What causes hyperchloremia in a normal person?

What Causes High Chloride in a Normal Person

In a normal person, hyperchloremia most commonly results from excessive administration of chloride-rich intravenous fluids (particularly 0.9% normal saline), gastrointestinal bicarbonate losses (especially diarrhea), and less commonly from renal tubular acidosis. 1

Iatrogenic and Fluid-Related Causes

The most frequent cause of hyperchloremia in hospitalized individuals is excessive administration of 0.9% normal saline, which contains supraphysiologic chloride concentrations (154 mEq/L) compared to plasma (approximately 100-106 mEq/L). 1, 2

Key iatrogenic sources include:

• Intravenous fluid resuscitation with normal saline, which delivers chloride loads that exceed the kidney's capacity to excrete excess chloride 1, 2
• Total parenteral nutrition solutions high in chloride content, particularly when sodium is provided predominantly as sodium chloride rather than balanced with sodium acetate or lactate 1
• Medication diluents that contribute cumulative chloride loads often going unrecognized until significant hyperchloremia develops 1, 2
• Cardiopulmonary bypass priming solutions using unbalanced crystalloids or colloids 1

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 Losses

Diarrhea is the primary gastrointestinal cause, resulting in bicarbonate loss in stool with compensatory chloride retention by the kidneys to maintain electroneutrality. 1, 3

Other gastrointestinal sources include:

• Intestinal fistulas and drainage tubes that cause bicarbonate-rich fluid losses with relative chloride retention 1
• Ileostomies with similar mechanisms of bicarbonate depletion 1

Pathophysiologic Mechanism

The Stewart physicochemical approach explains how hyperchloremia affects acid-base balance: an increase in plasma chloride relative to sodium decreases the strong ion difference (SID), which directly lowers pH and bicarbonate concentration, causing hyperchloremic metabolic acidosis. 1

Special Clinical Contexts

Diabetic ketoacidosis recovery: Patients are at particular risk due to excessive saline use for fluid replacement, as chloride from IV fluids replaces ketoanions lost during osmotic diuresis. 1

Premature infants: Those on parenteral nutrition are particularly vulnerable when receiving high chloride loads from amino acid solutions and sodium chloride. 1

Perioperative patients: Those undergoing major abdominal or pancreatic surgery with prolonged fluid therapy face increased risk. 1

Renal Causes (Less Common in "Normal" Persons)

While less likely in truly normal individuals, renal tubular acidosis can cause hyperchloremia through impaired renal acid excretion with compensatory chloride retention. 1, 3

Water Loss Exceeding Electrolyte Loss

Hyperchloremia can occur when water losses exceed sodium and chloride losses, leading to concentration of chloride in the remaining extracellular fluid. 4

Clinical Consequences

Hyperchloremia is not benign—it causes:

• Decreased renal blood flow and glomerular filtration rate, exacerbating sodium retention 1
• Reduced gastric blood flow and impaired gastric motility 1
• Splanchnic edema with increased abdominal pressure and delayed gastrointestinal recovery 1
• Increased risk of acute kidney injury in hospitalized patients 2, 5