Body Fluid Compartments

Body fluids are distributed across distinct, dynamically equilibrated compartments separated by selectively permeable membranes. Understanding their volumes, the indicators that measure them, and the Starling forces that move fluid between them is the foundation for everything in fluid therapy, electrolyte disorders, and oedema — and is among the most repeatedly tested General Physiology topics in NEET PG.

Total body water and its distribution

Total body water (TBW) is the single biggest "number" in physiology. It varies with age, sex, and adiposity because fat is essentially anhydrous.

• TBW ≈ 60% of body weight in an average adult male (the classic "60-40-20 rule").
• Of body weight: 40% is intracellular fluid (ICF) and 20% is extracellular fluid (ECF).
• ECF is further split into interstitial fluid (~15% of body weight, ¾ of ECF) and plasma (~5% of body weight, ¼ of ECF).

High-yield: The "60-40-20" rule: TBW = 60% BW, ICF = 40% BW, ECF = 20% BW. Within ECF, interstitial:plasma = 3:1.

Because adipose tissue holds little water, TBW falls with increasing body fat. Hence:

Group	TBW (% of body weight)
Newborn / infant	70–75% (highest)
Adult male	60%
Adult female	50% (more body fat)
Elderly	45–50% (sarcopenia, ↓ lean mass)
Obese individual	as low as 45%

High-yield: Infants have the highest TBW (~75%), making them most vulnerable to dehydration. Females and the elderly have lower TBW than young males.

A useful way to picture the compartments as fractions of TBW (not body weight): ICF = 2/3 of TBW, ECF = 1/3 of TBW. Do not confuse the "fraction of TBW" figures with the "fraction of body weight" figures — examiners love this trap.

Transcellular fluid

A small, specialised subset of ECF (~1–2% BW) sequestered behind epithelial layers: cerebrospinal fluid, aqueous and vitreous humour, synovial, pleural, peritoneal, pericardial fluid, and GI secretions. It is secreted by cells and is not freely exchangeable; pathological expansion forms a "third space" (e.g., ascites, bowel obstruction, burns, peritonitis), where fluid is functionally lost from the circulation.

Composition of the compartments

The defining feature of each compartment is its ionic composition, maintained chiefly by the Na⁺/K⁺-ATPase.

Ion	ECF (plasma)	ICF
Na⁺	~140 mEq/L (main extracellular cation)	~10–14 mEq/L
K⁺	~4 mEq/L	~140–150 mEq/L (main intracellular cation)
Cl⁻	~100–105 mEq/L (main extracellular anion)	~4 mEq/L
HCO₃⁻	~24 mEq/L	~10 mEq/L
Ca²⁺ (free)	~2.4 mEq/L	very low (~10⁻⁷ M free)
Phosphate / proteins	low	high (main intracellular anions)

High-yield: Na⁺ is the chief ECF cation; K⁺ is the chief ICF cation. Phosphates and proteins are the dominant intracellular anions. This asymmetry is sustained by the Na⁺/K⁺-ATPase (3 Na⁺ out / 2 K⁺ in).

Plasma vs interstitial fluid differ mainly in protein content: plasma is protein-rich (~7 g/dL), the interstitium is nearly protein-free. This protein gap creates a small ionic redistribution called the Gibbs–Donnan effect: the impermeant negatively charged plasma proteins retain extra cations (slightly higher Na⁺ in plasma) and exclude some anions, and they generate the colloid osmotic (oncotic) pressure that holds fluid in the vasculature.

High-yield: Osmolarity of all compartments is equal (~285–295 mOsm/kg) at steady state, because water moves freely until osmotic equilibrium is reached. Effective osmoles (Na⁺ for ECF, K⁺ for ICF) determine compartment volume.

Measuring compartment volumes — the indicator dilution method

This is the single most examined sub-topic. The principle:

Volume = Amount of indicator injected (corrected for losses) ÷ Concentration at equilibrium.

Stepwise approach:

1. Inject a known quantity of a marker that distributes ONLY in the compartment of interest.
2. Allow time to equilibrate.
3. Subtract any amount excreted/metabolised during equilibration.
4. Measure the plasma concentration.
5. Volume = (Amount injected − amount lost) / plasma concentration.

The choice of indicator is the whole game — each marker is confined to one compartment.

Volume measured	Indicator(s)	Notes
Total body water	³H₂O (tritiated water), D₂O (deuterium oxide), antipyrine, aminopyrine	Diffuses everywhere
ECF volume	Inulin, sucrose, mannitol, ²²Na, ³⁶Cl, thiosulphate, thiocyanate	Stay outside cells
Plasma volume	Evans blue (T-1824), ¹²⁵I/¹³¹I-labelled albumin (RISA)	Bind to/stay with plasma proteins
Blood volume	⁵¹Cr-labelled / ³²P-labelled RBCs; or plasma volume ÷ (1 − Hct)	Tag red cells

High-yield: Evans blue (T-1824) and radioiodinated serum albumin (RISA) measure plasma volume. Inulin / mannitol / sucrose / radioactive sodium measure ECF. Deuterium / tritiated water / antipyrine measure TBW.

Volumes that are calculated, not directly measured

Some compartments have no specific indicator and must be derived by subtraction:

• ICF = TBW − ECF
• Interstitial fluid = ECF − Plasma volume
• Blood volume = Plasma volume / (1 − Haematocrit), where Hct is expressed as a fraction.

High-yield: ICF and interstitial volume cannot be measured directly — there is no indicator confined to the inside of cells or to the interstitium alone. They are obtained by subtraction. This is a classic single-best-answer stem.

Blood volume ≈ 8% of body weight (~5 L in a 70 kg adult), of which plasma is ~3 L and red cell mass ~2 L.

A worked example: if you inject 1 g of an ECF marker and the equilibrated plasma concentration is 0.07 g/L (after correcting losses), ECF volume = 1 / 0.07 ≈ 14 L — close to the expected ~14 L in a 70 kg man.

Starling forces — fluid exchange across the capillary

Movement of fluid across the capillary wall is governed by the balance of hydrostatic and oncotic pressures — the Starling equation:

Jv = Kf × [(Pc − Pi) − σ(πc − πi)]

Where:

• Pc = capillary hydrostatic pressure (pushes fluid OUT)
• Pi = interstitial hydrostatic pressure (usually slightly negative; pulls/pushes)
• πc = capillary (plasma) oncotic pressure (pulls fluid IN) — mainly from albumin
• πi = interstitial oncotic pressure (pulls fluid OUT)
• Kf = filtration coefficient (permeability × surface area)
• σ = reflection coefficient (1 = wall fully impermeable to protein; 0 = freely permeable)

The net filtration pressure drives the direction of flow.

Direction of net movement → outward (filtration) at the arteriolar end → inward (reabsorption) at the venular end, because Pc falls along the capillary while πc stays roughly constant.

Approximate classic Landis–Pappenheimer figures:

Force	Arteriolar end	Venular end
Pc (capillary hydrostatic)	~30–35 mmHg	~10–15 mmHg
πc (plasma oncotic)	~25–28 mmHg	~25–28 mmHg
Net force	Outward (filtration)	Inward (reabsorption)

High-yield: Plasma oncotic pressure (~25–28 mmHg) is generated mainly by albumin (smaller, more numerous than globulins). Capillary hydrostatic pressure is the chief filtration force; plasma oncotic pressure is the chief reabsorption force.

The small excess of filtered fluid (~2–4 L/day net) that is not reabsorbed is returned to the circulation by the lymphatics. The revised Starling principle (modern teaching) emphasises that the endothelial glycocalyx layer is the true semipermeable barrier, and that in most tissues there is little or no venular-end reabsorption at steady state — filtered fluid is cleared almost entirely by lymph. The subglycocalyx oncotic pressure, not the bulk interstitial value, opposes filtration.

High-yield: Net capillary filtration that is not reabsorbed is drained by the lymphatic system. Lymphatic obstruction → protein-rich oedema (lymphoedema). This is the no-pitting, brawny oedema of filariasis and post-mastectomy.

Oedema — the most-tested clinical integration

Oedema = excess fluid in the interstitial space. It results from disruption of one or more Starling forces, or from lymphatic failure. Four core mechanisms:

Mechanism	Pathophysiology	Classic examples
↑ Capillary hydrostatic pressure	venous congestion / Na⁺–water retention	CHF, cirrhosis, renal failure, DVT, pregnancy, drugs (CCBs)
↓ Plasma oncotic pressure (hypoalbuminaemia)	albumin loss or ↓ synthesis	Nephrotic syndrome, cirrhosis, protein-losing enteropathy, kwashiorkor
↑ Capillary permeability (↑ Kf, ↓ σ)	endothelial injury, inflammation	Burns, sepsis, ARDS, allergic/angioneurotic oedema, inflammation
Lymphatic obstruction	impaired drainage	Filariasis, malignancy, post-radical mastectomy, congenital (Milroy)

High-yield: Pitting oedema = low-protein fluid (hypoalbuminaemia, cardiac, renal). Non-pitting oedema = high-protein/lymphatic fluid (lymphoedema, myxoedema of hypothyroidism). Myxoedema is non-pitting because of glycosaminoglycan deposition, not free fluid.

Mnemonic for oedema causes — "LHOP": Lymphatic obstruction, Hydrostatic ↑, Oncotic ↓, Permeability ↑.

High-yield: In nephrotic syndrome the mechanism is ↓ oncotic pressure (heavy albuminuria) → periorbital and dependent oedema. In cirrhosis, both ↓ albumin synthesis AND portal hypertension (↑ hydrostatic) combine, with secondary hyperaldosteronism → ascites.

Fluid shifts: how compartments respond to disturbances

The Darrow–Yannet diagram concept is high-yield. Adding or losing fluid of different tonicities shifts water between ICF and ECF according to osmolarity:

• Isotonic loss (haemorrhage, vomiting, diarrhoea): ECF volume ↓, osmolarity unchanged → no shift into/out of cells.
• Hypotonic gain / pure water gain (SIADH, excess D5W): ECF osmolarity ↓ → water moves into cells, both compartments expand, cells swell.
• Hypertonic gain (hypertonic saline, mannitol): ECF osmolarity ↑ → water drawn out of cells, ECF expands, ICF shrinks.
• Hypertonic loss / pure water loss (diabetes insipidus, fever, hyperventilation): ECF osmolarity ↑ → water leaves cells, ICF shrinks.

High-yield: Infusing isotonic (0.9%) saline expands only the ECF (it stays extracellular). 5% dextrose (D5W) is effectively free water once glucose is metabolised, so it distributes across TBW — only ~1/3 stays in ECF and only ~1/12 stays intravascular. This is why D5W is poor for resuscitation.

Practical resuscitation corollary: to raise plasma/intravascular volume you give colloids or isotonic crystalloids, not free water. Roughly, of 1 L isotonic crystalloid, only ~250 mL remains intravascular (the rest enters the interstitium), which is why crystalloid:colloid replacement ratios are ~3:1.

Regulation of body fluid volume and osmolarity

Two separate control systems, frequently confused in MCQs:

• Osmolarity is regulated by ADH (vasopressin) and thirst, both responding to plasma osmolality sensed by hypothalamic osmoreceptors. ADH controls water balance.
• ECF volume / effective circulating volume is regulated by the renin–angiotensin–aldosterone system (RAAS), ANP/BNP, and renal sympathetic activity. Aldosterone controls Na⁺ balance, and "where sodium goes, water follows."

High-yield: ADH defends osmolality (water); aldosterone/RAAS defends volume (sodium). The most powerful stimulus for thirst and ADH is a rise in plasma osmolality (osmoreceptors); volume depletion (baroreceptors) is a less sensitive but more powerful override.

Eponyms, criteria, and named concepts

• Starling's hypothesis / Starling forces — capillary fluid exchange (Ernest Starling).
• Gibbs–Donnan equilibrium — uneven ion distribution due to impermeant plasma proteins.
• Evans blue / T-1824 dye — plasma volume marker.
• Darrow–Yannet diagram — graphical depiction of ECF/ICF volume and osmolarity changes.
• Milroy disease — congenital lymphoedema.
• Glycocalyx model (revised Starling principle) — modern correction de-emphasising venular reabsorption.

Recently asked / exam angle

• "Which indicator measures plasma volume?" → Evans blue / RISA (radioiodinated serum albumin). Distractors: inulin (ECF), antipyrine/D₂O (TBW).
• "Which volume cannot be measured directly?" → ICF (and interstitial fluid) — derived by subtraction.
• Calculation stems: given plasma volume and haematocrit, compute blood volume = PV / (1 − Hct). Or given indicator amount and concentration, compute the compartment volume.
• "Main intracellular cation / anion?" → K⁺ / phosphate (and proteins).
• Oncotic pressure is generated mainly by albumin — recurrent one-liner.
• Integrated clinical: a nephrotic / cirrhotic / CHF / burns vignette asking the dominant Starling mechanism of oedema.
• Tonicity of IV fluids: which fluid expands ECF only (0.9% saline) vs distributes to TBW (D5W). Resuscitation favours isotonic crystalloid/colloid.
• Pitting vs non-pitting — myxoedema and lymphoedema are non-pitting.
• TBW highest in newborns; lower in females and elderly.
• Third-space loss examples (ascites, bowel obstruction, burns) and its effect on effective circulating volume.

Rapid revision

1. 60-40-20 rule: TBW = 60% BW, ICF = 40%, ECF = 20%; ICF = 2/3 of TBW, ECF = 1/3.
2. Within ECF, interstitial : plasma = 3 : 1 (15% vs 5% BW).
3. TBW highest in infants (~75%), lower in females and elderly (more fat / less lean mass).
4. Na⁺ = chief ECF cation; K⁺ = chief ICF cation; proteins/phosphate = chief ICF anions.
5. TBW → tritiated/deuterium water, antipyrine; ECF → inulin, mannitol, sucrose, radio-Na; plasma → Evans blue, RISA.
6. ICF and interstitial fluid are calculated by subtraction, never measured directly.
7. Blood volume = plasma volume / (1 − Hct); blood volume ≈ 8% BW (~5 L).
8. Starling: Jv = Kf [(Pc − Pi) − σ(πc − πi)]; Pc filters out, πc (albumin) reabsorbs in.
9. Plasma oncotic pressure ~25–28 mmHg, mostly albumin; excess filtrate returned by lymphatics.
10. Oedema (LHOP): Lymphatic block, ↑ Hydrostatic, ↓ Oncotic, ↑ Permeability.
11. Pitting = low-protein (cardiac/renal/nephrotic); non-pitting = lymphoedema and myxoedema.
12. D5W distributes across all TBW (free water); 0.9% saline stays in ECF — key to fluid therapy choices.