Could constipation contribute to hyperkalemia in my patient with chronic kidney disease?

Yes! Constipation may be an important contributor to hyperkalemia in some patients with chronic kidney disease (CKD).

 Under normal conditions, 80-90% of excess dietary potassium (K+) is excreted by the kidneys, with the remainder excreted through the GI tract.1 However, in advanced CKD, particularly in the setting of end-stage kidney disease (ESKD), the GI tract assumes a much more important role in maintaining K+ balance. 

As early as 1960’s, the daily fecal excretion of K+ was found to be directly related to the wet stool weight, irrespective of creatinine clearance. Furthermore, K+ excretion in stool was as high as ~80% of dietary intake (average 37%) in some hemodialysis (HD) patients compared to normal controls (average 12%). 2

Such increase in K+ excretion in the GI tract of patients with CKD was later found to be primarily the result of K+ secretion into the colon/rectum rather than reduced dietary K+ absorption in the small intestine 1,3, was inversely related to residual kidney function, and as a consequence could serve as the main route of K+ excretion in patients with ESKD. 4

Collectively, these findings suggest that in addition to non-dietary factors such as medications, we may need to routinely consider constipation as a potential cause of hyperkalemia in patients with advanced CKD or ESKD. 1

Bonus Pearl: Did you know that secretion of K+ by the apical surface of colonic epithelial is mediated in part by aldosterone-dependent mechanisms? 5

References

  1. St-Jules DE, Goldfarb DS, Sevick MA. Nutrient non-equivalence: does restricting high-potassium plant foods help to prevent hyperkalemia in hemodialysis patients? J Ren. Nutr 2016;26: 282-87. https://www.ncbi.nlm.nih.gov/pubmed/26975777
  2. Hayes CP, McLeod ME, Robinson RR. An extrarenal mechanism for the maintenance of potassium balance in severe chronic renal failure. Trans Assoc Am Physicians 1967;80:207-16.
  3. Martin RS, Panese S, Virginillo M, et al. Increased secretion of potassium in the rectum of humans with chronic renal failure. Am J Kidney Dis 1986;8:105-10. https://www.ncbi.nlm.nih.gov/pubmed/3740056
  4. Cupisti A, Kovesdy CP, D’Alessandro C, et al. Dietary approach to recurrent or chronic hyperkalemia in patients with decreased kidney function. Nutrients 2018, 10, 261;doi:10.3390/nu10030261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872679/
  5. Battle D, Boobes K, Manjee KG. The colon as the potassium target: entering the colonic age of hyperkalemia treatment. EBioMedicine 2015;2: 1562-1563. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740340/pdf/main.pdf

 

Contributed in part by Alex Blair, MD, Mass General Hospital, Boston, MA.

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Could constipation contribute to hyperkalemia in my patient with chronic kidney disease?

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?

Although a characteristic clinical history and biochemical pattern of liver injury can strongly suggest the diagnosis of alcoholic hepatitis (AH), a definitive diagnosis is confirmed with liver biopsy only. In fact, in 30% of patients clinically diagnosed as having AH, a liver biopsy may lead to an alternative diagnosis.1Understandably, many physicians are reluctant to proceed with biopsy in this fragile patient population given the associated risks, notably bleeding. For this reason, most patients with AH are clinically diagnosed without a liver biopsy. However, there are certain instances in which a biopsy can be helpful, including when:2

  • Diagnosis of AH is in doubt
  • Suspicion for another disease process that may be contributing in parallel to AH is high
  • Obtaining prognostic data or identification of advanced hepatic fibrosis or cirrhosis in AH is desired

Thus, liver biopsy findings may influence short- and long-term management in AH. For these reasons, the European Association for the Study of the Liver recommends consideration of a liver biopsy in patients with AH.3 To minimize the bleeding risk, the transjugular approach is preferred.

References

  1. Mookerjee RP, Lackner C, Stauber R, et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 2011; 55:1103-1111 Link
  2. Altamirano J, Miquel R, Katoonizadeh A, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014;146: 1231-1239. PDF
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399-420. PDF

Contributed by Jay Luther, MD, Gastrointestinal Unit, Mass General Hospital, Boston, MA.

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?

Is it possible to have acute pancreatitis with normal serum lipase?

Yes! Although an elevated serum lipase has a negative predictive value of 94%-100% for acute pancreatitis (1), there are ample reports in the literature of patients with CT findings of pancreatitis in the presence of abdominal symptoms but with normal serum lipase and/or amylase (2,3).

A case series and review of literature of acute pancreatitis with normal lipase and amylase failed to reveal any specific risk factors for such observation (2). More specifically, the etiologies of acute pancreatitis in the reported cases have varied, including drug-induced, cholelithiasis, alcohol, hypertriglyceridemia, and postoperative causes.

But what accounts for this phenomenon? Many cases have been associated with the first bout of pancreatitis without evidence of pancreatic calcifications which makes the possibility of a “burned-out” pancreas without sufficient acinar cells to release lipase as a frequent cause unlikely. Other potential explanations for normal lipase in acute pancreatitis have included measurement of serum lipase at a very early phase of the disease before significant destruction of acinar cells has occurred (increases in 3-6 h, peaks at 24 h [4]) and more rapid renal clearance of serum lipase due to tubular dysfunction (2).

Of note, unlike amylase, lipase is totally reabsorbed by renal tubules under normal conditions (5). Thus, it’s conceivable that even a reversible tubular dysfunction may lead to increased clearance of serum lipase and potentially lower its levels.
References
1. Ko K, Tello LC, Salt J. Acute pancreatitis with normal amylase and lipase. The Medicine Forum. 2011;11 Article 4. https://jdc.jefferson.edu/tmf/vol11/iss1/4/
2. Singh A, Shrestha M. Acute pancreatitis with normal amylase and lipase-an ED dilemma. Am J Emerg Med 2016;940.e5-940.e7. https://www.ncbi.nlm.nih.gov/pubmed/26521195
3. Limon O, Sahin E, Kantar FU, et al. A rare entity in ED: normal lipase level in acute pancreatitis. Turk J Emerg Med 2016;16:32-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882216/
4. Shah AM, Eddi R, Kothari ST, et al. Acute pancreatitis with normal serum lipase: a case series. J Pancreas (Online) 2010 July 5;11:369-72. PDF
5. Lott JA, Lu CJ. Lipase isoforms and amylase isoenzymes: assays and application in the diagnosis of acute pancreatitis. Clin Chem 1991;37:361-68. https://www.ncbi.nlm.nih.gov/pubmed/1706232
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Is it possible to have acute pancreatitis with normal serum lipase?

Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Although there are many potential sources for Klebsiella sp. bacteremia, C. difficile infection (CDI) itself may be associated with GI translocation of enteric organisms.

A retrospective study of over 1300 patients found an incidence of 1.8% for CDI-associated bacteremia. E. coli, Klebsiella sp. , or Enterococcus sp. accounted for 72% of cases. History of malignancy, neutropenia (at the time of CDAD), and younger age (mean 59 y) were among the risk factors.1 Another study reported over 20 cases of bacteremia caused by C. difficile plus other bacteria often of enteric origin such the aforementioned organisms, Bacteroides sp, Candida sp, and Enterobacter sp.2

CDI is thought to predispose to bacterial translocation through the GI tract by alteration of mucosal indigenous microflora, overgrowth of certain pathogens, and presence of inflammation in the mucosa.3 Interestingly, C. difficile toxin A or B may play an active role in the bacterial adherence and penetration of the intestinal epithelial barrier.4  

Bonus pearl: Did you know that C. difficile may be found in the normal intestinal flora of 3% of healthy adults, 15-30% of hospitalized patients, and up to 50% of neonates? Why neonates seem immune to CDI is another fascinating story!

 

References

  1. Censullo A, Grein J, Madhusudhan M, et al. Bacteremia associated with Clostridium difficile colitis: incidence, risk factors, and outcomes. Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 943, https://doi.org/10.1093/ofid/ofv133.659 https://academic.oup.com/ofid/article/2/suppl_1/943/2635179
  2. Kazanji N, Gjeorgjievski M, Yadav S, et al. Monomicrobial vs polymicrobial Clostridum difficile bacteremia: A case report and review of the literature. Am J Med 2015;128:e19-e26. https://www.amjmed.com/article/S0002-9343(15)00458-1/abstract
  3. Naaber P, Mikelsaar RH, Salminen S, et al. Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection. J Med Microbiol 1998; 47: 591-8. https://www.ncbi.nlm.nih.gov/pubmed/9839563 
  4. Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium. Arch Surg 1999;134: 1235-1242. https://jamanetwork.com/journals/jamasurgery/fullarticle/390434
Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

How much blood is needed in the GI tract to cause melena?

Melena, characterized by black tarry stools, can occur with as little as 50 cc of blood in the stomach. How do we know this? We need to go back to clinical experiments involving oral administration of citrated blood in human subjects back in 1930’s and 40’s. 1-3 One study was performed on a group of “healthy medical students” who drank their own blood!3

Melena suggests an upper GI bleeding source where there is more time for enzymatic breakdown to transform blood to melena. Although gastric acid may also contribute to its formation, it does not appear to be a pre-requisite to melena as blood inserted into the small bowel or cecum can also produce melenic stools if it stays there long enough. Melena is dependent primarily on the length of transit time of blood in the GI tract, such that very rapid movement of 1 liter of blood from upper GI tract may lead to bright red blood per rectum, not melena, within 4 hours.2,4

Don’t get melena confused with other causes of dark stools such as oral iron supplementation and bismuth-containing medications (eg, Peptobismol®). In addition to its tarry texture, melena also has a characteristic pungent odor.

References

  1. Schiff L, Stevens R, Shaprio N, et al. Observations on the oral administration of citrated blood in man. Am J Med Sci 1942;203:409-12.
  2. Srygley FD, Gerardo CJ, Tran T, et al. Does this patient have a severe upper gastrointestinal bleed. JAMA 2012;307:1072-79. https://jamanetwork.com/journals/jama/article-abstract/1105075?redirect=true
  3. Daniel WA, Egan S. The quantity of blood required to produce a tarry stool. JAMA 1939;113:2232.
  4. Wilson ID. Hematemesis, melena, and hematochezia. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths:1990. Chapter 85. Available from: https://www.ncbi.nlm.nih.gov/books/NBK411/

 

Contributed in part by Brad Lander, MD, Mass General Hospital, Boston, MA.

How much blood is needed in the GI tract to cause melena?

Can Salmonella enterocolitis predispose to inflammatory bowel disease?

Yes, enteric pathogens such as Salmonella can predispose patients to inflammatory bowel disease (IBD) through several potential mechanisms: 1

  • Causing permanent changes in the intestinal microbiota
  • Altering the epithelial barrier in the gut
  • Altering the interaction between the body’s immune system and the intestines

More specifically, Salmonella utilizes oxidized endogenous sulfur compounds released during acute intestinal inflammation to outgrow the fermentative microbiota of the colon.2  In addition, the neutrophil response to Salmonella infection can alter the constituent microbiome.3 Salmonella also modifies the tight junctions in the intestinal epithelium as it invades, thus activating the immune system (particularly toll-like-receptors), and creating a pro-inflammatory state with structural loss of the intestinal mucosa. 4 Lastly, Salmonella promotes cytokine release and neutrophil migration through pathogen recognition receptors, leaving the intestine in a pro-inflammatory state even following resolution of the infection. 1

Keep in mind that initial Salmonella infection may also mimic IBD, as it causes diffuse lesions in the colon similar to ulcerative colitis, and may cause ileitis in some patients. Stool cultures and biopsies of the colonic mucosa should help differentiate IBD from Salmonella infection. 5

 

References

  1. Schultz BM, Paduro CA, Salazar GA, et al. A potential role of Salmonella infection in the onset of inflammatory bowel diseases. Front Immunol 2017;8:191. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329042/pdf/fimmu-08-00191.pdf
  2. Winter SE, Baumler AJ. A breathtaking feat: to compete with the gut microbiota, Salmonella drives its host to provide a respiratory electron acceptor. Gut Microbes 2011;2:58-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225798/pdf/gmic0201_0058.pdf
  3. Gill N, Ferreira RB, Antunes LC, et al. Neutrophil elastase alters the murine gut microbiota resulting in enhanced Salmonella colonization. PLoS ONE 2012;7:e49646. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049646
  4. Bueno SM, Riquelme S, Riedel CA, et al. Mechanisms used by virulent Salmonella to impair dendritic cell function and evade adaptive immunity. Immunology 2012;137:28-36. https://www.ncbi.nlm.nih.gov/pubmed/22703384
  5. De Hertogh G, Geboes K. Crohn’s disease and infections: a complex relationship. MedGenMed 2004;6:14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1435589

 

 

 

 

 

 

Contributed by Yasmin Islam MD, Mass General Hospital, Boston, MA.

Can Salmonella enterocolitis predispose to inflammatory bowel disease?

My patient with ulcerative colitis has had colectomy. Can she still get C. difficile infection?

Yes! Although a common cause of colitis, an increasing number of reports in the literature suggest C. difficile can cause enteritis as well.Antibiotic use is a major risk factor in most reports, with nearly one-half of the cases reported in patients with inflammatory bowel disease, many post-colectomy. 1-3

Mortality of C. difficile enteritis based on the first 83 cases in the literature appears to be 23%,1 but as high as 60%-83% depending on the report!2 Its diagnosis post-colectomy requires a high index of suspicion, as patients may not complain of “diarrhea” with chronically loose stools in the ileostomy bag.  Be particularly on the lookout for C. difficile enteritis in these patients when there is increased stool output, fever, hypotension, and/or leukocytosis2, and when in doubt, send a stool specimen from the ileostomy bag for C. difficile testing.

Although the pathophysiology of C. difficile enteritis is not fully understood, few observations are particularly intriguing: 

  • Small bowel mucosa may be colonized by C. difficile in about 3% of the population, potentially serving as a reservoir.2
  • Patients with ileostomy may develop a metaplasia of the terminal end mimicking colonic environment.4  
  • Exposure of rabbit ileum to C. difficile toxin A also causes significant epithelial necrosis with destruction of villi and neutrophil infiltration.5

 

References

  1. Dineen SP, Bailey SH, Pham TH, et al. Clostridium difficile enteritis: a report of two cases and systematic literature review. World J Gastrointest Surg 2013;5:37-42. https://www.wjgnet.com/1948-9366/full/v5/i3/37.htm
  2. Boland E, Thompson JS. Fulminant Clostridium difficile enteritis after proctocolectomy and ileal pouch-anal anastomosis. Gastroenterology Research and Practice 2008; 2008: Article ID 985658. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633454/pdf/GRP2008-985658.pdf
  3. Freiler JF, Durning SJ, Ender PT. Clostridium difficile small bowel enteritis occurring after total colectomy. Clin Infect Dis 2001;33:1429-31. https://pdfs.semanticscholar.org/333b/d84978cfc4ac8fd21a15bc8fd26ff3160387.pdf
  4. Apel R, Cohen Z, Andrews CW, et al. Prospective evaluation of early morphological changes in pelvic ileal pouches. Gastroenterology 1994;107:435-43. http://www.gastrojournal.org/article/0016-5085(94)90169-4/pdf
  5. Triadafilopoulos G, Pothoulakis C, Obrien MJ, et al. Differential effects of Clostridium difficile toxins A and B on rabbit ileum. Gastroenterology 1987;93:273-279. https://www.ncbi.nlm.nih.gov/pubmed/3596162
My patient with ulcerative colitis has had colectomy. Can she still get C. difficile infection?