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Basic Concepts

PHYSIOLOGY
SYLLABUS
Introduction
General functional organization of human body
Body fluid compartments (p. 205): Functions of electrolytes, dehydration and overhydration (p. 208)
Define and explain terminology: (p. 210)
Hypertonic , hypotonic, isotonic
Osmotic pressure: Crystalloid and oncotic, Osmosis
Cell membrane transport (p. 211)
Cell to cell and local communication (p. 218)
Intracellular mechanism of signal transduction (p. 221)
Homeostasis (p. 221)
Definition, Maintainance, Control of internal environment, Different regulatory system in homeostasis
Principles of control systems: General characteristics and components of biological control system, concept of
negative and positive feedbackcorrection, error, gain
Hormonal control mechanisms:
Definition of hormones, Receptors and target cell, Role of hormones in homeostasis
Neural control mechanism: Role in homeostasis I
Musculoskeletal
Neuromuscular transmission
Bioelectricity (p. 225)
Terminology: (p. 225)
Excitable cells (p. 225), neurons and muscles and their excitable properties
Functional anatomy of neurons
Resting membrane potential (p. 227), Nernst equation (p. 228)
Action potential (p. 228): Ionic basis of its genesis and propagation, Its refractory period (p. 226)
Receptor (p. 229): Generator potential, Classification and functions
Cutaneus receptors (p. 229): Classification and functions, Generator potential, properties and transduction

FAST TRACK BASIC SCIENCE MBBS -203-


Physiology

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Basic Concepts

PHYSIOLOGY
Daily loss of body water
BODY FLUID COMPARTMENTS
1. Insensible water loss
FUNCTIONS OF ELECTROLYTES
- It occurs continually in all living humans though
Past Quesitons:
we are not consciously aware of it.
1. Write briefly on: (2+3=5) [03 July] - Loss of water by evaporation from the
a. Difference between intracellular and extra respiratory tract & diffusion through the skin (≈
cellular fluid 700ml/day)
b. Interstitial fluid (2) [09 Jan] - Independent of sweating; present even in
2. Enumerate the different body fluid people who are born without sweat glands.
compartments and state the starling forces Note:
that determine the net movement of fluid In cold weather, there is dry feeling in the respiratory
across the capillary wall. (2 + 2 = 4) [03 Dec] passages. It is because, as the atmospheric vapour
3. Name the body fluid compartments and state pressure decreases to nearly zero, there is even
greater loss of water from lungs.
the biophysical principles (Starling’s
Hypothesis) that govern the transport of fluid 2. Fluid loss in sweat
in between capillary and tissue spaces. - Depends upon physical activity &
(3+3=6) [11 July] environmental temperature (≈100ml/day)

4. Name the different fluid compartment in the - In very hot weather or during heavy exercise,
water loss in sweat occasionally increases to 1
I
body, the size of each in percentage and liters
to 2 L/hour.
(in a 70kg man). (4) [05 Dec]
3. Water loss in feces
5. Mention the differences between: (2) [07 July]
- Small amount lost ( ≈100 ml/day)
a. Intracellular and extracellular fluid.
- Increases in diarrhoea.
4. Water loss by kidneys
Daily intake of water
- Most important means by which the body
♦ Sources of water in the body are:-
maintains a balance between intake and
1. Ingested in the form of liquids or water in the output of most electrolytes.
food (≈ 2100ml/day)
Total Body water
2. Synthesized in the body as a result of oxidation
♦ In an average 70- kg adult man, the total body
of carbohydrates (≈ 200ml/day) water is about 60% of the body weight or about
Total water intake = (2100 +200) 2300ml/day 42 liters.
♦ Water intake varies among different people & Factor affecting total body water
even within the same person on different days a. Age
depending on climate, habits & level of physical - As a person grows older, the percentage of
activity. total body weight that is fluid gradually
decreases.

FAST TRACK BASIC SCIENCE MBBS -205-


Physiology

- Aging is associated with an increased Constituents of ECF & ICF


percentage of the body weight being fat, which ECF ICF
decrease the percentage of water in the body.
( mEq/L) (mEq/L)
b. Gender
Na+ 142 10
- Women have more body fat than men.
- The total body water comprises K+ 4 140
1. 40% of body weight of young male adult. Ca + 2.4 0.0001
2. 50% of body weight of young female adult. Mg++ 1.2 58
c. Degree of obesity
Cl- 103 4
- Due to accumulation of fat, total body water
decreases. HCO3 - 28 10
Body fluid compartments [11, 05, 03] Phosphates 4 75
Total body water (42 liters)(60%) Proteins 2g/dl 16g/dl
Donnan effect
A p B
Extracellular fluid Intracellular fluid (40%)
+
( 20%) (14 liters) (28 liters) K K+
- -
Cl Cl
Pr -

Interstitial Blood Transcellular X (equilibrium)


Fluid ( 15%) Plasma fluid (synovial, A p B
I (5%) peritoneal, pericardial,
intraocular spaces, K+ K+
- -
cerebrospinal fluid Cl Cl
Pr -

A. Intracellular fluid compartment Y (equilibrium)


- Constitutes about 28 of the 42 liters of fluid in A p B
body (2/3rd of total body water). ↑ K+ K+
- Present inside the 100 trillion cells. -
↑Cl -
Cl
B. Extracellular fluid compartment
Pr -
- All the fluids outside the cells are collectively
called the extracellular fluid. Z (equilibrium)
- Constitutes about 14 liters of the 42 liters of - Let us consider side ‘A’ and side ‘B’ in a
total fluid (1/3rd of total body water). compartment & is separated by semi-
- It is divided into: permeable membrane “p” .

1. Interstitial fluid (11 Liters) - In X,


2. Plasma (3 liters) both sides are electrically neutral.
3. Transcellular fluid (very small amount) i.e, Charge in A = Charge in B
- ECF constitutes the body’s internal Or,
environment. ( K + + Cl - + Pr - ) in A = (K + + Cl-) in B
-206- FAST TRACK BASIC SCIENCE MBBS
Basic Concepts

This shows that the Cl- concentration is higher is B Principle


than A. This method is based on the conservation of mass
- In Y, principle, which means that the total mass of a
Now the Cl- moves down along the substance after dispersion in the fluid
concentration gradient to A and K + will follow compartment will be the same as the total mass
to maintain electrical neutrality. injected into the compartment.
- In Z,
• Protein (Pr -) is impermeable, so it remains
in A.
• Due to this there will be ultimately more
ions is the side A than B (as it is gaining
some Cl - & K+ but not losing any protein)
• As a result, there occurs a difference of
osmotic pressure and the cells swell up and
the plasma volume increases (sides with
protein) hence their volumes are
maintained .
This is called Donnan effect.
- The most important difference between the
plasma and the interstitial fluid is the higher
concentration of protein in the plasma (due to
Donnan effect) In above figure,
- Protein is negatively charged & impermeable - A small amount of dye or other substance I
through capillaries. contained in the syringe is injected into a chamber
- As the proteins tend to bind cations (K+/Na+ ) and the substance is allowed to disperse
there is high concentration of positively throughout the chamber until it becomes mixed in
charged cations is plasma. equal concentrations in all areas.
- Conversely, the negatively charged ions tend to - Then a sample of fluid containing the dispersed
have a slightly higher concentration in the substance is removed and the concentration is
interstitial fluid compared with plasma, analyzed chemically, photoelectrically or by
because the negative charges of the plasma other means.
protein repel the negative charged ions. - If none of the substance leak out of the
Measurement of fluid volumes in the compartment,
different compartments The total mass of substance in the
compartment = Total mass of the substance
The Indicator - Dilution Method
injected
- An indicator substance is placed in the
Or, (Volume B × Concentration B) = (Volume A ×
compartment and allowed to disperse evenly
Concentration A)
through the compartment fluid.
Or,
- The extent to which the substance becomes
diluted is analyzed. Volume A × Concentration A
Volume B = Concentration B

FAST TRACK BASIC SCIENCE MBBS -207-


Physiology

For Specific body fluid compartments: Effect of adding isotonic, hypertonic &
Volume Indicators hypotonic solution to ECF after osmotic
equilibrium
1. Total body water 3H2O, 2H2O, antipyrine
22
2. Extracellular fluid Na,125I-iothalamate,
thiosulphate, inulin
3. Intracellular fluid Calculated as:
( Total body water - ECF)
125
4. Plasma Volume I-albumin, Evans blue dye ( T-
1824)
51
5. Blood Volume Cr - labeled red blood cells,
Or, calculated as:
Plasma volume
Blood volume = 1-hematocrit

(Extracellular fluid - plasma


volume)
6. Interstitial fluid Calculated as:
ECF - plasma volume
Blood volume
- Contains both ECF (the fluid in plasma) and ICF
(the fluid is the red blood cells)
I - The average blood volume of adults is about 7
percent of body weight (or about 5 liters).
- About 60% of blood is plasma & 40% is RBC’s.
Hematocrit (Packed Red cell volume)
- The hematocrit is the fraction of the blood
composed of red blood cells.
- It is determined by centrifuging blood in a
“hematocrit tube” until the cells becomes
tightly packed in the bottom of the tube.
- About 3 to 4 % of plasma remains entrapped
among the cells, hence the true hematocrit is
only about 96% of the measured hematocrit.
- In anemia, hematocrit is normally about Dehydration and Overhydration [05]
0.40 in male ♦ The primary measurement that is readily available
0.36 in female to the clinician for evaluating a patient’s fluid
- In polycythemia, hematocrit may rise to 0.65 status is the plasma sodium concentration.
Fluid movement among compartments ♦ Because sodium and its associated anions (mainly
- Continuous exchange and mixing of fluid chloride) account for more than 90 % of the solute in
between compartments occur due to the extracellular fluid, plasma sodium concentration is
a. Osmotic pressure a reasonable indicator of plasma osmolarity under
b. Hydrostatic pressure many conditions.

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Basic Concepts

A. Hyponatremia - Dehydration may occur due to severe burns,


- Plasma sodium concentration is reduced more prolonged vomiting, water deprivation, profuse
than a few milli equivalents below normal sweating etc.
(about 142 mEq / L) - Signs & symptoms:
- Results in swelling of cells. • Cottony or sticky oral mucosa.
- Cause brain cell edema & neurological • Dry skin
symptoms including headache, nausea, • Parched lips
lethargy and disorientation.
• Decreased urine output
- If plasma sodium concentration rapidly falls
- There are two types of dehydration:
below 115 to 120 m mol/L, brain swelling may
1. Hyper osmotic dehydration
lead to seizures, coma, permanent brain
damage & death. 2. Hypo osmotic dehydration
- As the skull is rigid, brain cannot increase its 1. Hyper osmotic dehydration
volume by more than 10 percent without it - Primary loss of water from ECF resulting in
being forced down the neck (herniation), which increased concentration of sodium ions in ECF.
can lead to permanent brain injury & death. Causes: Diabetes insipidus
Correction of hyponatremia Excessive sweating
- When hypertonic solutions are added too 2. Hypoosmostic dehydration
rapidly to correct hyponatremia, this can - Loss of water and decrease in osmolarity.
outspace the brain’s ability to recapture the Causes: Diarrhoea
solutes lost from the cells & may lead to Vomiting
osmotic injury of neurons that is associated Over use of diuretics
with demyelination (loss of myelin sheath) Adrenal insufficiency (Addison’s disease)
- This can be avoided by limiting the correction Overhydration I
of chronic hyponatremia to less than 10 to 12 - It occurs when water input exceeds the water
m mol/L in 24 hours & to less than 18 m mol/L output over a period of time.
in hours. (i.e. at a slow rate) - May occur if too much water is taken
B. Hypernatremia immediately after dehydration or after physical
- Plasma sodium concentration is elevated activity.
above normal. - If ECF is diluted, it can be dangerous.
- Results in cell shrinkage. - There are two types of over hydration.
- Severe hypernatremia can occur in patients 1. Hyper osmotic over hydration.
with hypothalamic lesions that impair their 2. Hypo osmotic over hydration.
sense of thirst, in infants who may not have 1. Hyper osmotic overhydration
ready access to water, or eldery patients with - Excess extracellular sodium chloride resulting
altered mental status. in water retention by Kidneys.
Correction of hypernatremia Causes: Cushing’s disease
- By administrating hypo-osmotic sodium Primary aldosteronism
chloride or dextrose solution. 2. Hypo osmotic overhydration
Dehydration - Excess water retention which dilutes the
- It occurs when water output exceeds intake sodium in the ECF.
over a period of time. Causes: Excess ADH (SIADH)
- Body is in negative fluid balance. Bronchogenic tumors

FAST TRACK BASIC SCIENCE MBBS -209-


Physiology

Abnormalities of body fluid volumes [05]


+
Abnormality Cause Plasma Na Extracellular Fluid Intracellular
Concentration Volume Fluid Volume
Hyponatremia-dehydration Adrenal insufficiency; ↓ ↓ ↑
overuse of diuretics
Hyponatremia-overhydration Excess ADH (SIADH); ↓ ↑ ↑
bronchogenic tumors
Hypernatremia-dehydration Diabetes insipidus; ↑ ↓ ↓
excessive sweating
Hypernatremia-overhydration Cushing's disease; primary ↑ ↑ ↓
aldosteronism
Tonicity [05] a. Isotonic fluid
Tonicity of fluids - A solution which has the same osmolarity with
- The term “tonicity” is used to compare the that of plasma is known as isotonic solution.
osmolarity of a solution in respect of - If a cell is placed in a solution of impermeant
impermeant solutes with that of the plasma or solutes having an osmolarity of 280 mOsm/L
extracellular fluid. (isotonic solution), the cell will not shrink or
swell.
280 mOsm/L
- As the water concentration in both is same,
solutes cannot enter or leave the cell.
Eg, 0.9% solution of NaCl,
5% solution of glucose, etc.
b. Hypotonic fluid
I ISOTONIC - A solution which has osmolarity lower than
SOLUTION
(No change) that of plasma is known as hypotonic
fluid/solution.
200 mOsm/L
- If a cell is placed in a hypotonic solution, the
cell will swell.
- The water moves from the solution into the
cell until both the solutions have same
osmolarity.
c. Hypertonic fluid
HYPOTONIC
SOLUTION
- A solution which has osmolarity greater than
(Cell swells)
that of plasma is known as hypertonic solution.
- A cell will shrink if placed in hypertonic solution.
360 mOsm/L - The water continues to diffuse out of the cell
until equilibrium is maintained.
Osmosis and osmotic pressure
Osmosis
- Osmosis is the net diffusion of water across a
selectively permeable membrane from a region
HYPOTONIC
SOLUTION
(Cell shrinks)

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Basic Concepts

of high water concentration to one that has a - Osmotic pressure exerted by crystalloids in a
lower water concentration. solution.
- Cell membrane is selectively permeable - Important in relation to the stability of RBC and
membrane as it is relatively impermeable to the size of all the cells in the body
most solutes but highly permeable to water. - When the ECF becomes dilute, the cell swells
- Whenever there is a higher concentration of up & when the ECF becomes concentrated,
solute on one side of the cell membrane, water the cell shrinks.
diffuses across the membrane toward the b. Colloidal osmotic tension
region of higher solute concentration. - Osmotic pressure exerted by colloids in the
Osmolarity solution.
- Number of osmoles per litre of solution. - Colloids are not evenly distributed in the body.
Osmolality - Plasma has plasma proteins, plasma lipids, etc.
- Number of osmoles per kg of solvent but the concentration of these colloids is
Osmotic Pressure: negligible in ECF.
- Osmotic pressure is the force under which a - So, plasma has more colloidal osmotic tension
solvent moves from a solution of lower solute (COT) than ECF which helps to keep water in it
concentration to a solution of higher solute and thus to maintain its volume. It also
concentration when a selectively permeable regulates formation and absorption of tissue
membrane separate the solution. fluid.
- It depends upon the number of particles in the
CELL MEMBRANE TRANSPORT
solution and not on the type or size or
concentration of the substance. Past Quesitons:
Osmotically active particles may be: 1. Draw the structure of cell membrane. Name the
cell membrane proteins and mention their
I
a. Crystalloids
functions. (2+3 = 5) [07 July]
- These particles dissolve in water resulting in a 2. Mention the functions of cell membrane. What is
clear permanent true solution/crystalloid meant by tight junction and its importance?
solution. (2+1 = 3) [07 Dec]
- They form crystals when passed through a 3. Describe briefly with the help of diagram the
parchment paper. structure of cell membrane. Name the different
modes of transport across cell membrane. What
- Size of particles is usually less than 1 mµ.. Eg:
is diffusion potential? (2+2+1=5) [03 June]
sugar, urea, Nacl. 4. Describe briefly with the help of diagram the
b. Colloids structure of cell membrane. Name the different
- These particles form a thick opalescent modes of transport across cell membrane. What
unstable solution when dissolved in water. is diffusion potential? (2+2+1 = 5) [03]
(colloid solution) 5. Name: [03 Dec]
a. Cell membrane proteins and give their
- Size of particles is usually from 1 µm to 200 functions (1+2=3)
mµ. E.g., proteins, starch, glycogen, etc. b. Types of intracellular communications with
c. Suspension examples (1+2=3)
- When size of particles >200µm. 6. a. Name different types of intracellular
According to the above particles, osmotictension/ connections. (1)
pressure also has two component: b. Describe the functions of gap junctions.
a. Crystalloid osmotic tension (2) [11 July]

FAST TRACK BASIC SCIENCE MBBS -211-


Physiology

7. What are the differences between tight junction Structure of Membrane:


and gap junction? (4) [04 Dec] Fluid mosaic model
8. Name the types of intercellular communications - By Singer & Nicolson.
and describe each of them with examples. - Membrane is asymmetric due to the irregular
(2+2 = 4) [06 June] distribution of proteins.
9. Name the different types of transport - The lipid & protein subunits of the membrane
mechanism across cell membrane and describe give an appearance of mosaic or ceramic tile.
primary and secondary active transport. - Unlike a fixed ceramic tile, the membrane
(2+3 = 5) [06 Dec] freely changes, hence the structure of the
10.Describe passive transport mechanisms and membrane is considered fluid mosaic.
active transport mechanisms with examples.
(2+4=6) [10 July]
12.Name different types of membrane transport.
Add a note on active transport.
(2+2 = 4) [04 June]
13. Differentiate (2⋅3=6) [10 Jan]
a. Co-transport and counter transport
b. Tight junction and gap junction
c. Osmosis and diffusion
14.Compare and contrast (4⋅3=12) [09 July]
a. Active transport and secondary active
transport
I 15.Explain briefly:
a. Cell membrane proteins (3) [05 June]
b. Gap junctions
a. Lipid bilayer
(2, 3) [08 Jan, 05 June, 05 Dec, 09 July]
- The basic structure is a lipid bilayer.
c. Active transport (2) [08 July]
- A thin, double-layered film of lipids - each
Cell Membrane (Plasma-membrane) [07, 03] layer only one molecule thick - that is
- It acts as an envelope surrounding the cell that continuous over the entire cell surface.
separates and protects the cell from the - The basic lipid bilayer is composed of
external hostile environment. phospholipid molecules.
- Thin, pliable, elastic structure only 7.5 to 10 - One end of each phospholipid molecule is
nanometers thick. soluble in water (hydrophilic) and the other
Composition: end is soluble only in fats (hydrophobic)
- Composed almost entirely of protein and lipids. i. Hydrophilic end
• The phosphate end of phospholipid
a. Protein (55%)
• Constitute the two surfaces of the
b. Phospholipids (25%)
complete cell membrane, in contact with
c. Cholesterol (13%) intracellular water on the inside of the
d. Carbohydrates (3%) membrane & extracellular water on the
e. Other lipids (4%) outside surface.

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Basic Concepts

ii. Hydrophobic end ii. Peripheral proteins


• The fatty acid portion of phospholipid • These are loosely held to the surface of
• Repelled by water the membrane and are often attached to
• Mutually attracted to one another and the integral proteins.
they have a natural tendency to attach • Can be easily separated eg, cytochrome
to one another in the middle of the C of mitochondria.
membrane. Functions:
• The lipid layer in the middle of the • Act as enzymes
membrane is impermeable to the usual • Act as controllers of transport of substances
water- soluble substances, such as ions, though the cell membrane “pores”
glucose & urea. c. Membrane Carbohydrates (The cell
• Conversely, fat- soluble substances, such “Glycocalyx”)
as oxygen, CO2, and alcohol can easily - Occur in combination with proteins or lipids
penetrate this portion of the membrane. in the form of glycoproteins and glycolipids
• The cholesterol molecules are dissolved respectively.
in the bilayer of the membrane. They - Most are glycoproteins.
control the fluidity of the membrane and - The “glycol” portions of these molecules
determine the degree of permeability (or almost invariably protrude to the outside of
impermeability ) of the bilayer to water - the cell.
soluble constituents of body fluids. - Other carbohydrate compounds are
b. Membrane proteins [07] proteoglycans (carbohydrate substances
− Globular masses floating in the lipid bilayer. bound to small protein cores)
− There are two types of cell membrane proteins. Functions:
i. Integral proteins. - Many are negatively charged which gives
I
• Protrude all the way though the most cells an overall negative surface
membrane charge that repels other negative objects.
• They are tightly bound to the lipid - Glycocalyx of one cell attract another, thus
bilayer only. attracting cells to one another.
• Can be separated only by the use of - Act as “receptor substance” for binding
detergents or organic solvents. Eg, hormones such as insulin. This binding
hormone receptors, cytochrome P450. activates attached internal proteins which
Functions: then activates a cascade of intracellular
- Provide structural channels (or pores) enzymes.
through which water molecules & water Transport across membrane (chart below)
soluble substance (especially ions) can [04, 03]
diffuse between ICF & ECF. Cell- membrane Transport
- Act as carrier proteins for transporting
substances that otherwise could not Diffusion Active transport Vesicular
penetrate the lipid bilayer. transport
Simple
- Some act as enzymes. diffusion Primary Exocytosis
- Some help in active transport of substances. transport
Facilitated
- Also serve as receptors for water soluble diffusion Secondary transport Endocytosis
chemicals like peptide hormones. a. Co-transport
Osmosis b. Counter transport

FAST TRACK BASIC SCIENCE MBBS -213-


Physiology

A. Diffusion Ion Channels


- All molecules and ions in the body fluids are in a. Leak channel
constant motion. • K+ leak channel
- The motion never ceases under any condition • Open to movement of substance all the
except at absolute zero temperature. time
- A single molecule in a solution bounces among • Opening of leak channel tend to decrease
the other molecules first in one direction, then the concentration of K + in ICF.
another and so forth, randomly bouncing • Not permeable to sodium
thousands of times each second.
(Reason : In hydrated form Na+> K+ in size
- The continual movement of molecules among due to high molecular force of attraction in
one another in liquids or gases is called sodium, Hence, Na+ doesn’t pass)
diffusion.
b. Gated Channels
1. Simple diffusion
• Gating of protein channels provide a means
• It is the kinetic movement of molecules or of controlling ion permeability of the
ions that occurs through a membrane channel.
opening or through intermolecular spaces • Some gates are actual gate like extensions
without any interaction with carrier of the transport protein molecule which can
proteins in the membrane. close the opening of the channel or can be
• Simple diffusion can occur by two pathway: lifted away from the opening by a
a. Through the interstices of the lipid bilayer conformational change in the shape of the
if the diffusing substance is lipid soluble. protein molecule itself.
b. Through watery channels that penetrate • Sodium gates open & close on the outside &
I all the way through some of the large the potassium gates open & close on the
transport proteins. inside.
• The rate of diffusion is determined by:
i. Concentration gradient
ii. Velocity of kinetic motion
iii. The number & sizes of openings in the
membrane.
Diffusion through lipid bilayer
• Depends upon the lipid solubility of the
substance. Eg, O2,N2, CO2, alcohol, etc.
Diffusion through protein channels
• Pores are composed of integral cell
membrane protein
• Lipid insoluble substances pass.
• Protein channels are selectively permeable
a. Sodium channel→strongly negatively
charged
b. Potassium channel→tetrameric

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Basic Concepts

The opening & closing of gates are controlled in Mechanism


two principal ways: - “Ping- pong” model
i. Voltage gating - A transport (carrier) protein exists in two
- The molecular conformation of the gate or conformations.
of its chemical bonds respond to the - In the pong, conformation, it is exposed to
electrical potential across the cell the side with high solute concentration. This
membrane. allows the binding of solute to specific sites
on the carrier protein.
a. Voltage gated sodium channels
- The protein then undergoes a
• Located on the outside of membrane.
conformational change (ping state) to
• The gates remain closed as long as there expose to the side with low solute
is strong negative charge on the inside of concentration where the solute molecule is
the cell membrane. released.
• When the inside of the membrane loses - Hormones regulated facilitated diffusion.
its negative charges, the gates open to eg, glucose transport, amino acid transport,
allow Na+ to enter. etc.

• This is the basic mechanism for causing


action potential.
b. Voltage gated Potassium channels
• Located on inside
• Open when the inside of the cell
membrane is positively charged. I
Difference between simple & facilitated diffusion
• This is responsible for termination of
action potential.
ii. Ligand gating
- Ligand gated channels open by binding of a
chemical substance (a ligand) with the
protein.
- This causes a conformational or chemical
bond change in the protein molecule that
opens/closes the channel.
Eg: Ligand gated Na+ channel,
Acetylcholine channel, etc.
2. Facilitated diffusion (carrier - mediated
diffusion)
- The carrier facilitates diffusion of the
substance to the other side.
- No energy is required.

FAST TRACK BASIC SCIENCE MBBS -215-


Physiology

Simple diffusion Facilitated diffusion Na + - K+ Pump


- Rate of simple - Rate of diffusion increases
diffusion is to a maximum (Vmax) as the
directly concentration of diffusion
proportional to substance increases, then,
the availability it remains constant.
of substance. - This is due to the fact that
- Rate the process of
continuously conformational change of
increases. protein is limited.
3. Osmosis
(Refer to before described Osmosis)
B. Active- transport [04]
- It is the uphill movement of ions or molecules - This transport process pumps sodium ions
across a cell membrane using energy. outward through the cell membrane of all cells
and at the same time pumps potassium ions
- An uphill transport may be
from the outside to the inside.
• Against concentration gradient
- The pump is responsible for maintaining the
• Against electrical gradient
sodium & potassium concentration differences
• Against pressure gradient across the cell-membrane, as well as for
- Active transport maintains the difference in establishing a negative electrical voltage inside
concentration of ions in ECF & ICF, so that the cells.
there is always movement across the - It is also the basis of nerve function.
I membrane. Components:
- It is also a carrier - mediated process. - The carrier protein is a complex of two
1. Primary transport separate globular proteins:
- The energy is directly derived from α subunit ( larger)
breakdown of adenosine triphosphate (ATP) β subunit
or of some other high- energy phosphate - The larger α subunit has following three
compound. specific features:
- The carrier is capable of imparting energy to a) It has three receptor sites for binding
the transported substance moving it against sodium ions (on the portion of the protein
the electrochemical gradient. that protrudes to the inside of the cell)
Eg, Na+ - K+ pump b) It has two receptor sites for potassium ions
Ca++ pump (on the outside)
Substances transported by primary transport c) The inside portion of this protein near the
are: sodium binding sites has ATPase activity.
- Sodium Basically it has 5 different binding sites;
i. Na+ binding site
- Potassium
ii. K+ binding site
- Calcium iii. Ouabain - binding site
- Hydrogen iv. Phosphorylation site
- Chloride v. ATP - binding site

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Basic Concepts

Ouabain
- A digitalin drug that act as an inhibitor of Na+ -
K+ pump
- Na+ concentration increase in ICF resulting in
increased impulse generation, contractility &
heart rate.
Mechanism
- When 2 K+ ion bind on inside, 3 Na+ bind on
the outside

ATPase function of protein gets activated
b. Counter- transport
↓ - It is the simultaneous transport of two
Cleavage of ATP Into different molecules in the opposite
direction.
Eg, Na+ - H+ counter transport
ADP High energy phosphate bond

Cause a chemical & conformational change in
the protein carrier molecule
↓ I
+ +
3 Na move outside & 2 K move inside
2. Secondary transport [07]
- The energy is derived secondarily from
energy that has been stored in the form of
ionic concentration differences of c. Vesicular Transport
secondary molecules or ionic substances i. Endocytosis
between the two sides of a cell membrane.
• It is the movement of macromolecules
- It uses the concentration gradient created from outside the cell to the inside of the
by primary active transport. cell by the active invagination of the
Types: plasma membrane.
a. Co-transport Mechanism
- It is the phenomenon in which the diffusion - The plasma membrane contains coated pits.
energy of an ionic substance can pull other - These pits can be internalized to form
substances along with it through the cell coated vesicles which contain an ususual
membrane. protein called “clathrin”
Eg, Na+ co-transport with glucose Eg., uptake of LDL by cell
aminoacids, etc.

FAST TRACK BASIC SCIENCE MBBS -217-


Physiology

On the basis of state of the substance taken up CELL TO CELL AND LOCAL
endocytosis is divided into: COMMUNICATION
a. Phagocytosis Past Questions:
• It is the process by which the solid 1. Name: [03 Dec]
materials a. Cell membrane proteins and give their
(E.g., bacteria, dead tissue) are engulfed functions (1+2=3)
by cells. b. Types of intracellular communications with
b. Fluid- phase endocytosis (Pinocytosis) examples (1+2=3)
- It is the process of uptake of molecules 2. a. Name different types of intracellular
in solution connections. (1)
i. Constitutive endocytosis b. Describe the functions of gap junctions.
(2) [11 July]
• Vesicles continuously fuse with the
3. What are the differences between tight junction
cell membrane
and gap junction? (4) [04 Dec]
ii. Receptor - mediated endocytosis
4. Name the types of intercellular communications
• The molecule to be internalized binds
and describe each of them with examples.
to a receptor on the surface of the
cell which then concentrate at (2+2 = 4) [06 June]
clathrin - coated pits. 5. Write short notes on:
ii. Exocytosis a. Tight junction and gap junction
- It is the process by which macro molecules b. Gap Junctions (2,3)
are packaged in secretory vesicles and then [08 Jan, 05 June, 05 Dec, 09 July]
extruded from the cell.
I - It requires both calcium & energy Intercellular connections [11, 04]
Eg: Secretion of homones like insulin, ♦ It means connection between the cells of a tissue.
parathyroid, etc.
♦ These connections are required to hold the cells of
a. Constitutive secretion
a tissue together or for communication between
b. Regulated exocytosis
the cells.

Intercellular connections

Mechanical CAMs Gap


(Cell Adhesion junction
Molecules)

Tight Maculae Zonulae


junctions adherens adherns

Desmosmes Hemidesmosomes

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Basic Concepts

A. Mechanical connections - These junctions involve small areas


1. Tight junction (Zonulae occludens) between two membranes.
- Adjacent areas become thickened & the
space in between is filled with filament like
material containing Cadherin and some
other membrane proteins.
- Fibers radiated to the interior of each cell
from the thickened portions of the
membrane.
ii. Hemidesmosomes

- These connections are formed by ridge - like


structures which are made up of proteins like
cingulin, etc.
- Contributed by the membranes of both the
adjacent cells.
- Situated in the apical region of the cells
forming a selective barrier.
- Help to maintain the functional polarity of a - Half desmosomes found in the basal sides
cell by localizing the membrane proteins in one of the epithelial cells is contact with the I
place. basement membrane.
- Found between epithelial cells lining a lumen. - Contain protein Integrin.
Eg:In intestinal mucosa, renal tubules, etc. B. Cell adhesion molecules (CAMs)
2. Zonulae adherens
- These are the protein molecules that bind the
- Present in between epithelial cells and in
tissue cells in between the different junctions.
continuation with the tight junction towards
the basal side. - The CAMs of adjacent cells bind together giving
- Made up of protein Cadherin. stability to the tissue.
3. Maculae adherens - The CAMs may be:
i. Desmosomes i. Hetrophilic → Bind to the same type
ofmolecules.
ii. Homophilic → Bind to different type of
molecules.
Role of CAMs
- Development, in inflammation, in would
healing and in metastases tumours.
- CAMs also bind to the extracellular matrix with
the help of laminins in ECM.

FAST TRACK BASIC SCIENCE MBBS -219-


Physiology

Following are different CAMs: Intercellular communications


i. Cadherins
- Ca++ dependent molecules that bind
homophilically
Neural Electrical (through Chemical
ii. Selectins gap junction)
- Carbohydrate binding CAMs
iii. Integrins
iv. Ig G Adhesion molecules Endocrine Paracrine Autocrine
- Immunoglobulins that bind both A. Neural communication
homophilically & heterophilically. - One cell communicates with other by means
C. Gap junctions [09, 08, 05] of electrical impulse via nerves.
- Provide gaps in the membranes of the adjacent - Neurotransmitters are released at synaptic
cells though which the cells can communicate junctions from nerve cells and act across a
with each other. narrow synaptic cleft on a past synaptic cell.
- Two adjacent membranes come closer and B. Elecrical communication
pore is formed by membrane protein called - Through gap junction, cell communicates
connexons. with each other.
- The pore diameter is regulated by Ca2+ C. Chemical communication [05, 04]
membrane voltage and pH.
1. Endocrine communication
Connexons:
- Hormones and growth factors reach the cells
- Hexagonal protein units that have a central via blood. Eg: TSH secreted by anterior
I hole which passes through and through the pituitary reach thyroid glands (by blood &
membrane . stimulate the thyroid cells)
- When such proteins of opposing members 2. Paracrine communication
come in alignment, a pore is formed
- A local chemical diffuses to ECF (extracellular
connecting the two cells.
fluid) and reach the nearby cell.
Functions of gap junction:
Eg: Glucagon from α cells of the islets of
- Provide passage for transfer of ion, sugar, Langerhans inhibits the β cells.
amino acid, chemical messengers, etc.
3. Autocrine Communication
- Provide a low impedance electrical pathway
- The chemical acts on the same cell from
in between cells.
where it is produced.
(Important in cardiac muscle and single unit
Eg: Platelet activating factor (PAF) is
smooth muscles).
produced by platelets and act upon the
• Depolarises the whole tissue by platelets themselves
conduction of electrical impulse is those
tissue.
Juxtracrine communication
♦ A form of intercellular communication where
Intercellular communication
the cells communicate through interaction of
♦ Communication between the cells for the specific cell surface proteins of the adjacent
orderly function of the body. cells.

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Basic Concepts

♦ A/C to W.B cannon, Homeostasis is “the various


HOMEOSTASIS physiological arrangements which serve to restore
Past Questions: the normal state, once it has been disturbed.”
1. Define homeostasis. Explain with examples the ♦ As the interstitial component of ECF is the actual
negative feedback control (1+3=4) [09 July] environment of the cells of the body, the normal
2. Define homeostasis and explain the concept of cell function depends on the constancy of this
negative feedback correction giving suitable fluid.
examples. (1 + 3 = 4) [05 June] ♦ The constancy is maintained by monitoring &
I
3. What is homeostasis? Explain briefly with regulating the function of circulatory, digestive,
examples. (1+4 =5)[03 June] regulatory, renal and musculoskeletal system.
4. Explain briefly the role of feedback mechanism ♦ The process is co-ordinated via nervous &
for regulation of hormones. (5) [06 Dec] endocrine systems.
5. Define (5×1=5) [07 July] Regulation of body functions
a. Homeostasis Requirements for regulation of body functions:
6. Compare and contrast [09 July] a. Receptors
a. Negative and positive feedback mechanism b. Co-ordinating & integrating mechanism
7. Write briefly on: [03 July] (control center)
a. Role of feedback mechanism in regulation of c. Effectors
secretion of hormone. Intergrating center
b. Homeostasis [08 July]
c. Homeostasis with two examples [10 July]
d. Negative feedback mechanism [06 June] Receptor Receptor
♦ Homeostasis is defined as the “regulatory
mechanism that act to maintain the constancy of
the internal environment, necessary for well - Stimulus Response
being of the cell.”

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Physiology

1. Nervous regulation 2. Buffering action of Hb


Composed of Decreased O2 in cells
a. Sensory input portion ↓
b. Central nervous system (integrative portion) Over accumulation of CO2 & H+
c. Motor output portion ↓
Pathway via nerves: Buffering action of hemoglobin (Hb)
Sensory receptors (input) by binding with H+ than to O2
(detect the state of body or surrounding) ↓
↓ Formation of Hb-H+ & decreased Hb-O2 formation
Sensory fibers ↓
↓ Increased release of O2 to cells
Brain & spinal cord ↓
(Integrating center) Hypoxic condition restored to normal
↓ Characterstic of control system
Motor fibers (Output)
- Feedback system

Physiological changes in body • Cycle of events in which the status of a
returning it to normal state body conditions is continually monitored,
2. Hormonal regulation evaluated, changed, re-monitored, re-
- Through hormones secreted by different evaluated & so on.
endocrine glands - The control system works by the following
- Pathway via circulation mecanisms:
Eg: Thyroid hormones increases the basal
A. Negative feedback mechanism
metabolic rate, insulin controls glucose
metabolism, etc. B. Positive feedback mechanism.
Control systems of body [10, 08] A. Negative feedback mechanism
I
♦ Operate within the organ to control function of - The effects are negative with respect to the
individual parts or control inter-relation between initiating stimulus, i.e, it initates impulse that
organs. inhibits more of the same response to happen. Eg:
♦ Some examples are given below:
• Regulation of CO2 concentration in ECF
Regulation of O2 & CO2 concentration in the
body • Temperature regulation
1. Respiratory system in association with CNS • Regulation of arterial BP
Increased CO2 in ECF a. Regulation of arterial BP

↑ BP in body
Dissolves in H2O to form H2 CO3


Arterial baro-receptors in carotid arteries &
HCO3- + H+
aortic arch stimulated

Acidic environment ↓
Nerve impulse to brain (Vasomotor centre)

Stimulation of respiratory centre ↓
Inhibition of vasomotor centre

Increased respiration ↓
Decreased sympathetic output to blood vessels

& heart
CO2 released out by expiration


Decreased BP
Decrease in CO2 level back to normal

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Basic Concepts

Medulla

Parasympathetic-bradycardia
Sympathetic-tachycardia
NTS : Nucleus of Tractus solitarius
NTS RVLM : Rostral ventrolateral medulla
CVLM : Caudal ventrolateral medulla
IVLM : Intermediate ventrolateral medulla
GABA IVLM GABA : Gamma aminobutyric acid
- acts as inhibitor
Glu Glu : Glutamine
- acts as excitatory reflex mechanism
CVLM
- release due to increased BP
IVLM
IX and X cranial nerve is called buffer nerve

IX

IML I
Carotid
labyrinth Thoracic cord

Aortic arch

Heart

Baroreceptor reflex mechanism

FAST TRACK BASIC SCIENCE MBBS -223-


Physiology

b. Temperature regulation B. Positive feedback mechanism


♦ The response to a stimulus enhances or intensifies
Tempetature – sensitive the original stimuli, i.e, intiates impulse causing
↓Body nerve ending
temperature more or the same response to happen.
Afferent pathway ♦ Very few control systems of body operate via it.
– Brain & Spinal Useful positive feedback systems
cord a. Clotting of blood
Rupture of blood vessels
(Nerve
fibres)
Efferent pathway ↓
Activation of clotting factors

↑ Constriction of Curling Contraction Act on inactivated enzymes
smooth muscle in up of skeletal ↓
skin blood vessels muscles Clot formation
b. Birth of child
Strong uterine contraction + baby’s head
passing through cervix
↓ Heat loss form ↑ Heat ↓
body production Activation of stretch receptors

Release of oxytocin from hypothalamus

Regulation of BP (Renin - angiotensin system)
Futher uterine contraction
↓ Arterial pressue ↓

I ↓ Child birth
c. Generation of nerve signals
Renin production ( Kidney)
Stimulation of neuron
↓act upon ↓
Increased leakage of Na+ ions interiorly due to
Renin substrate (Angiotensinogen) more opening of channels
↓ ↓
Creation of action potential
Angiotension I Positive feed back as a viscious cycle
Angiotensinogen ♦ May cause instability & often death
Converting Enzyme (Lungs)
Loss of more than 2L blood from body
Angiotensin II

Blood shortage in body

Renal retention Vasoconstriction Inactivation of Decreased cardiac output of heart
of salt and water angiotensinase ↓
Decreased arterial BP

Cardiac muscle perfusion decreased

↑ Arterial Weakening of heart
pressure ↓
Diminished pumping

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Basic Concepts

Gain of control system 4. What is resting membrane potential? Describe


- The degree of effectiveness with which control ionic basis of action potential with a diagram.
system maintains homeostasis is gain of (1+3=4) [10 July]
negative feedback. 5. Define resting membrane potential. Draw and
- Error signal → It is the deviation from the label a diagram showing phases of action
original value. potential. Describe the ionic basis of
depolarization. (1+3+2=6) [04 June]
Gain = Correction / Error
6. Describe with the help of a diagram the ionic
Let the temperature decrease from 37° C to 34° C basis of action potential. What is meant by the
& negative feed back bring the temperature to 36°C. refractory period? (5+1 = 6) [04 Dec]
Now, 7. Describe with the help of a diagram the ionic
Correction by feed back system = 36 - 34 = 2 basis of action potential. (5) [08 July]
Error remaining still in correction = 37-36 = 1 8. What is action potential? Describe with the help
Then, Gain = 2/1= 2 of diagram the ionic basis of action potential.
Feed forward control (adaptive control) (1+4 = 5, 2+5=7) [08 Jan, 02 June]
- This mechanism is used when some 9. What is the difference between action potential
movements of body are occurring so rapidly and membrane potential? Describe with the help
that there is not enough time for signals to of a diagram the ionic basis of action potential.
travel through peripheral nerves from different (2+4=6) [07 Dec]
parts to brain & then again back to periphery. 10.Define RMP. Describe briefly the action potential
- It is also called delayed negative feed back with labelled diagram. (1 + 4 =5) [05 Dec]
adaptive control. 11.Describe with the help of a diagram the ionic
Mechanism: basis of action potential. What is meant by
Detection of degree of requirement of correction refractory period? (5+1=6) [04 Dec]
of movement by brain via sensory nerves 12.Write short notes on:
I
↓ a. Receptors (1) [07 July]
If it is not completely corrected, correction is b. Excitatory postsynaptic potential (EPSP)
made next time (2) [06 June, 09 July]
↓ Excitable cells
Correction in further next cycle continue till ♦ Those cells which respond to a particular
the movement is completely corrected threshold stimuli either by contracting or
BIOELECTRICITY conducting electrical impulses.
Past Questions: Eg: Muscles and nerves
1. Define: [07 July] Nerves
a. Receptor a. Functional anatomy ( Refer to anatomy)
b. Refractory period b. Properties of nerve fibres
c. Action potential i. Resting membrane potential: Nerve fibres
shows RMP of about -70 mV
2. Compare and contrast [09 July]
ii. Excitability: Ability to respond to a stimulus is
a. First messenger and second messenger
called excitability. A nerve fibre responds to a
b. Threshold potential and generator potential threshold stimulus by production of action
3. Write briefly on: [03 July] potential.
a. What is membrane potential? (1) The measure of excitability is chronaxie.
b. How does action potential differ from Thicker fibres are more excitable than thinner
generator potential? [11 July] fibres.

FAST TRACK BASIC SCIENCE MBBS -225-


Physiology

iii. Latent period: The time interval between the vii. Accommodation: When a stimulus fails to
application of stimulus and the response stimulate a nerve fibre, it is said to be
obtained is called latent period. accommodated and the process by which the
iv. Electrotonus: Passive change in membrane stimulus is made ineffective by nerve fibre is
potential (MP) due to application of stimulus. called accommodation.
v. Local response viii. All or none law
- The change in MP with active participation - A nerve fibre is said to obey 'all or none'
of membrane (but not AP) is called local law.
response.
- It is true only in case of AP formation.
- Occurs due to entry of Na+ in nerve fibre
after channel opening. - “If AP is produced, it is produced fully only
for a threshold stimulus and it is never
- Also called generator potential/receptor
produced partially.”
potential.
- Defined as change of potential in the - The size of AP formed in a particular fibre is
receptor membrane due to stimulus which always same whatever may be strength of
may generate an impulse in related sensory stimulus provided other conditions remain
nerve. constant.
- Eg: EPSP, IPSP etc. ix. Conductivity
vi. Action potential - Ability to conduct the AP along nerve fibre.
- Is the sequential change of membrane - Velocity of conduction is higher in
potential after application of a threshold myelinated nerve fibres due to saltatory
stimulus. conduction.
- Starts at site of application of stimulus and - Thicker the fibre higher is the velocity of
moves along the membrane in all conduction.
I directions.
x. Refractory period (RP): [07]
Action Potential [08] Generator Potential [08] The time period after an action potential
a. There is change in a. Change in membrane during which a new stimulus cannot be elicited
membrane potenital potentials towards is called refractory period.
and complete firing level. It is of two types.
depolarisation occurs.
a. Absolute RP
b. Impulse conducted b. Impulse remains - The period during which a second action
along membrane locally. potential cannot be elicited even with a
without change in its
strong stimulation is called absolute RP.
size.
- It is initial part of RP and corresponds to
c. Cannot be summated. c. Can be summated. period of AP from the firing level upto
d. Can be caused only by d. Can be caused even by 1
the initial 3rd of repolarization.
threshold stimulus. subthreshold stimulus.
e. Obey 'all and none' law e. Doesn't obey 'all and b. Relative RP
provided other none' law. - After absolute refractory period is a relative
conditions remains refractory period during which stronger
constant. than normal stimuli can excite the fibre.
f. Size doesn't depend on f. Size depends on - During this, tissue is less excitable than
strength of stimulus. strength of stimulus. normal.

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Basic Concepts

Causes of RP g. Membrane potential:


+
- Most of Na channels opened during the AP, - It is the difference of electrical potential
remain inactivated during ARP. between inside and outside of the membrane
- In RRP, many of them return to normal. of cell.
- This is in the range of -10mV to -90mV
Some terminology
- The -ve sign indicates the polarity of cell is
a. Stimulus
inside of membrane (-90 mV means that
- Defined as a sudden change in the interior of the cell is -ve by 90 mV in respect to
environment which brings about response in outside)
an excitable tissue.
h. Resting membrane potential (RMP) [10,04]
- May be mechanical, electrical, thermal, - When the membrane potential is measured in
chemical, etc. a resting cell it is called resting membrane
b. Rheobase potential (RMP).
- It is the minimum strength of stimulus which - Normally inside of cell membrane has negative
when applied for a very long time, just excites charge and outside has positive charge.
the tissue. - So, RMP is -ve.
c. Chronaxiae: Causes of production of RMP
- When the strength of stimulus is double that of I. Due to presence of Na+-K+ pump in membrane
rheobase, the minimum time required for
excitation of a tissue is called chronaxiae 2K+ 3Na+
d. Summation:
- It is the addition of electrical or physical Outside
changes due to application of repeated stimuli. I
e. Synapse:
- It is the neuroneuronal or neuromuscular Inside
junction in the nervous pathway.
- It is junction between pre-synaptic and post
synaptic membrane or presynaptic membrane 2K+ 3Na+
and motor end plate of muscles.
- It pumps 3 Na+ ions outside and 2K+ inside
- The space between presynaptic and post and as a result net one +ve charge moves
synaptic membrane is called synaptic cleft. out by each cycle.
- Impulse is transmitted across it by release of - So, there is positivity outside and negativity
neurotransmitter. inside.
f. Threshold stimulus II. Due to Donnan Membrane Equilibrium
- The stimulus which is just sufficient to produce - Most of Na+ leak channels remain closed
an AP in an excitable cell/tissue is called during the resting conditions so very little
threshold stimulus. Na+ can diffuse inside.
- Stimulus stronger then threshold stimulus is - K+ leak channels are almost all open.
called suprathreshold stimulus. - So, K+ which is high inside diffuses outside.
- Stimulus weaker than threshold stimulus is III. Efflux of K+ is 50-100 times more than influx of
called subthreshold stimulus. Na+

FAST TRACK BASIC SCIENCE MBBS -227-


Physiology

IV. Inside the cell there is non-diffusible anion,


protein, SO4-- etc.
RMP
- Smooth muscles - 55 mV
K+ K+ Na+ Na+
- Skeletal muscles - 90 mV
- Cardiac muscles - 80 mV
- Nerve fibres - 70 mV
- RBC + 9 mV -94mv +61mv
i. Nernst Equation Anions Anions
- There are some ions which has its maximum Nerve fibre
concentration inside the cell Eg: SO4--, Cl-, K+
j. Action potential [11, 10, 08, 07, 04]
and some have its maximum concentration
It is the sequential change of membrane potential
outside the cell Eg: Na+ etc
after application of a threshold stimulus which
- As a result, of difference in net -ve or +ve starts at the site of application of stimulus and
charge inside and outside cell respectively, moves along the membrane in all directions.
there is development of electrical potential.
To conduct a nerve signal, the AP moves along the
- The potential difference across the membrane nerve fibre until it comes to the fibres end.
can be calculated by an equation celled Nernst
ε1 Cinside +35 Overshoot
Equation as: (emf)
= ± 61 log C (in mV) Spike potential
outside

where,
I ε = potential difference or Emf in mv
Cinside = Concentration inside cell for an ion
Coutside = Concentration outside cell for same
Firing level
ion
-70
If, membrane is permeable to different ions, Resting
Hyperpolarization
diffusion potential depends on 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
a. The polarity of electrical charge of each ion Time (ms)
b. The permeability of membrane (p) to each ion Action potential
c. The concentration (c) of respective ions on This above graph shows successive changes in
inside and outside the membrane. membrane potential over a few 10,000ths of a
and second illustrating the explosive onset of action
Goldman equation or Goldman-Hodgkin Katz potential and almost equally rapid recovery.
equation is used: The successive stages of action potential are:
CNa+i PNa+ + CK+i PK+ + CCl– OPCl– a. Resting stage/ latent period: This is resting
ε = -61 log membrane potential before the action
CNa+O PNa+ + CK+OPK+ + CCl– i PCl–
potential begins. The membrane is said to be
Where, i = inside polarized during the stage because of -90 mv (-
O = outside ve membrane potential) that is present.

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Basic Concepts

b. Depolarization So, explosive Na+ entry resulting in rapid


- At this stage, due to some stimulus the depolarization.
membrane suddenly becomes permeable to - In thick nerves, MP may reach to +35 mv.
sodium ions allowing tremendous number iii. Repolarization
of positively charged Na+ to diffuse to
- Na+ entry stop due entry of sufficient Na+
interior of membrane of nerve.
inside and concentration gradient is
- The normal polarized state of -90 mv is decreased and electrical gradient is
immediately neutralized by inflowing +vely reversed.
charged Na+ ion.
- Plenty of voltage gated K+ channels open up
- Potential rises rapidly in positive direction. and K+ leaks outside rapidly.
- In large nerve fibres, the great access of
So, MP is rapidly restored.
positive sodium ions moving to inside
- This results rapid repolarization
causes the membrane potential to actually
'over shoot' beyond zero level to become - Later K+ efflux becomes slow resulting in
somewhat +ve. after the depolarization causing after-
- In small fibres over shoot is not seen. hyperpolarization.

iii. Repolarization k. Receptor: [08, 07]

- Within few 10,000th of a second after the - It is defined as a macromolecule or binding site
membrane becomes highly permeable to located on the surface or inside the effector
sodium ions, the sodium cannels begin to close cell that serves to recognize the signal
and K+-channels begin to open more than molecule / ligand and initiate the response to it
normal. but itself has no other functions.
- Then rapid diffusion of potassium ions to Classification I
exterior reestablishes the normal negative i. Ion channel linked receptor: Receptor of ACh,
resting membrane potential. NE etc.
Factors that cause depolarization and repolarization ii. G-Protein coupled receptor: This receptor in
- Transport channels through nerve membrane turn alters ion channels or activity of
- Voltage gated sodium and potassium channels intracellular enzymes

- Na+-K+ pump E.g. adenylyl cyclase or phospholipase C.


- K+ leak channels iii. Enzyme linked hormone receptors:
Ionic basis of its genesis [10, 08, 04, 02] Eg: leptin receptor, Tyrosine kinase of Janus
kinase (JAK)
i. Latent period/resting stage: After application
of stimulus, some time is required before any iv. Intracellular hormone receptors:
changes in MP occurs called latent period. Eg: Steroid receptor for adrenal and gonadal
ii. Depolarization hormones.
- Then MP gradually becomes less negative to According to sensory modalities:
reach firing level due to Na+ entry through i. Cutaneous receptors
voltage gated Na+ channels. - Pain receptors: Free nerve endings
+
- Due to Na entry, MP reduces further. So, - Touch pressure receptors: Pacinian
more Na+ channels are opened and it corpuscle, meissner's corpuscle.
continues in +ve feedback manner. - Temperature receptors: Nerve endings
FAST TRACK BASIC SCIENCE MBBS -229-
Physiology

ii. Proprioceptors iii. Intensity discrimination


Movement, sense and position of body in Weber-Fechner law:
space. Sensation felt ∝ log I
iii. Special sense receptors [where,I = Intensity of stimulus]
Visions - Rods and cones i.e. if stimulus is increased 10 times its intensity
Hearing - Hair cells sensation felt is doubled.
Taste - Taste buds iv. Law of projection:
Types of Receptor - If any part of sensory pathway is stimulated
i. Free nerve endings: i.e. from receptor to sensorium (cerebral
cortex), the sensation felt is at site of
- Peripheral end of a sensory nerve without
receptor.
any obvious special structure in it. Eg:
Receptors for pain, touch, temperature etc. E.g. Phantom limb phenomenon.
ii. Expanded nerve endings: v. Doctrine of specific nerve energies:

- Merkel's disc, Ruffini end bulbs for touch - Sensation felt depends on type of specific
pressure. receptor.
iii. Encapsulated endings: vi. Receptor potential/Generator potential
- Pacinian corpuscles vii. Adaptation
iv. Specialized cells: viii.Recruitment:
- Rods and cones for light - When intensity of stimulus is increased, the
no. of receptors stimulated also increases.
v. Sense organs:
Function of receptors
I - Taste buds for gustation
a. Biological transducer:
Properties of Receptors
- Sensory receptor can convert/transduce
i. Adequate stimulus:
various forms of energy to AP in nerve
- A receptor is most sensitive to a particular fibres.
type of stimulus which is called adequate
E.g. Light in rods and cones.
stimulus for that receptor. E.g. light for rods
and cones b. Helps to maintain homeostasis

ii. Specificity c. Interpreters:

- A receptor is much more specific to their - Can translate different language (pressure,
action. temperature) into electrical language which
nervous system can understand.
- A particular type of receptor responds to a
particular type of stimulus to produce
particular response only.

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Basic Concepts

SPECIAL POINTS FOR MCQs


1. Na+ is less permeable across cell membrane as compared to K+ due to having larger hydrated
diameter.
2. Causes of resting membrane potential are
a. Na+ - K+ pump in membrane.
i.e. 3 Na+ goes out of cells
2 K+ enters cells and net one +ve charge goes out of cells.
b. Efflux of K+ is 50-100 times more than Na+ entry.
c. Presence of non-diffusible anions, SO4¯¯ etc inside cell.
3. The magnitude of membrane potential at any given moment can be determined with considerable
accuracy by Goldman Hodgkin Katz (GHK) equation.
4. Point at which rate of depolarization in a neuron increases is called firing level.
5. Rheobase is weakest current strength which can excite a tissue.
6. Chronaxiae can be considered as unit of excitability.
7. Chronaxiae is longer in less excitable tissue.
8. An excitable cell adapts to applied stimulus due to slower and delayed opening of voltage gated
K+ channels.
9. The bimolecular lipid layer in cell membrane has characteristics of a fluid due to presence of
cholesterol.
10. Substances are delivered from the outer membrane of cell proper to membrane of nucleus by
endoplasmic reticulum.
11. Steroids are synthesized by smooth endoplasmic reticulum. I
12. Rough ER is responsible for protein synthesis.
13. Peroxisomes are responsible for destroying products formed from oxygen especially H2O2.
14. The major force affecting the distribution of water and solutes in different body compartment is
diffusion.
15. Osmotic pressure depends upon no. of ions or particles dissolved in solution.
16. Osmolality of human plasma is 277 - 295 mOsm/l
17. Isotonic solution are
- 0.9% sodium chloride
- 5% glucose
- 20% urea
18. Active transport means transport of any substances using ATP against concentration gradient,
pressure gradient, and electrical gradient.
19. In normal man of 70 kg, water content is 42 l.
20. ECF compartment includes:
- Plasma, Interstitial fluid and Transcellular fluid
21. ECF of body water account for 20% of body weight. ICF of body water account for 40% of body weight.
22. Transcellular fluid are digestive secretions, sweat, CSF, synovial, intraocular and pericardial fluids.
23. D2O (Deuterium oxide) is used to measure volume of total body water.
24. Sodium is largely in ECF. K+ is largely in ICF.
25. Nissl bodies are composed of RNA with protein.

FAST TRACK BASIC SCIENCE MBBS -231-


Physiology

26. Myelinated nerve fibres conduct impulse by saltatory conduction.


27. Postganglionic parasympathetic neuron is an unmyelinated neuron.
28. The jumping of depolarization from one node of Ranvier to other node is called saltatory
conduction.
29. Greater the diameter of a given nerve fiber, greater is speed of conduction and magnitude of spike.
30. Aδ and C fibres carry pain sensation.
31. Appearance of multiple peaks in action potential is called compound action potential.
32. BMR depends on surface area.
33. Energy expenditure in resting state depends on lean body mass.
34. Examples of negative feedback mechanisms are
a. BP
b. GH formation/pituitary hormones formation and release
c. Regulation of CO2 conc. in blood
35. Examples of +ve feedback mechanisms are
a. Blood clotting/Thrombus formation
b. Child birth
c. Generation of nerve signals (depolarization in AP)
d. LH surge
e. Entry of Ca++ in sarcoplasmic retinaculum.
36. Function of phospholipid in cell membrane is transduction of signals.
37. Membrane fluidity in cell membrane is increased by polyunsaturated fatty acid (PUFA) e.g.
Linoleic acid.
38. Lipids and proteins interact with each other in cell membrane by H-bonds.
I 39. Membrane integrity of RBC is due to spectrin.
40. Among Na+, K+, Mg++, Ca++, Cl¯ most important contributor for resting membrane potential is K+.
41. For sodium potassium pump, the coupling ratio is 3 : 2.
42. Na+ - K+ pump is heterodimer and heterogeneous.
43. In cold weather there is dry feeling in the respiratory passages due to more loss of water from the lungs.
44. Women have more body fat than men.
45. ECF constitutes the body’s internal environment.
46. There is higher concentration of protein in plasma than in the interstitial fluid due to Donnan effect.
47. The indicator dilution technique is based on conservation of mass.
48. The true hematocrit value is only 96% of the measured hematocrit.
49. Hematocrit value doesn’t change in old age.
50. Plasma membrane is mainly composed of proteins.
51. Membrane fluidity is increased by linolenic acid.
52. Inner mitochondrial membrane has the highest protein content per gram tissue.
53. Glycophorin is present in RBC.
54. The coupling ratio for Na+-K+ pump is 3:2.
55. Type IV collagen is found in the basement membrane of the kidneys.
56. Clathrin helps in receptor mediated endocytosis.
57. Most accurate measurement of ECF can be done by inulin.
58. Osmoreceptors are located in the anterior hypothalamus.
59. Collagen has a triple helix.

-232- FAST TRACK BASIC SCIENCE MBBS

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