1

GENERAL PHYSIOLOGY

1.Cell Membrane - Structure

Features:
Plasma membrane is a dynamic structure and its constituents are constantly renewed.
The thickness of membrane is about 7.5 nm
Semipermeable - allowing some substances to pass through while excluding others
Components:
Phospholipids
Cholesterol 40%
Proteins -------------- 55%
Carbohydrate -------- 5%
Arrangement of the components:
Explained by Fluid Mosaic Model proposed by Singer & Nicolson
- Phospholipids forms a fluid structure in which proteins and other components are
embedded to give a mosaic pattern.
- Fluidity helps the substances dissolved in lipid layer to move to different places in
the membrane
Lipid Bilayer:
- Made up of two layers of phospholipid molecules
- Each phospholipid molecule has a hydrophilic phosphate head and two hydrophobic
fatty acid chains
- These molecules are arranged in two layers in opposite direction
- The inner and outer surfaces of the lipid bilayer are hydrophilic and the interior of
the bilayer is hydrophobic
Proteins:
Two types of proteins: Peripheral & integral or transmembrane proteins
Peripheral proteins are attached to the outer and inner surfaces of membrane
Integral proteins extends through the membrane from outside to inside
Carbohydrates:
Oligosaccharide molecules are attached to the surface of membrane.
The molecules which are attached to membrane proteins are glycoproteins
The molecules which are attached to phospholipid molecules are glycolipids
These molecules form “Glycocalyx” surrounding the cell
Significance of each component:
Phospholipids - Maintains the membrane in fluid state & provides flexibility to the
membrane
Cholesterol – Provides rigidity (stiffness) to the membrane
Proteins – Critical components of membrane as it performs many functions
Glycocalyx – Helps in cell to cell recognition
Functions of cell membrane:
1. Forms a protective barrier surrounding the cells
2. Semipermeability of the membrane differentiates the concentration of ECF from ICF
3. which is responsible for development of biopotentials
4. Links adjacent cells together by intercellular connections
5. Provides anchoring sites for filaments of cytoskeleton
6. Allow cell to cell recognition – Glycocalyx
7. Provides a binding site for enzymes/hormones
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2. Cell membrane Proteins

Embedded in the fluid lipid bilayer

Peripheral proteins
Integral proteins

Types: Peripheral & integral or transmembrane proteins

1.Peripheral proteins :
 Loosely bound to the membrane
 Non-covalently bound to integral proteins
 Provides structural integrity to the cell membrane
Types
1. Intrinsic - anchored to cytoskeleton of the cell
2. Extrinsic - act as cell adhesion molecules (CAM)
2. Integral proteins (Transmembrane proteins ) :
 Covalently bond
 Penetrate lipid bilayer
Functions of integral proteins:
 Channels: Provide channels for the ions to diffuse in both directions e.g., Na+ Channels (allow
sodium ions to diffuse inside). Diffusion of ions through channels is simple diffusion
 Carriers: Transport the substances along the concentration gradient. Diffusion with the help of
carrier proteins is called facilitated diffusion. E.g., transport of glucose by a carrier protein GLUT
 Pumps: Transport the substances against the electrochemical gradient e.g., Na+-K+ ATPase
pump. The pumping of substances with the help of transport protein is called primary active
transport
 Receptors: Receive the chemical signals from outside e.g., Hormones & neurotransmitters
 Antigens: Differentiates the self from non-self e.g Human Leukocyte Antigen (HLA) & Blood
group Antigens
 Enzymes: Catalyze the reactions at surface of the membranes e.g Adenylate cyclase
 Cell Adhesion Molecules: Help to anchor the cells to neighboring cells and to the basal lamina
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3. Glycocalyx
Glycocalyx is a coat on the external surface of the plasma membrane. This coating consists of several
carbohydrate moieties (glycolipids and glycoproteins)
Functional significance:

contribute to cell-cell recognition, communication, and intracellular adhesion

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distinguish between own healthy cells and transplanted tissues, diseased cells, or invading organisms.

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Lipid Bilayer as semipermeable membrane::

The phospholipid bilayer structure with specific membrane proteins accounts for the selective
permeability of the membrane
Small molecules and larger hydrophobic molecules move through easily. e.g. O2, CO2, N2 and alcohol
Hydrophilic molecules have lower solubility to penetrate the membrane slowly. E.g. Ions, glucose and
urea ,
Importance of Semipermeability:
Semipermeability of plasma membrane determines the concentration difference between ECF & ICF
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Transport Across the Membrane
Membrane Transport

Passive Transport Active Transport

Passive transport mechanisms:
 Diffusion
 Facilitated Diffusion
 Osmosis
 Capillary filtration
 Bulk Flow / Solvent drag
DIFFUSION
Diffusion is the net movement of molecules (or ions) from a region of their high concentration to a
region of their lower concentration.
Characteristic features of diffusion
 The molecules move down a concentration gradient.
 Requires no energy
 Molecules move about randomly by kinetic energy
 As a result of diffusion, molecules reach equilibrium (no net movement of molecules from either
side).
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Factors Affecting Diffusion

 Cell membrane permeability
 Concentration Gradient
 Pressure gradient
 Electrical potential gradient
Cell membrane permeability depends upon:
 Solubility of the substance in the lipid bilayer
 Molecular size of the particle
 Charge of the particle
 Charge at the pore
 Surface area
 Thickness
 Number of protein channels
 Temperature
Fick’s law of Diffusion:
J = DA (C1-C2)
---------------
T
J = Rate of Diffusion T = Thickness of membrane
C1-C2 = concentration gradient D = Diffusion coefficient
A = Cross sectional area
Types of diffusion:
1. Simple diffusion
2. Facilitated diffusion

1. Simple Diffusion
Diffusion without the help of a carrier protein
Mode of Simple Diffusion

Through Lipid Bilayer Through Channels

Molecules that pass through the lipid bilayer by diffusion

 Gases (oxygen, carbon dioxide)
 Water molecules (rate is slow due to polarity)
 Lipids (steroid hormones)
 Lipid soluble molecules (hydrocarbons, alcohols, some vitamins)
 Small noncharged molecules (NH3)
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Molecules that pass through the Channels by diffusion

 Ions (Na+, K+, Cl-)
 Small water soluble molecules
 Water (faster rate)
Gating of Protein channels
Types of gated channels
1. Voltage gated channels – open when there is a change in the resting membrane potential
e.g., Na+ channels along the nerve fiber

2.Ligand gated channels – open when a chemical binds to the receptor which is attached
to the channel e.g., channels attached to the acetylcholine receptors in synapse or Neuro-
muscular junction

Mechanical gated channels – Open when there is a mechanical stretch

e.g Channels in the smooth muscle fiber
Drugs that block channels:
Sodium channels – Tetrodotoxin (TTX) & Saxitoxin
Potassium channels – TEA (Tetra Ethyl Ammonium)
Calcium channels – Verapramil (to treat hypertension)

2. Facilitated diffusion
Movement of solutes from high concentration to low concentration through the membrane
with the help of a carrier protein
Features of Facilitated Diffusion
 Occurs along the concentration gradient
 Does not require energy
 Involves carrier protein
 Carrier proteins are highly specific for molecules
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 Have saturation point. Diffusion increases with increase in concentration gradient in simple
diffusion whereas in facilitated diffusion, diffusion depends on availability of carrier proteins.
When the carrier proteins are saturated, facilitated diffusion stops
 Competitive inhibition occurs
Mechanism of Facilitated Diffusion
 Molecule binds to carrier
 Carrier changes conformation
 Molecule released on other side
 Purely passive process- stops when concentrations are equal

e.g., Glucose transport in to the cells with the help of a carrier protein GLUT (Glucose Transporter)
 Glucose molecule from interstitial fluid binds to GLUT
 GLUT changes its confirmation
 Glucose molecule is released in to the ICF

OSMOSIS
The diffusion of water from an area of high concentration of water molecules (high water potential) to an
area of low concentration of water (low water potential) across a partially permeable membrane.
Osmosis occurs through water channels called “Aquaporins”
Osmotic pressure
The minimum pressure which when applied on the side of higher solute concentration prevents osmosis
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Colloidal osmotic pressure

 The osmotic pressure exerted by colloidal substances in the body is colloidal osmotic pressure
 The colloidal osmotic pressure of blood due to plasma proteins is called ONCOTIC PRESSURE
 Oncotic pressure or colloidal osmotic pressure of blood is normally 25 – 30 mmHg
 80% of the oncotic pressure is determined by albumin
 colloidal osmotic pressure of blood is one of the factors influencing the capillary filtration
 colloidal osmotic pressure of blood opposes filtration and thereby prevents edema
 A decrease in colloidal osmotic pressure due to hypoproteinemia increases capillary filtration
and causes development of edema. E.g., Malnutrition, Liver cirrhosis and nephrotic syndrome
Osmolarity
 Number of osmotically active substances per Liter of a solution is called osmolarity
 Normal osmolarity of body fluid is 290 milliosmoles / liter
 Osmolarity of body fluid is mainly determined by sodium, Chloride and bicarbonate
 Osmolarity is also influenced to some extent by glucose, urea, plasma proteins etc.,
Tonicity
The effective osmotic pressure of a solution relative to the plasma is called tonicity
Isotonic solutions:
Solutions having same osmolarity as that of plasma ie., 290 milliosmoles/lt
Examples of isotonic solution:
 0.9% sodium chloride solution (isotonic saline)
 5% glucose solution
 20% urea solution
 10% mannitol solution
Significance of isotonic solution:
Isotonic solutions (0.9% NaCl / 5% glucose / 20% urea) can be infused in case of dehydration to
restore the body fluid volume without upsetting the osmotic equilibrium of the cells
Hypertonic solutions:
Fluids whose osmolarity is greater to that of plasma ie., > 290 milliosmoles/lt
Hypotonic solutions
Fluids whose osmolarity is lesser to that of plasma ie., < 290 milliosmoles/lt
CAPILLARY FILTRATION
 It is a process by which a fluid is forced through a membrane due to variation in the hydrostatic
pressure
 Major route of transport between blood and interstitial space.
 Filtration is determined by difference in various pressures of blood & interstitial space.
 The normal rate of net filtration in the entire body is only about 2ml/min.
 This fluid is drained by the lymphatics from the interstitial space.
Starling’s hypothesis:
 At any capillary bed the rate of filtration is determined by forces acting across the capillary
membrane.
 Any imbalance in these forces may lead to edema (accumulation of fluid in tissue spaces) or
dehydration (fluid loss from the body)
Starling’s Forces: The forces acting on the capillary membrane and influencing the rate of capillary
filtration are called Starling’s forces.
The forces are:
 Capillary hydrostatic pressure – favours filtration
 Capillary osmotic pressure – oppose filtration
 Interstitial fluid hydrostatic pressure – oppose filtration
 Interstitial fluid osmotic pressure – favours filtration
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At arterial end
Hydrostatic pressure of blood = 30 mmHg
Oncotic pressure of blood = 28 mmHg
Interstitial hydrostatic pressure = - 3 mmHg
Osmotic pressure of interstitial fluid = 8 mmHg
OUTWARD FORCES - INWARD FORCE = 30 + 8 – (-3) +28
= 30 + 8 + 3 – 28
= 13 mmHg (net filtration pressure)
At venous end
Hydrostatic pressure of blood = 10 mmHg
Oncotic pressure of blood = 28 mmHg
Interstitial hydrostatic pressure = - 3 mmHg
Osmotic pressure of interstitial fluid = 8 mmHg
OUTWARD FORCES = 10 + 8 + 3 = 21 mmHg
INWARD FORCE = 28 mmHg
28 – 21 = 7 mmHg (net absorption pressure)

SOLVENT DRAG
Transfer of solutes by being carried along with the water flow driven by osmotic gradients across cell
membranes.
Example: Transfer of fluid along with its constituents across the intestinal wall & Capillary
ACTIVE TRANSPORT
 Substances are transported against the chemical or electrical gradient (from the region of low
concentration to the region of high concentration)
 Utilizes energy from ATP
 Up-hill process
 Utilizes a transport protein (pump)

Pump
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Types of Active Transport

1) Primary
2) Secondary
3) Bulk/Vesicular Transport
a) Exocytosis
b) Endocytosis
i) Phagocytosis
ii) Pinocytosis
iii) Receptor-Mediated endocytosis
1.Primary active transport
The energy is derived directly from the breakdown of ATP or some high- energy phosphate compound.
Examples:
 Sodium-potassium ATPase pump
 Calcium ATPase pump
 Hydrogen ATPase pump
Sodium-potassium pump (a specific case of active transport)
Structure
α Subunit (100, 000 MW)
β Subunit (55000 MW)
3 Intracellular sites:
1. Sodium binding site
2. ATP binding site
3. Phosphorylation site
2 Extracellular sites
1. Potassium binding site
2. Ouabin binding site

Mechanism of the pump:

 Cytoplasmic Na+ binds to the sodium-potassium pump.
 Na+ binding stimulates phosphorylation by ATP.
 Phosphorylation causes the protein to change its shape. Na+ is expelled to the outside.
 K+ binds on the extracellular side and triggers release of the phosphate group
 Loss of the phosphate (dephosphorylation) restores the protein’s original shape.
 K+ is released, and the cycle repeats
 Three sodium ions are pumped outside where as two potassium ions are pumped inside
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Functions of Na+ -K+ Pump

1. Maintains Na+ & K+ gradients across the membrane essential for genesis of RMP (Resting
Membrane Potential).
2. Maintains Cell volume: If the pump is paralyzed, sodium ions which enter the cell remain
inside & water follows, causing swelling and rupture of cells.
3. Important role in secondary active transport.
4. Maintains high intracellular K+ which is important for protein synthesis
2. Secondary active transport
The energy is derived secondarily (indirectly) from the energy which has been stored in the form of
ionic concentration differences, created in by primary active transport. In other words the downhill
energy (energy of diffusion) of one substance is utilized for uphill movement (active transport) of
another substance
Types:
 Co-transport (symport)
 Counter transport (Antiport)
Co – transport: Both the substances are transported in the same direction
e.g., Sodium – Glucose Co-transport & Sodium-Amino acid Co-transport
Counter transport: Two substances are transported. One substance is transported in opposite
direction to the other substance
e.g., Sodium-Hydrogen counter transport & Sodium- Calcium counter transport

Sodium - Glucose co-transport:

 An example for secondary active transport
 Sodium and glucose are transported together from ECF to ICF through the cell membrane by a
transport protein
 The transport protein is SGLT (Sodium Dependent Glucose Transporter)
 This occurs secondary to Na+-K+ ATPase pump (secondary active transport) which maintains the
concentration gradient of sodium
 The diffusion energy of sodium is utilized by glucose for its active transport
 As this transport does not utilize energy directly, this is secondary active transport
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Sites of Sodium - Glucose co-transport

Absorption in Intestine
Reabsorption in Kidney
Clinical use of secondary active transport:
This is used in oral rehydration therapy which helps to restore the volume of body fluid which is lost
in dehydration
ORS (Oral Rehydration Solution)
 simple treatment for dehydration
 It consists of a solution of salts and sugars which is taken by mouth.
 As both substances are osmotically active particles, they increase the absorption of water. This
will restore the body fluid effectively
3.VESICULAR TRANSPORT
 Vesicular transport is an active process in which materials move into or out of the cell enclosed as
vesicles.
 Vesicles are small membrane sacs. They can form at the cell membrane or can fuse with the
membrane.
 Transports macromolecules like protein and even cells like bacteria
 There are two basic types of vesicular transport-endocytosis and exocytosis.
Exocytosis:
A process by which the contents of secretory vesicles move out of the cell and into the
extracellular space.
Mechanism of exocytosis:
intracellular vesicle moves to the plasma membrane
↓
fusion of the vesicular membrane and plasma membrane
↓
Rupture of membrane and release of contents outside
Examples
secretion of proteins like enzymes, peptide hormones and antibodies from cells, release of
neurotransmitter from presynaptic neurons
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Endocytosis
Process by which the macromolecules are transported in to the cells
Types:
1. Pinocytosis
2. Phagocytosis
3. Receptor mediated endocytosis
1. Pinocytosis
 Process in which the cell takes in surrounding fluids, including all solutes present.
 Pinocytosis is nonspecific in the substances that it transports.
 Also called as “cell drinking”
Mechanism of pinocytosis:
 Cell forms an invagination
 Vesicles are formed within the cell
 These pinocytic vesicles subsequently fuse with lysosomes to hydrolyze (break down) the
particles.
Example:
Absorption of antibodies in the intestine of baby from mother’s milk

2. Phagocytosis
Process by which microorganisms like bacteria and other particulate materials are engulfed in to the
Cell. Also called as “cell eating”
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Mechanism of Phagocytosis:

Example: Engulfing of bacteria by phagocytes (Neutrophils & Macrophages)

3. Receptor mediated endocytosis

This type of endocytosis is triggered by various ligands binding to the receptors on the cell surface
Mechanism:
 Binding of chemical molecules to the receptors in the clathrin-coated pits
 Contraction of clathrin
 The pit is then pinched off forming a coated vesicle
 The vesicle then becomes endosome
Example: Uptake of cholesterol
Transport of iron
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CELL JUNCTIONS
The cell membranes of adjoining cells are connected with one another through intercellular junctions.
Types
 Tight junctions
 Anchoring junction
- Desmosomes
- Hemidesmosomes
- Adherence junction
Focal adhesion
 Gap junction
1.Tight junctions (Zona Occludens or occluding zone):
 The cell membranes of two adjacent cells fuse with each other
 Obliteration of the space between them.
E.g: blood brain barrier, Intestinal epithelial cells
Functions:
 Form strong union between neighboring cells which provides strength & stability to the cells
 Barrier to the movement of ions and other solutes from one cell to other (Useful in Blood brain
barrier & Blood testis barrier)
 Prevents lateral movement of proteins  maintains polarity of cells
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2.Anchoring junction:
 Provide firm structural attachment between two cells or between a cell and the extracellular
matrix
 The attachment is provided by either actin or intermediate filaments
Desmosomes
 Cell membrane of adjacent cells is separated by 200A gap.
 A part of the gap is occupied by a solid structure which provides a strong union between the cells
 The proteins involved are Cadherins
 Seen in skin and neck of uterus
Hemidesmosomes:
 Appears like half desmosomes
 Anchor cells to the basement membrane
 The proteins involved are integrins
Adherence junctions
 Connect actin filaments of one cell to those of another cell
 The membranes of the adjacent cells are held together by transmembrane proteins called
cadherins
 Present at the basal regions of tight junction in cardiac muscle and epidermis of skin
Focal adhesions:
 Attach cells to basal lamina
 Also connect the actin filaments of the cell to the extracellular matrix
 The transmembrane proteins involved are integrins
 Seen in epithelia of various organs
3. Gap junction:
 Cell membrane of adjacent cells is separated by a gap of 2-3 nm
 The gap is connected by protein cannels
 One half of the protein cannel is contributed by one cell and the other half from the adjacent cell
 The protein channel contributed by each cell is called connexon and is made up of six subunits
enclosing a channel of about 2 nm
 Present in cardiac muscle, smooth muscle & astrocytes
Functions of Gap junctions
 Allow two way transmission of low molecular weight substances like glucose, aminoacids &
other ions
 Direct movement of ions between cells helps in rapid propagation (conduction) of impulses
 Synchronize the activity of neurons or muscle fibers in an all or none manner
 In astrocytes, play an active role in signaling in the brain through chemical messengers
Importance of gap junctions in cardiac muscle:
By synchronizing the activity of cardiac muscle fibers, make the heart to function as a syncytium
(single cell). Direct ionic movement and rapid propagation of electrical impulses through the fibers
play an important role in this
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----------------------------------------------------------
What are Starling’s forces? How they help in tissue fluid formation? Explain Starling’s hypothesis
in connection with the passage of fluid across capillary wall
Starling’s hypothesis:
At any capillary bed, the filtration of fluid through the capillary membrane is determined by pressures
acting across the membrane.
Starling’s forces:
The forces that act across the capillary membrane are called starling’s forces. They influence the
filtration and absorption of fluid across the capillary. The Starling’s forces are:
1) Capillary hydrostatic pressure (Pc) – Favors filtration
2) Capillary colloidal osmotic pressure (c) – Opposes filtration & favors absorption
3) Interstitial fluid hydrostatic pressure (Pi) – Opposes filtration when it is positive (but
usually it is negative)
4) Interstitial fluid osmotic pressure (if) – Favors filtration (but the pressure is negligible)

Tissue fluid formation:

Tissue fluid or Interstitial fluid is formed by net filtration of fluid from capillary into interstitial
Space

Net Filtration= Kf X (Pc+ if) –(c +Pif)

Net filtration through the muscle capillary:

Arterial end of capillary:
Capillary hydrostatic pressure (Pc) = 30 mmHg
Capillary colloidal osmotic pressure/ oncotic pressure (c) = 28 mmHg
Interstitial fluid hydrostatic pressure (Pif) = 8 mmHg
(As the capillary hydrostatic pressure is higher than oncotic pressure, filtration occurs&
tissue fluid is formed)
Venous end of capillary:
Capillary hydrostatic pressure (Pc) = 10 mmHg
Capillary colloidal osmotic pressure/ oncotic pressure (c) = 28 mmHg
Interstitial fluid hydrostatic pressure (Pif) = 8 mmHg
(As the oncotic pressure is higher than capillary hydrostatic pressure, absorption of tissue
fluid occurs)

Excess tissue fluid is returned to the blood vessels via the lymphatic system.
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HOMEOSTASIS
Definition:
Maintenance of constant internal environment within certain physiological range inspite of changes in the
external environment. Internal environment refers to ECF especially interstitial fluid.
- The term ‘homeostasis’ was coined by Canon
- The term ‘Millieu interior’ which means internal environment was coined by Claude Bernard
Systems involved in enforcement of homeostasis:
- Nervous system
- Chemical system
Role of different body systems in homeostasis:
1. Supply of oxygen and nutrients – Respiratory, Digestive, circulatory & musculoskeletal
2. Removal of metabolic waste products – Renal, Respiratory & slin
3. Volume & composition – Renal, Respiratory, Digestive & skin
4. Temperature – CVS, nervous, Endocrine, Musculoskeletal & skin
5. pH – Renal, respiratory & blood buffers
Components of homeostatic system:
Sensors: Recognize any deviation from normal level and feed to control center.
Control center: Receives information from sensors and activate appropriate effector system
Effector: Corrects the deviation (corrects the deviation rapidly where as chemical systems take a
longer time)

Normal
Correction
Deviation
Sensors Effectors

Control
center

REGULATION OF HOMEOSTASIS (Feedback Mechanisms)

The deviation is corrected to normal by two types of mechanisms:
1. Feedback mechanisms
2. Adaptive control system (Feed forward signals)
Two types of feedback mechanisms:
1. Negative feedback
2. Positive feedback
Negative feedback mechanism:
- A stimulus(change in the environment) produces a response which inturn depresses or stop
the stimulus. This type of feedback mechanism is negative feedback mechanism.
- Stimulus and response are in opposite direction
- Consists of two variables. The first variable stimulates the second one which inturn inhibits
first one
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Examples:
a) Regulation of thyroxine secretion from thyroid gland
Increased TSH secretion from anterior pituitary will stimulate thyroid gland. The
response will be increased secretion of thyroxine from thyroid gland. Increased
concentration of thyroxine above the normal level in the blood depresses the
secretion of TSH from anterior pituitary.
Anterior pituitary ---

TSH

Thyroid gland

Thyroxine

b) Regulation of Blood Pressure:

Any deviation from normal blood pressure is sensed by Baroreceptors which feed the information
to cardiac and vasomotor centers in the brain. The centers will influence the activity of autonomic
nerves which will produce a response in opposite direction to stimulus.

Increase in Blood Pressure

Stimulation of Baroreceptors

Cardiovascular centers

Stimulation of Vagus & Inibition of sympathetic fibers

Decreased heart rate & vasodilation

Decrease in blood pressure.

(Opposite happens in condition of decrease in blood pressure)

Features of Negative feedback mechanisms:
1. Response decreases the strength of stimulus
2. Comprises most of regulating mechanisms (about 99%)
3. Participate only in physiological conditions
4. Occurs in conditions that need frequent monitoring & adjustment within physiological limits
Positive feedback mechanism:
- A stimulus(change in the environment) produces a response which inturn reinforces the
stimulus. This type of feedback mechanism positive feedback mechanism.
- Stimulus and response are in the same direction
- Consists of many variables. The first variable stimulates the second one which inturn
stimulates the next variable.
Examples:
a) Parturition:
Contraction of uterus push the foetus down Stimulation of uterine cervix  Nerve impulses to
hypothalamus  release of oxytocin  reinforces the strength of contraction of uterus. This goes on
till the baby is born
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b) Blood clotting:
Activation of few clotting factors  activate other clotting factors in the coagulation cascade till the
blood clots.
Features of Positive feedback mechanisms:
1. Response increases the strength of stimulus
2. Comprises only 1% of regulatory mechanisms
3. Participate both in physiological & pathological conditions
4. Occurs in isolated conditions which do not require continuous monitoring
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MUSCLE PHYSIOLOGY K.SENTHAMIL SELVI

10 marks
1. NEUROMUSCULAR JUNCTION
Neuro Muscular Junction is the junction between a motor nerve ending and a
muscle fiber
Physiologic Anatomy
- Terminal buttons(End Feet) – Divisions at the end of axon of motor neuron
- Synaptic gutter - the depression on the skeletal muscle fiber in which the
axon terminal lies
- Motor end plate - the thickened part of the muscle membrane (sarcolemma)
which makes a close contact with the axon terminal
- Junctional folds - folds of motor end plate
- Presynaptic membrane – membrane of the axonic terminal which is in
connection with the muscle fiber
- Postsynaptic membrane - muscle membrane
- Synaptic cleft - The space between the two membranes
- Synaptic vesicles – Vesicles containing the neurotransmitter Acetyl choline
at presynaptic nerve terminal
- Ach receptors – Receptors found on the post synaptic membrane)

Synaptic gutter

Motor End plate

Events in transmission

Arrival of nerve impulse (action potential) at the presynaptic nerve terminal

↓
Depolarisation of the presynaptic nerve terminal
↓
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Opening up of the Ca++ channel and entry of calcium into the presynaptic membrane
↓
Release of the neurotransmitter (Ach) from vesicles into the synaptic cleft
↓
Fusion of the synaptic vesicle with the presynaptic membrane
↓
Rupture of vesicles & release of Ach into the synaptic cleft
↓
Binding of the Ach with the receptors on the post synaptic membrane
↓
Permeability of post synaptic membrane to Na+ increases
↓
Depolarisation of the post synaptic membrane-generation of a local potential - End Plate
Potential (non propagated)
↓
End Plate Potential reaches threshold & an action potential is produced which is
propagated.
DRUGS ACTING ON NMJ
1. Neuro Muscular Blockers
a) Inhibition of Ach release
Botulinum toxin –
A bacterial toxin which inhibits the synthesis or release of Ach
b) Antagonizing the action of Ach
Tubocurarine
By competitive inhibition. Both curare and Ach compete for the same
nicotinic receptor
c) By persistent Depolarisation
Suxamethonium(Succinyl choline)
Causes local energy exhaustion resulting in muscle relaxation
 Bungarotoxin
By irreversible combination with the receptor
2. Drugs that stimulate Transmission
a) By inactivating Anticholinesterase:
Neostigmine, Physostigmine- Prolonged depolarisation
Used in treating Myasthenia gravis
b) Di isopropyl flurophosphate-
Used in insecticides. Inactivates Anticholinesterase in an irreversible manner.
2.EXCITATION-CONTRACTION COUPLING

DEFINITION:
The process in which depolarization of the muscle fiber initiates its
contraction is called excitation-contraction coupling.
i.e electrical phenomenon is converted in to mechanical phenomenon.
Nerve Action Potential
↓ Neuromuscular transmission
Muscle Action Potential
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↓ Excitation contraction coupling

Muscular contraction
EVENTS

• Release of Acetylcholine from nerve terminal

• Binding of acetylcholine to the receptors present on the motor end plate
• Increased Na+ and K+ conductance in end- plate membrane
• Generation of end plate potential
• When the end plate potential reaches the firing level  generation of action
potential in muscle fibers.
• Spread of depolarization along T tubules to interior of the musclefiber
• Change in configuration of DHP receptors in membrane of “T” tubule  opens
ryanodine receptors (Ca2+ channels) of cisternae release of calcium into the
cytosol
• Ca2+ diffuses to thick and thin filaments.
• Thin actin filaments slide over the thick myosin filaments
• Z lines come closure  Shortening of sarcomere Muscle contraction

Action potential

Motor end plate

Cisternae

3. MECHANISM OF MUSCULAR
CONTRACTION
EVENTS DURING MUSCULAR CONTRACTION
 Electrical events
 Mechanical events
 4

 Chemical events
 Thermal events
ELECTRICAL EVENTS
• Transmission of nerve impulse to muscle across NMJ
• Excitation of muscle  development of muscle action potential
• Transmission of muscle action potential through “T” tubules to interior of muscle fiber
• Change in configuration of DHP receptors in membrane of “T” tubule  opens
ryanodine receptors (Ca2+ channels) of cisternae release of calcium into the cytosol
MECHANICAL CHANGES OR MOLECULAR EVENTS (FORMATION OF ACTO-
MYOSIN
COMPLEX)
• Explained by sliding filament theory-proposed by Huxley and Huxley in
1969. Most accepted theory
• States that muscular contraction is due to sliding of actin filaments over the
myosin filaments.
• The sliding reduces the length of sarcomere from its resting length of 2.2 µ to 1.5
µ
• Involves two important sequences:
• Exposure of myosin binding sites of actin molecules
• Cross bridge cycle
Exposure of myosin binding sites of actin molecules
• Binding of calcium to troponin C
• Conformational change of troponin C. (no longer can keep the tropomyosin on actin)
• Lateral movement of tropomyosin – troponin complex from actin filaments
• Exposure of myosin binding sites of actin molecules
• Exposure of myosin binding sites of actin molecules
Cross bridge cycle
1. Activation of myosin ATPase enzyme in the head of myosin molecule
2. Hydrolysis of an ATP molecule  release of energy  activation of myosin crossbridges
Hydrolysis
3. ATP ----------- ADP + P + Energy
4. Binding of crossbridges (myosin head) to the actin filaments
5. Bending of myosin head when ADP and P are released from the crossbridges  pulls the
actin filament towards the centre of sarcomere (powerstroke)
6. Binding of another ATP molecule  detachment of crossbridges from actin filaments
7. Binding of another ATP molecule  Attachment of crossbridge to another distal actin
molecule
CROSSBRIDGE CYCLE
Attachment – Swivel (power stroke) – detachment – attachment again.
RELAXATION OF MUSCLE
• Depends on reuptake of Ca2+ into sarcoplasmic reticulum (SR)
• Acetylcholinesterase breaks down ACh at neuromuscular junction
• Muscle fiber action potential stops
• When local action potential is no longer present, Ca2+ is pumped back into sarcoplasmic
reticulum
• Troponin-tropomyosin move back to their position and cover the active sites of actin
filaments.

 Interaction between the actin & myosin ceases

 5

 The muscle relaxes

 The cycle repeats
 Actin filaments slide over the myosin
 Maximum contraction occurs when there is a maximum overlap between the actin
and the cross bridges of the myosin filament. This occurs at the normal resting
length of the muscle (2.2um)

CHEMICAL EVENTS (Energetics of muscle contraction)

• Energy is provided by hydrolysis of ATP & creatine phosphate
• Glycogen stores in the muscle are utilized for resynthesis of ATP
• Glucose and fatty acids are also utilized for energy production
Contraction-Relaxation Steps Requiring ATP
• For binding of myosin crossbridges to actin filaments
• Detachment of crossbridges from actin filaments
• Active transport (Pumping) of Ca2+ back into sarcoplasmic reticulum
THERMAL EVENTS DURING CONTRACTION
• Resting heat: Heat produced during resting state
• Initial heat:
– Activation heat:- Heat produced by chemical changes in the muscle before
the actual contraction
 6

– Shortening heat:- Heat produced by shortening of muscle (mechanical

event during contraction)
• Recovery heat: Heat produced by chemical changes in the muscle during
recovery period (restoration to precontractile state)
• Relaxation heat: Heat produced by mechanical changes in the muscle during
relaxation

5 MARKS
MYASTHENIA GRAVIS – Discussed in applied

3 MARKS
1.SARCOMERE

Sarcomere is the contractile unit of the muscle fiber. It is the distance between two “Z”
lines. It consists of “A” band at the center and half of the “I” band at the sides. “A” band
is made up of thick myosin filaments and “I” band is made up of thin actin filaments.
The length of sarcomere at rest is about 2.5 µm. During muscle contraction the length of
sarcomere reduces to 1.5 µm. During stretching it increases in length to 3.5µm.

2. MOTOR UNIT
Definition: A single motor neuron with all its axonic terminals and the muscle fibers
supplied by it
Size principle:
The size of the type I motor unit is larger i.e., the number of muscle fibers supplied
by a single motor neuron is high. Type I motor unit controls the gross movements & the
muscle fibers involved are slow red muscle fibers.
 7

The size of the type II motor unit is smaller i.e., the number of muscle fibers
supplied by a single motor neuron is low. Type II motor unit controls the fine skilled
movements & the muscle fibers involved are fast white muscle fibers.

3.SMOOTH MUSCLE CONTRACTION

Steps involved:

1. Depolarisation of smooth muscle fibers

2. Release of calcium from sarcoplasmic reticulum
3. Calcium bind to “Calmodulin”(calcium binding protein in smooth
muscle fibers)
4. This calcium- calmodulin complex activates myosin light chain
kinase
5. The enzyme light chain kinase causes phosphorylation of myosin
6. Sliding of actin over myosin
 NERVE PHYSIOLOGY 2013
1. ACTION POTENTIAL
Definition: Transient change in the resting membrane potential caused by electro chemical
changes across the membrane when the membrane is excited by a threshold stimulus
It is a property of excitable cells( nerve cells and muscle cells)
Resting membrane potential
• RMP is the electrical potential across living cell membranes at rest
• varies between –70mv to 100mv
Genesis of action potential
• depolarization – reversal of polarized state i.e., decrease in electronegativity of the interior of
the resting cell
• repolarization – return of RMP to negative value
• depolarization beyond threshold leads to action potential
• action potential is all or none principle
depolarization exceeds threshold
↓
sodium channels open
↓
sodium ions rush in
↓
membrane potential reverses
↓
shifts from -70 mv to +60 mv
↓
as membrane potential reaches +40mv , the
sodium channels close and are inactivated
↓
potassium channels open
↓
Potassium ions diffuse out
↓
membrane repolarizes
↓
Membrane potential returns to negative value (-70mv)

5 7

4 8

-55 mv
1 3
-70 mv 9
2
 PHASES OF ACTION POTENTIAL
1. Stimulus artifact
2. Latent period
3. Slow depolarization
4. Firing level
5. Rapid depolarization
6. Spike potential
7. Rapid repolarisation
8. Slow repolarisation
9. Hyperpolarisation
IONIC BASIS OF ACTION POTENTIAL
Stimulus artifact – A brief irregular deflection of the baseline at the beginning of
recorded AP. It marks the point of stimulus
Latent period – the period between the application of stimulus and the beginning of
action potential. This is the time taken by the impulse to travel along the axon.
Slow depolarization – This is due to Na+ influx through the sodium leakage channels
Firing level – The point at which the rate of depolarization increases
Rapid depolarization – This is due to rapid entry of Na+ through voltage gated Na+
Channels
Spike potential – The sharp rise and rapid fall are the spike potential of the axon
Rapid repolarization – This is due to rapid exit of K+ through the voltage gated K+ channels
After depolarization – a slower fall of potential at the end of repolarisation. This is due
to slow exit of K+
After Hyperpolarization – Overshooting of tracing in the hyperpolarizing direction. This is
due to continuous efflux of K+ through slow K+ channels
5 MARKS
1. RESTING MEMBRANE POTENTIAL ( RMP)
Definition : The potential difference existing across the cell membrane when the cell is at rest is
called resting membrane potential
RMP of different cells:
Nerve fibers = -70 mv
Skeletal muscle fiber = -90 mv
Smooth muscle fiber = -50 mv
Cardiac muscle fiber = -90 mv
Genesis of RMP:
a) K+ Efflux: K+ is mainly responsible for the development of RMP. The membrane is
more permeable to K+ than Na+ (50 times). As a result a lot of K+ can
diffuse out creating negativity inside the cell (- 94 mv)
b) Na+ influx: Na+ that enters in to the cell may neutralize up to 8 mv
c) Cl- influx : Though membrane is more permeable to chloride ions its entry is
checked by electronegativity inside the cell
+ +
d) Na - K Pump:
Direct role – Pumps 3Na+ out and 2k+ in creating a negativity inside (- 4 mv)
Indirect role – Maintains the gradient for Na+ and K+ across the membrane so that
they can passively diffuse to the other side and cause RMP
Summary of net effect:
K+ diffusion to outside = - 94 mv
+
Na diffusion to inside = + 8 mv
Cl- diffusion to inside = 0 mv
Na+ - K+ Pump = - 4 mv
Net effect = +90 mv
Significance of intracellular proteins:
- Proteins carry negative charges
- Proteins are non diffusible anions
- Proteins remain inside the cell
Because of the above properties, intracellular proteins contribute to electronegativity inside the
cell (RMP) to some extent
2. CONDUCTION OF NERVE IMPULSE
• The action potential generated at the initial segment of the axon is conducted along the axon to
the nerve terminals
• Conduction of nerve impulse takes place in sequential depolarization of the adjacent area of the
nerve fiber
CONDUCTION IN UNMYELINATED FIBERS
• Explained by LOCAL CIRCUIT THEORY
• Conduction is by spread of +ve curent to adjacent area of membrane interiorly
• Exteriorly the circuit is completed
• This local circuit current reduces the membrane potential to firing level, increasing the sodium
permeability and the adjacent area becomes active(depolarized)
• When depolarisation reaches threshold, an action potential is produced
• Thus, by local circuit current flow, an active region stimulates the adjacent inactive regions to the
threshold.
• The impulse is conducted in both directions at constant speed

CONDUCTION IN MYELINATED NERVE FIBRES (SALTATORY CONDUCTION)

• The myelin sheath acts as an insulator. It does not allow passage of any ions through the
membrane. So the conduction of impulse is not continuous as in unmyelinated fiber
• The nerve impulse is conducted from one node of Ranvier to the next node of Ranvier
• The action potential “jumps” from one node to the next. Hence called saltatory conduction
• Local circuit current flows between active and inactive node
 Advantages of saltatory conduction
• Conduction velocity in myelinated fibres is greater than conduction velocity in unmyelinated
fibres. This helps in faster conduction of impulses
• Energy is saved as sodium potassium pumps are only required at specific points along the axon.
3. CLASSIFICATION OF NERVE FIBRE
• Structure:
• Myelinated nerve fibre 8
• Non mylinated nerve fibre
• Distribution:
• Somatic-supply the muscles of the body
• Visceral or autonomic –supply varies internal organ.
• Origin:
• Cranial nerves – arise from the brain
• Spinal nerves – arise from the spinal cord
• Functional:
• Motor – carry motor impulses from the CNS
• Sensory – Carry sensory impulses towards higher centre.
Numerical classification

Number Origin

I–a Muscle spindle, annulospiral ending

I–b Golgi tendon organ

II Muscle spindle–flower spray ending

Touch, pressure

III Pain, temperature

IV Pain and other receptors

Erlanger gasser classification

Fibre type Function Diameter (µm) Conduction

velocity(m / s)
A-α Proprioception, 12 – 20 70 – 120
Somatomotor
A-β Touch, Pressure 5 – 12 30 – 70

A-γ Motor to spindle 3–6 15 – 30

A-δ Pain, temperature, touch 2–5 12 – 30

B Preganglionic autonomic 3 3–5

C Dorsol root pain 0.4 – 1.2 0.5 – 2

4. Describe the degenerative changes in a peripheral nerve after cut injury. Or describe Wallerian
degeneration
• When a peripheral nerve is cut, the part of the nerve separated from the cell body (i.e., distal part)
shows a series of chemical and physical degenerative changes called as Wallerian degeneration.
Early Phase(1st -7th day):
Functional changes:
– Changes in the enzymatic activity (choline acetylase & acetyl choline esterase)
– Decrease in the activity of ionic channels
– Decrease in the conduction velocity
– Failure in the conduction of nerve impulse
Late Phase (8th – 32nd day)
– Neurofibrils disappear
– Axis cylinder swells & breaks into fragments
– Debris collects in the axis cylinder place
– Myelin sheath slowly disintegrates into fat droplets
– Neurilemma remains intact
– Schwann cells proliferate rapidly
– Macrophages remove debris of axis cylinder
– Neurilemmal tube becomes empty (ghost tube)
– Schwann cell cytoplasm fills the neurilemmal tube
Changes in cell body:
– Starts after 48 hrs of nerve injury
– First nissle granules disintegrates into fragments - chromatolysis
– Golgi apparatus disintegrates
– Cell body swells due to accumulation of fluid and becomes round.
– Nucleus is pushed to the periphery.
Changes in the proximal part:
-- Same degenerative changes as in the distal part (anterograde degeneration)
Regenerative changes in nerve following injury.
- Sprouting of a large number of small branches from the cut fibers
- Entry of some of these branches into the peripheral stump
- Proliferation of Schwann cells & formation of continuous tubes. This bridges the gap
between proximal & distal stumps
 - The growth of filaments is also guided towards the periphery
- When one branch grows in to the periphery, the other branches degenerate
- The growth towards denervated fibers is due to some chemical attraction called
neurotropism
- Myelin sheath begins to appear in about 15 days and proceeds peripherally
- Complete functional recovery takes 3 years
5.COMPOUND ACTION POTENTIAL
Compound action potential is a multipeak potential recorded from a nerve trunk.
Basis of compound action potential:
A nerve trunk is made up of different group of fibers.
Each group of nerve fibers has different conduction velocity. Hence the
impulses reach the recording electrode at different times. The first peak belongs to
fast conducting fibers & the last peak belongs to slow conducting fibers

6. Define the terms All or none law and refractory period as applicable to different
excitable tissues
The excitable tissues are nerve and muscle.
All or none law states that the tissue is excited to maximum by a threshold stimulus & do
not respond at all to a subthreshold stimulus.
All or none is applicable to a single nerve fiber, a single skeletal muscle fiber & whole
cardiac muscle
Refractory period is the period of excitation during which the tissue does not respond to
a second stimulus.
For nerve fibers, the absolute refractory period is from firing level to 1/3 of repolarization
& for skeletal muscle fibers, the absolute refractory period is first half of latent period.
But for cardiac muscle fiber, the whole of contraction period is refractory period. This
long refractory period of cardiac muscle does not allow it to go for tetanic contraction
7. Why regeneration does not occur in the central nervous system?
Neurolemma, the outermost layer surrounding the myelin sheath of an axon is found
only in peripheral nerve fibers, Presence of this layer is must for nerve regeneration.
Absence of this later in CNS does not allow regeneration in CNS
 1

BLOOD
1. ERYTHROPOIESIS
* Refers to the process of production and maturation of Red Blood
Cells (erythrocytes)
* Site of production – Red bone marrow of all the bones upto 20
years of life. After 20 years, only flat bones produce RBCs.
Stages of Erythropoiesis :
1. Hemocytoblast
2. BFU –E, Blast Forming Unit – E
3. CFU-E, Colony Forming Unit – E
4. Proerythroblast
5. Early normoblast
6. Intermediate normoblast
7. Late normoblast
8. Recticulocyte
9. Mature erythrocyte
1. Hemocytoblast:
- 18 – 23 um in diameter
- Large Nucleus
- Thin rim of basophilic cytoplasm
- Pleuripotent stem cells
2. Blast Forming Unit – E:
- Unipotent progenitor cell.
- Less Sensitive to Erythropoietin
3. CFU (E) – Colony Forming Unit
- Matured unipotent progenitor cell
- Highly sensitive to erythropoietin
4. Proerythroblast:
- 14-19 µm in diameter.
- Large nucleus with distinct nucleoli
- Basophilic cytoplasm.
- Vit B12 & Folic acid are required for the conversion of this stage into next stage.
5. Early normoblast;
- 11-17 µm in diameter.
- Dense nucleus
- Basophilic cytoplasm.
6. Intermediate normoblast:
- 10-12 µm in diameter
- more condensed nucleus
- Hb (Hemoglobin) is formed
- Polychromatophilic cytoplasm.
7. Late normoblast:
- 8-12 µm in diameter.
- Dense nucleus (Pyknotic)
- Nucleus extrudes after this stage & disintegrates
- Acidophilic cytoplasm.
8. Reticulocyte:
- Almost of the same size of matured RBC
- A small reticulum is seen in the cytoplasm.
10. Mature Erythrocyte:
- About 7.2 um in diameter.
- No nucleus
- Acidophilic cytoplasm
 2

Regulation of Erythropoiesis

1. Erythropoietin a hormone secreted by kidneys

- Stimulates the bone marrow tissue to produce more RBCs.

2. Hypoxia: Lack of O2 is the main condition which stimulates erythropoietin secretion.

Lack of O2 (Hypoxia)

Kidneys

Erythropoietin

Red Bone marrow

RBC Production

Restoration of O2 Supply
 3

3. Nutrients:
a) Proteins for synthesis of Hb.
b) Minerals:
i) Iron : for synthesis of heme part of Hb.
ii) Copper: for synthesis of Hb.
4. Vitamins:

a) Vitamins B12 & Folic Acid: Required for synthesis of DNA. These factors are called
maturation factors.
b) Vitamin C is also required.

5. Hormones:
Thyroxine stimulate erythropoietin
Glucocorticoids
Testosterone
Growth hormone RBC Production

Normal Count of RBC:

- Male 5-6 million/cu mm of blood
- Female 4.5 – 5.5 millions/cu mm of blood.
---------------------------------------------------------------------------------------------------------------------
2.WBC – White Blood Cells
Leucocytes (anucleated, colourless)

Granulocytes Agranulocyte

Neutrophils (50 - 70%) Monocyte (2-8%)

Eosinophils (1-4%)
Basophils (0-1%) Lymphocyte (20-40)

Cell Type Size Nucleus Cytoplasm

Neutrophil 10-14 u Multilobed Fine granules
(1-5 lobed) Purple coloured
Eosinophil 10-14 u Bilobed, Spectacle, Coarse granules brick
shaped red coloured
Basophil 10-14 u Bilobed ‘S’ shaped Thick granules, Blue
coloured , obscure or
mask the nucleus
Monocyte 15-20 u Kidney shaped, Abundant cytoplasm,
eccentric (towards no granules
periphery)
Lymphocyte 7-10 u Round Nucleus filling A Thin rim of
(Small) the cells cytoplasm

Large 12-16 u Large Round Nucleus Abundant cytoplasm.

 4

Functions of WBCs:

1. Neutrophils: Phagocytosis

Process of Phagocytosis:

a. Margination The neutrophils slow down in the circulation and get attached to
the wall of capillary endothelium.

b. Diapedesis - Neutrophils squeeze through the pores of capillary wall and

enter the tissue.

c. Chemotaxis – Neutrophils are attracted towards the infected site by the

chemicals released from the site.

d. Phagocytosis – Neutrophils, when comes in contact with bacteria ,the

membrane invaginates & enclose around the bacteria.

Then the enclosed vesicle is pinched off from the membrane. This forms a phagosome.
This combines with lysosomes. Lysosome releases lytic enzymes which digest the contents of
phagosome.
 5

Examples:
- Phagocytosis of bacteria.
- Phagocytosis of dead cells.
- Phagocytosis of antigen - antibody complex
- Phagocytosis of foreign particles like carbon particles, sodium urate crystals.
2. Eosinophil:
a. Anti-allergic – Eosinophils contain anti – inflammatory histaminase which
inactivate histamine.

b. Anti-Parasitic – Eosinophils contain a basic protein which destroys larval

parasites.

c. clot lysis – Eosinophils produce prefibrinolysin when activated, lyse the clot.

d. Phagocytosis – Engulf antigen – antibody complexes.

e. Detoxification: Certain foreign proteins are detoxified.

3. Basophil:

a) Release histamine which takes part in allergic reactions.

b) Release heparin which takes part in prevention of intravascular clotting.

4. Monocyte:
a. Enter the tissues & form tissue macrophages.
b. The main function of monocytes in circulation & tissues is phagocytosis.
c. Macrophages also co operate with B & T cymphocytes in both hormonal &
cell mediated immunity.

5. Lymphocytes:
B- Lymphocytes and T- Lymphocytes

B Lymphocytes: Take part in humoral immunity on exposure to antigens

B- Lymphocytes.

Plasma cells.
 6

Secretion of antibodies
T. Lymphocytes: Take part in cell-mediated immunity
i) Rejection of foreign grafts
ii) Destruction of cancer cells
iii) T helper cells take part in humoral immunity.
iv) T Suppressor cells prevent auto immunity.
v) Major defence against bacterial, Viral & fungal infections.
--------------------------------------------------------------------------------------------------------------------
3. IMMUNITY

Definition: The resistance of the body to the diseases caused by micro organisms (infectious
diseases) is called immunity.

Classification:

Immunity

Innate immunity (inherent) Acquired immunity

(Skin, mucous, membrane, (after exposure to micro-
GIT secretions, Micro & Macrophages, organisms.)
Natural killer cells etc.)

Natural Artificial

Passive Active Passive Active

Transfer of antibodies - Clinical Injection of Vaccination
Through placenta to fetus Disease activated
& through colostrums - Sub clinical lymphocytes
infection & Serum with
antibodies

Humoral immunity Cell-mediated

Activation of B Lymphocytes Activation of ‘T’ Lymphocyte

Plasma cells Formation of 4 Types of T cells

Antibodies a) Cytotoxic ‘T’ cells

b)T helper
c)T Suppressor
d)T Memory cells
 7

HUMORAL IMMUNITY

- B Lymphocytes participate in humoral immunity.

- on exposure to antigens  activation of B- lymphocytes to plasma cells  produce
specific antibodies against foreign antigens.
Mechanism pf Humoral immunity
- Antigen is fragmented by macrophages.
- A fragment of antigen binds to MHC Class II protein in the cell membrane of macrophages
and forms a complex.
- this complex is presented to the B cell by macrophages ( Antigen Presenting cell).
- Macrophage also secretes interleukin 1 which activates both T-Helper cells and B-
Lymphocytes.
- ‘T’ helper cells secrete IL2, IL4, IL5, IL6 (cytokines).
- these cytokines act on ‘B’ lymphocytes.
- ‘B’ Lymphocytes undergo proliferation & differentiation
- ‘B’ lymphocytes form plasma cells.
- Plasma cells produce specific antibodies.
Antibodies: Types Ig G, Ig A, Ig M, Ig D, Ig E.
1. Ig G antibodies:
- 75% of the total antibodies in the body.
- can cross the placenta.
- secreted into colostrum
- role in immunity in the fetus & the new – born.
2. Ig A Antibodies:
- 20% of total antibodies.
- present in mucosal secretions.
- protect the mucosal surface from infections.
3. Ig M antibodies:
- Mostly intra vascular.
- Destroy the organisms that enter the circulation.
4. Ig D antibodies
- Present in the surface of immature B- lymphocytes.
- help in the functional maturation of B- Lymphocytes.
5. Ig E antibodies:
- Present mainly on the surface of mast cells and basophils.
- Responsible for hypersensitive immune reactions (Allergy)
Functions of Antibodies:

1. Neutralisation of Antigen : - Antibodies neutralise the toxic effect of some bacterial

toxins.
2. Immobilization of bacteria: Immobilise the cilia or flagella of motile bacteria.
This limits the spread of disease.
3. Enhancement of phagocytosis: (Opsonisation):
- Ig G antibodies form an attachment to the antigen and enhances the phagocytic
activity of neutrophils and macrophages.
4. Antibody dependant cellular cytotoxicity:
- Antibodies link the target cells with Natural killer cells which kill the targets
secreting toxic chemicals.
5. Agglutination & Precipitation of antigen:
By cross linking antibodies make the pathogens to clump together (agglutination) &
the soluble antigens to form precipitation. This helps in easy phagocytosis.
6. Activation of complement:
- Antibodies bound to antigens activate a group of proteins in the plasma called
complement proteins. They facilitate the exudation of phagocytes towards the site
of infection.
 8

7. Provide fetal & newborn immunity:

- By the transfer of antibodies from mother through placenta & colostrums, the
fetus & newborn acquire immunity.
Cell – Mediated Immunity
- T Lymphocytes are involved in cell mediated immunity.
- They are produced in the bone marrow.
- They attain functional maturity in ‘Thymus’ under the influence of a hormone called
‘Thymopoietin” secreted from Thymus.
- They are 4 types of ‘T’ cells.
a) T helper cells (CD 4)
b) T Killer/Cytotoxic T Cells (CD 8)
c) T Suppressor cells.
d) T memory cells.
a) Activation of T Helper cells:

Antigen binds to MHC class II protein on the surface of Macrophage (Antigen presenting cell)

Forms a complex

secretion of IL-1

Presentation to “T” cell “

Activation of “T” Helper cells

B) Activation of cytotoxic ‘T’ Cells:

i) Antigen in virus infected cells, cancer cells & foreign grafts.

Processing of antigen to peptide fragments

Peptide fragments of processed antigen bind to MHC class I protein & forms a complex.

Presented to cytotoxic ‘T’ cells.

Activation of cytotoxic ‘T’ Cells.

-------------------------------------------------------------------------------------------------------------------
ii) Another way of activation of cytotoxic ‘T’ Cells

Antigen + MHC class II protein on the surface of macrophages (APC)

Interleukin – 1

Activation of ‘T’ helper cells.

Production of IL-2 by ‘T’ helper cells.

 9

Activation of cytotoxic ‘T’ cells.

Function of Activated cytotoxic ‘T” Cells;

Activated cytotoxic ‘T’ Cells

Perforin lymphotoxin

Forms holes in the Activates damaging

Plasma membrane of enzymes in the target cell
Target cells - Entry of ECF-

Swelling & burst of cell Destruction of DNA

Cell death Cell death

Examples: Death of virus infected cells, Tumour cells & foreign graft cells.

a) Function of ‘T’ helper cells:

Take place in both humoral & cell mediated immunity
i) Role in humoral immunity:

T- helper cells(TH2)

Interleukin – 2,4,5 & 6 (cytokines)

Activation of B Cells

Plasma cell

Secretion of antibodies
(ii) Role in cell-mediated immunity:
T- helper cells (TH1)

Interleukin – 2

Activation of cytotoxic ‘T’ Cells

Release of perferins & lymphotoxins

Death of target cells

b) Function of cytotoxic ‘T’ Cells:
- Destruction of Virus infected cells.
- Destruction of cancer cells.
- Rejection of foreign grafts.
- Major defence against viral, fungal & bacterial infection.
c) Functions of ‘T’ Suppressor cells:
- Suppress the production of antibodies against the own tissue.
- this prevents the auto immune diseases like Rheumatoid arthritis etc.
d) Function of ‘T’ Memory cell:
- Facilitates the activation of ‘T’ lymphocytes faster during secondary response.
 10

4.HEMOSTASIS
Definition:
Prevention of blood loss by arrest of bleeding
Stages:
Vasoconstriction
Platelet plug formation
Blood coagulation
Clot retraction
Fibrinolysis
Growth of fibrous tissue to repair the ruptured/damaged vessel permanently
a. Vasoconstriction:
Ruptured blood vessel
↓
Vasoconstriction
↓
Reduction in bleeding
-vasoconstriction due to Nervous reflexes, Local myogenic spasm & local humoral
factors (e.g Serotonin from platelets)
b. Platelet plug formation:
Platelets circulate in a resting, inactive state
↓
When blood vessel wall is injured
↓
Platelets adhere to collagen, laminin and von –
Willibrand factor in the vessel wall.
↓
Platelet activation
(Activated platelets change shape, release ADP & stick to each other platelet
aggregation.Platelet activating factor (PAF) secreted by neutrophil, monocytes &
platelets increase aggregation)
Thromboxane A2 increases platelet aggregation; helps in formation of temporary
hemostatic plug
c. Blood clotting or coagulation:
Damage to the tissues of Damage to the blood
blood vessel wall

EXTRINSIC INTRINSIC
PATHWAY PATHWAY

Formation of Prothrombin Activator Complex

↓
Prothrombin Thrombin
↓
Fibrinogen Fibrin (clot)

d. Clot retraction:
Definition:
Reduction in the size of clot
 11

Mechanism:
Fibrin stabilizing factor & thrombosthenin produced by platelets cause
strong contraction of platelets which are attached to fibrin
↓
Reduction of clot into smaller mass

9.Fibrinolysis (lysis of clot):

Damaged vascular endothelium
↓
Releases Thrombomodulin
↓
Thrombomodulin + Thrombin complex
↓
Activates protein c

Inactivates factors V &VIII Inhibits the inhibitor of Tissue

Plasminogen Activator
↓
Activation of tPA ( Tissue Plasminogen Activator)
↓
Plasminogen  Plasmin(lysis of clot)

5. BLOOD COAGULATION/ CLOTTING

Introduction:
When blood comes out of the blood vessel, it looses its fluidity & becomes a
semisolid jelly. This process is called clotting.
Definition:
Defined as the sequence of events leading to the formation of fibrin from fibrinogen
Coagulation factors:
- these are substances required for coagulation
- all these substances are present in plasma in an inactive form
- these are activated and take part in coagulation when the blood vessel wall is
injured
I - Fibrinogen
ii - Prothrombin
iii - Tissue thromboplastin
iv - Calcium
v - Proaccelerin,labile factor
vi - Accelerin
vii - Proconvertin,stable factor
viii - Anti hemophilic factor A
ix - Plasma Thromboplastic Component(PTC), christmas factor, antihemophilic
factor b
x - Stuart-prower factor
xi - Plasma Thromboplastin antecedent(PTA),
Anti Hemophilic factor C
 12

xii - Hageman factor,

xiii - Fibrin stabilizing factor
HMW- K - High Molecular Weight Kininogen,
pre-k - Prekallikrein
ka - kallikrein
PL - Platelet Phospholipid
Mechanism of coagulation:
3 main steps are involved
1. Damage to the blood vessel wall/ blood - Formation of Prothrombin Activator
Complex
2. Prothrombin Activator Complex activates prothrombin to thrombin
3. Thrombin converts fibrinogen to fibrin
Pathways of coagulation:
1. Extrinsic pathway
2. Intrinsic pathway

Extrinsic mechanism of clotting:

Triggered by tissue injury
Injured tissues release factor III (tissue factor)

VII VIIa
PF3
Ca2 + & III

X Xa
Va Prothrombin
Ca2+ Activator
tissue phospholipids Complex

Intrinsic mechanism of clotting:

Contact of blood with collagen, HMW kininogen, kallikrein
↓
Release of platelet phospholipids
&
activation of factor XII XIIa
↓
XI XI a
↓
IX IXa
PL
Ca2+
VIIIa

X Xa
Va Prothrombin
Ca2+ Activator
Platelet phospholipids Complex
 13

common pathway:
Both intrinsic and extrinsic pathways activate
Factor X Xa
PF3
Ca2+
V

Prothrombin (II) thrombin

XIIIa
stabilization

fibrinogen(I) fibrin (clot)

Clot: A meshwork of fibrin threads entrapping the blood cells and a fluid called serum
6. BLOOD GROUPS
Discovered by Landsteiner
Awarded Nobel Prize
Blood group systems:
ABO system
Rh System
Lewis System
MN system
Luthern System
ABO system
Grouping depends on presence/absence of Antigens/Agglutinogens
Antigens –A & B
Blood groups are A(A1&A2), B, AB(A1B & A2B) & O
Antibodies/Agglutinins Are in plasma
Landsteiner’s Law:
- If an agglutinogen is present on the RBC, corresponding agglutinin will be
absent in the plasma
- If an agglutinogen is absent corresponding agglutinin will be present
[Exception to the 2nd part is Rh System - Rh-ve people will not have Rh
Antibodies]
Rh Blood Group:
Discovered by Landsteiner & Weiner
The Rh Antigens are C, D, E. The common antigen is D antigen
People having ‘D’ antigen are called Rh +ve (85%)
People not having ‘D’ antigen are called Rh-ve (15%)
There are no naturally occurring antibodies
Blood Group Agglutinogen and Agglutinin:
Genotype Blood Group Agglutinogen Agglutinin
(RBC) (plasma)

AA, AO A A Anti B
BB, BO B B Anti A
AB AB AB Nil
OO O Nil Anti A
Anti B
 14

Determination of Blood Group:

Cells (R.B.C)
Anti A serum Anti B serum
A + --

B -- +

AB + +

O -- --

+ Agglutination -- No Agglutination
Uses of Blood Grouping:
In Blood Transfusion
In Pregnancy
In Disputed Paternity
Infertility and Early Fetal loss
Disease Relation e.g O group have twice incidence of Duodenal ulcer than A or B
In forensic science
In Anthropological studies
Blood Transfusion:
Transferring blood from one person to another person
Cross matching :
Major cross matching
Recipient’s Serum + Donor’s RBC
Minor Cross matching
Recipient’s RBC + Donor’s Serum
Universal Donor - O group persons have no agglutinogen and so can give blood to
anyone.
Universal Recipient - AB group persons have no agglutinins and so can receive any
type of blood
The above are no longer valid as complications can be produced by Rh and other
sub groups. But in case of extreme emergency O-ve blood can be used
ABO incompatibility:
- ABO incompatibility rarely produces hemolytic disease of newborn
- Anti A & Anti B antibodies are of IgM
- Cannot cross the placenta
Rh Incompatibility:
When 2nd time Rh +ve blood is transfused into negative blood–severe reactions occur
In women – during pregnancy incompatibility leads to ERYTHROBLASTOSIS
FOETALIS – a hemolytic disease of new born
 15

BLOOD – 5 MARKS
1.Functions of plasma proteins
Important plasma proteins are Albumin, Globulin & Fibrinogen
Normal Albumin/Globulin ratio = 1.7 : 1
a. Colloidal osmotic pressure: Albumin is mainly responsible for the development of
colloidal osmotic pressure. The normal colloidal osmotic pressure of blood is 25-30
mmHg. This is mainly responsible for the passage of fluid across the capillary
membrane
b. Viscosity of blood: Globulin maintains the viscosity of blood to some extent.
Viscosity is one of factors that influence blood pressure
c. Immunity: Antibodies (Immunoglobulins) belong to gammaglobulins. Antibodies
neutralize the antigen
d. Coagulation: Both prothrombin & fibrinogen take part in clotting process
Prothrombin activator

Prothrombin Thrombin

Fibrinogen Fibrin (clot)

e. Transport:
i) CO2 is transported by carbamino proteins
ii) Transferrin – transports iron
iii) Ceruloplasmin – transports copper
iv) TBG – Thyroxine Bound Globulin
v) CBG – Cortisol Bound Globulin
f. Acid-Base Balance – Plasma proteins act as buffers & neutralize any change in
blood pH
g. Protein reserve – Serve as storehouse of protein. Provides proteins to tissues during
starvation
h. ESR : Fibrinogen & Globulin increase the ESR. Albumin decreases the ESR
i. Haptoglobin: Forms the complex with hemoglobin & prevent its filtration into the
kidney
2. ANTICOAGULANTS
Anticoagulants are the substances that prevent clotting
a. Natural anticoagulants:
Heparin – produced by mast cells & basophils
Mechanism of action: facilitates antithrombin – III which inhibits the clotting
factors II, IX, XI & XII
b. Anticoagulants used in blood bank:
Acid Citrate Dextrose (ACD): Calcium chelating agent
Mechanism of action: forms a complex with calcium ions and decreases ionic
calcium level
c. Anticoagulants used in the laboratories:
Sodium citrate – Forms double salt with calcium ions
Double oxalate (Oxalates of K+ & NH4) - Precipitation of calcium
EDTA- Ethylene Diamine tetra acetate – Preparation of calcium ions
d. Therapeutic anti coagulants:
Dicoumarol – prevents the synthesis of blood clotting factors II, VII, IX, X by
competitive inhibition with vitamin .K.
------------------------------------------------------------------------------------------------------------
---------
 16

3. PHAGOCYTOSIS (Neutrophil response during inflammation)

Definition: The process of engulfing of macromolecules like bacteria, dead cells & particulate
matter by neutrophils, monocytes & tissue macrophages is called phagocytosis.
Steps involved in the process
Margination: Neutrophils slow down in the circulation & get attached to the capillary wall. The
cell adhesion molecules adherin, Integrin & selectin are involved.
Diapedesis: Neutrophils squeeze through the pores in the capillary wall into the tissues.
Chemotaxis : Neutrophils are attracted towards the site of damage ( infection & inflammation)
by the chemicals released at the site of damage.
Engulfing :
Microbes are coated with complement & antibodies (opsonization)
↓
Neutrophil membrane invaginates enclosing the microbe
↓
Formation of vacuole
↓
Vacuole fusing with lysosome
↓
Lysosomes release hydrolyzing enzymes & bactericidal agents like hydrogen peroxide,
mycloperoxidase etc
↓
Killing & digestion of the microbe.
---------------------------------------------------------------------------------------------------------------------

4. ANTICLOTTING MECHANISMS (Factors that prevent intravascular

coagulation)
1. Physical characteristics of the endothelium (e.g) Smoothness of vascular endothelium
Atherosclerotic (deposit of fat) plague in the vascular endothelium gives a rough surface which
activates platelets & initiate clotting.
2. High blood flow rates: Increased velocity of blood flow prevents clotting.
3.Presence of natural anticoagulants: Anticoagulants like heparin, anti thrombin III & α2macro
globulin are some of the natural anti coagulants present in the circulation and prevent the intra
vascular clotting .
4. Fibrinolytic system: When small clots are formed in the vessels they are immediately lysed by
the system.
Tissue Plasminogen Activator (tPA)
↓
Plasminogen → Plasmin (digests the fibrin into soluble fragments dissolving the clot)
---------------------------------------------------------------------------------------------------------------
5. COMPOSITION & FUNCTIONS OF LYMPH
Composition of Lymph
Electrolytes – same as that of plasma
Minerals – Ca₂₊ & phosphorous are lower than plasma
Protein – lower than that of plasma
Aminoacids – same as that plasma
Urea & creatinine – same as that of plasma
Glucose & chlorides – more than that of plasma
Cells – Lymphocytes & plasma cells are present
Clotting factor and antibodies are present.
Functions of Lymph
 Returns protein, electrolytes and water to the blood from the tissue spaces
 Removes the bacteria and particulate matter
 Fat absorption in the intestine by the lacteals
 17

 The lymphocytes and antibodies present in the lymph take part in body defence against
infectious diseases
 Helps in the redistribution of body water
 Transport antibiotics and other drugs injected intramuscularly
---------------------------------------------------------------------------------------------------------------------
6. FIBRINOLYTIC SYSTEM
Fibrinolysis refers to the process of dissolution of fibrin. Fibrinolytic system refers to the
substances taking part in fibrinolysis.
The important components of fibrinolytic system:
Protein C, tissue plasminogen activator & plasmin or fibrinolysin which is present in an inactive
form (plasminogen)
Protein C → Activated protein C

Inactivates clotting Inactivates inhibitor of tissue plasminogen activator

Factors V a & VIIIa ↓
Activation of tissue plasminogen activator
↓
Plasminogen Plasmin (fibrinolysis)
Fibrinolysin lyses fibrin into soluble fragments called as fibrin degradation products which inhibit
thrombin
Plasminogen Activaor system
Intrinsic: Factor XIIa and Kallikrein
Extrinsic: Tissue plasminogen activator, Streptokinase and staphylokinase
Physiological role of fibrinolytic system
 Cleans the minute clots of tiny vessels
 Promotes normal healing process
 Dissolution of menstrual clot
 Dissolution of sperms in the epididymis
Therapeutic role of fibrinolytic system
Streptokinase and staphylokinase are bacterial enzymes that activate plasminogen to
plasmin. So they are used in the treatment of early myocardial infarction.
---------------------------------------------------------------------------------------------------------------------
7.HAZARDS OF BLOOD TRANFUSION
Complications of whole blood transfusion
1. Hemolytic reaction due to red cell incompatibility
2. Transmission of certain diseases like hepatitis malaria, AIDS, Syphilis etc.,
3. Transient hyperkalemia followed by hypokalemia
4. Hypocalcemia
5. Volume overload
6. Bacterial contamination
7. Thrombophlebitis
8. Air embolismEffect of mismatched blood transfusion

Mismatching refers to transfusion of incompatible blood groups

a. Mild hemolytic reaction
Aggultination
↓
Hemolysis
↓
Bilirubin
↓
Jaundice
 18

b. Severe immediate hemolytic reaction

Wide spread agglutination leads to development of following signs and symptoms.
1. Chill and rigors
2. Fever and headache
3. Breathlessness
4. Chest pain and abdominal pain
5. Nausea and vomiting
6. Joint pain
7. Circulatory shock (due to release of histamine and other vasodilators)
Feathers of post shock phase
8. Hemolysis of agglutinated cells
9. Release of hemoglobin and its excretion into the urine
10. Jaundice
11. Anemia
12. Renal shut down due to precipitation of Hb in the renal tubules
13. Hyperkalemia and uraemia
c. Delayed hemolytic reaction:
1. Occurs 3days to 3weeks after transfusion only as 1 in 3200 transfusions
2. Antibodies that develop against donor cells cause agglutination and hemolysis
3. Symptoms are often mild or absent.
--------------------------------------------------------------------------------------------------------------------------------
8. FUNCTIONS OF PLATELETS
Platelets/Thrombocytes are biconvex discs produced by bone marrow
Size: 2 to 4μ
Normal count: 1.5 to 4 lakhs/cumm of blood
Granules of platelets: α granules and dense granules
α granules : consists of factor V, Fibrinogen, Von williebrand Factor, Platelet
factor IV, PGDF
Dense granules: Consists of ADP, Calcium, serotonin

Functions of Platelets
1. Primary hemostasis – Arrest of bleeding by temporary platelet plug formation is
referred as primary hemostasis.
Injury to wall of blood vessel
↓
Exposure of collagen
↓

Platelet adherence to damaged vessel wall

↓

Release of ADP and Thromboxane A2

↓
Activation of more platelets
↓
Aggregation and adherence of platelets (enhanced by platelet activation
factor produced by platelets and macrophages)
 19

↓
Temporary platelet plug

2. Secondary Hemostasis: Arrest of bleeding by the definite clot formation is called

secondary hemostasis
Platelet phospholipids and platelet activation factor III are the factors which are
involved in clotting.
3. Clot retraction: Contraction of contractile proteins (actin, myosin and
thrombosthenin) present in the platelets play an important role in clot retraction
4. Repair of capillary endothelium: Platelets adhere to the von – willebrand factor in
the wall of damaged blood vessels and release platelet derived growth factor
(PDGF). This factor plays an role in the repair of endothelium
5. Vasoconstriction: Platelets release serotonin which is a vasoconstrictor.
6. Defense /Phagocytosis: Platelets are helpful in phagocytosis of carbon particles,
viruses and immune complexes
--------------------------------------------------------------------------------------------------------------------------------
9.Oral Anticoagulants
Refers to anticoagulants which are used as drugs. These substances are given through
mouth to prevent clotting.
The substances which are used as oral anticoagulants - coumarin derivatives (Dicoumarol
and warfarin)
Dicoumarol
- It is a synthetic product
- It resembles vitamin K in structure

Mechanism of action
- Vitamin K is required for synthesis of clotting factors II, VII, IX, X protein C and
Protein S
- By competitive inhibition with Vitamin K, dicoumarol inhibits the synthesis of the
above factors from liver

Other Vitamin K antagonists

Warfarin, Phenindione, Nicoumalone
Therapeutic use:
Patient with hypercoagulability (increased tendency of blood to clot) are given
these oral anticoagulants for preventing the formation of thrombus
Oral anticoagulants are not effective invitro as they are vitamin K competitive
inhibitor and can act only inside the body
 1

Digestive System
10 Marks
1. Deglutition
The process of passage of food from mouth into the stomach is called swallowing or deglutition. This
process is divided into three stages
1. Oral phase
2. Pharyngeal phase
3. Oesophageal phase

ORAL PHASE PHARYNGEAL OESOPHAGEAL

PHASE PHASE

1) Oral phase: Passage of food from mouth to pharynx. It is a voluntary process

- the tongue is elevated and pressed against the hard palate
- the soft palate is also elevated
- the bolus is propelled into pharynx
- myolohyoid, styloglossus & intrinsic tongue muscles help this stage
2) Pharyngeal phase: Passage of food from pharynx into oesophagus. It is a reflex process. This
reflex is called swallowing reflex
Receptors: Stretch receptors in the anterior and posterior pillars of fauces and tonsils
Stimulus: Presence of bolus
Afferent: Sensory fibers of trigeminal, vagal & glossopharyngeal (V, IX & X cranial nerves)
Center: Swallowing center in medulla
Efferent: Motor fibers of 5th , 9th , 10th & 12th cranial nerves
Events during the second stage of following:
 Elevation of soft palate  closure of nasopharynx  prevents the reflux of food into
nasal cavities
 The vocal cords of the larynx are closely approximated & epiglottis close the glottis
(opening of larynx). Both the above events prevent the entry of food into the larynx
 Larynx is pulled upwards & forwards  stretches the opening of esophagus
 Upper esophageal sphincter relaxes  allows the food to pass into esophagus
 Superior pharyngeal constrictor muscle contracts  produces a rapid peristaltic wave
(primary peristaltic wave)  propels the food downwards (into esophagus)
 2

 Persistent elevation of the tongue maintains the high pressure gradient. This prevents the
entry of bolus again into the oral cavity
All the above events are the protective mechanisms during second stage of deglutition
3) Esophageal stage of swallowing: The passage of food from pharynx to stomach through
esophagus is the third phase of swallowing
Events:
 Upper esophageal sphincter relaxes allowing the food from pharynx into esophagus
 Three types of peristaltic waves are seen in the body of esophagus.
A) primary peristaltic wave – continuation of the peristaltic wave produced
in the pharynx by superior constrictor muscle
B) Secondary peristaltic wave – produced in the esophagus by the distension
of esophagus by retained food
C) Tertiary peristaltic wave – occurs irregularly & locally in the esophagus
 Lower esophageal sphincter relaxes & allows the food to pass into the stomach
Applied – Disorders of swallowing
1. Achalasia
2. Gastroesophageal Reflux Diseases – GERD/Heart bur n
3. Dysphagia
1. Achalasia:- Failure of lower esophageal sphincter (LES) to relax. So food is not emptied into
the stomach
Cause: Degeneration of the myenteric plexus in the lower part of the esophagus
Features: Dilation of esophagus due to accumulation of the food – called as
megaesophagus
Treatment
A) Antispasmodic drugs to relax – to relax LES
B) Botulinium toxin – to inhibit the release of acetylcholine  relaxation of
LES
C) Surgery – to open the LES
2.GERD/ heart burn – Reflux of gastric contents into the esophagus due to failure of
closure of LES. Also called as hiatus hernia.
Features: Heart burn – due to regurgitation of acid containing meals into the lower part
of esophagus. Chest pain, feeling of lump in the throat are other features.
Treatment: Antacids, H2 – blockers, Proton pump blockers
3. Dysphagia - Difficulty in swallowing due to disorders in any stage

2. GASTRIC SECRETION
Gastric juice is secreted from the gastric gland of stomach. Gastric glands are made up of six
types of cells
Type of cell Secretion
1. Parietal or oxyntic cell HCl, Intrinsic factor
2. Chief cells Pepsinogen
3. Mucous cell Mucus
4. Enterochromaffin Like Cell (ECL cell) Histamine
5. “D” cells Somatostatin
6. “G” cells Gastrin
 3

Composition of Gastric juice

- 1 to 1.5 lt of gastric juice is secreted/day
- Secretion is maximum during meals & minimum during sleep
Gastric juice

Water (99.45%) Organic & Inorganic substances

Inorganic:- HCl, Na+, K+, Cl- & HCO3-

Organic:-
1. Soluble & Insoluble mucus – Protects the gastric mucosa from HCl
2. Intrinsic factor – Regulates erythropoiesis by facilitating the absorption of Vit. B12 at illeum
3. Enzymes:
a. Pepsinogen: activated to pepsin by HCl
b. Renin: Acts on milk in the presence of Ca2+ & cause precipitation  curdling of
milk
c. Lipase: Acts chiefly on tributyrin & loe molecular weight triglycerides
d. Gelatinase: Digestion of gelatin
Mechanism Of HCl secretion:
HCl is secreted by parietal or oxyntic cells of gastric glands
2 components of secretion:
a) Secretion of H+ ions into the lumen
b) Secretion of Cl- ions into the lumen

Secretion of H+ ions:
i) By hydration of CO2, H2CO3 is formed in the parietal cell
CO2 + H2O  H2CO3
ii) Carbonic acid splits into H+ and HCO3-
H2CO3  H+ + HCO3-
iii) HCO3 is transported into the blood by antiport with Cl- (active transport)
-

iv) H+ combines with OH- to form H2O

H+ + OH-  H2O
v) H2O (water) dissociates into H+ & OH-
vi) Hydrogen ions are actively secreted into the lumen in exchange for one K+ ion
Secretion of Chloride ions:
i) For each HCO3- ion transported into the blood, one chloride is transported into the
cell by antiport
ii) This chloride ion diffuses into the lumen passively
iii) For each H+ ion secreted into the lumen, one chloride ion is secreted
iv) H+ combines with Cl- to form HCl
 4

Stimulants of HCl secretion:

Vagal stimulation, Acetylcholine, Histamine, Gastrin, Caffeine, Protein & protein digested
Products
Inibitors of HCl secretion:
Somatostatin, H2 blockers, Atropine
Regulation of Gastric secretion
Gastric secretion occurs in four phases:
a) Cephalic phase
b) Gastric phase
c) Intestinal phase
d) Interdigestive phase
a) Cephalic phase – Secretion of gastric juice even before food enters the stomach. This phase is
regulated by vagus nerve. This involves two reflexes
i) Unconditioned reflex
ii) Conditioned reflex
Food in the oral cavity ------ Unconditioned reflex ---------- NTS

Smell, sight & thought of food –Conditioned reflex ----- cortex, -- vagus
hypothalamus
Limbic system
Acetylcholine Direct effect
Vagus Chief cell & Parietal cell HCl & enzyme
GRP  G cell -- Gastrin

b) Gastric phase: Secretion of gastric juice when food enters the stomach. This phase is regulated
by both neural & hormonal mechanisms
i) Neural regulation:
Presence of food in stomach
↓
Stretching of gastric mucosa

Long vagovagal reflex Local reflex

(vagal stimulation) (Intrinsic nerve plexus)

Enhance gastric secretion

Mecanism:
Food in the stomach
↓
Ach release  Direct
Distension of
Gastric mucosa Local & vagal - GRP ------- Gastrin Gastric juice
secretion
ECL cells ------- Histamine  Direct
Release
ii) Hormones:
Gastrin
Acetylcholine
Histamine
 5

Mechanism:
1. “G” cells ----- Gastrin-- Gastrin receptor ↑ in intracellular
Ca2+
2. ECL cells ----- Histamine H2 receptor --- cyclic AMP  Gastric juice
secretion
3. Vagus ----- Ach ------- Ach receptor -↑ in intracellular
Ca2+
c) Intestinal phase : Secretion of gastric juice when food enters the intestine. This phase is mainly
regulated by hormones. Depending upon the type of food entering into the
intestine, there may be secretion or inhibition of secretion
i) Protein digested products in the duodenum
(Peptides, Peptones & aminoacids)

Stimulate the intestinal “G” cells

Release of gastrin

Stimulation of gastric secretion

ii) Acid, fat & hyperosmolar solution in the duodenum

Release of secrtin, CCK-PZ, bulbogastone

Inhibition of gastrin release & gastic juice secretion

\
iii) Enterogastric reflex: (Neural mechanism)
Presence of food in duodenum

Stretching of duodenal wall

Activation of locale nerve plexus

Activation of sympathetic fibers

Inhibition of gastric secretion & motility

d) Interdigestive phase: Minimal secretion of gastric juice when there is no food in GI tract. This
represents basal acid secretion
3. MOVEMENTS OF SMALL INTESTINE
Types of movements:
1. Mixing movements
a. Segmentation
b. Pendular
2. Propulsive movements
a. Peristalsis
b. Peristaltic rush
c. Interdigestive peristalsis
3. Movements of villi

SEGMENTATION:
- Ring like contractions at regular intervals divide the loop of intestine into a
number of segments of equal size
 6

- Each of the segments quickly divide again & reunite to form new segments
- Enhanced by vagus & hormones gastrin, CCK & motilin
Functions:
- Agitation of intestinal contents
- Subdivision of food particles
- Mixing of food with digestive enzymes
- Facilitates absorption of food
PENDULAR:
- Side to side swaying movements accompanied by lengthening and shortening of the
intestine
- Causes to and fro movement of the intestinal contents
PERISTALSIS:
-
A wave of contraction preceded by a wave of relaxation which always travel in
aboral direction.
- Mechanism:
- Presence of food in GI tract
- ↓
- Stretching of GI wall
- ↓
- Local myenteric plexus
- ↓ ↓
- Ach NO , VIP
- ↓ ↓
- Contraction Relaxation
- - 0.5 – 2 m/s
- - always move towards the aboral direction(Law of intestine)
- - helps in proper propulsion & digestion of food in intestine
- Factors influencing peristalsis:
- After meals – increases
- vagal stimulation – increases
- Sympathetic stimulation – decreases
- Injury of GI tract – decreases
- Gastrin & CCK – increases
INTERDIGESTIVE PERISTALSIS:
- - peristalsis during fasting i.e., when there is no food in the intestine
- - takes origin in duodenum & spreads to ileum
- - helps to clear any food residue that remains after previous meal
PERISTALTIC RUSH:
- - peristaltic waves sweeping over long segments of intestine in
- response to powerful irritation of intestinal mucosa
- - helps to relieve intestine from irritants
- - results in diarrhea
ANTIPERISTALSIS:
- - movement of peristalsis towards oral (mouth) direction
- - results in vomiting (expulsion of food through mouth)
MOVEMENTS OF VILLI:
- Initiated by presence of local nervous reflexes in response to chyme in the
intestine
- Two types of movements – Lashing & Lengthening – shortening
- Facilitates absorption by increasing the blood flow
 7

4. PANCREATIC JUICE
Phases of Secretion
Cephalic Phase
Gastric phase
Intestinal Phase
a) Cephalic Phase:
Contributes to about 15-20% of secretion
Sight, smell, thought secretion of pancreatic juice (conditioned reflex)
Presence of food in mouth  secretion of pancreatic juice (Unconditioned reflex)
Nervous Regulation:
Vagal stimulation  Acetylcholine  Pancreatic secretion rich in enzymes.
b) Gastric Phase
Contributes to about 5-10% of secretion
Both neural & hormonal regulation
Neural Mechanism
Presence of food in the stomach (distension)

Vagal stimulation (Gastropancreatic reflex)

Secretion of pancreatic juice

Hormonal Mechanism
Food in the stomach

Release of Gastrin from gastric mucosa

Secretion of pancreatic juice rich in fluids and bicarbonate

c) Intestinal Phase
Contributes to about 75% of secretion
Mainly hormonal regulation
i) Acid food in the duodenum
↓
Release of secretin

Secretion of pancreatic juice rich in fluids and bicarbonate

ii) Partially digested proteins & fatty acids in the duodenum

↓
Release of CCK-PZ (Cholesystokinin)

Secretion of pancreatic juice rich in enzymes
5MARKS

1. GASTRIC EMPTYING

The emptying of food from stomach into duodenum is called gastric emptying.
Mechanism:
The antrum, pylorum of stomach & the upper part of duodenum act as a unit in emptying of stomach
Antrum – peristaltic waves grind the food into chyme
 8

Pylorum – act like a sphincter & does not allow the food to pass into duodenum
until food becomes fluid
Duodenum – gives a feedback effect on gastric emptying
Factors influencing gastric emptying:
Gastric factors :
i) Increased food volume in the stomach
↓
Stretching of stomach wall
↓
Local myentric plexus
↓
Increase in gastric emptying

ii) Presence of protein digestion products

↓
Release of gastrin
↓
Promotes gastric emptying
Duodenal factors:
i)Enterogastric nervous reflex
Presence of protein digestion products,distension,acid & hypotonic or hypertonic fluid
in duodenum
↓
Through myenteric nerve plexus
↓
Inhibition of gastric emptying
ii) Hormonal feed back
Presence of Fat in duodenum
↓
Secretion of CCK
↓
Inhibition of gastric emptying
2. PERISTALSIS
Definition:
A wave of contraction preceded by a wave of relaxation which always travel in aboral
(opposite to mouth ) direction.
Mechanism:
Presence of food in GI tract
↓
Stretching of GI wall
↓
Local myenteric plexus
↓ ↓
Ach NO , VIP
↓ ↓
Contraction Relaxation
Rate of movement:
0.5 – 2 m/s
Peristalsis in Esophagus:
Primary peristaltic wave
 9

Secondary peristaltic wave

Tertiary peristaltic wave
Primary peristalsis –
- continuation of the peristaltic wave produced in the pharynx
- function is to propel food through the oesophagus to the stomach.
Secondary peristalsis -
- initiated by local stimulation of by food in oesophagus
- serves to reinforce the primary peristalsis
Tertiary peristalsis –
- occurs irregularly, significance not clear.
Peristalsis in stomach:
- called as digestive peristalsis
- occurs at a rate of 3/ m
- takes origin from a pacemaker zone
- helps in mixing & propelling the food through stomach
Peristalsis in small intestine:
- same mechanism of production of peristaltic wave
- rate of movement—o.5 to 2 m/s
- always move towards the aboral direction(Law of intestine)
- helps in proper propulsion & digestion of food in intestine
Factors influencing peristalsis:
After meals – increases
vagal stimulation – increases
Sympathetic stimulation – decreases
Injury of GI tract – decreases
Gastrin & CCK – increases
Interdigestive Peristalsis:
- peristalsis during fasting i.e., when there is no food in the intestine
- takes origin in duodenum & spreads to ileum
- helps to clear any food residue that remains after previous meal
Peristaltic rush:
- peristaltic waves sweeping over long segments of intestine in
response to powerful irritation of intestinal mucosa
- helps to relieve intestine from irritants
- results in diarrhea
Antiperistalsis:
- movement of peristalsis towards oral (mouth) direction
- results in vomiting (expulsion of food through mouth)
3. DEFAECATION
Definition:
-The process of removal of unwanted food residues or faeces from rectum at
regular intervals
Mechanism of defaecation reflex:
Stimulus – Presence of faeces in rectum increasing the rectal pressure to 20 – 25 cm
of water
Receptors – stretch receptors
Afferent fibers – sensory fibers in pelvic nerve
Centre – sacral segments of spinal cord (S2, S3 & S4 )
Efferent fibers – motor fibers in pelvic nerve
Effect or Response – contraction of rectum & relaxation of internal anal sphincter)
Other events during defecation:
 10

relaxation of external anal sphincter(controlled by pudendal nerve)

contraction of abdominal muscles
straightening of anorectal muscles

4. DIETARY FIBERS

Dietary fiber is the indigestible portion of food derived from plants. The main dietary fibers are
cellulose, hemicelluloses and lignin components of the vegetable products.
Physiological role ofdietary fibers
1.The ingested dietary fibers reach the large intestine in an essentially unchanged state
and thus add bulk to the feces. This play a role in defecation reflex by distending the
colon.
2.Speeds the passage of foods through the digestive system, which facilitates regular
defecation. This prevents constipation
Role of dietary fibers in prevention of diseases
1.Dietary fibers bind to bile acids in the small intestine, making them to get excreted in
the feces; this in turn lowers cholesterol levels in the blood.[3] Lowers total and LDL
cholesterol, which may reduce the risk of hypercholestremia, atherosclerosis and
cardiovascular disease
2.Dietary fibers increase food volume without increasing caloric content, providing
satiety which may reduce appetite. This helps to reduce obesity
3.Reduce the absorption of digested food stuffs. Delayed absorption of glucose regulates
blood sugar. This may lower risk of diabetes[63]
4.Insoluble fiber increases the rate at which wastes are removed from the body. This
means the body may have less exposure to toxic substances produced during digestion.
This gives protection against colorectal cancer
Therapeutic role of dietary fibers
The daily recommended intake of dietary fibers is about 25 to 35 gm/day
High fiber supplements have therapeutic role in following conditions:
In constipation
In spastic colon and diverticular disease
In diabetes and high cholesterol levels
3 MARKS

Describe the role of bile in digestion and absorption.

Role of bile in digestion:
Takes part in digestion of fat. The bile salts emulisify the fat i.e., reduce the
surface tension of fat there by breaking the fat globules into small size so that
water soluble enzymes (lipase) can act on it to digest.
Role of bile in absorption:
Takes part in absorption of fat. Bile salts form ‘Micelles’ in the centre of
 11

which the fat digested products are dissolved. Fat is carried in this form to the
intestinal villi through the chyme. The ‘ferrying’ action of bile salts plays an
important role in absorption of fat & fat soluble vitamins

Laxative role:
By increasing the motility of intestine, bile salts increase the passage of food through intestine

Bacteriostatic role:
Bile salts inhibit the growth of bacteria in the intestinal lumen

Choleretic action:
Bile salts stimulate the secretion of bile from the liver

Cholagogue action:
Bile salts stimulate the secretion of CCK which increases the expulsion of bile from gall bladder

Bile salts prevent gall stone formation by excreting cholesterol

-----------------------------------------------------------------------------------------------------------------------
 EXCRETION K.SENTHAMIL SELVI

10 MARKS

1. PROCESS OF URINE FORMATION

Every day kidney produces 1 – 2 liters of urine.
The mechanism of urine formation involves three processes:
a) Glomerular filtration
b) Tubular reabsorption
c) Tubular secretion
a) Glomerular filtration:
- Process by which the fluid along with the substances dissolved in it passes from the
glomerular capillaries in to the Bowman’s capsule is called glomerular filtration
- Blood cells and plasma proteins are not filtered
- Filtration occurs through filtering membrane which is made up of 3 layers – Fenestrated
capillary endothelium, basement membrane & podocytes (epithelial cells of Bowman’s
capsule) with filtration slits
- The fluid which gets collected in the capsule is called filtrate
- The amount of filtrate formed per minute (GFR – Glomerular Filtration Rate) is 125ml.
- This is mainly determined by net filtration pressure which depends upon the Starling forces
acting across the filtering membrane – Glomerular capillary hydrostatic & colloidal osmotic pressure,
Bowman’s capsule hydrostatic pressure
b) Tubular reabsorption:
- Passage of water and solutes from the filtered fluid in the kidney tubule into the blood is called
tubular reabsorption
- Solutes which are reabsorbed are nutrients (glucose & aminoacids), electrolytes (sodium,
potassium & chloride) & ions such as bicarbonates.
- Ihe modes of transport are both passive & active transport mechanisms
Reabsorption At Proximal Convoluted Tubule:
- Majority of reabsorption takes place at PCT as the surface area is increased due to presence
of brush border microvilli
- 65% of filtered water, sodium, chloride, potassium and other solutes
- 100% of glucose and aminoacids
- Sodium is reabsorbed by secondary active transport along with substances like glucose and
aminoacids
- This is followed by osmosis of water into the blood. The reabsorption of water at PCT is
called obligatory reabsorption of water
- The reabsorption of water and sodium are exactly proportional. So the fluid which leaves
the PCT is isotonic
Reabsorption At Loop of Henle:
- Loop of Henle consists of three segments - Descending limb, thin ascending limb &
thick ascending limb
- About 20% of filtered sodium and chloride, 15% of filtered water and cations such as K+,
Ca2+ and Mg2+ are reabsorbed in the Loop of Henle
- In the descending limb, water absorption occurs passively because of hypertonic
interstitial fluid in this part
- The thin ascending limb is impermeable to water. Limited passive absorption of sodium
and chloride occurs
- Thick ascending limb is impermeable to water. 20% of filtered sodium and chloride and
other cations are reabsorbed here by the following mechanisms:
 - Sodium, potassium – 2 chloride symporter mediated active transport of sodium
- Na+ - H+ antiporter mediated active reabsorption
- Paracellular passive reabsorption of Na+, K+, Ca2+ & Mg+
- Sodium reabsorbed here is the main driving force behind the countercurrent multiplier
system which concentrates sodium and urea in medullary interstitium
- As the reabsorption of solutes is not followed by water reabsorption, the fluid that leaves
this segment is hypotonic compared to plasma. Hence this segment is called diluting
segment
Reabsorption At Distal Convoluted Tubule (DCT) & Collecting Duct (CD)
- Approximately 7% of filtered NaCl & 8 to 17% of water is resbsorbed
- Late DCT & CD have two cell types - “P” (Principal) cells & “I” (Intercalated) cells
- Principal cells reabsorb Na+, Cl- & H2O
-
Intercalated cells reabsorb K+
- H2O reabsorption by principal cells is influenced by the hormone ‘ADH’-Anti Diuretic
Hormone. The reabsorption of water at this segment is called facultative reabsorption of
water.
-
Na+ reabsorption by principal cells is influenced by the hormone aldosterone which is
secreted from the adrenal cortex
c)Tubular Secretion:
The substances which escape filtration are transported from peritubular capillary in to the tubular fluid.
This transport is called tubular secretion.
Substances secreted:
-
H+ ions, K+, NH3-
-
Drugs
-
Pencillin
-
Creatinine
Secretion at PCT:
-
Organic anions & cations
-
Exogenous organic compounds
-
Certain drugs
-
H+ & NH3- are secreted. H+ is secreted in exchange with Na+ absorption. This is mainly
utilized for the absorption of HCO3-
Secretion at DCT & CD:
- K+ secretion by principal cells takes place. This is increased by hormone aldosterone
- H+ & NH3- are secreted. H+ secretion by intercalated cells is mainly responsible for
acidification of urine

2. GFR (GLOMERULAR FILTRATION RATE) & ITS REGULATION

Definition: The amount of filtrate that is formed by both the kidneys per minute is called
glomerular filtration rate
Normal value:
125 ml / minute
180 lt / minute
Factors regulating GFR:
GFR = Kf X EFP ( Kf – Filtration coefficient, EFP – Effective Filtration Pressure)
1. Kf = Filtration coefficient which denotes the efficiency of the filtering membrane to filter
the plasmaThis depends upon the following factors:
A. Thickness of filtering membrane: Inversely proportional to Kf . Increase in thickness
reduces Kf and thereby reduces GFR also
 B. Surface area of the membrane: Directly proportional to Kf & GFR
– the normal surface area is about 0.8 m2
– Contraction of the messangial cells compresses the glomerulus & reduces the area
of the membrane
C. Permeability of the membrane:
– Glomerular capillaries are 50 times more permeable than capillaries of skeletal
muscle.
– Permeability of the membrane is influenced by
– size of the particles filtered
– charge of the particles filtered
– Charge of the pores in the filtering membrane
- Particles below 4 nm size (both negative & positive charged) are filtered easily
- Particles above 8 nm size ( both negative & positive charged) are not filtered
- Particles of 4-8 nm size are filtered with difficulty (Positively charged particles
are filtered in this size range where as negatively charged particles are not
filtered)
Reason: The negative charge of the pores in the filtering membrane repel the
negatively charged particles
E.g – Albumin which is about 6 nm size is not filtered as it is negatively charged
particle
2. Effective Filtration Pressure: It is the net outward pressure which determined by forces
acting across the filtering membrane. These forces are called Starling forces.
Starling Forces acting across the filtering membrane:
1. Glomerular capillary hydrostatic pressure (PGC) = 45 mmHg (favors filtration)
2. Glomerular capillary osmotic pressure (πGC) = 25 mmHg (oppose filtration)
3. Bowmans capsular hydrostatic pressure (PBS) = 10 mmHg (oppose filtration)
4. Bowmans capsular osmotic pressure (πBS) = 0 (no effect on filtration)
EFP = Forces favoring filtration – Forces opposing filtration
EFP = PGC + πBS – PBS + πGC
= (45+0) – (10 + 25)
= 10 mmHg
Thus GFR = Kf X EFP
= 12.5 X 10
= 125 ml / minute
Conditions which alter Starling’s forces:

Glomerular Hydrostatic pressure (PGC):

i) Change in systemic blood pressure – drectly proportional to PGC

ii) Constriction of afferent arteriole – decreases PGC
iii) Constriction of efferent arteriole - increases PGC

Glomerular osmotic pressure (πGC):

i) Dehydration - increases πGC

ii) Malnutrition - decreases πGC
 Bowman’s capsular Hydrostatic pressure (PBS):

i) Ureteral obstruction – increases PBS

ii) Edema of the kiney inside the tight renal capsule – increases PBS

C) Renal blood flow:

- directly proportional to GFR. Renal bood flow is influenced by nerves, hormones like
catecholamines, angiotensin, dopamine & ANP

D) Sympathetic stmulation:
-strong acute sympathetic stimulation  constriction of both afferent and efferent
arterioles decrease in renal blood flow  decrease in GFR
-------------------------------------------------------------------------------------------------------------------------------
3. COUNTERCURRET MECHANISM OF CONCENTRATING THE URINE
Normal osmolarity of urine: 300 mosm/lt
Osmolarity of diluted urine: Upto 50mosm/lt
Osmolarity of concentrated urine: Upto 1200mosm/lt

Requirements for concentrating the urine:

1. ADH
2. Hyperosmolar medullary interstitium

Factors contributing to hyperosmolarity of medullary interstitium:

1. Countercurrent system
2. Reabsorption at DCT & CD
3. Urea recirculation

1. Countercurrent system: A system in which the inflow runs in parallel, in opposite direction
& in close proximity to the outflow
Components of countercurrent system in kidney:
a) Loop of Henle (contercurrent multiplier)
b) Vasarecta (countercurrent exchanger)
Role of Loop of Henle as countercurret multiplier in countercurrent mechanism:
To generate osmotic gradient & hyperosmolarity of medullary interstitium
Mechanism –
- Diffusion of water out of thin descending limb of LOH (This makes the fluid in the
tip of the loop to become more concentrated than the surrounding interstitum)
- Passive reabsorption of solutes from the hypertonic fluid in the tin ascending limb
(This helps in multiplication of interstitial osmolarity)
- Active reabsorption of sodium & chloride in the thick ascending limb of Loop of
Henle (This helps in building up of a higher interstitial osmolarity)
 Role of vasa recta as countercurrent exchanger in countercurrent mechanism:
To maintain the osmotic gradient & hyperosmolarity of medullary interstitium
Mechanism –
Descending limb of vasa recta :
- Solutes diffuse into the lumen
- Water diffuses out
- The osmolarity of blood increases from 300 milliosmoles to 1200 milliosmoles towards
the tip of vasarecta
Ascending limb of vasa recta:
- Solutes move out
- Water diffuses in
- The osmolarity of the blood decreases from 1200 milliosmoles to 300 milliosmoles from
the tip upwards
So the solutes are exchanged for water between the ascending and the descending limbs
of vasarecta. This maintains the hypertonicity of medulla

Loop of Henle & Collecting duct

2. Reabsorption in the DCT & Collecting duct:

 Sodium ions are actively absorbed from distal tubule and collecting duct under the
influence of aldosterone.
 Sodium ions are accompanied passively by chloride ions.
 This also increases the medullary osmotic gradient

3. Urea recirculation:
 Large amounts of urea is reabsorbed in the medullary collecting duct.
 The urea which moves into the interstitium is secreted in to the descending &
ascending limb of LOH.
  Again it is reabsorbed in the medullary collecting duct.
 This recirculation of urea before it is excreted in the urine helps to generate medullary
osmotic gradient
 Urea recirculation contributes 40% to hyperosmolarity of medullary interstitium
ADH: Increases urea reabsorption (This increases the interstitial osmolarity)
Increases water reabsorption (This makes the urine concentrated)
Renal blood flow: Slow rate of blood flow through the medulla causes retention of sodium in
the medullary interstitium

5 marks & 3 marks

1. SPECIAL FEATURES OF RENAL CIRCULATION
a. Renal Blood Flow (RBF): The normal blood flow to kidney is about 1200 ml. This
forms about 25% of cardiac output. Kidney receives the maximum blood flow next to
liver.
b. Portal circulation: An arteriole is interposed between two capillaries. Glomerulus
(capillary tuft) – Efferent arteriole – Peritubular capillary
c. High pressure system: The pressure in the glomerular capillaries is 45 mmHg. This is
much higher compared to the pressure in the systemic capillaries which is 30 mmHg.
This high pressure is the main driving force for glomerular filtration
d. Vasa recta: Longest capillaries in the form of hairpins. It runs parallel to LOH of
juxtamedullary nephron. It acts as countercurrent exchanger and maintains the osmotic
gradient from the cortex towards the inner medulla of kidney
e. Autoregulation: The ability of kidney to regulate its own blood flow is called
autoregulation. This helps the kidney to maintain the blood flow constant between a
systemic pressure of 90 – 220 mmHg. Autoregulation is achieved by myogenic principle
and tubuloglomerular feedback mechanism
f. Regional blood flow: Cortex receives the maximum blood flow whereas the inner
medulla receives the minimum blood flow
g. Arterio-venous difference of oxygen is minimal compared to the other organs
h. Renal O2 consumption is high
2. JUXTAGLOMERULAR APPARATUS
Juxta Glomerular Apparatus refers to the collection of specialized cells located very near to the
glomerulus
Components:
a) Juxtaglomerular cells
b) Macula densa cells
c) Mesangial cells
Juxtaglomerular cells:
- Modified smooth muscle cells of afferent arteriole
- Secrete renin
Macula densa Cells:
- Specialized tubular epithelial cells at DCT
- Act as chemoreceptors ( detect the changes in the concentration of sodium and chloride in
tubular fluid)
Messangial cells:
- Supporting cells present around glomerulus
- Contractile in nature
Functions of JG Apparatus:
1. JG cells secrete renin that activates Renin- Angiotensin system which takes part in
regulation of blood volume and pressure
2. Macula densa cells act as sensor in Tubuloglomerular feedback which takes part in
autoregulation of renal blood flow and GFR
3. JG apparatus helps to regulate the volume and osmolarity of ECF
4. It secretes erythropoietin which influences erythropoiesis

3. TUBULOGLOMERULAR FEEDBACK
Tubuloglomerular feedback refers to a mechanism which maintains a constant renal blood flow
& GFR inspite of the changes in mean arterial pressure.
It involves the feedback signals from DCT when there is a change in the concentration of sodium
chloride in the tubular fluid
Increased renal arterial pressure Decreased renal arterial pressure
↓ ↓
Increased RBF & GFR -- Decreased RBF & GFR +
↓ ↓
Increased NaCl concentration Decreased NaCl concentration
In the tubular fluid in the tubular fluid
↓ ↓
Sensed by macula densa cells Sensed by macula densa cells
↓ ↓
Feedback effect Feedback effect
(Release of adenosine) (Less release of adenosine)
↓ ↓
Constriction of afferent arteriole Dilation of afferent arteriole
 4. MICTURITION & CYSTOMETROGRAM
Micturition
Definition: The periodic complete voluntary emptying of the bladder is called micturition
Events involved:
- Micturition is basically a spinal reflex
- Influenced by higher centers
a) Micturition reflex
b) Voluntary control of micturition
c) Role of other muscles in micturition
a) Micturition reflex:
Stimulus: Filling of bladder by 300 to 400 ml of urine
Receptors: Stretch receptors in the detrussor muscle
Afferent: Sensory fibers in pelvic nerve
Center: S2, S3 & S4 of sacral segments
Efferent: Motor fibers in pelvic nerve
Effector organ: Detrussor muscle of urinary bladder & internal urethral sphincter
Response: Contraction of detrussor muscle of the bladder & relaxation of the urethral
Sphincter
(Excitation of parasympathetic afferent fibers causes inhibition of pudendal nerve 
relaxation of external urethral sphincter)
b) Voluntary control of micturition: (Role of supraspinal centers)
Supraspinal centers involved
Pons – Facilitate
Mid brain – Inhibits
Posterior hypothalamus – Facilitate
Limbic system -- Facilitate
Basal ganglia – Inhibits
Cerebral cortex – Inhibits
c) Role of other muscles:
Perineal & abdominal muscles help the emptying of bladder
Cystometrogram
Definition: Cystometrogram is a graphical record showing the relationship between the
intravesicular volume and pressure of urine in the urinary bladder
Phases of normal cystometrogram:
a) Phase Ia
b) Phase Ib
c) Phase II
a) Phase Ia : Initial rise in intravesicular pressure
- Rise in intravesicular pressure when about 50 ml of urine is collected in the
bladder
Basis: Filling of bladder with urine  stretching of bladder wall  contraction of
muscles of bladder wall  increase in pressure from 0-10 cm of H2O
b) Phase Ib: (Pleateau phase)
- No rise in the pressure (remains at 10 cm of H2O) till the bladder volume is
400 ml
 Basis: Can be explained by Laplace Law (Laplace law: P = 2T / R where ‘P’ is the
pressure, ‘T’ is the tension in the wall & ‘R’ is the radius of the bladder
Explanation:
Urine accumulation  increase in tension of the bladder wall, but there is
increase in radius of the bladder too (called as plasticity of the smooth muscle). The
effects of these two factors get neutralized & the pressure remains same.
c) Phase II: Steep rise in intravesicular pressure:
- Starts beyond 400 ml
- Tension of wall increases due to contraction of detrussor muscle, but
radius is not increased. So, the pressure increases (20 cm to 40 cm of
H2O)
-This stimulates voiding sensation (triggering the micturition reflex)

5. ACIDIFICATION OF URINE
- Normally the urine is acidic with a pH range from 4.5 to 6.0.
- Acidification of urine is brought about by H+ secretion in to the tubular fluid
- H+ secretion takes place throughout nephron.
- H+ secreted at PCT & LH is utilized for absorption of HCO3-. Does not contribute to
acidification of urine.
- H+ secreted in small amounts in the DCT & CD is responsible for the acidification of
urine
Mechanism Of H+ secretion:
BLOOD Tubular Epithelial Cell LUMEN

H2O + CO2
↓
H2CO3

HCO3- HCO3- H+ ATP H+ (In DCT)

H+
+
K K+ (In CD)
Fate of H+ ion in the lumen:
1. Reaction with HCO3-:
BLOOD TUBULAR CELL LUMEN

H2O + CO2 CO2 H2O

H2CO3 H2CO3

HCO3 - HCO3- H+ H+ + HCO3-

2. Reaction with Ammonia (NH3)

Blood Cell Lumen

Na Na + Cl
CO2 + H2O

H2CO3

HCO3- H+
H+ + Cl
Glutamine NH3 NH4Cl

NH3

3. Reaction with Na2HPO4 (Titratable acidity)

CELL
Blood Lumen

Na2HPO4

Na + NaHPO4
HCO3- +
H
H+ + NaHPO4
H2CO3
NaH2PO4
CO2 + H2O
 6.PLASMA CLEARANCE
Definition – Defined as the volume of plasma that is cleared of a substance in one minute by
excretion of that substance in urine
Clearance tests used to measure
GFR – Inulin clearance, Creatinine clearance & Urea clearance
RBF (Renal Blood Flow) – PAH clearance
Plasma clearance of Inulin :
- Inulin is freely filtered in the glomerulus
- neither reabsorbed nor secreted in the tubules
- so used to determine GFR
The formula used to calculate Inulin clearance:
UxV
---------- (U- Inulin concentration in urine(mg/ml), V- Volume of urine
P excreted(ml/mt), P- Plasma concentration of Inulin mg/ml)
Normal value – 125ml/min
Urea clearance:
Two types: Maximum & Standard urea clearance
Maximum urea clearance: Uu X V
----------- when the urine output is more than 2ml/m
Pu
Normal value = > 75 ml / minute
Standard urea clearance: Uu X√V
----------- when the urine output is less than 2ml/m
Pu
Normal value = 57 ml / minute
Plasma clearance of PAH:
- 90% cleared from plasma
- used to determine renal plasma flow
Formula to calculate RPF:
Clearance of PAH
--------------------------
PAH extraction ratio

Clearance of PAH: UxV

--------
P
Normal Value – 630 ml / minute
6. DIURETICS
Diuretics are the substances which cause diuresis (increase in urine volume). They either inhibit
the reabsorption of water or inhibit the reabsorption of solutes. Unreabsorbed solutes hold the
water in the tubules and cause osmotic dieresis
CLASSIFICATION SUBSTANCE SITE OF MECHANISM OF ACTION
ACTION

WATER DIURETIC Water - Inhibits ADH secretion

 Alcohol - Inhibits ADH secretion

Coffee & Tea - Increase GFR & decrease reabsorption

of Na+
Lithium ADH antagonists
& Democlocycline -

OSMOTIC
DIURETIC

1. Carbonic Acetazolamide PCT Inhibit the enzyme – carbonic anhydrase

anhydrase inhibitor Methazolamide Inhibit the reabsorption of Na+ & HCO3-

2. Loop Diuretic Furosemide (Lasix) Thick Ascending Inhibit the Na+ - K+ - 2Cl- Cotransporter
Bumetanide Limb of LH Inhibit the reabsorption of Na+
Ethacrynic acid

3. Thiazide Hydrochlorothiazide Early DCT Inhibit Na+- Cl- symport

Chlorothiazide
Trichlormethiazide
Metolazone

4. K+ sparing Spironolactone Collecting duct Aldosterone antagonist

diuretics Amiloride Block the epithelial Na+ channels
Triamterene

1. CORTICAL & JUXTAMEDULLARY NEPHRON

CORTICAL NEPHRON JUXTAMEDULLARY NEPHRON

Location of Glomerulus Cortex Near junction of cortex and medulla
Number 85% 15%
Loop of Henle Short Long
Vasarecta Absent Present
Fluid flow Faster Slow
Major Function Excretion of waste Concentration of urine by
products countercurrent system
 2. FILTERING MEMBRANE COMPLEX
- Filtration membrane is otherwise called as filtration barrier or glomerulo-capillary
membrane
- It is the membrane through which the fluid from the plasma of glomerular capillaries pass
in to the Bowman’s Capsule.
Components:
1. Capillary endothelium:
– Fenestrated (contains pores of 70-90 nm diameter)
– Freely permeable to water, small solutes & small proteins
2. Basal lamina:
– Union of glomerular capillary basement membrane & Bowman’s capsule
basement membrane
– Consists of glycoproteins & mucopolysaccharides

– Prevents filtration of proteins as strong negative charges are associated with

proteoglycans in the basal lamina
3. Bowman’s Capsule Visceral Epithelium:
– Formed by special cells called podocytes
– Podocytes have finger like processes called pedicels
– The pedicels interdigitate to cover the basement membrane & they are separated
by gaps called filtration slits (25 nm diameter)

3. INNERVATION OF URINARY BLADDER

Sympathetic nerve supply (Hypogastric nerve) – T12 to L2
Site of supply: Trigone of bladder & internal urethral sphincter
Functions:
a) Carry pain sensation from bladder
b) On stimulation, causes relaxation of bladder & contraction of internal
urethral sphincter (called as nerve of filling)
Parasympathetic nerve supply (Pelvic nerve) – S2, S3 & S4
Site of supply: Trigone of bladder & internal urethral sphincter
 Functions:
a) Carry stretch and pain sensation from bladder
b) On stimulation, causes contraction of bladder & relaxation of internal
urethral sphincter (called as nerve of emptying)
Somatic nerve supply (Pudendal nerve) – S2, S3 & S4
Site of supply: External urethral sphincter
Function:
On stimulation, causes contraction of external urethral sphincter (voluntary
control of micturition)

WATER REABSORPTION
Amount of filtrate formed = 125 ml/minute or 180 lt/day
Amount of filtrate reabsorbed = 124 ml / minute or 178.5 lt/day
Amount of fluid excreted in urine = 1.5 lt /day
Reabsorption at PCT (65% of filtered fluid)
Mechanism: Pumping of sodium out of tubular epithelial cells by Na+-K+ ATPase pump
↓
Passive diffusion of Na+ along with other solutes
↓
Hypoosmolarity of tubular fluid
↓
Osmosis of water into the cells
(through water cannels called “aquaporins”)
This type of osmosis of water in PCT is called “obligatory water reabsorption”
Reabsorption at LH: About 15% of filtered fluid is absorbed at the thick ascending limb of
Loop of Henle
 Mechanism: Diffusion independent of solute reabsorption
Reabsorption at DCT & CD: (5% at DCT & 14.7% at CD)
Mechanism: Osmosis of water through aquaporins is influenced by the hormone ADH (Anti
Diuretic Hormone) secreted from posterior pituitary. This type of water
reabsorption at DCT & CD under the influence of ADH is called
“ facultative water reabsorption”.
4. PROTEINURIA
Presence of protein in urine more than the usual amount (100 mg/dl) is called proteinuria
Most common protein found is albumin. So the defect is commonly called albuminuria
Cause:
- Usually the proteins are not filtered. As they are negatively charged, they are repelled by
negative charges at the pores of glomerular capillary wall
- In cases of renal diseases like nephritis, the negative charges are dissipated.
- The permeability of the glomerulus to protein is increased.
Effects:
- Loss of protein from plasma leads to hypoproteinemia
- Hypoproteinemia leads to decreased colloidal osmotic pressure
- Decreased colloidal osmotic pressure  decreased plasma volume & edema
Orthostatic proteinuria:
Proteinuria in standing position
5. AUTOREGULATION
Definition: Ability of the kidneys to regulate their own blood flow inspite of the changes in
systemic blood pressure is called autoregulation
- Seen between a pressure range of 90 – 120 mmHg
- Seen even after cutting of renal nerves & in an isolated kidney perfused with isotonic saline
Mechanisms:
a) Myogenic theory
b) Tubuloglomerular feedback
Myogenic theory:
Increase in blood pressure  stretching of smooth muscle of afferent arteriole 
contraction of smooth muscle  vasoconstriction  decrease in blood flow
Tubuloglomerular feedback (also called as chloride feedback theory):
Mechanism: Increase in blood pressure  Increased renal blood flow  Increased GFR
 increased chloride concentration at macula densa  increased
absorption of chloride at macula densa  increased absorption of chloride
at macula densa  release of adenosine by JG apparatus  constriction of
afferent arteriole & contraction of messangial cells  decrease in RBF &
GFR
Decrease in in blood pressure  Decreased renal blood flow  Decreased
GFR  decreased chloride concentration at macula densa

Vasoconstrictor mechanism Vasodilator mechanism

(production of angiotensin II & activation of (Release of dopamine & NO
Sympathetic fibers) Less release of adenosine)
(The opposing effect of the above mechanisms maintains the constant blood flow to the
kidney)
 1

ENDOCRINE K.SENTHAMIL SELVI

10 marks
1. THYROXINE
Synthesis:
1. Synthesis of thyroglobulin by follicular cells
2. Trapping of iodide by Na+ - I symport
3. Oxidation of iodide to iodine
Peroxidase
Iodide Iodine
4. Iodination of tyrosine --- MIT - Monoiodotyrosine (iodine at 3rd position) &
DIT - Diiodotyrosine (iodine at 3rd & 5th position)
5. Oxidative Condensation:
MIT + DIT T3 (Triiodothyronine)
DIT + DIT T4 (Thyroxine)
Secretion:
Thyroglobulin molecule (with MIT, DIT, T3 & T4) in the lumen of follicle
Endocytosis

Follicular cell

Fuse with lysosome

Lysis of thyroglobulin & release of MIT, DIT, T3 & T4 in the cytoplasm

T3 & T4 diffuse into the blood stream and reach the target organs
Mechanism of action:
T3 & T4 diffuse into the cell

Bind with receptors in the nucleus

Forms hormone –receptor complex

Binding of complex to DNA

Transcription of mRNA

Diffusion of mRNA to cytoplasm

Synthesis of new proteins (structural & functional)

(Also increase the number & size of mitochondria, rate of ATP synthesis &
activity of Na-K ATPase)

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Actions:
I. Effect on metabolism:
1. General metabolism
2. Carbohydrate metabolism
3. Protein metabolism
4. Fat metabolism
II. Effect on growth
1. Body growth
2. Growth differentiation
3. Neural growth
III. Effect on systems
Effect on metabolism:
1. General metabolism :
– stimulates metabolism of the tissues (maintains the BMR)
– increases O2 consumption
– increases heat production (Thermogenic effect)
Hypothyrodism – Low BMR & intolerance to cold
Hyperthyrodism – High BMR & intolerance to heat
2. Carbohydrate metabolism: Causes hyperglycemia by
- increasing glucose absorption in the intestine
- increasing glycogenolysis
- increasing gluconeogenesis
- Increasing insulin breakdown
Hypothyrodism – Hyperglycemia
Hyperthyrodism – Hypoglycemia
3. Protein metabolism:
Normal doses – Protein synthesis
Large doses - Proteolysis
Hyperthyrodism – Thin muscles & loss of weight
4. Fat metabolism:
- Increases cholesterol synthesis as well as breakdown & excretion
- As the breakdown is greater than the synthesis, thyroxine lowers the blood
cholesterol level
- Also causes lipolysis & increases free fatty acids & its oxidation
Effect on Growth
a. Body growth: Stimulates body growth directly by stimulating metabolism
and indirectly by increasing the production of GH (Growth Hormone) & IGF
(Insulin like Growth Factor)
b. Growth differentiation: Stimulates tissue differentiation and maturation
c. Neural growth : Thyroxine stimulates the growth of brain

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Effect on Systems:
a. CNS:
- Thyroxine maintains the normal growth & activity of CNS
- stimulates the growth of brain in fetus & newborn (mainly cerebral cortex, basal
ganglia & cochlea)
- increases the branching of dendrites, number of synapses & myelination
Hypothyroidism: slow mental activity, low memory power, slow
reflexes & excessive sleep
Hyperthyroidism: Increased nervous excitability  irritability,
emotional, restlessness & anxiety
b. CVS:
Thyroxine acts on SA Node and cardiac muscle & maintains normal heart
rate, cardiac output & blood pressure
Hyperthyroidism – Tachycardia & hypertension
Hypothyroidism – low heart rate & blood pressure
c. Blood: Stimulates erythropoiesis
d. Muscle: Maintains normal muscle mass & strength.
Hypothyroidism – Muscular weakness – due to depression of BMR
Hyperthyroidism - Muscular weakness – due to breakdown of muscle
proteins
e. Bones: Facilitates excretion of Ca2+ & PO4- in to the urine.
Hyperthyroidism – mobilization of calcium & Phosphate from bone 
osteoporosis
f. Skin: Maintains the normal texture.
Hypothyroidism – Dry & scaly skin
Hyperthyroidism – Soft , warm & wet skin
g. GIT: Stimulates a) Appetite & food intake b) Motility & secretions
Hyperthyroidism – Diarrhea
Hypothyroidism – constipation
h. Vitamins: Thyroxine converts β carotene into vitamin A. It is also required for
activation of B complex vitamins
i. Excretion: Maintains the normal renal blood flow of, GFR & function of
nephron
j. Endocrine: Increases the sensitivity of the tissues to catecholamines. Acts with
catecholamines to stimulate thermogenesis, lipolysis,
glycogenolysis & gluconeogenesis.
k. Reproduction: Thyroxine is required for normal sexual development &
gonadal function.
Hypothyroidism:
Children – Hypogonadism & absence of secondary sexual characteristics
Women – Reduced fertility, loss of libido & menstrual abnormalities
Men – Oligospermia, impotency and sterility
l. Respiration: Stimulates respiration & maintains normal ventilation

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2. GLUCOCORTICOIDS (CORTISOL)
Adrenal cortex:
Layer - Hormone
1. Zona glomerulosa - Mineralocorticoid (e.g Aldosterone)
2. Zona fasciculata - Glucocorticoid (e.g Cortisol)
3. Zona reticularis - Androgens (e.g Androstenedione)

Actions Of Cortisol:
1. Effect on Metabolism:
a. Carbohydrate metabolism:
Increases blood glucose level by
- Stimulating gluconeogenesis in liver
- Inhibiting glucose uptake & utilization by the tissues
b. Protein metabolism:
Decreases tissue protein & increases plasma amino acids
- Reduces protein synthesis in all tissues except liver
- Facilitates breakdown of tissue proteins
c. Lipid metabolism:
Increases the free fatty acid level in the blood & also increases the oxidation
of fatty acids
d. Mineral metabolism: Promotes retention of K+, Ca2+ & PO4-
e. Water metabolism: Facilitates water excretion in to the urine
2. Effect on immunity:
a. Anti-inflammatory effect: Cortisol prevents inflammation by
-
Stabilizing the lysosomal membrane
-
Decreasing the permeability of the capillaries
-
Preventing the synthesis of vasoactive substances like histamine
-
Inhibiting the migration of leucocytes to the affected area
b. Antiallergic effect: Cortisol prevents allergic reactions by
-
Inhibiting the formation of histamine from histidine
-
Reducing the number of basophils and mast cells
c. Immunosuppressive effect: Cortisol suppresses the immune system by
-
Decreasing the number of lymphocytes
-
Suppressing the activity of lymphoid tissue
d. Autoimmunity: Cortisol suppresses the production of autoantibodies
3. Effect on stress: Cortisol avoids the harmful effects of stress by
-
Releasing fatty acids for providing energy
-
Increasing blood flow to the tissues to provide O2 supply and remove the
metabolic products
-
Minimizing the effect of stress on tissues
4. Effect on systems:
a. Blood:
- Decreases the number of circulating eosinophils, lymphocytes & basophils
- Increases the number of RBCs, platelets & neutrophils
- Inhibits the proliferation of lymphoid tissue
- Maintains the normal blood volume

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b. Muscle:
- Causes destruction of muscle proteins releasing amino acids
c. Bones:
- Inhibits bone formation & enhances bone resorption
- Inhibits absorption of calcium & phosphate in intestine by opposing the effect of
vitamin D
d. GIT:
- Stimulates HCl and enzyme secretion from the gastric mucosa
- Cortisol produces peptic ulcers when given in excess
e. CVS:
- Positive ionotropic effect on heart and increases cardiac output
- Enhances the vasoconstrictor effect of catecholamines and increases BP
f. CNS:
- Maintains the normal functioning of nervous system
- Influences the sleep pattern, mood, cognition and reception of sensory input
5. Effect on Fetus:
- Stimulates the secretion of surfactant
- Helps in maturation of pancreatic beta cells & enzymes in the liver
- Play a role in the change from foetal Hb to adult Hb
6. Permissive role:
- Enhances the calorigenic, lipolytic, broncodilatory and vasoconstrictor effects of
catecholamines
- Enhances the effect of growth hormone on growth
CLINICAL USES OF GLUCOCORTICOIDS:
Glucocorticoids are used as drugs:
- To suppress rejection in organ transplantation
- To suppress the antibody formation in autoimmune diseases
- To suppress inflammatory reactions in conditions like Rheumatoid arthritis
- To suppress allergic reactions
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3. CALCIUM HOMEOSTASIS
Calcium Distribution in the body

1000 mg (0.1%)

ECF
1 Kg (99%)
g

BONE

11 gm (0.9%)

TISSUES
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Total content of calcium in the body: 1200 g

Bones & teeth - 1000 gm (99%)
Extracellular fluid – 1 gm (0.1%)
Intracellular fluid – 11gm (0.9%)
Normal Plasma calcium level in the body – 9 to 11 mg / 100 ml of blood

Hormones regulating plasma calcium level:

1. Parathormone from parathyroid gland Influence blood calcium
2. Calcitonin from thyroid gland and phosphorous by
3. Vitamin D (1, 25 – dihydrocholecalciferol) acting on bone, kidney
& GIT
ACTIONS OF PARATHORMONE:
Increases blood calcium level and decreases blood phosphate levels
On Bones: PTH causes resorption of bones in two phases:
Rapid phase: PTH binds to receptors on the membrane of osteocytes &
increases the cyclic AMP. This causes entry of calcium in to
the cell. The accumulated calcium activates the calcium pump
allowing the calcium to diffuse out of osteocytes into the
interstitial fluid.
Slow phase: PTH stimulates osteoclasts which release proteolytic, lysosomal
enzymes and acids. The enzymes digest organic matrix and
the acids dissolve bone salts. All dissolved substances
including Calcium enter ECF. Phosphate is also released
On Kidney: PTH facilitates the reabsorption of calcium from the thick ascending
limb of Loop of Henle & distal nephron and inhibits the absorption of
Phosphate from PCT
On GIT: PTH increases absorption of calcium and Phosphate from the gut. This
effect is mediated through 1, 25 (OH)2 cholecalciferol
On lactating mammary glands: PTH decreases the calcium content of milk,
sweat and GIT fluids and thus conserves Ca2+ in the body fluids.
ACTIONS OF CALCITONIN:
- Secreted from parafollicular or “C” cells of thyroid gland.
- Calcitonin decreases calcium as well as phosphate in plasma
1. On Bone:
a) Calcitonin antagonizes the effect of PTH on bone
b) It increases the calcium deposition to bone
c) It increases osteoblastic activity and decreases the osteoclastic activity
2. On Kidney:
a) Facilitates excretion of calcium and phosphate.
b) Decreases the formation of 1,25 Di Hydroxy Cholecalciferol
3. On GIT:
- Inhibits absorption of calcium & phosphate.
Clinical uses of Calcitonin:
- Given for relieving bone pain and maintaining normal bone structure
- Protects the bones of the mother from excess calcium loss during pregnancy and
lactation

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ACTIONS OF VITAMIN D:
- Vitamin D increases blood Calcium & Phosphate levels
1. On GIT:
- Vitamin D binds to a cytoplasmic receptor in the intestinal epithelial cells and
reaches the nucleus. Acting on DNA it increases the production of calcium-
binding protein (calbindin).This protein increases the absorption of both calcium
and phosphate, Thus 1,25 dihydroxy cholecalciferol (vitamin D) increases the
serum levels of both calcium and phosphate
2. On Bones:
- Acting on DNA it increases the production of calcium-binding protein. This
inturn increases the entry of calcium in to the osteocytes. The increased
intracellular calcium leads to accumulation of lactic acid and citric acid. These
acids dissolve the bone salts and calcium is released (bone resorption). But
Vitamin D also increases the calcium deposition in the bones.
3. On kidney:
- Vitamin D increases the reabsorption of calcium and phosphate in the kidney
tubules
OTHER HORMONES:
Estrogen:
- Elevate plasma calcium and phosphate levels
- Stimulates osteoblastic activity and inhibits osteoclastic activity
- Causes calcification and ossification of bones
- Favours bone formation and bone growth especially at the time of puberty
Cortisol:
- Depresses bone formation by inhibiting the synthesis of protein matrix
- Increases osteoclasts formation
- Causes destruction of protein matrix
- Decreases calcium absorption from the gut and reabsorption from the kidney
tubules

4. GLUCOSE HOMEOSTASIS
- The normal fasting blood glucose level is 70-100 mg/100 ml of blood
- This is mainly regulated by hormones secreted from Islet tissue of pancreas
Pancreatic hormones which regulate blood glucose level are:
1) Insulin from β cells
2) Glucagon from α cells
ACTIONS OF INSULIN:
Effect on membrane:
1) Facilitates the entry of glucose in to all the cells except the brain, liver & RBC
there by increases the utilization of glucose by the tissues
2) Promotes the entry of aminoacids and fatty acids into the cells
3) Also facilitates the entry of K+ into the cells.
Effect on Metabolism:
1) Carbohydrate metabolism:
- Insulin increases peripheral utilization of glucose by the tissues by stimulating the
enzymes of glycolysis

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- Promotes entry of glucose into adipose tissue and muscle

- Promotes glycogenesis (synthesis of glycogen from glucose)
- Inhibits glycogenolysis (breakdown of glycogen to glucose0
- Inhibits gluconeogenesis by inhibiting the enzymes participating in it.
2) Protein metabolism:
- Insulin promotes entry of aminoacids into the cells
- Facilitates protein synthesis
- Inhibits proteolysis
3) Fat metabolism:
- Insulin facilitates the entry of free fatty acids into adipose cells.
- Incorporates FFA into neutral fat (triglycerides) in adipose tissue
- Promotes lipogenesis
- Inhibits lipolysis
(In diabetes mellitus, there is increased lipolysis & FFA in the blood. The FFA are
converted into ketone bodies)
ACTIONS OF GLUCAGON:
1. Stimulates glycogenolysis through cAMP. The enzymes involved in the process
are stimulated
2. Stimulates gluconeogenesis by stimulating the enzymes participating in it
3. Stimulates the hormone sensitive lipase enzyme which causes lipolysis and
increases the plasma free fatty acids
4. Glucagon has calorigenic action. It may be due to increased hepatic deamination
of aminoacids
OTHER HORMONES:
1. EPINEPHRINE AND NOREPINEPHRINE: Increase blood glucose by
- Stimulating glycogenolysis in liver and muscle. This increases blood glucose and
lactate levels.
- These hormones activate the enzyme phosphorylase which participates in
glycogenolysis
2. GLUCOCORTICOIDS: Increase blood glucose level by
- Stimulating gluconeogenesis. Glucocorticoids cause breakdown of proteins and
make the aminoacids available for gluconeogenesis
- Decrease the uptake of glucose by the tissues
5.GROWTH HORMONE
• A polypeptide containing 188 aminoacids
• Secreted from somatotropes (acidophilic cells ) of anterior pituitary
ACTIONS OF GROWTH HORMONE
Direct effects - growth hormone binding its receptor on target cells
Indirect effects - through Somatomedin a polypeptide secreted from the liver in
response to growth hormone.
Somatomedins are Insulin – like Growth Factor I & II ( IGF I & II)
• Effect on growth
• Effect on metabolism
• Effect on milk production
• Effect on erythropoiesis & lymphopoiesis

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Effect on growth
on cartilage
stimulates proliferation of chondrocytes (cartilage cells), resulting in bone
growth
on bone
stimulates osteoblastic activity (conversion of chondrocyte into osteocytes)
on muscle
increases the skeletal muscle mass by stimulating both the differentiation and
proliferation of myoblasts. It also stimulates amino acid uptake and protein
synthesis in muscle.
on other organs
stimulates the growth of visceral organs like kidney, liver, heart etc.,
Effect on metabolism
On carbohydrate metabolism
Hyperglycemic hormone (anti insulin effect)- increases blood glucose by
- decreasing peripheral utilization of glucose
- increasing formation of glucose (gluconeogenesis)
So GH is a diabetogenic hormone
Proof: Pancreatectomy in an animal diabetes
Hypophysectomy in that animal  diabetes comes under control
(Houssay animal)
On protein metabolism
Protein anabolic hormone – increases protein synthesis by
- increasing the rate of aminoacid uptake into the cells
- Stimulating mRNA transcription from DNA
- increasing protein synthesis in ribosomes
On fat metabolism:
- stimulates lipolysis & increases free fatty acids
On mineral metabolism
- increases renal absorption of Ca2+, PO4- & Na+.
- promotes the retention of Na+, K+ & Cl-
(By increasing Ca2+, GH promotes bone mineralization in growing children)
Effect On lactation:
enhances milk production in mammary gland
Efect On erythropoiesis:
stimulates erythropoiesis by increasing the secretion of erythropoietin from
kidney
Effect On lymphopoiesis:
stimulates the growth of lymphoid tissue & also proliferation of lymphocytes
Effect On gonads
stimulates the growth of gonads

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6.Anterior Pituitary Hormones & their functions

1) GH (growth hormone)/STH (somatotropic hormone)
Stimulates cell division & differentiation & there by influences physical growth
2) TSH (thyroid stimulating hormone) / Thyrotropin
Stimulates the growth of thyroid gland & secretion of thyroid hormones
3) ACTH (adrenocorticotropic hormone)/ corticotropin
stimulates adrenal cortex to secrete hormones
4) FSH (follicle stimulating hormone)
Stimulates development of ovarian follicles, secretion of ovarian sex hormones,, and sperm
production (spermatogenesis)
5) LH (luteinizing hormone)
stimulates ovulation, stimulates corpus luteum to secrete progesterone, stimulates testes to
secrete testosterone
6) PRL (prolactin)
stimulates mammary gland development, synthesis and secretion of milk

7.Posterior pituitary Hormones

1. Antidiuretic hormone (ADH) or vasopressin (SUPRAOPTIC NUCLEUS)
2. Oxytocin (PARAVENTRICULAR NUCLEUS)
1. ADH (vasopressin)
A polypeptide containing 9 aminoacids is produced mainly in SupraOpticNucleus of
hypothalamus.
ADH activates (2) second messenger systems:
1. cAMP
2. IP3/Ca2+
Action of ADH
1.  water re-absorption (retention) by distal tubules & collecting ducts of the kidneys .
This effect is regulated by V2 receptors, through the action of cAMP
2. In large doses, acts on blood vessels and causes vasoconstriction
This effect is regulated by V1 receptors, through the action of IP3/Ca2+.
Regulation of ADH secretion
-  in osmolarity of the ECF as in dehydration shrinkage of osmoreceptors in the
hypothalamus  stimulation of osmoreceptors   ADH secretion from SON of
hypothalamus
-  blood volume (Hypovolemia)   stimulation of mechanoreceptors in the great
arteries (aorta & carotids) & right atrium   ADH secretion from SON of
hypothalamus
2. Action of oxytocin
1.Contraction of smooth muscles of the uterus during parturition  enhance labor.
2.Ejection of milk from mammary glands as a reflex in lactating women.
3.Act on non pregnant uterus to facilitate sperm transport in the female genital tract upto
fallopian tube where fertilization takes place
4. Men   at the time of ejaculation (causes contraction of smooth muscles of vas deferens
propelling sperm towards urethra)

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5 marks
1. Hypothalamic control of pituitary /
hypothalamo-hypophyseal portal system & tract
Control of anterior pituitary
Hypothalamus (Arcuate nucleus)

Releasing hormones & Inhibitory hormones

Through
Stimulates Inhibits Hypothalamo - hypophyseal
portal system
Anterior pituitary
Hypothalamo - hypophyseal portal system
- Releasing & Inhibiting hormones are secreted into the median eminence
region of hypothalmus

- Hormones enter into the capillary plexus of superior hypophyseal artery

- Transported through long portal veins to anterior pituitary
- Exit of hormones from the secondary capillary plexus in the anterior pituitary
- Regulation of secretion of anterior pituitary hormones
Releasing & Inhibiting hormones
Growth hormone releasing hormone
Growth hormone inhibiting hormone
Thyrotropin releasing hormone
Corticotropin releasing hormone
Gonadotropin releasing hormone
Prolactin releasing hormone
Prolactin inhibiting hormone
Control of posterior pituitary
Supraoptic nucleus & Paraventricular nucleus (Hypothalamus)
Hypothalamo- hypophyseal tract

Posterior pituitary
Hypothalamo- hypophyseal tract
Cellbodies of neurosecretory cells of supraoptic & Paraveentricular nuclei of
hypothalamus

Secrete oxytocin & vasopressin which travel down the axons in neuro secretory granules

Axons pass through the infundibular stem & form a series of dilated nerve endings in
neurohypophysis called as “Herringbodies”

Hormones are stored in the nerve terminals in the posterior pituitary & released by
exocytosis on stimulation of cell bodies

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2.Aldosterone functions
• A mineralocorticoid secreted by zona glomerulosa

1. REGULATION OF PLASMA ELECTROLYTES

SODIUM:
a. Increases the reabsorption of sodium in the DCT & CD of kidney tubules (by
activating Na+-K+ ATPase pump & increasing the number of epithelial sodium
channels)
b. Increases the absorption of sodium in the colon

POTASSIUM:
 Increases excretion of potassium into the urine. So the plasma potassium
level decreases

2. REGULATION OF ECF VOLUME:

a. Increases sodium absorption. This is followed by water absorption  Increase in
ECF volume

3. REGULATION OF BLOOD VOLUME & PRESSURE:

Renin-angiotensin system:

4. HYDROGEN ION SECRETION:

By increasing Na+ reabsorption, it causes H+ secretion
5. Mild glucocorticoid activity and influences Carbohydrate metabolism
6. Takes part in stressful conditions

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3. Acromegaly
Clinical condition caused by hypersecretion of GH in adults after the closure of epiphysis
Features:
- Acral (peripheral) – hands & feet & Megaly – large. So large hands & feet
- Acromegalic face (coarse facial features) –due to overgrowth of malar, frontal & facial
bones
• Thick lips
• Macroglossia ( large tongue)
• Broad & thick nose
• Prominent eyebrows
• Thickened skin
• Prognathism (protrusion of mandible)
- gorilla like appearance with kyphosis (forward bending due to improper growth of
vertebrae)
- increased amount of body hair
- enlargement of visceral organs
• Cardiomegaly
• Hepatomegaly
• Splenomegaly
• Renomegaly
- bitemporal hemianopia (inability to see objects in temporal fields of both the eyes) due to
damage of binasal fibers of optic chiasma caused by compression of pituitary tumor
over optic chiasma
- Hyperglycemia (about 25% of acromegalic patients are diabetic)
Reason - Hyperglycemia excess insulin secretion  over activity of beta
cells of pancreas  exhaustive degeneration of beta cells 
deficiency of insulin  diabetes mellitus
- Gynacomastia (development of breast in males)
- Excessive sweating & hypertension due to increased sympathetic activity
Treatment :
- Surgical removal of pituitary tumour
- Administration of somatostatin
4. Diabetes insipidus.
A clinical condition caused by inadequate secretion / action of ADH
a. Neurogenic (central, or cranial) – Inadequate secretion of ADH
Problem in Hypothalamus or Post pituitary gland
Treatment: ADH
b. Nephrogenic
Resistance of V2 receptors in collecting ducts of the kidneys.
Symptoms:
Polyurea  20 L/day (N  1.5 L/d)
Polydipsia,
Dehydration
 specific gravity of urine
Treatment:
Drugs – Desmopressin, Clofibrate ( increases ADH secretion) &
Chlorpropamide (increases renal response to vasopressin)

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5.CRETINISM
A clinical condition caused by hypo secretion of thyroxine from thyroid glands in
children
Features:
- Physical & mental retardation
- Short stature
- Protruded tongue
- Macro-glossia (enlargement of tongue)
- Pot belly
- Lethargic attitude
- Puffy face
- Dry coarse & scaly skin
- Scanty hair
- Delayed developmental milestones
- Infantile facial features
- Obese & stocky
- Flat nose
- Hypogonadism
Lab findings-
- Low BMR(less than 50%)
- Radio-active iodine uptake low
Treatment:
- Administration of iodine or thyroxine
6.MYXOEDEMA
A clinical condition caused by hypo secretion of thyroxine from thyroid glands in adults
Features:
- Puffiness of the face
- Obesity and weight gain
- Lethargy (tiredness)
- Slow mentation
- Intolerance to cold
- Skin – dry & coarse
- Non-pitting edema
- Hoarse voice
- Hypoglycemia
- Anemia
- Hypotension
- Low BMR
- High cholesterol
- Menstrual disorders
- Excessive sleep (somnolence)
Tests to confirm the diagnosis: (Thyroid Function Tests)
1) Radioactive iodine uptake (Low)
2) Estimation of total serum thyroid hormones level (T3 & T4) - Low
3) TSH level – High

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4) Determination of BMR – Low

Treatment:
- Levothyroxine (oral thyroxine) – Life long
7.HYPERTHYRODISM / THYROTOXICOSIS
A clinical condition caused by hypersecretion of thyroxine from thyroid glands
Features:
- Inability to sleep (insomnia)
- Frequent bowel movements
- Excessive sweating and heat intolerance
- Loss of weight inspite of good appetite
- Increased pulse rate
- Hypertension
- Fine tremors visible in outstretched hands
- Voracious appetite
- Thirst
- Palpitations
- Nervousness
- Anxiety
- Muscle weakness
- Soft, warm & wet skin
- Polycythemia
- Hyperglycemia
- Low cholesterol
Tests to confirm the diagnosis: (Thyroid Function Tests)
1) Radioactive iodine uptake (high)
2) Estimation of total serum thyroid hormones level (T3 & T4) - High
3) TSH level - low
4) Determination of BMR - High
EXOPHTHALMIC GOITRE: Above features + Following features
- Goitre : Warm swelling in the neck that moves with deglutition
- Exophthalmos – Protrusion of eyeball (due to swelling of extraocular muscles &
increase in retrobulbar pressure. This is caused by accumulation of
glycosaminoglycans at retrobulbar region of the orbit. Glycosaminoglycans are
produced by infiltrated fibroblasts)
- Retraction of upper eyelids
8.TETANY
A clinical condition caused by hypocalcemia
Causes:
1. Hypoparathyrodism
2. Vitamin D deficiency
3. Alkalosis
Features:
- Numbness and tingling sensation especially in face and extremities.
- Stiffness of hands
- Muscular cramps
- Accoucher’s hand or carpopedal spasm: There is flexion at elbow, wrist &

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metacarpophalangeal joints & extension at interphalangeal joints .

- Laryngeal stridor: Loud noisy sound during inspiration
Latent Tetany (features that develop on examination)
Trousseau’s sign: Development of carpopedal spasm when BP cuff is applied over
the arm and arresting the blood flow temporarily
Chvostek’s sign: quick contraction of the ipsilateral facial muscles by tapping over
the facial nerve at the angle of the jaw.
Erb’s sign: Contraction of hand muscles on applying galvanic current
Diagnosis: Estimation of plasma calcium level
Treatment: Providing calcium rich food & Injection of calcium gluconate
9.ADDISON’S DISEASE
Addison’s disease is due to adreno cortical insufficiency (chronic deficiency of
both mineralocorticoids & glucocorticoids)
Features:
- Hyponatremia
- Hyperkalemia
- Inability to withstand any stress
- Marked pigmentation on the skin
- Chronic hypotension (low BP)
- Anemia
- Muscle weakness & easy fatiguability (due to hyperkalemia & hypoglycemia)
- Hypotension
- Hypovolemia
- Less resistance to stress and infection
- Anorexia, nausea, vomiting and weight loss
Diagnosis:
serum Cortisol, urinary 17-OHCS, plasma K, Na & serum glucose
Treatment:
Hormone replacement therapy (Administration of mineralocorticoid &
Glucocorticoid)
10. CUSHING SYNDROME
Excess secretion of glucocorticoids leads to Cushing syndrome.
Features:
- centripetal distribution of fat – truncal obesity with thin arms & legs but excess of
fat accumulates on the face, abdomen, buttocks & back of the neck
- Moon face
- Buffalo hump
- Obese but poor muscular development (feeling very weak)
- Poor wound healing capacity
- Pendululous abdomen
- Reddish striae on the skin of abdomen & upper thigh
- Hyperglycemia
- Hirsutism (excess growth of hair over the face)
- Polycythemia, lymphocytopenia & eosinopenia
- Muscular wasting
- Hyperglycemia

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- Hypertension
- Peptic ulcer
- Mental disturbances
Diagnosis:
– ACTH stimulation test
– Dexamethasone suppression test
– Estimation of 17-hydroxy corticosteroids
Treatment: Removal of pituitary or adrenal gland in respective tumour.
11. ADRENOGENITAL SYNDROME / VIRILISM
Increased secretion of adrenal androgens with concomitant decreased secretion of
glucocorticoids & mineralocorticoids
Features in females:
- Change in voice (masculine)
- Growth of hair in the face (Hirsutism)
- Baldness
- Masculine distribution of hair
- Growth of clitoris
- Amenorrhea
- Heavy limbs with increased muscle mass
- Increased pigmentation
- Smaller breast glands
Features in Males:
After puberty- Exaggeration of existing masculine characters
Prepuberty – Precocious puberty
Diagnosis:
 Low Cortisol
 Elevated plasma ACTH levels
 Low Aldosterone
 High androgens
 Serum electrolytes & glucose
 Low Sodium & high potassium
 Fasting hypoglycemia
 Urinary steroid profile
 Chromosomes

12. Diabetes Mellitus

Characterized by hyperglycemia
Two types:
1. Primary (related to insulin)
2. Secondary
Primary DM:
1. Insulin - dependant DM (due to deficiency of insulin)
2. Non-insulin dependant DM (Due to insulin resistance of tissues)
Features:
1. Hyperglycemia

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2. Glycosuria
3. Polyuria (↑ urine formation)
4. Polyphagia (↑ food intake)
5. Polydipsia (↑ thirst)
6. Hyperlipidemia
7. Hypercholesteraemia
8. Acidosis
9. Fatigue
Complications:
1. Nephropathy
2. Retinopathy
3. Neuropathy
4. Ketoacidosis
5. Coma
Diagnosis:
1. Oral glucose tolerance test
2. Estimation of blood Hb A1C
3. Urine and blood glucose estimation
Treatment:
1. Insulin injection
2. Oral hypoglycemic drugs

18
 1

REPRODUCTIVE SYSTEM
10 marks

1. MENSTRUAL CYCLE
- Refers to cyclical changes that takes place in the women
- Preparatory step for fertilization and Pregnancy
Duration - 25 – 35 Days
Average – 28 Days
Changes include:
Ovarian Cycle
Uterine Cycle
Cervical Cycle
Vaginal Cycle
Ovarian Cycle
Follicular Phase
Ovulation
Luteal Phase
1. Follicular Phase
-Involves the development of a follicle
- One follicle matures each month
- During the lifetime of a female only 400 follicles mature
Stages of follicular development:
Primordial follicle  Primary Follicle  Secondary follicle  Tertiary follicle
(Involves addition of granulosa cells surrounding the oocyte & also formation
of theca cells)Antral follicle(Having fluid filled space)  Matured
Graafian follicle
2. Ovulatory Phase
The process of expulsion of secondary oocyte from ovary into peritonial cavity
following rupture of mature graffian follicle
Timing:
14th day of sexual cycle
Events of Ovulation
- Rapid swelling of follicle
- Formation of stigma
- Release of proteolytic enzymes
- Dissolution of capsular wall
- Rupture of graffian follicle
3. Luteal Phase ( 15th - 28th Day)
Events :
- Formation of corpus hemorrhagicum (ruptured follicle filled with blood)
- Formation of corpus luteum (clotted blood replaced with yellow colored
lipid rich luteal cells)
- Formation of corpus albicans ( regression of corpus luteum)
 2

Uterine (Endometrial) Cycle

Menstrual (Bleeding) Phase
Proliferative phase
Secretory phase
1.Menstrual Phase
The lining of the uterus (endometrium) breaks down and is lost from the body. This is
called menstruation or a period
Duration - Days 1-5
Components:
- 30 – 50 ml blood (75% Arterial)
- Ovum - unfertilized
- Mucus
- Endometrial debris – damaged endometrial tissue, serous fluid, a large amount
of prostaglandins & fibrinolysin
Mechanism of menstruation
1. steroid production declines.
2. shrinking of endometrial tissue
3. reduction in blood flow to superficial layers – ischemic hypoxia & damage to
the epithelial and stroma cells & constriction of spiral arteries
4. Individual arteries re-open  tearing and rupturing the ischemic tissues.
5. Bleeding into the cavity
- About 50% of degenerating tissues is resorbed and 50% is lost as 'menstrual
bleeding'.
2. Proliferative Phase
- Days 6-13
- increase in estrogen causing the endometrium to thicken (from 1mm to 4 mm)
- angiogenesis
- stimulation of endometrial glands to grow
3. Secretory Phase
Days 15-28 :
increase in progesterone causes
- endometrial thickness
- increased vascularity
- secretion of endometrial glands
(in preparation for the developing embryo)
Cervical Cycle
1. Preovulatory Phase - Estrogen is predominant hormone
- Cervical mucus - Thin, Watery & Alkaline
2. Postovulatory Phase - Progesterone
- Cervical mucus - Thick & Tenacious
Vaginal Cycle
1. Preovulatory Phase - Estrogen predominance
Thick & Cornified Epithelium
2. Postovulatory Phase - Progesterone predominance
Thick & viscid secretion
Infiltrated with Leucocytes
 3

Hormonal Control of Sexual Cycle

Gonadotropins from Anterior pituitary
FSH - development of follicles (follicular phase)
LH - triggers ovulation
Ovarian Hormones
Estrogen – influences proliferative phase of endometrial cycle
Progesterone – influences secretory phase of endometrial cycle

Menstrual Disorders
Premenstrual Syndrome
Amenorrhoea - Absent
- Primary
- Secondary – Pregnancy
Menorrhagia – Excess bleeeding
Metorrhagia – intermenstrual bleeding
Oligomenorrhoea – decreased frequency
Dysmenorrhoea – painful menstruation
 4

2. CONTRACEPTION
- Refers to prevention of Conception
Methods of Contraception
Temporary Permanent
1. Barrier Methods 1. Vasectomy
2. Natural Methods 2. Tubectomy
3. Intrauterine Devices
4. Hormonal Contraception (Oral pills)
1. Barrier Methods
- Prevention of deposition of sperms in vagina
Mechanical Methods
Males - Nirodh (Condoms)
Females - Pouch (Female condom)
Diaphragm
Cervical Cap
Chemical Methods
Spermicides - Kill the Sperms
Jelly
Cream
Sponge
Combined (Mechanical & Chemical) - More Effective
2. Natural Methods
Rhythm Method – Following safe period
Coitus Interruptus
Complete abstinence
SafePeriod
Definition – the period of least fertility during menstrual cycle
Duration - 5-6 days after menstruation & 5-6 days before next cycle
Significance – rhythm method of contraception
3. Intrauterine Devices
Lippe’s Loop
Cu T 200
Multiload Cu T-250
Progestasert
Mechanism of Action
Increase tubal motility
Prevent implantation
Spermicidal activity
4.Hormonal /Oral Contraceptives
Sex Hormones - Oral Pills
Mechanism of Action
Negative feedback mechanism
Suppress FSH & LH secretion
Pills
Combined Pill - Progesterone & Oestrogen
21 Days - From the day bleeding stops
 5

Withdrawal bleeding occurs

Sequential Pill - 15 days Oestrogen + Combination
Mini pill - Low dose estrogen
Postcoital pill – within 72 hours after sexual intercourse
Complications of oral contraceptives
Thromboembolic phenomenon
Increase in weight
Jaundice
Avoid in Diabetics
Fibroid Uterus
Permanent Contraceptive Methods
Vasectomy
Tubectomy
Medical Termination of Pregnancy (MTP) or Abortion
Dilatation & curettage (D&C)
Vacuum aspiration
Administration of prostaglandins
---------------------------------------------------------------------------------------------------------

5 MARKS
1. SERTOLI CELLS
Sertoli cells are the supportive cells found in the seminiferous tubules of testis.
Functions:
1. Play a role in the maturation of sperms
2. Provide nutrition to the developing spermatozoa
3. Play a part in the mechanism of blood testis barrier
4. Phagocytize damaged germ cells.
5. Takes part in aromatization of testosterone into estrogen
6. Secretes the following substances:
- MIS (Mullerian Inhibiting substance)
- Inhibins
- Androgen binding protein
7. Influence Leydig cell secretion through activins & inhibins
2. SPERMATOGENESIS
Definition: The development and maturation of spermatozoa (male gametes) is called
spermatogenesis.
Stages:
I.Spermatocytogenesis: Development of spermatogonia into spermatids
1. Spermatogonium A: Primitive germ cells which are diploid (44+XY) and
divide by mitosis to spermatogonium B cells
2.Spermatogonium B: These are also Primitive germ cells which are
diploid (44+XY) and divide by mitosis. These cells
give rise to primary spermatocyte
3. Primary spermatocyte: Diploid cells which divide by meiosis to form
secondary spermatocyte.
 6

4. Secondary spermatocyte: These are haploid cells (22+X or Y). They

undergo second meiotic division to form spermatids
5. Spermatids: Haploid cells which transform into motile spermatozoa.
II.Spermiogenesis: Transformation of spermatids into tailed, motile spermatozoa
(sperms)
Spermatozoa: Matured male gamates, haploid and posses a head, middle
piece and a tail. About 512 spermatozoa develop from a single
spermatogonium

Spermatocytogenesis

Spermiogenesis
 7

Regulation of Spermatogenesis:
A.Hormones:
1. Testosterone: Secreted from Leydig cells of testis. Acts on seminiferous
tubules and stimulates the proliferation of spermatogonia into
primary spermatocyte
2. FSH: Stimulates proliferation as well as maturation of spermatozoa. Trophic to
Sertoli cells which play an important role in maturation.
3.LH: Stimulates the Leydig cells to produce testosterone which is required for
Spermatogenesis
4. Other hormones which are required for spermatogenesis: Thyroxine, Growth
hormone & Insulin
B.General factors:
1. Temperature: Speramatogenesis requires 2 to 3oc less than the core temperature
of the body
2. Irradiation: Exposure to harmful radiation causes degeneration of seminiferous
tubules and leads to sterility
3. Toxins: Bacterial and viral toxins may cause selective destruction of
seminiferous ubules. E.g. Mumps
4. Vitamins: Vitamins A, C & E are required for spermatogenesis

3. TESTOSTERONE.
Secreted from Leydig cells of testis. About 4-9 mg is secreted per day.
Mechanism of Action:
It combines with cytoplasmic receptor and reaches DNA. It acts on DNA and
stimulates mRNA and protein synthesis
Functions:
1. In Fetus:
a) Sex differentiation: Stimulates the development of Wolffian duct into
male accessory sex organs. Development of male external genitalia
requires dihydrotestosterone which is derived from testosterone
b) Descent of testes: Along with MIS, testosterone stimulates the descent of
testes from abdominal cavity into scrotum through inguinal canal
2.During Puberty:
a) On accessory sex organs: Stimulates the development and growth of the
male accessory organs like vas deference, seminal vesicles,
prostate, scrotum & penis
b) On distribution of body hair: General body hair increases. Moustache &
beard appear.Pubic hair appear & attains male pattern
c) On voice: Becomes deeper and low pitched due to growth of vocal cords &
larynx
d) On skin: Thick with more sebaceous secretion. Acne appears on face
e) Mental behavior: More aggressive
3. Spermatogenesis: Stimulates the proliferation of spermatogonia into primary
spermatocyte in seminiferous tubules.

4. On growth: Stimulates skeletal growth. But finally it causes fusion of

 8

epiphyseal plates and arrest growth

5. On muscle mass: Testosterone is a protein anabolic hormone. It increases
protein synthesis.This increases the muscle mass and muscle power in
males.
6. On erythropoiesis: Stimulates the production of erytropoietin there by
increases RBC count. Hence males have higher RBC count than females

4. PLACENTA
Nutritive Function
-Transport of Glucose, Amino acids , Fatty acids & Vitamins from maternal blood
to foetal blood
- Storage of Glycogen, Lipids, Fructose
Respiratory Function
-Diffusion of O2 from maternal blood to foetal blood
-Diffusion of CO2 from foetal blood to maternal blood
Double Bohr effect
- Increased affinity of Foetal Hb (Hb F) shifts the ODC of foetal blood to left
- Increased Level of CO2 shifts the ODC of maternal blood to right
(Both the effects increase the O2 content of foetal blood)
Excretory function: Transport of metabolic waste products like urea, uric acid,
creatinine from foetal blood to maternal blood
Endocrine function
Placental Hormones
-Human Chorionic Gonadotrophin (HCG)
- Human Placental Lactogen (HPL, HCS - Human Chorionic
Somatomammotrophin)
-Human Chorionic Thyrotrophin (HCT)
-Oestrogen , Progesterone
-Relaxin
Human Chorionic Gonadotrophin (HCG)
Growth of Corpus Luteum
Presence in Serum & Urine - Diagnostic of Pregnancy
Growth of Testis / Ovarian Follicles in Fetus
Human Placental Lactogen
- Maternal Growth Hormone of Pregnancy
- Growth of Breast glands
- Retention of Nitrogen, Calcium , Sodium
- Makes Glucose & Fats available to the Fetus
Oestrogen
- Growth of ducts of Breast glands
- Increases the sensitivity of uterus to Oxytocin
Progesterone
- Growth of alveoli of Breast glands
- Maintenance of Pregnancy
-
Relaxin - Relaxes Pelvic joints & Pubic symphysis
 9

Softens and dilates the uterine cervix Facilitates delivery

6. INDICATORS OF OVULATION
1. Basal Body Temperature- A rise of 0.50C after ovulation
2. Billings Method -
Cervical Mucus :
Before ovulation- Elastic, Stretchable upto 10 cms (Spinnbarkeit effect)
After ovulation – Thick and can not be stretched
3. Fern Test
Before Ovulation –cervical mucus produce a fern pattern when dried on a glass
slide
After Ovulation – Fern pattern disappears
4. Biopsy of the endometrium – checking for the secretory phase
5. Endoscopy
6. Blood Gonadotrophins Level
7. Ultrasound Abdomen
7. NEUROENDOCRINE REFLEXES
Partiturition/Ferguson Reflex
Uterine contraction
 10

Milk let down or suckling reflex

Suckling of breast by the baby
↓
Stimulation of mechanoreceptors on nipple & areola
↓
Afferents (somatic nerve)

spinal cord
↓
Hypothalamus

Anterior pituitary Posterior pituitary

(Lactotrops) (Paraventricular nucleus)
↓ ↓
Prolactin Oxytocin

8. FETO_PLACENTAL UNIT
- Fetus & Placenta function as a unit in synthesising estrogen & progesterone
- Helps to maintain the level of steroids which inturn maintain the pregnancy
Maternal blood Placenta Foetal Adrenal
Progesterone Progesterone Cortisol, Corticosterone

Acetate

Pregnenolone DHEAS

16 – OH DHEAS 16 – OH DHEAS

Estrogen Estrogen

9. HCG
-Secreted by syncytiotrophoblast of placenta
-Reaches its maximum level at 60th -70th day of pregnancy
Functions:
- Growth of corpus luteum
- Secretion of progesterone & estrogen from Corpus Luteum
- Growth of testes & testosterone secretion in male foetus
- Androgen production from fetal adrenal cortex
- Formation of primordial follicle in fetal ovary
- Growth of breast
- High level in urine – diagnosis of pregnancy
 1

1. CARDIAC CYCLE

Definition: The cyclical changes that take place in the heart during each beat (one systole and
one diastole)
Duration for one cycle = 0.8 sec
Phases:
 Atrial systole - 0.1 sec
 Atrial diastole- 0.7 sec
 Ventricular systole – 0.3 sec
 Ventricular diastole – 0.5 sec
ATRIAL SYSTOLE
 Contraction of atria & expulsion of blood into ventricles
 Contributes 25% of the ventricular filling
 Last phase of ventricular diastole
 Produces fourth heart sound
ATRIAL DIASTOLE
 Gradual filling of atria by blood brought by veins
VENTRICULAR SYSTOLE
 Contraction of ventricles & expulsion of blood into respective blood vessels
 Includes three phases
Isovolumetric contraction-0.05sec
Maximal ejection – 0.1 sec
Reduced ejection – 0.15 sec
Isovolumetric contraction
 Period between closure of AV valves & opening of semilunar valves
 Ventricles contract as closed chambers
 No change in the volume of blood in the ventricles
 Intraventricular pressure increases
Maximal Ejection phase
 Increase in intraventricular pressure
 Semilunar valves are forced to open
 Due to High Pressure gradient, blood is rapidly ejected out of ventricles
 About 2/3rd of stroke volume is ejected
Reduced ejection
 Due to decreased pressure gradient, the rate of ejection of blood is reduced
 About 1/3rd of stroke volume is ejected
VENTRICULAR DIASTOLE
 Filling of ventricles by the blood flowing from atria
 Includes five phases
Protodiastolic period – 0.04 Sec
Isovolumetric relaxation – 0.08 Sec
Rapid inflow – 0.11
Diastasis – 0.19
Atrial systole – 0.11
 2

Protodiastolic phase
 Ventricle relaxes
 Intraventricular pressure in less than the pressure in the aorta/Pulmonary Arteries
 Semilunar valves close to prevent the back flow of blood from arteries into ventricles
 Closure of SLV produces second heart sound
Isovolumetric relaxation
 Period between closure of semilunar valves & opening of AV valves
 SLV and AV valves are closed
 Ventricle relaxes as closed chamber
 No change in the volume of blood in the ventricles
 Intraventricular pressure decreases
Rapid inflow phase
 Intraventricular pressure less than intra atrial pressure
 Hence AV valves open
 Blood flows from atria to ventricle at a faster rate
 Turbulence due to rapid flow produces third heart sound
Diastasis
 Increase in intraventricular pressure
 Blood flow from atria to ventricle at low rate or static
Atrial systole
 Last phase of ventricular diastole
 Contributes additional 25% of ventricular filling
HEART SOUNDS
4 recordable heart sounds (Phonocardiogram)
 First heart sound-S1 – Caused by closure of AV valves. Occurs at the beginning of
ventricular systole
 Second heart sound S2- Caused by closure of Semi Lunar Valves. Occurs at the end
of ventricular systole
 Third heart sound- Due to rapid ventricular filling
 Fourth heart sound- Caused by atrial systole
HEMODYNAMIC CHANGES
Pressure and volume changes in the atria & ventricle during cardiac cycle
 Intra atrial pressure curve
 Intraventricular pressure curve
 Aortic pressure curve
 Ventricular volume curve
Intra-atrial pressure curve
3 Positive waves – a, c & v (caused by increase in intraatrial pressure)
2 Negative waves - x & y (caused by decrease in intraatrial pressure)
 ‘a’ wave - due to atrial systole
 ‘c’ wave – due to bulging of AV valve into the ventricles during isovolumetric
contraction
 ‘v’ wave – due to filling of atria after the closure of AV valves
 3

Intraventricular pressure curve: (Left ventricular pressure)

 During isovolumetric contraction phase – Pressure rises steeply due to a rise in
tension
 Maximum ejection phase – Maximum pressure (120 mmHg) develops as the ventricle
is contracting with a maximum force
 Reduced ejection phase – Pressure is less during this phase
Aortic pressure Curve:
 During diastole of heart, the aortic pressure is maintained at 80 mmHg
 During systole of the heart, it rises to 120 mmHg
Ventricular volume curve:
 End diastolic volume – During diastole, ventricular volume increases. The maximum
volume of blood in the ventricle at the end of diastole is called End Diastolic
volume. It is normally 130 ml.
 Stroke Volume: Volume of blood ejected out from ventricle during systole. It is 80 ml
 End Systolic Volume: The minimal volume of blood remaining in the heart at the end
of systole
ECG:
“P” wave = is due to atrial depolarization which occurs before atrial systole
“QRS” complex = is due to ventricular depolarization which occurs before ventricular
Systole
“T” wave is due to ventricular repolarization which occurs before ventricular diastole

Wiggers Chart
 4

2. CARDIAC OUTPUT
A) Definition:
Cardiac output (CO) – Volume of blood ejected by each ventricle / minute
Stroke volume (SV) – Volume of blood ejected by each ventricle / beat
Cardiac Index (CI) – Cardiac output / square meter of the body surface Area
End Diastolic Volume (EDV) – Volume of the blood in the ventricle at the end of diastole
Ejection Fraction (EF) – Fraction of the end diastolic volume that is ejected
Peripheral Resistance (PR) – The resistance offered to the blood flow in the peripheral
blood vessels
B) Normal values:
Cardiac output – 5 lts / min
Stroke volume – 70 ml/ beat
Cardiac index – 3 lts/ min/square metre of body surface area
End diastolic volume – 120 ml
Ejection Fraction -- 65%
METHODS TO DETERMINE CARDIAC OUTPUT
Direct method
Indirect method
 Fick principle
 Dilution principle (Dye. Isotope & Thermo dilution)
 Ballistocardiography
 Pulse pressure contour
 X – ray cardiometry
FICK PRINCIPLE
The cardiac output is calculated by the following formula
X
Q = ----------
A – V difference
Q – Blood flow
X – Amount of substance taken up by an organ
A -- V difference = Arterio venous difference in the concentration of a substance
As pulmonary blood flow is equal to cardiac output, pulmonary blood flow determined
by Fick principle is taken as cardiac output.
Pulmonary blood flow = amount of O2 taken by the lungs/minute
--------------------------------------------------
Arterio venous difference of O2
For example
Amount of oxygen taken by lungs / minute = 250 ml
(Determined by spirometer)
Arterial oxygen content = 20 ml / 100 ml of blood
(Estimated from any peripheral artery)
Venous oxygen content = 15 ml / 100 ml of blood
(Estimated from right atrium)
Pulmonary blood flow = 250
--------- X 100 = 5000 ml 0r 5 lts
20 - 15
 5

As pulmonary blood flow = cardiac output, CO = 5 lts

DYE DILUTION PRINCIPLE
A known amount of dye is injected into the peripheral vein and blood samples are
collected from the peripheral artery and the concentration of the dye in each sample is
estimated.
Cardiac output can be calculated by using the following formula:
Amount of the dye injected
-----------------------------------------
Mean concentration of the dye over a period of 1 minute
The commonly used dye is EVAN”S BLUE (T—1824)
C) Regulation of Cardiac output:
Cardiac output = Stroke volume x Heart rate
-------------------------------------
Peripheral resistance

Stroke volume = Myocardial contractility X End Diastolic Volume (EDV)

Heart rate End Diastolic Volume

(chronotropic) Cardiac Output (Pre load)

Myocardial Peripheral resistance

Contractility (After load)
(Ionotropic)

Cardiac Output Regulation

Heterometric regulation Homometric regulation

(Factors which cause an increase in the initial (Factors which do not cause any change
length of cardiac muscle before contraction) in the initial length of cardiac muscle
before contraction)
Heterometric regulation of cardiac output
I. Intrinsic factors regulating myocardial contractility
Frank – Starling Phenomenon:
The force of contraction is directly proportional to the initial length of the
cardiac muscle. The initial length of the muscle depends on the end diastolic
volume. Any increase in the EDV stretches the ventricular myocardium,
increasing the length of the muscle fiber
Importance:
– helps to match the stroke volume of the ventricles
– helps to maintain the minute output
– prevents venous engorgement
 6

Force Frequency relation:

Any increase in the frequency of heart beat increases myocardial contractility
within physiological limits. The increase in contractility is due to accumulation of
intracellular calcium ions
II. End Diastolic volume:
End Diastolic Volume (EDV) is the volume of blood in the ventricles
at the end of diastole. Any increase in the EDV increases the cardiac output by
increasing the stroke volume.
Mechanism: Increase in EDV  stretching of ventricular muscle fibres 
Increase in the length of fibres  stronger muscle contraction
Increase in cardiac output (Frank Starling’s law)
Factors influencing EDV:
i) Venous return
ii) Ventricular compliance
iii) Diastolic pause
iv) Atrial systole
Venous return: The volume of blood that returns to the atria through the veins in
one minute. This increases EDV & there by increases cardiac
output.
Factors influencing venous return:
1. Cardiac pump: The pumping action of ventricles increases
venous return by 2 forces:
 Vis – a – tergo (propelling force from behind):
- Left ventricular contraction during systole and
elastic recoiling of arteries during diastole push
the blood from aorta towards the right atrium
 Vis – a –fronte (suction force from front) – Right
atrial pressure:
- Less pressure in right atrium during diastole helps
in suction of blood from the great veins into the
right atrium
2. Capacity of venous reservoir: This factor is inversely
proportional to venous return .
Venoconstriction  decrease in venous capacity  increase
in venous return
3. Blood Volume: Directly proportional to venous return.
e.g., hemorrhage  decrease in blood volume  decrease in
venous return
4. Respiratory pump: Venous return increases during inspiration
Inspiration  negative intrathoracic pressure  suction of
blood into thoracic big veins  increased venous return
5. Muscle pump: Intermittent contractions of skeletal muscle
particularly leg muscle  squeeze the veins  increases the
flow of venous blood towards the heart  increase in venous
return
 7

6. Abdominal pump: Contractions of abdominal muscles 

compresses the great veins, pushing venous blood towards the
heart

Right atrial pressure

Blood volume Respiratory pump

Cardiac pump Venous return Vascular capacity

Abdominal pump Muscle pump

Ventricular compliance:
- refers to the stretchability of ventricular myocardium
- any increase in the compliance reduces EDV and thereby stroke volume
e.g constrictive pericarditis & pericardial effusion
Diastolic pause:
- refers to the duration of diastole of ventricles
- this influences the ventricular filling
- this factor is directly related to EDV within physiological limits
Atrial systole:
- contributes 20% of ventricular filling at rest
- influences EDV directly
e.g
- increase in atrial systole during exercise  increase in EDV
- in atrial flutter & fibrillation, the contribution of atrial systole in ventricular
filling is reduced
Homometric Regulation of Cardiac Output
I . Extrinsic Factors Regulating Myocardial Contractility
a) Neural factors:
Sympathetic stimulation: Releases nor-epinephrine  binds to β1 receptors  increases
cAMP  increase in intracellular calcium  increase in myocardial contractility
Parasympathetic stimulation: Releases acetylcholine  binds to muscarinic receptors
(M2)  hyperpolarization of SA nodal and myocardial cells  decrease in myocardial
contractility
b) Hormones:
Epinephrine & Nor-epinephrine: Bind to β1 receptors increase in cAMP  increase in
intracellular calcium  increase in myocardial contractility
Glucagon: Increases myocardial contractility by increasing intracellular calcium without
binding to β1 receptors
Thyroxine: Increases the myocardial contractility by increasing the metabolic rate.
c) Ions:
Sodium & Potassium – decreases the myocardial contractility
Calcium – increases the myocardial contractility
 8

d) Drugs:
β – blockers: e.g Propanaolol – block the β – receptors and decreases the myocardial
contractility
Calcium-channel blocker: e.g Verapramill – block the calcium channel  decrease in
intracellular calcium  decrease in myocardial contractility
Digitalis: Blocks Na+ - K+ ATPase  decrease in Na+ gradient across the membrane 
calcium accumulation inside the cell  increase in myocardial contractility
e) Coronary blood flow:
Decrease in coronary blood flow
↓
Hypoxia, hypercapnia & acidosis
↓
Decrease in myocardial contractility

Intrinsic Factors Extrinsic Factors

M
Sympathetic
Y
Frank-Starling phenomenon O Neural
C Parasympathetic
A
R Catecholamines
D Hormonal Glucagon
I Thyroxine
Force – Frequency relation A
L Ions (Na+, K+ & Ca2+)
C β-blockers
O
Drugs Calcium channel blockers
N
T Digitalis
R
A Coronary blood flow
C
T
I
L
I
T
Y

Influence of heart rate on cardiac output

- Direct relationship between heart rate and cardiac output
Increase in HR
↓
Increase in intracellular calcium
↓
Increase in force of contraction
 9

- This happens by two ways:

1. As a multiplying factor
2. Staircase phenomenon
(This relation is linear upto 180 BPM. Beyond this level, venous return falls 
decrease in cardiac output)
Influence of peripheral resistance on cardiac output:
- Initially, the variation in peripheral resistance tends to influence cardiac output
- But the indirect effects maintain the cardiac output
---------------------------------------------------------------------------------------------------------------------
3. BLOOD PRESSURE
Definition:
Blood Pressure : The lateral pressure exerted by the moving column of blood on the walls
of the arteries
Systolic BP : The maximum BP in the arteries during systole of the heart.
Diastolic BP : The minimum BP in the arteries during diastole of the heart.
Pulse pressure : The difference between systolic and diastolic pressure
Mean Arterial BP : The average BP in the arteries. This is calculated as Diastolic BP + 1/3 of
pulse pressure
Normal Values:
Blood Pressure : 120/80 mm Hg
Systolic BP : 90 – 140 mm Hg
Diastolic BP : 60 – 90 mm Hg
Pulse pressure : 40 mm Hg
Mean Arterial BP : 95 mm Hg

Regulation Of Arterial Blood Presssure:

Short – Term or Rapid Acting Mechanisms

1. Baroreceptor reflex
2. Chemoreceptor reflex
3. Cushing reflex
4. Stress relaxation & inverse stress relaxation
5. Capillary fluid shift
6. Hormones
Baroreceptor reflex:
- Also called as “Marey’s reflex” or “Sino-Aortic reflex”
- Initiated by increase in blood pressure
- Receptors are mechanoreceptors which respond to stretch in blood vessel wall
- Receptors are called “Baroreceptors”. They are present in the carotid sinus and
aortic arch
- This mechanism can correct 2/3rd of fall in BP
- The working range of BP is 60-200 mm Hg
 10

Increase in BP
↓
Stimulation of baroreceptors
(Carotid sinus and aortic arch)
↓
Stimulation of NTS (Nucleus of Tractus Solitarius) in medulla
↓

Inhibition of VMC Stimulation of CVC

(Vasomotor center) (Cardiovascular center-
Nucleus Ambiguus)

Inhibition of SNS
(Sympathetic Nervous Stimulation of vagus
System)

Decreased Increased vagal tone

sympathetic tone

Blood vessel Adrenal medulla Heart

Vasodilatation Decreased catecholamine Bradycardia

Venodilatation secretion

Net effect:
Decreased Peripheral resistance
&  Decrease in BP
Decrease in cardiac output

Decrease in BP
↓
Inhibition of baroreceptors
(Carotid sinus and aortic arch)
↓
NTS is not stimulated
↓

stimulation of VMC Inhibition of CVC

(Vasomotor center) (Cardiovascular center-
Nucleus Ambiguus)
 11

Stimulation of SNS
(Sympathetic Nervous Inhibition of vagus
System)

Increased sympathetic Decreased vagal tone

tone

Blood vessel Adrenal medulla Heart

Vasoconstriction Increased catecholamine Tachycardia

Venoconstriction secretion

Net effect:
Increased Peripheral resistance
&  Increase in BP
Increase in cardiac output

CNS ischemic response:

- This mechanism occurs due to ischaemia of brain
- This may result due to severe fall in BP below 40 mmHg
- If this response is specifically due to increase in intracranial pressure, it is called
as “Cushing reflex”
- The response is called “last ditch effort” as it tries to prevent the death of a
person
- The working range for this mechanism is 15-50 mm Hg
- It can correct 90% of the fall in BP
Decrease in BP (below 40 mm hg)
↓
Decreased blood flow to the brain
↓
Ischemia of brain
↓
Stimulation of VMC
(Vasomotor center)
 12

Stimulation of SNS
(Sympathetic Nervous
System)

Increased sympathetic
tone

Blood vessel

Vasoconstriction

Increase in BP

Chemoreceptor Reflex:
- Receptors respond to chemicals. So called as chemoreceptors
- Two types of receptors – peripheral & central chemoreceptors
- Peripheral chemoreceptors - Carotid bodies & Aortic bodies
- Stimuli for receptors : Hypoxia, Hypercapnia & Acidosis

Decrease in BP (<40 mm Hg)

Cerebral hypoxia, hypercapnia & acidosis

Stimulation of VMC
(Vasomotor center)

Stimulation of SNS
(Sympathetic Nervous
System)

Increased sympathetic
tone
 13

Blood vessel

Vasoconstriction

Stress relaxation and reverse stress relaxation mechanism:

Increase in BP  Stretching of blood vessels  Stress relaxation  Loss of
vasomotor tone  increased capacity of vascular bed  Pooling of blood 
Decrease in circulating blood volume  Decrease in BP

Decrease in BP Blood vessels are not stretchedIncrease in vasomotor tone 

decreased capacity of vascular bed Increase in circulating blood volume Increase
in BP
Capillary Fluid Shift Mechanism:

Increase in BP Decrease in BP

Increase in capillary Decrease in capillary

Hydrostatic pressure Hydrostatic pressure

Fluid Decrease in BP Fluid Increase in BP

Interstitial space Interstitial space

Hormones:
1. Catecholamines: Fall in BP  release of catecholamines (epinephrine &
norepinephrine) from adrenal medulla  Vasoconstriction & increase in cardiac output
 increase in BP
2. ADH: In large amounts ADH causes vasoconstriction  increase in BP
3. Glucocorticoids: Cortisol and corticosterone sensitize the vascular smooth muscle to the
action of catecholamines (permissive role)
4. Nitric oxide (Endothelium Derived Relaxing factor) :released by endothelium and acts
locally causing vasodilatation
Long Term Regulation of Blood Pressure
1. Renal body fluid mechanism
2. Renin-Angiotensin mechanism
3. Hormones – Aldosterone & ADH
 14

Renal body fluid mechanism:

Increase in BP Decrease in BP

Increase in renal blood flow Decrease in renal blood flow

Increase in GFR Decrease in GFR

Increase in urine formation Decrease in urine formation

Decrease in ECF volume Increase in ECF volume

Decrease in BP
Increase in BP
(Restoration of BP)
(Restoration of BP)

Renin – Angiotensin Mechanism:

Decrease in BP

Decrease in renal blood flow

Decrease in GFR

Renal ischemia or decreased

Na+ & Cl- at macula densa

Release of renin from

juxtaglomerular cells of
kidney
 15

Angiotensinogen Angiotensin I

Angiotensin II
&
Angiotensin III

Angiotensin II & Angiotensin III

Vasoconstriction reabsorption of Aldosterone ADH secretion

Na+ & Cl- secretion
(direct effect on kidney)

reabsorption of reabsorption of
Na+ & Cl- water

Increase in ECF volume

Increase in blood volume

Increase in blood pressure

Hormones Regulating Blood Pressure:

Aldosterone: Secreted from adrenal cortex in response to decrease in ECF volume.
Increases the reabsorption of Na+ & Cl- in kidney tubules. This causes
increase in ECF volume and blood pressure
ADH: Secreted from posterior pituitary. Increases water reabsorption from kidney 
increase in ECF volume and blood pressure
ANP: Secreted from atrial myocardium in response to increase in ECF volume facilitates
Na+, Cl-& H2O excretion into urine  decrease in ECF volume & blood pressure
 1

CVS -- 5 MARKS
1. . PACE MAKER POTENTIAL
• Potential that is produced in pacemaker cells of heart (mainly by SA node)
• R.M.P is low(–60mV )
• Unstable RMP - ie there is a slow depolarization between Action potentials,&
when it reaches threshold value action potential is triggered
• After repolarization again there is a slow depolarization & an action potential &
this process is repeated
• The slow depolarization between action potentials is the Pacemaker potential or
prepotential
Ionic basis of pacemaker potential
• Is due to decrease in Potassium efflux-forming the 1st part of the prepotential
• In the later part Transient (T) Ca ++ channels open up completing the
prepotential
• Slow depolarization occurs till threshold (firing level) is reached
• At the threshold level long lasting Ca ++ channels (L channel) open up causing
Action potential
• Action potential is largely due to Ca++ entry with very little contribution by Na+
• When AP reaches the peak the K+ channel open up K + efflux occurs &
repolarization follows

Action potential
Ca++(L)

Prepotential

1
 2

Effect of Stimulation of Sympathetic

• Stimulation increases the slope of prepotential (steep)
• Facilitates opening of Ca++ channel & Ca ++ entry 
• Reaches the firing level sooner
• So heart rate is rapid

Sympathetic
stimulation

Vagal stimulation

Effect of Stimulation of Vagus

• When the vagal fibre are stimulated the membrane becomes hyperpolarized &
the slope of the prepotential is  (slope is flat) because of  K permeability
• So there is a delay in reaching the firing level & the rate is slow
------------------------------------------------------------------------------------------------------------
2. CONDUCTING SYSTEM OF HEART

2
 3

Origin & Conduction of cardiac impulse

Internodal pathways
• Connects S-A node to A-V node
• Comprise of three bundles
• Anterior - Bachman
• Middle – Wenkebach
• Posterior - Thorel
Conduction Rate (meter/second)
• SA Node ---- -- 0.05 m/s
• AV Node ----- -- 0.05 m/s
• Atrial Pathway ----- 1 m/s
• Ventricular Muscle— 1 m/s
• Bundle of his ---------- 1 m/s
• Purkinje Fibres -------- 4 m/s
AV Nodal Delay
• AV Nodal Delay- O.1sec
• Allows Atria to complete its contraction
• Helps in proper filling of ventricles
• Decreases in stimulation of sympathetic nerves
• Increases in stimulation of vagus
Septal activation
 Depolarization of the ventricular muscle starts on the left side of the
interventricular septum and moves to the right across the mid portion of the
septum
 Wave of depolarization spreads down the septum to the apex of the heart &
activates the apex on either side
• From the apex the impulse passes along the ventricular walls towards the base of
the heart at the AV groove
• Endocardial surface of the ventricle is activated by the Purkinje fibres
• Impulse passes from the endocardial to epicardial surface of the ventricle
• The last part of the heart to be depolarized posteriobasal portion of the left
ventricle (Pulmonary conus & uppermost portion of the septum)

3
 4

3. THE PHYSIOLOGY OF CORONARY CIRCULATION

Arterial supply
• 2 coronary arteries.
• 20% humans - left coronary artery predominates.
• 50% - right coronary artery predominates
• 30% - equal supply by both.
• Main arteries lie on the surface, while small arteries penetrates the muscle mass.
Venous drainage
• 2 systems (superficial & deep)
• Superficial – Ends in coronary sinus & anterior cardiac vein.
• Deep system – opens directly in to the cardiac chambers.
Via 3 sets of vessels (arteriosinusoidal, arterioluminal, thebesian)
SPECIAL FEATURES OF CORONARY CIRCULATION
1. 1st branch to arise from aorta.
2. Blood flow is more during diastole.
3. Only organ to generate its own perfusion pressure.
4. Coronary arteries are functional end arteries, however, when occlusion occurs
slowly collaterals do develop.
5. Shortest circulation - Mean transit time. 6 – 8 seconds.
6. The veins drain directly in to the chambers adding deoxygenated blood to the
oxygenated blood.(Physiological shunt).
7. The diameter of the cardiac muscle fiber is smaller than the skeletal muscle fiber
& the capillary density is more than the skeletal muscle.
8. Autoregulation in coronary blood flow is present between 60 – 150 mmHg of
mean arterial pressure.
9. Hypoxia – Powerful vasodilator (Acts via adenosine)
ATP becomes ADP,  adenosine, acts on vessel wall  vasodilatation.
10. Oxygen extraction is nearly maximal even at resting heart rate,
Arterial PO2 = 19 ml %.
Venous PO2 = 7 – 8 ml %.

19 – 07 X 100 = 63 %
19
ie oxygen utilization by the cardiac muscle at rest is more ( 63%) than other organs
in the body (25%)
11. During systole the pressure in the subendocardial muscle is more than the outer
layers ( Epicardial).
Applied – subendocardium is maximally prone for ischemia.
12. Compensatory protective mechanism for the left ventricular subendocardium is
(1)  Capillary density.
(2)  Myoglobin content

4
 5

PHASIC FLOW OF CORONARY CIRCULATION

PHASIC CORONARY FLOW

During isovolumetric contraction
• Ventricles contract without any change in the length of the muscle fiber.
• Blood is not leaving the chamber.
• Blood flow to LV muscle reduces to zero
During ejection
Aortic pressure increases but the contracting ventricles are compressing the vessels,
thus the flow is present but less.
During isovolumetric relaxation
• Ventricles are relaxing.
• Sharp increase in the coronary blood flow
• Maximum coronary blood flow
During diastasis & late filling
• Aortic pressure decreases, so the coronary blood flow is less

Regulation of Coronary Blood Flow

Mechanisms involved:
1. Autoregulation
2. Neural regulation
3. Hormonal regulation
Autoregulation:
- Heart regulates its own blood flow. This is called as autoregulation
- Autoregulation is by two mechanisms – Myogenic & chemical

5
 6

Myogenic: The contraction and relaxation of the vascular smooth muscle

adjust the coronary blood flow when the blood flow is altered
Chemical regulation:
1. Hypoxia
2. Other metabolites ( CO2, H+, K+ & lactate)
3. Local vasodilators
Hypoxia: Increases coronary blood flow by causing vasodilatation
This is done by two mechanisms:
a. Direct effect:
Decreased myocardial oxygen
↓
Intracellular acidosis
↓
Less calcium binding
↓
Relaxation of vascular smooth muscle
↓
vasodilatation
↓
Increase in coronary blood flow

b. Trough adenosine: (Berne’s hypothesis)

 in myocardial metabolism
↓
Hypoxia & adenosine (from ATP)
↓
Vasodilatation
↓
Increase in coronary blood flow
Other metabolites : ( CO2, H+, K+ & lactate)
Decrease in coronary blood flow
↓
Accumulation of metabolites
↓
Vasodilatation
↓
Increase in coronary blood flow
Local vasodilators: (NO (EDRF), Prostacyclin & bradykinin)

Decrease in coronary blood flow

↓
Release of vasodilators by vascular endothelium
↓
Vasodilatation
↓
Increase in coronary blood flow

6
 7

Neural regulation:
Sympathetic nervous system (nor-adrenergic fibers)
• Stimulation of the  receptors  vasoconstriction decrease in coronary blood
flow (direct effect)
• Stimulation of  receptors  increase in heart rate & myocardial contractility 
accumulation of metabolites  vasodilatation  increase in coronary blood flow
(Indirect effect)
• Coronary vascular dilatation  Preservation of the supply to the heart.
parasympathetic nervous system
• Stimulation
-- directly  vasodilatation.
-- indirectly  vasoconstriction
Hormonal regulation:
1. Catecholamines: Same as that of sympathetic stimulation
2. Acetylcholine: Same as that of parasympathetic stimulation
3. Vasopressin: Vasoconsrtiction
4. Angiotensin: Vasoconstriction
5. Thyroxine: Increases metabolism  Hypoxia  vasodilatation  increase in
coronary blood flow
---------------------------------------------------------------------------------------------------------------------
4. Describe the factors affecting venous return
Venous return: The volume of blood that returns to the atria through the veins in
one minute. This increases EDV & there by increases cardiac output
Factors influencing venous return:
1. Cardiac pump: The pumping action of ventricles increases venous return by 2
forces:
 Vis – a – tergo (propelling force from behind):
- Left ventricular contraction during systole and elastic recoiling of
arteries during diastole push the blood from aorta towards the right
atrium
 Vis – a –fronte (suction force from front) – Right atrial pressure:
- Less pressure in right atrium during diastole helps in suction of
blood from the great veins into the right atrium
2. Capacity of venous reservoir: This factor is inversely proportional to venous
return .
Venoconstriction  decrease in venous capacity  increase in venous return
3. Blood Volume: Directly proportional to venous return.
e.g., hemorrhage  decrease in blood volume  decrease in venous return
4. Respiratory pump: Venous return increases during inspiration
Inspiration  negative intrathoracic pressure  suction of blood into thoracic
big veins  increased venous return
5. Muscle pump: Intermittent contractions of skeletal muscle particularly leg
muscle  squeeze the veins  increases the flow of venous blood towards
the hear t  increase in venous return
6. Abdominal pump: Contractions of abdominal muscles  compresses the great
veins, pushing venous blood towards the heart

7
 8

Right atrial pressure

Blood volume Respiratory pump

Cardiac pump Venous return Vascular capacity

Abdominal pump Muscle pump

3 marks:
1. Draw a labeled diagram of JVP & give the physiological basis of genesis of each wave of
JVP

Jugular Venous Pulse / Phlebogram

As the jugular vein is directly connected to right atrium, the right atrial pressure changes
are reflected in the venous pulse
3 Positive waves – a, c & v (caused by increase in intraatrial pressure)
2 Negative waves - x & y (caused by decrease in intraatrial pressure)
 ‘a’ wave - due to atrial systole
 ‘c’ wave – due to bulging of AV valve into the atrium during isovolumetric
contraction
 ‘v’ wave – due to filling of atria after the closure of AV valves
 ‘x’ wave – due to downward movement of AV ring during ejection phase
 ‘y’ wave – due to the rushing of blood from atria to ventricles immediately after
the opening of AV valves

2. What is A – V nodal delay and its physiological significance?

 The delay in the conduction of cardiac impulse through AV node is called
AV nodal delay
 It is for about 0.1 second
Causes:
- Small & primitive fibers
- Presence of few gap junctions
- RMP is more negative
Significance:
- Gives sufficient time for completion of atrial contraction
- Prevents overlapping of atrial and ventricular systole
- Allows sufficient time for ventricular filling

8
 9

3. Cardiac muscle can not be tetanized. Justify the statement with proper diagram &
labeling / Define refractory period. What is the significance of this period in heart?

Refractory period: It is the period of excitation during which the muscle will not respond
to a second stimulus. It includes two phases – absolute & relative
Absolute refractory period: During this phase, even a stronger second stimulus will not
produce any response. It is for about 200 ms
Relative refractory period: During this phase, a second stronger stimulus may produce a
response. It is for about 50 ms
Significance:
- The whole contraction period of cardiac muscle is refractory period
- Cardiac muscle cannot be tetanized because of this long refractory period

4. What is ejection fraction and its significance?

The fraction of the end diastolic volume that is ejected out of ventricle is called ejection
fraction

It is calculated by: EDV – ESV EDV-End Diastolic Volume

----------------- ESV- End Systolic Volume
EDV
Normally it is about 65%

5. What is Starling’s law of muscle contraction? How is it applicable to cardiac muscle?

Starling’s law of muscle contraction: The initial length of muscle is directly
proportional to the force of contraction within physiological conditions.
Application to cardiac muscle: Increase in venous return  Increase in End Diastolic
Volume  Stretching of ventricular myocardium  Increase in the initial length of
cardiac muscle  increase in strength of myocardial contractility

9
 10

6. Explain the components of triple response giving their physiological basis.

Triple Response of Lewis:

A three phased cutaneous response that occurs from firm stroking of the skin is
called as triple response.
Phases:
Red reaction: Reddening along the line of stroke
Flare: Spread of reddish colour around the redline
Wheal: Local diffuse swelling along the line of stroke
Red reaction:
- Occurs within 10 seconds of application of the stroke
- It is due to relaxation of precapillary sphincters which increases blood
flow through capillaries
- This is mediated through histamine and bradykinin
- Not dependent on nerves
Flare:
- Occurs within 15-20 seconds of application of the stroke
- It is due to dilatation of arterioles, venules & relaxation of precapillary
sphincters
- Dependent on nerves. Caused by axonal reflex
Mechanism of axonal reflex:
Chemicals released from injured tissue
↓
Stimulate sensory nerve endings
↓
Sensory impulses to spinal cord
↓
Antidromic conduction of impulses through
Collateral fibers to blood vessels
↓
vasodilatation
Wheal:
- Occurs within 1-3 minutes of application of the stroke
- It is due to increase in permeability of capillaries and venules 
exudation of protein rich fluid from the capillaries and venules

10
 11

- Caused by chemicals such as histamine, bradykinin, P substance, K+ and

prostaglandins from the injured tissue
- Not dependent on nerves
7. What is Windkessel effect? Mention the physiological significance of it.
- Large arteries (Aorta & their branches) have more elastic & collagen
fibers in their walls. So these vessels are stretchable
- During systole, when excess blood is pumped into these vessels. They
expand to accommodate excess blood temporarily
- During diastole, when heart is not pumping, their elastic walls recoil, and
blood in them is propelled forward
- This property of large arteries is called Windkessel effect.
Functions:
- Pulsatile ejection of blood is converted to steady outflow
- Maximum exchange between blood & tissues is achieved
Significance:
- Helps to prevent too much rise of pressure in the arteries during systole
- Helps to maintain pressure & blood flow when heart is not pumping in
diastole
Applied:
In old age, loss of windkessel effect due to hardening of arterial walls leads
to hypertension
8. Draw a labelled diagram of normal sphygmogram

11
 1

Respiratory system – Part 3

Hypoxia

1. What is hypoxia? Explain the different types of hypoxia with examples. Describe the
effectiveness of O2 therapy in various types of hypoxia
Definition: Decreased PO2 in the tissue is called hypoxia
- due to inadequate supply of O2 to tissue
- due to failure of tissue to utilize the available O2
Types:
a) Hypoxic hypoxia
b) Anemic hypoxia
c) Stagnant hypoxia
d) Histotoxic hypoxia
a) Hypoxic hypoxia
– decreased O2 tension of the arterial blood
– also called as arterial hypoxia
Causes:
– low PO2 in the inspired air (High altitude)
– hypoventilation (Asthma – Air way obstruction)
– diffusion of oxygen across respiratory membrane (Lung collapse)
b) Anemic hypoxia
– decreased O2 transport or O2 dissociation from Hb
Causes:
- decreased Hb content (anemia)
- decreased saturation of Hb (carbon monoxide poisioning)
c) Stagnant hypoxia
– Inadequate blood flow to the tissues
Causes :
– slow flow of blood (congestive heart failure)
– obstruction in blood flow (vasoconstriction)
d) Histotoxic hypoxia
– tissue can not utilize O2
Causes :
– paralysis of cytochrome oxidase enzyme (Cyanide poisoning)
Oxygen therapy
a) Hypoxic hypoxia - highly beneficial – O2 therapy increases the alveolar PO2 and also the
entry of O2 into the blood – increases the arterial blood content of O2 both in
dissolved and combined forms
b) Anemic hypoxia – moderately beneficial - helpful in increasing the dissolved oxygen
c) Stagnant hypoxia – less useful
d) Histotoxic hypoxia – not useful - as tissue is not able to utilize the oxygen that is
delivered.
---------------------------------------------------------------------------------------------------------------------
 2

2. What is cyanosis? Differentiate peripheral and central cyanosis

Cyanosis is a diffused bluish colouration of the skin and mucous membranes
Cause: caused by increased amount of reduced hemoglobin (deoxyhemoglobin)
To produce cyanosis the reduced Hb should be more than 5 gms / 100 ml of blood
Types
1) Peripheral cyanosis
2) Central cyanosis
Peripheral cyanosis
- Due to stagnant hypoxia
- Venous unsaturation is more
- only skin becomes bluish
Conditions which cause peripheral cyanosis
- cardiac failure
- shock
- exposure cold environment (Peripheral vasoconstriction --- stagnant hypoxia)
Central cyanosis

- Due to hypoxic hypoxia

- Arterial unsaturation is more
- Skin & mucous membranes become bluish
Conditions which cause central cyanosis
- congenital heart diseas
- AV admixture
- Lung diseases
- Presence of methaemoglobins and sulphaemoglobin
Reason for absence of cyanosis in the following condition
Anemic hypoxia: As the anemic patients have less hemoglobin, they can not produce
more than 5 gms of reduced hemoglobin / 100 ml of blood so cyanosis does not
occur
Histotoxic hypoxia: As tissues do not utilize oxygen, oxygen is not dissociated from Hb.
So reduced Hb is not formed in greater amounts (more than 5 gms/100 ml of
blood) to produce cyanosis.
Carbonmonoxide (CO) poisoning: Causes cherry red colour which hides the bluish
Colouration
---------------------------------------------------------------------------------------------------------------------
3. Decompression Sickness /Caisson’s disease /Dysbarism /sickness/Diver’s
palsy/bends
Definition: The symptoms produced when an individual ascends rapidly to sea level after
sufficient exposure to high atmospheric pressure in deep sea
Mechanism or physiological basis:
At high atmospheric pressure, nitrogen dissolves in the body fluids. As nitrogen is lipid
soluble, it get dissolved in the cell membranes & sphingomyelin of myelim sneath.
During rapid ascent, the gas (nitrogen) escapes from the tissue at a faster rate. This
forms bubbles which block the blood vessels producing tissue ischaemia & tissue death.
 3

Symptoms or features:
a) Pain in joints and muscles of legs (called as bends)
(Presence of bubbles in the myelin sheath of sensory nerve fibers in joints and muscles)
Paraesthesia – pricking & itching may follow
b) Temporary paralysis due to bubbles in motor nerve fibers
c) Chokes – shortness of breath due to bubbles in pulmonary veins
d) Myocardial ischaemia – due to bubbles in coronary blood vessels.
e) Brain damage due to bubbles in cerebral blood vessels.
Prevention:
Slow decompression (the ascend to the surface should not be faster than 3 km/ hour)
Treatment:
Recompression followed by slow decompression along with hyperbaric O2 therapy.
---------------------------------------------------------------------------------------------------------------------
4. Asphyxia
Definition:- Condition in which hypoxia (PO2) is associated with hypercapnia (PCO2) due to
obstruction in the air way.
Causes: Strangulation, drowning, tracheal obstruction (due to entry of food or choking) and
paralysis of diaphragm.
Stages:
I stage - Stage of hyperopnea
II stage - Stage of central excitation
III stage - Stage of central depression

I-Stage of hyperopnea:- (lasts for 1 minute)

Features
 increase in rate & depth of respiration
 Expiratory effort
 Dysponea, cyanosis
 Prominence of eyeballs
(due to stimulation of respiratory centers by PCO2)
II – stage of convulsions (lasts for a minute)
Features
 Violent expiration
 increased HR & systolic BP
 constriction of pupil
 exaggeration of all reflexes
 convulsions & loss of consciousness
(due to stimulation of respiratory centers by PCO2 & O2)
III- Stage of exhaustion & collapse (lasts for 2-3 minutes)
 Convulsions disappear
 HR & systolic BP
 Dilatation of pupil
 Gasping (shallow & low frequency respiration)
 Death
 4

5. Pneumothorax
- refers to presence of air in the pleural space
Cause: Either through a rupture in the lung or a hole in the chest wall (stab injury, gun shot
wound etc.,)
Types:
a) Open or sucking pneumothorax
b) Closed pneumothorax
c) Tension pneumothorax
Open or sucking pneumothorax:
The communication between the pleural space and the exterior remains open
Closed pneumothorax:
Hole through which the air enters the pleural space is sealed off.
Tension pneumothorax:
A flap of tissue lies over the hole in the lung or chest wall acts as a valve. This will allow
air to enter the pleural space during inspiration but does not allow air to exit during
expiration.
Features:
- Collapse of lung on affected side (As the pleural pressure becomes positive, the
elastic recoil of lungs leads to collapse)
- Mediastinum shifted towards normal side
- Respiratory distress (due to stimulation of respiratory centers by hypoxia and
hypercapnia)
--------------------------------------------------------------------------------------------------------------------
6. Periodic breathing
- Periodic breathing is characterized by alternate periods of apnoea and hyperopnea
Types:
1. Cheyne – stokes respiration
2. Biot’s breathing
Cheyne – stokes respiration – characterized by gradual waxing and waning, followed by a
period of apnoea
Condtions: Premature infants, High altitude, voluntary hyperventilation, heart failure
Physiological basis:
Hyperventilation  Wash out of CO2 (respiratory alkalosis) Inhibition of respiratory
Center Apnoea (cessation of breathing) Build up of PCO2 & in PO2 (Hypoxia and
hypercapnia) Stimulation of respiratory center Hyperopnea
(The cycle continues till normal breathing is restored)
Biot’s breathing: Abrupt apnoea & hyperopnea - No waxing and waning
Conditions: increase in intracranial pressure, morphine poisioning & damage to brain stem
-------------------------------------------------------------------------------------------------------------------
7. Mountain sickness
Symptoms that occur due to rapid ascend to high attitude are together called as mountain
sickness
Types:
a) Acute mountain sickness
b) Chronic mountain sickness
 5

Acute mountain sickness:

(Symptoms appear within a day after reaching the high attitude and last for 4-8 days)
Features:
fatigue, headache, insomnia, irritablity and palpitation
loss of co-ordination and memory, Euphoria and emotional changes
(Above features are due to mild cerebral hypoxia & also due to mild cerebral edema)
-Nausea, vomiting & diarrohoea
(due to distension of GIT by expansion of gases in hypoxia)
-Hyperopnea & dysponea
(due to stimulation of respiratory center by hypoxia)
Physiological basis
All the effects are due to hypoxia in high attitude
Treatment:
- Shifting the person to a lower attitude
- Hyperbaric O2 therapy to relieve hypoxia
- Glucocorticoids to reduce cerebral edema
- Carbonic anhydrase inhibitor ( reduce cerebral edema)
- Nifedipine (Ca+ channel blocker) to reduce pulmonary hypertension
Chronic mountain sickness (Monge’s disease)
Seen in long term residents of high attitude
Features:
Polycythemia, fatigue, pulmonary hypertension, right ventricular failure and heart
failure (due to chronic hypoxia)
---------------------------------------------------------------------------------------------------------------------
8.Oxygen toxicity
Increase in the amount of dissolved O2 -- increases the PO2 proportionally. This is called as
oxygen toxicity
Causes: Breathing O2 at a higher pressure
Conditions: Hyperbaric O2 therapy (100% O2 therapy for more than 8 hours)
Deep sea diving
Features:
On CNS:
Nausea, irritability, dizziness, disorient at facial twitching and convulsions.
On respiration:
- Congestion and irritation of the airway
- in surfactant
- Pulmonary edema
- Atelectasis (collapse of lung)
On special senses:
- Tinnitus (spontaneous ringing in the ear)
- Loss of equilibrium
- Blurring of vision
- Retrolental hyperplasia ((formation of an opaque membrane behind the lens)
Physiological basis:
Accumulation of oxidizing free radicals like super oxide (O3), hydrogen peroxide (H2O2) 
Oxidise the PUFA (Poly unsaturated fatty acids) & destroy the cellular enzymes
 6

9.Artificial Respiration
- Refers to ventilation of lung artificially when there is respiratory failure
Indications:
In subjects with respiratory deficiency but with a functional heart
Conditions: Drowning, gas poisoning, electric shock, overdose of sedatives, head injury
surgery etc.,
Methods:
Positive pressure
1. Instrumental
Negative pressure
2. Manual methods
Instrumental:
Positive pressure method – Lung is inflated with air +O2 mixture at positive pressures (used in
operation theater)
Negative pressure method – Alternate compression and relaxation of chest wall
Drinker’s mehod
Bragpaul method
Boyle”s apparatus
Manual methods
Holger – Neilson Method
Eve’s rocking method
Mouth to mouth breathing:
Mouth to mouth breathing:-
Mechanism - Subject in supine position
- Clean the mouth and nose of food, vomitus etc.,
- Head is extended backward
- Kneel on one side, open the mouth of subject and close the nose
- Exhale air smoothly into the mouth of victim
- This inflates the subject’s lungs
- remove the mouth to allow for passive expiration
- repeat this procedure three times to saturate the victim’s blood with O2
- continue the procedure regularly at the rate of about 12 times per minute

Advantages of this method:

- can be applied immediately and quickly
- simple and most effective (most effective because CO2 present in the expired air
directly stimulate the respiratory center and facilitate the onset of respiration)
- large tidal volume of about 1000 ml (1 liter can be obtained)
- Can be applied in all age groups.
 RESPIRATORY SYSTEM
10 marks

1. Draw the respiratory centers. Explain in detail the mechanism of neural regulation
of respiration.
Respiratory Centers

Medullary centers Pontine centers

Dorsal Group Ventral Group Apneustic center Pneumotaxic center

Of neurons of neurons

NERVOUS CENTERS FOR RESPIRATION

PONS
inhibits

MEDULLA

Respiratory Centres:
Medullary respiratory Centers
a) Dorsal respiratory group (DRG) of neurons
b) Ventral respiratory group (VRG) of neurons
Pontine respiratory centers:
a) Pneumotaxic center (Upper pons)
b) Apneustic Center (lower pons)
PNEUMOTAXIC CENTRE:
Location: Located bilaterally in the upper pons (Nucleus Parabrachialis)
Functions: Shortens inspiration through ‘Apneustic center’ & switching
off the ‘DRG’  Increases respiratory rate & decreases the depth of
respiration.
APNEUSTIC CENTRE:
Location: Located bilaterally in the lower part of the pons
Function: Prevents the switch off of the ‘DRG’

’ Increases the tidal volume & duration of inspiration

Deeper and more prolonged inspiratory effort (Apneusis)

DRG:
Location: Located in the nucleus of Tractus solitarius (NTS) of medulla.
Function: Spontaneous rhythmic discharge of impulses
 2

Causes inspiration
(impulses are called ‘inspiratory ramp signals’ )
VRG:
Location: Located lateral & ventral to DRG in the nucleus ambiguus.
Function: Discharge impulses during forced breathing
Inactive during quiet breathing.
Pre-Bot Zinger Complex:
Location: On either of medulla between nucleus ambiguus & lateral reticular
nucleus.
Functions: Initiate the respiratory rhythm.
Experimental evidences:
Complete transection of brain stem above the pons breathing continues
Complete transection of the brain stem below medulla breathing stops
Section at mid pontine level Apneusis (arrest of respiration in inspiration)
Section between pons & medulla rhythmic, but irregular respiration
Mechanism of respiratory rhythm:
DRG Neurons (Dorsal Respiratory Groups of Neurons at Medulla)

Discharge of impulses steadily & spontaneously (Called as inspiratory ramp signal)

Steady & Sustained contraction of inspiratory muscles.

Expansion of chest wall & lungs.

Entry of air into the lungs (Inspiration)

Impulses through vagal afferent fibers & impulses from pneumotaxic center.

Arrest of inspiratory ramp from DRG.

Relaxation of inspiratory musles.

Recoiling of lung & chest wall.

Air is expelled out of lungs (Expiration)

Interconnections Between Respiratory Centres

Upper Pons: Pneumotaxic

Center

-
Lower Pons: Apneustic
Center
-
+
Medulla: Ventral Respiratory Dorsal Respiratory
Neurons Neurons
+ -
Inspiratory Muscles Vagal Afferents

Inspiration From Lung

Factors That Influence Respiratory Centers:

REFLEXES HIGHER CENTERS

 3

Herring-Breuer Reflex Cerebral Cortex

Sneezing Reflex Limbic System
Coughing Reflex Hypothalamus
Swallowing Reflex
Speech
RESPIRATORY CENTERS

DRUGS PERIPHERAL RECEPTORS

Catecholamine Baroreceptors
Caffeine, Nicotine Chemoreceptors
Anesthetics J - receptor
Proprioceptor
Pain receptor
Thermoreceptors
Higher centers:
Cerebral cortex – voluntary control over respiration
Limbic system – control ventilatory changes during emotions
Hypothalamus - Influences ventilatory changes to temperature
Peripheral receptors:
Baroreceptors: Stimulation of Baroreceptors  inhibits respiratory centers
Chemoreceptors: Stimulation of chemoreceptors  stimulation of respiratory
Centers
J – receptors: Stimulation of J receptors  apnoea followed by tachypnoea
Proprioceptor: Stimulation of propioceptors  stimulates breathing
Reflexes:
Herring – Breuer reflex: When tidal volume increases above 1000 ml 
stimulation of pulmonary stretch receptors arrest of inspiration 
initiates expiration  increase in respiratory rate
Sneezing reflex: Irritation of nasal mucosa  deep inspiration followed by
explosive expiration through nose
Coughing reflex: Irritation of the tracheobronchial mucosa  deep inspiration
followed by explosive expiration through mouth
Swallowing reflex: Swallowing  stops respiration (deglutition apnoea)
Drugs : Catecholamines, caffeine, nicotine & nikethamide  stimulates respiration
Anaesthetic agents & sedatives  inhibits respiratory centers ↓ventilation
-------------------------------------------------------------------------------------------------------
2. Where is chemosensitive area situated? Describe the chemical control of
respiration.
The activity of the respiratory center is altered by the variation in the chemical
composition of plasma, CSF and interstitial fluid of the brain.
Chemicals that alter the activity of the respiratory center
1) Carbon dioxide (CO2)
2) Oxygen (O2)
3) Hydrogen (H+)
Mechanism of action of the chemicals on respiratory centers.
The chemicals act through chemoreceptors
Types of Chemoreceptors:
Peripheral chemoreceptors
Central chemoreceptors

Peripheral Chemoreceptors
Includes aortic bodies & carotid bodies
Location: -
 4

- Carotid bodies are located on either side near the bifurcation

of common carotid artery.
- Arotic bodies are located near the arch of aorta.
Afferent nerve:
- Sinus nerve (Branch of IX cranial nerve from carotid bodies)
- Aortic nerve (Branch of X cranial nerve from aortic bodies)

Central chemorceptors:
Location: Located in the ventral surface of the medulla.
Function: Monitor the H+ ion concentration of CSF & interstitial fluid of the
brain.
Ventilatory Responses to oxygen, Co2 & H+ ions.
Ventilatory response to O2 content:
(Effect of Hypoxia on Respiration)

PO2 in inspired air

Alveolar PO2

Arterial PO2 (below 60mm Hg)

Stimulation of peripheral Chemoreceptors

Activity of respiratory center

Contractility of inspiratory muscles

Ventilation

Ventilatory response to CO2

(Effect of Hypercapnia on respiration)
 5

Hypercapnia ( PCO2 in the inspired air)

Aleveolar PCO2

Arterial PCO2

Arterial H+ PCO2 of brain CSF

Activity of peripheral H+ ions of brain CSF

Chemoreceptors
Activity of central
Chemoreceptors

Activity of respiratory center

Ventilation

Ventilatory response to H+ ions

(Effect of acidosis on respiration)

Diabetic ketoacidosis, starvation ketoacidosis, Loss of alkali in diarrhoea, renal

failure to excrete H+ ions.
Accumulation of lactic acid

In arterial pH (Metabolic acidosis)

Stimulation of peripheral chemoreceptors

Stimulation of respiratory center

Increase of pulmonary ventilation

Overall chemical regulation of respiration

1. H+ ions in ECF of brain 1. Arterial PCO2 (Hypercapnia)

2. Arterial PCO2 2. Arterial H+ (acidosis)

3. Arterial PO2 (Hypoxia)

Central chemoreceptors Peripheral chemoreceptors

at medulla (Carotid body, aortic body)

Stimulation of respiratory Centers

Ventilation

-----------------------------------------------------------------------------------------------------
3. Describe the process of transport of Gases
Transport of Oxygen
Oxygen is transported by the blood from the lungs to tissues
 6

This transport can be dealt under the following events

- Uptake of oxygen in the lungs by pulmonary blood
- Transport in the blood
- O2 dissociation curve and the factors influencing it
- O2 delivery to the tissues
Uptake of O2 in the lungs
Due to the pressure gradient between alveolar oxygen & pulmonary capillary blood
oxygen, oxygen diffuses from alveolus into the pulmonary capillary blood

Transport in the blood

Oxygen is transported in the arterial blood in two forms
- In dissolved form (3%)
- In combination with hemoglobin (oxyhemoglobin) (97%)
In dissolved form
O.3 ml of O2 is dissolved in the plasma of 100 ml of blood
The dissolved oxygen is proportional to PO2
In combination with Hemoglobin
Oxygen from alveolus

Enters into the blood

Combines with Hb by the process of Oxygenation

Steps involved

Hb4+O2 Hb4O2
Hb4O2+O2 Hb4O4
Hb4O4+O2 Hb4O6
Hb4O6+O2 Hb4O8

i.e., four oxygen molecules combine with one molecule of hemoglobin

O2 carrying capacity of Hb
1 molecule of Hb - 4 molecules of O2
1 gm of Hb - 1.34 ml of O2
15 gms/100 ml of blood - 1.34 X 15 = 20 ml of O2
Oxygen – dissociation curve
- Curve obtained by plotting the relationship between PO2 (partial
pressure of oxygen) and the percentage of Hb saturation
- the percentage saturation of Hb increases with the increase in PO2 of
arterial blood
- the curve is sigmoid shaped due to variation in the affinity of Hb to O2 at
varied atmospheric PO2
 7

- the pleateau (upper flat part) of the curve is the loading zone which is
related to the process of O2 uptake in the lungs
- the steep portion the curve is the dissociation (unloading) zone which is
concerned with the O2 delivery in the tissue
O2– Dissociation Cuve

97

90
%
s 75
a
t
u
r 50
a
t
i
o
n

PO2 (mm Hg)

-At PO2 of 26 mm Hg – 50% saturation (p-50)
-At PO2 of 40 mm Hg – 75% saturation (Venous blood)
-At Po2 of 95 mm Hg – 97% saturation (Arterial blood)
Curve shifting to Right
- signifies the decreased affinity of Hb for O2
Factors causing right shift
- Decrease in PO2 (hypoxia)
- An increase in Pco2 (Bohr’s effect)
(loading of Co2 by the blood causes unloading of oxygen from blood to
tissues)
- A decrease in the pH of blood
- An increase in the temperature
- An increase in the concentration of 2,3 – BPG
Factors causing left shift
- Decreased PCO2 of blood
- Increased pH of blood
- Decreased temperature
- Fetal Hb
 8

Delivery of O2 to body cells per minute

Arterial O2 content = 20 ml / 100 ml of blood
Venous O2 content = 19 ml / 100 ml of blood
Cardiac out put = 5 lt / minute
O2 delivery to the entire body /minute = 20-15/100 X5000 = 1000 ml or 1lt/mt
Transport of CO2
CO2 is transported by blood from tissues to lungs
The transport of Co2 can be described under the following events
- Uptake of CO2 by the blood in the tissues
- Transport in the blood
- CO2 dissociation curve
- CO2 delivery in the lungs
Uptake of CO2 by the blood in the tissue
- The pressure gradient is the motive force for the diffusion of CO2 from
tissue cell to the capillary blood

Transport of CO2 in the blood

CO2 is transported in the blood in three forms
- In dissolved state (7%)
- In bicarbonate form (70%)
- In carbamino compound form (23%)
In dissolved form
0.3 ml of CO2 is transported from tissues to lungs in dissolved form
 9

In bicarbonate form
CO2 is converted into bicarbonate inside the RBC and then diffuses into plasma
-the steps involved are
CO2 in the tissues

Enters into the blood

Enters into the RBC

Combines with H2O to form carbonic acid in the presence of enzyme “carbonic
Anhydrase”

Carbonic acid dissociates into bicarbonate ions (HCO3-) and Hydrogen ions (H+)

Diffusion of bicarbonate into the plasma and H+ are buffered by hemoglobin

Chloride Shift:

- Diffusion of HCO3- out of RBC into plasma  less negative inside to

neutralize this effect negatively charged chloride ions diffuse from
plasma into the RBC
- this movement of chloride ions into the RBCs is called chloride shift

In carbamino form
CO2 + Aminogroup of plasma proteins – Carbamino proteins
CO2+ Aminogroup of Hb - Carbaminoglobin
CO2 dissociation curve
- Curve obtained by plotting the relationship between PCO2 and total
CO2 content of the blood
- the total CO2 content of the blood is directly proportional to PCO2 of
the blood
Factors affecting the curve
1) Oxygen
- Increase in PO2 causes increase in CO2 dissociation (Haldane’s effect)
(loading of O2 in lungs causes unloading of CO2)
- Shifts the curve to right
2) 2, 3 – DPG
- Competes with CO2 to combine with Hb
- Shifts the curve to right
 10

Delivery of CO2 in the lungs:

Involves the following steps
1. Release of CO2 from carbaminohaemoglobin into plasma
Entry of O2 into RBC – Oxygenation of Hb

Oxyhaemoglobin has low affinity for CO2

Release of CO2
2. bicarbonate is converted into CO2 by reverse chloride shift
Oxyhemoglobin releases H+ ions

Entry of HCO3- from plasma into RBC in exchange for Cl- ions
(Reverse chloride shift)
H+ combines with HCO3- to form carbonic acid

Carbonic acid dissociates into H20 & CO2

CO2 diffuses out of RBC into plasma

Diffusion of CO2 from plasma to alveoli

- Difference in the partial pressure of CO2 between alveoli and

pulmonary capillary blood makes the CO2 to diffuse out of blood
into the alveoli
Amount of CO2 delivered in the lungs
CO2 content of venous blood – 52 ml/100 ml
CO2 content of Arterial blood – 48 ml/100 ml
So CO2 delivered into the lungs – 4 ml / 100 ml
Total amount of CO2 transported = 4 /100 X 5000 (cardiac output) = 200 ml/minute

4. Describe the mechanism of respiration

Respiration is the process by which the body acquires oxygen and expels carbon di
oxide. It includes two phases:
1. Inspiration
2. Expiration
Inspiration:
- It is the process of air entering into the lungs
- It is an active process
Mechanism:
The contraction of the inspiratory muscles  expansion of thoracic cavity 
intrapleural pressure becomes more negativeincrease in transpulmonary pressure
 lungs expand  decrease in intrapulmonary pressure  air flows in to the lungs
Inspiratory muscles
Diaphragm – 75% of the increase in intrathoracic volume (increases the vertical
diameter of chest)
External intercostal muscles – increases the anteroposterior diameter of the chest
Accessory muscles during deep inspiration
Scalene and sternocieido mastoid muscles
Movement of ribs:-
a. Bucket handle movement
(upward and outward) - Increase in transverse diameter of thoracic cage
 11

b. Pump handle movement

(upward and forward) - Increase in anteroposterior diameter of thoracic cage

Volume changes during inspiration:

Tidal volume – Volume of air in the lungs increases by 500 ml
Pressure changes during inspiration
a) Intrapulmonary pressure
At the end of inspiration and expiration – 0mm Hg (same as that of
atmospheric pressure i.e., 760 mm Hg)
During inspiration ----- - 1 mm Hg (759 mm Hg)
During expiration ----- +1 mm Hg (760 mm Hg)
b) Intrathoracic pressure
At the end of inspiration and expiration -- - 2.5 mm Hg (757.5 mm Hg)
During inspiration ---- - 6 mm Hg (754 mm Hg)
During forced inspiration ---- - 30 mm Hg
 12

b) Work of breathing during inspiration

1. Elastic resistance work (65%)
2. Non elastic resistance
a) Viscous resistance work (7%)
b) Airway resistance work (28%)
Expiration:
- It is the process of air expulsion from the lungs
- It is a passive process
Mechanism:
The relaxation of the inspiratory muscles  recoiling of thoracic cavity 
intrapleural pressure is restored to normal  decrease in transpulmonary pressure 
lungs recoil  increase in intrapulmonary pressure  air flows out of lungs
Accessory muscles during forced expiration
Internal intercostal muscles & abdominal muscles
-----------------------------------------------------------------------------------------------------
10 marks
1. Pyramidal tract
Origin :
 Primary motor Cortex (Area 4 – from large cells of Betz in the v layer of precentral
gyrus) - 30 %
 Premotor Cortex (area 6) & Supplementary motor cortex (Area 6) - 30%
 Somatosensory cortex (Areas 3,1, 2, 5 & 7) - 40%
Course:
 Corona radiata: Fibers forming a radiating pattern in the subcortical areas
 Internal Capsule: Converge through the genu and anterior 2/3rd of posterior limb of
internal capsule
 Mid brain: Fibers occupy middle 1/5th of cerebral peduncles
 Pons: The tract is split into a number of bundles by the presence of pontine nuclei
 Medulla:
Upper part:
Fibers join to form a single bundle. This forms a distinct bulge anteriorly close to the
midline called pyramid
Lower part:
80% of the fibers cross to the opposite side & 20% of the fibers descend on the same side
(The crossing of fibers from each side to opposite side is called motor decussaation)
 Spinal cord:
The crossed fibers form the lateral corticospinal tract and descend in the lateral white
column of spinal cord.
The uncrossed fibers form the anterior corticospinal tract and descend in the anterior
white column of spinal cord
Termination:
Fibers of lateral corticospinal tract – synapse with anterior horn cells directly and supply to
the distal limb muscles
Fibers of anterior corticospinal tract – cross at the segmental level and synapse with the anterior horn
cells through internuncial neurons. The fibers of this tract supply the axial and proximal limb
muscles
 55 % of the fibers end in the cervical region
 20% of the fibers end in the thoracic region
 25 % of the fibers end in the lumbosacral region
Functions:
 Control of voluntary fine and skilled movements (lateral corticospinal tract)
 Control of gross voluntary movements (anterior corticospinal tract)
 Facilitates muscle tone
 Facilitates superficial reflexes
 Mediates the actions of basal ganglia and cerebellum
 Concerned with direct sensory – motor coordination

( Refer book for diagram)

 2. CEREBELLUM

Functional divisions, their connections & functions

Functional divisions:
 Vestibulocerebellum (Flocculonodular lobe)
 Spinocerebellum (Vermis & intermediate zone)
 Neocerebellum (cerebrocerebellum)

Vestibulocerebellum:
 Connected to vestibular apparatus
 Role in control of body posture, equilibrium & visual fixation
Spinocerebellum:
 Mainly connected to spinal cord
Vermis: Controls muscle movements of axial body, neck, shoulder, hips  Maintains
posture via vestibulospinal & reticulospinal pathways
Intermediate zone: Control of muscular contraction of upper & lower limbs via
corticospinal tract
Cerebrocerebellum:
 Connected with pons and cerebral cortex
 Concerned with overall planning and programming of sequential motor movements
 Coordinates the timing and duration of contraction of different groups of muscles
Connections:

Peduncles Afferent fibers Efferent fibers

Superior Cerebellar Ventral spinocerebellar tract Dentato thalamocortical fibers
Peduncle Tectocerebellar Dentatorubral fibers
Trigemino cerebellar fibers

Middle Cerebellar Cerebro ponto cerebellar ----------------------

Peduncle

Inferior Cerebellar Dorsal spinocerebellar Cerebello reticular

Peduncle Cuneo cerebellar Cerebello vestibular
Reticulo cerebellar
Vestibulo cerebellar
Olivo cerebellar

Functions:
1. Control of body posture & equilibrium (Vestibulocerebellum & Spinocerebellum)
 Influences antigravity muscles through medial motor system and maintains
posture
 Influences muscles through vestibulospinal tract and maintains equilibrium during
standing, walking etc.,
(Vestibular apparatus  Vestibular nucleus of brain stem Vestibulo cerebellar
fibers  Vestibulocerebellum  Cerebello vestibular fibers  Vestibular
nucleus  Vestibulospinal tract)
2. Control of Gaze (Movements of eyeballs) – Vestibulocerebellum
 Controls eye movements and coordinates with head through medial longitudinal
fasciculus
3. Control of muscle tone & Stretch reflex (Spinocerebellum)
 Facilitates γ motor neurons in the spinal cord
 Forms an important site of α – γ linkage
4. Control of voluntary movements (Neocerebellum)
 Regulates time, rate, range(extent), force and direction of muscular activity
 Controls coordination of movements, but does not initiate movements
 Influences the activity of agonists, antagonists & synergistic muscles
 Planning and programming of voluntary movements
 Correction of purposeful movements (comparator of a servo-mecanism)
 Smooth transition of movements
 Cognition
 Learning of motor skills
 Mental rehearsal of complex action
5. Other functions: Influences autonomic functions
 3. BASAL GANGLIA / BASAL NUCLEI-
 Subcortical nuclear masses of grey matter, present at the base of the cerebral hemispheres
Components:
1. Caudate nucleus
2. Putamen
3. Globus pallidus
- Externa
- Interna
4. Substantia nigra
- Pars compacta
- Pars reticulata
5. Subthalamic Body of Luys
Connections:

Direct pathway:
+ Cortex

+ Glutamine

Striatum Dopamine Substantia nigra

D1

- GABA
Globus pallidus Interna

+
Thalamus
- Excitatory pathway
- Facilitates the intended movement

Indirect pathway:
-
Cortex

+ Glutamine

Globus pallidus Externa Striatum Dopamine Substantia nigra

D2
- GABA
Subthalamic nucleus + Globus pallidus Interna

PPN -
Brain stem & Spinal cord Thalamus

- Inhibitory pathway
- Inhibits the unwanted movement
Basal Ganglia functions
 Lower animals – center for motor activity
 Initiation of voluntary movements
 Suppression of unwanted movements
 Planning and Programming of a voluntary movement
 Execution of automatic associated movement
- Swinging of arms during walking
- Gestures during speech
 Cognitive control of motor activity ie., timing and scaling of movements through caudate circuit
 Inhibits muscle tone – inhibits γ motor neuron discharge by stimulating inhibitory medullary
reticular formation
 Regulation of posture
 Role in mood & behavior
-------------------------------------------------------------------------------------------------------------------------------

4. PAIN PATHWAY
Pain is carried by two pathways:
i) Neospinothalamic pathway
ii) Paleospinothalamic pathway
Neospinothalamic tract: (carries fast pain)

1st order neuron: Aδ fibers from receptors to lamina I and V of spinal cord

2nd order neuron: From dorsal horn of spinal cord  cross to opposite side  ascend in the lateral
white column  end in the ventral postero lateral (VPL) & ventral postero
medial (VPM) nuclei of thalamus.
(Gives few collaterals to reticular formation)

3rd order neuron: From VPL & VPM nuclei of thalamus to somatosensory cortex (areas 3, 2 &1)
of post central gyrus.

Paleospinothalamic tract: (carries slow pain)

1st order neuron: ‘C’fibers from receptors to lamina IV and V of spinal cord

2nd order neuron: From dorsal horn of spinal cord  cross to opposite side  ascend in the lateral
white column  end in intralaminar & midline nuclei of thalamus
(Gives collaterals to reticular formation, PAG and tectum of midbrain)

3rd order neuron: Arise from intralaminar & midline nuclei of thalamus & reach the entire cerebral
Cortex
Special features:
Neospinothalamic tract: concerned with localization and interpretation of quality of pain
Paleospinothalamic tract: concerned with perception of pain, arousal and alertness
 (Refer book for diagram)

Please learn dorsal column tracts from the book

 1

CNS Notes 2nd Part

1.Synaptic inhibitions & facilitation

1. Direct postsynaptic inhibition:
Stimulation of an afferent neuron inhibits an efferent neuron. The inhibition is direct and is
usually through an internuncial neuron. The neurotransmitter released is inhibitory in nature
Example: Golgi bottle neuron inhibition in reciprocal innervation and crossed extensor reflex
Mechanism : Stimulation of an afferent neuron from muscle spindle activates a golgi bottle
neuron that releases glycine which causes hyperpolarisation of the motor neuron
that supply to the antagonistic muscles.
2. Indirect postsynaptic inhibition:
Inhibition that occurs due to the effects of previous discharge from the postsynaptic neuron.
Mechanism: 2 ways:
i) Postsynaptic neuron remains refractory to the incoming stimuli because it has just fired and is
in the refractory period
ii) Neurons which initiate an excitatory impulse may inhibit themselves in a negative feedback
fashion.
Example: Renshaw cell inhibition:
The spinal motor neuron regularly gives recurrent collateral which synapses with an inhibitory
interneuron that terminates on the cell body of the same neuron. This inhibitory interneuron is
called Renshaw cell . This prevents excess discharge from the anterior horn cell
3. Presynaptic inhibition:
Inhibition occurs usually at the presynaptic terminals before the signal reaches the synapse.
Mostly modulatory in nature and usually axo-axonic type.
Example: Pain modulation in the spinal cord
Mechanism: A reflex response to stimulation of an afferent nerve is either abolished or
decreased by stimulating another afferent nerve .The second afferent nerve ending
synapses with presynaptic nerve terminal through an inhibitory interneuron. The
inhibitory neurotransmitter (Eg . GABA) released by this interneuron decreases
the depolarization of the presynaptic nerve terminals. Calcium entry into the
nerve terminals is decreased causing a decreased release of excitatory
neurotransmitter. This leads to a reduced response
4. Feedforward inhibition:
The afferent fibers first stimulate the efferent fibers and then inhibit the same fibers through
interneurons
Example: In cerebellum , the afferent fibers first stimulate the deep nuclei and then inhibit
them through purkinjee cells.
PRESYNAPTIC FACILITATION
A reflex response to stimulation of an afferent nerve is increased by stimulating another afferent
nerve.The second afferent nerve ending synapses with presynaptic nerve terminal through an
interneuron. The excitatory neurotransmitter (mostly serotonin) released by this interneuron
decreases the K+ current at presynaptic nerve terminals and increases the duration of
depolarization of the presynaptic nerve terminals. Calcium entry into the nerve terminals is
increased causing a increased release of excitatory neurotransmitter. This leads to an increased
response
-----------------------------------------------------------------------------------------------------------------------------
 2

2. Properties of Receptors
a. Specificity:
Each type of receptor is highly specific for a particular stimulus for which it is designed and is
non responsive to normal intensities of other type of stimuli (e.g) Rods and cones respond to
normal intensities of light, but respond to only high intensity of touch.
b. Adequate stimulus:
The stimulus which can easily stimulate a receptor is the adequate stimulus for that receptor.
(e.g) Light is the adequate stimulus for rods & cones.
c. Labelled Line Principle:
The specificity of nerve fibers for transmitting only one modality of sensation is called labeled
line principle.
d. Doctrine of specific nerve energies:
Also called as Muller’s law. The sensation evoked by impulses generated in a receptor depends
in part upon the specific part of the brain they ultimately activate.
e. Law of projection:
When a stimulus is applied anywhere in the pathway of a sensation, the sensation is projected to
the receptors. (e.g) Phantom limb & Phantom pain
Phantom Limb: The non existing limb in an amputated person gives the sensation of pain &
proprioception as if it is existing.
Phantom pain: The pain sensation from the non existing limb of an amputated person can be
explained by law of projection ie., the stimulus applied anywhere in the pathway causes
projection of sensation to receptors)
Mechanism
Amputation  formation of neuromas  discharge of impulses by pressure or
Spontaneously sensation produced is projected to the place where the receptors were
presented.
f. Adaptation:
Reduction in sensitivity of receptors in the presence of a constant stimulus
 Phasic receptors: Fast adapting receptors (e.g) receptors for smell & pacinian corpuscles.
 Tonic receptors: Slow – adapting receptors (e.g) proprioceptors
 Receptors that do not adapt at all - Pain receptors (Nociceptors)
g. Intensity discrimination:
Weber Fechner Law: The magnitude of sensation felt is proportionate to the log of intensity of
stimulus
R=KSA
(R = Magnitude of sensation felt, S=intensity of stimulus, K & A = constants)
Intensity discrimination depends upon
 Number of receptors stimulated (spatial summation)
 Frequency of action potential reaching the cortex (Temporal summation)
------------------------------------------------------------------------------------------------------------------------------
 3

3. Sensory Tracts
1.Dorsal column pathway
Origin: From the dorsal column of spinal cord
Course:
I order neuron
 In the posterior nerve root
 After entering into spinal cord, ascend in the dorsal column of spinal cord
 Terminate in the nucleus gracilis & nucleus cuneatus of medulla
II order neuron
 From nucleus gracilis & nucleus cuneatus
 Cross to the opposite side (sensory decussation)
 Crossed fibers (called as inter nal arcuate fibers) upward in the medial lemniscus through pons &
mid brain.
 Terminate in the ventral postero lateral nucleus of thalamus (VPLN)
III order Neuron
 From VPLN of thalamus
 Pass through posterior limb of internal capsule
 Terminates in the SI & SII areas of cortex
 Sensations carried:
Fine touch, tactile localization, tactile discrimination, vibration, pressure, pain, conscious
proprioception & stereognosis.

2. Antero – lateral pathway

Origin: From the dorsal horn of spinal cord
Course:
I order neuron
 In the posterior nerve root
 After entering into spinal cord ascend up 1-3 segments or immediately end in nuclei of dorsal
horn.
II. Order neuron
 Starts from dorsal horn spinal cord
 Cross to opposite side in the anterior commissure
 Form 2 pathways
- Anterior spinothalamic tract
- Lateral spinothalamic tract
 Anterior spinothalamic tract runs in the anterior white column
 Lateral spinothalamic tract runs in the lateral white column of spinal cord
 Pass through medulla, pons, & mid brain
 Terminate in the VPLN of thalamus
III. Order neuron:
 from VPLN of thalamus
 pass through internal capsule
 terminate in the somatosensory cortex
Sensations carried:
Anterior spinothalamic tract – crude touch & pressure
Lateral spinothalamic tract – pain & temperature
 4

4. Regulation of Muscle Tone

Resistance of the muscle to stretch due to continuous state of tension in the muscle is called
muscle tone
Control of muscle tone:
 Muscle tone is purely a spinal segmental reflex.
 Produced by continuous, asynchronous, low frequency discharge from anterior horn motor
neurons
 This depends up on the activation of muscle spindle & stretch reflex.
Role of muscle Spindle
 Receptor organ present in the muscle
 Consists of infrafusal fibers (nuclear bag and nuclear chain fibers)
Sensory supply
 Group-Ia (annulospiral ending) – supply both fibers
 Group-II (Flower spray endings) – supply only nuclear chain fibers
Motor nerve supply
Gamma motor neuron
Muscle spindle participate in stretch reflex which play an important role in regulation of muscle tone
and posture
Role of stretch reflex
Reflex arc:
 Receptor - Muscle spindle
 Stimulus – Stretch
 Afferent – Group Ia & II fibers
 Center – Spinal Cord
 Efferent limb – motor nerve fiber ( α motor neuron)
 Response: Contraction of extra fusal fibers
Two types of reflexes
Dynamic stretch reflex: (phasic stretch reflex)
Activation of Group Ia fibers - contraction of agonist muscle and relaxation of antagonistic
muscle (helps is movement)
Tonic stretch reflex:
Activation of Group Ia & II fibers - continuous steady contraction of the antigravity muscles due
to asynchoronous discharge of motor units supplying the muscle
(necessary for maintaining muscle tone and posture)
Role of γ motor neurons on muscle tone
 γ motor neuron increases the sensitivity of muscle spindle to stretch
 increase inγ motor (gamma motor) neuron discharge increases muscle tone
 γ motor neuron discharge is increased in following conditions
noxious (painful) stimulation of skin
anxiety
Jendrassik phenomenon
Role of higher centers in regulation of muscle tone
Brainstem:
Brain stem reticular formation
Facilitatory reticulospinal tract(Pons) Inhibitory reticulospinal tract(Medulla)

Facilitates motor neuron discharge Inhibits motor neuron discharge

↑muscle tone ↓muscle tone

 5

Cerebellum: Increases muscle tone by

Facilitating motor cortex
Facilitating descending pathways
Cerebral cortex

Cerebral cortex Indirect pathway

Pyramidal tract Brain stem nuclei

Facilitates muscle tone Inhibits muscle tone

Applied
Hypotonia: ↓in muscle tone (lower motor neuron lesion & cerebellar lesion)
Hypertonia: ↑ in muscle tone (UMN lesion)
Spasticity – hypertonia only in antagonistic muscles (clasp knife rigidity)
(e.g) Hemiplegia due to pyramidal lesion
Rigidity: Hypertonia in both agonistic & antagonistic muscle
e.g Basal ganglia lesion – Parkinsonism
-------------------------------------------------------------------------------------------------------------------------------
5. VESTIBULAR APPARATUS
Components:
Vestibule (Utricle & Saccule)
Semicircular canals
Receptors:
Vestibule (otolithic organ) – Macula
Semicircular canals – Crista ampullaris
Stimulus
Vestibule - Linear acceleration
Semicircular canals – angular rotation
Activation of semi circular canals
Angular rotation

Movement of fluid in the semi circular canals

Bending of stereocilia towards the kinocilium

Entry of K+ into the hair cell

Depolarization

Calcium influx

Release of excitatory neurotransmitter (Glutamate)

On the opposite side:
Stereocilia move away from kinociliun

Hyperpolarization

Inhibition of Semicircular canals on opposite side

-Both of these cause relaxation of muscles on same side & contraction of muscles on opposite side
 6

Functions of Semicircular canals:

-helps to maintain equilibrium during rotational movements
-helps in visual fixation during angular rotation of head (vestibule-ocular reflex)

Otolith organ (vestibule) activation

Utricle responds to horizontal acceleration & Saccule responds to vertical acceleration
Functions of otolithic organ:
-gives information about static position of head
-respond to linear acceleration in different directions
Vestibular pathway

Vestibular apparatus

Vestibular division of VIII cranial nerve

Vestibular nucleus (Brain stem)

Vestibulo – cerebellar tract

Vermis of cerebellum

Cerebellar cortex Vestibular nucleus Vestibulospinal tract Spinal cord

6. Nuclei & Functions of Hypothalamus (important - regulation of water
balance, regulation of food intake & body temperature)
Nuclei of hypothalamus
1. Supra optic area: Includes supra optic, Suprachiasmatic, paraventricular & anterior nuclei
2. Preoptic area: Medial & lateral preoptic nuclei
3. Tuberal area: Ventromedial, dorsomedial, arcuate, lateral & posterior nucleus
4. Mammillary area: Medial & lateral mamillary, pre & supramamillary nuclei.
Functions of Hypothalamus
a) Regulation of food intake

Ventromedial Nucleus Lateral Nucleus

(Satiety center) (Feeding Center)

Inhibits feeding center Hunger

↑Food intake ↓food intake

b) Regulation of water intake

Tonicity of body fluid ECF volume

Osmoreceptors Baroreceptors

Thirst center Thirst center Angiotensin II

↑Water intake ↑Water intake Subfornical organ

Thirst center
 7

c) Regulation of body Temperature

Pre optic nucleus of anterior hypothalamus (heat loss center)  Sweating and vasodilatation
Posterior hypothalamus (heat gain center)  Shivering & vasoconstriction
d) Control of ANS
(Acts as a head ganglion of ANS)

Stimulation of anterior Stimulation of posterior

Hypothalamus Hypothalamus

↑HR, BP & HCL secretion ↓HR & BP, Pupillary dilatation,

Micturition, erection of penis sweating & piloerection
(Parasympathetic effects) (sympathetic effects)
e) Control of Pituitary
Hypothalamus Supra optic & paraventricular nuclei of hypothalamus

Releasing &
inhibitory
Hormones

Anterior pituitary Posterior pituitary

Trophic hormones ADH Oxytocin

Target endocrine gland Water re-absorption Milk secretion

In kidney in mammary glands
&
contraction of uterus
f) Role in circadian rhythm
-Hypothalamus play a role in influencing the changes in body functions tuned to the day and night
cycle (circadian rhythm)

Retina

Optic tract

Suprachiasmatic nucleus of hypothalamus

Pineal gland

Melatonin

Day & night variations

g) Role in emotions:
Hypothalamus is a part of papez circuit which is responsible for emotional behavior.
 8

h) Role in stress
Hypothalamus helps to protect the body from damaging effects of stress
Stress

Cerebral cortex & Limbic system

Sympathetic
Nervous system Hypothalamus Adrenal cortex Adrenal medulla

Glucocorticoids Catecholamines
i) Role in sleep wakeful cycle
Hypothalmus has 2 sleep centers
- diencephalic sleep zone
- basal fore brain sleep zone
j) Role in sexual behavior
Hypothalamic areas (Preoptic & anterior hypothalamus) are responsible for sexual behavior like
mating, attracting the opposite sex etc.
k) Reward & punishment
Ventromedial nucleus – Reward center
Posterior & lateral nucleus - Punishment center
Important Functions:
a) Role of Hypothalamus in food intake
Food intake is controlled by 2 nuclei. They are
i) Ventromedial nucleus (VMN) – Satiety center
Inhibits the feedings center
Produces satiety (satisfaction) after taking food
Destruction of VMN - Hyperphagia & obesity
Stimulation of VMN - Hypophagia (↓food intake)
ii) Lateral nucleus (LN) – Feeding center
Stimulaters appetite
Produces hunger
Destruction of LN – aphagia & starvation
Stimulation of LN – Hyperphagia (↑ food intake)
Hypothesis about food intake
1. Glucostatic Hypothesis
Hyperglycemia in blood  ↓VMN activity  ↓ food intake
Hypoglycemia in blood ↑VMN activity ↑ food intake
2. Lipostatic Hypothesis:
Adipose tissue secretes “leptin”  inhibits hypothalaminus ↓ food intake
3. Gut peptide Hypothesis
Presence of food in GI tract  release of intestinal peptides (GRP, glucagon, somatostatin &
CCK)  acts on brain  satiety
4. Thermostatic Hypothesis
↓Body temperature ↑ food intake
↑Body temperature ↓ food intake
b) Role of Hypothalamus in regulation of water intake
 Mainly involves ‘thirst center
 Dorsal or lateral hypothalamus acts as thirst center
 Water intake mainly depends upon the stimulation of thirst center
 Thirst center is stimulated in 2 conditions
 9

a) in the increased tonicity of the body fluid

b) in the decreased ECF volume
a) Increase in the tonicity of body fluid

Stimulation of osmoreceptors

Stimulation of thirst center

Water intake
b) Decrease in ECF volume

Baroreceptors

Stimulation of Thirst center Angiotensi II

↑Water intake Subfornical organ

Thirst center
C. Regulation of Body Temperature
 Hypothalamus is called as ‘biological thermostat as it controls the body temperature constant
 Involves preoptic region of the anterior hypothalamus & posterior hypothalamus
Preoptic nucleus of anterior hypothalamus -- heat loss center
Posterior hypothalamus -- heat gain center
Stimulation of the centers occurs through 2 mechanisms
a) Cutaneous thermoreceptors
b) Blood flowing through hypothalamus
(-mediated through serotonergic pathway)
Stimulation of anterior hypothalamus Stimulation of posterior hypothalamus

Vasodilatation, sweating Vasoconstriction

& panting Shivering & Piloerection
-------------------------------------------------------------------------------------------------------------------------------
7. THALAMUS
Specific sensory nuclei
 ventrobasal group (VPLN & VPMN)
 medial & lateral geniculate bodies
Non specific sensory nuclei
 midline & intralaminar nuclei
Nuclei concerned with efferent control
 ventrolateral & ventro Anterior Nuclei
Nuclei concerned with higher functions
 dorsomedial, dorsolateral, pulvinar, posterolateral & Anterior nucleus
Functions
a) Sensory Relay Center:
sensory relay center for the following sensations:
 Tactile sensation
 vibration
 pressure
 conscious proprioception
 10

 stereognosis
 sexual sensation
 visual sensation (LGB)
b) Centre for crude sensations:
 Perceives the crude touch, pain & Temperature Sensation
c) Integrator of motor signals
 controls the smooth, slow and coordinated movements by its connections with cerebellum basal
ganglia & cerebral cortex.
d) Role in memory & emotions
 Being a part of Papez circuit, it influences recent memory & emotions.
Papez circuit
Mammillary body of Hypothalamus

Anterior Nucleus Hippocampus

Of thalamus

Cingulate gyrus
e) Role in sleep wakefulness cycle
 influences sleep wakefulness cycle.
 stimulation causes alertness of animal which facilitates learning process
 produces the B-rhythm of EEG
 Non-specific Nuclei are responsible for them
 Connections involved. (Reticulo thalamo cortical & Cortico thalamo reticular)
--------------------------------------------------------------------------------------------------------------------
8. Withdrawl reflex
Refers to the withdrawal of body parts by flexion of limbs when a painful (noxious)
stimulus is applied.
 -It is a polysynaptic reflex
Receptors: Nociceptors
Afferent Limb: Type III & IV somatic afferents
Center: Spinal Cord
Efferent fibers: Somatomotor neuron supplying the flexor muscles of same side and
extensor muscles of opposite side.
Response:
Mild stimulus- flexion of limb of same side and extension of limb of opposite side.
Stronger stimulus - response in all four limbs.
(Reason: a) Irradiation of impulse, b) Recruitment of more motor units)
Special features:
 Withdrawl reflex is a protective reflex (protects the tissue from damage)
 Pre potent (stops all other spinal reflexes temporarily)
 Shows local sign ie., response depends upon the location of the stimulus
 Stronger stimulus causes wide spread and prolonged response
(Causes: After discharge due to involvement of many interneuronal pathways
& reverberatory circuits in the spinal cord)
 11

----------------------------------------------------------------------------------------------------
9. Modulation of Pain/ Endogenous Pain Relief System
Analgesia [inhibition of pain]:
1. Gate control theory
2. Endogenous pain relief from PAG(Peri Aqueductal Grey matter) & NRM / Central Pain
suppressing Mechanisms
3. By release of Endogenous opioid peptides (Enkephalins & Endorphins)
Gate control theory of pain
- the posterior or dorsal horn acts as a Gate for pain
- pain impulses in the spinal cord can be modified or gated by other afferent impulses [touch
,pressure vibration] that enter the spinal cord
- Large myelinated A fibers interact with small unmyelinated C fibers via
inhibitory cells of the Substatia gelatinosa of the spinal cord
- Stimulation of C fibers inhibits SG cells & favours passage of impulses along
the pathway of pain in the spinal cord.
- Stimulation of large ‘A’ fibers increases SG activity & block impulse
transmission to nerve cells concerned with pain-
(inhibit transmission of pain from the ‘C’ fibers to Spinothalamic tract.-
presynaptic inhibition)
- pain inhibiting opioids also act at the level of gate
Endogenous pain relief from PAG/central pain suppressing mechanism
- Descending pathways arise from Periaqueductal gray matter [surrounding aqueduct of Sylvius]
[release Encephalin]  Descend & connect with Nucleus raphe magnus of medulla release
of Serotonin  posterior horn cells of spinal cord  inhibits the release of substance “P” from
the pain fibers
 12

Opioid peptides:
oEnkephalins—
 Met enkephalins ,Leu enkephalins
o Endorphins-
 Beta endorphins, & Dynorphins
o Similar in action to Morphine
o Present in PAG (peri aqueductal gray matter),NRM( nucleus raphae
magnus),periventricular
o areas, posterior horn cells, GITract & Hypothalamus
o Endogenous morphine - ENDORPHINE
 Two sites of action:
-Terminals of pain fibers (receptors) & decrease the response of the receptors
to nociceptive stimuli
-At spinal level – binds to opioid receptors & decreases the release of
substance - P
---------------------------------------------------------------------------------------------------- --

10. REFERRED PAIN

Visceral pain instead of being felt at the site of the viscera is frequently felt at some
distance,on somatic structures. This is called referred pain
Eg: Appendicitis pain at the umbilicus
Cardiac pain at the inner aspect of left arm
Cholecystitis at the tip of the shoulder.
Theories of referred pain: (mechanism of referred pain)
1. Convergence theory: Fibers carrying pain- both from the viscus & the
corresponding dermatome (somatic structures) converge on the same pathway to
the cortex
2. Facilitation theory: The visceral pain produces a subliminal fringe effect on the
Substantia Gelatinosa Rolando [SGR] cells which receive somatic pain nerves

CONVERGENCE THEORY
 13

11. Inverse Stretch Reflex

Refers to relaxation of muscle in response to a strong stretch.
Also called as lengthening reaction or clasp knife reflex.
Receptors: Golgi tendon organ
Afferent fibers: Group Ib fibers
Center: Corresponding spinal segment
Efferent fibers: α motor neuron to the corresponding muscle
Response: Inhibition of α motor neuron by the inhibitory interneuron and relaxation of the
corresponding muscle.
Functions:
-Monitors the force generated in the muscle
-reflex is called autogenic inhibition
-monitors muscle tension and prevents rupture of muscle
-along with stretch reflex maintains optimal motor responses for postural adjustments
-----------------------------------------------------------------------------------------------------------------------------------
12. Reciprocal innervations
-refers to the contraction of agonist muscles and relaxations of the antagonistic muscles in response to
the stimulation of an afferent nerve
Circuit:
Afferent fibers: Group Ia & II fibers
Center: spinal card
Efferent fibers: motor neurons supplying agonist and antagonistic muscle
Response: contraction of agonist muscle and relaxation of antagonistic muscle
(relaxation is due to stimulation of an inhibitory interneuron)
Importance:
-essential for normal physiological movements like walking
-useful in eliciting crossed extensor reflex between two upper limbs

13. Crossed extensor reflex

- stimulation of a limb causes flexion of limb on same side and extension of opposite limb.
- Mediated through interneurons
-Take part in withdrawal reflex
 1

CONDITIONED REFLEXES
Learning refers to a neural mechanism by which the individual changes his or her behavior on the
basis of past experience or acquisition of new information by the individual

Learning

Reflex Learning Incidental Learning

Non Associative Associative

Associate learning can be studied by conditioned reflexes
Conditioned Reflexes

Classical conditioning Operant conditioning

Classical conditioning
-refers to a reflex response to a stimulus that is acquired by repeatedly pairing the stimulus with
another stimulus that does not normally produce the response.

The stimulus which normally produce the response-- unconditioned stimulus

The stimulus that normally does not produce the response – conditioned stimulus

Pavlov’s experiment
Meat placed in the mouth of a dog --- salivation
(unconditioned stimulus)

Bell ringing alone --- no salivation

(conditioned stimulus)

UCS + CS --- salivation

After repetition of UCS + CS for many times

Conditioned stimulus alone ---salivation

(bell ringing)

Operant conditioning

The animal has to operate first to learn the process

(e.g) the animal presses a bar to get a food pellet.

Features of conditioned reflexes

If the CS is presented repeatedly without UCS, the conditioned reflex eventually disappears. This
is called extinction or internal inhibition.

It the CS is presented repeatedly with UCS, the conditioned reflex is reinforced. This is a must
for maintaining a conditioned reflex.

Physiological basis of conditioned reflex

The development of a conditioned reflex is due to formation of a new functional connection
between the neurons of CNS

HABITUATION & SENSITIZATION

Habituation
Refers to decrease in response to a benign stimulus when the stimulus is presented repeatedly.
When the stimulus is applied for the first time. It is novel & evokes reaction. This response is
called “orientation reflex” or “what is it” response.
Eventually the subject totally ignores the stimulus and gets habituated to it.
 2

Physiological basis of Habituation

Gradual inactivation of Calcium channels and consequent reduction in the release of a
neurotransmitter.
Example for Habituation
Riding a bicycle for the first time may be exciting. After repeating it, it becomes a habit.
Sensitization
When a habituated stimulus is coupled with a distinctly pleasant or unpleasant stimulus, a greater
response is produced.
Physiological basis of Sensitization
-due to increased levels of cAMP via an increase in Ca2+ levels in the post synaptic neuron
-the response in transient but can be prolonged
Example for sensitization
-the mother who sleeps through many kinds of noise but wakes promptly when her baby cries.
Importance of / significance of Habituation and sensitization
-Habituation & sensitization take part in learning & memory
-Habituation takes part in negative memory which prevents over burdening of memory storage.
-Sensitization takes part in positive memory
---------------------------------------------------------------------------------------------------------------------
Papez Circuit
Mammillary body of Hypothalamus
Mammillo thalamic
tract

Anterior Nucleus of thalamus Hippocampus

Cingulate gyrus
Significance of this circuit
-Hippocampus connections to diencephalon (thalamus & hypothalamus) takes part in recent
memory
-Hippocampal connections to amygdala is involved in emotions related to memory
-Hippocampus is a part of limbic system which is concerned with emotional behavior like anger,
fear, etc.,
-Anterior Nucleus of thalamus forms a part of diencephalic sleep zone – stimulation of which
produces slow waves in EEG –
---------------------------------------------------------------------------------------------------------------------
Memory
-Refers to the ability to recall past events at a conscious or a subconscious level.
Types of memory
On the basis of recall of stored information
a) Non declarative (implicit) memory
-Subconscious recall of skills, habits & classical conditioned reflexes
-Also called as reflexive memory
(e.g) cycling, driving etc.,)
b) Declarative (Explicity) memory
-conscious recollection of stored information
2 types
i) short term memory
-recalling within a few minutes or few days
(e.g) recalling a phone number to dial immediately after memorizing it.
ii) Long term memory: (remote memory)
-recalling the stored information even after few days or few years
(e.g) remembering about the picnic enjoyed
Mechanism of short term memory
1. Post titanic potentiation or facilitation
When an excitatory presynaptic neuron is stimulated for a brief period by a tetanizing current,
the synapse becomes more excitable after stoppage of stimulus.This is due to accumulation of
Calcium in presynaptic nerve endings.
 3

2. Reverberatory circuit theory

Reverberation of impulses between cerebral cortex brainstem and subcortical nuclei
through reverberating circuits.
3. Presynaptic facilitation
The presynaptic neuron is facilitated for a long time by neurons that lie on presynaptic
Terminals. Neurotransmitter involved is serotonin
Mechanism of long term memory
Long term potentiation
Physiological changes
-changes in the gene expression in postsynaption neuron
- in the synthesis and release of excitatory neurotransmitter
-changes in the response of receptors in the post synaptic membrance
Anatomical changes
-changes in the member & shapes of dendritic spines
-changes in number & size of synapses
-thickening of cortex
-formation of new synaptic connections
Chemical changes
-increase in RNA, protein & neurotransmitter synthesis
Consolidation of recent memory into permanent (long term memory)
-refers to the transfer of information from short term memory to long term memory
-recent memory initiates chemical, physical and structural changes in the synapses that
are responsible for permanent memory
-Hippocampus is the area mainly responsible for recent memory and its consolidation in
permanent memory
-consolidation will be lost in case of
-brain injury
-electric shock
Neural connections involved in memory (Learn from book)
Applied
Amnesia – loss of memory
Korsakoff’s syndrome – loss of memory in alcoholics
Reterograde amnesia – inability to remember the events that occurs before the
impairment of brain function
Anterograde amnesia – failure to learn new things, but long term memory is intact
CEREBROSPINAL FLUID
Cerebrospinal fluid is the fluid present in te ventricular system of the brain, subarachnoid space &
central spinal canal
Formation of CSF

CSF is mainly formed by choroidal plexus, which are covered by specialized ependymal cells.
The choroidal plexus are located in the cerebral ventricles (lateral, third and fourth). About 500
ml of CSF is secreted per day.

Normal CSF pressure – 60 – 100mm Hg of water

Amount of CSF - 160 Mgml

Circulation:
Lateral ventricles
Foramen of Manroe
III Ventricle
Aqueduct of sylvius
IV ventricle

Foramina of magendie Foramina of luschka

Subarachnoid space Subarachanoid space

80% dural sinus 20% spinal veins

 4

Absorption
Arachnoid villi play an important role in absorption of CSF
The CSF is removed through arachnoid villi into dural venous sinuses in the cranium

Functions:
1) Protective function:
-forms a liquid cushion surrounding brain and spinal cord. The brain simply floats in the fluid.
This prevents any mechanical injury
-gives buoyancy to brain. This reduces brain weight by 97% and thus prevents the brain from
crushing under its own weight

2) Medium of exchange
-nutritive substances are provided to the cells of CNS by CSF only. CSF is in direct contact with
neurons.
-CSFacts as a lymph and removes proteins and waste products of metabolism from the cells.

3. Reservoir function / regulation of cranial content volume

Monro Kellie Doctrine – The volume of blood, CSF & brain in the cranium at any time must be
relatively constant.
CSF regulates the contents of cranium
-increase in blood volume of brain  drainage of CSF
-decrease in blood volume of brain  retention of CSF
Thus the total volume of cranial content is kept constant.
4.Other functions
- Provides a proper chemical environment for the optimal activity of the neurons
-Useful for the diagnosis of brain disorder as it reflects the brain function
Applied
1. Lumbar puncture:- CSF is drawn from subarachnoid space by inserting needle between the L3
& L4
CSF can also be drained by cisternal and ventricular puncture
2. Hydrocephalus: Accumulation of CSF
Causes: increase in production of CSF, obstruction to CSF circulation
If CSF accumulates in ventricles --- internal hydrocephalus
If CSF accumulates in subarachnoid space --- external hydrocephalus
3.Counter – coup injury: When the head receives a severe blow, the brain gets injured on the
opposite side of blow
-----------------------------------------------------------------------------------------------------------------
APHASIA
Definition
Speech disorders in the comprehension or production of spoken or written language. The
disorders are not due to defects of vision or hearing or due to motor paralysis, but caused by
lesions in the association areas which are responsible for integrating activity.
Types
Sensory or wernicke’s or Fluent aphasia
Motor or Broca’s or Non-fluent aphasia
Global Aphasia
Anomic Aphasia
Causes:
1. Cerebral thrombosis
2. Cerebral infarction
3. Injury to the brain during accidents
4. Inadequate blood flow to the parts of the brain due to vascular changes
5. Tumours of the brain
 5

Type of Site of lesion Characteristic features Characteristic

Name errors (e.g)
aphasia Chair
Fluent Wernicke’s area Excessive talk with full of Stool or choss
a) Wernicke’s (Area 22) Jargon & Neologisms (Neologisms)
aphasia
(sensory
aphasia)
b) Conduction
Aphasia

1) Pure word Angular gyrus/ Trouble in understanding the I know.. I have

blindness Visuopsychic area written language or pictures. lots of them
Can not name the colors or
objects
(Pure word blindness)
2) Pure word Areas 40, 41 & 42 Trouble in comprehending the Flair……. no
deafness (in and around spoken word. Unable to repeat swair……..fair
auditory cortex) or write on dictation
Non fluent Broca’s area (Area Slow speech, words are hard to “Tssair”
c) motor/ Broca’s 44) come by, limited to two or three
aphasia words to express the whole
range of meaning & emotion
d) Global Both wernicke’s & Scanty non fluent speech.
Aphasia Broca’s area All aspects of speech and
language are impaired

-----------------------------------------------------------------------------------------------------------------
Reticular Formation
Reticular formation – Functions
1. Role in muscle tone regulation:
- Descending extrapyramidal tracts from reticular formation (Reticulo spinal tract) -
regulate muscle tone, posture & equilibrium
- mainly modulates the tone of antigravity muscles.
Two tracts:
Lateral Facititatory reticulo spinal tract from pons
Medial Inhibitory reticulo spinal tract from medulla
2. Role in sleep & wakefulness cycle
The ascending reticular activating system of reticular formation has a role in this process
ARAS:
RF of midbrain

Intralaminar Nuclei of Thalamus (Non specific nucles)

Cerebral cortex (all parts)

Activation of ARAS Wakefulness, alertness & consciousness

Inactivation of ARAS  Sleep
Other functions of ARAS
- Influences learning and memory
- Keeps the person in alert state
- Responsible for the genesis of EEG waves
3) Modulation of pain:
Raphae magnus nucleus of retircular formation

Descending serotonergic fibers

Excites SGR (substantia gelatinosa of Rolando) cells of spinal cord

Modulation of pain
 6

4) Control of visceral / vegetative functions:-

VM (Vaso Motor Center), Cardia Center, Respiratory center
Vomiting Center, Salivary Centers, etc., in descending Reticular formation of brain stem

Through Autonomic Nervous system

Control visceral functions (Gastric Secretion, GI mofility, BP, heart rate, respiratory rate,
salivation, vomiting etc.,

5) Control of neuroendocrine systems in the hypothalamus

6) Influences biological clocks (circadian rhythm) by its connections with hypothalamus
--------------------------------------------------------------------------------------------------------------
ELECTROENCEPHALOGRAM(EEG)
Definition:
Electroencephalogram is a record of summated potentials of the cerebral cortex recorded from the
surface of the scalp
Hans Berger is called the father of modern electroencephalography

Normal EEG pattern: (the waves of normal EEG)

Alpha rhythm
Beta rhythm
Theta rhythm
Delta rhythm

α Rhythm : (alpha rhythm)

-prominent component of EEG
-obtained from adult humans who are awake but with closed eyes.
-recorded from parieto – occipital area
-also called as Berger rhythm
Frenquency: 8-13 Hz
Voltage: 50uv

β(beta) rhythm:
-obtained when the eyes are opened
-indicates an alert state
-recorded from parietal and frontal regions
Frequency: 18-30 Hz (Faster rhythm)
Voltage: 5-10 uv
Theta rhythm:
-recorded from the parietal and temporal regions of children.
-do not occur in normal waking adult
But obtained from adults in emotional stress and many brain disorders
Frequency: 4-7 hz
Amplitude: (10uv)
Delta waves:
-present during sleep
-absent in wakeful adults, but present in wakeful infants
-presence of these waves in wakeful adults indicates some lesion of the brain
-recorded from occipital and other regions.
Frequency: 1-4 Hz
Amplitude: 200 uv
Applied – alpha block
-refers to a phenomenon in which alpha waves are replaced by B-rhythm (fast, irregular
waves of low amplitude)
Occurs in
-when the eyes are opened
-in conscious mental activity
-application of a stimulus
 7

USES OF EEG

Useful in:

Diagnosis of epilepsy
Localization of lesions in brain
Neurophysiological investigation
Studying of sleep pattern
Finding out the prognosis of head injuries and vascular lesions
Differentiating organic and functional disorders of brain

--------------------------------------------------------------------------------------------------------------------
SLEEP
What are the types of sleep? Differetniate them
Types of sleep:
Rapid eye movement sleep (REM)
Slow wave sleep or NREM
Differences

NREM Sleep REM Sleep(Parodoxical sleep)

1. Rapid Eye movement Absent Present
2. Brain activity Less More
3. Muscle tone Hypotonia More hypotonia
4. EEG δ( Delta) waves) β (beta) rhythm
5. Dreams Can not be recalled can be recalled
6. PGO (ponto
Geniculo occipital
Spikes No PGO spikes Present

7. Pulse, BP &
Respiratory rate Low & regular increased & irregular

8. Hormonal level Decrease in serotonin Decrease in nor adrenaline

content of raphae content in locus cerulus
Nucleus Increase in Acetylcholine
Of cortex
9. Threshold for arousal Elevated Further elevated

10. % of total sleep

Duration 75% 25%

11. O2 consumption Less More

-------------------------------------------------------------------------------------------------------------------

LIMBIC SYSTEM
Components
Amygdala
Hippocampus
Cingulate gyrus
Septal Nuclei
Medial Forebrain Bundle
Pre pyriform cortex
Entorhinal cortex
Diagonal brand of Broca
 8

Functions
a) Emotional behavior
Seat of emotions
mainly due to papez circuit involvement
Physical changes during emotions.
a) Somatic changes – Grinding of teeth, shouting, crying etc.,
b) Visceral changes -↑HR,↑RR,↑BP, Sweating etc.,
Mental changes
Awareness of sensation (cognition)
Feeling (Affect)
Urge to take action (conation)
- Amygdala stimulates emotions
- Lesion of amygdala  placidity
b) Feeding behavior
- Limbic system is responsible for discriminative feeding
- Amygdala is mainly involved
- Lesion in amygdala  hyperphagia with indiscriminative ingestion of all kinds
of food.
c) Maternal behavior
- refers to the nursing (breastfeeding) and protection of the off spring by the mother.
- Cingulate gyrus & retrosplenial portion of the limbic cortex are involved in this
- Lesion in these areas depress mater nal behavior
d) Sexual behavior
- refers to the basic sex drive (urge to copulate)
- Limbic system suppress the sexual behaviour
- Piriform cortex of limbic lobe is involved
- Bilateral lesion in this area ↑ in sexual activity
- (attempt to copulate even the animals of other species & inanimate things)
e) Motivational behavior
- refers to the motivation of learning and behavior
- reward & punishment centers in the limbic system are responsible for motivation
- septal nuclei (Reward center) & entorhinal cortex (punishment center) are parts of
limbic system
f) Autonomic functions
- Stimulation of many parts of the limbic system specially that of amygdala produces
autonomic responses such as
- changes in cardiovascular system
- changes in respiratory system
- changes in GI system
- changes are mediated through hypothalamus
 1

Special senses

10 marks
Describe the visual pathway & the effect of lesions at various levels with the suitable
diagram
The visual pathway consists of
1. Retina
2. Optic nerve
3. Optic chiasma
4. Optic tract
5. Lateral geniculate nucleus
6. Optic radiation(geniculo-calcarine tract)
7. Visual cortex
 2

1. Retina:
- rods & cones in the retina convert light in to electrical impulses.
2. Optic nerve:
- formed by the fibers of ganglion cells.
- the fibers in the lateral (temporal ) half of the nerve carry the impulses from the nasal field of the
same eye.
- the fibers in the medial half of the nerve carry impulses from the temporal field of the same eye.
3. Optic chiasma:
- formed by the crossing of medial fibres of both the optic nerves.
4. Optic tract:
- consists of nasal fibres from the opposite optic nerve and temporal fibers from the optic nerve of the
same side.
- fibres run backwards and relay in lateral geniculate nucleus of thalamus.
5. Lateral geniculate nucleus(LGN):
- The LGN is divided into six layers of cells.
- The crossed fibers of the optic tract terminate in layers 1, 4 and 6 while the uncrossed fibers terminate
in layers 2, 3 and 5.
6. Optic radiation:
- arise from the LGN
- is also referred as geniculo-calcarine tract
- the fibers are arranged supero medially & infero laterally
- terminates in primary visual area(17)
- also projected to visual association areas 18 and 19.
7. Visual cortex:
- The primary visual cortex is Brodmann area 17
- also known as V1
- located on the medial surface of the occipital lobe along the walls and lips of calcarine fissure.
Other connections
1. to suprachiasmatic nucleus of hypothalamus - concerned with circadian rhythm.
2. to pretectal nucleus which inturn sends fibres to 3rd cranial nerve nucleus = mediates the light
reflex.
3. From the occipital cortex to the frontal eye field (area 8) - concerned with the movement of
eyeball (convergence) & accommodation reflex
4. From occipital cortex to superior colliculi and from there to III, IV, VI cranial nuclei and to the
spinal cord - mediate tone, posture, equilibrium and visuospinal reflexes.

Effect of lesion of visual pathway at different levels

• The loss of vision in one entire visual field is referred as anopia.

• Loss of vision in one half of the visual field is called hemianopia. It is of two types:
– Homonymous hemianopia
– Heteronymous hemianopia
 3

Site of lesion Condition Diagram

1 Right optic Right eye anopia
nerve
2 Optic Bitemporal
chiasma hemianopia
3 Lateral Binasal
Fibers hemianopia
4 Right optic Left homonymous
Tract Hemianopia

5 Rjght optic Left homonymous

radiation Hemianopia
1 6 Inferolateral Left homonymous
2
3 fibers of Superior
optic Quadranopia
radiation
4
7 Superomedial Left homonymous
Fibers of Inferior
5 Optic Quadranopia
radiation
6
8 Inferolateral Left homonymous
fibers of Superior
7 optic Quadranopia
radiation in With macular
calcarine Sparing
fissure
8 9 Superomedial Left homonymous
9 fibers of Inferior
optic Quadranopia
radiation in With macular
10 calcarine Sparing
fissure
10 Visual cortex Left homonymous
Hemianopia
With macular
Sparing
 4

5 marks
1. Describe the circulation & functions of aqueous humour.
Aqueous humour
 Homogenous fluid that fills the anterior & Posterior chambers
 pH 7.1-7.3
 Refractive index 1.33
 Composition – Less glucose & more Lactic Acid than plasma with high ascorbic acid
Formation of Aqueous Humour:
 Formed by the ciliary processes-
 Mechanism:
1. Active secretion
2. Ultra-filtration
 Rate of formation: 2-3 cu.mm per minute
Circulation of Aqueous Humour:
 Aqueous humor circulates within the eye
 Formed by the ciliary processes
 Secreted into posterior chamber
 Passes between ligaments of lens
 Passes through pupil into Anterior chamber
 Flows into angle between cornea & iris
 Flows through trabeculae
 Flows into canal of Schelmn & extra ocular veins
 Re-enters blood circulation

Functions Of Aqueous humour:

 Provides nutrition to cornea & lens (avascular structures)
 Maintains IOP (Intra ocular pressure)
 Maintains shape of eyeball
 Acts as refractive medium
------------------------------------------------------------------------------------------------------------------------------
2. Describe the mechanism of accommodation for near vision
• It is the ability of the eye to see distant and near objects clearly. This involves the process of
adjusting the shape of the lens so that the external image falls exactly on the retina.
Accommodation of the Lens for near vision
• Ciliary muscles contract
• Ciliary body pulls forward and inward
• Tension on suspensory ligaments of lens is decreased
• Lens becomes thicker (rounder) due to its elasticity
• Pupils constricts
Near point:
• It is the nearest point to the eyes at which an object can be brought into clear focus by
accommodation.
– At age 10: Near point – 9 cm
– At age 60: Near point – 83 cm
• The near point recedes with age.
Near response
1. Convergence of eye ball
2. Constriction of pupil
3. Curvature (anterior) change in lens
 5

Accommodation of the Lens for far vision

• Ciliary muscle is relaxed
• Ciliary body is pulled backward and outward
• Tension on suspensory ligaments of lens is increased
• Lens becomes thinner (flatter) due to its elasticity
• Pupils dilate
Accommodation Reflex
Changes in the eye in response to changing the gaze from long distant to short distant
Responses:
Constriction of pupil
Convergence of eyes (medial )
Curvature of lens (increase in anterior)
Pathway of the Accommodation reflex

Near vision
.
Retina

Optic nerve

LGN

Visual cortex

Frontal eye field

Superior colliculus

III cranial nerve nucleus

Ciliary ganglion

Short ciliary nerve

Sphincter papillae Ciliary muscle Medial rectus

Constriction of pupil Curvature of lens Convergence of eye balls

(increase in anterior)
 6

-------------------------------------------------------------------------------------------------------------------------------
3. Briefly describe the mechanism of dark adaptation
Adaptation to dark (Scotopic vision)
On entering dark room from bright area, initially the vision is poor, later it improves.This decline
in visual threshold is called dark adaptation.
Time duration for dark adaptation depends
1. Intensity of light
2. Duration of exposure
3. Vit A Content
Two phases
1. Adaptation of the cones (5min)
2. Adaptation of rods (20min)

Changes in the eye during dark adaptation

1. Pupils dilate
2. Sensitivity of the photoreceptors to light increases
3. Resynthesis of photo pigments
4. Decrease in visual acuity
5. Vision changes from cone to rods (photopic to scotopic). This is called PURKINJE SHIFT.
Visual Purple//Rhodopsin Cycle

Rhodopsin (11 cis retinal+ opsin ) Pre-lumi rhodopsin

Light
Dark Lumi rhodopsin

Meta rhodopsin I
Opsin
Meta rhodopsin II
+
Retinal isomerase
11 cis retinal All transretinal
Isomerase
11 cis retinol All transretinol (Vitamin A)
 7

---------------------------------------------------------------------------------------------------------------------------
4. Write short notes on colour vision
• A sensation evoked by different wavelengths of light.
• Function of cones.
Physiological Basis of colour vision
• Three different types of cones
• Three types of pigments (the opsin protein part differs from rhodopsin),
• Each pigment has maximum absorption at different wavelengths
• blue-absorbing cones – cyanopsin pigment (max absorption at 445nm)
• green-absorbing cones – Iodopsin pigment (max absorption at 535 nm)
• red-absorbing cones – porphyropsin pigment (max absorption at 570 nm)
Primary colours
• Red
• Green
• Blue
Theories of colour vision
• Young – Helmholtz theory
• Granit modulator & dominator theory
• Hering opponent colour theory
• Land’s retinex theory
Young – Helmholtz theory
• Trichromatic theory
• Red , green , blue – 3 primary colours
• The 3 types of cones have 3 different pigments
• Each pigment is maximally sensitive to one primary colour
- But also responds to other 2 primary colours
• Sensations of various colours are due to stimulation of different receptors at
different intensities.
Processing of colour perception
• Analysis of colour occurs in the retina
• Information is then passed on to the brain for interpretation.
• Centre of fovea is blue blind.
• Blue cones are absent here.
• Retina , lateral geniculate nucleus , visual cortex all have a combined role in
perception of colour.
Colored light strikes the retina
↓
Depending on the color mixture cone will respond
↓
Response is in the form of local potentials
↓
LP transmitted in bipolar cells
↓
Ganglion cells activated
↓
Signals from the 3 cones are processed in the ganglion cell
↓
Reach the layers of LGN
↓
Processed in LGN
 8

↓
Transmitted to cortex V1
↓
Impulses reach V4

COLOUR BLOBS

• Primary visual area 17 contains color blobs – clusters of colour sensitive peg shaped neurons.
------------------------------------------------------------------------------------------------------------------------------

5. What are the errors of refraction? How will you correct it?
• In a normal human eye light rays are focused on retina.
• If not focused on retina-called Refractive errors.
• Due to abnormality in cornea or lens.
• Normal eye is called Emmetropic Eye
• Abnormal focus is called Ametropic Eye
Refractive Errors
1. Myopia (short sight)
2. Hypermetropia (Long sight)
3. Presbyopia
4. Astigmatism
5. Anisometropia
6. Aphakia
7. Cataract
Error Defect Cause Feature Correction

Myopia Long distant objects Longer eye ball / high Light rays are Biconcave
not clear refractive power of lens focused in front of lens
retina

Hypermetropia Short distant objects Shorter eye ball / Low Light rays are Biconvex
not clear refractive power of lens focused behind the lens
retina

Presbyopia Short distant objects Loss of elasticity & Decrease in the Biconvex
not clear plasticity of lens and power of lens
also decrease in power accommodation of
of ciliary muscle due to eye
aging

Astigmatism Blurring of vision Ununiform curvature of Light is focussed Cylindrical

the cornea at multiple points lens
on retina

Aniso Difference in the Congenital Eye with high Correction

metria refractive power refractive power – of each eye
between the two eyes Dominant eye separately
Eye with less with
refractive power – appropriate
 9

Suppressed eye lenses

Aphakia Diplopia & Removal of lens Complete loss of Wearing

Astigmatism due to following cataract accommodation spectacles
absence of lens surgery / dislocation of (hypermetropic) with power
lens of + 11
diopters/IOL
implantation

-----------
--------------------------------------------------------------------------------------------------------------------6.
Describe the functions of middle ear.
Components of middle ear:
1. Three small bones (ossicles):
1)Malleus
2)Incus
3)Stapes
2. Two small muscles:
1)Tensor tympani
2)Stapedius muscle
Functions of middle ear
1. Tympanic Reflex:
• When loud sounds are transmitted through the ossicular system (Malleus, Incus, stapes) into
the CNS, a reflex occurs to cause contraction of both Stapedius and tensor tympani muscles.
This is called tympanic reflex or attenuation reflex
• The contraction of tensor tympani muscles pulls the handle of the malleus inward, while the
stapedius muscle contraction pulls the stapes outward
• These two forces oppose each other and this causes rigidity of the entire ossicular system
which greatly reduces the transmission of low frequency sounds.
Significance of tympanic reflex
to protect the cochlea from damaging vibrations caused by excessive loud sound i.e. low
frequency sounds.
2. Impedance Matching:-
• Whenever sound wave travels from a thinner medium to denser medium, some
amount of sound energy is lost at the interphase of two medium.
• This happens in ear also. When sound travels from air filled middle ear into
denser fluid medium of inner ear, there is a loss of sound energy at oval window
• Middle ear compensates this by increasing the sound energy level by several times at oval
window.
• Middle ear achieves this by three mechanism which are combinely referred as impedance
matching.
The mechanism are:-
1. Area difference
• As the area of the tympanic membrane is large than the area of the oval window,
the forces collected over the tympanic membrane are concentrated on a smaller
area of oval window.
• This increases the pressure at the oval window by 17 times.
2. Lever action of the middle ear bones.
• The arm of incus is shorter than that of malleus and this produces a lever action.
• This increases the force by 1.32 times and decreases the velocity at the stapes.
 10

3. Buckling factor:-
• The tympanic membrance is conical in shape. As the membrane moves in and out
it buckles so that the arm of the malleus moves less than the surface of the
membrane.
• This also increase the force and decreases the velocity
3. Function of Eustachian tube:
Equalizes the pressure on both sides of tympanic membrane
-------------------------------------------------------------------------------------------------------------------------------
7. Describe organ of corti
Organ of Corti
• Receptor organ of hearing
• Situated on the basilar membrane
• Extends from the base to apex of cochlea
Main components of Organ of Corti

1. Inner hair cells

2. Outer hair cells
3. Rods of corti
4. Tunnel of Corti
5. Lamina reticularis
6. Basilar membrane
7. Tectorial membrane
8. Deiters' cells
9. Hensen's cells

2 7

1 5

3 9

8
6
4

• INNER HAIR CELLS

- one row ( 3500 in number)
- flask shaped
- connected to lamina reticularis
- Stereocilia of hair cells float freely
• OUTER HAIR CELLS
- three or four rows ( 20000 in number)
- test tube shaped
- stereocilia –embedded in the tectorial membrane
 11

8. Trace the pathway for hearing

I order neuron :
From the bases of the hair cells  cell bodies form the spiral ganglion around the modiolus
 axons form the cochlear nerve joins with the vestibular nerve to form the
vestibulocochlear nerve  end in cochlear nuclei
II order neuron :
From cochlear nuclei  ascend to the nearby superior olivary nucleus (of both sides)  then
ascend in the lateral lemniscus  end in inferior colliculi of midbrain
III order neuron:
From inferior colliculi to medial geniculate bodies of thalamus
IV order neurons: complete the pathway from thalamus to primary auditory complex
 12

9. Trace the olfactory pathway

receptor cell axon

↓
pierce the cribriform plate of ethmoid
↓
enters olfactory bulb
↓
synapse with dendrites of mitral cells to form olfactory glomeruli
↓
axons of mitral cells pass posteriorly through olfactory stria
↓
olfactory cortex
(anterior olfactory nucleus, olfactory tubercle, prepyriform cortex, amygdala, entorhinal cortex
↓
From the olfactory cortex signals reach
↓
– Orbito frontal cortex
– Hypothalamus
– Hippocampus
Thus olfactory impulses are projected both to
– Neocortex
Perception & discrimination of odours
– Limbic system
Emotional, motivational, behavioral & physiological effects of odours

Olfactory
Cribriform plate of ethmoid bone Glomerulus
straie
bone

Olfactory bulb

Olfactory
neuron

Olfactory receptors
 13

10. High light the special features of olfactory pathway

Pathway involves only two sets of neurons

Receptor is a modified neuron
Neurons are in direct contact with external environment
Neurons degenerate & regenerate periodically
No relay in thalamus
Olfactory signals do not reach somatosensory cortex but reach orbitofrontal cortex
Impulses reach limbic system & so related to food and sex related beaviour
-------------------------------------------------------------------------------------------------------------------
11. Trace the taste pathway
Taste buds

Taste fibres in vii, ix & x nerves (I order neuron)

Tractus solitarius (in medulla)

Nucleus tractus solitarius (II order neuron)
 Cross over
Joins medial leminiscus

VPM (Ventral Postero Medial Nucleus of thalamus (III order neuron)

Brodman’s area 43

Gustatory Pathway from Taste

Buds

Figure 16.2
 14

12. Name the primary taste sensation. How are they distributed on the tongue?
Outline the basic taste modalities & explain the mechanism of taste sensation

Primary taste sensations

1. Sweet
2. Salt
3. Sour
4. Bitter
5. Umami

BASIC TASTE PRODUCED BY MECHANISM OF PART OF TONGUE MOST

SENSATIONS STIMULATION SENSITIVE

Sweet Sugars, glycols & ↑ cAMP→↓K+ Tip

aldehydes. conductance

Bitter Alkaloids ↑ IP3→ ↑Ca++ release Back

Sour H+ ions Blocking K+ channels Posterior ½ of lateral

Salt Anions of ionised salts Na+ ion permeability Anterior ½ of lateral

Umami Monosodium -------- ---------

Glutamate

3. Sensory Tracts
1.Dorsal column pathway
Origin: From the dorsal column of spinal cord
Course:
I order neuron
 In the posterior nerve root
 After entering into spinal cord, ascend in the dorsal column of spinal cord
 Terminate in the nucleus gracilis & nucleus cuneatus of medulla
II order neuron
 From nucleus gracilis & nucleus cuneatus
 Cross to the opposite side (sensory decussation)
 Crossed fibers (called as inter nal arcuate fibers) upward in the medial lemniscus through pons &
mid brain.
 Terminate in the ventral postero lateral nucleus of thalamus (VPLN)
III order Neuron
 From VPLN of thalamus
 Pass through posterior limb of internal capsule
 Terminates in the SI & SII areas of cortex
 15

 Sensations carried:
Fine touch, tactile localization, tactile discrimination, vibration, pressure, pain, conscious
proprioception & stereognosis.

2. Antero – lateral pathway

Origin: From the dorsal horn of spinal cord
Course:
I order neuron
 In the posterior nerve root
 After entering into spinal cord ascend up 1-3 segments or immediately end in nuclei of dorsal
horn.
II. Order neuron
 Starts from dorsal horn spinal cord
 Cross to opposite side in the anterior commissure
 Form 2 pathways
- Anterior spinothalamic tract
- Lateral spinothalamic tract
 Anterior spinothalamic tract runs in the anterior white column
 Lateral spinothalamic tract runs in the lateral white column of spinal cord
 Pass through medulla, pons, & mid brain
 Terminate in the VPLN of thalamus
III. Order neuron:
 from VPLN of thalamus
 pass through internal capsule
 terminate in the somatosensory cortex
Sensations carried:
Anterior spinothalamic tract – crude touch & pressure
Lateral spinothalamic tract – pain & temperature

7. THALAMUS
Specific sensory nuclei
 ventrobasal group (VPLN & VPMN)
 medial & lateral geniculate bodies
Non specific sensory nuclei
 midline & intralaminar nuclei
Nuclei concerned with efferent control
 ventrolateral & ventro Anterior Nuclei
Nuclei concerned with higher functions
 dorsomedial, dorsolateral, pulvinar, posterolateral & Anterior nucleus
Functions
a) Sensory Relay Center:
sensory relay center for the following sensations:
 Tactile sensation
 vibration
 pressure
 conscious proprioception
 16

 stereognosis
 sexual sensation
 visual sensation (LGB)
b) Centre for crude sensations:
 Perceives the crude touch, pain & Temperature Sensation
c) Integrator of motor signals
 controls the smooth, slow and coordinated movements by its connections with cerebellum basal
ganglia & cerebral cortex.
d) Role in memory & emotions
 Being a part of Papez circuit, it influences recent memory & emotions.
Papez circuit
Mammillary body of Hypothalamus

Anterior Nucleus Hippocampus

Of thalamus

Cingulate gyrus
e) Role in sleep wakefulness cycle
 influences sleep wakefulness cycle.
 stimulation causes alertness of animal which facilitates learning process
 produces the B-rhythm of EEG
 Non-specific Nuclei are responsible for them
 Connections involved. (Reticulo thalamo cortical & Cortico thalamo reticular)

10. REFERRED PAIN

Visceral pain instead of being felt at the site of the viscera is frequently felt at some
distance,on somatic structures. This is called referred pain
Eg: Appendicitis pain at the umbilicus
Cardiac pain at the inner aspect of left arm
Cholecystitis at the tip of the shoulder.
Theories of referred pain: (mechanism of referred pain)
1. Convergence theory: Fibers carrying pain- both from the viscus & the
corresponding dermatome (somatic structures) converge on the same pathway to
the cortex
2. Facilitation theory: The visceral pain produces a subliminal fringe effect on the
Substantia Gelatinosa Rolando [SGR] cells which receive somatic pain nerves

4. PAIN PATHWAY
Pain is carried by two pathways:
i) Neospinothalamic pathway
ii) Paleospinothalamic pathway
Neospinothalamic tract: (carries fast pain)

1st order neuron: Aδ fibers from receptors to lamina I and V of spinal cord
 17

2nd order neuron: From dorsal horn of spinal cord  cross to opposite side  ascend in the lateral
white column  end in the ventral postero lateral (VPL) & ventral postero
medial (VPM) nuclei of thalamus.
(Gives few collaterals to reticular formation)

3rd order neuron: From VPL & VPM nuclei of thalamus to somatosensory cortex (areas 3, 2 &1)
of post central gyrus.

Paleospinothalamic tract: (carries slow pain)

1st order neuron: ‘C’fibers from receptors to lamina IV and V of spinal cord

2nd order neuron: From dorsal horn of spinal cord  cross to opposite side  ascend in the lateral
white column  end in intralaminar & midline nuclei of thalamus
(Gives collaterals to reticular formation, PAG and tectum of midbrain)

3rd order neuron: Arise from intralaminar & midline nuclei of thalamus & reach the entire cerebral
Cortex
Special features:
Neospinothalamic tract: concerned with localization and interpretation of quality of pain
Paleospinothalamic tract: concerned with perception of pain, arousal and alertness