General Physiology

BODY FLUID COMPARTMENTS

Personal Notes
Total Body Water (TBW) = 60% of the body weight (70 kg healthy adult male)

Total Body Water (TBW) 42L

2/3 rd 1/3 rd
Extracellular Fluid (ECF) 28L Intracellular Fluid (ICF) 14L

3/4 th 1/4 th

Interstitial 11L Plasma 3L

Cellular Component (3% of Body weight) Blood (8% of Body weight = 5L)

Approximately 1L of extracellular fluid belongs to the transcellular fluid

compartment that is enclosed as CSF, synovial fluid, pleural fluid, pericardial
fluid, peritoneal fluid and fluid in various spaces.

MEASUREMENT OF BODY FLUID COMPARTMENTS

Indicator Dilution Method/Steward Hamilton principle/Dye Dilution Method

Steps
| Selection of indicator

™ Initial mass of indicator = I (Units in gram as per given)

Ideal Property:
| Should uniformly disperse in compartment

| Should not leave the compartment

| Remain free and unbound to proteins
| Injected into compartment

Sample collected and the concentration of the indicator is measured =

CV (Volume of Compartment) = I/C
If A (Mass/amount of indicator leaves the compartment, by urinary loss etc)
V = (I-A)/C
INDICATORS
Personal Notes
For the measurement of,

TBW (Total Body Water) Deuterium oxide (D2O), Tritium oxide, Aminopyrine

ECF Non metabolic saccharides like Inulin (Most

common), Mannitol, Sucrose

ICF Indirectly measured as ICF = TBW - ECF

Plasma Volume Albumin radiolabelled by I-131 isotope

Cell volume (Blood) Given by Hematocrit times blood volume – Hct

(Measured by Wintrobe and Westergren method)

RBC volume Cr-51 tagging of RBCs

New-borns are more prone to dehydration:
| Greater metabolic rate

| Inability to communicate thirst

| Higher evaporative loss due to more surface area to volume ratio

Disturbance in Body Fluid Compartment

Isotonic dehydration GI fluid loss, burns, hemorrhage

Hypertonic dehydration Diabetes mellitus, diabetes

insipidus, chronic alcoholism,
Dehydration
administration of lithium salts

Hypotonic dehydration Primary hypoadrenocorticism or

aldosterone insufficiency

Isotonic overhydration Oral/IV isotonic NaCl

Hypertonic overhydration Oral/IV hypertonic NaCl

Overhydration
Hypotonic overhydration SIADH (Natriuretic diuresis:
Euvolumic hyponatremia)

CELL MEMBRANE

Milieu interior: ECF (Internal environment)

Homeostasis: Maintaining the stability of the internal environment

ICF ECF

Na+ Low High

K+ High Low

Ca Low High

2 Physiology
Impermeable anions: Proteins and phosphates (ICF)
Personal Notes
| Excess anions in the ICF
| Excess cations in the ECF: Donnan effect

Endolymph: Actually ECF but contains excess potassium so it resembles ICF.

Sodium
| Concentration gradient: ECF to ICF
| Electrical gradient: ECF to ICF (Considers all the cation)

Potassium
| Concentration gradient: ICF to ECF
| Electrical gradient: ECF to ICF (Considers all the cation)

CELL MEMBRANE

Fluid Mosaic Model

Cell membrane
Membrane proteins (55%) Lipid bilayer (42%) Carbohydrates (3%)

| Schwann cell (76% lipid) and Oligodendrocyte cell membrane has the
highest lipid content of all cell membranes.
| During nitrogen narcosis, the nervous system is the most affected system.
| Highest protein to lipid ratio is found in membranes of inner mitochondrial
membrane and presynaptic membrane- due to receptors for docking of
vesicles.

General Physiology 3
Proteins
| Integral
Personal Notes
| Peripheral proteins
| The serpentine G-Protein Coupled Receptor GPCR- called so because it
traverses the cell membrane 7 times is an example of integral protein.
| GPI-linked proteins that are attached to the cell membrane via GPI anchor.
| Examples are CD59, Decay Accelerating factor.
| Present in the red cell membrane.
| Function: Prevent compliment attack on RBC.
| Defect: Complement induced lysis.
| Hemoglobin is released in urine: Paroxysmal nocturnal haemoglobinuria

MEMBRANE PROTEINS AND JUNCTIONAL COMPLEXES

CELL TO CELL JUNCTIONS

4 Physiology
 Cell Junction Location Function Applied Personal Notes
Desmosomes/ skin, cervix High tensile -
macula strength and
adherens regions of high
wear and tear

Gap Heart and Freely permeable 1. Charcot marie tooth

Junctions/ GI smooth junctions between disease:
Electrical muscle cells adjacent cells
Defective Connexin
synapses (Low resistant
32 (A demyelinating
passages)
disorder that affects gap
Formed by junctions found between
connexons schwann cells)
6 connexins join 2. I
 diopathic atrial
to form connexon fibrillation:
Defective Connexon 40
in atrial myocardial cells

Tight Found in Made up of -

junctions/ lining of GI Claudins,
zonula tract mucosa Occludins and
occludens and Blood- Junctional
Brain Barrier Adhesion
(Endothelial Molecules (JAMs)
cells)
These are
selectively
permeable

TRANSPORT PROTEINS IN THE CELL MEMBRANE

They are of 4 types:

Transport protein Examples

Pores (Passive) Water channels: Aquaporins, perforins

Channels (Simple diffusion) Sodium leaky channels

1. Leaky channels Sodium voltage gated channel
2. Gated channels Nicotinic AChR, GABAA
| Voltage gated Muscarinic receptor, GABAB channel,
| Ligand gated channel/ funny channel in heart
Ionotropic receptor and channel Slow calcium channel
| Cyclic Nucleotide Gated Potassium channel in nerve
Channel/Metabotropic Receptor
Associated Channel Touch receptor
| Time gated channel
| Mechanical gated

General Physiology 5
Special Gating Mechanisms: O2 sensitive K+ channel in pulmonary Personal Notes
vessels - carotid body
Chemical gated channels
ATP sensitive K+ channel in Pancreatic
beta cells, systemic vessels

Carriers (Active) Facilitated diffusion: Uniport

(Example- GLUT)
Secondary active transport:
Symport
Antiport (Example- sodium calcium
exchanger)

Pumps/ATPases (Active) Primary active transport (Na+, K+

pump)

TRANSPORT PROCESS

1. ACROSS THE MEMBRANE (VESICULAR TRANSPORT)

Endocytosis
| Large molecules

| Particles
| Foreign substances
| Phagocytosis (Cell eating), eg: Bacteria enter into neutrophil
| Pinocytosis (Cell drinking), eg: Soluble protein enter the cell

Clathrin: LDL entry

Exocytosis
| Neurotransmitter secretion at the synapse

2. THROUGH THE MEMBRANE

Diffusion: Passive transport/Downhill transport

Two types:

1. Simple Diffusion
| Kinetic energy

Factors
Fick’s law, J=-D.A x Δ C/d
1. Lipid solubility
™ CO2 > O2
2. Number of channels
™ K+ > Na+

6 Physiology
3. Temperature
Personal Notes
™ Directly proportional
4. Surface area available for diffuse
™ Directly proportional
5. Thickness of the membrane
™ Inversely proportional
6. Size/molecular weight/radius
™ Na+ -2.2nm
™ K+ -2.0nm
7. Concentration gradient
™ Na+ -14
™ K+ -145
8. Pressure gradient
™ Electrical gradient

2. Facilitated Diffusion
| Passive (No ATPs)

| Downhill transport
| Carrier

Properties
1. Saturability

tr�ns�or�er�me�ia�ed
diffus�on
ra�e of tr�ns�or�

V ma�

1/�Vma� si�pl�
diffus�on

Km co��en�ra�io� of
tr�ns�or�ed mo�ec�le

General Physiology 7
2. Specificity
Personal Notes
3. Inhibition

GLUT TRANSPORTERS

GLUT 1 Constitutively expressed and ubiquitous

GLUT 2 Pancreatic beta cell

GLUT 3 Neuron

GLUT 4 Insulin dependent, adipose tissue, muscle

GLUT 5 Fructose

ACTIVE TRANSPORT

| Use of ATP
| Uphill transport (Low to high)
| 2 types:

1. ATP used directly:

™ Primary
™ NA+ K+ pump

2. ATP used indirectly:

™ Secondary active transport
™ 2 types
™ Symport or co-transport: SGLT
™ Antiport or countertransport or exchange: NCX 3:1, Band 3

NA+K+ PUMP

| Primary active transport

| All membranes
| Active all the time
| 3 subunits: Alpha, beta and gamma
| Functions:
™ Opposes the equilibrium
™ Cell volume
™ Recharging
™ BMR
™ Electrogenic
™ -4mv to RMP

8 Physiology
 Stimulators Inhibitors Personal Notes
Diuretics | Aldosterone increase Na+ reabsorption

Thyroid | Digitalis

Catecholamine (Muscle) | DNP

Insulin

General Physiology 9
 Muscle (Part-I)
NEUROMUSCULAR JUNCTION (NMJ)
Personal Notes
| It is the junction between the motor neuron and the muscle fiber membrane.

Ach Vesicles
| Membrane bound cell organelles are produced in the nerve cell body.
| Enzymes for the synthesis and destruction of Ach are present in the nerve
terminal.
| Vesicles fuse with the presynaptic membrane and release the Ach into the
gutter.
Note: Mitochondria present at bouton/synaptic bulb.
Ach receptors are nicotinic receptors:
| Nicotinic receptors are present in neuromuscular junction, ganglia, CNS.
| Muscarinic receptors are present in the organs.
| It is also known as ligand gated channel or ionotropic receptors with
channel or non-specific cation channel.
| Nicotinic cation channel that allows both entry of sodium and exit of
potassium from the myocyte (Non-specific).
| RMP of skeletal muscle membrane is -90mV.
| Since, the more RMP drifts away from equilibrium nernst potential of an
ion, the more readily the ion gets transported.
| Hence, at RMP, K+ going out of the cell is low.
END PLATE POTENTIAL (EPP)
Personal Notes
| When an impulse reaches the nerve terminal it releases 60 vesicles.
| Each vesicle contains 10,000 molecules of Ach.
| Muscle membrane is depolarized by 40 mV.
| This local depolarisation is called end plate potential, when it reaches
threshold action potential is developed.

MINIATURE END PLATE POTENTIAL (MEPP)

| Refers to the voltage developed in the motor end plate when no impulse
arrives despite asynchronous discharge/release of Ach.
| It produces potential in microvolts.
| The value of potential developed associated with each vesicle of acetylcholine
is about 0.4 mV- supporting the quantal release of acetylcholine.

APPLIED

Autoimmune Disorders

Lambert-Eaton Myasthenic
Myasthenia Gravis
Syndrome (LEMS)

Autoimmune disorder Autoimmune disorder

Antibodies develop against the VGCC Antibodies develop against AChR

(Voltage Gated Calcium Channel)

Acetylcholine vesicles don’t get Ach do not bind with nicotinic

released due to less calcium entry receptors in the postsynaptic
membrane

Muscle weakness present Muscle weakness present

It gets better after exercise (As Ca2+ After continuous physical activity-
availability increases in the terminal) worsens the condition

Treatment: Pyridostigmine Treatment: Anticholinesterases

(Increases levels of Acetylcholine)
Examples are Neostigmine and
Physostigmine

EXCITATION- CONTRACTION COUPLING

| It is the coupling between the electrical excitation and mechanical process
of contraction.
| Calcium is the coupling agent.
| Occurs in the sarcotubular system of skeletal muscle (Triad-2 T tubules and
1 L-tubule).
| 2 T-tubules per sarcomere in front of the junction of A and I band.

2 Physiology
| Terminal cistern is the storage of calcium.
Personal Notes
| DHPR: Dihydropyridine receptor - voltage sensor.
| RyR: Calcium release channel.

SARCOTUBULAR SYSTEM

APPLIED

Malignant Hyperthermia
| Genetic defect in the gene codes RyR.
| Administration of halothane/ether and succinylcholine there is a massive
release of calcium.
| Increased muscle contraction, shivering happens and increase in
temperature.
| Treatment is administration of uncoupler dantrolene.

Muscle (Part-I) 3
SARCOMERE
Personal Notes
| Basic structural unit of the muscle is the Sarcomere.
| Muscle → Muscle fiber (Lined side by side) → Sarcomere.

| Myofilaments are the contractile proteins of the myofibril.

| They are grouped as two categories: Actin and Myosin.
| There is interdigitation between thin and thick filaments in a sarcomere.
| Each thick filament is surrounded by 6 thin filaments.
| The ratio thin filaments to thick filaments = 2:1
| The length of sarcomere is defined as distance between any two adjacent
Z- lines.
| The Z- lines serve as anchors for thin filaments- made of Actin. Like dense
bodies in smooth muscle.
| Normal resting length of a sarcomere= 2 microns.
| This is denoted by Li/Lrest =2 microns.
| The length of a sarcomere is directly proportional to length of a muscle
fiber and hence length of a muscle applying there is a dynamic change in
muscle and muscle cell is alive.

STARLING’S LAW
| Within physiological limits, greater the initial length of the muscle/muscle
fiber/sarcomere, greater will be the strength of contraction.
| Optimum length of sarcomere for strongest contraction Lopt/Lo
= 2.2 microns.

4 Physiology
| Maximum length of sarcomere to generate any force of contraction, Lmax
= 3.65 microns
Personal Notes
| At and beyond this length, the force of contraction is zero.
| All the fibers contract together and shorten the length of the muscle.

PROTEINS IN SARCOMERE

1. Dystrophin (Coded by the largest gene in the human body)

2. Titin (Largest protein of the human body)

Titin
| The thick filaments might seem like they are floating in the air, but actually
the protein titin.
| Largest protein in the body.
| It plays an important role in linking the thick filaments to the Z line.
| It anchors the central part of thick filaments (M-line) to the Z line.
| Function is alignment of thick filament of sarcomere.
| Associated clinical correlations include: Limb-Girdle Muscular Dystrophy
and Tibial Muscular Dystrophy.

Dystrophin

Laminin

Dystroglycans Sarcoglycans Integrins

Caveolin

Syntrophins nN
OS 1 Sarcospan

Dystrobrevin Dystrophin

Actin

| Largest human gene codes dystrophin in the body.

| Attached on one side to the thin filaments and goes on to sarcolemma
(Analogous to plasma membrane in cell).
| In sarcolemma, it attaches to the beta subunit of dystroglycan, which has
alpha- and beta- subunits respectively.

Muscle (Part-I) 5
| Also associated are four more protein subunits alpha-, beta-, gamma- and
delta- of sarcoglycans.
Personal Notes
| This makes an association with six proteins in the sarcolemma.
| Alpha dystroglycan is linked to extracellular matrix protein laminin.
| Thus, it helps in transmitting the muscle tension to the surface of the body.
| Clinical correlation is Duchenne Muscular Dystrophy.

6 Physiology
 Muscle Part-II
SARCOMERE
Personal Notes
| Sarcomere is the distance between two successive Z-lines.
| Bands: I band (Thin filaments) and A band (Thick and thin filaments)
| One sarcomere contains one A band and two half I band.

| H zone: Consist only of thick filaments.

| M line: Contain protein called myomesin.
| Pseudo H zone: Dark M line and adjoining light areas.
| In the skeletal muscle two T tubules per sarcomere at the junction of
I and A band.
| In cardiac muscle one T tubule per sarcomere in front of the Z line.
During contraction:
Personal Notes
1. H zone disappears

2. I band shortens

3. A band remains unchanged

4. M line becomes prominent: CM band (Contraction M band)

MOLECULAR BASIS OF SKELETAL MUSCLE CONTRACTION

1. Thick Filaments
| Each thick filament is made up of 500- 1000 myosin molecules.
| 2 heavy chains and 4 light chains.

The myosin head contains two binding sites and has ATPase activity:
| One for actin
| One for ATP

2. Thin Filaments
| Composed of Actin : Troponin : Tropomyosin (3 proteins) in the ratio 7 : 1 : 1.
| Actin has active sites which are covered by troponin: Tropomyosin complex.
| Troponin C is present in thin filament and has affinity for calcium.
| Troponin T has affinity for tropomyosin.
| Troponin I has affinity for actin.
| The calcium released due to Excitation contraction coupling is released
from the Sarcoplasmic reticulum situated near the T-tubules.

2 Physiology
CROSS BRIDGE CYCLE
Personal Notes

RIGOR MORTIS

| After death, there is exhaustion of ATP.

| The myosin head can’t use ATP by virtue of its ATPase activity to break the
formed cross-bridge.
| Hence, myosin head remains attached to the active site on actin.
| This causes muscle stiffness after death referred to as ‘Rigor Mortis’.

Contraction Includes
1. Tension developed (This is proportional to the number of active cross-
bridges in muscle fiber at a time)

2. Shortening of length of muscle (The velocity of shortening of muscle is

directly proportional to speed of cross bridge-cycling)

TYPES OF CONTRACTION

Isometric Contraction Isotonic Contraction

Length of the muscle remains the Shortening of the muscle fiber

same happens

Tension increases Tension developed remains the same

Muscle Part-II 3
No work done Work done Personal Notes
Less releases of heat More heat loss

Example: Holding a weight in the Example: after you hold the load
upper limb in anatomical position, for some time, the tension doesn’t
the biceps-length remains same but change in biceps anymore, but there
‘tension’ in biceps increases is flexion at elbow joint which causes
shortening of the muscle fiber

SMOOTH MUSCLE

| Two types:

1. Single unit: All muscles have single innervation. Example: GI smooth

muscle.

2. Multi unit: Different innervation. Example: Iris, erector pili, blood

vessels.
| Electrical activity:

1. RMP is oscillating: -35 to -45 mV

| No Z lines, instead it contains dense bodies.

| On either side thin filament arises.
| Thin : thick filament: 15 : 1
| No troponin C
| It contains calmodulin, a calcium binding protein.
| MLCK: Myosin Light Chain Kinase
| Thick filament regulated contraction

4 Physiology
 Personal Notes

| Latch bridge mechanism: Lesser ATP consumption, lesser shortening and

sustained tension.

Muscle Part-II 5
 Membrane Potential
MEMBRANE POTENTIAL
Personal Notes
| Every cell in the body excess negative charges lined up on the inner surface
of the membrane.
| This creates the membrane potential.

Cell Types RMP

RBC, epithelial cells -8mV to -20mV

Smooth muscle cell -35mV to -45mV

SA nodal cell -55mV to -65mV

Nerve -70mV

Skeletal muscle, Purkinje fiber -90mV

| For all the cells mentioned above ECF potential is taken to be 0 mV.
| Then the transmembrane electrical gradient of skeletal muscle is 90mV.
| Exception is hair cells in cochlea inside is -70mV and the outside is not
0mV.

| Outside is made up of endolymph which consist of excess potassium ions.

| Endocochlear or endolymphatic potential is +80mV.
| So, the transmembrane electrical gradient across the haircell is 150mV.
| This is the most excitable cell in the body since it has the highest
transmembrane electrical gradient.
Resting Membrane Potential (RMP)
| Nerve = -70 mV
Personal Notes
| Skeletal muscle = -90 mV

NERNST EQUATION

EMF (mV) = ± 61 x log [C1 / C2]

EMF for Na+ = ± 61 x log (141/14)
= + 61 x 1 = + 61 mV
K+ = -96 mV
| RMP is -90 mV.

| K+ is the greatest contributor to the development of RMP.

| Since, the membrane is more permeable to K+ (50 – 100x).
| Most diffusible Ion is K+.
EP of Cl- = -89 mV (When RMP is established, Cl- hardly moves)

HODGKIN – HUXLEY EQUATION

| Also known as Goldmann’s constant Field Equation.

Expanded Nernst Equation

= -86 mV

| Na+ - K+ pump contributes -4 mV in RMP.

| RMP of nerve is -70mV.

In the Nerve Membrane

Ions Equilibrium Potential

Na+ +60mV

K+ -90mV

Cl- -70mV
| The RMP of nerve is close to the equilibrium potential of K+.

ACTION POTENTIAL (AP)

Properties of Stimulus
1. Intensity: Rapidly rising stimulus (Slowly rising intensity ⇒ membrane
accommodation) Na+ channel opens slowly.
2. Duration: The best stimulus to excite a nerve/muscle are:
(i) Rectangular pulse
(ii) Exponential pulse

2 Physiology
 Personal Notes

1. Rheobase:
™ Minimum strength of stimulus
™ Excited tissue
2. Chronaxie:
™ Time taken by tissue to excite.
™ Stimulus = 2 x Rheobase
™ Chronaxie- measure of excitability.
™ Myelinated nerve (Shortest Chronaxie)
↓ >
Unmyelinated nerve
↓ >
Skeletal muscle
↓ >
Cardiac muscle
↓ >
Smooth muscle (Longest)

IMPULSE PROPAGATION
| 2 types:
1. Electrotonic conduction
2. AP generation
1. Electrotonic conduction:
™ Direct spread of charges
™ Decremental conduction
™ 10mm length of the nerve

Membrane Potential 3
 ™ This happens at:
Personal Notes
1. Dendrite to axon hillock
2. Node to node conduction
3. Retina
2. Action potential:
™ Recorded by Cathode Ray Oscilloscope (CRO)

+4�

+2�
Ov�r sh�ot
0
Am�li�ud� (m�Vo�t)

-2�

-4�
Af�er de�ol�ri�at�on
-6�

-8� Fi�in� le�el

La�en� pe�io�
0
St�mu�us ar�if�ct Af�er hy�er�ol�ri�at�on

0 0.� 0.� 0.� 0.�

Ti�e (m�se�)

Phases
1. Depolarisation:
™ Due to Na+ influx
™ RMP to threshold
™ Positive feedback cycle of sodium channels
Hodgkins cycle:
In�ct�va�io� of Na+ ch�nn�ls
te�mi�at� th� pr�ce�s

Th�es�ol� de�ol�ri�at�on�
op�ni�g Na+ ch�nn�ls

Up�tr�ke
(d�po�ar�za�io�)

Op�ni�g of a se� of
Na+ ch�nn�ls ac�iv�te
ot�er Na+ ch�nn�ls
Ra�id ri�e in
me�br�ne po�en�ia�

Fu�th�r op�ni�g of
Na+ ch�nn�ls

4 Physiology
 ™ Most diffusible ion - K+.
Personal Notes
™ Most diffusible ion for an excitable cell - K+.
™ Most diffusible ion for an exciting cell - Na+.

2. Repolarisation:
™ K+ exit
™ At +35 mV K+ exit is very rapid

3. After depolarization:
™ Exit K+ slows down
™ Ionic basis

Ionic Basis
ENa
50

Open channels per um2 of membrane

Action potential
Membrane potential (mV)

Na+ conductance (Na+ channels)

40

K+ conductance (K+ channels)

20
-50

EK

Membrane Potential 5
 Nerve
NERVE
Personal Notes
| Neuron
| Nerve fibers
| Wallerian Degeneration

NEURON

| Action potential first occurs at the axon hillock/initial segment.

| No new neuron is formed after birth except the olfactory neuron.

Types of Neurons

Multipolar neuron Cerebral cortex and cerebellum

Bipolar neuron Olfactory neuron, retina

Pseudounipolar neuron Cell in dorsal root ganglia

Anaxonic neuron Amacrine cells in the retina, Postganglionic

parasympathetic

CLASSIFICATION OF NERVE FIBERS

Erlanger and Gasser Classification

Based on diameters: In descending order
Aα Proprioception, alpha-motor neuron Personal Notes
Aβ Touch, pressure
Aγ Gamma motor neuron
Aδ Fast Pain, Temperature
B fibers Preganglionic autonomic
C fibers Slow pain, postganglionic sympathetic

Numeric Classification

Ia Proprioception
Ib GTO
II Proprioception
III Touch & pressure
IV Pain & Temperature
| A & B are myelinated nerve fibers.
| C is non-myelinated nerve fibers.
| CNS: Myelination by Oligodendrocyte (1 : 20)
| Periphery: Myelination by Schwann cell (20 : 1)

MYELINATED NERVE FIBERS

| Conduction velocity is directly proportional to 6 times the diameter.

| A α = 20 μm diameter, so velocity = 120 m/sec.

NON-MYELINATED NERVE FIBERS

| Velocity is directly proportional square root of the diameter.

Susceptibility
| Fibers are most susceptible to pressure.
| B fibers are most susceptible to hypoxia.
| C fibers are most susceptible to Local anaesthetics.

INJURIES TO THE NERVE FIBERS

Sunderland’s Classification

1° Mild pressure/hypoxia
2° Severe sustained pressure
3° Axonal transection

2 Physiology
4° Fascicle disrupted Personal Notes
5° Nerve trunk transection

Sedan’s Classification

Neuropraxia 1° & 2°
Axonotmesis 3°
Neurotmesis 4° & 5°

WALLERIAN DEGENERATION

Nerve 3
24-48 hrs Chromatolysis Personal Notes
Up to 3 days Distal stump functional
6th day Axis cylinder breaks, Axonal degeneration
10th day Myelin degeneration
15th day Sprouting from the proximal end
Schwann cell proliferation from the distal end
80th day Repair

4 Physiology
 Blood
| Blood is a liquid connective tissue, It is a part of ECF.
| pH of blood: 7.4, pH of ICF: 7.2
Personal Notes
| Specific gravity of whole blood: 1.060
| Specific gravity of cells: 1.090
| Specific gravity of plasma: 1.030
| In hemoconcentration specific gravity of blood increases.
| Relative viscosity of Water: Plasma: Whole blood is 1:3:5
| Blood Volume: 8% of body weight (5% plasma (55%) & 3% cells (45%)).

PLASMA

Plasma Proteins

Normal value: 7 - 8 gm%

Plasma Proteins Normal Value Functions

Albumin 4 - 4.5 gm% Exerts plasma colloid osmotic pressure:

28-32 mmHg
Transport protein: bilirubin, hormones

Globulin 2 - 2.5 gm% 3 types

1. Alpha globulin Transport globulins, synthesized by liver

2. Beta globulin Transport globulins, synthesized by liver

Ceruloplasmin: Copper
Transferrin: Iron
Haptoglobin: Hemoglobin

3. Gamma globulin Immunoglobulins, synthesized by B cells

Fibrinogen 0.2 - 04 gm% Involved in clotting mechanism

Albumin: Globulin ratio = 2:1 (Reversed in hepatocellular disease)

CELLS
Personal Notes
Red Blood Cell (RBC)
| 8µm diameter
| Biconcave shaped: Surface area to volume ratio is high - gas transfer is
easy.
| Non- motile, non- nucleated cells.
| Normal range:
™ Female: 4.5 - 5.5 million cells/cu.mm
™ Males: 5-6 million cells/cu.mm
| Life span: 120 days
| t1/2: 60 days
| Stored blood t1/2: - 28- 32 days

Erythropoiesis

Mesoblastic stage | 1-3 months

(Hematopoiesis)

Hepatic stage | 3 to 6 months

Myeloid stage | >6 months: 18 years - bone marrow of all bones

| >18 years: Flat bones will have red bone marrow
(Sternum, vertebral bodies, anterior superior iliac
spine, proximal ends of long bones)

Stages

2 Physiology
Salient Points
Personal Notes
| Hemoglobin synthesis begins in intermediate normoblast
| In early stages cytoplasm is basophilic and from intermediate normoblast
it is polychromatophilic.
| Punctate basophilia: Seen in lead poisoning, arrests the RBC maturation.
| Cell division is present till late normoblast (Nucleus +).
| Reticulocyte to erythrocyte conversion takes 24 hours.
| Normal reticulocyte count: 0.2 - 2%.
| Physiological increase is seen in newborns and infants.
| It is increased in hypoxia (Reticulocyte count: 5-10%).
| Entire process of erythropoiesis takes place in 7 days.

Factors Influencing Erythropoiesis

| Hypoxia:
™ Stimulates the secretion of Erythropoietin.
™ Synthesized by type 1 cortical interstitial cells.
| Testosterone, growth hormone and thyroid hormone stimulates
erythropoiesis
| Dietary factors:

1. Iron: Heme

2. Proteins: Globin

3. Vitamin B12 and folic acid: 5, 10 Methyl tetrahydrofolate for DNA

synthesis in RBC precursors.

Fate of RBCs
| Life span: 120 days
| RBC membrane becomes rigid and becomes ghost cells.
| Ghost cells are taken by splenic macrophages. So, the spleen is a graveyard
for RBCs.
| Heme is converted to bilirubin.

Blood 3
 Personal Notes

JAUNDICE
| Yellowish discoloration skin and mucous membrane.
| Increase in bilirubin level >3 mg/dl.
| 3 types:
1. Prehepatic/hemolytic: Hemolysis
2. Hepatic: Hepatitis
3. Post hepatic/Cholestatic: Obstructive jaundice

ANEMIA

Classification of Anemia

Morphological Classification Etiological Classification

Due to impaired RBC

Microcytic Normocytic Macrocytic production

Iron Deficiency

B-12 Folate Deficiency

Vitamin C Deficiency

Blood Loss

4 Physiology
Morphological Classification of Anemia
Personal Notes
Ir�n defici�nc� an�mi�
Mi�ro�yt�c An�mi� Th�la�se�ia
(H�po�hr�mi�) Si�kl� ce�l an�mi�

Ac�te bl�od lo�s

No�mo�yt�c An�mi� Ch�on�c di�ea��
An�mi�
(N�rm�ch�om�c) Ap�as�ic an�mi�
He�ol�ti� an�mi�

Ma�ro�yt�c An�mi�
Vi�am�n B1� defici�nc�
(M�ga�ob�as�ic
Fo�at� defici�nc�
an�mi�)

Clinical Classification of Anemia

| Based on hemoglobin level (<10 gm%) classified into 3 grades:

Grade Hb Concentration Treatment

Mild 8 - 10 gm% Oral Iron supplements

Moderate 6 - 8 gm% Injectable Iron preparations

Severe <5 gm% Blood transfusion

| 1 pint of blood will increase the hemoglobin by 2 gm%.

Blood Indices

Normal
Parameter Definition Units Formula
value
Packed Cell Percentage Percentage RBC volume
Volume (PCV) of RBCs in PCV = x 100 38-45
whole blood Blood volume

Mean Average Femtoliters

Corpuscular volume of (FL) Hematocrit (%)
MCV = × 10 78-94
Volume the RBC RBC (x1012/L)
(MCV)
Mean Average Picograms
Corpuscular weight of (PG) Hb (gm/dL)
MCH = × 10 28-32
Hemoglobin hemoglobin RBC (x1012/L)
(MCH) the RBC
Mean Average gm/dL
Corpuscular concent-
Hemoglobin ration of Hb (g/dL)
MCHC= ×100 32-38
Concentration hemoglobin Hematocrit (%)
(MCHC) in the RBC
volume

Blood 5
Color Index Average Personal Notes
content of Hb (%)
(CI) - CI = 0.8-1
hemoglobin RBC (%)
in one RBC
MCH - normal, MCHC - reduced : Megaloblastic anemia

WBCS
| Normal count: 4000 to 11000 cells/cu.mm
| Two types:
1. Granulocytes
2. Agranulocytes

Granulocytes
1. Neutrophils
™ 50-70%
™ First line defense
™ Multi lobed nucleus
™ Life span 4-8 hrs in circulation and 4-5 days in the tissue.
™ Arneth count (Count of neutrophils based on their nuclear lobes)

5 stages:
™ Stage 1: 5%

™ Stage 2: 15%
™ Stage 3: 35-45%
™ Stage 4: 10-15%
™ Stage 5: 5%

6 Physiology
 Shift to left: Infection
Personal Notes
Shift to right: Bone marrow depression
™ Schilling’s index: For neutrophil count and contains 4 stages

2. Eosinophils:
™ 1-4%
™ Lifespan similar to neutrophil also can stay in the tissue longer.
™ Bilobed nucleus and red coloured granules.
™ Increased in parasitic infestation and allergic condition.

3. Basophils:
™ 0-1%
™ Seen in allergic conditions
™ In the tissues they can get converted into the mast cells.

Agranulocytes
1. Lymphocytes:
™ 20-30%
™ Third line defense
™ Increased in chronic infection.
™ 2 types:

1. Small lymphocyte: Mature lymphocyte.

2. Large lymphocyte: Lymphoblast divides into 2 large lymphocytes.

™ Lifespan - 300 days

2. Monocytes:
™ 2-8%
™ Converted into macrophages when they enter into tissues.
™ Longest span among all the blood cells.
™ Second line defense
™ Largest wbc
™ Increased in conditions like malaria.

PLATELETS

| It is formed from megakaryocytes in the bone marrow.

| One megakaryocyte forms 1000 - 4000 platelets.
| 2- 4 micrometers in diameter.
| Non-motile, non-nucleated

Blood 7
 Personal Notes

| Life span: 9-12 days

| t1/2: 4 days
| t1/2 of stored platelet: Less than one day
| Platelet plug formation: 1 - 3 minutes (Bleeding time)
| Normal count: 1.5- 3 lakh cells/cu. mm
| Less than 40000 cells/cu.mm: Critical platelet count
| Platelet count falls below 40000 cells/cu.mm of blood, clotting of bleeding
is very difficult and bleeding time will be prolonged. (Thrombocytopenia or
thrombocytopenic purpura)

CLOTTING MECHANISM

Two Pathways
1. Intrinsic pathway
2. Extrinsic pathway

Clotting Factors

Factor I Fibrinogen

Factor II Prothrombin

Factor III Tissue thromboplastin

Factor IV Calcium

Factor V Labile factor

Factor VII Stable factor

Factor VIII Antihemophilic factor

8 Physiology
Factor IX Christmas factor Personal Notes
Factor X Stuart prower factor

Factor XI Plasma thromboplastin antecedent

Factor XII Hageman

Factor XIII High molecular weight kininogen

Factor XIV Prekallikrein

| Normal clotting time: 4-9 minutes

| All the steps in the clotting mechanism in both pathways require calcium
except 1st 2 steps in the intrinsic pathway.
| Prothrombin time: Extrinsic pathway, Normal value: 9-14 seconds, done on
heparinized patient.
| Activated partial thromboplastin time: Intrinsic pathway, done to diagnose
clotting disorder like hemophilia.

BLOOD GROUP
| Antigens: RBC membrane
| Antibodies: Plasma
| ABO blood group

Blood Group Antigen Antibody

A A Beta

B B Alpha

AB A, B -

O - Alpha, beta

Blood 9
| Universal donor: O negative
Personal Notes
| Universal recipient: AB positive
| Bombay blood group : O’h’ : Absence of H antigen (Recessive h gene),
presence of three antibodies : Anti A, anti B, anti H
| Anti A and anti B called as natural agglutinins : IgM type
| Anti Rh antibody is an induced antibody : IgG type : Cross the placenta
| Erythroblastosis fetalis: Hemolytic disease of newborn

10 Physiology
 CVS Part-I
(Properties of Cardiac Tissue)
PROPERTIES OF CARDIAC TISSUE
Personal Notes
| Excitability, Contractility, Autorhythmicity, Long refractory period.
| Syncytium: The heart operates as two functional syncytia (Atria and
ventricles) due to the presence of gap junctions that allow the free passage
of ions between cells, ensuring coordinated contraction.
| Intercalated discs: Electro-mechanically tethering
| Excitation contraction coupling:
™ T-tubule: There is one T-tubule per sarcomere, located in front of the
Z-line.

Mechanism

KEY POINTS

| ECF Calcium affects the cardiac contradictorily

| Hypocalcemia: Cardiac contractility is affected, while skeletal muscle
contractility remains unaffected.
| Calcium Channel Blockers (CCBs): Antihypertensive drugs that reduce
calcium influx into cardiac and smooth muscle cells.
| Dihydropyridine Receptor Blocking Drugs (e.g., Nifedipine): These CCBs
affect cardiac and smooth muscle contractility but do not influence skeletal
Personal Notes
muscle.

CC�s

Bl�ck L ty�e Ca++ ch�nn�ls

Ca cu�re�t an� Ca en�ry in�o

++ ++

ca�di�c an� va�cu�ar sm�ot� mu�cl�s

He�rt ra�e, ca�di�c co�tr�ct�li�y

Co�du�ti�n ve�oc�ty
Va�cu�ar sm�ot� mu�cl� re�ax�ti�n

2 Physiology
 CVS Part-II
(Properties of Cardiac Tissue)
CONDUCTING SYSTEM OF HEART
Personal Notes
| SA Node
| AV Node
| Bundle of His
| Right & left branches
| Purkinje fibers

1. SA Node
| Superolateral wall of right atrium.

2. Internodal Pathways
| Connecting SA node & AV node.
| Anterior Bachmann’s bundle branch to the left atrium.
| Middle Wenckebach’s bundle.
| Posterior Thorel’s bundle.

3. AV Node
| Situated in the right atrium.
| Gateway to ventricles
| Relatively has less number of gap junctions and small diameter of cells.

4. Bundle of His
| Very short
| Bundle gives off a left branch and continues as a right branch.
5. Purkinje Fibers
Personal Notes
| Take impulse from apex to base.
| Purkinje fibers near the apex are called gate cells.
| At the same time from endocardium to epicardium.

Bundle of Kent
| An abnormal branch connecting the SA node directly to the bundle of His
without the AV node.
| Because of this there will be the presence of a bundle of Kent causing a
syndrome called Wolff-Parkinson White Syndrome.
| In ECG, it appears as a delta wave without a PR interval.

SPREAD OF IMPULSE

Depolarization
| Apex to base
| Endocardium to epicardium
| Last to depolarize:
™ Epicardium of base of LV.
™ Pulmonary conus
™ Upper most part of the inter ventricular septum.

Repolarization
| Last to repolarize: Apical endocardium

2 Physiology
ACTION POTENTIALS IN HEART
Personal Notes
Slow Response Type Fast Response Type

| SA node | Purkinje fiber

| AV node | Ventricular fiber

| Less negative | More negative

| -55 to -65 mV | -90mv

BASIC PATHOPHYSIOLOGY FOR ARRHYTHMIAS

| Enhanced abnormal automaticity

| EADs/DADs Triggered activity: Extrasystoles
| Reentry/circus movement: Dilatation of chamber

Rate of Depolarization
Impulse conduction speed:

Part in the Heart Speed m/sec

SA node 0.05-0.1

AV node 0.05-0.1

Bundle of His 1

Purkinje fiber 1.5-4 m/sec

| Fastest conduction of the heart is purkinje fibers.
| Slow conduction of the heart is an AV node.

CVS Part-II (Properties of Cardiac Tissue) 3

AV node:
Personal Notes
| Least diameter
| Least no of gap junctions

Rate of Repolarization
Intrinsic (Natural) rhythmicity:

Part Rhythmicity

| SA node | 80-100/min

| AV node | 60/min

| Purkinje fiber | 15-40/min

| Fastest repolarisation part of heart is SA node

IONIC BASIS FOR AP

0
Me�br�ne po�en�ia� (m�)

0 3

I ca�
IK

Th�es�ol�
-4�
I ca� �
�ia 4
Ih en
p o�
r�
-6� Ik P

0 15� 30�
Time (ms)

1. Repolarisation
| K+ exit

2. K+ Exit Stops
| K+ starts accumulating inside membrane

3. Na+ Funny Current

| HCN

4. Reaching of Threshold
| Ca2+(T)

4 Physiology
5. Ca2+(L)
Personal Notes

Phase 0 = fast Na+ channels

Phase 1 = K+ exit
Phase 2 = Plateau (Slow Ca++ channels)
Phase 3 = K+ exit
Phase 4 = RMP

Plateau
| Long AP duration
| Long recovery
| Long refractory period
| No tetanus
| No fatigue

CVS Part-II (Properties of Cardiac Tissue) 5

 CVS Part-III
(Cardiac Output)
| Cardiac Output (CO) is the amount of blood pumped out by each ventricle
per minute. Personal Notes
| Cardiac output = Stroke volume x Heart rate

= (70 – 90 ml) x 72/minute

= 5 L/min
| Cardiac index = Cardiac output/BSA

= 5 L/min/1.7 m2
= 3 L/min/m2

FACTORS DETERMINING CO

STROKE VOLUME (SV)

| Amount of blood pumped by the heart in one systole/one contraction.

| SV ∝ strength of contraction.
| Determined by:

1. Intrinsic regulation (Heterometric)

2. Extrinsic regulation (Homeometric)

Intrinsic Regulation
| By Frank Starling law,
| SV ∝ EDV ∝ Venous return (Preload)
| SV ∝ 1/ Afterload (5-7 times higher for LV)
| Work output of LV is 5 - 7 times higher than RV

Application of Frank Starling Law

| ESV remains constant

Condition 1 (EDV Normal) Condition 2 (EDV Increased)

EDV - 130 mL EDV - 150 mL

EF - 80 mL EF - 100 mL

ESV - 50 mL ESV - 50 mL
| Heart pumps out all the extra amount of venous return.
Extrinsic Regulation
Personal Notes
| EDV and EDL will be the same.
| ESV will decrease.

EDV - 130 mL

EF - 100 mL

ESV - 30 mL (Decreases)

| Myocardial contractility or Positive inotropy.

| Adrenergic drugs
| Catecholamines
| Increased sympathetic discharge
| Digitalis

HEART RATE

| CO = SV x HR
| ↑ HR → ↓ cardiac cycle duration

Diastole suffers more

Ventricular filling suffers

↓ stroke volume → This should have happened,

| However, ↑ HR → ↑ SV (Upto a certain limit)
| This is explained by:

1. ↑ HR (72 → 130 bpm)

↑ HR → ↑ SV (Staircase effect)

2 Physiology
Staircase Effect
Personal Notes
St�ir�as�
Fo�ce of co�tr�ct�on ph�no�en�n

In�re�se in he�rt ra�e

| Strength of contraction ∝ amount of sarcoplasmic calcium,

2. 130 → 160 bpm

| ↑ HR → SV (Constant)

↓
↑ CO
| ↓ diastole duration

↓
Diastasis disappears from diastole
↓
Filling remains unaffected
↓
SV → same

CVS Part-III (Cardiac Output) 3

3. At 160 bpm
Personal Notes
| Filling affected (Filling ↓)

↓
↓SV
| 160 → 180 bpm

↑ HR but ↓ SV
CO remains constant

4. >180 bpm
↓
CO drastically reduces
| ↓↓↓↓ SV → CO very low

KARVONEN FORMULA

HRmax = (220 - age)

SV
Ejection fraction = X 100
EDV
70 ml
= X 100
130 ml
= 60-65%

LEFT VENTRICULAR SHORTENING FACTOR (LVSF)

(LVEDL - LVESL)
X 100
LVEDL
Normal value = 40%

CHRONOTROPIC EFFECT

Effect on heart rate:

| Sympathetic stimulation → +ve effect
| Vagal stimulation → -ve effect

Vasovagal syncope: Sudden inhibition of sympathetic and firing of vagal tone

results in fainting.

BAINBRIDGE REFLEX

On giving I.V saline to patient

↑ Venous return to RA
↓
Stretching of RA

4 Physiology
 ↓
Personal Notes
SA node stimulated
↓
HR ↑
↓
CO ↑

DROMOTROPIC EFFECT

| Impulse conduction speed

| Sympathetic stimulation → +ve
| Vagal stimulation → -ve

INOTROPIC EFFECT

| Contractility
| Sympathetic stimulation → +ve
| Vagal stimulation → -ve

BATHMOTROPIC EFFECT

| Effect of general excitability on heart.

| Sympathetic stimulation → +ve
| Vagal stimulation → -ve

LUSITROPIC EFFECT

| Reliability and diastolic function.

| Related to sympathetic discharge.

SYMPATHETIC STIMULATION (CATECHOLAMINES)

| Effect on heart
| Generally if HR ↑, stroke volume ↓ as duration of both systole and diastole
decreased
| Sympathetic stimulation → ↑ Rate of cross bridge cycling development

↓
↑ Tension is generated in small period of time
↓
Leads to increased stroke volume in shorter systole
| On sympathetic stimulation, ↓ Diastole duration, but ↑ ventricular filling.
| Due to +ve lusitropic effect.
| Catecholamines block the action of phospholamban through phosphorylation.

CVS Part-III (Cardiac Output) 5

| Phospholamban inactivities SERCA required for ca2+ withdrawal from
sarcoplasm.
Personal Notes
Phospholamban inhibition leads to increased activity of SERCA
↓
↑ Cardiac muscle relaxation in diastole
↓
↑ Ventricular filling

PHYSIOLOGICAL INFLUENCES ON CARDIAC OUTPUT

↑ CO ↓ CO

| Exercise | Sleep
| Anxiety | Posture (Standing)
| Emotions, Anger
| Pregnancy
| After eating

PATHOLOGIC INFLUENCES

↑ CO ↓ CO
| Anemia | Hypothyroidism
| Hyperthyroidism (Due to ↑ | Congestive Heart failure (Pump
BMR) failure)

METHODS OF MEASUREMENT OF CARDIAC OUTPUT

1. Fick’s Method
O2 consumption (ml/min)
CO =
Arteriovenous O2 difference
| AV O2 difference = Arterial O2 concentration - Venous O2 concentration
| Arterial O2 concentration → sample from any peripheral art
| Venous O2 concentration → Only from pulmonary artery (Mixed venous
blood)

2. Indicator Dilution Method

Indicator: Stewart-Hamilton dye
Known amount of dye injected into a vein
↓
Heart
Stroke volume↓

6 Physiology
 ↓
Personal Notes
Dilutes the dye↓
↓
Ejects out the dye into systemic circulation
↓
5-6 samples collected from an arterial blood
↓
Mean arterial concentration of dye calculated
| Based on the dilution of dye, stroke volume is determined.

1
Stroke volume ∝
Mean Arterial Concentration of dye (MAC)
Initial volume of dye injected
CO = x 60
MAC of dye x t
T = time at which dye first in arterial blood
| If dye leaks out from capillaries, No effect in measurement of CO.
| If dye leaks out from pulmonary capillaries, then Co is enormously high.
| If dye is sticky, then MAC is less, and CO is high.
| This method not used in Conditions like:
1. Septal defects
2. Regurgitant valves

CVS Part-III (Cardiac Output) 7

 Cardiac Cycle Part-I
DEFINITION
| The changes that occur in the heart during one heartbeat is called cardiac
Personal Notes
cycle.
| Duration: 0.8 seconds
60
| Duration =
Heart Rate
| Duration is inversely proportional to the heart rate.

EVENTS
| Systole: Contraction
| Diastole: Relaxation
| Valves operate on the basis of pressure gradients in the chambers and the
vessels.

Atrial Events (0.8 sec)

Systole (0.1 sec) Diastole (0.7 sec)

Ventricular Events (0.8 sec)

Systole (0.3 sec) Diastole (0.5 sec)

 Personal Notes

2 Physiology
 Personal Notes

Heart
Phases Duration Events Valves
Sounds

Atrial systole 0.1 sec Myotonic contraction - Fourth

heart
2 parts:
sound
| Dynamic
contraction
(0.05 sec)
| Adynamic
contraction
(0.05 sec)

Atrial diastole 0.7 sec 7 parts - -

Ventricular 0.3 sec 3 parts - -

systole | Auxotonic
contraction (LV
1. I
 sovolumetric ventricular systolic AV valve First
ventricular ejection) closes heart
contraction sound
| It starts at end
2. R
 apid ejection of atrial systole Semilunar -
because of AV valve
nodal delay opens

3. R
 educed - -
ejection

Cardiac Cycle Part-I 3

Ventricular 0.5 sec 5 parts - - Personal Notes
diastole

1. Protodiastole Semilunar Second

valve heart
closes sound

2. Isometric - -
relaxation

3. Rapid filling Mitral Third

valve heart
opens sound

4. S
 low filling/ - -
diastasis

5. Atrial systole/ - Fourth

last rapid heart
filling sound

4 Physiology
 Cardiac Cycle Part-II
1. Arterial pulse
2. Atrial pressure changes
Personal Notes
3. Left ventricular pressure volume loops

ARTERIAL PULSE
| Dudgeon’s sphygmograph: Instrument used to record arterial pulse
| Recorded from radial pulse.
| Pulse wave pattern:

130
Bp(mm Hg)

90

50
Aorta Carotid Brachial artery Radial artery

Central Artery (Carotid) Peripheral Artery (Radial)

Upstroke rises to a rounded dome Upstroke is steeper

Ascending limb has an anacrotic Anacrotic notch in the ascending limb

notch disappears

Descending limb has incisura Incisura in descending limb is replaced

followed by dicrotic notch by dicrotic notch followed by dicrotic
wave

Ti�al wa�e

Di�ro�ic no�ch

An�cr�ti�
no�ch

Pe�cu�si�n wa�e

Sy�to�e Di�st�le
Percussion wave (P wave) True systolic peak Personal Notes
Tidal wave (T wave) Oscillation created by meeting of the ongoing
pulse and the reflected pulse from the periphery

Dicrotic notch Due to abrupt closure of aortic valve

Dicrotic wave It is the reflected wave from the peripheral

vasculature

ATRIAL PRESSURE CHANGES

| Right atrial pressure changes are recorded as JVP.

| Left atrial pressure changes are recorded as PCWP.

JUGULAR VENOUS PULSE (JVP)

| Recorded from the right internal jugular vein.

| Normal value is 0-5 cm H2O. (±5 for changes during respiration, inspiration
atrial pressure fall and expiration it rises)
| Waves:

Ti�e (s�co�d)
0 0.� 0.� 0.� 0.�
In�ra�at�ia� pr�ss�re

10 a c a 10
(m� Hg�

v
0 x 0
y
x5

At�ia� sy�to�e At�ia� sy�to�e

Is�me�ri� co�tr�ct�on Sl�w fill�ng
Ej�ct�on pe�io� Ra�id fill�ng

Is�me�ri� re�ax�ti�n

Pr�to�ia�to�e

a wave Atrial contraction

c wave Isovolumetric contraction of RV, bulging of tricuspid valve

into RA

x descent RV ejection

v wave Venous blood accumulates in the RA because of isovolumetric

relaxation of RV (Tricuspid valve not yet opened)

y descent Ventricular filling

2 Physiology
Large ‘a’ wave Tricuspid stenosis Personal Notes
Cannon ‘a’ wave Atrioventricular (AV) dissociation

Abnormal y descent Constrictive pericarditis, cardiac tamponade

PULMONARY CAPILLARY WEDGE PRESSURE (PCWP)

| 5 mmHg
| 5 - 8 cm H2O
| Reflects the left atrial pressure.
| Larger v wave : In the left atrium (LA receives 1 to 2% extra blood volume
compared to RA, it is the blood bronchial venous blood)

LEFT VENTRICULAR PRESSURE VOLUME CHANGES (LV PV LOOPS)

Left ventricular
pressure (mm Hg)
140

120

100
D
80
C
60 Stroke volume

40 End-systolic End-diastolic
volume volume
20
A B
0
50 70 120
Left ventricular volume (ml)

PHASES

| I: Ventricular filling
| II: Isovolumetric contraction
| III: Ventricular ejection
| IV: Isovolumetric relaxation

Cardiac Cycle Part-II 3

End diastolic volume (Preload) 130 ml Personal Notes
End systolic volume 50 ml
Stroke volume EDV - ESV
130-50
80 ml
| Width of the loop indicates stroke volume.
| Height Of the loop indicates after load.

VALVULAR EVENTS

| At Point A : Mitral valve opens

| At point B : Mitral valve closes
| At point C : Aortic valve opens
| At point D : Aortic valve closes
| Point B corresponds with arterial diastolic pressure.
| Point C corresponds with arterial systolic pressure.

4 Physiology
 Blood Pressure Part-I
DETERMINANTS OF THE ARTERIAL BLOOD PRESSURE
Personal Notes
Ohm’s Law
Q = ΔP/R
Q = Flow (Cardiac output)
P = Pressure (Blood pressure)
R = Resistance (Total peripheral resistance)
On rearranging,
CO = BP/Total Peripheral resistance
BP = CO X TPR
TPR = BP/CO
Note: 1 PRU = 1 mmHg/1 mL/sec

TYPES OF BLOOD PRESSURE

| Systolic Blood Pressure (SBP): The maximum pressure exerted during systole.
(Force of contraction)
| Diastolic Blood Pressure (DBP): The minimum pressure exerted during
diastole. (Peripheral resistance)
| Skeletal muscle resistance contributes more than 50% of total peripheral
vascular resistance.
| Cutaneous circulation contributes 30% of total peripheral vascular
resistance.

Pulse Pressure (PP): The difference between the systolic and the diastolic blood
pressure
| PP = SBP - DBP
| It indicates the stroke volume.
| Ratio of systolic : diastolic : pulse pressure = 3 : 2 : 1

Mean Arterial Pressure (MAP): Average pressure in the circulation.

| MAP = DBP + ⅓ rd PP
| Closer to diastolic blood pressure.
| Because diastole is of longer duration (0.5s)
MEASUREMENT OF THE BLOOD PRESSURE
Personal Notes
| Palpatory method: Detects only systolic blood pressure, slightly lower
pressure than actual.
| Auscultatory method: Compared to directly measured intravascular
pressure, sphygmomanometry will give slightly higher pressure because of
the dissipation of cuff pressure.
| Higher in conditions like:

1. Atherosclerosis

2. Obesity
| Small cuff: Erroneously high blood pressure.
| Auscultatory gap: Low systolic and normal diastolic BP.

2 Physiology
 Kidney/Excretory System
INTRODUCTION
Personal Notes

The kidney is made up of nephrons,

| 85% of nephrons are Cortical nephrons.
| Short loops
| Normotonic urine

Juxta Medullary Nephrons

| 15% of nephrons are juxtamedullary nephrons.
| Long loops
| Concentrated urine or Hypertonic urine.

Renal Blood flow goes through the cortex.

| O2 consumption is slightly greater in the medulla.
JUXTAGLOMERULAR APPARATUS
Personal Notes

1. AFFERENT ARTERIOLES

JG Cell
↓ Blood volume
↓
↓ BP
JG cell → Renin → Angiotensinogen (Liver)
↓
Angiotensin I
↓ Lungs
↓ ACE
Angiotensin
↙ ↘
Vasoconstriction Aldosterone
↙ ↘
BP Na+ retention water
↓
↑ Blood volume

2. MACULA DENSA

| Early DCT
| Tubuloglomerular feedback

2 Physiology
 ↑ RBF
Personal Notes
↓
↑ GFR
↓
↑ Na+ filtration & water
↓
Sensed by macula densa in early DCT
↓
ATP breakdown
↓
Adenosine
↓
Constriction of afferent arteriole
↓
↓ RBF and ↓ GFR

3. MESANGIAL CELL/LACIS CELL OR GOORMAGHTIGH CELL

| TG feedback
| Alter the vessel diameter
| Erythropoietin: Type I cortical interstitial cell (Peritubular capillaries)

PECULIARITIES OF RENAL CIRCULATION

| Dual capillary bed

| Capillaries → Arterioles
| Capillary hydrostatic pressure:
™ 60 mmHg (Highest)
| Capillary filtration coefficient:
™ 12.5 mL/min/mmHg (Highest)
| Arteriovenous O2 difference:
™ 10-12% (Least)
| Elsewhere in the body, Metabolic rate → regulates the blood flow.

In the Kidney, Blood flow → regulates the metabolic rate

↑ RBF
↓
↑ GFR
↓

Kidney/Excretory System 3
↑ Na+ filtration
Personal Notes
↓
↑ Na+ load for reabsorption
↓
↑ ATP breakdown
↓
↑ O2 consumption

4 Physiology
 Renal Tubular Functions

Personal Notes

| The glomerular filtrate is isotonic to plasma.

| By the end of the PCT, the tubular fluids are still isotonic.

PCT
The substance reabsorbed is,
| 65-70% sodium
| 65-70% water
| 100% glucose
| 100% amino acids
| 90% bicarbonate
| 70-75% potassium, chloride, calcium
Loop of Henle
Personal Notes
| 10-15% water reabsorbed from the loop of Henle (Solvent drag).
| Thick ascending limb sodium is removed and the transporter is called as
NKCC (Impermeable to water).
| The Thick Ascending Limb (TAL) is called as Diluting segment of the nephron.

DCT
| Fluid reaching the early DCT is always hypotonic.
| NCC transporter

CD
| CD reabsorbs water under the influence of ADH.
| CD referred to the Concentrating segment of the nephron.

WATER REABSORPTION

| PCT reabsorption is called as obligatory reabsorption.

| The CD is described as facultative water reabsorption (10-12% water).
| In the absence of ADH: 88% water is reabsorbed.
| In the presence of ADH: 99% water is reabsorbed.

The CD contains 2 types of cells:

1. P cell - Principal cell

™ Na+ reabsorbed and secreted K+

2. I cell - Intercalated cell

™ K+ reabsorbed and secreted H+

TRANSPORT MAXIMUM (TM)

The maximum rate at which a substance moves across the tubule

↓↓

Carrier proteins

TmG ≥ 373 mg/min for Men

303 mg/min for Women

Renal threshold for glucose: 180 mg%

↓↓

Heterogeneity among nephron

2 Physiology
CONCENTRATED URINE FORMATION
Personal Notes
| Hypertonic urine
| It requires the ability to separate solutes and water.
| TAL part of the loop of Henle and CD.

1) Hypertonicity of medullary interstitium

2) Role of ADH
™ Juxta medullary nephrons (15%): Long loops
™ Hypertonicity or Hyperosmolarity of medullary interstitium

Solutes
| Na+: Required in the body
| Urea: Excreted into the urine
| Countercurrent multiplier mechanism: Countercurrent flow of the tubular
fluids
| Countercurrent exchange mechanism.

Countercurrent Multiplier Mechanism

| Starts in the TAL
| Na+ was removed and water stayed back.

a) Horizontal Osmotic gradient (TAL): 1 : 2

b) Vertical Osmotic gradient: 1 : 4

Tip of the Loop of Henle

| 1200 mosm/kg of water
| Max concentrated urine → 1200 mosm/kg of water

Renal Tubular Functions 3

ROLE OF UREA
Personal Notes
| Contributes 40-50% of the total osmolality.

Countercurrent Exchange
| Vasa recta
| Sluggish blood flow
| Do not contribute to hyperosmolarity of the interstitium.

↓↓
| They only prevent its dissipation.
| Max concentrated urine → 1200 mosm/L
| Most dilute urine 50 mosml/L
| A healthy adult → Excretes 600 mosm/day
| With most concentrated urine 0.5L/day required

OBLIGATORY URINE OUTPUT

0.5L/day
↓↓
400ml/day or less is called as Oliguria.
100ml/day or less is called as Anuria.

Most Dilute Urine

| Max output → 18L/day

4 Physiology
Bladder Function and Micturition Reflex
INNERVATION OF THE BLADDER
Personal Notes

MICTURITION REFLEX

Proprioceptors

↓↓
Spinal cord

↓↓
First event: Contraction of detrusor muscles
↗ ↘
Spinal cord Relaxation of sphincters
↖ ↙
Receptors ← Few drops in the posterior urethral wall
VARIOUS BLADDER CAPACITIES
Personal Notes
50ml Residual volume
100ml-150ml First reflex from the bladder wall
250ml Desire for micturition
>400 ml Urgency
>600 ml Painful Urgency
800ml Physiologic capacity
>900 ml Anatomic capacity

CYSTOMETROGRAM

Law of Laplace’s
P = 2T
R

TYPES OF BLADDER

Type of Bladder Lesion

1. Atonic bladder Afferents are cut
2. Isolated bladder Both afferent and efferent cut
3. Automatic bladder Reflex are intact sacral segments above S2
4. Overflow incontinence Spinal shock, lesion in spinal cord
5. Neurogenic bladder (Spastic/ Cortex and lower centers
uninhibited) urge incontinence

2 Physiology
PHYSIOLOGY OF ACID-BASE BALANCE
Personal Notes
Buffer System
| pH of the ECF = 7.4
| Intracellular pH = 7.2

1. Chemical buffers (Few Seconds)

2. Respiratory system (9-12 min)

3. Kidney (Few hours)

1. Chemical Buffers
a) HCO3-:
™ Most plentiful in ECF
™ pKa is 6.1

b) Phosphate:
™ pKa is 6.8
™ Intracellular fluids, Renal tubular fluids

c) Proteins:
™ >70% buffering in ICF
™ pKa is close to 7-7.1

2. Respiratory System
| Otherwise called a ‘‘Physiological buffer’’.
| Metabolic acidosis/alkalosis
| Regulating CO2 level
| The respiratory system is a stronger buffer in acidic pH.

3. Kidney
| In respiratory acidosis/alkalosis

i) Reabsorption of filtered HCO3-

ii) Generation of new HCO3-

iii) Ammonia, Phosphate buffer

i) Reabsorption of filtered HCO3-

™ Px X GFR

(24mEq /L x 180 L/day)

= 4320mEq /day

Bladder Function and Micturition Reflex 3

 ™ Secretes H+
Personal Notes
PCT → 4320mEq /day
+
80 mEq /day → Net acid output/day
Total = 4400mEq /day
ii) Generation of new HCO3-

Glutamine
↑↓ → 2HCO3-
2 ammonia

iii) Phosphate, ammonia:

™ Ammonia → Chronic respiratory acidosis
™ Non-ionic diffusion (Disuse trapping)
™ pKa of ammonia is 9.0

Titratable Acidity
| Maximum acidic urine = pH 4.5
| Urine sample → Titrate with NaOH

↓↓
7.4
| Acid is buffered by phosphates in the kidney and eliminated in the urine.

4 Physiology
 GFR
INTRODUCTION
Personal Notes
| Filtrate formed by the kidney per unit time.
| Ultrafiltrate (Filtrate formed under pressure)
| Normal filtrate: 125mL/min
| 180L/day

FACTORS DETERMINING GFR

| Starling’s forces involved

I. Factors Favoring
™ Glomerular capillary hydrostatic pressure: 60mmHg
™ Hydrostatic pressure is exerted on the accumulated fluid.
™ Greater will be hydrostatic pressure.
™ Force pushes the fluid away from it into the neighbouring compartment.

II. Factors Opposing

i. Plasma colloid oncotic pressure: 32mmHg

ii. Bowman’s capsule hydrostatic pressure: 18mm Hg

Total pressure: 50mmHg

Net filtration pressure = I-II

60-50 = +10mmHg
Capillary filtration coefficient: 12.5ml/min/mmHg x 10 = 125ml/min

Filtration Fraction
| RBF = 25% of CO = 1250 ml/min
| RPF = 625-650 ml/min
GFR
| Filtration fraction =
RPF
125 ml/min
=
625 ml/min
= 20% or 1/5th
FACTORS INFLUENCING GFR
Personal Notes
Factor GFR RPF Filtration Fraction
1. Dilation of afferent arteriole ↑ ↑ →←
2. Moderate constriction of efferent ↑ ↓ ↑↑
arteriole
3. Severe sustained constriction of efferent ↓ ↓ →←
arteriole
4. High protein diet ↑ ↑ →←
5. Nephrolithiasis ↓ →← ↓

MEASUREMENT OF GFR
| Inulin (Ideal)
| Filtered = Excreted
| Creatinine (Most commonly)
| Creatinine clearance is an overestimate of GFR.
| Some creatinine comes by tubular secretion.

Cockroft & Gault Formula

(140-age) x Body weight
Creatinine clearance =
72 x Pcr
RBF & PPF: Para- amino Hippuric acid (PAH) is used
| It is eliminated into the urine in a single pass (Renal vein = Zero).
RBF = RPF x 1
1-HCE

CLEARANCE
| The volume of plasma completely cleared of a substance per unit of time.
UxV
Clearance =
Px
Ux = Urinary concentration of x (mg/mL)
V = Volume of urine (mL/min)
Px = Plasma concentration of x (mg/sec)
Ux Px V GFR
I II
[Px X GFR] [Ux X V]
Total filtered amount Total excreted amount
I > II = Reabsorbed
I < II = Secreted

2 Physiology
 Pulmonary Circulation and Ventilation
to Perfusion Ratio
VENTILATORY INDICES
Personal Notes
1. Respiratory minute volume = (TV) x (RR) = 6-8L/min.
2. Alveolar ventilation = [TV-DSV] x (RR) = (500ml) - (150ml) = (350) x
(12-14/min) = 4-4.2 L/min.
3. Maximum Breathing Capacity/Maximum voluntary ventilation (MBC/MVV)
-125-170 L/min.
4. Breathing reserve = [MVV] - [RMV] = 125-8
5. Dyspneic index = BR x 100
MVV = 95%
<70% : Dyspnoea

PULMONARY CIRCULATION/LESSER CIRCULATION

| The pulmonary artery and umbilical artery carry deoxygenated blood.
| Low resistance:
™ Pulmonary artery pressure: 25/8 mmHg
™ Pulmonary capillary pressure: 15 mmHg
| High compliance:
™ 24 times
™ Reservoir of blood: -15-18% of blood volume
Pulmonary capillary pressure Pulmonary capillary wedge pressure
↑↓ ↑↓
15mmHg Left atrial pressure 5mmHg or 5-8cm H2O

Dual Blood Supply

Pulmonary circulation → Gas exchange
Bronchial circulation (1-2%) → O2 supply
↘
Bronchial vein
↘
Pulmonary vein
↘
The left side of the Heart
| The left side of the heart receives 1-2% extra blood
Personal Notes
| The left side of the heart receives deoxygenated blood
Hypoxia
↓↓
Vasoconstriction
Elsewhere in the body: Hypoxia → Vasodilation
In Vascular Smooth Muscle Cells
Systemic → ATP - sensitive K+ channel: Vasodilation
Pulmonary → O2 - sensitive K+ channel: Vasoconstriction
Zones of Blood Flow in the Lung

Zone I: No blood flow

Zone II: Intermittent blood flow
Zone III: Continuous blood flow
In supine posture entire lung → Continuous blood flow

VENTILATION PERFUSION RATIO

Alveolar ventilation
Perfusion
4L/min V
= =
5L/min Q
= 0.8
↑V
Physiological dead space = = 3.5
↓Q

↑V
Physiological shunt = = 0.5
↑↑↑↑ Q

2 Physiology
 Regulations of Breathing
1. NEURAL REGULATIONS
Personal Notes
| Voluntary regulation comes from the cortex.
| Automatic breathing regulation (Involuntary) is controlled by the
respiratory center in the brain stem.

| Pacemaker for spontaneous breathing: Pre-Botzinger complex

| Pneumotaxic center: Shallow and rapid breathing
| Apneustic center: Slow and deep breathing

Hering Breuer Reflex

1. Inflation reflex: Tidal volume > 1L
2. Deflation reflex: Yawning
Head’s Paradoxical Reflex
| Seen at birth
Personal Notes
| Complete distension of the lungs

EFFECT OF LESIONS

Lesion Effects

Vagotomy Prolonged inspiration

Transection in the lower medulla Spontaneous breathing stops
Transection in the upper medulla Spontaneous breathing continues ±
irregular, jerky
Midpontine transection Prolonged inspiratory spasms
Damage to the lower part Rapid shallow breathing

2. CHEMICAL REGULATIONS

Chemoreceptors
1. Peripheral
2. Central

Peripheral Chemoreceptors
| Located in the carotid artery and arch of the aorta.

The carotid body has got massive blood flow: 2000ml/100gm/min

2 Physiology
Glomus Cell
| O2: Sensitive K+ channel
Personal Notes
| Sensitive to
™ Hypoxia
™ Arterial H+ (Metabolic acids, lactic acids, ketoacids)

O2 can drive the breathing in hypoxia only when PO2 < 60 mmHg

Central Chemoreceptors
| Sensitive only to H+ in CSF in interstitial fluid.

| Sensitive to changes in arterial CO2.

Arterial CO2
↓
Crosses Blood brain barrier
↓
CO2 + H2O → H2CO3
↙ ↘
H+ HCO3
| ↑CO2/H+: Stimulates central chemoreceptors

| ↓CO2/H+: Depress central chemoreceptors

HIGH ALTITUDE

Hypoxic hypoxia
↓
Pulmonary vasoconstriction
| Dyspnea
| 2-3 days
| ↑ 2-3 Bisphosphoglycerate
| ↑ Sensitivity of peripheral chemoreceptors.
| ↓ Sensitivity of central chemoreceptors.

Regulations of Breathing 3
 Gas Transport in Blood
DIFFUSION-LIMITED CARBON MONOXIDE (DLCO)
Personal Notes

| The diffusing capacity of the respiratory membrane is measured by Carbon

monoxide [DLCO].
| Diffusion limited: Never reaches equilibrium
| O2, CO2 → Perfusion limited

OXYGEN TRANSPORT

| From atmospheric air to blood

| In blood to tissues

From Atmospheric Air to Blood

1. PO2 in the atmospheric air at sea level:

760 mmHg
↙ ↘
N2 O2
(80%) (20%)
PO2 = 159mmHg
2. PO2 in the dead space (Inspired air):
™ Humidification of air

PH2O = 47mmHg

PO2 = 20% of 713

= 149 mmHg
3. PO2 in alveolar air:
Personal Notes
[149] - [45] = 104mmHg
Alveolar air equation:
[PACO2]
PAO2 = [FiO2 x (PB - PH2O)] -
R
CO2 evolved
R = Respiratory quotient (RQ) =
O2 consumed
= 0.8 (Mixed diet)
= 1.0 (-CHO rich)
= 0.7 (Fat-rich)
4. PO2 in arterial blood:
PO2 in arterial blood = 95mmHg

O2 TRANSPORT IN BLOOD
| With Hb (97%)
| Free/dissolved in plasma (3%): PO2
Dissolved O2 context
Dissolved O2 = (PO2) x (Solubility coefficient for O2)
↓↓
0.003ml/100ml/mmHg

O2 Carried by Hb
O2 - Carrying capacity
1gm of Hb → 100% sat → 1.39ml of O2
1gm of Hb → 97% sat → 1.34ml of O2

Total O2 Content
= [Hb(gm%) x 1.39 x %saturation] + [PO2 x solubility coefficient]
Hb Free
↓↓ ↓↓
[19.6ml] + [0.4ml]
= 20 ml of O2/100 ml of arterial blood
| Minimum required O2
6mL/100mL of blood
| Hyperbaric O2 is given in CO-poisoning

O2 Utilization Coefficient
5
= 25%
20

2 Physiology
A- V O2 difference = 25%
Personal Notes
| Heart → Highest → 75%
| Kidney→ Lowest → 10-12%

Oxygen Dissociation Curve

| ‘S’ shaped (Sigmoid)

| Deoxy Hb → Globin chains

↓↓
‘T’ State (Tensed)
| O2 affinity for Hb is low

↓↓
1st O2 molecules combine
↓↓
Globin → ‘R’ state (Relaxed)
O2 affinity for Hb↑

Gas Transport in Blood 3

Advantage
Personal Notes
| O2 dissociation from Hb
| P50 = 25-28mmHg

1) PO2 = 100 → 60mmHg

™ Any fall in PO2
™ Hb holds its O2

2) PO2 = 60 → 30mmHg
™ Small fall in PO2
™ Rapid decrease in % saturation of Hb.
™ Hb gives out its O2 readily (To maintain O2 level in tissues)

Shift to Right Shift to Left

| ↑ H+ in tissues | ↓ H+
| ↑ PCO2 in tissues (Bohr’s effect) | ↓ PCO2
| ↑ Temperature in tissues | ↓ Temperature
| ↑ 2, 3 - BPG in RBCs | ↓ 2, 3 - BPG
- | HbF → Shift to left
- | CO - poisoning

CO2 TRANSPORT

| 78% → HCO3-
| 20-25% → Carbamino - Hb
| 5-7% → Free/dissolved in plasma

4 Physiology
CHLORIDE SHIFT/HAMBURGER SHIFT
Personal Notes
| Band 3 protein/AE-1: Chloride exchanger in RBCs

Haldane’s Effect
| Effect of O2 on CO2 liberation.

| In the absence of O2: 2 volume % of CO2 liberated

| In the presence of O2: 4 volume % of CO2 liberated

Gas Transport in Blood 5

 Lung Volumes and Capacities
| Hutchinson’s spirometer measures lung volumes and capacities.
Personal Notes
LUNG VOLUMES

| Tidal Volume (TV): 500 mL

| Inspiratory Reserve Volume (IRV): 3000 mL
| Expiratory Reserve Volume (ERV): 1100 mL
| Residual Volume (RV): 1200mL

CAPACITIES

| Inspiratory capacity: [TV+RV] = 3500mL

| Functional residual capacity: [ERV+RV] = 2300mL
| Vital capacity: [IRV+TV+ERV] = 4600mL
| Total lung capacity (TLC): [IRV+TV+ERV+RV] = 6 L

Functional Residual Capacity (FRC): Equilibrium position of the respiratory

system

Closing Volume (CV) of the Lungs

| The airway at the base of the lungs begins to close.

With aging: CV approaches FRC

Restrictive Disease
Personal Notes
| Pulmonary fibrosis, ILD
| Decrease in the vital capacity
| Breathing: Shallow and rapid near lower lung volumes.

Timed Vital Capacity or Fevt

| FEV1 = 80%-84%
| FEV2 = 90%-94%
| FEV3 = 97%
FEV1 < 70% → Obstruction (COPD)
↓↓
Expiration is difficult

FEV1/VC Ratio
| ↓Decreased → COPD
| ↑Increased → Restrictive disease

Small Airway Obstruction

| MMFR (FEV 0.25-0.75)
| Normal value: 3-3.25L/sec

Flow-Volume Loops

2 Physiology
| PIFR = 3L/sec
Personal Notes
| PEFR = 10-12L/sec

COPD → Slow & deep

↓↓
Near higher lung volumes

Spirometry Cannot Measure RV

| Helium dilution

| Nitrogen washout method

DEAD SPACE
| Part of the respiratory passage that does not take part in gaseous exchange.
| Volume → 1mL/pound of body wt = 150ml

1. Anatomic Dead Space

| First 16 generations

| Fowler’s method (Single breath Nitrogen analysis)

2. Total/Physiologic Dead Space

| Anatomic + alveolar

| Bohr’s method (Expired PCO2 analysis)

In Deep Forceful Inspiration

| ↑Increased Anatomic dead space

| ↓Decreased Alveolar dead space

Tracheostomy: Done to reduce dead space

Lung Volumes and Capacities 3

 Mechanism of Breathing Part-I
TOPICS
Personal Notes
| Surfactant
| Compliance
| Work of breathing

SURFACTANTS

↓ Surface tension
↓↓
↓ Collapsibility
↓↓
↑ Distensibility
| Secreted by type II Pneumocytes

Type I Pneumocytes
| 93% surface area
| Gas transfer

Type II Pneumocytes
| Corners of the alveoli
| 5% surface area
The ratio of type I and II is 1 : 1
Earliest evidence → 17-20 weeks
Type III Pneumocytes
| 2% surface area
Personal Notes
| Chemoreceptor

Precursor
| Tubular myelin

| Lamellar inclusion bodies

Constituents
1) DPPC
2) Surface apoproteins (SP- I, II, III, IV)
3) Ca++ → faster spread

Functions
1) ↓Surface tension
↓↓

↑Compliance
2) Helps in gas transfer
3) Keeps alveoli dry
4) Stabilizes the alveolar interdependence

Laplace’s Law
2T
P=
R

Applied: ARDS [Hyaline membrane disease]

COMPLIANCE
| Distensibility of lung
1
| Compliance ∝
Surface tension

Compliance= ΔV/ΔP

2 Physiology
Types
Personal Notes
1. Static:
™ 200ml/cmH2O

2. Specific compliance:

Compliance
=
FRC
3. Dynamic compliance:
™ Changing compliance with the stage of breathing

(I) At the start of inspiration:

‘ Alveoli are small
‘ High compliance
‘ At lower lung volumes

(II) By the end of inspiration:

‘ Alveoli are large
‘ Compliance is low
‘ At higher lung volumes

Restrictive Lung Disease

| Shallow and rapid toward lower lung volumes

Hysteresis

Mechanism of Breathing Part-I 3

 Personal Notes

| More work done during the expiration

↓↓
COPD

WORK OF BREATHING
| ΔP/ΔV
| 3 types
(1) Compliance work (65%)
(2) Airway resistance work (28%) → COPD
(3) Tissue resistance work (7%) → ILD/Fibrosis

4 Physiology
 Mechanism of Breathing Part-II
Inspiration: Active process
Expiration: Passive process
Personal Notes
MUSCLES OF RESPIRATION

Primary Muscles Accessory Muscles

| Diaphragm (Males): Abdominothoracic | Scalene
| Contract and it increases the vertical
diameter of the chest wall

Inspiration | External intercostals (Female): | Serratus

Thoracoabdominal anterior
| Contract and it increases the
anteroposterior diameter of the chest
wall
| Abdominal muscles -
Expiration
| Internal intercostals -

PRESSURES

1. Intrathoracic/Intrapleural Pressure
| Mostly negative

| To keep the lung distended

| Elastic recoil of the lung
| Except during forceful expiration
Role of pleural fluid:
| Keeps the pleurae together (During inspiration).

| Hydraulic traction

Quiet breathing: | – 5 cm H2O

| State of inspiration | –7.5 cm H2O
| End of Inspiration
Forceful breathing: | –30 cm H2O
| Sigh | –30 cm H2O
| Yawn | –60 cm H2O
| First cry
Muller’s maneuver | –100 cm H2O Personal Notes
Forced expiration: | +30 to + 50 cm H2O
| Dry cough, sneeze | +60 to 80 cm H2O
| Opera, yelling | +100 to +150 cm H2O
| Valsalva maneuver

2. Intra - Alveolar Pressure

| Inspiration: –1

| Expiration: +1

3. Transpulmonary Pressure
| Transpulmonary pressure = Alveolar pressure - Intra pleural

4. Transthoracic Pressure
| Transthoracic pressure = Alveolar pressure - pressure on the external part
of the thorax
| Pressure across the thorax

5. Transmural Pressure
| Transmural pressure = Pressure inside the airway - pressure outside the
airway

2 Physiology