What are the causes and effects of hyperchloremia?

Hyperchloremia Causes

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 iatrogenic:

• Excessive 0.9% normal saline administration is the leading iatrogenic cause, as this solution contains 154 mEq/L chloride—a supraphysiologic concentration compared to plasma 1
• Total parenteral nutrition solutions high in chloride content cause hyperchloremia, especially 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 consistently lead to hyperchloremic acidosis 1
• Medication diluents and IV fluids used for volume resuscitation all contribute to cumulative chloride load 2

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 3

Gastrointestinal Causes

Bicarbonate-rich fluid losses lead to compensatory chloride retention:

• 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 causes urinary reabsorption in the ileum, leading to chloride retention and bicarbonate loss 4

Renal Causes

• Renal tubular acidosis (both proximal and distal) results in hyperchloremic normal gap metabolic acidosis through either insufficient renal bicarbonate regeneration or filtered bicarbonate wasting 5
• The avidity for chloride reabsorption increases when effective extracellular volume is reduced from loss of NaHCO3 or NaA 5
• Impaired renal capacity to handle excessive chloride loads overwhelms normal regulatory mechanisms 6

Pathophysiologic Mechanisms

• Water losses exceeding sodium and chloride losses create a concentration effect leading to hyperchloremia 6
• The Stewart physicochemical approach explains that increased plasma chloride relative to sodium decreases the strong ion difference, which directly lowers pH and bicarbonate concentration 1
• Excessive chloride gain relative to sodium or excessive loss of sodium relative to chloride disrupts normal electrolyte balance 7

High-Risk Populations

Specific patient groups are particularly vulnerable:

• Premature infants on parenteral nutrition receiving high chloride loads from amino acid solutions and sodium chloride 1
• Diabetic ketoacidosis patients during recovery, as chloride from IV fluids replaces ketoanions lost during osmotic diuresis 1
• Major abdominal or pancreatic surgery patients receiving prolonged perioperative fluid therapy 1
• Patients with renal impairment following ileal conduit diversion, where compromised renal function exacerbates acidosis 4

Clinical Effects

Hyperchloremia produces significant physiologic consequences:

• Excess 0.9% saline causes hyperosmolar states, hyperchloremic acidosis, and decreased renal blood flow and glomerular filtration rate, exacerbating sodium retention 1
• Hyperchloremic acidosis reduces gastric blood flow, decreases gastric intramucosal pH, and impairs gastric motility 1
• Splanchnic edema results in increased abdominal pressure, delayed recovery of gastrointestinal function, increased gut permeability, and potential anastomotic dehiscence 1
• Associated with increased incidence of acute kidney injury and metabolic acidosis 2

Key recognition point: Cumulative chloride from multiple sources (IV fluids, medications, nutrition) often goes unrecognized until significant hyperchloremia develops 1