Tuesday, October 20, 2015

Chronic Diarrhea and Metabolic Acidosis

Today's case involved an elderly woman with end-stage renal disease on intermittent hemodialysis who had presented with chronic (2 months) diarrhea.

She had been admitted previously with a diagnosis of gastroenteritis and subsequently discharged.  On presentation to the ED, she was significantly hypovolemic and had a blood pressure in the 80’s/50’s.  She was volume-resuscitated at which point further history was obtained.  She had not had infectious symptoms, sick contacts, recent antibiotics, or changes in her food/eating habits.  She had attempted a lactose-elimination diet to no avail.  The diarrhea was non-bloody and contained some mucous.  Her initial laboratory investigations revealed a mild lactic acidosis, a significantly elevated plasma anion gap, and a negative C. difficile toxin test.  Initial abdominal imaging with a plain X-ray revealed no free air or “thumbprinting” and a CT abdomen with contrast showed some fluid in the bowels but no significantly localizing problems.  She is currently being slated for endoscopic bowel investigation.  The leading hypotheses are either microscopic colitis or ischemic colitis.

There were multiple learning points:

-Like everything in medicine, there are categorizations of diarrheal illness.  Acute diarrhea (many would define as less than 2-4 weeks in duration) is generally infectious and therefore bacterial, viral, and parasitic pathogens need to be considered and ruled out.  Chronic diarrhea typically has a more interesting differential diagnosis.  One has to consider functional causes like irritable bowel syndrome as a diagnosis of exclusion.  Inflammatory disorders like Crohn disease and ulcerative colitis are commonly thought to occur in people aged 15-40, but certainly can occur in a second bimodal peak in people aged 50-80.  Microscopic colitis typically occurs in elderly and middle-aged individuals and characteristically has a normal-appearing bowel mucosa – two types (lymphocytic and collagenous colitis) have been identified; they are distinguished from other causes based on biopsy results.  Malabsorption of certain nutrients can also lead to diarrhea – conditions associated include chronic pancreatitis, celiac disease, lactose intolerance, and small-bowel intestinal overgrowth (often in association with anatomical/surgical changes to the bowel).  Finally, chronic infections should be considered – these include Candida species, C. difficile, Giardia, amobae, cryptosporidium, and Whipple disease.

-Testing stool is something that can aid in the diagnosis.  Stool can first be categorized as watery, inflammatory, and fatty.  The fatty stool is typically associated with some type of malabsorption, while the inflammatory diarrhea (containing strands of blood and mucous) can be associated with an inflammatory or infectious process.  Watery diarrhea is further subdivided into secretory and osmotic and the two can be distinguished based on the osmotic gap (typically greater than 125 in secretory diarrhea).  Secretory diarrheas characteristically continue despite fasting and can be associated with certain chronic infections, as well as hormonal mediators of secretion (Zollinger-Ellison syndrome, carcinoid syndrome, etc.).  Osmotic diarrhea is typically the result of an osmotic agent like sorbitol, so further testing is probably not necessary.

--The patient was found to have an anion gap metabolic acidosis.  We discussed the differential diagnosis for this.  While commonly-used acronyms like MUDPILES are routinely taught in medical school, paraldehyde is so rarely used as a drug that I don’t think it deserves its own place in limited memory-spans.  Instead, it is helpful to think of things that cause an elevated anion gap and possible mechanisms that those could be produced:
                  -Lactic acid – shock, hypoperfusion, metformin
                  -Ketoacids (note that ketones themselves are not acidic but betahydroxybutyrate and acetoacetic acid are) – Diabetic Ketoacidosis, Alcoholic ketoacidosis, Starvation Ketoacidosis
                  -Renal failure – leads to buildup of inorganic acids like sulphates
                  -Toxins – salicylates, toxic alcohols (methanol, ethylene glycol), note that ethanol does not produce an acidosis directly but can produce alcoholic ketoacidosis as mentioned above through other hepatic mechanisms

Further Reading:

Camilleri, M. (2004). Chronic diarrhea: a review on pathophysiology and management for the clinical gastroenterologist. Clinical Gastroenterology and Hepatology, 2(3), 198-206.

Image Credit: https://sites.google.com/site/gracemedicalschool/2.1.3.10intestinalinflammation


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