What are the causes and effects of hyperchloremia?

Causes of Hyperchloremia

Hyperchloremia most commonly results from excessive administration of chloride-rich intravenous fluids (particularly 0.9% normal saline), gastrointestinal bicarbonate losses, and renal tubular acidosis. 1

Iatrogenic and Fluid-Related Causes

The most frequent cause in hospitalized patients is excessive 0.9% normal saline administration, which contains supraphysiologic chloride concentrations (154 mEq/L) compared to normal plasma levels. 1 This is particularly problematic because:

• Cumulative chloride loading from multiple sources often goes unrecognized until significant hyperchloremia develops 1
• Total parenteral nutrition solutions high in chloride content contribute when sodium is provided predominantly as sodium chloride rather than balanced with sodium acetate or lactate 1
• Cardiopulmonary bypass priming solutions using unbalanced crystalloids or colloids lead to hyperchloremic acidosis 2
• Medication diluents and IV fluids used for volume resuscitation all contribute to chloride accumulation 3

A critical pitfall: switching from 0.9% NaCl to 0.45% NaCl does not resolve hyperchloremia—the latter still contains 77 mEq/L chloride, delivering supraphysiologic concentrations. 2

Gastrointestinal Losses

Gastrointestinal bicarbonate loss is a major non-iatrogenic cause:

• Diarrhea causes hyperchloremia through bicarbonate loss in stool, with compensatory chloride retention by the kidneys to maintain electroneutrality 1
• Intestinal fistulas, drainage tubes, and ileostomies result in bicarbonate-rich fluid losses with relative chloride retention 1
• Ileal conduit urinary diversion leads to urinary reabsorption in the ileum, causing chloride retention and bicarbonate loss 4

Renal Causes

Renal mechanisms include:

• Renal tubular acidosis (both proximal and distal) results in either bicarbonate wasting or insufficient new bicarbonate generation, with compensatory chloride retention producing hyperchloremic normal gap metabolic acidosis 5
• The kidney's capacity to handle excessive chloride can be overwhelmed 6
• Renal insufficiency initially presents with normal gap acidosis before progressing to anion gap acidosis with severe GFR reduction 5

Pathophysiologic Mechanisms

The Stewart physicochemical approach explains the acid-base effects:

• An increase in plasma chloride relative to sodium decreases the strong ion difference, which directly lowers pH and bicarbonate concentration 1
• Water losses exceeding sodium and chloride losses can concentrate chloride 6
• Serum bicarbonate decreases with concomitant chloride rise in normal anion gap metabolic acidosis or respiratory alkalosis 6

High-Risk Populations

Certain patient groups are particularly vulnerable:

• Premature infants on parenteral nutrition are especially susceptible when receiving high chloride loads from amino acid solutions and sodium chloride 1
• Patients recovering from diabetic ketoacidosis commonly develop hyperchloremia from excessive saline use for fluid and electrolyte replacement, as chloride from IV fluids replaces ketoanions lost during osmotic diuresis 7
• Patients undergoing major abdominal or pancreatic surgery receiving prolonged perioperative fluid therapy 7

Clinical Effects of Hyperchloremia

Beyond the electrolyte disturbance itself, hyperchloremia causes significant physiologic derangements:

• Excess 0.9% saline causes hyperosmolar states, hyperchloremic acidosis, and decreased renal blood flow and glomerular filtration rate, which exacerbates sodium retention 7
• Hyperchloremic acidosis reduces gastric blood flow, decreases gastric intramucosal pH, and impairs gastric motility 7
• Splanchnic edema results in increased abdominal pressure, delayed recovery of gastrointestinal function, increased gut permeability, and potential anastomotic dehiscence 7, 2