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General Physiology - Complete Answers

LAQ 1: Action Potential - Origin, Phases, Ionic Phases & Difference from Graded Potential

Definition & Origin

An action potential is a rapid, transient change in membrane potential that spreads along the nerve fiber membrane. It originates when a stimulus depolarizes the membrane to a threshold level (approximately -55 mV), triggering a self-propagating electrical signal.

Resting membrane potential: -70 mV
Threshold for firing: ~-55 mV (i.e., ~15 mV above resting)

Phases of Action Potential

Phase	Membrane Potential	Ionic Event
Resting (Polarized)	-70 mV	Membrane at rest; Na+ channels closed
Depolarization	-70 mV → +30 mV	Threshold reached; voltage-gated Na+ channels open → Na+ rushes IN
Overshoot	+30 to +40 mV	Na+ influx continues; potential becomes positive
Repolarization	+30 mV → -70 mV	Na+ channels inactivate; voltage-gated K+ channels open → K+ rushes OUT
Hyperpolarization (Undershoot)	Below -70 mV	K+ channels remain open slightly longer than needed; membrane overshoots
Return to Resting	Back to -70 mV	K+ channels close; Na+/K+ ATPase pump restores gradient

Ionic Phases in Detail

1. Voltage-Gated Sodium Channel (Two gates):

Activation gate (outside): Closed at rest; opens rapidly when threshold is reached
Inactivation gate (inside): Open at rest; closes a few 10,000ths of a second AFTER activation gate opens
This brief window of dual-gate opening allows Na+ influx (permeability increases 500-5000 fold)
Once the inactivation gate closes, Na+ entry stops → repolarization begins

2. Voltage-Gated Potassium Channel:

Opens with a delay after the Na+ channels activate
K+ flows OUT, restoring the negative membrane potential
Closes slowly, causing brief hyperpolarization

Refractory Periods:

Absolute refractory period: Na+ inactivation gates are closed; no new AP possible regardless of stimulus strength
Relative refractory period: Hyperpolarization phase; a stronger-than-normal stimulus can fire an AP (Guyton and Hall Textbook of Medical Physiology)

Action Potential vs. Graded Potential

Feature	Action Potential	Graded Potential
Amplitude	Fixed (all-or-none)	Proportional to stimulus strength
Propagation	Travels without decrement along entire axon	Decays exponentially with distance
Threshold	Requires stimulus above threshold	Occurs at all stimulus strengths
Nature	Binary (fires or doesn't)	Continuous, graded
Example	Nerve impulse	Synaptic potential, receptor potential
Ionic basis	Voltage-gated Na+/K+ channels	Ligand-gated / mechanically gated channels

A graded response is proportional to stimulus intensity and decays with distance along the axon, while the action potential is all-or-none and propagates without losing amplitude. (Medical Physiology)

LAQ 2: Transport Mechanisms Across a Cell

1. Diffusion

Simple diffusion is the passive movement of molecules from high to low concentration across the lipid bilayer without any carrier protein.

Factors affecting rate of diffusion (Fick's Law):

Concentration gradient - greater gradient = faster diffusion
Temperature - higher temperature = faster movement
Surface area - larger area = more diffusion
Thickness of membrane - thinner membrane = faster diffusion
Molecular size - smaller molecules diffuse faster
Lipid solubility - non-polar molecules diffuse more easily

2. Facilitated Diffusion

Facilitated diffusion is passive transport driven by the transmembrane concentration gradient but requires specific carrier proteins (transporters/permeases). It does NOT require energy (ATP).

Key features (resembling enzyme-substrate interaction):

Specific binding site for the solute
Carrier is saturable - has a maximum transport rate (Vmax)
Has a binding constant (Km) - whole system has affinity kinetics
Structurally similar molecules act as competitive inhibitors
Transporters do NOT modify their substrates (unlike enzymes)

Types of transporters:

Uniport: moves one type of molecule bidirectionally
Symport: moves two solutes in the SAME direction (e.g., Na+-glucose cotransporter)
Antiport: moves two molecules in OPPOSITE directions (e.g., Na+ in / Ca2+ out)

Comparison - Transporters vs. Ion Channels:

Transporters	Ion Channels
Bind solute + undergo conformational change	Form pores in membrane
Both passive AND active transport	Only passive transport
Significantly slower transport	Significantly faster transport

3. Active Transport

Active transport moves molecules against an electrical or chemical gradient and therefore requires energy (ATP). It always moves molecules from low to high concentration.

Primary Active Transport:

Directly uses ATP hydrolysis
Example: Na+/K+ ATPase pump - pumps 3 Na+ out and 2 K+ in per ATP molecule

Secondary Active Transport (Cotransport):

Uses the gradient of one substrate (created by primary active transport) to drive another substrate against its gradient
Example: Na+-glucose cotransporter - uses the Na+ gradient (established by Na+/K+ ATPase) to pull glucose into the cell

Vesicular Active Transport:

Endocytosis: membrane engulfs material to bring it INTO the cell
- Phagocytosis (large particles)
- Pinocytosis (fluid/small molecules)
- Receptor-mediated endocytosis (specific ligands)
Exocytosis: vesicles fuse with membrane to release contents OUT of the cell
- Example: neurotransmitter release at synapses (Harper's Illustrated Biochemistry, 32nd Ed)

SAQ/VSAQ 1: Homeostasis and Feedback Mechanisms

Homeostasis is the ability of the body to maintain a stable internal environment despite changes in the external environment.

Negative Feedback (most common):

Response opposes the original stimulus
Brings the variable back to the set point
Example: Body temperature regulation - when temp rises, sweating brings it back down

Positive Feedback:

Response amplifies the original stimulus
Drives the variable further from the set point (until an endpoint is reached)
Example: Childbirth (oxytocin release), blood clotting, action potential depolarization phase

Feedforward Control:

An anticipatory response that occurs BEFORE the disturbance is detected
Based on prior experience or prediction
Example: Heart rate and ventilation increase at the START of exercise (before O2 actually drops), chemoreceptor feedback supplements the initial feedforward command to minimize disruptions in homeostasis (Fishman's Pulmonary Diseases and Disorders; Principles of Neural Science)

SAQ/VSAQ 2: Apoptosis

Apoptosis (from Greek: "falling off, as petals from flowers") is a physiologic, caspase-dependent programmed cell death that eliminates unwanted cells without damaging neighboring cells.

Key Features:

Cell is an active participant in its own death ("cellular suicide")
Maintains cell membrane integrity - "dies with dignity"

Pathways:

Intrinsic (Mitochondrial) Pathway: activated by internal signals; releases cytochrome c and SMAC/DIABLO → activates caspase cascade
Extrinsic Pathway: death receptors on cell surface (e.g., FasL/Fas); cytotoxic T lymphocytes using perforins and granzymes

Morphological Features:

Cell shrinkage (loss of cytoplasmic volume)
Membrane blebbing (plasma membrane outpouchings)
DNA fragmentation (by Ca2+/Mg2+-dependent endonucleases into oligonucleosomal fragments)
Chromatin aggregation and nuclear fragmentation
Formation of apoptotic bodies
Phagocytosis of apoptotic bodies (no inflammation)

Apoptosis vs. Necrosis:

Feature	Necrosis	Apoptosis
Cell swelling	+	-
Cell shrinkage	-	+
Plasma membrane damage	+	-
Membrane blebbing	-	+
Chromatin aggregation	-	+
DNA fragmentation	Random	Oligonucleosomal (ladder pattern)
Caspase activation	-	+
Inflammation	+	-

(Histology: A Text and Atlas, Pawlina)

SAQ/VSAQ 3: Intercellular Communications / Cell Junctions

Types of Cell Junctions:

1. Tight Junctions (Zonula Occludens):

Seal adjacent cells completely; no paracellular passage
Formed by proteins: claudins, occludins, ZO-1
Function: barrier (e.g., blood-brain barrier, intestinal epithelium)

2. Adherens Junctions (Zonula Adherens):

Belt-like junction below tight junctions
Mediated by cadherins (calcium-dependent)
Connected to actin cytoskeleton intracellularly
Function: mechanical adhesion between cells

3. Desmosomes (Macula Adherens):

Spot-like junctions; very strong mechanical anchoring
Mediated by desmogleins and desmocollins (cadherins)
Connected to intermediate filaments (keratin)
Common in skin, cardiac muscle

4. Gap Junctions (Nexus):

Direct cytoplasmic communication between cells
Formed by connexins (6 connexins form one connexon; two connexons from adjacent cells form a gap junction channel)
Allow passage of small molecules (<1000 Da): ions, cAMP, metabolites
Function: electrical coupling (cardiac muscle, smooth muscle), metabolic cooperation

5. Hemidesmosomes:

Anchor epithelial cells to the basement membrane
Use integrins connecting to extracellular laminin

Intercellular Communication Methods:

Direct (via gap junctions): ions and small molecules pass directly
Paracrine signaling: local chemical mediators affect nearby cells
Autocrine signaling: cell signals to itself
Endocrine signaling: hormones travel through blood to distant targets
Synaptic signaling: neurotransmitters released into synaptic cleft

These answers cover all the topics in your question bank: the LAQs on action potential and transport mechanisms, and the SAQ/VSAQs on homeostasis/feedback, apoptosis, and intercellular communications/cell junctions. Let me know if you want any section expanded further with diagrams or more detail!

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