2.5: Body Fluids, Electrolytes, & Acid-Base Balance

2.5: Body Fluids, Electrolytes, & Acid-Base Balance

Maintaining the volume, osmolality, and pH of body fluids is essential for cellular function, neuromuscular transmission, and enzymatic activity. For the OPRA exam, pharmacists must be able to analyse fluid compartments, manage electrolyte imbalances (specifically sodium and potassium), and systematically interpret arterial blood gas (ABG) panels.

1. Fluid Compartments and Dynamics

Water constitutes approximately 60% of total body weight (TBW) in adult males, and 50% in adult females and elderly individuals. The lower proportion of water in females and the elderly is due to a higher percentage of adipose tissue, which is hydrophobic and contains less water than lean muscle tissue.

Total body water is distributed across two primary compartments:

1. Intracellular Fluid (ICF): Represents approximately two-thirds (67%) of TBW. The major intracellular cation is Potassium (K+), and the major anions are organic phosphates and proteins.
2. Extracellular Fluid (ECF): Represents approximately one-third (33%) of TBW. The major extracellular cation is Sodium (Na+), and the major anions are chloride (Cl-) and bicarbonate (HCO3-).
   • The ECF is further divided into:
     • Interstitial Fluid (ISF): Surrounds the cells, accounting for 75% of the ECF volume.
     • Intravascular Fluid (Plasma): The liquid component of blood, accounting for 25% of the ECF volume.

Fluid movement between the intravascular and interstitial compartments is governed by Starling forces acting across the capillary membrane:

• Capillary Hydrostatic Pressure: Pushes water out of the capillaries.
• Plasma Colloid Osmotic (Oncotic) Pressure: Exerted primarily by dissolved albumin, which pulls water back into the capillaries.
• Clinical Correlation: Hypoalbuminaemia (serum albumin <35 g/L), caused by severe liver failure (impaired synthesis), nephrotic syndrome (renal loss), or malnutrition, reduces plasma oncotic pressure. This leads to a net movement of fluid from the intravascular space into the interstitial tissues, presenting clinically as peripheral pitting oedema or ascites.

2. Sodium Imbalances (Dysnatraemias)

Sodium is the principal solute of the ECF and the primary determinant of plasma osmolality. Imbalances in sodium concentration generally reflect disturbances in water balance rather than sodium balance.

A. Hyponatremia (Serum Na+ < 135 mmol/L)

Hyponatremia is classified clinically based on the patient's volume status:

1. Hypovolaemic Hyponatremia: Loss of both sodium and water, with sodium loss predominating. Common causes include thiazide/loop diuretics (which promote renal sodium excretion) and gastrointestinal losses (vomiting/diarrhoea). Treatment involves volume expansion with isotonic saline (0.9% NaCl).
2. Euvolaemic Hyponatremia: Total body water increases while sodium remains constant. The classic cause is SIADH (Syndrome of Inappropriate Antidiuretic Hormone), which can be drug-induced (e.g., SSRIs like sertraline, carbamazepine, venlafaxine). Treatment is fluid restriction (<1 L/day) and addressing the underlying cause.
3. Hypervolaemic Hyponatremia: Water retention exceeds sodium retention, leading to volume overload. Common causes are congestive heart failure, renal failure, and liver cirrhosis. Treatment involves fluid restriction and loop diuretics.

• Clinical Presentation: Mild hyponatremia presents with headache, nausea, confusion, and gait instability. Severe acute hyponatremia (<120 mmol/L) leads to cerebral oedema, seizures, coma, and death.
• Critical Safety Pearl (Osmotic Demyelination Syndrome): In chronic hyponatremia, the brain adapts by shedding intracellular osmolytes to prevent swelling. If hyponatremia is corrected too rapidly, water moves out of the brain cells into the hypertonic ECF, causing osmotic demyelination syndrome (central pontine myelinolysis). This manifests as flaccid paralysis, dysarthria, dysphagia, and mutism. Under Australian guidelines, sodium correction must not exceed 8–10 mmol/L within any 24-hour period, with a safer target of 4–6 mmol/L in patients at high risk of ODS.

B. Hypernatremia (Serum Na+ > 145 mmol/L)

Hypernatremia represents a relative water deficit.

• Causes: Impaired thirst mechanism (common in elderly and unconscious patients), unreplaced water loss (fever, burns), central or nephrogenic diabetes insipidus (the latter can be drug-induced by lithium), or administration of hypertonic saline or sodium bicarbonate.
• Clinical Presentation: Thirst, dry mucous membranes, lethargy, irritability, and in severe cases, seizures and coma.
• Management: Slow administration of free water (orally or via IV 5% glucose). The correction rate must be slow to prevent cerebral oedema, as brain cells that have accumulated organic osmoles to protect themselves during hypernatremia will rapidly absorb water if ECF osmolality drops too fast.

3. Potassium Imbalances (Deskalaemias)

Potassium is the primary determinant of the resting membrane potential in excitable tissues, particularly the myocardium. Minor fluctuations in serum potassium can have fatal cardiac consequences.

A. Hypokalemia (Serum K+ < 3.5 mmol/L)

• Causes: Renal loss (thiazide and loop diuretics), gastrointestinal loss (severe vomiting or diarrhoea), intracellular shifting (beta-2 receptor agonists like salbutamol, insulin therapy, or systemic alkalosis).
• Clinical Presentation: Muscle weakness, cramps, hyporeflexia, constipation, and cardiac arrhythmias.
• ECG Findings: Flattened T waves, ST-segment depression, and prominent U waves (an extra wave after the T wave).
• Management:
  • Mild-Moderate (3.0–3.4 mmol/L): Managed with oral potassium supplements (e.g., Span-K, a sustained-release formulation).
  • Severe (<3.0 mmol/L) or symptomatic: Requires intravenous potassium chloride.
  • Safety Rules for IV Potassium:
    1. Never administer potassium chloride as an IV push/bolus; it will cause immediate cardiac arrest.
    2. The standard rate of infusion in a peripheral line is 10 mmol/hour (to prevent chemical phlebitis and pain).
    3. Infusion rates up to 20 mmol/hour require a central venous catheter and continuous ECG monitoring.

B. Hyperkalaemia (Serum K+ > 5.5 mmol/L)

• Causes: Renal impairment (chronic kidney disease or acute kidney injury), potassium-sparing diuretics (spironolactone, amiloride), ACE inhibitors (ramipril), ARBs (candesartan), NSAIDs, trimethoprim, metabolic acidosis, and cellular lysis (rhabdomyolysis).
• Clinical Presentation: Muscle weakness, flaccid paralysis, palpitations, and cardiac conduction abnormalities.
• ECG Findings: Tall, peaked T waves (early sign), prolonged PR interval, widening of the QRS complex, progressing to a "sine wave" pattern and ventricular fibrillation.
• Emergency Management Protocol:
  1. Myocardial Membrane Stabilisation: Administer IV Calcium Gluconate 10% (10 mL over 5–10 minutes). This does not lower serum potassium but antagonises the cardiotoxic effects by shifting the threshold potential of cardiac cells, preventing ventricular arrhythmias. This is the absolute first-line therapy if ECG changes are present.
  2. Intracellular Shifting: Administer IV short-acting insulin (10 units of Actrapid) together with IV glucose (e.g., 50 mL of 50% glucose) over 15–30 minutes to stimulate the Na+/K+ ATPase pump. Nebulised salbutamol (10–20 mg) can also be used as adjuvant therapy.
  3. Potassium Elimination: Administer oral potassium binders like sodium polystyrene sulfonate (Resonium A) or sodium zirconium cyclosilicate (Lokelma) to bind potassium in the gastrointestinal tract. In cases of severe renal failure or refractory hyperkalaemia, haemodialysis is indicated.

4. Acid-Base Disturbances & ABG Interpretation

Arterial blood gas (ABG) interpretation is a core competency for hospital pharmacists.

• Normal Reference Ranges: pH: 7.35 – 7.45; paCO2 (respiratory component): 35 – 45 mmHg; HCO3- (metabolic component): 22 – 26 mmol/L.

Step-by-Step Interpretation Method

1. Evaluate pH: pH < 7.35 indicates acidosis; pH > 7.45 indicates alkalosis.
2. Determine Primary Driver:
   • If pH and paCO2 move in opposite directions, it is a primary respiratory disorder (e.g., low pH and high paCO2 = respiratory acidosis).
   • If pH and HCO3- move in the same direction, it is a primary metabolic disorder (e.g., low pH and low HCO3- = metabolic acidosis).
3. Assess Compensation: The body will attempt to return pH to normal using the opposite system.
   • No compensation: The compensatory parameter is within its normal range.
   • Partial compensation: The compensatory parameter has altered, but the pH remains outside the normal range.
   • Full compensation: The compensatory parameter has altered, and the pH is within the normal range (7.35–7.45).