Joseph Li, MD


July 15, 2003


My patient is a 74-year-old white woman who experienced recent atrial fibrillation with RVR that converted to normal sinus rhythm. She was found to have an elevated chloride level (85). Her blood urea nitrogen (BUN) was 41 and her basic metabolic profile was otherwise normal. Repeat testing 3 days later confirmed the high chloride level. What should be considered in the differential diagnosis?

Regina L. Harmon, DO


Joseph Li, MD

Chloride is one of several electrolytes essential to human life. The normal range varies from lab to lab. At my hospital laboratory, the normal range is 100-112 mEq/L. Assuming the value of "85" is in mEq/L, this would be a low, rather than high, value in most laboratories. Without knowing which lab you use and what units are attached to the figure, I will do my best to address your question of why a patient might have a "high" chloride in the setting of a BUN of 41 and an otherwise normal basic metabolic panel (or SMA-7). In most laboratories, a "normal" figure for BUN is less than 20. I will assume that the figure of "41" is an elevated figure for BUN.

The body excretes BUN via glomerular filtration in the kidneys. Changes in the BUN concentration can suggest a change in glomerular filtration rate (GFR; or plasma creatinine concentration). BUN is typically inversely related to the GFR but it is important to remember 2 exceptions to this[1]:


  • Urea production is variable; the BUN increases with a high-protein diet or increased tissue breakdown and vice versa.

  • Fifty percent of urea is reabsorbed, most of which occurs in the proximal tubule as urea follows sodium and water. In hypovolemic states, the increased absorption of BUN in the proximal tubule increases BUN at a rate disproportionate to changes in the GFR.


Among the differential diagnoses for an elevated BUN and normal serum creatinine in your patient, it is important to consider a gastrointestinal bleed (blood in the gut becomes a "high protein" diet) and a prerenal, hypovolemic state. The elevated BUN may be a clue to why the chloride level is elevated.

The body's pH normally remains steady, around 7.40. The lungs remove carbon dioxide (CO2) and the kidneys remove hydrogen (H+) to achieve this steady state. Acid-base disorders arise when the body is unable to make these adjustments. Abnormal chloride elevation is most commonly seen in forms of metabolic acidosis.[2] The anion gap calculation is useful to distinguish among the different causes of metabolic acidosis:


Anion gap = (Na) - (bicarbonate [HCO3] + chloride)



Normal anion gap = 6-12 mEq



Decreased anion gap < 6 mEq



Increased anion gap > 12 mEq


Either increased unmeasured cations or decreased unmeasured anions can decrease the anion gap.[2,3] The anion gap will decrease if the sodium concentration remains normal but the HCO3 and chloride concentrations increase. This occurs in the setting of decreased unmeasured anions. This most commonly occurs with low albumin levels. The anion gap decreases 2 mEq/L for each 1-g/dL decrease in serum albumin.

If your patient's anion gap is decreased and she is catabolic with a low serum albumin, this could be one reason why she might have an elevated BUN as well as an elevated chloride level. Alternatively, if the patient's anion gap is normal, renal tubular acidosis or gastrointestinal loss of HCO3 should be considered. In both disorders, low HCO3 is associated with elevated chloride levels.

In renal tubular acidosis (RTA), the kidney is either unable to generate sufficient HCO3 or is inappropriately absorbing too much HCO3.[2] There are 4 types of RTA:

Type I: classic distal renal tubular acidosis

Type II: proximal renal tubular acidosis

Type III: glomerular insufficiency renal tubular acidosis

Type IV: hyporeninemic hypoaldosterone renal tubular acidosis

Hypokalemia is seen in RTA Types I and II. Normokalemia is seen in Type III, and hyperkalemia in Type IV.

In the gastrointestinal tract, small bowel and pancreatic secretions contain significant amounts of HCO3. In the setting of diarrhea or pancreatitis, HCO3 secretion is accompanied by retention of chloride, resulting in hyperchloremia. Patients with ureterosigmoidostomies develop hyperchloremic metabolic acidosis for the same reason.

At this point in time, I have insufficient data to more accurately assess the cause of your patient's laboratory abnormalities, but it is my hope that this discussion will help elucidate the etiology.