ANZCA Primary
Physiology
Biochemistry
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Fluid and Electrolyte Physiology

Total body water (TBW) is approximately 60% body weight in males, 50% in females, 65-70% in infants, 50% in elderly. Distribution : 2/3 intracellular (ICF), 1/3 extracellular (ECF). ECF divided into interstitial fluid...

Updated 2 Feb 2026
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  • Severe hyponatremia (<120 mmol/L) with neurological symptoms
  • Severe hypernatremia (>160 mmol/L)
  • Severe hypokalemia (<2.5 mmol/L) with ECG changes
  • Severe hyperkalemia (>6.5 mmol/L) with peaked T waves

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Quick Answer

Total body water (TBW) is approximately 60% body weight in males, 50% in females, 65-70% in infants, 50% in elderly. Distribution: 2/3 intracellular (ICF), 1/3 extracellular (ECF). ECF divided into interstitial fluid (ISF, 3/4) and plasma (1/4). Osmolality: 285-295 mOsm/kg (regulated by ADH, thirst). Sodium: Primary extracellular cation (135-145 mmol/L), maintains ECF osmolality and volume. Potassium: Primary intracellular cation (3.5-5.0 mmol/L), critical for resting membrane potential. Calcium: 2.2-2.6 mmol/L total (50% free/ionized), essential for neuromuscular function, coagulation, cardiac contractility. Magnesium: 0.75-0.95 mmol/L, cofactor for ATPases. Chloride: 95-105 mmol/L, main extracellular anion. Fluid shifts: Follow osmotic gradients (water moves from low to high osmolality). Starling forces: Determine transcapillary fluid exchange (hydrostatic vs oncotic pressure). Anaesthetic implications: Preoperative fasting deficits, third space losses, blood loss replacement, glucose management, fluid overload prevention. [1-10]

Body Water Distribution

Total Body Water (TBW)

Percentage of Body Weight:

  • Adult males: 60% (60 kg in 70 kg male)
  • Adult females: 50-55% (35-38 L in 70 kg female)
    • Lower due to higher body fat percentage
  • Infants: 65-70% (higher water content)
  • Elderly: 50% (decreased muscle mass)
  • Obesity: Lower percentage (fat has low water content)

Compartments:

1. Intracellular Fluid (ICF):

  • Volume: 40% body weight (2/3 of TBW)
  • Location: Inside all cells
  • Composition:
    • High potassium (140 mmol/L)
    • Low sodium (10-15 mmol/L)
    • High magnesium (40 mmol/L)
    • High phosphate and protein anions
    • Osmolality: 285-295 mOsm/kg (same as ECF)

2. Extracellular Fluid (ECF):

  • Volume: 20% body weight (1/3 of TBW)
  • Subcompartments:
    • Interstitial fluid (ISF): 15% body weight (75% of ECF)
      • Between cells, outside vessels
    • Plasma: 5% body weight (25% of ECF)
      • Intravascular fluid
    • Transcellular fluid: Small volume (CSF, synovial, pleural, peritoneal)

Summary Table:

Compartment% Body Weight% TBWVolume (70 kg male)
ICF40%67%28 L
ECF20%33%14 L
- Interstitial15%25%10.5 L
- Plasma5%8%3.5 L
Total60%100%42 L

Gibbs-Donnan Effect:

  • Principle: Non-diffusible anions (proteins) in plasma create unequal distribution of diffusible ions
  • Effect: Slightly higher chloride and bicarbonate in ISF vs plasma
  • Result: Plasma has slightly higher osmotic pressure than ISF (oncotic pressure)

Electrolyte Physiology

Sodium (Na⁺)

Physiological Role:

  • Primary extracellular cation: 135-145 mmol/L (plasma)
  • Osmolality maintenance: Primary determinant of ECF osmolality (Posm ≈ 2[Na⁺] + glucose/18 + BUN/2.8)
  • ECF volume: Determines ECF volume (water follows osmotic gradients)
  • Resting membrane potential: Contributes (less than K⁺)
  • Acid-base balance: Na⁺ reabsorption linked to H⁺ secretion

Daily Requirements:

  • Intake: 1-2 mmol/kg/day (70-140 mmol for 70 kg adult)
  • Distribution: 98% extracellular
  • Regulation:
    • Aldosterone: Na⁺ retention (distal tubule)
    • ADH: Water retention (collecting duct)
    • ANP: Na⁺ excretion (atria)

Clinical Disorders:

Hyponatremia (<135 mmol/L):

  • Symptoms: Headache, nausea, confusion, seizures, coma (if <120 mmol/L or rapid decline)
  • Classification by volume status:
    • Hypovolemic: Loss of Na⁺ and water (diuretics, vomiting, Addison's)
    • Euvolemic: Water excess (SIADH, hypothyroidism, cortisol deficiency)
    • Hypervolemic: Edema states (heart failure, cirrhosis, nephrotic syndrome)
  • Treatment: Depends on cause and severity
    • Acute symptomatic: 3% NaCl (100 mL bolus)
    • Chronic: Slow correction (max 8-12 mmol/L/day to avoid osmotic demyelination)

Hypernatremia (>145 mmol/L):

  • Symptoms: Thirst, confusion, seizures, coma (if >160 mmol/L)
  • Mechanism: Water deficit or Na⁺ excess
  • Treatment: Free water replacement (oral or IV D5W)

Potassium (K⁺)

Physiological Role:

  • Primary intracellular cation: 140 mmol/L (ICF), 3.5-5.0 mmol/L (ECF)
  • Resting membrane potential: Primary determinant (Nernst equation)
    • Hyperkalemia: Depolarization (excitable tissues)
    • Hypokalemia: Hyperpolarization (weakness)
  • Cardiac conduction: Critical (ECG changes with K⁺ disturbances)
  • Acid-base: K⁺ shifts with H⁺ (acidosis → hyperkalemia, alkalosis → hypokalemia)

Daily Requirements:

  • Intake: 1 mmol/kg/day (70 mmol for 70 kg adult)
  • Regulation:
    • Insulin: Drives K⁺ into cells
    • Catecholamines (β-2): Drive K⁺ into cells
    • Aldosterone: K⁺ excretion (distal tubule)
    • Acid-base status: Affects distribution

Clinical Disorders:

Hypokalemia (<3.5 mmol/L):

  • Causes: Diuretics, vomiting, diarrhea, alkalosis, insulin, β-agonists
  • ECG: Flattened T waves, ST depression, U waves, prolonged QT
  • Effects: Muscle weakness, ileus, arrhythmias (especially with digoxin)
  • Treatment: Oral preferred, IV if severe (max 20 mmol/hour via central line)

Hyperkalemia (>5.0 mmol/L):

  • Causes: Renal failure, acidosis, cell lysis, K⁺ sparing diuretics, ACE inhibitors
  • ECG: Peaked T waves, widened QRS, sine wave, VF/asystole
  • Emergency treatment:
    1. Calcium (stabilize membrane)
    2. Insulin/glucose (shift K⁺ intracellular)
    3. Bicarbonate (if acidotic)
    4. β-agonists (salbutamol)
    5. Dialysis (if refractory)

Calcium (Ca²⁺)

Physiological Role:

  • Total calcium: 2.2-2.6 mmol/L (plasma)
    • Ionized (free): 50% (1.1-1.3 mmol/L) - physiologically active
    • Protein-bound: 40% (mostly albumin)
    • Complexed: 10% (with phosphate, citrate, bicarbonate)
  • Albumin correction: [Ca²⁺] decreases 0.02 mmol/L per 1 g/L decrease in albumin (below 40 g/L)

Functions:

  • Neuromuscular: Neurotransmitter release, muscle contraction
  • Cardiac: Contractility, conduction
  • Coagulation: Factor IV (required for multiple steps)
  • Bone: Structural (hydroxyapatite)
  • Intracellular signaling: Second messenger

Regulation:

  • Parathyroid hormone (PTH): Increases Ca²⁺ (bone resorption, renal reabsorption, intestinal absorption via vitamin D)
  • Vitamin D: Increases Ca²⁺ absorption
  • Calcitonin: Decreases Ca²⁺ (bone uptake)

Clinical Disorders:

Hypocalcemia (<2.2 mmol/L total, <1.1 mmol/L ionized):

  • Causes: Hypoparathyroidism, vitamin D deficiency, hypomagnesemia, citrate (massive transfusion), alkalosis (↓ionized)
  • Symptoms: Tetany, Chvostek's sign, Trousseau's sign, seizures, hypotension
  • ECG: Prolonged QT interval
  • Treatment: Calcium chloride or gluconate IV, magnesium if low

Hypercalcemia (>2.6 mmol/L):

  • Causes: Malignancy, hyperparathyroidism, sarcoidosis, immobilization
  • Symptoms: "Bones, stones, groans, moans, psychic overtones"
  • Treatment: Hydration, bisphosphonates, calcitonin, steroids

Magnesium (Mg²⁺)

Physiological Role:

  • Concentration: 0.75-0.95 mmol/L (plasma), 15 mmol/L (ICF)
  • Cofactor: ATPases (Na⁺/K⁺-ATPase, Ca²⁺-ATPase)
  • Enzyme activation: >300 enzymes
  • Neuromuscular: Required for PTH release, modulates NMDA receptors
  • Cardiac: Antiarrhythmic (class effect)

Clinical Disorders:

Hypomagnesemia (<0.75 mmol/L):

  • Causes: Diuretics, alcoholism, malabsorption, proton pump inhibitors
  • Effects: Refractory hypokalemia and hypocalcemia, tremor, seizures, arrhythmias (torsades de pointes)
  • Treatment: Magnesium sulfate IV (1-2 g over 15 min, then infusion)

Hypermagnesemia (>1.1 mmol/L):

  • Causes: Renal failure, magnesium administration (tocolysis, preeclampsia)
  • Effects: Neuromuscular blockade, hypotension, bradycardia, respiratory depression
  • Treatment: Calcium antagonist, dialysis if severe

Chloride (Cl⁻)

Physiological Role:

  • Concentration: 95-105 mmol/L (plasma), major extracellular anion
  • Acid-base balance:
    • Hypochloremic alkalosis: With vomiting (lose HCl), diuretics
    • Hyperchloremic acidosis: With saline administration (dilutional)
  • Strong ion difference: Part of Stewart approach to acid-base

Phosphate (PO₄³⁻)

Physiological Role:

  • Concentration: 0.8-1.4 mmol/L (plasma)
  • Functions: ATP, 2,3-DPG, bone mineralization, cellular signaling
  • Clinical: Hypophosphatemia with refeeding syndrome, hyperphosphatemia in renal failure

Fluid Physiology

Osmolality and Tonicity

Osmolality:

  • Definition: Number of osmotically active particles per kg solvent (mOsm/kg)
  • Normal plasma osmolality: 285-295 mOsm/kg
  • Calculation: 2[Na⁺] + [glucose]/18 + [urea]/2.8 (normal glucose and urea contribute ~10 mOsm/kg)
  • ICF and ECF osmolality: Equal (water moves freely across cell membranes)

Tonicity (Effective Osmolality):

  • Definition: Osmolality that causes water movement (excludes urea which crosses membranes freely)
  • Effective osmoles: Na⁺, glucose, mannitol (do not cross membranes easily)
  • Ineffective osmoles: Urea, ethanol (cross freely, equilibrate)
  • Clinical importance: Tonicity determines cell volume (brain cells swell in hypotonic states)

Regulation of Fluid Balance

Thirst Mechanism:

  • Stimulus: ↑plasma osmolality (>295 mOsm/kg), ↓ECF volume
  • Response: Water intake
  • ADH release: Simultaneous with thirst

Antidiuretic Hormone (ADH/Vasopressin):

  • Source: Posterior pituitary (synthesized in hypothalamus)
  • Stimuli:
    • Osmotic: ↑plasma osmolality (very sensitive, 1% change triggers)
    • Volume: ↓ECF volume >10% (less sensitive)
  • Action: Aquaporin-2 insertion in collecting duct → water reabsorption
  • Result: Concentrated urine, water retention

Aldosterone:

  • Source: Adrenal cortex (zona glomerulosa)
  • Stimuli: ↓Na⁺, ↓ECF volume, ↑K⁺, angiotensin II
  • Action: Na⁺ reabsorption, K⁺ excretion (distal tubule)
  • Result: Volume expansion

Natriuretic Peptides (ANP, BNP):

  • Source: Atria (ANP) and ventricles (BNP)
  • Stimuli: Atrial stretch (volume overload)
  • Action: Na⁺ and water excretion, vasodilation
  • Result: Volume reduction

Capillary Fluid Exchange

Starling Forces:

Forces moving fluid OUT of capillary (filtration):

  • Capillary hydrostatic pressure (Pc): 30-35 mmHg (arterial end), 10-15 mmHg (venous end)
  • Interstitial oncotic pressure (πi): 5 mmHg (minimal protein in ISF)

Forces moving fluid INTO capillary (reabsorption):

  • Interstitial hydrostatic pressure (Pi): -2 to -5 mmHg (negative due to lymphatic drainage)
  • Capillary oncotic pressure (πc): 25-28 mmHg (albumin)

Net filtration pressure (arterial end): = (Pc + πi) - (Pi + πc) = (30 + 5) - (-3 + 25) = 35 - 22 = +13 mmHg (filtration)

Net reabsorption pressure (venous end): = (15 + 5) - (-3 + 25) = 20 - 22 = -2 mmHg (reabsorption)

Clinical Implications:

  • Increased Pc (venous congestion): Edema (heart failure, fluid overload)
  • Decreased πc (hypoalbuminemia): Edema (liver disease, nephrotic syndrome)
  • Increased capillary permeability: Edema (sepsis, burns, inflammation)
  • Lymphatic obstruction: Edema (filariasis, malignancy)

Anaesthetic Implications

Preoperative Fluid Management

Fasting Deficit:

  • Standard calculation: Hourly maintenance × hours fasting
  • Maintenance (4-2-1 rule):
    • First 10 kg: 4 mL/kg/hour
    • Next 10 kg: 2 mL/kg/hour
    • Remaining weight: 1 mL/kg/hour
  • Example: 70 kg patient NPO 8 hours
    • Hourly: 40 + 20 + 50 = 110 mL/hour
    • Deficit: 110 × 8 = 880 mL
    • Replace 50% in first hour, 25% in next 2 hours

Fluid Choice for Deficit:

  • Isotonic crystalloid: 0.9% saline, Hartmann's, Plasma-Lyte
  • Avoid hypotonic: D5W, 0.45% saline (post-neonatal period)

Intraoperative Fluid Therapy

Goals:

  1. Replace fasting deficit
  2. Replace ongoing losses (blood, third space, evaporation)
  3. Maintain perfusion (BP, urine output, lactate)
  4. Avoid fluid overload

Types of Fluid Loss:

1. Sensible Losses:

  • Blood loss: Measure (suction, sponges), replace
    • <500 mL: Crystalloid (3:1 ratio)
    • 500 mL: Consider colloid or blood

  • Urine output: Monitor, maintain >0.5 mL/kg/hour
  • Evaporation: From surgical field (variable)

2. Insensible Losses:

  • Respiratory: Humidified gases reduce loss
  • Cutaneous: Open abdomen increases loss significantly

3. Third Space Losses (Redistribution):

  • Definition: Fluid shifts from intravascular to interstitial (non-functional)
  • Sites: Surgical trauma, inflammation, bowel obstruction
  • Estimates:
    • Minor surgery: 0-2 mL/kg/hour
    • Moderate surgery: 2-4 mL/kg/hour
    • Major surgery: 4-8 mL/kg/hour
    • Open abdomen: Up to 10-15 mL/kg/hour
  • Replacement: Isotonic crystalloid

Fluid Choice:

Crystalloids:

  • 0.9% Sodium Chloride (Normal Saline):
    • 154 mmol/L Na⁺, 154 mmol/L Cl⁻
    • Pros: Cheap, compatible with blood, isotonic
    • Cons: Hyperchloremic metabolic acidosis (dilutional), renal vasoconstriction
  • Hartmann's (Lactated Ringer's):
    • 131 Na⁺, 111 Cl⁻, 5 K⁺, 2 Ca²⁺, 29 lactate (converts to bicarbonate)
    • Pros: Balanced, less acidosis
    • Cons: Slightly hypotonic, calcium precipitates with citrate (blood)
  • Plasma-Lyte 148:
    • 140 Na⁺, 98 Cl⁻, 5 K⁺, 1.5 Mg²⁺, 23 gluconate, 27 acetate
    • Pros: Balanced, no calcium, acetate/gluconate metabolized to bicarbonate
    • Cons: More expensive

Colloids:

  • Albumin (4%, 20%):
    • Pros: Expands intravascular volume effectively
    • Cons: Expensive, blood product (theoretical risks), no survival benefit shown
  • Hydroxyethyl Starch (HES):
    • Avoid: Nephrotoxic, coagulopathy, mortality concern (6S, CHEST trials)
  • Gelatins (Gelofusine):
    • Pros: Cheap, effective short-term plasma expansion
    • Cons: Allergic reactions, short duration

Blood Products:

  • Indications:
    • Hb <70 g/L (or <80-90 g/L if cardiovascular disease)
    • Ongoing bleeding
    • Symptomatic anemia
  • Transfusion ratio (massive hemorrhage): 1:1:1 (PRBC:FFP:Platelets)

Glucose Management

Perioperative Considerations:

  • Stress response: Hyperglycemia (catecholamines, cortisol, insulin resistance)
  • Risk of hypoglycemia: If fasting on insulin/oral hypoglycemics
  • Target: 6-10 mmol/L (avoid hypoglycemia and severe hyperglycemia)

Diabetes Management:

  • Type 1: Must continue basal insulin (risk of DKA)
  • Type 2: Stop metformin 48 hours pre-op if using contrast or if eGFR <60
  • Monitoring: Regular BSLs, insulin sliding scale if needed

Postoperative Fluid Therapy

Goals:

  • Maintain euvolemia
  • Replace ongoing losses (NG tube, drains, fistulas)
  • Restore electrolyte balance
  • Transition to oral intake

Complications to Avoid:

  • Fluid overload: Peripheral edema, pulmonary edema (especially in elderly, cardiac failure)
  • Fluid restriction: Acute kidney injury, hypoperfusion
  • Electrolyte disturbances: Monitor K⁺, Na⁺ daily, replace as needed

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Patients

Higher Risk:

  • Higher rates: Renal disease (affects fluid/electrolyte handling), diabetes (glucose management)
  • Remote access: Dialysis-dependent patients may be far from centers
  • Hospital presentation: Often dehydrated or fluid overloaded

Cultural Considerations:

  • Kidney health: High importance in Aboriginal communities (high ESKD rates)
  • Medication adherence: Complex regimens (fluid/electrolyte management in dialysis)
  • Communication: Explain fluid restrictions clearly

Māori Health Considerations

Health Disparities:

  • Higher rates of diabetes and renal disease
  • Access to nephrology and dialysis services

Cultural Safety:

  • Whānau involvement: Family support for patients on dialysis (fluid/diet restrictions)
  • Communication: Clear explanation of fluid balance concepts
  • Dietary support: Low-sodium, fluid-restricted diets (culturally appropriate)

ANZCA Primary Exam Focus

Key Concepts

Body Water Distribution:

  • TBW: 60% (males), 50% (females)
  • ICF: 40% body weight (2/3 TBW)
  • ECF: 20% body weight (1/3 TBW)
    • ISF: 15%
    • Plasma: 5%

Electrolytes:

  • Na⁺: 135-145 mmol/L (ECF osmolality, volume)
  • K⁺: 3.5-5.0 mmol/L (resting membrane potential)
  • Ca²⁺: 2.2-2.6 mmol/L total (neuromuscular, cardiac)
  • Mg²⁺: 0.75-0.95 mmol/L (enzyme cofactor)

Osmolality:

  • Normal: 285-295 mOsm/kg
  • Formula: 2[Na⁺] + glucose/18 + urea/2.8
  • Tonicity: Effective osmoles (Na⁺, glucose) vs ineffective (urea)

Fluid Therapy:

  • Maintenance: 4-2-1 rule
  • Fasting deficit: Calculate and replace
  • Third space: 0-8 mL/kg/hour depending on surgery
  • Blood loss: 3:1 crystalloid or 1:1 colloid/blood

Common Exam Questions

"Calculate the fluid deficit for a 70 kg man fasting 10 hours."

  • Hourly maintenance: (10×4) + (10×2) + (50×1) = 40 + 20 + 50 = 110 mL/hour
  • Deficit: 110 × 10 = 1100 mL
  • Replace: 550 mL in first hour, 275 mL in hours 2 and 3

"Why is normal saline not 'normal'?"

  • Na⁺ 154 mmol/L (higher than plasma 140)
  • Cl⁻ 154 mmol/L (higher than plasma 100)
  • Results in hyperchloremic metabolic acidosis (dilutional)
  • Hartmann's or Plasma-Lyte more "physiological"

"What are the Starling forces governing capillary fluid exchange?"

  • Outward: Capillary hydrostatic pressure (Pc), interstitial oncotic pressure (πi)
  • Inward: Interstitial hydrostatic pressure (Pi), capillary oncotic pressure (πc)
  • Net filtration = (Pc + πi) - (Pi + πc)
  • Arterial end: Net filtration (+13 mmHg)
  • Venous end: Net reabsorption (-2 mmHg)
  • Lymphatics return excess interstitial fluid

"How does acid-base status affect potassium?"

  • Acidosis: H⁺ enters cells, K⁺ exits to maintain electroneutrality → hyperkalemia
  • Alkalosis: H⁺ exits cells, K⁺ enters → hypokalemia
  • Clinical: Correct acidosis gradually to avoid rapid K⁺ shifts

References

  1. ANZCA. Primary Examination Syllabus. Physiology Section.
  2. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed. McGraw-Hill; 2001.
  3. Campbell D et al. Fluid management. BJA Educ. 2015;15(3):118-123.
  4. Hahn RG. Fluid therapy in clinical medicine. BJA. 2021;126(2):417-424.
  5. Lobo DN et al. Perioperative fluid management. BMJ. 2011;342:d1736.
  6. Miller RD et al. Miller's Anesthesia. 9th ed. Elsevier; 2020:1755-1780.
  7. Grocott MPW et al. Perioperative fluid management. N Engl J Med. 2005;353(11):1077-1080.
  8. ATSI Health. Chronic kidney disease in Aboriginal and Torres Strait Islander peoples. Australian Institute of Health and Welfare; 2020.