Page 3 of 10

PY1.1-7 | General Physiology — Part 2

Body Fluid Compartments — Where Water Lives (PY1.2)

Your body is approximately 60% water by weight (about 42 litres in a 70 kg adult). This water is distributed across compartments separated by cell membranes and capillary walls.

Two main compartments:

• Intracellular fluid (ICF) — water inside cells. This accounts for about two-thirds (~28 L) of total body water. The dominant cation here is potassium (K⁺) (~150 mEq/L), with phosphate and protein as the major anions.

• Extracellular fluid (ECF) — water outside cells. This accounts for about one-third (~14 L). The dominant cation here is sodium (Na⁺) (~140 mEq/L), with chloride and bicarbonate as the major anions. ECF is further divided into:
• Plasma (~3.5 L) — the fluid portion of blood, within the vascular system
• Interstitial fluid (~10.5 L) — fluid bathing the cells, between the capillaries and the cell membranes
• Transcellular fluid (~1 L) — CSF, synovial fluid, aqueous humour, pleural/peritoneal fluid

A simple way to remember: "2/3 in, 1/3 out" — two-thirds of body water is intracellular, one-third is extracellular. "K in, Na out" — potassium is the major intracellular cation, sodium is the major extracellular cation.

Why does this matter clinically? When you give a patient 1 litre of normal saline (0.9% NaCl — an isotonic solution), it stays in the ECF (because Na⁺ stays extracellular). Only about 250 mL enters the vascular space; the rest distributes into the interstitial fluid. But if you give 1 litre of 5% dextrose (which quickly becomes free water after the glucose is metabolised), it distributes evenly across ALL body water — only about 80 mL stays in the vascular space. This is why you use normal saline, not dextrose, to resuscitate a patient with low blood pressure.

In Anatomy right now, you're learning anatomical terminology — the language for describing where body parts are. Body fluid compartments are the physiological equivalent: they tell you where WATER is, and understanding this distribution is essential for IV fluid therapy.

Transport Across Cell Membranes — Passive Transport (PY1.3)

Molecules cross cell membranes by two fundamental mechanisms: passive transport (no energy required, moves DOWN the concentration gradient) and active transport (energy required, moves AGAINST the gradient). We'll cover passive first.

Figure: Transport Across Cell Membranes — Passive Transport (PY1.3)

1. Simple diffusion — molecules move from high concentration to low concentration through the lipid bilayer.
• Works for: small, nonpolar molecules (O₂, CO₂, N₂, steroid hormones)
• No protein required — they dissolve directly through the lipid core
• Governed by Fick's Law: Rate of diffusion = (Concentration difference × Membrane area × Permeability) / Membrane thickness
• Clinical example: Gas exchange in the lungs — O₂ diffuses from alveoli (high pO₂) into blood (low pO₂), and CO₂ diffuses the other way.

2. Osmosis — the movement of water through a selectively permeable membrane from a region of low solute concentration to high solute concentration.
• Water moves to dilute the more concentrated side
• The force driving water movement is called osmotic pressure
• Osmolarity — the total concentration of all solutes in a solution (measured in mOsm/L). Normal plasma osmolarity is ~290 mOsm/L.
• Tonicity — describes the effect of a solution on cell volume:
- Isotonic (same osmolarity as the cell): no net water movement. Example: 0.9% NaCl (normal saline)
- Hypotonic (lower osmolarity): water enters the cell → cell swells → may lyse. Example: pure water
- Hypertonic (higher osmolarity): water leaves the cell → cell shrinks (crenation in RBCs). Example: 3% NaCl

Think of osmosis as water chasing solute: Water always moves toward the side with MORE dissolved particles.

3. Facilitated diffusion — molecules move down their concentration gradient, but they cannot cross the lipid bilayer alone. They need a transport protein (channel or carrier).
• Channel-mediated: Ion channels (Na⁺, K⁺, Cl⁻ channels) — fast, specific, can be gated (opened/closed by voltage, ligands, or mechanical stretch)
• Carrier-mediated: GLUT transporters move glucose into cells. The carrier binds glucose on one side, changes shape, and releases it on the other side. This shows saturation kinetics — at high glucose concentrations, all carriers are occupied (Vmax).
• No ATP required — the concentration gradient provides the driving force
• Clinical example: GLUT-4 transporters in muscle and fat cells are insulin-dependent. In Type 2 diabetes, insulin resistance means fewer GLUT-4 transporters reach the membrane → glucose can't enter cells → blood glucose rises.

Active Transport — Moving Against the Gradient (PY1.3)

Sometimes the body needs to move molecules AGAINST their concentration gradient — from low concentration to high concentration. This requires energy, usually from ATP hydrolysis.

Figure: Active Transport — Moving Against the Gradient (PY1.3)

Primary active transport — directly uses ATP.

The most important example is the sodium-potassium pump (Na⁺/K⁺-ATPase):
• Found in virtually every cell membrane
• For each cycle: pumps 3 Na⁺ OUT of the cell and 2 K⁺ IN
• This maintains the concentration gradients: high Na⁺ outside, high K⁺ inside
• It's electrogenic — pumping 3 positive charges out and only 2 in creates a net negative charge inside the cell (contributes to the resting membrane potential)
• This single pump consumes about 30% of the body's total ATP at rest — that's how important it is
• Analogy: The Na⁺/K⁺ pump is like a bouncer at a club — it keeps throwing sodium out and pulling potassium in, maintaining the crowd composition (concentration gradient) that the cell needs to function.

Other primary active pumps:
• Ca²⁺-ATPase — pumps calcium out of the cell or into the sarcoplasmic reticulum (critical for muscle relaxation)
• H⁺/K⁺-ATPase — in the stomach's parietal cells, pumps H⁺ into the stomach lumen (creating gastric acid, pH ~2). Clinical note: Proton pump inhibitors (PPIs) like omeprazole block this pump to treat acid reflux and ulcers.

Secondary active transport — uses the energy stored in an ionic gradient (created by primary active transport) to move another substance.
• Cotransport (symport) — both substances move in the SAME direction. Example: SGLT1 (sodium-glucose linked transporter) in the intestine — Na⁺ moves down its gradient (into the cell) and drags glucose WITH it (against glucose's gradient). This is the basis of oral rehydration therapy (ORS): adding glucose to the salt solution enhances sodium and water absorption.
• Countertransport (antiport) — substances move in OPPOSITE directions. Example: Na⁺/H⁺ exchanger — Na⁺ enters the cell, H⁺ is expelled (important for pH regulation).

Clinical pearl: Oral Rehydration Solution (ORS) exploits SGLT1 cotransport. The WHO-ORS formula contains glucose + sodium + potassium + citrate. The glucose is not there for calories — it's there to DRIVE sodium absorption via SGLT1, and water follows sodium by osmosis. This simple physiological principle saves millions of lives from diarrhoeal dehydration every year.