General Physiology

Definition

Key Topics in General Physiology

1. The Cell - The Basic Living Unit

• The human body contains approximately 35 to 40 trillion cells
• Every cell, regardless of type, shares core characteristics: energy metabolism, chemical reactions, and the ability to reproduce
• The body also harbors trillions of microorganisms (microbiota) living in symbiosis - in the gut alone, 400 to 1000 microbial species are present
• Guyton and Hall, p. 20

2. Homeostasis - The Central Principle

• Coined by American physiologist Walter Cannon in 1929
• Homeostasis is the maintenance of a stable internal environment - it is a dynamic, not static, process that constantly adjusts body functions
• Operates at every level: molecular, genetic, cellular, organ, and whole-body
• Key examples:
  • Blood hydrogen ion concentration varies less than 5 nanomoles/L (extremely tight regulation)
  • Blood sodium is also tightly regulated despite variable dietary intake
• Disease is often a state of disrupted homeostasis - but even in disease, compensatory mechanisms continue to operate
• Guyton and Hall, p. 22

3. The Extracellular Environment ("Internal Environment")

• Claude Bernard (19th century) first described the concept of the "milieu intérieur" (internal environment)
• The extracellular fluid (ECF) surrounds all cells and provides them with nutrients, oxygen, and removes waste products
• The ECF has two main compartments: plasma (in blood vessels) and interstitial fluid (between cells)
• Regulation of the ECF composition is the central task of most organ systems

4. Cell Membrane Structure

• The cell membrane is a lipid bilayer 7.5 to 10 nanometers thick
• Composition: ~55% proteins, 25% phospholipids, 13% cholesterol, 4% other lipids, 3% carbohydrates
• Phospholipids are amphipathic: hydrophilic phosphate heads face the watery environment; hydrophobic fatty acid tails face inward
• Cholesterol regulates membrane fluidity and permeability
• Sphingolipids (especially in nerve cells) help with protection, signal transmission, and adhesion
• Guyton and Hall, p. 31

5. Membrane Proteins

• Integral proteins: span the full thickness of the membrane; form ion channels, carrier proteins, and receptors
• Peripheral proteins: attached to surface; often function as enzymes or structural anchors
• Membrane proteins enable selective transport of specific ions (Na+, K+, Ca2+, Cl-) and molecules
• Guyton and Hall, p. 31

6. Transport Across Cell Membranes

• Diffusion (passive): movement down a concentration gradient - no energy needed
  • Fat-soluble substances (O2, CO2, alcohol) pass freely through the lipid bilayer
  • Water-soluble substances (ions, glucose) require protein channels or carriers
• Active transport: requires ATP; moves substances against their concentration gradient (e.g., Na+/K+ ATPase pump)
• Osmosis: diffusion of water across a semipermeable membrane
• Endocytosis/Exocytosis: bulk movement of large molecules into or out of cells via membrane vesicles

7. Control Systems and Feedback Loops

• The body uses negative feedback to maintain homeostasis - a deviation from normal triggers a corrective response that brings it back
• Example: a rise in blood pressure triggers reflexes that lower it
• Positive feedback amplifies a change (e.g., childbirth contractions, blood clotting)
• Feedback systems involve: a sensor (detector), a control center (integrator), and an effector

8. Energy Metabolism at the Cellular Level

• All cells extract energy by oxidizing carbohydrates, fats, and proteins
• The fundamental energy currency is ATP (adenosine triphosphate)
• Cellular respiration occurs primarily in mitochondria
• The basic chemical mechanisms for energy transformation are essentially the same in all cell types

Scope and Subdivisions

Why General Physiology Matters

• It is the foundation for clinical medicine - understanding disease (pathophysiology) requires knowing normal function first
• It connects basic sciences (biochemistry, molecular biology, anatomy) to clinical practice
• It explains why drugs, procedures, and treatments work the way they do

Biophysics in Human Physiology

1. Membrane Biophysics

Cell Membrane Structure

• A lipid bilayer (7.5-10 nm thick): 55% proteins, 25% phospholipids, 13% cholesterol
• Hydrophobic core blocks water-soluble ions; fat-soluble gases (O₂, CO₂) cross freely

Diffusion

• Simple diffusion: movement down a concentration gradient, no energy needed
• Facilitated diffusion: via protein channels (e.g., aquaporins for water, ion channels for Na⁺/K⁺)
• Rate depends on: concentration gradient, membrane surface area, temperature, molecular size

Osmosis

• Net movement of water across a semipermeable membrane from low solute → high solute side
• Osmotic pressure: the pressure needed to stop osmosis
• Drives cell swelling or shrinking depending on tonicity of surrounding fluid

2. Bioelectricity - Membrane Potentials

Resting Membrane Potential (-70 to -80 mV)

• Inside of the cell is negative relative to outside
• Maintained by:
  • High K⁺ permeability at rest (K⁺ leaks out)
  • Low Na⁺ permeability at rest
  • Na⁺/K⁺ ATPase pump: pumps 3 Na⁺ out and 2 K⁺ in (electrogenic)
• Ion concentrations at rest (nerve fiber):

• Described mathematically by the Nernst equation and Goldman equation

Action Potential (the nerve impulse)

• A rapid depolarization and repolarization of the membrane
• Phases:
  1. Resting (-70 mV): Na⁺ channels closed
  2. Depolarization: stimulus opens voltage-gated Na⁺ channels → Na⁺ rushes in → membrane goes to +35 mV
  3. Repolarization: Na⁺ channels inactivate; K⁺ channels open → K⁺ flows out
  4. Hyperpolarization: brief overshoot below resting potential
  5. Restoration: Na⁺/K⁺ pump restores ion gradients
• All-or-nothing law: once threshold (~-55 mV) is reached, a full action potential fires

3. Active Transport (Biophysics of Pumps)

• Primary active transport: uses ATP directly (e.g., Na⁺/K⁺ ATPase, Ca²⁺ pump)
• Secondary active transport: uses the Na⁺ gradient created by the pump to co-transport other substances (e.g., glucose-Na⁺ cotransport in the gut)

4. Fluid & Pressure Physics (Hemodynamics)

• Blood flow follows Poiseuille's Law: flow ∝ pressure difference × radius⁴ / vessel length
• Capillary exchange governed by Starling forces: hydrostatic pressure vs. osmotic (oncotic) pressure
• Laplace's Law: wall tension = pressure × radius (explains why large aneurysms rupture more easily)

5. Mechanics of Breathing

• Boyle's Law: pressure × volume = constant; lung expansion lowers pressure → air flows in
• Surface tension in alveoli reduced by surfactant (prevents alveolar collapse)
• Compliance: the ease of lung stretching (ΔVolume / ΔPressure)

6. Optics & Sound in Physiology

• Eye: acts as a biophysical lens system; light refraction by cornea + lens focuses image on retina
• Ear: sound waves (mechanical pressure waves) converted to electrical nerve signals via hair cells in the cochlea

Summary Table

How Action Potentials Propagate Along Axons

1. The Core Mechanism - Local Current Flow

• Positive charges (Na⁺ ions) flow inward through the depolarized membrane
• These positive charges then travel along the inside of the axon in both directions
• On the outside, current flows back toward the depolarized zone
• This local current raises the voltage in adjacent resting membrane segments to threshold (-55 mV)
• Voltage-gated Na⁺ channels in those adjacent segments open → new action potential fires
• The cycle repeats, moving the wave of depolarization along the entire fiber

• A: Resting fiber (positive outside, negative inside)
• B: Depolarization at midpoint - local currents spread in both directions
• C & D: Adjacent segments reach threshold and fire; the wave expands outward

2. Why It Only Goes Forward (Unidirectional)

3. Unmyelinated vs. Myelinated Fibers

Unmyelinated Fibers (Continuous Conduction)

• Local current spreads continuously along the entire membrane surface
• Every patch of membrane depolarizes in sequence
• Slow - conduction velocity ~0.5 to 2 m/s
• More energy costly (whole membrane must be re-polarized)

Myelinated Fibers - Saltatory Conduction

• Action potentials can only fire at nodes of Ranvier
• Electrical current jumps through the axoplasm and extracellular fluid from node to node
• The impulse "jumps" along the fiber - this is saltatory conduction (from Latin saltare = to jump)

1. Speed: 5- to 50-fold faster than unmyelinated fibers (up to 120 m/s in large myelinated fibers)
2. Energy efficiency: Only nodes depolarize → ~100x less ion movement → far less ATP needed to restore ion gradients via Na⁺/K⁺ pump

4. Conduction Velocity - What Determines It?

• Large myelinated (Aα fibers): 70-120 m/s (motor neurons, proprioception)
• Small myelinated (Aδ fibers): 5-30 m/s (fast pain, cold)
• Unmyelinated (C fibers): 0.5-2 m/s (slow/burning pain, warmth)

5. Clinical Relevance

• Demyelinating diseases (e.g., Multiple Sclerosis, Guillain-Barré): destroy myelin → saltatory conduction fails → slowed or blocked nerve signals → weakness, numbness, paralysis
• Local anesthetics (e.g., lidocaine): block voltage-gated Na⁺ channels → prevent propagation → no pain signal reaches the brain
• Nerve conduction velocity (NCV) studies: measure propagation speed to diagnose neuropathies