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Hypokalemia and Hyponatremia - Complete MBBS Guide

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PART 1: HYPOKALEMIA

Definition & Normal Values

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Pathophysiology of K+ Homeostasis

1. Internal balance - distribution between ICF and ECF (regulated by insulin, catecholamines, acid-base status)
2. External balance - intake vs. renal excretion (regulated by aldosterone, distal tubular flow, AVP)

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Causes of Hypokalemia

1. Transcellular Shift (Redistribution) - K+ moves INTO cells

MBBS pearl: In thyrotoxic periodic paralysis, high-dose propranolol (3 mg/kg) rapidly reverses hypokalemia by blocking the adrenergic drive to Na+/K+-ATPase - Harrison's Principles of Internal Medicine 22E

2. Renal Losses (Urine K+ > 20 mEq/L or TTKG > 4)

• Primary hyperaldosteronism (Conn's syndrome)
• Secondary hyperaldosteronism (RAS, CHF, cirrhosis)
• Cushing's syndrome (cortisol has mineralocorticoid activity)
• Liddle syndrome (gain-of-function ENaC mutation)
• 11β-HSD deficiency (apparent mineralocorticoid excess)

• Diuretics (thiazides, loop diuretics) - most common cause
• Vomiting/NG suction (alkalosis → bicarbonaturia → urinary K+ loss)
• Bartter syndrome (loop diuretic-like defects)
• Gitelman syndrome (thiazide-like defect - NCC mutation)

• Renal tubular acidosis type 1 and 2
• Diabetic ketoacidosis (total body K+ depleted despite possibly normal serum K+)
• Amphotericin B toxicity

3. Extrarenal (GI) Losses (Urine K+ < 20 mEq/L)

• Diarrhea (large intestinal secretions rich in K+)
• Laxative abuse
• Malnutrition / poor dietary intake (rare alone)
• Excessive sweating (K+ in sweat is ~5-10 mEq/L)
• Fistulae, ileostomy

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Clinical Features

Neuromuscular

• Weakness (especially proximal muscles, lower limbs)
• Fatigue, cramps, myalgia
• Hypo/areflexia
• Ascending paralysis (severe)
• Rhabdomyolysis (K+ < 2.5 mEq/L)

Cardiac (most dangerous)

• Palpitations, arrhythmias
• Increased risk of digitalis toxicity
• Ventricular tachycardia/fibrillation in severe cases

Renal

• Polyuria, polydipsia (hypokalemic nephropathy - impairs urinary concentrating ability)
• Metabolic alkalosis (K+ depletion promotes H+ secretion and HCO3- reabsorption)

GI

• Constipation, ileus (smooth muscle hypo-excitability)
• Nausea

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ECG Changes in Hypokalemia

Mnemonic: "No pot, no T" - flattening of T wave is the hallmark of hypokalemia Barash Clinical Anesthesia 9e - "ECG manifestations include flattened T waves, prominent U waves, ST depression, prolonged QU interval - a prodysrhythmic state"

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Mechanisms of Diuretic-Induced Hypokalemia

1. Increased distal tubular flow - BK channel-mediated K+ secretion
2. AVP stimulation (nonosmotic) - ROMK-mediated secretion
3. Aldosterone secretion (RAAS activation) - ENaC/ROMK activation
4. Metabolic alkalosis - K+ shift into cells + increased distal K+ secretion

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Investigation of Hypokalemia

• Urine K+ < 20 mEq/L or TTKG < 3: Extrarenal loss or poor intake
• Urine K+ > 20 mEq/L or TTKG > 4: Renal wasting

• Hypertension + high urine K+ → hyperaldosteronism, Cushing's, Liddle syndrome
• Normotension + metabolic alkalosis + low urine Cl- → vomiting/bulimia
• Normotension + metabolic alkalosis + high urine Cl- → diuretics, Bartter/Gitelman

• TTKG (transtubular K+ gradient) < 3 = appropriate renal conservation
• Urine K+/creatinine > 13 mmol/g = inappropriate renal wasting
• Plasma aldosterone:PRA ratio > 50 → primary hyperaldosteronism

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Treatment of Hypokalemia

General Principles

1. Determine urgency based on: severity, cardiac disease, digoxin use, rate of fall
2. Patients with prolonged QT or arrhythmia require continuous cardiac monitoring
3. Always correct hypomagnesemia first - hypomagnesemic patients are refractory to K+ replacement because Mg2+ is needed for Na+/K+-ATPase function

Oral Replacement (Preferred)

• KCl is the first choice - corrects both K+ and Cl- deficit (important in metabolic alkalosis)
• Potassium bicarbonate/citrate for those with concomitant metabolic acidosis
• Potassium phosphate if hypophosphatemia coexists

IV Replacement (When oral not feasible, severe hypokalemia, arrhythmias)

• Standard rate: 10-20 mEq/hr via peripheral vein
• Maximum rate: 40 mEq/hr (only with continuous cardiac monitoring, central line)
• Concentration: ≤ 40 mEq/L via peripheral IV (higher concentrations are painful and sclerotic)
• Do NOT use dextrose solutions (glucose stimulates insulin → drives K+ into cells, worsening hypokalemia)

Special Situations

• Redistributive hypokalemia (TPP, theophylline): High-dose propranolol (3 mg/kg) - corrects without rebound hyperkalemia risk
• DKA: K+ replacement essential even if initial K+ is normal or high, as insulin therapy will drop it

Preventing Recurrence

• K+-sparing diuretics: spironolactone, eplerenone (block aldosterone), amiloride/triamterene (block ENaC)
• ACEi/ARBs reduce RAAS-driven kaliuresis
• Increase dietary K+ intake (fruits, vegetables, nuts)

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PART 2: HYPONATREMIA

Definition & Epidemiology

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Pathophysiology

Plasma [Na+] = (Exchangeable Na+ + Exchangeable K+) / TBW

1. Excess circulating AVP (arginine vasopressin/ADH) - retains free water
2. Increased renal sensitivity to AVP
3. Combined with free water intake
4. Exception: low solute intake (beer potomania)

• Osmotic: plasma hyperosmolality (normal)
• Nonosmotic: hypovolemia, pain, nausea, drugs, CNS disease (pathological)

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Classification and Causes

Step 1 - By Plasma Osmolality

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Step 2 - Hypoosmolar Hyponatremia by Volume Status

A. HYPOVOLEMIC HYPONATREMIA (Total body Na+ decreased)

Thiazide-specific mechanism: Unlike loop diuretics, thiazides inhibit urinary dilution but not concentration. This makes them 12 times more likely to cause hyponatremia. 80% of cases occur in older females with low body mass. Develops within the first 2 weeks. Mechanism involves a prostaglandin transporter variant (SLCO2A1) that causes AVP-independent free water reabsorption. - Brenner and Rector's The Kidney

B. EUVOLEMIC HYPONATREMIA (Total body Na+ normal, excess water)

C. HYPERVOLEMIC HYPONATREMIA (Total body Na+ increased, but water even more increased)

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Causes of SIADH

• Hypo-osmolality (plasma Osm < 280 mOsm/kg)
• Inappropriately concentrated urine (Uosm > 100 mOsm/kg)
• Urine Na+ > 40 mEq/L (with normal salt and water intake)
• Clinical euvolemia
• Normal renal, thyroid, and adrenal function
• No recent diuretic use

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Clinical Features of Hyponatremia

Acute Hyponatremia (< 48 hours)

• Headache, nausea, vomiting
• Confusion, lethargy
• Seizures, obtundation
• Cerebral herniation (life-threatening)
• Women (especially premenopausal) and children are more vulnerable - estrogen impairs brain cell adaptation

Chronic Hyponatremia (> 48 hours)

• "Asymptomatic" but subtle: gait instability, cognitive deficits, attention problems
• Increased risk of falls and fractures
• Decreased bone density
• Nausea, confusion at Na+ < 125 mEq/L
• Seizures at Na+ < 105-110 mEq/L

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Investigation of Hyponatremia

1. Plasma Na+ - confirm hyponatremia (< 135 mEq/L)
2. Plasma osmolality - rule out pseudohyponatremia and hyperosmolar causes
3. Volume status - clinical exam (BP, skin turgor, JVP, edema)
4. Urine osmolality:
   • Uosm < 100 mOsm/kg = maximally dilute = appropriate response (psychogenic polydipsia, beer potomania)
   • Uosm > 100 mOsm/kg = inappropriately concentrated = AVP excess
5. Urine Na+:
   • < 20 mEq/L = extrarenal loss or hypervolemic state (Na+ avid kidneys)

   • 40 mEq/L = SIADH, diuretics, renal failure, adrenal insufficiency

6. Serum K+, glucose, creatinine, TSH, cortisol
7. Urine-to-plasma electrolyte ratio: (UNa + UK) / PNa
   • Ratio > 1 = every liter of urine excreted retains free water → need aggressive fluid restriction

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Treatment of Hyponatremia

1. Treat the underlying cause first

• SIADH from drugs → stop the drug
• Hypothyroidism → thyroxine replacement
• Adrenal insufficiency → hydrocortisone
• Volume depletion → isotonic saline (as AVP falls, water diuresis ensues)
• Hypervolemic (CHF) → optimize cardiac output (ACEi, diuretics cautiously)

2. Correction rate (CRITICAL to prevent ODS)

Maximum safe correction rate: 8-10 mEq/L in 24 hours, 18 mEq/L in 48 hours

3. Specific Therapies

Fluid Restriction (for SIADH/euvolemic)

• Urine-to-plasma ratio > 1 → restrict to < 500 mL/day
• Urine-to-plasma ratio ~1 → restrict to 500-700 mL/day
• Urine-to-plasma ratio < 1 → restrict to < 1 L/day

Vaptans (AVP Receptor Antagonists)

• Tolvaptan (oral, V2-selective) - produces electrolyte-free water excretion ("aquaresis")
• Conivaptan (IV, V1A + V2) - for hospitalized patients
• Use when fluid restriction fails in SIADH; avoid in hypovolemic hyponatremia
• Risk of rapid overcorrection - start low, monitor closely; avoid in liver disease (tolvaptan)

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Quick Comparison Table

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Key High-Yield Mnemonics for MBBS Exams

• Malignancy (SCLC)
• Neurological (meningitis, SAH)
• Infections (pneumonia, TB)
• SSRIs/Drugs
• Surgery/Stress
• Thyroid deficit (hypothyroidism)
• Cortisol deficit (adrenal insufficiency)

• Alcoholism
• Burn patients
• Chronic malnutrition / hypoKalemia / liver disease

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