) Thyroid hormones
Prolactin

Factors influencing prolactin secretion :


Factors increasing prolactin Factors inhibiting prolactin
secretion secretion
• Marked increase during • Somatostatin
pregnancy and lactation • Dopamine agonists
• Sexual intercourse (Like Bromocriptine)
• Dopamine blockers

Thyroid Hormones 00:15:48

Thyroid hormone synthesis :

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----- Active space -----


Made up of tyrosine and iodine from diet Thyroid hormone binding proteins :
• Thyroid binding globulin
• Albumin
• Prealbumin/ transthyretin : Binds to thyroid hormone and Vitamin A

Difference between T4 and T3 :

T3 (Physiological actions) T4 (pharmacological drug form)


It is more potent It is less potent
Half-life : 1 day (less) Half-life : 7 days (more)
Plasma protein binding is less It bind more tightly to plasma proteins
Action is fast Action is slow and sustained
Less in colloid (7%) More in colloid (35%)

Effects of thyroid hormone :


Target tissue Effect Mechanism
Throughout Calorigenic Stimulates O2 consumption.
the body in basal metabolic rate.
Heart Chronotropic and Increased number of
inotropic ß-adrenergic receptor
(Norepinephrine mediated).
Adipose tissue Catabolic Stimulates lipolysis.
Muscle Catabolic proteolysis.
Bone Developmental Promote normal growth and
skeletal development.
CNS Developmental Promotes myelination.
Cholesterol Catabolic Cholesterol levels.

Endocrine Pancreas 00:25:10

Cell type Secretion


A cells (or) Alpha cells Glucagon
B cells (or) Beta cells Insulin, Amylin, C peptide
(60 – 75%), maximum
Lie in center of islets
D cells (or) Delta cells Somatostatin
F cells Pancreatic polypeptide

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----- Active space ----- Insulin:


Major anabolic hormone (Hormone of insurance).
Produced by β Cells in the islets of Langerhans (Abundant in tail of pancreas).

Steps in release of insulin in islet of Langerhans :

Step-3

Step-2

Step-1
Step-4

Factors that influence insulin secretion :


Factors that increase insulin secretion Factors that inhibit insulin secretion
• Glucose : Most potent factor. • Somatostatin
• Aminoacids Ex : Arginine, leucine
• Sympathetic discharge : • Sympathetic discharge :
ß-Adrenergic receptor mediated α-Adrenergic receptor
• Parasympathetic : mediated
Vagal stimulation and acetylcholine • Streptozocin.
• Incretin hormones :
GI hormones like glucagon-like
peptide-1 (GLP1) and gastric inhibitory
peptide (GIP).

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Mechanism of action of insulin : ----- Active space -----

Insulin receptor
α α
β β Cell membrane

Tyrosine kinase

Insulin receptor substrates (IRS)

PI3 Kinase MAP kinase

Decreases blood glucose Mediates growth promoting


levels via GLUT-4 mediated and anabolic functions
facilitated diffusion

Influence of insulin in metabolic pathways :

Pathways stimulated by Insulin Pathways inhibited by Insulin


Glycolysis Glycogenolysis
Glycogenesis Gluconeogenesis
Lipogenesis Lipolysis

Hyperglycemic hormones :
Hormones antagonizing action of insulin → hyperglycemia.
a.k.a counter regulatory hormones :
• Cortisol
• Growth hormone
• Glucagon
• Epinephrine
• Thyroid hormone

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----- Active space ----- Adrenal Gland 00:35:19

Zona glomerulosa :
Secrete Aldosterone
Zona fasciculata :
Secrete cortisol

Zona reticularis :
Secrete sex steroids
Adrenal medulla
Secrete
Catecholamines

Aldosterone
Actions :
Aldosterone acts on principal cell of
Distal convoluted tubule
• Reabsorption of sodium : Through
Epithelial Na channels (ENac) in luminal
surface
• Reabsorption of water
• Excretion of potassium ions in urine :
Through Renal Outer Medullary K+
channels (ROMK channel).
• Excretion of H+ ions in urine

Stimulus for aldosterone release :


• Increase in K+ concentration.
• Renin Angiotensin Aldosterone System (RAAS) : Angiotensin II.
• ENac channel blocker : Amiloride, Triamterene.

Note : Liddle’s syndrome : Hypernatremia, Hypertension, Hypokalemia


Occurs d/t Gain of funtion mutation of ENac channel.

Aldosterone escape :
Normally increase in aldosterone causes sodium reabsorption.
To prevent indefinite reabsorption of sodium, Atrial natriuretic peptide (ANP) is
secreted to promote sodium excretion
Hence the sodium excreted despite the presence of aldosterone.
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Cortisol : ----- Active space -----

Effect Mechanism
On carbohydrate
“Hyperglycemic hormone” → gluconeogenesis
metabolism
• Catabolic to proteins present in the muscle
On protein
• Anabolic in liver : synthesis of plasma proteins
metabolism
from liver
On fat metabolism Lipolytic
On immune system Universal anti-inflammatory agent
• Cortisol the blood levels of : Eosinophils, Lympho-
cytes, Basophils
On blood cells
• Cortisol the blood levels of : Neutrophils,Platelets,
RBCs
• Alters mood and behaviour
On nervous system
• appetite
On kidney • glomerular filtration rate and calcium excretion
On bone bone resorption by activity of osteoclasts
On connective Inhibits fibroblast proliferation and collagen formation
tissues (Delay wound healing)

Adrenal Sex steroids :


Adrenal sex steroids produced from zona reticularis are :
• Dehydroepiandrosterone/DHEA (Maximum).
• Dehydroepiandrosterone sulfate (DHEAS).
• Androstenedione.
• Testosterone (Only small amounts).
Role in : Axillary and pubic hair development, libido.

Calcium Homeostasis 00:47:41

Normal value of calcium : 8.7 - 10.2 mg/dL


Ionized calcium Protein bound calcium
Around 50% of total calcium Remaining 50% of total calcium
Also called as free calcium or Also called as non diffusible calcium
diffusible calcium
Physiologically active form Storage form bound to albumin and
globulin

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----- Active space ----- pH changes and calcium :


Acidosis Alkalosis

Increased H+ ions Decreased H+ ions

Bind to albumin Calcium binds to albumin


Increased free calcium Decreased free calcium

Hypercalcemia Hypocalcemia

Absorption of calcium :
• Calcium absorption occurs mainly in duodenum.
• Absorption of calcium is facilitated by gastric acid, protein rich diet.
• Absorption of calcium is inhibited by phytates and oxalates (Form complexes
with calcium).

Hormonal regulation of calcium levels :

PTH Vitamin D Calcitonin


Stimulus in S. Ca2+ in S. Ca2+ in S. PO43- in S. Ca2+
in PTH
Bone bone resorption Both bone Inhibits bone
mineralization and resorption
resorption
Intestine Indirectly acts by S. Ca2+ & S. PO43- -
vitamin D absorption
Kidney S. Ca2+ resorption S. Ca2+ & S. PO43- S. Ca2+
S. PO43-excretion resorption excretion
(phosphaturic)
Overall effect S. Ca2+ & S. PO43- S. Ca2+ & S. PO43- in S. Ca2+

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PHYSIOLOGY REVISION 8 ----- Active space -----

Male reproductive system 00:00:23

Male sex development : SRY gene


(Short arm of Y chromosome)

Sertoli cells Leydig cells


↓ ↓
Mullerian Inhibiting Testosterone
Substance (MIS) ↓
Internal genital organs
development

Peripheral Initiates Pulsatile release of


At Puberty Leptin Kisspeptin
Signal GnRH
Before puberty, pulsatile release of GnRH inhibited by GABA.
Leptin : Has permissive role indicating adequate body fat stores.
Note :
• Spermatogenesis : Occurs in seminiferous tubules.
• Maturation & mobility of sperms : In epididymis.
• Forward progressive motility of sperm
requires activation of catsper (Ca2+ channel).
• Capacitation :
1. Occurs in female genital tract.
2. Forward motility .
3. Facilitation of acrosomal reaction.

Functions of sertoli cells :


1. Production of :
• Anti-Mullerian Hormone (AMH)/MIS. Spermiation

• Androgen Binding Protein (ABP).


• Inhibin : Inhibits FSH.
2. Form Blood-Testis Barrier (BTB).
3. Provide nutrients to sperms (Nurse cells of testis).

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64 08 Physiology

----- Active space -----


4. Testosterone Aromatase Estrogen.
5. Phagocytic function : Engulf dead sperms.

Semen :
Contribution Composition
Seminal vesicles : 60%. Seminal vesicles secretions Prostate secretions
Prostate : 20-30%. 1. Fructose. 1. Spermine (Barberio’s
Vas deferens : 10% 2. Phosphorylcholine test).
(Florence test). 2. Zinc.
3. Ascorbic acid. 3. Acid phosphatase.

Two cell-Two Gonadotropin model : Hypothalamo-pituitary-testicular axis.


Hypothalamus

GnRH

Anterior pituitary
-
LH FSH

- Leydig cells Sertoli cells -


+
Testosterone Inhibin B
Functions of testosterone :
1. Stimulation of Wolffian duct → Internal genital organs formation.
2. Stimulates Erythropoietin synthesis → ↑ RBC.
3. Protein anabolic effects → ↑ Muscle mass.
4. Stimulates bone growth.
5. Initiation and maintenance of spermatogenesis.
6. Stimulates ABP (production by sertoli cells).
7. Regulates libido.
Testosterone 5-a reductase Dihydrotestosterone (DHT)
Actions of DHT ( DHT during puberty) :
1. Masculinisation of external genitalia.
2. Development of prostate.
3. Responsible for : Facial hair, acne, temporal recession of hairline.
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Female Reproductive System 00:15:30 ----- Active space -----

Menstrual cycle :
Average cycle length : 28 days and ovulation occurs on day 14.
Follicles produce estrogen under influence of FSH.

Follicular phase Ovulation Luteal phase


Developing Dominant (constant
follicles follicle duration)

LH

FSH

Estrogen

Progesterone

LH surge (positive feedback) : Luteal phase :


↑ Estrogen → ↑ LH. • Occurs for 14 days after ovulation
Occurs : 24-36 hours before ovulation. • LH → Leutinisation.
LH peak : 8-10 hours before ovulation. • Corpus luteum formation
• Produces Progesterone.
FSH surge : ↑ FSH
• Regresses on 24th day (if ovum

not fertilised).
↑ Plasmin

Lysis of follicle wall

Release of ovum.
Dominant follicle has maximum FSH
Receptors.

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----- Active space -----


Uterine endometrial cycle :
Proliferative
Menses phase Secretory phase
Days 1-5 Days 6-14 Days 15-28

Cyclical changes :
Cervical mucus Vagina
Thinner, alkaline : D/t Estrogen. Parabasal cells : D/t lack of hormones acting.
For survival & transport of sperm. Intermediate cells : D/t Progesterone.
Thick, tenacious : D/t progesterone. Superficial cells : D/t Estrogen.

Regulation of female reproductive system :


Two cell-Two Gonadotropin model : Hypothalamo-pituitary-ovarian axis.
Hypothalamus Note : Estrogen provides
positive feedback to LH
GnRH
+ only around ovulation
Anterior pituitary

- +
LH FSH
-
Theca cells Granulosa cells

Androstenidione Androstenidione Progesterone Activin Inhibin B


Aromatase

Ovarian Hormones Estradiol


Effects of ovarian steroid hormones :
Organs Estrogen Progesterone
• ↑ Excitability. • ↓ Excitability.
Uterus
• ↑ Sensitivity to oxytocin. • ↓ Sensitivity to oxytocin.
20 sexual
+++ No effect
charcteristics
Stimulates ductal growth (GH of Stimulates Lobular growth.
Breast
breast).

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Organs Estrogen Progesterone ----- Active space -----

Bone Protective : Inhibits osteoclasts. No effect


Liver ↓ S. Cholesterol. No effect
Cardioprotective : Inhibits platelet
CVS No effect
activation.
Neuroprotective : Inhibits apoptosis. CNS depressant.
CNS
Thermogenic action.
Salt and water retention. Diuretic effect : In large
Kidney doses.
MOA : Blocks aldosterone.
RS No effect ↑↑ Respiration.
Ovarian peptide hormones :
Hormone Action
Activin ↑ FSH.
Note :
Inhibin A Inhibin A (Corpus luteum)
↓ FSH.
&B Inhibin B (Granulosa cells)
Follistatin ↓ FSH
Relaxes pubic symphysis. Facilitates delivery
Relaxin
Dilates uterine cervix.
Human Chorionic Gonadotropin (hCG) : hCG and LH :
Glycoprotein : • t1/2 LH = 30 min.
• a subunit : Similar to FSH, LH, TSH. • t1/2 hCG = 37 hours.
• b subunit (main actions) : Similar to LH. • hCG has 80 times the biological
activity of LH.
Functions of hCG :
• Maintenance of corpus luteum till 6 weeks of gestation.
• Stimulates Leydig cells → Produces testosterone.
• Immunosuppressive activity.
• Secretion of relaxin from corpus luteum.
Lactation :
3 phases

1. Lactogenesis 2. Mammogenesis 3. Galactokinesis


(Milk production) (Milk ejection)
↓ Ductal growth Lobular growth ↓
Prolactin ↓ ↓ Oxytocin
Estrogen Progesterone
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----- Active space ----- PHYSIOLOGY REVISION 9

Glomerular filtration rate (GFR) 00:00:12

• Normal GFR = 125 ml/min or 180 L/day.


• Ultrafiltration happens in kidneys.
• Proteins are not filtered because :
a. Charge [negatively charged protein repelled by heparan sulphate
(anion) in the basement membrane].
b. Size (fenestrations in capillaries restrict protein entry).
c. Slit diaphragm (formed by foot process of podocytes whose intergrity
maintained by nephrin).
i. Nephrin mutation : Steroid unresponsive congenital finnish type
nephrotic syndrome.
ii. Podocin mutation causes steroid resistant nephrotic syndrome.
iii. Alpha actinin mutation : FSGS.

Determinants of GFR :
Net filtration pressure = Capillary hydrostatic pressure (~60 mmHg) -
Bowmans capsule hydrostatic pressure (~18 mmHg) - Colloidal oncotic pressure
(~32 mmHg).

Clearance :
Gold standard GFR estimation Inulin clearance
Most commonly used Creatinine
New marker- GFR Cystatin C

• Cs : Clearance.
• Us : Urine concentration of substrate.
• V : Urine flow rate.
• Ps : Plasma concentration of substrate.

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Factors affecting GFR : ----- Active space -----

Factor RBF GFR


Constriction of :
Afferent arteriole ↓ ↓
(Example : Nor epinephrine)
Efferent arteriole ↓ Biphasic response :
(Example : Angiotensin-II) Initially GFR ↑, Later ↓
Dilatation of :
Afferent arteriole ↑ ↑
(By Prostaglandins- PGE2)
Efferent arteriole ↑ ↓
(Example : ACEI)
Mesangial cells (surround glomerular capillaries)

Contraction Relaxation

Compress glomerular Expansion of glomerular


capillaries capillaries

Decrease in GFR Increase in GFR

Example : Example :
Endothelin, angiotensin II Nitric oxide, ANP

Renal circulation 00:15:29

• Renal blood flow : 1250 ml/min (23% of cardiac output).


• Renal plasma flow = 55% of RBF = 625 ml/min.
• Filtration fraction = GFR/renal plasma flow=20%
• For GFR estimation : Inulin.
• For RPF estimation : Para-aminohippuric acid
(PAH).

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----- Active space -----


Nephron 00:00:00

Parts of nephron :
Proximal convoluted tubule Distal convoluted tubule
Glomerular capillaries
Collecting ducts

Ascending loop of Henle Descending


loop of Henle

Events in PCT :
• PCT has maximum reabsorption capacity.
• Brush border cells on the apical side : Increases surface area for resorption.
• Have large number of mitochondria to support active transport processes.
• Obligatory water reabsorption (no hormones involved).
• PCT reabsorbs :
a. 2/3rd (70%) of filtered NaCl, water, k+,
urea, Ca2+.
b. 80 % of filtered phosphate & bicarbonate.
c. 100% of filtered glucose & amino acids.

• Glucose resorption in PCT is by : SGLT-2


(example of secondary active transporter,
shows saturation kinetics).
• Transport maximum glucose = 375 mg/min
→ Corresponds to plasma glucose value of
180 mg/dL (renal threshold).

Events in LOH :
• Countercurrent mechanism seen in LOH.
• Fluid entering LOH is isotonic.
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----- Active space -----

• Vasa recta : Counter current exchanger.


• Na+ K+ 2Cl- cotransporter blocked by furosemide.

Events in DCT :
• NaCl cotransport blocker : Thiazide
diuretic.
• Nacl cotransporter mutation :
Gitelman syndrome.
• Ca2+ reabsorbed by TRPV5 channel
(stimulated by PTH & vitamin D).

Juxta glomerular apparatus : 00:33:58

Cells Function
1. Juxta glomerular cells aka granular cells : Produce renin (↑Na+ and H2O
(in afferent arteriole) reabsorption).
2. Macula densa GFR sensors, senses ↑in GFR → release adenosine
(in thick LOH) → constrict AA & ↓ GFR (tubulo glomerular
feedback)
3. Extra glomerular Supportive cells aka Lacis cells/polkissen cells.
mesangial cells
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72 09 Physiology

----- Active space -----

JGA
Collecting duct :
• Two parts : Cortical & medullary collecting duct.
• Two cells : Principal cells & intercalated cells
• Two hormones : Aldosterone & anti-diuretic hormone (Vasopressin).
• Facultative water resorption (hormone dependent) occurs in collecting duct.

Collecting duct
Vasopressin receptors :
• V1 receptor : Vasoconstriction.
• V2 receptor : Water resorption using aquaporin-2.
V2 blocker : Conivaptan for treatment of SIADH.
• V3 receptors : Releases ACTH from anterior pituitary.

Bladder innervation & control 00:41:32

• Parasympathetic system : Facilitates micturition by causing contraction of


detrusor muscle & relaxation of internal urethral sphincter.
• Sympathetic system : Least role in micturition (carry pain signals from
bladder).
• Somatic supply : From pudendal nerve → External urethral sphincter.
• Higher centres :
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Physiology Revision 9 09 73

a. Facilitatory centers in pons & posterior hypothalamus. ----- Active space -----
b. Inhibitory centre : In midbrain.
c. Cortical level control : Paracentral lobule (supplied by ACA).

Cystometrogram :
• 1a : As bladder starts to fill, volume and
pressure in the bladder increase.
• 1b : Volume increases but the pressure
remains constant (Laplace’s law).
• 11 : Tremendous rise in pressure which leads to
micturition.
• First urge to void : 150 ml.
• Marked sensation to void : 400 ml.

Acid base balance 00:46:31

• Normal pH : 7.35 – 7.45.


• pH values above 7.8 0r below 6.9 are not compatible with life.
• Enzymatic activity and protein structure are very sensitive to pH.
• pH changes can denature proteins.
• Low pH (acidosis) : CNS becomes less excitable.
• High pH (alkalosis) : There is hyperexcitability leading to muscle twitches.
• Regulation of H+ ion concentration :
1. First line : Buffer systems (fast).
2. Second line : Respiratory mechanism.
3. Third line : Solute excretion via kidneys (slow).

Buffers :
• Most important extracellular buffer : Bicarbonate.
• Important intracellular buffer & buffer in tubular fluid (Kidney) : Phosphate.
• Most plentiful intracellular buffers : Protein.

Respiratory regulation :
• Increase in ventilation : Causes CO2 washout and reduce H+ concentration.
• Decreased ventilation : Co2 accumilation and increases H+ concentration.

Role of kidneys in acid base balance :


• Reabsorption of bicarbonate in PCT.
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• Generation of new bicarbonate : Uses phosphate and ammonia buffer in
place of bicarbonate to neutralise acid.
• Intercalated cells in collecting duct : Type A is acid excreting during acidosis
& type B (Base excreting during alkalosis).
Hensin
A B
Conversion between A & B type cell during acidosis & alkalosis done by Hensin
protein.

Anion gap
• Refers to unmeasured anions.
• Mainly due to plasma protein anions, sulfate, phosphate.
• Anion gap = [Na+] - [HCO3- + Cl–] = [140 mEq/L] - [25 mEq/L + 105 mEq/L]
• Anion gap = 10 mEq/L.

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PHYSIOLOGY REVISION 10 ----- Active space -----

GIT Functions :
1. Secretion : Digestive enzymes.
2. Motility : D/t enteric nervous system (ENS), hormones.
Daily water turnover in GIT (ml)
Ingested fluid 2000
GI secretions
Salivary glands 1500
Stomach 2500 (Maximum)
Total secretion 9000
Reabsorption
Jejunum 5500
Colon 1300
Total reabsorbed 8800
Remaining 200 ml : Excreted in stool.

GIT Secretions 00:04:48

Saliva
• Contains digestive enzymes : Amylase (Ptyalin), lingual lipase.
• No enzymes for protein digestion.
• Protective function : Secretory IgA, lactoferrin, lysozymes.

Gastric mucosa & secretions :


(HCl)

Mucus
Stem cells
HCl, Intrinsic factor

Pepsinogen
Histamine
G-cells Gastrin

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Parietal cell :

in HCO3- levels post food intake → Post prandial alkaline tide

Increase gastric acid secretion Decrease gastric acid secretion


1. Histamine. 1. Acid.
2. Gastrin. 2. Somatostatins (D cells).
3. Acetylcholine. 3. Prostaglandins :
Side effect of NSAIDS : Gastric ulcer.
Phases of Gastric secretion :

Cephalic phase Gastric phase Intestinal phase


• Accounts for 30 %. • Accounts for 60 %. • Accounts for 10%.
• Initiated by thought, • Activated when • Digested protein
sight, Smell/ taste of food enters products stimulates
food. stomach. intestinal G cells to
release gastrin.

Exocrine pancreatic secretion

Nature : Alkaline pH (8.3).


Contains enzymes :
1. Pancreatic amylase (Carbohydrate digestion).
2. Lipase, colipase ( Lipid digestion).
3. Trypsin, chymotrypsin, carboxypeptidase (protein digestion) :
• Stored as zymogens (inactive forms).
• Activated in small intestine by enterokinase.
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Regulation of pancreatic secretion : ----- Active space -----

Secretin Cholecystokinin (CCK)


Makes pancreatic juice rich in HCO3-→ Makes pancreatic juice rich in
Neutralise gastric acid (Nature’s antacid). digestive enzymes.

Enteric Nervous System (ENS) : Little brain in gut.

Submucous/Meissner’s plexus Myenteric/Auerbach plexus


Present in submucosa. Present between muscle groups.
Control of secretions & blood flow (Mainly). Involved in motility.

GIT motility 00:23:33

General features of GI smooth muscles :


• Regulated by smooth muscles (Involuntary type).
• Pacemaker : Cajal cells.
• Fluctuation of Restless membrane potential/basal electrical rhythm/slow
waves of Cajal cells : -60 mv to -40 mv.
a. Activated by cholinergic system.
b. Inhibited by adrenergic system.
Special features of GI smooth muscles :
Rate of Basal electrical rhythm (BER) :
• No titin & not elastic : Plasticity.
• Duodenum (Highest) : 12/min.
• Calmodulin ( Ca binding protein).
• Caecum (Lowest ) : 2 /min.
• Latch bridge mechanism.
Gastric motility patterns :
1. Peristalsis :
• Stimulus : Stretch of gut (Fed state).
• Always move from oral end to anal end.
• Segments :
a. Contraction segment : Neurotransmitters (Acetylcholine, Substance P).
b. Relaxation segment : Nitric oxide, Vasoactive intestinal peptide.
2. Receptive relaxation : For storage/ gastric accommodation.
3. Retropulsion : Mixing & grinding of food → Chyle.
4. Gastric emptying :
a. Fastest for food rich in carbohydrates.
b. Slowest for fat rich diet.

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Factors influencing gastric emptying :
Gastric emptying Gastric emptying
1. Gastrin. 1. Cholecystokinin.
2. in gastric volume. 2. Undigested Carbohydrates, lipids & proteins
→ Enterogastric reflex.
3. Hyperosmolar contents.
Small intestinal (SI) motility patterns :
1. Peristalsis.
2. Segmentations (Both ends are contraction segments).

Large intestinal motility patterns :


1. Haustrations :
• Combined contraction of longitudinal & circular muscles.
• For absorption of water and electrolytes.
2. Mass movements :
• Mass of food to rectum → Rectal distension → Defecation.

Vomiting :
• Anti peristalsis.
• Control :
1. Neural : Chemoreceptor trigger zone (CTZ) at area postrema.
2. Humoral : Toxins.
• Sequence :
Nausea, salivation → Closure of glottis → Reverse peristalsis →
Contraction of diaphragm & abdominal muscles →Intragastric pressure
rises → Lower & upper esophageal sphincter opens → Vomiting.

Defecation reflex 00:37:11

• Sequence :
Rectal distension → Afferent to spinal cord → Parasympathetic input
→ Relaxation of internal anal sphincter → Relaxation of external anal
sphincter (Under voluntary control) → Contraction of abdominal muscles,
rectum, colon → Defecation.
• First urge to defecate : Rectal pressure of 18 mm Hg.
• Maximum rectal pressure : 55 mm Hg.
• Beyond maximum pressure → Soiling.
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Dietary fibres/ Roughage : ----- Active space -----


• Eg : Lignin, pectin, cellulose.
• Rich in fruits, vegetables, cereals.
• Function :
1. Bulk fibres in diet → Decrease appetite.
2. Slows absorption of glucose.
3. Reduces cholesterol levels.
4. Hold water → Bulking of stool.
5. Converted to short chain fatty acids by microflora → Energy source.

Migratory Motor Complex (MMC) :


• Fasting state motility pattern.
• Migrates from stomach to colon → Cleans GIT (Sweeper).
• 1 MMC once every 90 minutes.
• Regulated by motilin (time keeper hormone).
• Erythromycin → Acts via motilin receptor → Increase MMC motility → Used
in treatment of gastroparesis.

Note : Enteroendocrine cells in GIT :


Enteroendocrine cell Secreting hormone
G cells Gastrin.
I cells Cholecystokinin.
S cells Secretin.
Gastric inhibitory peptide/glucose
K cells
dependent insulinotropic peptide(GIP).
Mo cells Motilin.
D cells Somatostatin.

GI hormones 00:45:40

A. Gastrin :
• Produced by G cells in the antral portion of the gastric mucosa.
• Stimuli that increase gastrin secretion : Distension, peptides.
• Stimuli that decrease gastrin secretion : Acid, somatostatin.
• Acts via CCK B receptor.
• Actions : a. Stimulation of gastric acid.
b. Trophic action : Stimulation of growth of mucosa.
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B. Cholecystokinin/Pancreozymin :
• Secreted by I cells in mucosa of proximal SI.
• Stimuli : Peptides & fatty acids.
• Acts via CCK A receptor.
• Functions in gut :
a. Release of pancreatic juice rich in enzymes.
b. Contraction of gallbladder (Cholagogue).
c. Augments the action of secretin.
d. Inhibits gastric emptying.
e. Exerts a trophic effect on pancreas.

C. Secretin :
• Secreted by S cells.
• Stimulus : Acid chyme.
• Major actions : a. Release of pancreatic juice rich in bicarbonate.
b. Stimulate action of cholecystokinin.

D. Ghrelin :
• Secreted primarily by oxyntic gland & stomach.
• Stimuli : Peaks during fasting state.
Low in obese, high in anorexia nervosa.
• Functions :
a. Orexinergic : Increase appetite.
b. Increases gastric motility & gastric acid secretion.
c. Increases adipogenesis.
d. Increases growth hormone releasing protein.

Digestion & Absorption 00:53:23

Carbohydrate, lipids & proteins :

Digestion Carbohydrate Lipid Protein


Saliva Salivary amylase Lingual lipase No enzyme
Stomach No enzymes Gastric lipase Pepsin
Pancreatic lipase Trypsin, chymotypsin,
Pancreas Pancreatic amylase
& Co lipase carboxypeptidase
Small Intestine Lactase, sucrase No enzymes No enzyme

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Absorption Carbohydrate Lipid Protein ----- Active space -----

Site Duodenum & jejunum.


Cell Mucosal cells.
Glucose : By SGLT 1 Passive diffusion of PepT peptide
Transport Fructose : By GLUT 5. FFA from micelle to transporter along with
mucosal cells. H+ into mucosal cells.

Note : When ORS is taken, Na+ is absorbed along with glucose via SGLT-1.
Iron Absorption : 00:59:00
• Mainly from duodenum.
• Dietary source : Ferric form (Fe3+).
• Absorbable form : Ferrous (Fe2+).

Hepcidin :
• Produced by liver.
• Regulated by HFE gene.
• Negative regulator of iron absorption.
• Inhibits Fe release from macrophages & other cells by binding to ferroportin.
• Links Fe stores with Fe absorption.
• Mutations : Hemochromatosis (Iron overload).

Storage
form

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Exercise Physiology 01:03:10

Two types of exercises :


Isotonic exercise Isometric exercise
Dimensions
(Dynamic type) (Static type)
Tension Constant Increases
Length Changes Constant
Example Treadmill running Pushing against a wall
Energy sources for exercising muscles :
System ATP/Min Can sustain activity upto
Phosphocreatinine system 4 8 - 10 seconds.
Glycogen- Lactic acid system 2.5 1.3 - 1.6 minutes.
Aerobic system 1 Unlimited ( Till nutrients last).

Redistribution of blood flow during exercise :


• Coronary circulation : .
• Renal, GIT : .
• CNS : No change (Autoregulation).
• Cutaneous circulation : Initial , later (d/t heat dissipation).

BP changes during exercise :


• In isotonic : SBP ↑ & DBP ↓ (D/t decrease in total peripheral resistance).
• In isometric : SBP ↑ & DBP ↑ (D/t rise in total peripheral resistance).

Respiratory changes during exercise :


1. Anticipatory tachypnoea ( RR) : Proprioceptive impulse → Ventilation.
2. Arterial pH, PCO2, PO2 remain normal.
3. Increased oxygen uptake : MET (Metabolic equivalent) during exercise.
Terms related to oxygen uptake :
• V02 max : Maximum possible O2consumption (theoretical).
• Peak V02 : Maximum O2consumption at the end of exercise.
• EPOC (Excess post exercise O2consumption) : RR, O2 post exercise →
To replenish Hb & myoglobin O2 stores.

Note : 1 MET = Resting O2 consumption = 250 mL/min.

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