Section 8.2: Fluid, Electrolyte, & Acid-Base Disorders

Hyponatremia: Diagnostic Evaluation and Management Limits

Hyponatremia, defined as a serum sodium concentration < 135 mEq/L, is the most common electrolyte disorder in clinical practice. The initial step in evaluation is measuring serum osmolality to distinguish true hypotonic hyponatremia from isotonic or hypertonic states. Hypertonic hyponatremia (osmolality > 295 mOsm/kg) typically results from hyperglycemia or mannitol administration, where active osmoles draw intracellular water into the extracellular space. Every 100 mg/dL elevation in blood glucose above 100 mg/dL decreases measured serum sodium by approximately 1.6 mEq/L (or 2.4 mEq/L if glucose exceeds 400 mg/dL). Isotonic hyponatremia (osmolality 275–295 mOsm/kg) represents pseudohyponatremia, an artifact of hyperlipidemia or hyperproteinemia when using older flame photometry methods.

Hypotonic hyponatremia (osmolality < 275 mOsm/kg) represents true sodium dilution and is categorized by clinical volume status:

• Hypovolemic: Patients exhibit signs of volume depletion (dry mucous membranes, orthostatic hypotension, tachycardia). The next step is measuring urine sodium. A urine sodium < 20 mEq/L indicates extrarenal fluid loss (vomiting, diarrhea, third-spacing), where the kidneys appropriately conserve sodium. A urine sodium > 20 mEq/L indicates renal sodium wasting, commonly from diuretic use (thiazides are notorious for causing hyponatremia) or primary adrenal insufficiency. Treatment consists of volume expansion with 0.9% normal saline, which restores perfusion, terminates the carotid baroreceptor-mediated stimulus for antidiuretic hormone (ADH) release, and permits water diuresis.
• Euvolemic: Patients have normal extracellular volume without edema. The differential includes the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), hypothyroidism, secondary adrenal insufficiency, psychogenic polydipsia, and beer potomania. In SIADH, urine osmolality is inappropriately concentrated (> 100 mOsm/kg, often > 300) and urine sodium is > 40 mEq/L due to volume-expansion-induced natriuresis. Conversely, psychogenic polydipsia and beer potomania present with maximally dilute urine (osmolality < 100 mOsm/kg). SIADH management includes fluid restriction, oral salt tablets, loop diuretics (to disrupt the medullary concentration gradient), or vasopressin receptor antagonists (vaptans).
• Hypervolemic: Patients present with systemic volume overload (edema, ascites, pulmonary congestion) due to water retention exceeding sodium retention. Causes include heart failure, cirrhosis, and nephrotic syndrome. In heart failure and cirrhosis, effective arterial blood volume is reduced, triggering ADH and aldosterone release, yielding a urine sodium < 20 mEq/L. Treatment focuses on sodium and fluid restriction, alongside loop diuretics.

Regardless of etiology, rapid correction of chronic hyponatremia (> 48 hours duration) risks osmotic demyelination syndrome (ODS, or central pontine myelinolysis). In a hypotonic state, brain cells lose intracellular osmoles to prevent swelling. If the extracellular fluid is rapidly made hypertonic, water exits brain cells, leading to oligodendrocyte death and demyelination, presenting days later with dysarthria, dysphagia, quadriparesis, and the "locked-in" syndrome.

To prevent ODS, serum sodium correction must be limited to 4–6 mEq/L in 24 hours, and must not exceed 8 mEq/L in any 24-hour period. In patients with severe symptoms (seizures, obtundation, coma), emergent therapy requires a 100 mL bolus of 3% hypertonic saline over 10–15 minutes, which can be repeated up to two times to raise the sodium by 4–6 mEq/L and abort seizures. If overcorrection occurs, active re-lowering with desmopressin (dDAVP) and 5% dextrose in water (D5W) is indicated.

Potassium Disorders: Treatment Algorithms

Hyperkalemia (potassium > 5.0 mEq/L) is a medical emergency when levels exceed 6.0 mEq/L or if electrocardiographic (ECG) abnormalities are present (peaked T waves, PR interval prolongation, QRS widening, sine wave, or ventricular fibrillation). The management strategy is threefold:

1. Membrane Stabilization: Administer 10 mL of 10% calcium gluconate (or calcium chloride if central access is established) intravenously over 5–10 minutes. Calcium antagonizes the cardiotoxic effects of hyperkalemia by restoring the normal resting membrane potential gradient. It does not lower serum potassium.
2. Intracellular Shifting: Administer 10 units of regular insulin intravenously alongside 50 mL of 50% dextrose (D50) to shift potassium into cells by stimulating the Na-K ATPase. Nebulized albuterol (10–20 mg) and intravenous sodium bicarbonate (especially in metabolic acidosis) are adjunctive shifting agents.
3. Potassium Elimination: Remove potassium from the body using loop diuretics (furosemide) in patients with preserved renal function, oral cation exchangers (patiromer or sodium zirconium cyclosilicate), or emergent hemodialysis for refractory cases or oliguric renal failure.

Hypokalemia (potassium < 3.5 mEq/L) is managed with potassium repletion. Oral potassium chloride is preferred for mild-to-moderate asymptomatic hypokalemia. Intravenous potassium chloride is reserved for severe hypokalemia (< 3.0 mEq/L) or symptomatic patients (muscle weakness, ECG findings of flat T waves, ST depression, or prominent U waves). Intravenous administration must be limited to 10 mEq/h via peripheral lines to prevent chemical phlebitis, or up to 20 mEq/h via a central venous catheter with continuous cardiac monitoring.

The Magnesium Connection: Refractory hypokalemia is frequently caused by concurrent hypomagnesemia. Magnesium is a co-factor that normally inhibits potassium secretion through renal outer medullary potassium (ROMK) channels in the collecting duct. In the setting of magnesium depletion, this inhibition is lost, leading to accelerated renal potassium wasting. Thus, serum magnesium must be checked and aggressively repleted to successfully correct hypokalemia.

Step-wise Acid-Base Interpretation

Arterial blood gas (ABG) analysis requires a systematic approach:

1. Assess the pH: Normal is 7.35–7.45. A pH < 7.35 indicates acidemia; > 7.45 indicates alkalemia.
2. Determine the Primary Disorder: Examine pCO2 (normal 35–45 mmHg) and HCO3 (normal 22–26 mEq/L). If pH and pCO2 move in opposite directions, it is a primary respiratory disorder. If pH and HCO3 move in the same direction, it is a primary metabolic disorder.
3. Assess Compensation:
   • In metabolic acidosis, calculate the expected pCO2 using Winter's Formula: expected pCO2 = (1.5 * [HCO3]) + 8 ± 2. If the measured pCO2 is higher than expected, a concurrent respiratory acidosis is present. If lower than expected, a concurrent respiratory alkalosis exists.
   • In metabolic alkalosis, the expected pCO2 rises by 0.7 mmHg for every 1 mEq/L increase in HCO3.
   • For respiratory acidosis, acute compensation yields a 1 mEq/L increase in HCO3 for every 10 mmHg rise in pCO2; chronic compensation yields a 3.5 mEq/L increase.
4. Calculate the Anion Gap: For metabolic acidosis, calculate the anion gap (AG): AG = Na - (Cl + HCO3). A normal gap is 12 ± 2. If AG > 12, a high anion gap metabolic acidosis (HAGMA) is present.
5. Calculate the Delta Ratio (Delta-Delta) in HAGMA: Delta-Delta = (Measured AG - 12) / (24 - Measured HCO3). A ratio < 0.8 indicates a concurrent non-anion gap metabolic acidosis (NAGMA). A ratio > 1.2 indicates a concurrent metabolic alkalosis.