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Physiology Viva Notes — Topics 1–4

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TOPIC 1 — Basic Concepts and Principles of Normal Physiology

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Physiology as a Science

Guyton & Hall (Ch. 1): "The goal of physiology is to explain the physical and chemical factors that are responsible for the origin, development, and progression of life."

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Subject & Tasks of Normal Physiology

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Relationship with Other Disciplines

• Anatomy — structure and function go hand in hand
• Biochemistry — chemical basis of physiological processes
• Pathophysiology — physiology of disease (abnormal)
• Pharmacology — drugs modify physiological processes
• Clinical medicine — normal values define what is "abnormal"

Physiology is the bridge between basic sciences and clinical medicine.

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Biological Properties of a Living Organism

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Research Methods in Physiology

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Internal Environment & Homeostasis

• Internal environment = the extracellular fluid (ECF) that bathes all cells
  • Claude Bernard (1857): "The constancy of the internal environment is the condition of free life"
• Homeostasis = the process by which the body maintains a stable internal environment despite external changes
  • Walter Cannon (1929) coined the term
  • Achieved mainly through negative feedback mechanisms

Guyton & Hall (Ch. 1): The body contains ~60% water; ~40% is intracellular fluid (ICF), ~20% is ECF. Homeostasis keeps the ECF constant.

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Rigid and Plastic Constants

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TOPIC 2 — Physiology of Excitable Tissues

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Biological Membranes

• Phospholipid bilayer (hydrophilic heads outside, hydrophobic tails inside)
• Integral proteins (span the membrane — channels, pumps, receptors)
• Peripheral proteins (on surface — structural/signaling)
• Cholesterol (stabilizes fluidity)
• Glycoproteins/glycolipids (on outer surface — cell recognition)

1. Selective barrier — controls what enters/exits
2. Cell communication (receptors)
3. Electrical signaling (ion channels)
4. Enzyme activity
5. Cell-to-cell adhesion

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Transport Across Membranes

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

B. ACTIVE TRANSPORT (Energy required; moves against concentration gradient)

Guyton & Hall (Ch. 4): "The Na⁺/K⁺ pump is so important that it accounts for 20–40% of all the energy used by the body."

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Irritability, Excitability, and Stimuli

• Irritability = the ability of any living cell to respond to stimuli (universal property)
• Excitability = the ability of specialized cells (nerve, muscle) to generate an action potential in response to a stimulus

Types of Stimuli

Adequate stimulus = the specific stimulus a receptor is designed to respond to (e.g., light for the retina)

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Measures of Excitability

1. Threshold of Stimulation (Rheobase)

• Rheobase = minimum strength of stimulus (of infinite duration) needed to cause excitation
• Lower rheobase → higher excitability

2. Useful Time (Chronaxie)

• Chronaxie = time needed for a stimulus of 2× rheobase strength to excite the tissue
• Clinically important: shorter chronaxie = more excitable tissue
• Nerve: chronaxie ~0.1–0.3 ms; Muscle: ~1–10 ms

3. Lability (Functional Mobility)

• Lability = maximum number of action potentials a tissue can generate per second
• Unit: impulses/sec (Hz)
• Nerve: ~500–1000/sec; Skeletal muscle: ~200/sec; Cardiac muscle: ~200/sec
• Higher lability = more excitable

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Bioelectrical Potentials

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Resting Membrane Potential (RMP)

• Definition: The electrical potential difference across the membrane of an unstimulated cell
• Magnitude: –70 mV in neurons (negative inside relative to outside)
• Muscle: –90 mV; RBCs: –10 mV

Mechanism of Formation:

1. K⁺ diffuses out through leak channels (membrane more permeable to K⁺ at rest) → inside becomes negative
2. Na⁺ is relatively excluded (few open Na⁺ channels at rest)
3. Large negatively charged proteins trapped inside → contribute to negativity
4. Na⁺/K⁺-ATPase pump — electrogenic: pumps 3 Na⁺ out and 2 K⁺ in → net negative charge inside maintained
5. Nernst equation describes the equilibrium potential for each ion; Goldman equation gives actual RMP considering all ions

Guyton & Hall (Ch. 5): "The resting membrane potential of large nerve fibers is about –90 millivolts."

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Action Potential (AP)

• Definition: A rapid, self-propagating change in membrane potential when a threshold stimulus is applied
• Magnitude: In neurons, goes from –70 mV to +35 mV (total swing ~105 mV)

Mechanism:

1. Stimulus reaches threshold (~–55 mV)
2. Rapid depolarization: Voltage-gated Na⁺ channels open → massive Na⁺ rushes IN → inside becomes positive (+35 mV)
3. Repolarization: Na⁺ channels inactivate; Voltage-gated K⁺ channels open → K⁺ rushes OUT → inside becomes negative again
4. After-hyperpolarization (undershoot): K⁺ channels close slowly → briefly more negative than RMP (~–80 mV)
5. Recovery: Na⁺/K⁺ pump restores ionic balance

AP Curve Components:

        +35 mV
          /\
         /  \
        /    \
–55 mV /      \
______/        \_____ Undershoot
–70 mV              \____ Return to RMP

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Ion Pumps and Their Role

• Pumps 3 Na⁺ out and 2 K⁺ in per cycle (uses 1 ATP)
• Electrogenic (contributes ~−4 mV to RMP)
• Maintains concentration gradients essential for repeated APs
• Without the pump, repeated APs would equilibrate ion gradients and signals would fail

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All-or-None Law

"When a stimulus reaches threshold, the action potential is always maximal — it fires completely or not at all. The size of AP does NOT depend on the strength of the stimulus (as long as it is at or above threshold)."

• Applied to a single excitable cell (neuron or muscle fiber)
• Stimulus must reach threshold
• The cell must not be in the absolute refractory period
• Does NOT apply to whole nerves (composed of many fibers with different thresholds)

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Local Potentials

• Occur when subthreshold stimulus is applied
• Graded — proportional to stimulus strength (unlike AP)
• Decremental — decrease as they travel away from point of origin
• Non-propagating — cannot travel far
• Can summate (temporal and spatial) to reach threshold and trigger an AP
• Example: Generator potential in sensory receptors, EPSPs at synapses

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TOPIC 3 — Introduction to NS: Neurons and Synapses

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Neuron: Structure and Functions

Sembulingam (Ch. 13): Neurons are the longest-lived cells in the body and cannot regenerate once lost in most areas.

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Nerve Fibers: Structure and Elements

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Classification of Nerve Fibers

Anatomical Classification:

• Afferent (sensory) — carry impulses TO CNS
• Efferent (motor) — carry impulses FROM CNS to effectors

Histological Classification:

• Myelinated — have myelin sheath; faster conduction
• Unmyelinated — no myelin; slower conduction

Physiological Classification (Erlanger & Gasser):

Guyton & Hall (Ch. 48): Conduction velocity ≈ 6 × fiber diameter (in µm) for myelinated fibers.

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Mechanism of Conduction

Unmyelinated Fiber (Continuous conduction):

• Local currents spread between adjacent points
• Each segment depolarizes in sequence — slow and energy-costly

Myelinated Fiber (Saltatory conduction):

• AP "jumps" from one Node of Ranvier to the next
• Much faster and energy-efficient (ion exchange only at nodes)
• ~50× faster than unmyelinated

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Properties of Nerve Fibers

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Laws of Conduction Along Nerve

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Synapse: Concept, Structure, Classification

Structure (Chemical Synapse):

• Presynaptic terminal (bouton): Contains mitochondria and synaptic vesicles (neurotransmitters)
• Synaptic cleft: Gap of ~20–40 nm
• Postsynaptic membrane: Contains receptors for neurotransmitters

Classification:

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Mediators (Neurotransmitters)

• Synthesized in presynaptic neuron
• Stored in vesicles
• Released by exocytosis on Ca²⁺ influx
• Act on specific receptors
• Removed by reuptake, enzyme degradation, or diffusion

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Stages of Synaptic Transmission

1. AP arrives at presynaptic terminal
2. Voltage-gated Ca²⁺ channels open → Ca²⁺ enters
3. Vesicles fuse with presynaptic membrane → neurotransmitter released into cleft (exocytosis)
4. Neurotransmitter diffuses across cleft (~0.5 ms)
5. Binds to postsynaptic receptors → ion channels open/close
6. Postsynaptic potential (PSP) generated
7. Termination: reuptake, enzymatic degradation (e.g., AChE breaks ACh), or diffusion

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Postsynaptic Potentials (PSP)

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Basic Properties of Synapses

Guyton & Hall (Ch. 45): The synaptic delay is the main reason why total nerve pathway delay increases with each synapse in a reflex arc.

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TOPIC 4 — Physiology of Contractile Elements

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Classification of Muscles

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Functions of Muscles

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Macro-, Micro-, and Ultrastructure of Skeletal Muscle

Macrostructure:

• Surrounded by epimysium
• Divided into fascicles by perimysium
• Each muscle fiber surrounded by endomysium
• Each fiber = single multinucleated cell

Microstructure:

• Muscle fiber contains many myofibrils
• Sarcomere = basic contractile unit (Z-line to Z-line)
• Under microscope: A-band (dark, actin + myosin overlap), I-band (light, actin only), H-zone (myosin only), M-line (center of sarcomere), Z-line (anchors actin)

Ultrastructure (Sarcomere):

• Thick filaments: Myosin (with cross-bridges/heads)
• Thin filaments: Actin + Troponin + Tropomyosin
• Troponin (T, I, C subunits) — T binds tropomyosin; I inhibits; C binds Ca²⁺
• Sarcoplasmic reticulum (SR): Stores and releases Ca²⁺
• T-tubules: Transmit AP deep into fiber → trigger Ca²⁺ release from SR

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Properties of Skeletal Muscle

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Biomechanics of Muscle Contraction and Relaxation

Sliding Filament Theory (Huxley & Hanson, 1954):

• Actin and myosin filaments slide past each other — filaments themselves do NOT shorten
• Sarcomere shortens → fiber shortens → muscle contracts

Steps (Excitation-Contraction Coupling):

1. AP travels along sarcolemma → enters T-tubules
2. AP activates SR → releases Ca²⁺ into cytoplasm
3. Ca²⁺ binds Troponin C → conformational change in troponin-tropomyosin complex
4. Active sites on actin exposed
5. Myosin cross-bridges attach to actin → form actin-myosin complex
6. Power stroke: Myosin head bends → pulls actin → ATP hydrolysis drives this
7. Cross-bridge detaches when new ATP binds
8. Cycle repeats → actin filament drawn toward center

Relaxation:

1. AP stops → Ca²⁺ pumped back into SR by Ca²⁺-ATPase
2. Troponin-tropomyosin returns to blocking position
3. Actin-myosin cross-bridges detach → muscle relaxes

Guyton & Hall (Ch. 6): "Without ATP, the cross-bridges cannot detach from actin — this explains rigor mortis (all ATP depleted after death)."

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Types of Muscle Contractions

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Modes of Contraction

Single Twitch:

• Response to one suprathreshold stimulus
• Three phases: Latent period (0–10 ms) → Contraction → Relaxation

Tetanus:

• Response to repeated stimuli at high frequency

Tetanus force can be 3–4× greater than a single twitch (wave summation + calcium accumulation)

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Contracture vs. Fatigue

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Smooth Muscle: Features and Properties

Structural Features:

• Small spindle-shaped cells
• Single nucleus (unlike skeletal: multinucleated)
• No T-tubules (or poorly developed)
• Poorly developed SR — relies mainly on extracellular Ca²⁺
• Thin and thick filaments present but NOT arranged in regular sarcomeres (hence non-striated)
• Caveolae — shallow invaginations serve as Ca²⁺ store
• Connected by gap junctions (functional syncytium in visceral smooth muscle)

Ca²⁺ Mechanism in Smooth Muscle:

• Ca²⁺ binds calmodulin (not troponin) → activates myosin light chain kinase (MLCK) → phosphorylates myosin → contraction

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Comparative Table: Skeletal vs. Smooth Muscle

Sembulingam (Ch. 18): Smooth muscle can maintain prolonged contraction at very low energy cost — important for tonic functions like vascular tone.

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Quick Viva Summary Cards

RMP = –70 mV (neuron) | –90 mV (muscle) AP = –70 → +35 → –70 mV | Caused by Na⁺ in, K⁺ out Na⁺/K⁺ pump = 3 Na⁺ out, 2 K⁺ in, uses 1 ATP Chronaxie = time at 2× rheobase | Shorter = more excitable Synaptic delay = 0.3–0.5 ms | Ca²⁺-dependent Sliding filament: actin + myosin slide; Ca²⁺ + troponin unlocks Smooth muscle: Ca²⁺ + calmodulin → MLCK → contraction Tetanus = fused AP responses; rigor mortis = no ATP to release cross-bridges