Which of the following, if given in large volumes, can lead to hyperchloremic metabolic acidosis?

Correct Answer: D. Normal saline (NS)

Normal saline (0.9% NaCl) contains 154 mEq/L of chloride, which is hyperchloremic relative to plasma (98–107 mEq/L). When administered in large volumes, the excess chloride is filtered by the glomerulus and reabsorbed in the proximal tubule, but the accompanying sodium is partially reabsorbed via the Na-K-ATPase and other mechanisms. This creates a chloride load that exceeds the kidney's capacity to excrete it proportionally. The excess chloride is reabsorbed in the collecting duct via the chloride-bicarbonate exchanger (pendrin), which causes bicarbonate wasting and hyperchloremic metabolic acidosis. The mechanism is further exacerbated because large-volume NS administration dilutes plasma bicarbonate and suppresses aldosterone (due to volume expansion), reducing renal acid excretion. In Indian clinical practice, prolonged NS infusions for resuscitation or maintenance (especially in sepsis, trauma, or perioperative settings) are a recognized cause of hyperchloremic acidosis, which can impair renal perfusion and worsen outcomes. The chloride-to-sodium ratio in NS (154:154) is the culprit; balanced crystalloids (e.g., Ringer lactate) have lower chloride concentrations and are now preferred in many Indian ICUs.

Why the other options are wrong

A. Dextrose in NS (DNS) — DNS is essentially NS with added dextrose for caloric support. The dextrose itself does not cause hyperchloremic acidosis; the problem is still the high chloride content of the NS component (154 mEq/L). However, DNS is less commonly used in large volumes for resuscitation compared to NS alone, and the dextrose may provide some metabolic benefit. The chloride load is still present but the question specifically asks about the fluid itself—DNS is a variant of NS and would also cause hyperchloremic acidosis if given in truly large volumes, making it a weaker distractor than the pure NS. B. Ringer lactate — Ringer lactate contains only 109 mEq/L of chloride, which is closer to physiological plasma levels. The lactate anion (28 mEq/L) is metabolized to bicarbonate in the liver, providing a buffering effect and actually preventing hyperchloremic acidosis. This is why Ringer lactate is the preferred crystalloid in Indian trauma and sepsis guidelines (RNTCP, SCCM-adapted protocols) for large-volume resuscitation. It does not cause hyperchloremic acidosis even in large volumes. C. 5% dextrose in water — 5% dextrose in water is hypotonic and contains no electrolytes (chloride = 0 mEq/L). It is rapidly distributed into the intracellular compartment and does not cause hyperchloremic acidosis. In fact, large volumes of D5W can cause hyponatremia and cerebral edema due to free water excess, but not hyperchloremic acidosis. This is a classic NBE trap: students may confuse the complications of D5W (hyponatremia, hypo-osmolality) with those of NS (hyperchloremia, acidosis).

High-Yield Facts

Mnemonics

*NS = High Chloride, RL = Low Chloride NS: 154 Cl⁻ (hyperchloremic) | RL: 109 Cl⁻ (physiologic) + lactate → bicarbonate. Use this to remember which crystalloid causes hyperchloremic acidosis. CHLORIDE TRAP in NS Collecting duct reabsorbs excess Cl⁻ via pendrin → Hyperchloremic acidosis → Loss of Oscillating Renal Ion balance → Diminished E*xcretion. Mnemonic for mechanism.

NBE Trap

NBE pairs NS (a commonly used fluid) with a subtle electrolyte complication (hyperchloremic acidosis) that students often overlook because they focus on volume status rather than chloride load. The trap is that DNS (option A) looks similar to NS, and students may incorrectly assume dextrose prevents the problem, when in fact the chloride content is the culprit.

Clinical Pearl

In Indian ICUs and trauma centers, prolonged NS resuscitation (especially in sepsis or major surgery) is increasingly recognized as a cause of hyperchloremic acidosis that worsens renal perfusion and increases mortality. Many centers now preferentially use Ringer lactate or balanced crystalloids (e.g., Plasmalyte) for large-volume resuscitation, following international evidence and adapted Indian sepsis guidelines.

_Reference: KD Tripathi Pharmacology Ch. 32 (Fluid & Electrolyte Management); Harrison Ch. 48 (Acid-Base Disorders); Guyton & Hall Textbook of Medical Physiology Ch. 30 (Acid-Base Balance)_