Tuesday, January 10, 2017

Renal Grand Rounds - What Lurks in the Gap

I recently presented the case of a middle-aged man with a history of a remote Roux-en-Y gastric bypass, chronic diarrhea, and colon cancer on chemotherapy who initially presented with progressive fatigue and weakness in the setting of increased diarrhea. Shortly after admission he developed agitation that progressed to encephalopathy with dysarthria. His baseline labs from a month prior to presentation were notable for a chronically low serum bicarbonate of 15-17 with no anion gap. When he presented he was hypokalemic to 2.5 and his bicarbonate had dropped to 11 with a new elevated anion gap of 25 and normal L-lactate. Metabolic acidosis was confirmed on VBG. Interestingly, his urine electrolytes demonstrated a positive urine anion gap of 26.

He was ultimately diagnosed with D-lactic acidosis based on his clinical presentation which was confirmed with a serum D-lactate of 6.28. For the week prior to admission, he had been drinking 1.5 L of Gatorade (224 g of sugar!) daily to replace diarrhea losses.

This was a classic presentation of D-lactic acidosis in which overgrowth of gram positive anaerobes in the setting of short bowel syndrome is combined with a large carbohydrate load resulting in bacterial fermentation and D-lactate production.  He even had the classic neurologic findings!  His chronic non-gap acidosis likely represented chronic diarrhea and D-lactate production, and his rising anion gap when he presented was consistent with increased D-lactate production.

In D-lactic acidosis, the findings of hypokalemia and a positive urine anion gap can provide a helpful clue. With elevated serum D-lactate levels, the fractional excretion of D-lactate approaches 100%, i.e. everything that's filtered is excreted. This is because the stereospecificity of the sodium-L-lactate cotransporter in the proximal tubule results in poor reabsorption of D-lactate relative to L-lactate. The negatively charged D-lactate essentially drags positively charged sodium and potassium into the urine causing hypokalemia as well as a positive urine anion gap (Na + K - Cl) due to the increased urine sodium and potassium.

This patient did well after his Gatorade was cut off and he was treated with antibiotics to address gram positive anaerobic overgrowth.

Posted by Patrick Reeves

(Image taken from here - an educational blog for ED residents)


Anonymous said...

Interesting case. Can you please show us the urine electrolytes? Urine osmolar gap would be more helpful when you suspect high execration of negative anion in the urine.

Gearoid McMahon said...

We did not have a urinary osmolar gap. I do not have the numbers to hand but the urinary anion gap was strongly positive. Along with the low urine pH, this suggested the presence of an unmeasured anion in the urine. Agree that osmolar gap would add to this too as a confirmatory test but we felt it was not necessary given the low urine pH (which suggests that an RTA is not present).