General physiology REVISION NOTES PHYSIOLOGY

General physiology
TONY SCARIA
2010 KMC

Claude Bernard 
• MILEU INTERIOR
TONY SCARIA
2010 KMC

Variations
TONY SCARIA
2010 KMC

Water distribution in body
TONY SCARIA
2010 KMC

Measurement of fluid
compartment
TONY SCARIA
2010 KMC

Measured by indicator dilution method
• Based on ficks principle
TONY SCARIA
2010 KMC

Measurement of volume
TONY SCARIA
2010 KMC

Red cell volume 
TONY SCARIA
2010 KMC

• Whole blood volume = RCV + plasma volume
TONY SCARIA
2010 KMC

Impossible to measure ISF & ICF directly
• ISF = ECF- PV
• ICF = TBW- ECF
TONY SCARIA
2010 KMC

Input of fluid
Fluids
ingested
2250
From
metabolism
250
Total intake 2400
Fluid output
Sweat 200
Feces 100
Insensible loss
through skin
350
Insensible loss
through lung
350
Urine 1400
Total output 2400
TONY SCARIA
2010 KMC

COMPOSITION OF ECF & CIF
TONY SCARIA
2010 KMC

Transport
TONY SCARIA
2010 KMC

Osmosis
• Movement of solvent across a semipermeable membrane
(impermeable to solute)
• Movement of solvent to a solution where there is higher
concentration of solute
TONY SCARIA
2010 KMC

Osmolarity vs tonicity
• Osmolarity
• Total concentration of nonpermeable & permeable solute
• tonicity
• Total concentration of only non permeable particles
• Tonicity determines direction of osmosis
TONY SCARIA
2010 KMC

• Among osmoles (permeable & nonpermeable )
• Only non permeable are called effective osmoles  causes osmosis 9like Na+
& Cl-
• While permeable like urea are ineffective
TONY SCARIA
2010 KMC

ECF osmolarity
• Measured by osmometer
• Major contributor to ECF osmolarity Na+
• Normal srum osmolarity 290mOsm/L
TONY SCARIA
2010 KMC

Osmotic pressure depends
• Number of osmotically active particles
• One osmotically active particle exerts pressure 22.4 atmosphere
TONY SCARIA
2010 KMC

filtration
• Transport of substances (solvent or solute) along a pressure gradient
across membrane
TONY SCARIA
2010 KMC

Solvent drag
• In PCT
• Solvent moves into
• Carries solute along with
solvent
TONY SCARIA
2010 KMC

Bulk flow
• Also in PCT
• Also in CSF formation
• Large volume of solute
or solvent across a
pressure gradient
TONY SCARIA
2010 KMC

Diffusion
• Across cell membrane
• Along concentration gradient
• Diffusion is proportional to temperature & lipoid solubiluity
• Inversely proportional to charge of substance or size of particle
TONY SCARIA
2010 KMC

Ficks law of diffusion
TONY SCARIA
2010 KMC

Facilitated diffusion
• Faster than simple diffusion
• Along concn gradient
• For transport of larger molecules like sugar aminoacids
• Rate of diffusion proportional to availability of carriers
• Shosw saturation kinetics (as it is carrier mediated)
TONY SCARIA
2010 KMC

Saturation kinetics  carrier mediated
transport
TONY SCARIA
2010 KMC

Non ionic diffusion
• Undisssociated ions diffuse from one side of membrane to other side
then dissociate
• Helps in maintaining concentration gradient
• Involved in absorption of drugs in Git
• Excretion of NH3 in blood
TONY SCARIA
2010 KMC

Nonionic diffusion of ammonia
TONY SCARIA
2010 KMC

Active transport
• Against concentration gradient
• Mediated by carrier protein
• Requires ATP
• The active transport is of two types:
• Primary active transport and
• Secondary active transport
TONY SCARIA
2010 KMC

Primary active transport
• Energy is derived from hydrolysis
of ATP
• Na+ K+ ATPase pump
• Ca2+ pump
Secondary active transport
• Combination of primary active
transport with facilitated
diffusion
• Symport
TONY SCARIA
2010 KMC

Na + - K+ pump
• ATP ase
• Coupling ratio 3:2
• Electrogenic pump
• Contribute to only 4mV of total RMP (90 mV)
• Stimulated by
• increased intracellular concn of Na
• Thyroid hormone
• Aldosterone
• Insulin
• Inhibited by
• CRF
• CHF
• Digoxin toxicity
• Dopamine
TONY SCARIA
2010 KMC

Na + - K+ pump
TONY SCARIA
2010 KMC

Calcium pump
• The calcium pump helps in maintaining extremely low concentration
of calcium in the intracellular fluid (10,000 times less than the ECF)
• Primary active transport
TONY SCARIA
2010 KMC

Vesicular transport is also active
TONY SCARIA
2010 KMC

Endocytosis
• Constitutive
• Non specific continuous process
• Receptor mediated endocytosis
TONY SCARIA
2010 KMC

Regulated endocytosis
• Clathrin mediated / caveolin
mediated
• Coated pits
• Endocytosed vesicle fuses with
early endosome
• Low pH with in endosome 
breaks linkage b/w receptor
ligand complex & releases
receptor clathrin & membrane
fragment s
• It requires Ca2+ energy
contractile elements (actin &
myosin)
TONY SCARIA
2010 KMC

Exocytosis
• Requires Ca2+ & energu=y
• Regulated pathway
• SNARE proteins
• Constitutive pathway
TONY SCARIA
2010 KMC

Transcytosis
• In cells of epithelium
• Also seen in endothelial cells of blood vessel
• Always regulated
TONY SCARIA
2010 KMC

Enzyme linked
TONY SCARIA
2010 KMC

Tyrosine kinase receptor
• insulin
TONY SCARIA
2010 KMC

janus kinase pathway
• Erythropoetin
• Cytokines  interleukin
• colony stimulating factor
TONY SCARIA
2010 KMC

janus kinase pathway
TONY SCARIA
2010 KMC

Orphan ligands
• No ligands or unknown ligands
TONY SCARIA
2010 KMC

G protein coupled recptor
• 7 transmembrane spanning
TONY SCARIA
2010 KMC

Resting membrane potential
TONY SCARIA
2010 KMC

• Goldman-Hodgkin-Katz equation (G-H-K equation),
• Which takes into account the permeabilities and concentrations of the
multiple ions
TONY SCARIA
2010 KMC

Action potential
TONY SCARIA
2010 KMC

• Action potential is due to opening of voltage gated Na+
channels(during depolarisation) & voltage gated K+ channels (during
repolarisation)
TONY SCARIA
2010 KMC

• Amplitude of action potential is 105mV
• Threshold stimulus 15mv (-70mv to 55mv)
TONY SCARIA
2010 KMC

• Absolute refractory
period
• From firing level to
repolarisation is
complete until 1/3rd
• However strong
stimulus cannot cause
AP
• Relative refractory
period
• From end of ARP to end
of after depolarisation
TONY SCARIA
2010 KMC

Tetrodotoxin (TTX)
• one of the most potent poisons
known, specifically blocks the Na+
channel. TTX binds to the
extracellular side of the sodium
channel.
TONY SCARIA
2010 KMC

• Tetrodotoxin (TTX), one of the most potent
poisons
• known, specifically blocks the Na+ channel.
• The ovaries of certain species of puffer fish,
also known as blowfish, contain TTX.
• Raw puffer fish is a highly prized delicacy in
Japan. Connoisseurs of puffer fish enjoy the
tingling numbness of the lips caused by the
minuscule quantities of TTX present in the
flesh. TONY SCARIA
2010 KMC

• Tetraethylammonium (TEA+),
another
• poison, blocks K+ channels. TEA+
enters the K+ channel
• from the cytoplasmic side and
blocks the channel
• because TEA is unable to pass
through it.
TONY SCARIA
2010 KMC

Biphasic action potential
• If both electrodes are kept on
the surface of cell  biphasic
action potential
TONY SCARIA
2010 KMC

Compound action potential
• Seen in nerve bundle rather
than in a single axon
• Multipeaked
• Does not obey all or none
law
TONY SCARIA
2010 KMC

Properties of action potential
• Self propagation
• Propagated with out decrement
• All or none phenomenon
• It requires a threshold
• If below threshold no response
• If above threshold AP of definite
duration & amplitude
• d/t absolute refractory period
TONY SCARIA
2010 KMC

Suprathreshold stimulus  can cause
multiple AP in relative RP
TONY SCARIA
2010 KMC

Recording of action potential
• Cathode ray oscilloscope
• Micro electrodes
• Amplifier
TONY SCARIA
2010 KMC

Recording of action potential
• Patch clamp method
• Voltage clamp method
TONY SCARIA
2010 KMC

Patch clamp method
TONY SCARIA
2010 KMC

Voltage clamp method
TONY SCARIA
2010 KMC

Strength duration curve
• Rheobase
• Min amplitude of current
that can cause AP
• Chronaxie
• Minimum duration for a
stimulus double the rheobase
has to be applied
TONY SCARIA
2010 KMC

Chronaxie is a measure of excitability
• Chronaxie is shortest for
• Sensory N (lowest) <motor N<sk muscle <cardiac< smooth muscle (longest)
TONY SCARIA
2010 KMC

Local potential
TONY SCARIA
2010 KMC

Local potential
• Graded responses
• Strength increases with increasing strength of current
• AP is not graded
• Strength decreases after a short distance
• AP strength donot decreases
• Summation possible
• No summation for AP
• No refractory period
• No threshold
• Donot obey all or none law
TONY SCARIA
2010 KMC

Summation
• Single sub threshold stimulus fails to produce action potential
• But a second subthreshold stimuli applied quickly  summation
• Spatial
• Simultaneously
• Two subthreshold stimuli applied geographically closely
• Temporal
• When summation is in trlation to time
• One after the other
• At the same location
TONY SCARIA
2010 KMC

EPSP (Excitatory post synaptic potential)
• i. Definition: the increase in voltage above the normal resting potential — that is
to a less negative value — is called EPSP because if this potential rises high
enough, it will elicit on action potential in the neuron, thus exciting it.
• ii. EPSP is due to depolarization.
• iii. Production → rapid influx of Na+ to the interior neutralised part of the
negativity of RMP → RMP ↑ed from - 65 to 55 EPSP → excite the neuron.
• [Note → by openings of Na+ or Ca++ ions channels, producing an inward current].
TONY SCARIA
2010 KMC

IPSP (Inhibitory post synaptic potential)
• i. Definition → increase in negativity beyond the RMP level is called IPSP, that inhibits the neuron
to be excited.
• ii. Production - opening of the chloride channels will allows negatively charged chloride ions to
move to the interior
• CT ions influx) → membrane potential becomes more negative than normal; and opening of K+
channels will have K+ ions to move to the exterior (K+ ion efflux). → make membrane potential
more negative than usual. Thus Cl- influx and K+ efflux→ increase the degree of intracellular
negativity →called Hyperpolarization → inhibits the neuron to be excited.
• [ Note — In addition IPSP is also produced by K+ eflux and clossure of the Na+ or Ca++ channels]
TONY SCARIA
2010 KMC

Electrotonic potential
• Passive deposition of charge on
membrane
• Cathodic stimulation is
depolarising
• Anodic stimulation is
hyperpolarising
TONY SCARIA
2010 KMC

Propagation along both directions
TONY SCARIA
2010 KMC

Glial cells
TONY SCARIA
2010 KMC

• Neurons : glial cells = 1:15
TONY SCARIA
2010 KMC

Satellite cells are seen around dorsal root
ganglia
TONY SCARIA
2010 KMC

Myelin
• 40 % is H2O
• 60 % dry mass
• 70 – 85 %  lipids
• 15-30 % proteins
TONY SCARIA
2010 KMC

Oligodendrocyte myelinate in CNS
• Myelinate several axons
TONY SCARIA
2010 KMC

Schwaan cells myelinate in peripheral NS
• Myelinate only single axon
TONY SCARIA
2010 KMC

Nerve regeneration
TONY SCARIA
2010 KMC

Erlanger gasser classification
TONY SCARIA
2010 KMC

Numerical classification is for only sensory
fibres
• So Aγ B can be avoided
TONY SCARIA
2010 KMC

Proprioception
• Muscle spindle  muscle
length
• Golgi tendon organ  muscle
tension
TONY SCARIA
2010 KMC

• Most susceptible to pressure are A fibres
• Most susceptible to LA are C fibres
TONY SCARIA
2010 KMC

Post ganglionic sympathetic fibres are
unmyelinated  C fibres
reganglionic autonomic
both sympathetic &
arasympathetic ) B
Post ganglionic ONLY
SYMPATHETIC  C TONY SCARIA
2010 KMC

Kinesin carries membrane bound structures
microtubules
Kinesin
TONY SCARIA
2010 KMC

Neuromuscular junction
TONY SCARIA
2010 KMC

• Skeletal muscle
• 40% of body weight
• Well developed cross striation
TONY SCARIA
2010 KMC

I band  isotropic band
TONY SCARIA
2010 KMC

Sarcomere functional unit located b/w two
Z lines
TONY SCARIA
2010 KMC

• Titin
• Largest known protein
• Connects z line to M line
• Forms the frame work that holds actin & myosin in place
TONY SCARIA
2010 KMC

Troponin
• Binding of Ca2+ to troponin C
sliding of tropomyosin away
from active site of actin
TONY SCARIA
2010 KMC

Myosin
• Myosin in skeletal muscle  type II
• Thick filament
• Also acts as an ATPase
TONY SCARIA
2010 KMC

Thin filament is composed of
• Actin
• Tropomyosin
• Covers active site on actin (myosin binding site)
• Troponin
TONY SCARIA
2010 KMC

M line
• Thick line at middle portion of H
zone
• Contain creatine kinase
TONY SCARIA
2010 KMC

Pseudo H zone
• Part of H zone not
overlapped by myosin
heads
• Part of myosin with out
head
TONY SCARIA
2010 KMC

I band  isotropic band
• Made up of actin
• Divided in two by z line
TONY SCARIA
2010 KMC

Role of ATP
• ATP
• Causes dissociation of myosin head from actin filament
• Provides energy for power stroke
• ATP depletion in death  cannot cause dissociation of actin & myosin
 RIGOR MORTIS
TONY SCARIA
2010 KMC

• T tubules are infoldings of
sarcolemma
• Allow penetration of electrical
discharge to the inner core of
muscle cell
• Sarcoplasmic reticulum arranged
longitudinally  L tubules
• Terminal cisterns of sarcoplasmic
reticulum  store house of Ca2+
TONY SCARIA
2010 KMC

Triad of sarcoplasmic reticulum
TONY SCARIA
2010 KMC

• Dihydropyridine  voltage gated
• Physically coupled to ryanodine
receptors
• Ca2+ induced ca2+ release
TONY SCARIA
2010 KMC

• Voltage induced confirmational
change in dihydropyridine receptor
produces conformational change in
ryanodine receptor
TONY SCARIA
2010 KMC

• Mutattion in ryanodine receptor
 massive release of Ca2+
malignant hyperthermia
TONY SCARIA
2010 KMC

Muscle relaxation also requires ATP
TONY SCARIA
2010 KMC

SERCA or ca2+ ATPase
TONY SCARIA
2010 KMC

Tetanising frequency = 1/ contraction period
TONY SCARIA
2010 KMC

• Isotonic contraction increases muscle strength
TONY SCARIA
2010 KMC

Tone
• resistance to Passive stretch
• d/t gamma motor neuron discharge
TONY SCARIA
2010 KMC

Denervation hypersensitivity
• Fine irregular contraction of individual fibre
•  fibrillation
• In LMN lesion
• Not visible grossly
TONY SCARIA
2010 KMC

Smooth muscle
TONY SCARIA
2010 KMC

Smooth muscle
• Involuntary non striated
• Spindle shaped
• Innervated by autonomic nerves conatins beaded enlargement (clear
vesicle of Ach or dense vesicle of NE)
TONY SCARIA
2010 KMC

Z lines are absent instead they have dense
bodies
TONY SCARIA
2010 KMC

• Troponin is absent in smooth
muscles
• Instead of T tublules smooth
muscles have caveolae
• SR is not well developed
TONY SCARIA
2010 KMC

Z lines are absent instead dense bodies are
present
TONY SCARIA
2010 KMC

Contraction
TONY SCARIA
2010 KMC

2 types of smooth muscles
Single unit
• d/t gap junction entire muscle
mass acts as a single unit ie
syncytium
• Most smooth muscle gut ureters
Multi unit
• Discrete muscle fibres capable of
contracting independently
• Ciliary muscles smooth muscle
of iris trachea bronchi
TONY SCARIA
2010 KMC

ACTION POTENTIAL IN SMOOTH MUSCLE
TONY SCARIA
2010 KMC

• No troponin is present in smooth muscle
• Smooth muscle contains a calcium binding
protein called calmodulin & gets activated
•  activates myosin light chain kinas
(MLCK) which in turn phosphorylates
myosin  CROSSBRIDGE
PHOSPHORYLATION
TONY SCARIA
2010 KMC

Relaxation of smooth muscle
• Dephosphorylation of myosin by myosin light chain phosphatase
TONY SCARIA
2010 KMC

Latch effect in smooth muscle
• Dephosphorylation by MLCP does not necessarily lead to relaxation
 prolonged smooth muscle contraction
• With minimal expenditure of energy
• Low enegy is required to sustain smooth muscle contraction
• Contraction is slow & sustained in smooth muscles
TONY SCARIA
2010 KMC

Stretch
• Stretch can lead to development of spike potential even in the
absence of nervous innervation
TONY SCARIA
2010 KMC

Cardiac muscle
TONY SCARIA
2010 KMC

Cardiac smooth muscle
• Cardiac smooth muscle fibers branch interdigitate but each is a
complete subunit but each is a complete subunit with a centrally
located nucleus
TONY SCARIA
2010 KMC

Intercalated disc
• Muscle fibres are connected
end to end by gap junction&
fascia adheren
• Gap junctions because of
which cardiac muscle behaves
as a functional syncytium
• Gap junctions Behave as low
resistance bridges for spread
of excitation from one fiber to
another
TONY SCARIA
2010 KMC

Relaxation of muscle
• Sarcoplasmic ca2+ is lowered by
• SR ca2+ pump
• Ca2+ -- 3 Na+ antiport in sarcolemma
TONY SCARIA
2010 KMC

Phospholamban (PLN)
• Regulatory protein in cardiac
myocytes
• In dephosphorylated state binds to
SERCA & inactivates it prolongd
contraction
• Upon sympathetic stimulation
phosphorylation of PLN occurs
dissociates from SRCA  relaxation
occurs TONY SCARIA
2010 KMC

General physiology REVISION NOTES PHYSIOLOGY

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