Now I have comprehensive content from Guyton & Hall and Costanzo to compose a thorough answer.
Body Fluid Compartments and Their Regulation
1. Overview: Total Body Water
Total body water (TBW) accounts for 60% of body weight in an average 70-kg adult male (~42 L). This percentage varies with:
| Factor | Effect |
|---|
| High muscle mass | ↑ TBW (muscle is ~75% water) |
| High body fat | ↓ TBW (fat is ~10% water) |
| Female sex | ~50% (more adipose tissue) |
| Neonates/premature | 70–75% of body weight |
| Advancing age | Gradually decreases |
2. The Major Compartments
TBW is divided into two main compartments, separated by the cell membrane:
Figure: Summary of body fluid compartments in a 70-kg man (Guyton & Hall)
A. Intracellular Fluid (ICF)
- Volume: ~28 L (⅔ of TBW; 40% of body weight)
- Contains the fluid of all body cells collectively
- Remarkably similar composition across different cell types and species
- Major cation: K⁺ (~150 mEq/L)
- Major anions: PO₄³⁻ and organic anions, protein
B. Extracellular Fluid (ECF)
- Volume: ~14 L (⅓ of TBW; 20% of body weight)
- Divided into two main subcompartments separated by the capillary wall:
i. Plasma
- Volume: ~3 L (~¼ of ECF)
- Circulates within blood vessels
- Contains large plasma proteins (albumin, globulins) that do not cross capillary walls
- Major cation: Na⁺ (~142 mEq/L)
- Major anions: Cl⁻, HCO₃⁻
ii. Interstitial Fluid
- Volume: ~11 L (~¾ of ECF)
- Directly bathes the cells; an ultrafiltrate of plasma
- Virtually protein-free (capillary wall is impermeable to proteins)
- Ionic composition otherwise almost identical to plasma
iii. Transcellular Fluid (a specialized ECF)
- Volume: ~1–2 L
- Includes: CSF, synovial fluid, peritoneal fluid, pericardial fluid, intraocular fluid, pleural fluid
- May differ markedly in composition from plasma/interstitial fluid in some locations
C. Blood Volume
- ~5 L (~7% of body weight)
- Composed of plasma (~60%) + red blood cells (~40%)
- Normal hematocrit: ~0.42 in men, ~0.38 in women
- Considered a distinct functional compartment due to its circulatory role
3. Composition of Compartments
Figure: Major cations and anions in ICF vs ECF (Guyton & Hall)
| Ion | ECF (mEq/L) | ICF (mEq/L) |
|---|
| Na⁺ | 142 | 10–14 |
| K⁺ | 4–5 | 140–150 |
| Ca²⁺ | 5 (total) | <1 (ionized) |
| Mg²⁺ | 3 | 26 |
| Cl⁻ | 108 | 3–4 |
| HCO₃⁻ | 28 | 10 |
| PO₄³⁻ | 4 | ~75 |
| Protein | 16 | ~54 |
The electroneutrality principle holds in all compartments: the total cation charge equals the total anion charge.
4. Regulation of Fluid Compartments
A. Osmolarity — The Governing Principle
Normal ECF osmolarity is 290–300 mOsm/L. Because water moves freely across cell membranes, ICF osmolarity always equals ECF osmolarity in steady state.
Plasma osmolarity can be estimated by:
Posm = 2 × [Na⁺] + Glucose/18 + BUN/2.8
(Na⁺ in mEq/L, glucose and BUN in mg/dL)
Na⁺ (with its accompanying Cl⁻ and HCO₃⁻) determines ECF volume; osmolarity determines water distribution between ICF and ECF.
B. Regulation of ECF Volume (Na⁺ Balance)
ECF volume is primarily regulated by Na⁺ balance via the kidneys:
1. Renin–Angiotensin–Aldosterone System (RAAS)
- ↓ BP / ↓ ECF volume → renin released from juxtaglomerular cells
- Renin cleaves angiotensinogen → Angiotensin I → (ACE) → Angiotensin II
- Angiotensin II effects:
- Stimulates aldosterone secretion from adrenal cortex
- Aldosterone → ↑ Na⁺ (and water) reabsorption in collecting duct
- Direct vasoconstriction → ↑ BP
- Stimulates thirst and ADH release
2. Atrial Natriuretic Peptide (ANP)
- Released from atria when ECF volume/BP rises
- Causes natriuresis (Na⁺ excretion) and vasodilation → ↓ ECF volume
3. Sympathetic Nervous System
- ↓ volume → baroreceptor activation of sympathetics → ↑ renal Na⁺ retention
C. Regulation of Osmolarity (Water Balance)
1. ADH (Antidiuretic Hormone / Vasopressin)
- Synthesized in hypothalamus; released from posterior pituitary
- Stimuli: ↑ plasma osmolarity (detected by hypothalamic osmoreceptors), ↓ blood volume/pressure
- Action: Inserts aquaporin-2 channels in collecting duct → ↑ water reabsorption → dilute urine
- Net effect: ↓ plasma osmolarity, ↑ ECF volume
2. Thirst Mechanism
- Osmoreceptors in hypothalamus detect ↑ osmolarity → stimulate thirst
- Drinking water → ↓ osmolarity → restores fluid balance
- This is the primary long-term defense against hyperosmolarity
D. Water Shifts Between Compartments
The volume of each compartment depends on its solute content:
| Disturbance | ECF Osmolarity | Water Shift | Example |
|---|
| Pure water loss | ↑ (hyperosmotic) | ECF → ICF (cell shrinks) | Diabetes insipidus |
| Water gain (SIADH) | ↓ (hyposmotic) | ICF → ECF → cells swell | SIADH |
| Isotonic NaCl infusion | Normal | No shift | IV saline administration |
| NaCl gain (excess) | ↑ | Water drawn from ICF | Hypernatremia |
| Diarrhea/dehydration | ↑ | ICF water lost to ECF | Severe gastroenteritis |
Key principles:
- ECF volume is set by total NaCl content
- ICF volume is set by osmolarity (water follows osmoles)
- In steady state, ICF osmolarity = ECF osmolarity
- NaCl and mannitol stay in ECF; urea equilibrates across membranes (ineffective osmole)
E. Starling Forces (Plasma ↔ Interstitial Fluid Exchange)
Movement between plasma and interstitial fluid across the capillary wall is governed by Starling forces:
Net filtration = Kf [(Pc − Pi) − σ(πc − πi)]
| Force | Effect |
|---|
| Capillary hydrostatic pressure (Pc) | Pushes fluid OUT of capillary |
| Interstitial hydrostatic pressure (Pi) | Pushes fluid INTO capillary |
| Plasma oncotic pressure (πc) | Draws fluid INTO capillary |
| Interstitial oncotic pressure (πi) | Draws fluid OUT of capillary |
- Normally, a small net filtration at the arterial end is returned via lymphatics
- Loss of plasma proteins → ↓ πc → edema (e.g., nephrotic syndrome, liver failure)
5. Measuring Fluid Compartment Volumes
| Compartment | Indicator Used |
|---|
| TBW | ³H₂O, ²H₂O (deuterium), antipyrine |
| ECF | ²²Na, inulin, thiosulfate, ¹²⁵I-iothalamate |
| ICF | Calculated: TBW − ECF |
| Plasma | ¹²⁵I-albumin, Evans blue dye |
| Interstitial | Calculated: ECF − Plasma volume |
The dilution principle underlies all measurements: Volume = (Amount injected) / (Final concentration).
Summary
| Compartment | Volume (70-kg man) | % TBW | Key Solutes | Barrier |
|---|
| ICF | 28 L | 67% | K⁺, PO₄³⁻, protein | Cell membrane |
| ECF — Interstitial | 11 L | 26% | Na⁺, Cl⁻, HCO₃⁻ | Capillary wall |
| ECF — Plasma | 3 L | 7% | Na⁺, Cl⁻, protein | Capillary wall |
| Transcellular | 1–2 L | ~2% | Variable | Epithelial cells |
Fluid homeostasis is maintained by the kidneys (primary effector), RAAS, ADH/thirst axis, ANP, and the sympathetic nervous system working in an integrated feedback loop to keep both volume and osmolarity within narrow physiological limits.
Sources: Guyton and Hall Textbook of Medical Physiology; Costanzo Physiology 7th Edition