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/

Tuesday, October 6, 2015

Third Nerve Palsy and ESBL Sepsis

Today's case centred around an elderly man with a number of comorbidities including coronary artery disease, congestive heart failure, diabetes mellitus, atrial fibrillation, peripheral vascular disease, and chronic kidney disease. He had a

history of infection with Extended Spectrum Beta-Lactamases (ESBL).  He was admitted with fever and altered mental status, which is a common reason for admission at our hospital.

We talked about a few different learning points:

-Cranial Nerve III palsies are a favourite question for internal medicine residents.  CN III controls all of the extraocular muscles except for the lateral rectus (CN VI) and the superior oblique muscle (CN IV).  A CN III palsy results in the affected eye being “down and out” due to the unopposed actions of the aforementioned two muscles.  The nerve also controls the levator palpebrae muscle (which keeps the eye open) and the parasympathetic pupillary fibres (which constrict the pupil).  The organization of the nerve is important: the parasympathetic fibres are around the outside, while the motor fibres run in the centre of the nerve.  Why is this important?  It gets to the two etiologies of CN III damage.  The more worrisome type is from compressive lesions (berry aneurysms, raised intracranial pressure, mass effect, tumours, hemorrhage, uncal herniation, etc).  Since these lesions mechanically compress CN III, they impair its pupillary and motor fibres resulting in a fixed, dilated pupil (“blown pupil”).  The other type of CN III palsy typically happens to diabetic patients, and is a microvascular infarction of part of the nerve (sort of like a stroke).  These lesions spare the pupil because the blood supply to the core of the nerve is more sensitive to vascular events.  The reason this is important, is treatment of a pupil-sparing CN III palsy is supportive (gets better in months) while treatment of a compressive CN III palsy involves emergent calling of a neurosurgeon!

-We talked about Extended Spectrum Beta-Lactamase organisms (ESBL).  I think it’s important to remember that in the early 20th century, penicillin was our only antibiotic and killed virtually all bacteria.  Now it is used rarely due to resistance patterns, mostly from overuse.  ESBL organisms produce beta-lactamases that are capable of neutralizing most penicillins and cephalosporins.  They come in two varieties: those that constitutively express ESBL’s and those that are inducible.  The reason inducible resistance is a problem, is that in vitro testing will make the organism appear susceptible.  The mnemonic people use for organisms with inducible resistance is SPICE (Serratia, Providencia, Indole-positive proteus (i.e. not mirabillis), Citrobacter, and Enterobacter).  Some people add Acinetobacter to this list, and some people use the P to remember Pseudomonas even though its resistance mechanism isn’t the same.  ESBLs are treated with carbopenems (meropenem, imipenem, and ertapenem) and sometimes ciprofloxacin or aminoglycosides (gentamicin, amikacin).  You may want to consider avoiding some antibiotics in SPICE organisms once you’ve identified them.
-We talked about an approach to altered mental status or delirium.  I can’t emphasize enough that the “DIMS” framework should be considered, if only briefly, in everyone.  This includes drug causes (withdrawal or adverse effect), infectious causes, metabolic causes, or structural causes (CNS lesions, bleeds, etc.).  In the patient discussed today, pyelonephritis or an ascending urinary tract infection was the most likely culprit of his delirium.

-We talk a lot about asymptomatic bactiuria.  We have all heard of patients put on antibiotics “just in case” who have suffered complications like C. difficile infection and even death.  In general, bactiuria should only be treated if it produces symptoms like dysuria, frequency, urgency, etc.  Fever is a sore point from a lot of ID physicians because it should be thoroughly investigated before being attributed to a cystitis.  The example from today’s Morning Report was turning the patient over to find a deep sacral ulcer.  The final point I’ll make here is that Foley catheterization and urinary bleeding can all alter the urine dipstick findings to the point that it’s uninterpretable.

Further Reading:

Paterson, D. L., & Bonomo, R. A. (2005). Extended-spectrum β-lactamases: a clinical update. Clinical microbiology reviews, 18(4), 657-686.

Nadeau, S. E., & Trobe, J. D. (1983). Pupil sparing in oculomotor palsy: a brief review. Annals of neurology, 13(2), 143-148.