General Physiology - Exam Answers

Q1. Structure and Function of the Cell Membrane (5 marks)

Structure

• Two layers of phospholipid molecules, each with a hydrophilic (water-loving) head and two hydrophobic (water-repelling) fatty acid tails
• The tails face inward (away from water), heads face outward
• This arrangement forms a fluid, selectively permeable barrier
• Lipid-soluble substances (O2, CO2, steroids, alcohol) can diffuse directly through it

• Integral (transmembrane) proteins - span the full width of the membrane; act as:
  • Channel proteins - have watery pores that allow ions/water to pass through (e.g., Na+, K+, Ca2+ channels)
  • Carrier proteins - bind specific molecules, undergo conformational change to transport them (e.g., glucose transporters)
  • Pump proteins - ATPase enzymes (e.g., Na+/K+ ATPase)
  • Receptor proteins - bind hormones/ligands to trigger intracellular signaling
• Peripheral proteins - attached to inner or outer surface; act as enzymes or structural anchors

• Attached to outer surface as glycoproteins and glycolipids
• Form the glycocalyx - involved in cell recognition, immunity, and cell-cell adhesion

• Embedded in the lipid bilayer
• Regulates fluidity - prevents membrane from becoming too rigid (cold) or too fluid (heat)

Functions

1. Selective barrier - controls what enters/exits the cell
2. Transport - moves nutrients, ions, waste products
3. Cell recognition - glycocalyx identifies "self" vs "non-self"
4. Signal reception - receptor proteins receive hormonal and chemical signals
5. Structural support - maintains cell shape
6. Electrical excitability - generates and propagates action potentials via ion channels

Q2. Transport Mechanisms Across the Cell Membrane (5 marks)

A. PASSIVE TRANSPORT (No energy required - moves down concentration gradient)

• Random molecular movement from high to low concentration
• Lipid-soluble molecules (O2, CO2, fatty acids, steroids) diffuse directly through the lipid bilayer
• Very small uncharged molecules (water, urea) also pass through
• Rate depends on: concentration gradient, membrane permeability, surface area, temperature

• Ions (Na+, K+, Ca2+, Cl-) are water-soluble and cannot cross the lipid bilayer directly
• They pass through specific channel proteins that form water-filled pores
• Channels are selective (ion-specific) and may be:
  • Voltage-gated (open on depolarization - nerve/muscle)
  • Ligand-gated (open on binding of neurotransmitter)
  • Mechanically-gated (open on physical deformation)

• Water-soluble molecules (glucose, amino acids) move down their concentration gradient via carrier proteins
• Carrier binds substrate, undergoes conformational change, releases substrate on the other side
• No energy (ATP) required, but is saturable and specific
• Example: GLUT transporters for glucose in red blood cells

• Net movement of water through a semipermeable membrane from low solute to high solute concentration (from high water to low water)
• Driven by the osmotic pressure gradient

B. ACTIVE TRANSPORT (Requires energy - moves against concentration gradient)

• Energy comes directly from ATP hydrolysis
• Example: Na+/K+ ATPase pump (see below)
• Other examples: Ca2+ pump (SERCA), H+/K+ ATPase (stomach)

• Uses the electrochemical gradient created by primary active transport (especially Na+ gradient) as the energy source
• Co-transport (symport) - Na+ and glucose/amino acid move in the same direction (e.g., Na+-glucose transporter in intestinal epithelium)
• Counter-transport (antiport) - Na+ moves inward while another ion/molecule moves outward (e.g., Na+-Ca2+ exchanger in heart muscle)

C. VESICULAR TRANSPORT

• Phagocytosis (large particles, bacteria)
• Pinocytosis (fluid droplets)
• Receptor-mediated endocytosis (LDL cholesterol)

Q3. Cell Membrane (Short note, 3 marks)

• Phospholipids - amphipathic; hydrophilic heads face ECF/ICF, hydrophobic tails form the core barrier
• Proteins - integral (channel, carrier, receptor, pumps) and peripheral
• Cholesterol - stabilizes fluidity
• Glycocalyx - sugar coat on outer surface for recognition

Q4. Na+/K+ Pump (Na+/K+ ATPase)

Structure

• α subunit (mol. wt ~100,000) - the functional unit with:
  • 3 binding sites for Na+ (on the intracellular side)
  • 2 binding sites for K+ (on the extracellular side)
  • ATPase activity (near the Na+ binding sites)
• β subunit (mol. wt ~55,000) - anchors the complex in the membrane

Mechanism

1. 3 Na+ ions bind to the intracellular face of the α subunit
2. 2 K+ ions bind to the extracellular face
3. ATP is cleaved to ADP + Pi, releasing energy
4. This energy causes a conformational change in the protein
5. 3 Na+ are pumped OUT and 2 K+ are pumped IN per cycle
6. Net result: 1 positive charge moves out per cycle → electrogenic (contributes to negative resting membrane potential)

Importance

• Maintains high intracellular K+ and low intracellular Na+ (essential for cell excitability)
• Generates the resting membrane potential (-70 mV in neurons)
• Controls cell volume (prevents osmotic swelling)
• Creates the Na+ gradient that powers secondary active transport
• Is the basis for nerve impulse conduction

Q5. Passive Diffusion

Types

• Limited to lipid-soluble molecules (O2, CO2, N2, alcohol, steroid hormones) and very small uncharged molecules
• Rate governed by Fick's Law of Diffusion: Rate ∝ (Concentration gradient × Surface area × Permeability coefficient) / Membrane thickness

• Selective permeability (each channel type is specific to one ion)
• Governed by both concentration gradient AND electrical gradient (electrochemical gradient)

• Examples: glucose (GLUT transporters), amino acids, nucleosides

Characteristics

• No ATP required
• Movement is down the concentration/electrochemical gradient
• Reaches equilibrium (net diffusion stops when gradient is zero)
• Rate is proportional to the concentration difference
• Temperature-dependent (higher temp = faster diffusion)

Q6. Positive (+ve) Feedback Mechanism

Characteristics

• Self-augmenting (not self-limiting like negative feedback)
• Rare in normal physiology but important in specific situations
• Leads to an explosive or irreversible event

Physiological Examples

• Membrane depolarization → voltage-gated Na+ channels open → Na+ rushes in → more depolarization → more Na+ channels open → explosive upstroke of action potential
• This is the classic positive feedback loop producing the rapid, all-or-none spike

• Rising estrogen (follicular phase) → stimulates anterior pituitary to release LH and FSH → LH/FSH cause more estrogen secretion and follicle maturation → rapid burst (surge) of LH → ovulation
• The explosive event = LH surge triggering ovulation

• Cervical dilation → posterior pituitary releases oxytocin → uterine contractions → more cervical dilation → more oxytocin → stronger contractions
• The explosive event = delivery of the fetus

• Activation of clotting factors amplifies itself through the cascade, leading to rapid clot formation

• Severe bleeding → reduced cardiac output → reduced coronary blood flow → weaker heart → even less output → death (a "vicious cycle")

Key Point

Sources: Guyton and Hall Textbook of Medical Physiology (14th Ed.), Costanzo Physiology (7th Ed.)

General Physiology - Exam Answers with Diagrams

Q1. Structure and Function of the Cell Membrane (5 marks)

Structure - Fluid Mosaic Model (Singer-Nicolson, 1972)

1. Selectively permeable barrier between ECF and ICF
2. Transport of ions, nutrients, waste
3. Cell recognition and communication
4. Reception of hormonal signals
5. Generation and propagation of action potentials
6. Regulation of cell volume

Q2. Transport Mechanisms Across Cell Membrane (5 marks)

A. Passive Transport (No ATP, moves DOWN concentration gradient)

• Lipid-soluble molecules (O2, CO2, steroids, alcohol) pass directly through lipid bilayer
• Governed by Fick's Law: Rate ∝ Concentration gradient × Area / Thickness

• Ions (Na+, K+, Ca2+, Cl-) pass through protein-lined pores
• Channels are selective and may be voltage-gated, ligand-gated, or mechanically-gated

• Glucose, amino acids move via carrier proteins, still down gradient
• Saturable, specific, no ATP needed (e.g., GLUT transporters)

• Net movement of water through semipermeable membrane from low to high solute (high to low water concentration)

B. Active Transport (Requires ATP, moves AGAINST gradient)

• Uses ATP directly (e.g., Na+/K+ ATPase, Ca2+ pump, H+/K+ pump)

• Uses Na+ gradient created by Na+/K+ pump
• Symport (co-transport): Na+ + glucose/amino acids move same direction (intestinal absorption)
• Antiport (counter-transport): Na+ in, Ca2+ out (Na+/Ca2+ exchanger)

C. Vesicular Transport

• Endocytosis: phagocytosis, pinocytosis, receptor-mediated (LDL)
• Exocytosis: hormone/neurotransmitter secretion

Q3. Cell Membrane (Short note, 3 marks)

• Phospholipid bilayer: amphipathic molecules - hydrophilic heads face ECF and ICF; hydrophobic tails form the impermeable core
• Proteins: integral (channels, carriers, pumps, receptors) and peripheral (enzymes, structural)
• Cholesterol: embedded in bilayer, stabilizes membrane fluidity
• Glycocalyx: outer sugar coat for cell-cell recognition and immunity

Q4. Na+/K+ Pump

Structure

• α subunit (100,000 Da): 3 intracellular Na+ binding sites + 2 extracellular K+ binding sites + ATPase activity
• β subunit (55,000 Da): anchors the complex in the membrane

Mechanism (Step-by-step)

1. 3 Na+ bind to intracellular sites of α subunit
2. 2 K+ bind to extracellular sites
3. ATP is cleaved → ADP + Pi (energy released)
4. Conformational change in carrier protein
5. 3 Na+ extruded OUTSIDE; 2 K+ brought INSIDE
6. Net: 1 positive charge leaves → electrogenic pump

Importance

• Maintains Na+ low (10 mEq/L) and K+ high (140 mEq/L) inside cells
• Creates resting membrane potential (-70 mV)
• Prevents cell swelling (controls osmotic balance)
• Na+ gradient drives secondary active transport (glucose, amino acids)
• Basis for nerve impulse conduction

Q5. Passive Diffusion

Types

• O2, CO2, N2, fatty acids, steroids, alcohol
• Rate described by Fick's Law: J = DA(C1 - C2)/L
  • D = diffusion coefficient, A = area, C = concentration, L = thickness

• Na+, K+, Ca2+, Cl- move down electrochemical gradients
• Driven by both concentration AND electrical gradients

• Glucose (GLUT1-4), amino acids, nucleosides
• Saturable (maximum transport rate = Tmax)

• Water moves from hypotonic to hypertonic solution
• Osmotic pressure opposes further osmosis

Key Features of Passive Diffusion

Q6. Positive (+ve) Feedback Mechanism

Comparison

Examples with Diagrams

Depolarization
     ↓
Na⁺ channels open
     ↓
Na⁺ enters → more depolarization
     ↓
More Na⁺ channels open (POSITIVE FEEDBACK)
     ↓
Explosive action potential spike

• Rising estrogen → anterior pituitary releases LH/FSH → ovaries secrete more estrogen → more LH/FSH → explosive LH surge → ovulation

• Cervical dilation → oxytocin released → uterine contractions → more cervical dilation → more oxytocin → explosive delivery of fetus

• Factor activation triggers more factor activation → rapid clot formation

• Severe bleeding → low cardiac output → poor coronary perfusion → weaker heart → even lower output → death

Key Point

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Transport Mechanisms Across Cell Membrane

(Simple Language - Exam Ready)

First, understand the basic idea:

TRANSPORT ACROSS CELL MEMBRANE
         |
    _____|_____
    |         |
PASSIVE    ACTIVE
(No energy) (Needs energy/ATP)

GROUP 1 - PASSIVE TRANSPORT

"Lazy transport" - No ATP needed, substances move on their own from HIGH → LOW concentration

1. Simple Diffusion - "Walk through the wall"

• Substances move from more concentrated → less concentrated area
• They pass directly through the lipid bilayer (the fatty layer of membrane)
• Only fat-soluble (lipid-soluble) substances can do this

2. Osmosis - "Water's version of diffusion"

• Only water moves this way
• It moves through aquaporins (special water channels in the membrane)
• Movement is from hypotonic → hypertonic solution
• The pressure needed to STOP osmosis = osmotic pressure

Water is lazy - it moves toward where it's needed most (where solutes are concentrated)

3. Facilitated Diffusion - "Moving with a helper, still downhill"

• Uses carrier proteins (e.g., GLUT transporters for glucose)
• Still moves down the concentration gradient
• No ATP required
• But it is saturable - too much glucose = all carriers are busy = transport slows down

• Glucose entering RBCs (GLUT1)
• Glucose entering muscle and fat cells (GLUT4)
• Amino acid transport

4. Ion Channel Diffusion - "Ions rushing through open gates"

• These channels are selective (Na+ channel only lets Na+ through)
• They are controlled (gated):
  • Voltage-gated - open when membrane voltage changes (nerve impulse)
  • Ligand-gated - open when a chemical (neurotransmitter) binds
  • Mechanically-gated - open when physically stretched

• Na+ rushing into nerve cells during action potential
• K+ moving out during repolarization
• Ca2+ entering muscle cells to trigger contraction

GROUP 2 - ACTIVE TRANSPORT

"Hard work transport" - Needs ATP, moves substances from LOW → HIGH concentration (uphill, against the gradient)

5. Primary Active Transport - "Direct use of ATP"

STEP 1: 3 Na+ (inside cell) bind to the pump protein
         ↓
STEP 2: 2 K+ (outside cell) bind to the pump protein
         ↓
STEP 3: ATP is broken down → ADP + energy released
         ↓
STEP 4: Pump changes shape
         ↓
STEP 5: 3 Na+ thrown OUTSIDE, 2 K+ pulled INSIDE
         ↓
STEP 6: Pump resets → cycle repeats

• Na+ = HIGH outside (142 mEq/L) | LOW inside (10 mEq/L)
• K+ = LOW outside (4 mEq/L) | HIGH inside (140 mEq/L)
• Creates resting membrane potential (-70 mV)
• Pumps out more + charges than it brings in → electrogenic

• Ca2+ pump (keeps calcium low inside cells)
• H+/K+ ATPase (stomach acid secretion)

6. Secondary Active Transport - "Stealing energy from Na+ gradient"

• Na+ and glucose BOTH move INTO the cell together
• Na+ goes down its gradient (pulling glucose along)
• Glucose goes AGAINST its gradient (piggybacks on Na+)

OUTSIDE → [Na+ + Glucose] → carrier protein → INSIDE
          Na+ going downhill drags glucose uphill

• Na+ moves IN while another substance moves OUT
• Na+ going downhill pushes the other substance uphill

OUTSIDE ← [Ca2+] ← carrier protein ← [Na+] ← INSIDE
         Na+ going inward pushes Ca2+ outward

7. Vesicular Transport - "Bulk transport by packaging"

• Phagocytosis ("cell eating") - engulfs large particles like bacteria, dead cells
• Pinocytosis ("cell drinking") - engulfs droplets of fluid
• Receptor-mediated endocytosis - specific molecules (LDL cholesterol, insulin) bind receptors, then get engulfed

• Vesicles fuse with cell membrane and release contents
• Examples: Insulin secretion from pancreas, neurotransmitter release from nerve terminals, mucus secretion

Full Summary Diagram

Quick Revision Table

Memory Trick for Exam

"SOFT PAV E"

• Simple diffusion
• Osmosis
• Facilitated diffusion
• Tunnel (ion channels)
• Primary active transport
• Antiport/Symport (secondary active)
• Vesicular (endo/exocytosis)
• Exocytosis

Quick Revision - Transport Across Cell Membrane

Cell Membrane - Super Simple Explanation 🧠

Think of it like a SANDWICH 🥪

🍞 Top bread    = Hydrophilic heads (love water, face ECF)
🧈 Butter layer = Hydrophobic tails (hate water, face each other)
🍞 Bottom bread = Hydrophilic heads (love water, face ICF)

4 Main Components - "PPCC"

Proteins - 2 Types Only

INTEGRAL protein  = Goes ALL THE WAY through the membrane
                    (like a pipe through a wall)
                    → Acts as channels, pumps, receptors

PERIPHERAL protein = Sits on the SURFACE only
                    (like a sticker on a wall)
                    → Acts as enzymes, structural support

5 Functions - "STERC"

One Line to Remember Everything:

"A fatty sandwich with protein doors, cholesterol springs, and a sugar coat outside"

Na⁺/K⁺ Pump - Simple + Exam Ready

First, WHY does this pump exist?

The cell needs Na+ LOW inside and K+ HIGH inside. But both want to leak back to where they came from. So the cell has a pump that constantly fixes this - 24/7, non-stop.

The Simple Story 🔄

• Throws out 3 Na+ every time
• Lets in 2 K+ every time
• Charges 1 ATP as fee each cycle

INSIDE CELL                    OUTSIDE CELL
                    PUMP
   3 Na+  ────────────────→   3 Na+ (OUT)
   2 K+   ←────────────────   2 K+  (IN)
   ATP    ────→  ADP + Pi
         (energy used)

Structure (2 parts only)

1. 3 binding sites for Na+ (inside face)
2. 2 binding sites for K+ (outside face)
3. ATPase activity (breaks ATP for energy)

How it Works - Step by Step

Step 1️⃣  →  3 Na+ (inside) bind to pump
Step 2️⃣  →  2 K+ (outside) bind to pump
Step 3️⃣  →  ATP breaks → ADP + Pi + ENERGY
Step 4️⃣  →  Pump changes shape (conformational change)
Step 5️⃣  →  3 Na+ pushed OUT of cell
Step 6️⃣  →  2 K+ pulled IN to cell
Step 7️⃣  →  Pump resets → repeat forever

Result of this pump

Diagram

Why is it ELECTROGENIC?

3 positive charges go OUT, only 2 come IN Net = 1 extra positive charge leaves every cycle This makes the inside of cell more negative = -70mV resting membrane potential

Importance - "NERVE CAPS"

✍️ HOW TO WRITE IN EXAM

The Na+/K+ ATPase pump is a primary active transport mechanism present in virtually all body cells. It maintains the electrochemical gradient essential for cellular excitability.

The pump is a carrier protein complex consisting of two subunits:

• α subunit (mol. wt. ~100,000): contains 3 Na+ binding sites (intracellular), 2 K+ binding sites (extracellular), and ATPase activity
• β subunit (mol. wt. ~55,000): anchors the complex in the lipid bilayer

1. Three Na+ ions bind to intracellular sites of α subunit
2. Two K+ ions bind to extracellular sites
3. ATP is hydrolyzed → ADP + Pi, releasing energy
4. Conformational change occurs in the carrier protein
5. Three Na+ are extruded outside; two K+ are transported inside
6. Pump resets and cycle repeats

• Maintains Na+ low inside (10 mEq/L) and K+ high inside (140 mEq/L)
• Generates resting membrane potential (-70 mV) - electrogenic pump
• Controls cell volume by regulating osmotic balance
• Creates Na+ gradient used for secondary active transport
• Essential for nerve impulse and muscle contraction

The Na+/K+ pump is thus one of the most vital active transport mechanisms, consuming nearly 20-30% of total cellular ATP, reflecting its physiological importance.

3-Mark version (short note):

5-Mark version:

Passive Diffusion - Simple + Exam Ready

First, WHY is it called "PASSIVE"?

Because the substance does the work on its own. No energy (ATP) needed. It just flows downhill - from where there is MORE → to where there is LESS.

The Simple Story 🌬️

Imagine you spray perfume in one corner of a room. The smell automatically spreads to the whole room. Nobody pushed it. It moved on its own. That's passive diffusion.

3 Types - "SIF"

PASSIVE DIFFUSION
       |
  _____|_____________________
  |          |              |
Simple    Ion Channel   Facilitated
Diffusion  Diffusion    Diffusion
(through   (through     (through
lipid)     pores)       carrier)

Type 1 - Simple Diffusion

• Substance crosses directly through the lipid bilayer
• Only fat-soluble (lipid-soluble) substances can do this
• No protein needed

Type 2 - Ion Channel Diffusion

• Ions are charged → cannot cross fatty membrane
• They use protein channels (tunnels) = selective pores
• Still passive - ions rush through down their electrochemical gradient

Type 3 - Facilitated Diffusion

• Substance is water-soluble → can't cross lipid layer alone
• Uses a carrier protein as helper
• Still moves HIGH → LOW concentration
• No ATP needed
• BUT it is saturable (too much substance = carriers get full = slows down)

Osmosis - Bonus type (water's diffusion)

• Water moves from LOW solute → HIGH solute side
• Through aquaporins (water channels)
• No ATP needed

Fick's Law (Rate of Diffusion) - Just remember the concept

Rate of diffusion depends on:

Rate ∝  Concentration difference × Surface area
        ─────────────────────────────────────────
                  Membrane thickness

Quick Comparison Table

✍️ HOW TO WRITE IN EXAM

Passive diffusion is the movement of molecules across the cell membrane from a region of higher concentration to lower concentration, down the concentration gradient, without the expenditure of metabolic energy (ATP).

Lipid-soluble substances (O2, CO2, steroids, alcohol) diffuse directly through the phospholipid bilayer. The rate is governed by Fick's Law of Diffusion: Rate ∝ (Concentration gradient × Surface area) / Membrane thickness

Water-soluble ions (Na+, K+, Ca2+, Cl-) pass through specific protein-lined pores called ion channels. Channels are selective and may be voltage-gated, ligand-gated, or mechanically-gated.

Water-soluble molecules like glucose and amino acids move down their concentration gradient via specific carrier proteins (e.g., GLUT transporters). This process is saturable and specific but requires no ATP.

Water moves across a semipermeable membrane from a region of low solute concentration (high water concentration) to high solute concentration (low water concentration), through aquaporins.

• No energy (ATP) required
• Movement is always down the concentration gradient
• Net diffusion stops when equilibrium is reached
• Rate is proportional to the concentration difference
• Rate increases with temperature

Passive diffusion is the simplest and most energy-efficient method of membrane transport, playing a vital role in gas exchange, nutrient absorption, and maintenance of ionic gradients across cell membranes.

3-Mark version:

5-Mark version:

One Line Memory Trick:

"Passive = No Payment (no ATP) - flows freely downhill" "SIF = Simple, Ion channel, Facilitated"

• 👉 Re-explain Passive Diffusion in an even simpler way?
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• 👉 Something else from your physiology notes?