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🧂 ELECTROLYTE SERIES — DAY 1

SODIUM (Na⁺) & HYPONATREMIA (Low Sodium)

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PART 1: WHAT IS SODIUM?

Key Physiology Points

• Plasma Na⁺ concentration is the main determinant of plasma osmolality. Over 90% of ECF osmolality comes from Na⁺ and its associated anions (mainly Cl⁻).
• ADH (Arginine Vasopressin / AVP) is the primary hormone regulating water balance - it acts on renal collecting ducts to reabsorb water, concentrating urine.
• Aldosterone regulates Na⁺ reabsorption at the distal tubule, directly controlling total body Na⁺ content and thus ECF volume.
• A critical concept: plasma Na⁺ tells you about water balance, NOT volume status. A patient can be hyponatremic while being hypovolemic, euvolemic, OR hypervolemic.

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PART 2: HYPONATREMIA - THE LOW SODIUM CONDITION

Definition

Hyponatremia = serum Na⁺ < 135 mmol/L

Severity Classification

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PART 3: PATHOPHYSIOLOGY - HOW DOES HYPONATREMIA DEVELOP?

1. Too much water retained (with normal or even high ADH) = dilutional hyponatremia
2. Too much sodium lost from the body (vomiting, diarrhea, diuretics)
3. Both - sodium lost + water replaced with hypotonic fluids

The Kidney's Dilution Mechanism (and where it fails):

• Reduced GFR (from CHF, cirrhosis, age) = less filtrate delivered to diluting segments
• Loop diuretics block Na⁺/Cl⁻ reabsorption in the thick ascending limb
• Thiazides block Na⁺/Cl⁻ reabsorption in the distal convoluted tubule
• Vasopressin makes the collecting duct water-permeable, trapping water = most common cause of hyponatremia

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PART 4: CLASSIFICATION BY VOLUME STATUS

1. HYPOVOLEMIC Hyponatremia (Low total body Na⁺)

• Na⁺ is lost in excess of water
• Volume depletion stimulates ADH non-osmotically (baroreceptor reflex)
• ADH causes water retention despite low Na⁺

• Vomiting, diarrhea, tube drainage
• Burns, sweating, insensible losses

• Thiazide diuretics (most common drug cause)
• Addison's disease (aldosterone deficiency)
• Salt-losing nephropathies
• Cerebral salt wasting (CSW) - seen after subarachnoid hemorrhage, TBI

2. EUVOLEMIC Hyponatremia (Normal total body Na⁺)

• Water is retained, Na⁺ is normal - pure water excess
• SIADH is the most common cause (covered below)
• Other causes: Hypothyroidism, secondary adrenal insufficiency (pituitary disease), psychogenic polydipsia, beer potomania, MDMA ("Ecstasy")

3. HYPERVOLEMIC Hyponatremia (High total body Na⁺)

• Both Na⁺ and water are increased, but water retained disproportionately
• Urine Na⁺ typically very low (< 10 mmol/L) due to avid Na⁺ retention
• Causes: Congestive heart failure (CHF), cirrhosis, nephrotic syndrome, acute/chronic kidney failure

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PART 5: SIADH - THE KEY CAUSE YOU MUST KNOW

Causes of SIADH:

Diagnostic Criteria for SIADH:

1. Serum osmolality < 275 mOsm/kg
2. Urine osmolality > 100 mOsm/kg (inappropriately concentrated)
3. Clinical euvolemia (no edema, no dehydration)
4. Urine Na⁺ > 20-30 mmol/L on normal salt/water intake
5. Normal thyroid, adrenal, renal, and pituitary function
6. No recent diuretic use

• Hypouricemia with elevated fractional excretion of uric acid (>10%)
• No correction with volume expansion, but correction with fluid restriction

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PART 6: CAUSES OF ACUTE HYPONATREMIA (Rapid Onset)

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PART 7: SIGNS AND SYMPTOMS

Acute Hyponatremia (rapid drop, < 48 hours):

• Mild: Headache, nausea, vomiting, malaise
• Moderate: Confusion, lethargy, muscle cramps, gait disturbance
• Severe (Na⁺ < 120 mmol/L): Seizures, obtundation, respiratory arrest, central herniation, death
• Premenopausal women and children are at highest risk of severe neurological sequelae

Chronic Hyponatremia (> 48 hours):

• Brain adapts by extruding organic osmolytes (taurine, glutamate, myoinositol, creatine, betaine)
• Symptoms are less severe at the same Na⁺ level
• But even "asymptomatic" patients have: increased risk of falls, gait disturbance, cognitive deficits, increased fracture risk (from both neurological dysfunction AND reduced bone density)

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PART 8: DIAGNOSIS - STEP BY STEP

Diagnostic Algorithm:

Step-by-step approach:

• Low (< 275 mOsm/kg) = True hypotonic hyponatremia → proceed to step 2
• Normal or High = Pseudohyponatremia OR translocational:
  • Pseudohyponatremia: severe hypertriglyceridemia, hyperglobulinemia (lab artifact - Na⁺ is actually normal)
  • Translocational: hyperglycemia, mannitol, sorbitol (osmotically active substances draw water out, diluting Na⁺)
  • Correct formula: for every 100 mg/dL rise in glucose above 100, add ~1.6-2.0 mmol/L to measured Na⁺

• < 100 mOsm/kg (maximally dilute urine) = ADH is suppressed = Psychogenic polydipsia, beer potomania, low solute intake
• > 200 mOsm/kg (inappropriately concentrated) = ADH is active = proceed to step 3

• Hypovolemic → Check Urine Na⁺:
  • Urine Na⁺ < 20: extrarenal losses (GI, skin)
  • Urine Na⁺ > 20: renal losses (diuretics, Addison's, salt-wasting nephropathy, CSW)
• Euvolemic → SIADH, hypothyroidism, secondary adrenal insufficiency
• Hypervolemic → CHF, cirrhosis, nephrotic syndrome, renal failure

• Serum Na⁺, K⁺, glucose, BUN/creatinine, uric acid
• Serum osmolality
• Urine osmolality + urine Na⁺ + urine K⁺
• TSH (rule out hypothyroidism)
• Cortisol/ACTH stimulation test (rule out adrenal insufficiency)

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PART 9: MANAGEMENT

Three Governing Principles (Harrison's):

1. Symptom severity determines urgency - acute severe symptoms = emergency
2. Chronic hyponatremia must NOT be corrected too fast - risk of Osmotic Demyelination Syndrome (ODS)
3. Response to treatment is unpredictable - frequent monitoring is mandatory

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A. ACUTE SEVERE SYMPTOMATIC Hyponatremia (Seizures / Herniation)

• Can repeat x2 if no improvement
• Once symptoms controlled, slow the rate
• Total correction limit: 8-10 mmol/L in first 24 hours

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B. HYPOVOLEMIC Hyponatremia

• Repletes volume → ADH levels fall → kidneys excrete free water → Na⁺ rises
• Caution: Na⁺ can rise very rapidly once volume is corrected - monitor every 2-4 hours!

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C. EUVOLEMIC Hyponatremia (SIADH)

1. Fluid restriction - cornerstone of therapy
   • Use the urine-to-plasma electrolyte ratio (urine [Na⁺ + K⁺] / plasma Na⁺) to guide restriction level:
     • Ratio > 1: restrict to < 500 mL/day
     • Ratio ~1: restrict to 500-700 mL/day
     • Ratio < 1: restrict to < 1 L/day
2. Treat the underlying cause (e.g., stop the offending drug, treat underlying cancer or infection)
3. Increased dietary sodium and protein intake (raises solute excretion)
4. Tolvaptan or Conivaptan (V2 receptor antagonists / "vaptans") - block ADH at kidney
   • Cause aquaresis (pure free water excretion without electrolyte loss)
   • Used for persistent, severe SIADH
   • Monitoring intensive - risk of overcorrection
5. Demeclocycline (causes nephrogenic DI, older agent, rarely used now)
6. Urea - oral urea increases solute excretion, effective but unpalatable

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D. HYPERVOLEMIC Hyponatremia (CHF / Cirrhosis)

• Treat underlying disease (optimize CHF medications, manage cirrhosis)
• Fluid restriction + dietary Na⁺ restriction
• Loop diuretics (furosemide) - promote free water loss
• Vaptans (tolvaptan) - FDA approved for CHF-related hyponatremia
• Avoid isotonic saline (will worsen fluid overload)

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⚠️ THE DREADED COMPLICATION: Osmotic Demyelination Syndrome (ODS)

• In chronic hyponatremia (>48 hrs), brain cells adapt by extruding osmolytes to prevent swelling
• If Na⁺ is corrected TOO rapidly, brain osmolality rises faster than cells can recapture osmolytes
• Hypertonic stress in oligodendrocytes → ER stress → unfolded protein response → apoptosis → myelin sheath destruction

• Beer potomania (hypokalemia + alcoholism + malnutrition)
• Severe malnutrition
• Liver disease
• Hypokalemia (K⁺ correction also raises Na⁺ - count it toward your correction limit!)

• Appears 2-6 days after rapid correction
• Dysarthria, dysphagia
• Spastic quadriplegia
• Locked-in syndrome (in severe cases)
• Irreversible in many cases

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PART 10: QUICK MEMORY AID

HYPONATREMIA MNEMONIC - "LOW SALT"

L - Lethargy, Low urine Na in non-renal causes
O - Osmolality (serum) - always check first
W - Water excess is the core mechanism

S - SIADH is #1 euvolemic cause
A - ADH is almost always involved
L - Limit correction rate (≤10 mmol/L/24h for chronic)
T - Treat volume status (hypo/eu/hypervolemic approach)

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SUMMARY TABLE

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📅 COMING UP TOMORROW - DAY 2

• What is it, why does it happen
• Diabetes insipidus (central vs. nephrogenic)
• Signs, diagnosis, management
• The flip side of today's lesson!

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