Physiology

Functional principle

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 Chapter 1

Cell Physiology

✓ Cell → basic structural & functional unit of organism

✓ Molecules → Organelles (subcellular level) → Cells → tissues → organs → systems →
organism

Cell Structure and Function

I. Chemical Structure (chemical composition)

Five basic substances
1. Water (70-80%)
2. Electrolytes: cations and anions
3. Proteins (10-20%)
4. Lipids
5. Carbohydrates (10%)

II. Physical Structure

1. Organelles
I. Cytoplasmic membranous organelles
Cell membrane, Endoplasmic reticulum, Mitochondria, Golgi apparatus, Lysosomes,
Peroxisomes

II. Cytoplasmic nonmembranous organelles

Ribosomes, Centrioles, Microtubules and microfilaments, vaults

III. Nuclear membranous organelles

Nuclear membrane or envelope

IV. Nuclear nonmembranous organelles

Chromatin and nucleolus

2. Inclusion bodies
Nonliving temporary components of cytoplasm, lipid globules, glycogen granules, secretory
granules

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Structure of cell membrane
✓ dynamic, nonrigid, semipermeable and mosaic structure.
✓ 7.5 to 10 nm thick.
✓ composed primarily of protein and lipids (phospholipids and cholesterol).

✓ heads (phosphate) of phospholipid molecules → hydrophilic (water soluble).

✓ face ECF and cytoplasm.

✓ tails (fatty acid) of phospholipid molecules→ hydrophobic.

✓ face each other in the middle of the membrane →causes fluidity of the membrane
(nonrigid)

✓ Lipid insoluble substances have difficulty passing through the membrane→ selective
permeability (semipermeable)

✓ Constituents of the membrane → constantly renewed → dynamic

✓ Proteins are of various sizes and shapes → mosaic

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Types of proteins in the cell membrane
1. Integral proteins
✓ pass through the membrane → integral components of the cell membrane
✓ Transport proteins – selective permeability of cell membrane
e.g. channels, carriers, pumps
2. Peripheral proteins
✓ stud inside and outside of the membrane
✓ enzymes, antigens and cell adhesion molecules (CAMs), receptors

Functions of Cell Membrane

1. Individuality and integrity.

2. Transport of substances

2.1 Some proteins in the cell membrane function as "transport proteins"

a. Channels
Specific ions diffuse through channels.
Some are continuously open. Some are gated.
i. Voltage-gated channels
ii. Ligand or chemically-gated channels
iii. Second messenger gated channels (cAMP, IP3)
iv. Mechanically-gated channels

b. Carriers
- bind to the substances and transport them from one side of membrane to the other side
- move the substances along their concentration gradient.

c. Pumps
- carriers that move the substances against their concentration gradient. They have ATPase
activity. Energy is released from hydrolysis of ATP. Eg. Na+ K+pump

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Carriers or Pumps may also be classified into
1. Uniport: transports only one substance. Eg. Glucose transporter (GLUT)

2. Co-transporter: simultaneously transport more than one substance.

a. Symport: moves two or more different substances in the same direction. E.g. sodium dependent
glucose transporter (SGLT)

b. Antiport: moves two or more different substances in opposite direction.

i. Na+Ca2+antiport moves 3Na+ into and Ca2+
ii. Band 3 protein (anion exchanger) (HCO3- and Cl-)
iii. Na+ K+ pump moves Na+ and K+ in opposite directions

2.2. The cell membrane exhibits endocytosis and exocytosis for the transport of protein and
particulate matter.

3. Other proteins in the cell membrane function as

a. Receptors: biding sites for hormones and drugs

b. Enzymes: catalyze reaction at the membrane

c. Antigens: immunological identification marks, eg. blood group antigen, transplant antigens

d. Cell adhesion molecules (integrins, cadherins, selectins)

They attach cells to each other and give strength and stability to tissues.
They play an important role in
1. Development of nervous system
2. Holding tissues together
3. Inflammation
4. Wound healing and scar formation
5. Spread of tumors
6. Transmission of signals into and out of the cell

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 Mitochondria

Mitochondria are present in almost all cells. The more active the cell, the greater is the number
of the mitochondria.
Structure:
Each mitochondrion is a sausage-shaped structure. It is made up of double layer of unit
membrane.
The outer membrane is smooth and contains enzymes of biologic oxidation.
The inner membrane is folded and called cristae. On the cristae are repeating units and each
unit contains enzymes of respiratory chain and ATP synthase.
The space surrounding the cristae is the matrix containing enzymes of Krebs citric acid cycle.
The space between the membranes is intra-cristal space.
All of the above enzymes convert the product of carbohydrate, fat and protein metabolism to
CO2 and H2O with the synthesis of ATP (oxidative phosphorylation).
Function:
Mitochondria are the power-generating units of the cell because they produce
ATP. They can self-replicate whenever a cell required increased amounts of ATP.
They contain DNA which represents a second genetic system..

Nucleus (information center)

- present in all cells that divide.
1. Nuclear membranous organelles: nuclear membrane or envelope
2. Nuclear non-membranous organelles
Chromatin
Chromatin granules condense to form chromosomes during cell division.
Chromosomes carry genetic message.
Human cell contains 46 chromosomes (23 pairs)
Autosomes: 22 pairs
Sex chromosomes: 1 pair (Male XY, Female XX)
Chromosomes are made up of DNA and basic protein histone.
Function: Protein synthesis
Nucleolus
It functions as site of ribosomal RNA synthesis and for temporary storage of mRNA.

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 Ribosomes
- composed of 2 subunits, the larger 60s and smaller 40s subunits.
- contain about 65% RNA and 35% protein.
Function:
- the site of protein synthesis.
- Free ribosomes in the cytoplasm synthesized proteins utilized in the cell e.g., haemoglobin and
protein found in mitochondria.
Vaults
- Hollow, octagonal structures, the same shape and size as the nuclear pores.
-Function: transport mRNA or the ribosomal subunits from the nucleus to the cytoplasm for
protein synthesis.

Endoplasmic Reticulum (intracellular circulatory system)

- a complex series of tubules extending throughout cytoplasm.
- continuous with nuclear membrane, Golgi apparatus and cell membrane
- It serves as.
Two types:
1. Granular or rough-surface ER
ribosomes are attached to the membrane
Ribosomes are the site of protein synthesis such as hormones that are secreted by the cell.
2. Agranular or smooth-surface ER
lacks granules or ribosomes.
Functions
a. Metabolic functions: as site of
i. Steroid synthesis
ii. Detoxification e.g., liver cells
iii. Glycoprotein synthesis
b. Plays an important role in muscle contraction and relaxation.

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 Golgi Apparatus (Packaging unit)

- a collection of cistern
- continuous with endoplasmic reticulum and located near the nucleus.
- prominent in actively secreting cells..
Function: Package the proteins with membranes and modified for their final destination.

Lysosomes (suicide bags)

- contains many hydrolytic enzymes →destroy cellular components.

- ribonucleases, deoxyribonucleases, phosphatases, glycosidases, arylsulfatases, collagenases
and cathepsins

Function: Function as the digestive system of the cell.

1. defense and scavenger function (digest bacteria).
2. engulf and remove the worn-out components of the cell.
3. autolysis of the dead cells.
4. help in cellular differentiation and regression of tissues e.g., involution of uterus.

Peroxisomes
- contain various oxidases which generate H2O2 and catalase which converts H2O2 to H2O.
- They are most common in the liver and kidneys. They may be involved in gluconeogenesis.

Microtubules and Microfilaments

Microtubules - long and hollow structures about 15 nm in diameter, made up of tubulin protein
Microfilaments -long solid fibers 4 - 6 nm in diameter, made up to actin protein
Functions
1. Microtubules → tracks for substances → moved from one part of the cell to another
(intracellular traffic)
e.g. secretory granules or the chromosomes in mitosis

2. Microtubules and microfilaments form the skeleton of the cell.

The cytoskeleton →cell shape and permits it to change shape and movement.
3. Microfilaments play a role in muscle contraction, movement of microvilli in the intestinal
mucosa, cell movement and clot retraction.

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 Centrioles (Centrosomes)
- a pair of short cylinder-like structures located between the Golgi complex and nucleus.
- are at right angles to each other.
- wall is made up of microtubules.
Functions:
- concerned with the movement of the chromosomes during cell division by forming the poles
of the mitotic spindle.

Intercellular Connections
1. The junctions → strength and stability

a. Tight junction (zonula occluden):

✓ Made up of protein ridges, half from one cell and half from the adjacent cell.
✓ Found in epithelial cells of intestinal mucosa, renal tubules and choroid plexus.

b. Desmosomes:
Spot-like patches characterized by two adjacent cell membranes.

c. Hemidesmosome:
Half desmosomes that attach cell to basal lamina.

d. Zonula adherens:

2. Gap junction: (communication junction)

✓ Connexons (hexagonal protein) in the membrane of each cell line up with each other →
a single channel between two cells.
✓ permit substances such as ions, sugar and amino acids, rapid propagation of electrical
activity and exchange of chemical substances.
✓ found in cardiac and smooth muscles.
✓ form physical basis of "functional syncytium".

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(Zonula adherens)

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Intercellular Communication
Cells communicate with each other via chemical messengers.
Some messengers move from cell to cell via gap junctions without entering the ECF.
Cells are also affected by chemical messengers secreted into ECF.

1. Neural communication
neurotransmitters at released at synaptic junctions →act on post-synaptic cell.

2. Endocrine communication
hormones reach cells via the circulating blood.

3. Paracrine and Autocrine communication

product of cells diffuses in the ECF → affect neighboring cells (paracrine communication) or
bind to receptors on the cell that secreted them (autocrine communication).

4. Juxtacrine communication
Some growth factors attach to the trans-membrane proteins →bind to its receptor on
another cell.

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Hormone
Hormone
Paracrine
Receptor Receptor

Autocrine
Cell Cell
ISF

Hormone Receptor
Cell

Blood stream Endocrine

Cell
Neural
Juxtacrine
Nerve ending
ISF Growth factor
Neurotransmitter at
synaptic junction Receptor

Receptor
Postsynaptic membrane Cell

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 Chapter -2
Homeostasis
External and internal environment
Man (cell) and His environment
I. The External Environment (always changing)
The environment in which organisms (including man) exists may be termed the external
environment: it may be
1. physical (air, temperature, humidity, light, noise, radiation)
2. chemical (chemicals in air and water, dyes, drugs)
3. biological (plants, animals, bacteria, viruses, parasites)
4. social (family, friends, foes, human relations)
II. The Internal Environment
The chief constituents of living tissues is water.
Cells are not in direct contact with the external environment. Cells exist in body fluid (fluid =
water + dissolved substances)
Dissolved substances include:
(a) crystalloids e.g, glucose (b) electrolytes e.g, Na+, K+ (c) colloids e.g, plasma protein
The fluid environment of the cells is called the internal environment.

Body Fluid Compartment

TBW 60% of body weight in Kg

ICF ECF 20%

40%

5% IVF 15%
ISF

ECF = the internal environment.

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TBW = total body water
ICF = intracellular fluid
ECF = extracellular fluid
IVF = intravascular fluid (plasma)- internal environment of blood cells
ISF = interstitial fluid – internal environment of tissue cells

Blood vessel
Blood cell ICF

IVF

ECF

ISF

ICF ICF
Tissue cells

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Body fluid compartments and composition

Total body water (TBW) and body fluid compartments

Approximate composition of the body

Normal adult man Normal adult woman

Water (%) 65-70% 55-60%
Fat (%) 5 18
Lean (fat free) body mass 25 22

Percent total body water (TBW)

Infants have a large TBW, most of which is intracellular; this makes them very vulnerable to
dehydration.

Total body water (TBW) % body weight

Infant Male Female
Thin 80 65 55
Average 70 60 50
Fat 65 55 45

Some features of different fluid compartments

% body Major cation Major anion Osmolality pH

weight (mosm/kg)
TBW 60 - - - -
ICF 40 K+ =,
PO4 Protein 290+/-5 7.3
ECF:ISF 15 Na+ Cl- 290+/-5 7.4
ECF:IVF 5 Na+ Cl- 290+/-5 7.4

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Homeostasis
✓ ECF → Constant volume, H+, osmolarity, glucose, sodium, potassium, oxygen, carbon
dioxide and the blood pressure.

✓ The state of relative constancy of the internal environment of the body, as a

result of dynamic equilibrium, is called homeostasis (homeo = same; stasis =
constancy).

✓ Homeostasis ensures optimal cell function.

ECF temperature (37.C)

pH (7.4± 0.05)

ECF osmolality (290 ± 5

mosm/kg
Enzyme reaction

Cell size Chemical reaction

Blood pressure

Optimal cell function

✓ Mechanisms keep the internal environment relatively constant.

✓ These mechanisms are called homeostatic mechanisms.
✓ Homeostatic mechanisms are negative feedback and positive feedback
mechanisms.

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Homeostatic mechanisms
A. Negative feedback mechanisms

Definition: When the direction of the stimulus and the response of the system are opposite, it
is negative feedback.

Set value

Disturbance: increase Response: decrease towards set value

Net effect of negative feedback: the change caused by the disturbance is minimized. The set
value remains more or less the same (homeostasis).

Examples y z
1. At the molecular level, A B C

In a chemical reaction, y and z are enzymes and C is the end point. If C can inhibit these
enzymes, the concentration of C will remain more or less constant.

2. At the organ level,

A rise in blood glucose → stimulation of insulin secretion from pancreas→ insulin action→ falls
in plasma glucose back to normal.

Detector nerve
↑BP baroreceptor Medulla oblongata regulator

↓BP to normal
nerve
Heart
↓Heart rate
effector

Most functions in the body operate in a negative feedback fashion.

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B. Positive feedback mechanisms

Definition: When the response is the same as the disturbance, it is positive feedback.

Set value

Disturbance: increase Response: further increase

(B)

Net effect of positive feedback: sudden dramatic change within a very short period

+
Examples enterokinase
1. At the molecular level: Trypsinogen Trypsin
Thrombin → V and VIII
+

Thus, blood coagulation becomes faster.

2. At the cellular level: voltage changes across cell membrane →Na+ entry → more voltage
changes → more Na+ entry (generation of action potential, electrical impulse)
3. At the organ level:

contraction of uterus

descent of fetus in birth canal

discharge of stretch receptor

release of oxytocin from posterior pituitary +

further contraction of uterus

Positive feedback mechanisms may contribute towards the long-term goal of homeostasis.

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 Chapter 3
Membrane transport
Transport across the Cell Membrane
I. Passive transport mechanisms
A. Diffusion
1. Simple or free diffusion
2. Facilitated or carrier-mediated diffusion
3. Nonionic diffusion
B. Osmosis
C. Filtration

II. Active transport mechanisms

A. Primary active transport
B. Secondary active transport
C. Endocytosis
D. Exocytosis

I. Passive transport mechanisms

✓ do not depend on metabolic energy.
✓ occur along the gradient (concentration, electrical, pressure, osmotic).

A. Diffusion

- continuous random movement of molecules and ions along concentration or chemical

gradient or electrical gradient.

Fick’s law of diffusion

J=DAΔc
x
✓ net rate of diffusion (J)
✓ area available for diffusion (A)
✓ diffusion coefficient of the membrane for the diffusing substance (D)
✓ concentration ( or chemical) gradient (Δ c) and
✓ thickness of the membrane ( diffusion path) (x)

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1. Simple Diffusion
✓ Diffusion of substances across the lipid bilayer or diffusion of ions through the ion channels
✓ Eg. O2 diffusion through lipid bilayer and K+ diffusion through K+ leak channel

2. Facilitated Diffusion
✓ Diffusion of large uncharged molecules (such as glucose)
✓ facilitated by transport proteins called carriers.
✓ These proteins bind to the substance→ their configuration change → move the substance
from one side of the membrane to the other.
✓ E.g. Transport of glucose by the glucose transporter,

3. Non-ionic Diffusion
✓ It is diffusion of some weak acids or bases in non-ionic form. If in ionic form, diffusion
becomes difficult.
✓ E.g.it is NH3 and not NH4 +that readily diffuse across the renal tubular cell membrane

B. Osmosis
✓ Water will move across the semipermeable membrane from lower concentration of the
solute to the other side (diffusion of water along its concentration gradient)
✓ Osmotic pressure depends on the number of particles rather than the type of particles.

C. Filtration
✓ Fluid is forced through the membrane due to the difference in hydrostatic pressure,
✓ Depends on hydrostatic pressure gradient, the surface area and the permeability of the
membrane.
✓ Molecules smaller than the pores of the membrane pass through with the fluid and larger
molecules are retained.
✓ Filtration through the capillary wall is termed ultrafiltration because blood cells and protein
are retained.

Solvent Drag
✓ When the membrane is very permeable, the amount of fluid flowing in one direction
becomes very large (bulk flow) and the solvent tends to drag along some solute
✓ Significant in glomerular capillaries.

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II. Active Transport Mechanisms
✓ required metabolic energy
✓ the movement is against concentration or electrical gradients.

A. Primary Active Transport

✓ carried out by "protein pumps" in the cell membrane
✓ the energy is supplied by ATP

1. The Sodium-Potassium Pump (Na-K activated ATPase)

✓ alpha and beta subunits.

✓ alpha subunit has a Na+-K+ activated ATPase
✓ extrude 3Na+ from the cell and take 2K+ into it (coupling ratio=3:2).
✓ electrogenic (causes electrical charge difference across the membrane by producing net
movement of a positive charge out of the cell).

✓ 3 Na+ bind to alpha subunit from inside of the membrane → hydrolysis of ATP→
phosphorylation → protein changes its conformation → 3 Na+ are extruded from the cell.

✓ 2K+ bind to sites from outside of the membrane → dephosphorylation → protein returns to
its original conformation → releases 2K+ into the cell.

✓ found in almost all cells.

✓ It is the major energy using process in the body
1. sodium binding site

2. potassium binding site

3. ouabain (sodium potassium pump

inhibitor binding site)

4. phosphate binding site

5. ATP binding site

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2. H+-K +ATPase:
✓ extrudes H+ from the cells in exchange for K+.
✓ found in gastric mucosa and renal tubules.

3. Ca++–ATPase:
✓ pumps Ca++ out of the cytoplasm into the endoplasmic reticulum
✓ found in skeletal and cardiac muscle cells.

4. Proton-ATPase (V-ATPase):
✓ pumps protons (H) from cytoplasm into organelles such as lysosomes

5. F-ATPase: pumps proton from mitochondria matrix into intracristal space.

B. Secondary Active Transport

✓ When the transport of a substance is coupled to active transport of sodium, it is secondary
active transport.
✓ The Na+K+pump maintains the sodium gradient.
✓ The gradient → the sodium (into the cell) → substance (either into or out of the cell)
Metabolic energy is not used directly.

1. Sodium –dependent glucose transport (symport)

✓ SGLT (sodium dependent glucose transporter) in intestinal and renal tubular cells
✓ Another example: Sodium dependent amino acid transport & sodium dependent
potassium and chloride in intestinal and renal tubular cells.

2. Sodium dependent calcium transport (antiport)

✓ 3Na+ Ca++ antiport in cardiac muscle
✓ Another example: Sodium dependent H+ transport in renal tubular cells.

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C. Endocytosis
✓ Proteins and large molecules enter the cell without disruption of the cell membrane.
✓ There is loss of membrane.

There are 2 types:

1. Phagocytosis (Cell eating)
Large particulate matters (bacteria, dead tissue, or other materials visible under the
microscope) → transported into the cell.

Mechanism of phagocytosis:
✓ Contact of material with cell membrane
✓ Invagination of cell membrane and engulfment (forming pseudopodia around the
particle)
✓ Pinching off of the invagination
✓ Formation of phagocytic vacuole
✓ This vacuole combines with lysosome to form digestive vacuole.

2. Pinocytosis (Cell drinking)

Large molecules in solution (proteins) are transported into the cell.

Mechanism of pinocytosis:
✓ Contact of material with cell membrane
✓ Invagination of cell membrane
✓ Pinching off of the invagination
✓ Formation of pinocytic vacuole
✓ This vacuole may pass through the cell unaltered as in capillaries or combine with
lysosome to form digestive vacuole.

a. Constitutive endocytosis:
✓ uptake is proportionate to the concentration of the substance
✓ E.g. uptake of plasma proteins by endothelial cell of capillaries

b. Non-constitutive or receptor mediated endocytosis:

✓ receptor mediated selective process, required clathrin protein
✓ responsible for macromolecules such as protein hormones

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D. Exocytosis (cell vomiting)
✓ Extrusion of cellular secretions (protein hormones, enzymes)
✓ Adds to the total amount of cell membrane.

Mechanisms:
Proteins from Endoplasmic reticulum → Golgi apparatus.
In the Golgi apparatus→ packed into secretory granules or vesicles
Vesicles membrane fuses with the cell membrane → area of fusion breaks down
Exocytosis requires calcium, energy and "docking proteins".

Constitutive pathway: little or no prior processing or storage.

Nonconstitutive pathway: processing in the secretory granules
E.g. conversion of prohormones to mature hormones

Vesicular transport (Transcytosis or Cytopempsis)

Proteins are transported out of capillaries across the endothelial cells by endocytosis followed
by exocytosis on the interstitial side.

Protein
Endocytosis

Endothelial cell

Exocytosis

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 Chapter 4
Electrical properties of nerve and muscle cells

The ability of a living organism or cell to respond to a stimulus →Excitability.

Any change (electrical, chemical, and mechanical) in the environment of the cell →Stimulus.
The excitable tissues (nerve and muscle) respond to stimuli by changing their membrane potential →electrical
Response.

Electrical Properties of cell membrane

1. Membrane potential
2. Membrane resistance
3. Membrane capacitance

1. Membrane Potential

Under resting or unstimulated condition → an electrical potential difference across the cell membrane with the
inside negative relative to the exterior→ called the resting membrane potential (RMP) and polarized

RMP is found in almost all cells.

In a spinal motor neuron, RMP is 70 mV and is negative; the RMP is expressed as -70mV.

The decline in membrane potential (e.g from -70 mV to -60 mV) → depolarization.
The potential difference no longer exist →completely depolarized
The membrane potential towards its resting level (e.g back to -70 mV) →re-polarization
If the inside becomes positive relative to outside → the polarity is reversed
If there is an increase in membrane potential (e.g from -70 mV to -90 mV) → hyper-polarization

Genesis of Resting Membrane Potential

1. Na+-K+ pump maintains high intracellular K+ concentration and high extra-cellular Na+ concentration.

2. K+ ions diffuse out along the concentration gradient through K+ leak channels.
Intracellular anions (principally protein and organic phosphates) are no diffusible→ are not able to move out of
the cell along with K+.
Thus, there is an excess of positive charges (K+) outside the membrane and an excess of negative charges (protein
anions) inside the membrane→ a potential difference across the cell membrane.

3. Na+ tends to diffuse in along the concentration as well as electrical gradient. If there is as much Na + influx as K+
efflux, membrane potential created by K+ efflux would be abolished. This does not occur because the cell
membrane is a hundredfold less permeable to Na+ than K+. There are 2 reasons for this:
a. Although a Na+ ion is smaller than a K+ ion, its effective diameter is larger because it attracts a larger cloud of
water molecules.

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b. Many more K+ channels than Na+ channels are open in the resting membrane. Thus the K+ efflux effectively
outbalances the Na+ influx.

4. Cl- tends to diffuse in along the concentration gradient and this might increase the negativity of the membrane
potential. However, the electrical gradient opposes Cl- influx.

5. Direct electrogenic effect of Na+-K+ pump (3Na+ out for every 2K+ in, thus losing one positive charge from the
cell) contributes very little (only about 4%) to the resting membrane potential.

Maintenance of Membrane Potential

If RMP is decreased → more K+ efflux and more Cl- influx → RMP is restored

If RMP is increased → these ions move in opposite directions → RMP is restored

RMP is kept constant within narrow limits by two repolarizing forces: increased K+ efflux and increased Cl¯ influx.

2. Membrane Resistance

The cell membrane has non-polar bi-lipid layer → resists current flow across it
The current flows more freely along the membrane than across it → basis for spatial summation

3. Membrane Capacitance

The cell membrane can store electrical charges, acting as a capacitor→ the basis for temporal summation

Nerve

Functional anatomy of a neuron

The neurons → the basic building blocks of the nervous system

Functions →integration and transmission of nerve impulses

Four morphologically regions→ the cell body (soma), dendrites, axon and pre-synaptic terminals (endings)

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The cell body → the metabolic centre of the neuron
Anterograde transport → from the cell body to the synaptic knob along microtubules (axoplasmic flow)
Organelles and substances to be transported are moved along microtubules by a contractile protein (kinesin)
Reterograde transport → from the nerve ending to cell body along microtubules
(transport some used vesicles, nerve growth factor and various viruses)- mediated by dyenin

Dendrites →receiving the input to the neuron

The axon → transmits propagated impulses to the nerve ending

Most axons are myelinated, i.e. covered by a sheath of myelin, a protein-lipid complex made up of many layers of
the cell membrane of glial cells

The axon hillock and initial segment →trigger zone initiating the action potential
The terminal endings (synaptic knobs,end-feet, terminal buttons, or axon telodendria) → release synaptic
transmitter

From the functional point of view, neurons have four functional components:
a. an input component (dendrites)
b. site of origin of impulse (axon hillock and initial segment in spinal motor neuron; the first node of Ranvier
in cutaneous sensory neuron)
c. conductile component (axon)
d. an output component (terminal buttons).

Na+ channels are highly concentrated in the node of Ranvier and the initial segment in myelinated neurons.

Excitation of neuron

Grading of Electrical Stimuli

The stimulus, depending on its strength, produces two types of changes:
Local, non-propagated potential changes (e.g. receptor, postsynaptic, electrotonic or endplate potentials)
Propagated all-or-none action potentials (nerve or muscle impulses)

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1. Threshold (or liminal) stimulus:
Minimal current strength required to evoke an action potential.

2. Sub-threshold (or subliminal) stimulus:

Stimulus which just fails to evoke an action potential.
Two sub-threshold stimuli may summate to evoke a response.
When two sub-threshold stimuli are applied close to each other→ Spatial summation
When two sub-threshold stimuli are applied one after another in quick succession → Temporal summation

3. Supra-threshold stimulus:
Stronger than threshold stimulus but evokes the same response as that produced by the threshold stimulus.

Electrical responses of a neuron

1. Electrotonic Potentials

Cathode currents → a localized depolarizing change (catelectrotonic potential)

Anodal current → a hyper-polarization potential change (anelectrotonic potential)
They are passive changes in membrane polarization.
Re-polarizing forces restore the membrane potential.

Up to 7 mV of deflection, their size is proportionate to the strength of the stimulus. i.e. they are graded.

2. Local Response

With cathodal stimulation producing 7-15 mV of depolarization, voltage-gated sodium channels begin to open at
an increasing rate and resultant increase in Na+ influx causes a disproportionately greater response. This is called
the local response.

3. The Action Potential: the spike potential

At 15 mV of depolarization, there is sudden rapid decline of membrane potential, called the spike potential (action
potential). This is due to operation of the following regenerative positive feedback cycle (Hodgkin cycle).

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Na+ influx is so great that it temporarily swamps the repolarizing forces, completely abolishing the membrane
potential (the zero or isopotential line) and even reversing it (inside positive about +35 mV) briefly. The membrane
potential at which a runaway depolarization is initiated is called the firing level.

The falling (repolarizing) phase of the action potential is due to

1. cessation of an increase in Na+ influx as a result of rapid closure of Na+ channels (channel inactivation) and
reversal of the electrical gradient (inside positive).

2. increased K+ efflux due to slower and more prolonged opening of voltage gated K + channels.

The Action Potential: the after-depolarization

When repolarization is about 70% complete, the rate of repolarization decreases (the after-depolarization). This
may be due to decreased rate of K+ efflux as a result of build-up of K+ outside the membrane.

The Action Potential: the after-hyper polarization

This is a small (1-2 mV) but prolonged (about 40 ms) overshoot in the hyperpolarizing direction and is due to
continued increase in K+ efflux as a result of delayed closure of the voltage-gated K+ channels.

Stimulus artifact → due to the current leakage from the stimulating electrode to the recording electrode. It marks
the point at which stimulus was applied.

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Latent period (an iso-potential interval) → duration the impulse takes to travel along the axon from the site of
stimulation to the recording electrodes. CV = Distance / time taken. e.g. 4 cm / 2 ms = 20 m/s

Monophasic → action potential is primarily in one direction

All or none law

The action potential fails to occur if the stimulus is sub-threshold in magnitude. It occurs at or above the threshold
intensity.
Every action potential has the same shape, amplitude and duration.
This applies to single axon preparation under constant experimental conditions.

The information in the signal → the frequency and number of spikes

↑magnitude of stimulus → ↑frequency of spikes

↑duration of the stimulus→↑ the number of spikes

Effects of environmental ionic concentration on action potential

↑ECF K+ → ↓RMP

↓ECF Na+ → ↓the size of the action potential but has little effect on RMP

↓ECF Ca+ →↑increases the excitability of nerve and muscle

30
Changes in excitability during an electrical response
Phase Excitability
Anelectrotonic potential decreased : hyperpolarized membrane

Catelectrotonic potential and local response increased: (temporal summation can occur)

Action potential
Period from the time firing level is reached till repolarization totally inexcitable: absolute refractory period (no response
is one- third complete. at all however strong the stimulus is)

Period from the time repolarization is one – third complete decreased excitability: relative refractory period (may
to the start of after –depolarization respond if stimulus is stronger)

After – depolarization Increased excitability : supernormal period

After-hyper polarization decreased excitability: subnormal period

Conduction of nerve impulse

Unmyelinated axon

During an action potential, the membrane polarity is abolished and reversed.

This creates the area of negativity on the outside of the cell. This areas act as current sink, draws positive charge
from adjacent membrane. Local circular current flows are created.

The resulting depolarization initiates a local response and firing level. (electrotonic depolarization)

When firing level is reached, positive feedback cycle produces action potential.

The newly generated action potential in turn electrotonically depolarizes the membrane in front of it, generating
another action potential.

A moving impulse does not depolarize the area behind it because this area is refractory.

This sequence (circular current flow) occurs along unmyelinated axon.

Myelinated axon: Saltatory Conduction

Current flow through the insulating myelin is negligible. Therefore depolarization jumps from one node of Ranvier
to the next. The current sink at the active node depolarize electrotonically the node ahead. This is called saltatory
conduction. This jumping conduction is a rapid process. Myelinated axon conducts 50 times faster than the fastest
unmyelinated axons.

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Direction of Conduction

1. Orthodromic conduction (towards axon terminals)

2. Antidromic conduction (towards cell body) eg. Axon reflex

STRENGTH – DURATION CURVE

This curve relates the strength of a stimulus to the time applied to produce a response. The curve shows that
stimulus duration decreases with an increase in the threshold strength.
The irreducible minimum current strength required to evoke a response (when duration of stimulation is very long)
is called the rheobase (A).
The minimum duration for which a current of rheobase strength must be applied to get a response is the
utilization time (B).
The minimum duration for which a current strength of twice the rheobase must be applied to evoke a response is
the chronaxie (C).

Chronaxie varies with tissues; relatively constant in a given tissue provided conditions are the same. It is used

1. to compare the excitability of different tissues (nerve and muscle)

2. as an index of nerve degeneration (after injury) and recovery in reinnervated muscle.

Strength – Duration Curve

32
 NERVE FIBER TYPE AND FUNCTION

Based on conduction velocity (or axonal diameter) Erlanger and Gasser divided mammalian nerve into A, B and C
groups, subdividing the A group into α, β, γ and δ fibers.

Letter classification of nerve fibers

Fibre type Function Fiber diameter Conduction velocity

(μm) (m/s)
Aα Proprioception somatic 12 - 20 70 - 120
motor
Aβ Touch, pressure 5 - 12 30 - 70
Aγ Motor to muscle 3-6 15 - 30
spindles
Aδ Pain, temperature, 2-5 12 - 30
touch
B Preganglionic, 3 3 - 15
autonomic

C (dorsal root) Pain, temperature, 0.4 -12 0.5 - 2

reflex response

C (Sympathetic) Post- ganglionic 0.3 -13 0.7 - 2.3

A and B fibres are myelinated, C fibres are unmyelinated.

Susceptibility characteristics of nerve fibres

Susceptible to Most susceptible Intermediate susceptible Least susceptible

Hypoxia B A C
Local anaesthetics C B A
Pressure A B C

33
Sequence of events during Neuromuscular Transmission of skeletal muscle

• The nerve impulse arrives at the end of motor neuron.

• Voltage-gated Ca++ channels open and Ca++ enters the ending.
• This increases the exocytosis of the acetycholine containing vesicles.
• The acetycholine diffuses to the nicotinic acetycholine receptors on the motor endplate.
• Binding of acetycholine to these receptors increases the Na + and K+ conductance of the membrane.
• Along the concentration gradient, Na+ goes in and K+ goes out.
• Net effect is Na+ influx causing endplate potential.
• This depolarization again, by drawing of positive charges activates voltage-gated Na+ channels in the
muscle membrane adjacent to the endplate.
• Depolarization and regenerative action potential is produced.
• Action potentials thus generated are conducted away from the endplate in both directions along the
muscle fibers.
• The muscle action potential causes muscle contraction.
• After that acetycholine is rapidly broken down by acetycholine esterase.

Factors affecting Neuromuscular Transmission

1. The number of acetycholine released depends on the amount of Ca ++ entered.
2. Fall in ECF Ca++ concentration decreases ACh release.
3. Excess of ECF Mg++ decrease Ach release.
4. Tubocurarine (curare) competes for nicotinic ACh receptor sites at the endplate. Useful as muscle relaxant
during surgery.
5. In Myasthenia gravis, auto anti-bodies destroy ACh receptors.
6. In Lambert-Eaton syndrome, muscle weakness is caused by anti-bodies against one of the Ca++channels in
the nerve ending.

34
Nerve Endings in Smooth & Cardiac Muscle
Smooth muscle:
• Nerve fibers branch extensively
• Multiple branches are beaded with enlargements (varicosities)
• No Schwann cells over varicosities
• Nerve fibers may contain either cholinergic (clear) vesicles or noradrenergic (dense-core) vesicles
• No recognizable end-plate
• One neuron innervate many effector cells
• A neuron forms a synapse on the surface of another neuron or a smooth muscle cell and then passes on
to make similar contacts with other cell is called a synapse en passant
• EJP and IJP can be recorded (similar to EPP)
Cardiac muscle:
• Cholinergic and noradrenergic nerve fibers end on the SA node, AV node and the bundle of His
• Noradrenergic fibers also innervate the ventricular muscle
It also shows synapse en passant

Muscle

Skeletal muscle

Skeletal muscle → multi-nucleated, long and cylindrical cells called muscle fibers
It lacks anatomic and functional connections between the muscle fibers; usually has excitatory nerve supply and
does not normally contract in the absence of neural stimulation.

Morphology
A single muscle cell → a muscle fiber
cell membrane→ the sarcolemma
cytoplasm→ sarcoplasm
smooth -surfaced endoplasmic reticulum→ the sarcoplasmic reticulum
microfilaments→ the myofilaments; which are grouped in bundles called myofibrils

Myofilaments are made up of contractile protein molecules:

1. Myosin : An asymmetrical molecule with one end forming enlarged globular head. The structure of myosin II has
an actin binding site and an ATP-binding site. The latter is an open cleft.
Myosin form the thick filaments.

2. Actin : A globular protein forms two chains of double helix which is the backbone of the thin filaments.
3. Tropomyosin : Long filamentous protein in the groove of actin double helix
4. Troponin : Small globular protein, located at intervals along the filaments of tropomyosin; is made up of these
subunits.
i. Troponin T binds other subunits to tropomyosin
ii. Troponin I tightly binds to actin in resting muscle and thus maintains the position of tropomysin which
covers the myosin binding site of actin. Thus the troponin-tropomyosin complex inhibits the interaction
between actin and myosin, i.e. the complex acts as a 'relaxing protein'.
iii. Troponin C has binding sites for Ca++ ions. The binding of Ca++ ions to troponin C initials muscle
contraction. Troponin C has remarkable structural similarities to calmodulin, a ubiquitous Ca++ binding protein.
Actin, tropomyosin and troponin form the thin filaments.

35
Cross striations (light microsopy)
Cross striations are characteristic of skeletal muscle. They are due to regular arrangement of thick and
thin filament.

dark A bands → thick filaments

light I bands → thin filaments and is the region where they do not overlap the thick filaments
lighter H bands → the thin filaments do not overlap the thick filaments when the muscle is relaxed
M line → a central bulge in each of the thick filaments
Z line, made up of protein actinin which transects the fibrils and connects the thin filaments.
sarcomere (a contractile unit) → The area between two adjacent Z lines

Sarcotubular system

Muscle fibrils are surrounded by the sarcotubular system, which forms the link between excitation and
contraction.

1. The transverse Tubule (T tubule) System

Formed by the minute invigination of the muscle membrane and interweaving among the myofibrils. It is sealed off
from both the cytoplasm and the sarcoplasmic reticulum but communicate directly with the extra-cellular space.
It acts as an internal conduction system within the muscle. It rapidly transmits the action potential from cell
membrane to all the fibrils.

2. Sarcoplasmic reticulum
It is comprised of flattened bag-like structures enveloping myofibrils. It is sealed off from the intracellular space
containing the myofibrils. The longitudinal portion forms an irregular curtain around each myofibril.
Its function is active uptake of calcium ions to initiate muscle relaxation.
The transverse portion has dilated sacs (terminal cisterns) lying on either side of the T tubule, forming triad.
The terminal cisterns store Ca++, which is released into the sarcoplasm initiating muscle contraction. The
sarcoplasmic reticulum is also concerned with muscle metabolism.

Sequence of Events during skeletal muscle contraction

1. Action potential reaches terminal button and is transmitted across the neuromuscular junction.
2. Muscle action potential is conducted in both directions along the muscle membrane.
3. Then it is transmitted to all the myofibril along the T-tubule system.
4. T- tubule has dihydropyridine receptors which acts as voltage sensors and triggers unlock release of
calcium from terminal cisterns, through calcium channel called Ryanodine receptor.
5. These Ca++ diffuse towards thin and thick filaments.
6. When sarcoplasmic calcium concentration increases from 10-7 to 10-5 mole/L, muscle contraction can
start. This process is called excitation- contraction coupling.
7. The contractile Response
- Calcium initiates contraction by binds to troponin C.
- When all 4 binding sites are occupied, attachment of troponin I to actin become weakened.
Tropomyosin moves laterally, uncovering myosin-binding sites on actin. This allows actin-myosin
cross bridge.

36
 - At rest, myosin head is in a cocked position and binds to ADP.
- Upon formation of cross bridge, ADP is released. This causes conformational changes in myosin
head which produce power stroke.
- After that ATP bind to myosin head. This lead to detachment of myosin head from actin.
- ATP is hydrolysed and phosphate is released. Myosin head is recocked and completing the cycle.
- The process of attachment, power stroke and detachment continues as long as Ca ++ and ATP are
present.
- Each power stroke shortens muscle length by 1%.
- The sliding of thin filaments over thick filaments produces shortening of contractile elements.
(Sliding filament theory of muscle contraction).
8. Muscle Relaxation
- Calcium is pumped back into longitudinal portion of sarcoplasmic reticulum via Sarcplasmic or
Endoplasmic Reticulum Ca++ ATPase pump (SERCA pump) and stored in the terminal cistern.
- Sarcoplasmic calcium concentration decrease from 10-5 to 10-7 mole/ L, initiates mucle
relaxation.
- Troponin I tightly binds to actin. Tropomyosin moves back to its original place, covering the
myosin binding sites on actin.
- Troponin-tropomyosin complex constitutes ‘relaxing protein’.
- Both muscle contraction and relaxation require ATP.

The Muscle Twitch

In a skeletal muscle fibre, a single action potential (which lasts 2-4 ms with the absolute refractory period of 1-3
ms) causes a brief contraction followed by relaxation. This is known as muscle twitch.

The twitch starts about 2 ms after the start of depolarization of the membrane.

Duration → from 7.5 ms in fast muscle fibres to 100 ms in slow muscle fibres
Fast muscle fibres →less than 25 ms.
Slow muscle fibres (Gastrocnemius) →around 66 ms
Soleus → 200 ms

Summation of Contractions
In a muscle twitch, the muscle is still contracting when the electrical refractory period is over. Because the
contractile mechanism does not have a refractory period, a second stimulus applied before relaxation has occurred
produces additional activation of the contractile elements.

Tetanus (Tetanic contraction)

It is the fusion of individual contractile responses into one continuous contraction due to repeated stimulation of a
skeletal muscle before relaxation has occurred.
a. Complete tetanus occurs at high frequencies of stimulation when there is no relaxation in between producing
smooth continuous contraction.

37
b. Incomplete tetanus occurs at lower frequencies of stimulation when there are periods of relaxation (although
incomplete) between the stimuli.
In the living body, the skeletal muscles are in a state of partial tetanus due to asynchronous discharge of impulses
in the motor nerve supplying the muscle. Such a state of partial tetanus is referred to as muscle tone.

Treppe (Staircase phenomenon)

It is a progressive stepwise increase in tension developed by the skeletal muscle with each maximal stimulus
delivered at frequency just below the tetanizing frequency until uniform tension per contraction is reached.
Treppe may be due to increased availability of Ca++ to contractile proteins. Treppe also occurs in cardiac muscle
and may be the basis for force - frequency relation.
Therefore, when a muscle begins to contract after a long period of rest, its initial strength of contraction may be as
little as one half of its strength that obtained after performing 10 to 50 times of muscle twitches later.

Cardiac Muscle
Muscle fibres
• branched
• interdigitate
• abut on one another at the end
• intercalated discs
▪ cell membrane of muscle fibres: parallel through an extensive series of folds
▪ strong cell-cell adhesion
• gap junction (+): functional syncytium
• T system: at Z lines
• Cardiac muscle contracts fully if stimulated - obeys All-or-None Law
• Auto-rhythmicity
▪ the ability to generate action potential spontaneously (without external stimulation)
▪ in cells in conducting system (esp. Pacemaker tissue) and working myocardium (atrial &
ventricular muscle)

38
Unstable membrane potential and spontaneous generation of action potential in pacemaker
tissue (SA node) (autorhythmicity)

Ik – repolarization (K+ efflux)

Ih – prepotential (1st part) (Na+ influx)

ICaT – prepotential (complete) (Ca++ influx)

ICaL- AP (depolarization) (Ca++ influx)

SA node (pacemaker tissue) has unstable membrane potential and can produce AP spontaneously.
Opening of ICa L (voltage gated long lasting calcium channel) produce action potential.
IK cause repolarization.
Then IK decline and Ih is activated.
The channel is activated following hyperpolarization. Because of its unusual (funny) activation, it is also called f
channel. I channel can pass both Na+ and K+. Membrane depolarize and forming the first part of the prepotential.
Then ICa T channel (voltage gated transient calcium channel) open and complete the prepotential.
The prepotential or pacemaker potential trigger the impulse.

AP in SA node and AV node are largely due to Ca++ (little contribution by Na+ influx)
Therefore there is no sharp spike.
Prepotentials are normally predominant only in SA node and AV node.
Atrial and ventricular muscle fibre do not have prepotentials.

39
Action Potential of Working Myocardial cells

Phase 0: Rapid depolarization and overshoot are due to rapid increase in Na + conductance consequent to opening
of voltage-gated Na+ channels. (INa = Na+ current, inward)

Phase 1: Rapid re-polarization due to closure of Na+ channels and transient opening of K+ channels. (ITO =
transient, early outward K+ current).

Phase 2: Plateau phase of re-polarization due to a slower and prolonged opening of voltage-gated Ca++
channels. Ca++ influx offsets re-polarization due to K+ efflux through another set of K+ channel.

Phase 3: Final re-polarization due to closure of Ca++ channels and K+ efflux through 2 sets of K+ channels.
IKr = K+ current through inwardly rectifying K+ channels
IKs = K+ current through slowly activating (delayed rectifying) K+ channel
Phase 4: Restoration of the resting membrane potential

Depolarization proceeds rapidly, and an overshoot is present.

It is followed by plateau phase.
Depolarization lasts about 2 ms, but plateau phase and re-polarization last 200 ms or more.
Re-polarization is not complete until the contraction is half over.
Prolonged refractory period is present preventing from tetanic contraction.

40
Contractile Response of Cardiac Muscle (compared with that of skeletal muscle)
• begins just after the start of depolarization
• last ~ 1½ x AP
• ARP – Phase 0 - ½ Phase 3
• RRP – until Phase 4 → Tetanus of the type seen in skeletal muscle, therefore, cannot occur.
The role of Ca++ in excitation-contraction coupling is similar to its role in skeletal muscle.
Depolarization opens membrane voltage-gated Ca++ channels including those in T tubule (DHP or Dihydropyridine
receptors). ECF calcium that enter through these channels open Ca++ channels (Ryanodine receptors) in the
terminal cisterns releasing stored Ca++ (Ca++ - induced Ca++ release).
Relaxation occurs as Ca++ is removed from the cytoplasm by Ca++ pump of the SR and by Na+ / Ca++ exchange
(secondary active transport) across the cell membrane.

SMOOTH MUSCLE (NON-STRIATED, INVOLUNTARY)

1. Single unit smooth muscle (visceral smooth muscle)

(Hollow viscera, e.g. intestines)

2. Multi-unit smooth muscle

(iris, ciliary muscle of eye, piloerector muscles)

• Contractile proteins: myosin, actin, tropomyosin

• NO
– visible cross striation
– regular array
– troponin
• calmodulin
(calcium binding protein)
• poorly developed SR
• few mitochondria (rely on Glycolysis)

41
VISCERAL SMOOTH MUSCLE
• Actin filaments  attached to dense bodies  cell membrane
• thus, cells – bond together through dense bodies
• Force – transmitted thro’ these bonds
• Gap Junctions (+)
• functional syncytium
• the whole mass contract – as a SINGLE UNIT

They occur in gut, bile duct uterus, ureters, and in many blood vessels.

Action potential of smooth muscle

✓ unstable membrane potential
✓ continuous, irregular contraction (tone) independent of its nerve supply
✓ RMP → -50 mV
✓ Wave-like fluctuations superimposed on the membrane potential
✓ Pacemaker potentials generated in multiple foci

Molecular Basis of Smooth Muscle Contraction

Smooth muscle has a latch bridge mechanism by which dephosphorylated myosin cross bridges remain attached
to actin for some time after the cytoplasmic Ca++ concentration falls. This produces sustained contraction
(important is vascular smooth muscle).

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Three types of muscles
Skeletal m/s Cardiac m/s Visceral smooth m/s
Types Voluntary Involuntary Involuntary
Striations (+) (+) (-)
Long, cylindrical Branched Spindle, fusiform
Morpology
Sarcotubular system Well developed Well developed Poorly developed
Contractile proteins All present Present Troponin (-)
Ca++ binding protein Troponin C Troponin C Calmodulin
Source of Ca++ SR ECF, SR ECF, SR
SNS, voluntary ANS, involuntary, ANS, involuntary
Nerve control
always excitatory EJP, IJP EJP, IJP
Neuromuscular Synapse with nerve
Synapse en Passant Synapse en Passant
transmission endings
Denervation Paralysis - -
Muscle contraction & Myosin actin cross bridge
Myosin actin cross bridge Myosin actin cross bridge
relaxation Latch bridge
Gap junction (-) (+) (+)
Functional syncytia (-) (+) (+)
Pacemaker cells (-) (+) (+)
Autorhythmicity (-) (+) (+)
Plasticity (-) (-) (+)
Tetanus (+) (-) (+)

43
 Chapter 5
General principles of neurophysiology

AUTONOMIC NERVOUS SYSTEM

Anatomical classification
1. Central nervous system
2. Peripheral nervous system
Functional classification
1. Somatic nervous system (SNS)
2. Autonomic nervous system (ANS)
(a) parasympathetic nervous system
(b) sympathetic nervous system

SNS → controls the skeletal muscles

ANS → controls the activities of
– the viscera (heart, lungs)
– glands (sweat glands, lacrimal glands)
– smooth muscles (vascular, visceral smooth muscle)
• Known as vegetative, visceral or involuntary nervous system
• Function: Fine control over visceral or internal functions of the body (Homeostasis)

ORGANIZATION

The ANS (like the SNS) is organized on the basis of the reflex arc (the pathway by which a reflex occurs).
A reflex is an involuntary stereotyped response to a stimulus.
The components of reflex arc are (a) a receptor, (b) afferent (sensory) neuron, (c) integrating center, (d)
efferent (motor) neuron and (e) effector organ.

44
a. Sensory Receptors (visceral receptors)
✓ Transducers- convert any types of energy to electrical energy (action potentials)
✓ Interoceptors:

Receptor Stimulus
Osmoreceptors Change in plasma osmolality
Baroceptors Change in blood pressure
Chemoreceptor Change in blood chemistry e.g. PCO2, PO2
Volireceptors Change in circulating blood volume
Thermoreceptors Change in temperature
Glucostat cells blood glucose
Pain receptors Various chemicals
Stretch receptors Stretch

Function of receptor - code the information received and transmit it in the form of impulse
along the afferent pathways
b. Afferent Autonomic Pathways (Visceral Afferents)

Parasympathetic Afferents
✓ Cranial nerves V, VII, IX, X
✓ Sacral roots S 2, 3, 4
✓ Sensation arising from structures above the thoracic pain line and below the pelvic pain
line → carried by parasympathetic afferents.

Sympathetic Afferents
✓ thoracic and upper lumbar dorsal roots.
✓ Sensations arising from structures between the two pain-lines → carried by sympathetic
afferents.

Function of visceral afferent- transmit the information received from the receptor
→integrating centers in CNS

45
c. Integrating Centres
✓ Neurones at various levels in the central nervous system

Some reflexes - no integrating centre - Local reflex in GIT

Hypothalamus (head ganglion of ANS) - food intake, thirst, temperature
Function: process the incoming information → send impulse via the efferent pathways to bring
about the response.

d. Autonomic Outflow (Efferent pathways)

✓ comprised of sympathetic & parasympathetic divisions

✓ each has pre & post ganglionic neurones (2 neuron linkage)

Preganglionic neurones

• cell bodies (inside brain and spinal cord)

• myelinated B fibres

46
 Postganglionic neurones

• cell bodies (outside brain and spinal cord)

• unmyelinated C fibres

The Sympathetic Division

Preganglionic neurons synapse with postganglionic neurons at

a. the paravertebral sympathetic ganglion chain

b. collateral ganglia (coeliac, superior and inferior mesenteric)

c. the superior, middle and inferior cervical ganglia – (extension of the paravertebral ganglia
chain)

The adrenal medulla

- essentially a sympathetic ganglion but the postganglionic cells have lost their axons.

- release of catecholamines (the hormones adrenaline, noradrenaline and dopamine) → the

blood stream.

- widespread effect seen throughout the body (SYMPATHOADRENAL AXIS are diffused)

The Parasympathetic Division

Parasympathetic preganglionic neurons

Cranial nerves : III, VII, IX, X
Sacral nerves : S2, S3, S4

e. Visceral effectors
✓ cardiac muscles
✓ smooth muscles
✓ glands

Most organs have dual nerve supply

Responses
✓ Usually, antagonistic

47
48
Chemical Transmission at Autonomic Junctions

ACh- CHOLINERGIC NEURONES

NE- NORADRENERGIC NEURONES

Dopamine- DOPAMINERGIC NEURONES

Peptides - PEPTIDERGIC NEURONES

Cholinergic neurons

Synthesized and stored

• Synthesis occurs in the cytoplasm of nerve endings.
Acetyl-Co A + Choline acetylcholine (ACh)
• AC h is stored together with VIP (vasoactive intestinal peptide, the cotransmitter for
ACh).

Metabolism
• Acetylcholinesterase break down ACh into choline and acetate.
• Choline is taken up by the presynaptic membrane to reform ACh.
Examples
1. All preganglionic neurones
2. The anatomically parasympathetic postganglionic neurones
3. The anatomically sympathetic postganglionic neurones which innervate the sweat
glands and blood vessels of skeletal muscle.
4. The sympathetic neurone which innervate the adrenal medulla.
5. Somatic motor neurone
6. higher functions of CNS
Noradrenergic neurons

Synthesized and Stored

Phenylalanine → tyrosine → dopamine → noaradrenaline

Methylation
Noradrenaline adrenaline
PNMT

49
 • The nerve ending of noradrenergic neurons do not contain PNMT (Phenylethanolamine
N- methyl transferase).

• Therefore, the noradrenergic neurones cannot synthesize adrenaline.

• PNMT is present in adrenal medulla and some neurones in central nervous system.

Metabolism
✓ taken up by a NET (norepinepherine transporter) present in presynaptic membrane →
broken down by MAO (monoamine oxidase).
✓ MAO is plentiful in noradrenergic nerve endings.
✓ In the circulation→ metabolized by MAO and COMT (catechol-O- methyl transferase).
✓ COMT is widely distributed, particularly in the liver, kidneys and smooth muscles, but it
is not found in noradrenergic nerve endings.

Examples
Postganglionic sympathetic neurons are noradrenergic neurons.

Receptors of Postsynaptic tissues (drug receptors)

- Present in the cell membrane of postsynaptic tissue
- receive humoral agents

Acetylcholine receptors
There are two types of ACh receptors. (1) Muscarinic receptor (2) Nicotinic receptor

Muscarinic receptors

✓ activated by Ach and muscarine (the alkaloid responsible for toxicity of toadstools).
✓ blocked by atropine.
✓ 5 types of muscarinic receptors.
✓ M1, M4, M5 receptors are located in the CNS. M2 receptors are found in the heart, M3
are on glands and smooth muscles.

Nicotinic receptors

✓ activated by Ach and nicotine. They are not blocked by atropine.

✓ (1) Muscle type nicotinic Ach receptor – neuromuscular junctions
(2) Neural type – autonomic ganglia and CNS

50
Adrenergic Receptors
α and β receptors
α 1 α 2 and β 1 β 2 β 3
α 2 - presynaptic in nerve ending & postsynaptic in brain
α 1α2- more sensitive to noradrenaline
β 1 - equally sensitive to both
β 2 - more sensitive to adrenaline

Dopaminergic receptors -D1 to D5

Effects of parasympathetic stimulation

1. stimulation of smooth muscles of the respiratory tract, gut, urinary bladder and eyes
(sphincter muscle of iris)
2. stimulation of gland secretion
3. Inhibition of vascular smooth muscle
4. inhibition of heart activity
5. sphincter relaxation (prevail during sleep and digestion)

1. Eyes - contraction of sphincter muscle of iris, causing pupil constriction

(miosis)contraction of ciliary muscle for near vision
2. Heart – decrease in HR, decrease in contractility, decrease in conduction velocity
3. Arterioles – dilation of arterioles of salivary glands
4. Lungs – contraction of bronchial muscle (bronchoconstriction)
5. Stomach & intestine – increase in motility & tone, increase in secretion, sphincter
relaxation
6. Gall bladder – contraction of gall bladder
7. Urinary bladder – contraction of detrusor – relaxation of sphincter
8. Uterus – variable effect
9. Male sex organs – erection of penis
10. Pancreas – increase in secretion of pancreatic juice
11. Salivary glands – profuse, watery secretion of saliva
12. Lacrimal glands secretion of tear

51
Effects of sympathetic stimulation
alpha– usually stimulatory except on gut
vasoconstriction
pupillary dilation (radial muscle)
intestinal muscle relaxation
beta– usually inhibitory except on the heart
vasodilation
relaxation of bronchial muscles
increased force and rate of cardiac contraction
cholinergic
sweating
vasodilation in vessels of skeletal muscle

1. Eyes – contraction of radial muscle of iris, causing pupil dilation (mydriasis) (α1 effect)
2. Heart – increase in HR (β1 effect), increase in contractility (β1, β2 effect) – increase in
conduction velocity (β1, β2 effect)
3. Arterioles – vasoconstriction (α1, α2 effect), vasodilation (β2 effect)
4. Systemic veins – venoconstriction (α1, α2 effect) – venodilation (β2 effect)
5. Lungs – relaxation of bronchial muscle(bronchodilation) (β2 effect)
6. Stomach & intestine
– decrease in motility & tone (α1, α2, β2 effect) – sphincter contraction (α1 effect)
– inhibition of secretion (α2 effect)
7. Gall bladder – relaxation of gall bladder (β2 effect)
8. Urinary bladder -relaxation of detrusor (β2 effect) – contraction of sphincter (α1 effect)
9. Uterus – uterine contraction (pregnancy) (α1 effect) – uterine relaxation (β2 effect)
10. Male sex organs – ejaculation (α1 effect)
11. Pancreas – decrease in secretion of pancreatic juice (α effect)
12. Salivary glands – thick, viscous secretion of saliva (α1 effect)
13. Skin – piloerection (α1 effect) – adrenergic sweating or slight localized sweating (α1
effect) – cholinergic sweating or generalized abundant dilute secretion (muscarinic
effect)
14. Liver – glycogenolysis (α1, β2 effect)
15. Adipose tissue – lipolysis (α2, β3 effect)

52
Functions of the Autonomic Nervous System

Functions of the Parasympathetic Division

(The Anabolic Nervous System)
1. Maintenance of body homeostasis, e.g. control blood pressure and respiration
2. Control of vegetative aspects of day-to-day living, e.g. digestion and absorption
3. Conservative and restorative processes, e.g. inhibition of the heart

Function of Sympathetic Nervous System (Catabolic Nervous System)

1. Maintenance of body homeostasis. e.g. control blood temperature and temperature

2. Preparation of body for emergency and vigorous muscle activity.
Any stress activates the sympathetic system and sympathoadrenal axis.
Catecholamines exert widespread effects:
a. to increase blood supply
b. to increase energy supply
c. to increase oxygen delivery to exercising tissues.

a. Increase in blood supply

- by increase in cardiac output
(Increase in heart rate and force of contraction)
- by increase in blood pressure
- by vasodilation of blood vessels of skeletal muscle
- by vasoconstriction of splanchnic vessels
- by vasoconstriction of skin vessels

b. Increase in energy supply

- by glycogenolysis → raises blood sugar level
- by lipolysis → release free fatty acids

c. Increase in oxygen delivery to tissues

- by bronchodilation
- by increased blood supply

d. Other effects
- pupil dilatation
- activation of reticular activating system ( RAS )
which produces alertness
- increased pain threshold ( action of adrenaline )

▪ CANNON called the emergency – induced sympathetic discharge, flight or fight reactions.
▪ Life is possible without sympathetic nervous system, provided that the individual is protected from stress
e.g. extremes of temperature.

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 Implications and Clinical Correlates

1. means of increasing sympathetic activity

a. stimulates release of noradrenaline (e.g. ephedrine, amphetamine)
b. stimulates 1 receptor (e.g. methoxamine)
c. stimulates β receptors (e.g. isoproterenol)
d. inhibits catecholamine breakdown (e.g. MAO inhibitors)

2. means of reducing sympathetic activity

a. blocks synthesis (e.g. metyrosine)
b. interferes with storage (e.g. reserpine used in hypertension)
c. prevents release (e.g. guanethidine used in hypertension)
d. blocks alpha receptors (e.g. phentolamine, prazosin)
e. blocks beta receptors (e.g. propranolol, atenolol)
f. forms false transmitters (e.g. methyl dopa)

3. means of increasing acetylcholine effects

a. stimulates postganglionic neurones (e.g. nicotine)
b. inhibits acetylcholine esterase (e.g. DFP, parathion, malathion, physostigmine)

✓ Di-isopropyl fluorophosphate (DFP) is a component of 'nerve gas' used in chemical

warfare.
✓ Parathion and malathion are insecticides commonly used in agriculture.
✓ Insecticide poisoning manifests as vomiting and diarrhoea (increased GI motility and
secretion).
✓ They may be counteracted by atropinization or reactivation of acetylcholine esterase
with pralidoxime.

4. means of decreasing acetylcholine effects

a. blocks conduction, (e.g. hexamethonium)
b. blocks muscarinic receptors, (e.g. atropine, scopolamine)

Ancient North American Indians used curare on their arrows→ this drug competes for the Ach
receptors at the neuromuscular junction, which causes relaxation of muscles. When respiratory
muscles are affected, it is fatal.

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Clinical Correlates

Over-activity of the Parasympathetic System

✓ Gastric hypersecretion (vagal effect), can be counteracted by atropine.
✓ Peptic ulceration consequent upon gastric hypersecretion can be relieved by vagotomy
✓ Diarrhoea and vomiting due to food poisoning can be counteracted by atropine

Over-activity of the Sympathetic System

✓ Vasoconstriction of vessels of the hands (Raynaud's disease) or feet (Burger's disease)
may be relieved by sympathectomy
✓ Hypertension due to sympathetic overactivity may be treated by drugs which block
synthesis or release of noradrenaline

Effects of Sympathectomy
1. increased blood flow (removal of 1 effect)
2. loss of sweating and piloerection (loos of cholinergic and 1 effect)
3. failure to prevent pooling of blood by gravity (loss of reflex vasoconstriction) – postural
hypotension

Postural hypotension is a feature of autonomic neuropathy.

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Compare and contrast sympathetic and parasympathetic nervous system
Organization Sympathetic division Parasympathetic division
1. Out flow Thoracolumbar Craniosacral
T1 -L2 Cranial nerves: III, VII, IX, X
S2, 3, 4.

2. Length of Preganglionic axons Short Long

3.Location of ganglia Away from the Close to or in the organs

effector organs

4. Neurotransmitters ACh ACh

from preganglionic neurons

5. Receptor type in ganglion Nicotinic Nicotinic

6. Length of postganglionic neurons Long Short

7. Neurotransmitters from Mostly NA; ACh

postganglionic neurons ACh in cases of sweat
glands & blood
vessels of skeletal
muscles

8. Effector organs Smooth & cardiac Smooth & cardiac muscles,

muscles, glands glands

9. Receptor types in effector organs Adrenergic receptors Muscarinic receptors

αand β - M1 to M5
α 1,2 and β 1,2,3.

10. Effects Diffuse and prolonged. Short and localised.

Prevail during fight or flight response Prevail during sleep and digestion

11. Functions Homeostasis, Emergency Homeostasis, Vegetative functions

preparations

12. Synonym Catabolic nervous system Anabolic nervous system

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 Central nervous system

I. Anatomical Organization of the Nervous System:

1. CNS- brain and spinal cord
2. PNS- 43 pairs of nerves (cranial nerves 12 pairs; spinal nerves 31 pairs)
The peripheral nerves contain two kinds of fibers (axons):
i. afferent or sensory fibers carrying impulses from the sensory receptors to the CNS
ii. efferent or motor fibers carrying impulses from the CNS to effector organs (muscles, glands and
others)

II. Functional Organization of the Nervous System:

1. The autonomic nervous system - regulates the visceral functions.
It is also called involuntary or visceral nervous system.
2. The somatic nervous system - other non-visceral functions such as movements. It is also called voluntary
nervous system.
3. The special senses concerning with vision, hearing, smell, taste and motion such as linear or rotational
acceleration.

Functions of the Nervous System

The primary function of the nervous system is regulation and coordination of the bodily activities and
thus enabling the organism to adjust to its environment (internal or external); it maintains homeostasis (“the quick
component”).

External (e.g. light, sound, temperature)

Inputs Internal (e.g. muscle tension, distension of viscera, changes
in blood volume and chemical composition)
Afferent nerves (various levels in CNS)
Centres (various levels in CNS)
Efferent nerves (somatic, visceral)
Effectors:
Somatic: skeletal muscles
Visceral: Cardiac and smooth muscles, glands

Outputs: Movement, Secretion, Visceral Changes (Responses)

Stimulus-integration response pattern of coordination by the nervous system

Structural and Functional Component of the Nervous System

The human CNS contains about 1011 neurons and 10 – 50 times this number of glial cells.
neurons → the basic building blocks of the nervous system
reflex arc → the functional unit of the integrated neural activity.

Neurons
1. A receptor or dendritic zone where local potential changes are generated (graded electrogenesis).
2. Site of origin of conducted impulses (action potentials)

57
(initial segment in spinal motor neurons; first node of Ranvier in cutaneous sensory neurons)
3. axonal processes along which nerve impulses are conducted to the nerves endings
4. the nerve endings where synaptic transmitters are secreted.
In the CNS, most neurons are myelinated.

Glial Cells
A. Glial Cells in the PNS: Schwann Cells produce myelin.
B. Glial Cells in the CNS:
1. Microglia - component of macrophage system
2. Oligodendrogliocytes - form myelin
3. Astrocytes (in brain): -send processes to blood vessels and to neurons;
a. Fibrous Astrocytes - found primarily in white matter
b. Protoplasmic Astrocytes - found primarily in grey matter

Functions of Astrocytes:
1. Formation of blood-brain barrier
2. Maintenance of appropriate concentration of ions and neurotransmitters in the neuronal environment by taking
up K+ and other neurotransmitters.
3. Secretion of neurotrophic proteins called Neurotrophins

Synaptic Transmission

SYNAPSES are the junctions between two neurons or between a neuron and its effector organ.

Synaptic transmission may be

- Chemical (via the release of neurotransmitter),
- Electrical (movement of cations or electric current via the gap junctions between the two neurons) or
- Conjoint (both chemical and electrical). Many of the synapses are chemical.

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Sequence of Events during Synaptic Transmission

I. Events at the synaptic knobs at the endings of the pre-synaptic neuron

• arrival of nerve impulse (the action potential)
• voltage change across membrane
• Opening of voltage-gated Ca 2+ channels
• Ca 2+ influx
• a rise in Ca 2+ content
• release of transmitters by exocytosis
• small clear vesicles (Ach, glycine, GABA, glutamate), small dense core vesicles (catecholamines) release
their contents via active zones.
• Large dense core vesicles (peptides) release their contents from all parts of the nerve terminal.
• During exocytosis, synaptobrevin in the vesicle membrane locks with syntaxin in the cell membrane.
• These docking proteins are inactivated by tetanus and bolulinum toxins.
• Tetanus → spastic paralysis, botulism (food poisoning) → flaccid paralysis
• Small dose of botulinum toxin (botox) may be used to relieve achalasia and wrinkles.

II. Diffusion of transmitter across the synaptic cleft (20 -40nm wide)
III. Events at the postsynaptic cell membrane
1. Production of Postsynaptic Potentials:
In excitatory synapses,
• binding of the transmitter (e.g. glutamate) to the receptors on postsynaptic neuron
• opening of cation channels (Na+ or Ca 2+)
• influx of cations (the inward current) depolarizes the membrane
• but repolarizing forces restore the membrane potential
• the depolarization potential is called excitatory postsynaptic potential(EPSP)
• Spatial summation and temporal summation can occur.

59
In inhibitory synapses,
• binding of the transmitter (e.g. glycine, GABA, gamma-amino butyric acid) to the receptors on
postsynaptic neuron
• opening of anion channels (Cl-)
• influx of anions (the inward current) hyperpolarizes the membrane
• but repolarizing forces restore the membrane potential
• the hyperpolarization potential is called inhibitory postsynaptic potential(IPSP)
• Spatial summation and temporal summation can occur.
• Increasing chloride conductance is potentiated by diazepam, alcohol, barbiturates and inhaled
anaesthetics.

2. Generation of Action Potentials in the Postsynaptic Neuron

• Since postsynaptic neuron receives many EPSPs and IPSPs, the membrane potential is the algebraic sum.

• In the motor neuron, multiple EPSPs on the soma act as current sinks → drain off positive charges from
the initial segment of axon → firing level is reached → AP is propagated.

Inhibition at Synapses

Pre-synaptic Facilitation
Serotonin released by the neuron that ends on the pre-synaptic neuron closes its K+ channels (via cAMP),
thereby slowing re-polarization and prolonging the action potential. As a result, voltage-gated Ca2+ channels open
for a longer period, increasing the Ca2+ influx and subsequent excitatory transmitter release. The synaptic
transmission was thus facilitated.

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Functions of different parts of the brain

Cerebral hemispheres

Each hemisphere comprises four lobes: frontal, parietal, temporal and occipital lobes

Functions:

1. Frontal lobes → primary motor cortex (precentral gyrus)

2. Parietal lobes → somatic sensory cortex
3. Temporal lobes → integration of sensation, emotion, memory, learning and behavior, processing
of auditory and visual information
4. Occipital lobe→ vision

Hypothalamus
Functions
I. Temperature regulation
II. Neuroendocrine control of:
a. sympatho-adrenomedullary secretion of catecholamines
b. posterior pituitary secretion
c. anterior pituitary secretion
III. Control of Appetitive Behaviour
a. Thirst
b. Hunger
c. Sexual behavior
IV. Defensive reactions (rage and fear)
V. Control of body rhythms

Basal Ganglia

Basal ganglia: 3 large nuclear masses underlying the cortical mantle on each side of the brain:
1. Caudate nucleus
2. Putamen
3. Globus pallidus
(external and internal segments)
Functionally related nuclei:
4. Sub-thalamic nucleus
5. Substantia nigra
6. the red nucleus

Functions of the Basal Ganglia

1. Planning and programming of voluntary movements
2. control of gamma efferent discharge, and hence in regulation of muscle tone and posture

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Cerebellum
Functions of the Cerebellum
1. The Vestibulo-cerebellum is concerned with Vestibular Function:
i. control body equilibrium. Excessive stimulation of this area causes motion sickness. Lesion in this
area leads to loss of body equilibrium
ii. vestibulo-ocular reflex (visual fixation reflex)
2. The Spinocerebellum:
It compares the motor program to the actual performance (through the proprioceptive feedback input). It
coordinates and adjusts ongoing movement so that it is smooth and precise.
3. The Neocerebellum or Cerebro-cerebellum:
It interacts with the motor cortex in planning and programming movements.

Medulla Oblongata
Functions:
1. vital centres such as respiratory centre, the cardiac centres and vasomotor centres.
2. integrating centre for the following visceral reflexes:
Swallowing (deglutition) reflex
Vomiting reflex
Coughing reflex
Sneezing reflex
Gagging reflex
3. integrating centre for the following postural reflexes:

Midbrain
Functions:
1. Integration and control of the following postural reflexes:
a. righting reflexes
b. vestibular placing reactions
2. Control of pupillary light reflexes.
3. Control of visual fixation reflexes.

Spinal Cord
Functions:
1. Spinal cord serves as a conductive pathway from the periphery to the CNS and from the CNS to the periphery
2. Spinal cord serves as an integrating centre for:
Postural reflexes: Stretch reflexes, Positive and negative supporting reactions
Protective reflexes: Withdrawal reflexes, Crossed extensor reflex
Visceral reflexes: Evacuative reflexes: Micturition
Defaecation
Ejaculation

Reticular Activating System (RAS) in the brainstem reticular formation → responsible for wakefulness and sleep

Blood Brain Barrier (BBB) is due to the presence of tight junctions between the endothelial cells of the brain blood
vessels. Drugs which cross BBB slowly should be administered intrathecally

62
 Chapter 6
General principle of endocrine physiology
Two primary communication system concerned with homeostasis are nervous system and
endocrine system.

Endocrine System

Endocrine communication
Hormone: Chemical messengers secreted by endocrine cells enter the blood, and are
carried to distance organs or tissues (the target) to modify their activity.

Paracrine communication: Hormones secreted into the ECF to act on adjacent cells in a
given tissue.
Autocrine communication: Hormones act on the cells in which they are produced.

Biosynthesis and Modification of hormones

(1) Some hormones are synthesized and secreted in final form.

e.g. thyroid hormones, steroid hormones, catacholamines

(2) Some protein or polypeptide hormones are synthesized as preprohormone, and then
modified within the cells before they are secreted.
e.g. preproinsulin → proinsulin → insulin

(3) Some hormones are converted to more active forms in the peripheral tissues.
e.g. T4 to T3, testosterone to dihydro-testosterone (DHT)

Chemistry of hormones

NO (EDRF) - Gaseous
Catecholamines - Amines
Thyroid hormones - Amino acids (derived)
Adrenocortical h/m, sex h/m, 1, 25-DHCC - Steroids
Hypothalamic h/m (except PIH) - Peptides
Insulin, growth h/m - protein
TSH, FSH, LH, erythropoietin - glycoprotein

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Classification of Hormones by Mechanism of Action:
GROUP I
Hormones that bind to intracellular receptors and affect gene expression:
Steroid hormones
➢ Glucocorticoids (cortisol)
➢ Mineralocorticoids (aldosterone)
➢ Androgens, Estrogens Progesterone
➢ Calcitriol (1, 25 DHCC)
Thyroid hormones
➢ T3 & T4

GROUP II
Hormones that bind to cell surface receptors and use intracellular messengers:
A. Hormones that use cAMP as the second messenger:
CRH, Somatostatin
ACTH, TSH, LH, FSH, MSH
Vasopressin (renal action)
Parathyroid homone
Calcitonin
Catechlamines (beta-effects)
B. Hormones that use cGMP as the second messenger:
Atrial Natriuretic Peptide, EDRF (NO)
C. Hormones that use Calcium or Phosphatidylinositides: Diacylglycerol (DAG) or Inositol Triphosphate (IP3)
TRH, GnRH
Vasopressin (vascular action), Oxytocin
Catecholamines (alpha-effects)
Angiotensin II,
Gastrin, CCK – PZ
D. Hormones that increase tyrosine kinase
Insulin, some growth factors (GFs)
E. Hormones that activate JAK STAT pathway
Growth hormone, cytokines, CSFs

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Chemistry of Hormones
Chemical Nature Examples
Gaseous NO (EDRF)
Amines Catecholamines
Amino acids (derived) Thyroid hormones
Steroids Adrenocortical and sex hormones, 1, 25-DHCC
Peptides Hypothalamic hormones,Parathormone, Gut peptides
Proteins Insulin, Growth hormone
Glycoproteins TSH, FSH, LH, Erythropoietin

Thus apart from steroids and amino acid derivatives (catecholamines and thyroid which are
derived from the amino acid tyrosine) the rest of the general hormones can be said to be
peptides or proteins.

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Factors influencing the action of a hormone on the target tissue &
Mechanisms regulating hormone production (synthesis and secretion)

Hormonal interaction

( 1 ) Inhibitory interaction

occurs when two hormones have opposite effects on a target tissue

with no molecular interaction.

e.g. Insulin stimulate glycogen synthesis, glucagon cause glycogen

breakdown. (by acting on different enzymes )

( 2 ) Synergistic interaction

occurs when two hormones acting simultaneously give an effect

greater than the sum of either of them acting alone.

e.g. stimulatory effect of FSH and LH on the ovarian follicle.

( 3 ) Permissive interaction

occurs when the presence of one hormone (hormone A) is required

for another hormone (hormone B) to exert its full action. Hormone A
permits hormone B to exert its action. Hormone A itself does not
usually have that action. e.g. a small amount of glucocorticoids 66
must be present for catecholamines to produce pressor response (
vasoconstrictor ), bronchodilation and calorigenic and lipolytic
effects.
(Endocrine Glands and Other Tissues)

1.Hypothalamus: 7.2 Ovaries (in female):

1. Releasing and Inhibiting Hormones Oesterogens, Progestrone, Relaxin
(Hypophysiotropic hormones) (During pregenancy, the PLACENTA acts as a
2. Synthesizes vasopressin and oxytocin temporary endocrine organ producing sex
steroids, a gonadortrophin and other protein
(transported to and stored in the
hormones)
posterior pituitary)
8. GIT:
2. Pituitary Gland (Hypophysis): GI Hormones : Gastrin, Secretin etc.
2.1AnteriorPituitary (Andenohypophysis)
▪ Thyroid Stimulating hormone (TSH) 9. The kidneys:
(Thyrotropin) Erythropoietin, Renin (RAA),
▪ Adrenocorticotropic hormone (ACTH) 1, 25-DHCC, Prostaglandins
(Corticotropin)
▪ Gonadotropic hormones (Gonadotropins): 10. Liver
Erythropoietin
LH, FSH
Insulin-like Growth Factor I (IGF-I)
▪ Growth hormone (Somatotropin) Precursor of 1, 25-DHCC
▪ Prolactin
11. Pineal Gland (Epiphysis)
2.2Posterior Pituitary (Neurohypophysis) Melatonin
Vasopressin, Oxytocin
12. Pituitary : Intermedial Lobe
3. Thyroid Gland Melanocyte Stimulating Hormone
Thyroid hormones: T4, T3
Calcitonin 13. The Heart (Myocytes):
Atrial Natriuretic Peptide (ANP)
4. Parathyroid Gland
Parathormone 14. Blood Vessel Wall:
14.1 Endothelial Celld:
5. The Endocrine Pancreas: Endothelium-Derived Relaxing Factor
Insulin, Glucagon (EDRF) of NO
Endothelin
6. Adrenal Gland: Prostacyclin
6.1 Adrenal Corted: 14.2 Smooth Muscle:
Mineralocorticoids Prostacyclin
Glucocorticoids Renin (JG cells of kidney)
Sex hormones
15. Blood Platelets
6.2 Adrenal Medulla: Serotonin (5-HT)
Catecholmines: adrenaline, noradrenaline, Thromboxane A2
dopamine
16.Postganglionic Sympathetic Nerve Endings:
7. Gonads: Circulating noradrenaline
7.1 Tests ( in males):
Testosterone
Other sex steroids
67