Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

Short answer: Yes! Although we usually associate acute acalculous cholecystitis (AAC) with critically ill patients (eg, with sepsis, trauma, shock, major burns) in ICUs, AAC is not as rare as we might think in ambulatory patients. In fact, a 7 year study of AAC involving multiple centers reported that AAC among outpatients was increasing in prevalence and accounted for 77% of all cases (1)!

 
Although the pathophysiology of ACC is not fully understood, bile stasis and ischemia of the gallbladder either due to microvascular or macrovascular pathology have been implicated as potential causes (2). One study found that 72% of outpatients who developed ACC had atherosclerotic disease associated with hypertension, coronary, peripheral or cerebral vascular disease, diabetes or congestive heart failure (1). Interestingly, in contrast to calculous cholecystitis, “multiple arterial occlusions” have been observed on pathological examination of the gallbladder in at least some patients with ACC and accordingly a name change to “acute ischemic cholecystitis” has been proposed (3).

 
AAC can also complicate acute mesenteric ischemia and may herald critical ischemia and mesenteric infarction (3). The fact that cystic artery is a terminal branch artery probably doesn’t help and leaves the gallbladder more vulnerable to ischemia when arterial blood flow is compromised irrespective of the cause (4).

 
Of course, besides vascular ischemia there are numerous other causes of ACC, including infectious (eg, viral hepatitis, cytomegalovirus, Epstein-Barr virus, Salmonella, brucellosis, malaria, Rickettsia and enteroviruses), as well as many non-infectious causes such as vasculitides and, more recently, check-point inhibitor toxicity (1,5-8).

 
Bonus Pearl: Did you know that in contrast to cholecystitis associated with gallstones (where females and 4th and 5th decade age groups predominate), ACC in ambulatory patients is generally more common among males and older age groups (mean age 65 y) (1)?

 

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References
1. Savoca PE, Longo WE, Zucker KA, et al. The increasing prevalence of acalculous cholecystitis in outpatients: Result of a 7-year study. Ann Surg 1990;211: 433-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358029/pdf/annsurg00170-0061.pdf
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22. https://www.cghjournal.org/article/S1542-3565(09)00880-5/pdf
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52. https://bjssjournals.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2168.1997.02775.x?sid=nlm%3Apubmed
4. Melo R, Pedro LM, Silvestre L, et al. Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. Int J Surg Case Rep 2016;25:207-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941110/
5. Aguilera-Alonso D, Median EVL, Del Rosal T, et al. Acalculous cholecystitis in a pediatric patient with Plasmodium falciparum infection: A case report and literature review. Ped Infect Dis J 2018;37: e43-e45. https://journals.lww.com/pidj/pages/articleviewer.aspx?year=2018&issue=02000&article=00020&type=Fulltext  
6. Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis 2013;Article ID 407182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784234/pdf/CRIM.ID2013-407182.pdf
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12. https://casereports.bmj.com/content/12/4/e228306
8. Abu-Sbeih H, Tran CN, Ge PS, et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J ImmunoTherapy of Cancer 2019;7:118. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0604-2

 

 

Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

My elderly patient with abdominal pain has a negative Murphy’s sign on physical exam. How accurate is Murphy’s sign in diagnosing cholecystitis?

Not as accurate as we might like! In fact, no single clinical finding has been found to carry sufficient weight in ruling in or excluding cholecystitis and Murphy’s sign (inability to take a deep breath due to pain upon palpation of the right upper quadrant) is no exception. 1

A meta-analysis of patients with Murphy’s sign reported a sensitivity of 65% and a specificity of 87% (positive LR 2.8, negative LR 0.4, with 95% C.I. including 1.0 in both). 1,2  However, among the elderly (mean age 79 y), the sensitivity may be a slow as 48% 2 and in patients with gangrenous cholecystitis as low as 33%.3  

In contrast, Murphy’ s sign elicited at the time of ultrasound of the gallbladder (ie,“sonographic Murphy’s) is generally thought to very sensitive  (>90%) for acute cholecystitis;3,4 1 study reported a sensitivity of 63%, however (specificity 94%).5  Remember that altered mental status may also mask sonographic Murphy’s sign. 

Indirect fist percussion of the liver has been suggested by some authors as a more sensitive alternative to Murphy’s sign (100% vs 80%) in a small series of patients with cholecystitis.2

Bonus pearl: Did you know that another technique originally described by the famed American surgeon, John Murphy, to diagnose acute cholecystitis consisted of the “hammer stroke maneuver” in which percussion of the right midsubcostal region with the bent middle finger of the left hand was performed using the right hand to strike the dorsum of the left hand with hammer-like blows? 6

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References

  1. Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient have acute cholecystitis. JAMA 2003;289:80-86. https://jamanetwork.com/journals/jama/article-abstract/195707
  2. Ueda T, Ishida E. Indirect fist percussion of the liver is a more sensitive technique for detecting hepatobiliary infections than Murphy’s sign. Current Gerontol Geriat Res, Volume 2015, Article ID 431638. https://www.hindawi.com/journals/cggr/2015/431638/
  3. Simeone JF, Brink JA, Mueller PR, et al. The sonographic diagnosis of acute gangrenous cholecystitis. The importance of the Murphy sign. AJR 1989;152:289-90. https://www.ncbi.nlm.nih.gov/pubmed/2643262
  4. O’Connor OJ, Maher MM. Imaging of cholecystitis. AJR 2011;196:W36774. https://www.ajronline.org/doi/full/10.2214/AJR.10.4340
  5. Rallis PW, Lapin SA, Quinn MF, et al. Prospective evaluation of the sonographic Murphy sign in suspected acute cholecystitis. J Clin Ultrasound 1982;10:113-5. https://www.ncbi.nlm.nih.gov/pubmed/6804512
  6. Salati SA, al Kadi A. Murphy’s sign of cholecystitis-a brief revisit. Journal of Signs and Symptoms 2012;1:53-6. https://www.researchgate.net/publication/230820198_Murphy’s_sign_of_cholecystitis-_a_brief_revisit

 

 

My elderly patient with abdominal pain has a negative Murphy’s sign on physical exam. How accurate is Murphy’s sign in diagnosing cholecystitis?

My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

An increased risk of new gallstones following gastric bypass surgery (GBS) has been reported by several studies (1-5).  More specifically, a study involving patients with baseline normal gallbladder ultrasound found that at 6 months following GBS 36% of patients developed gallstones and 13% developed sludge (4).  Similarly, a gallstone formation rate of 32% has been reported after GBS among patients who did not receive prophylactic treatment (5). 

New cholelithiasis following GBS may be largely attributed to rapid weight loss following this procedure, not the surgery itself or its related anatomical changes. Of interest, rapid weight loss, even by dieting, has been shown to increase the risk of gallstones (6).

However, overweight patients also have an increased risk of developing cholelithiasis at baseline, in part related to increased cholesterol secretion resulting in bile supersaturation with cholesterol (1).  Though weight loss may be expected to decrease this risk, rapid weight loss is thought to change the bile composition towards higher concentrations of calcium and cholesterol and increased production of gallbladder mucin, contributing to the pathogenicity of gallstone formation (5). 

In light of these findings, some have recommended routine prophylactic cholecystectomy as part of the GBS (7,8),  while others have argued against it (9,10), largely due to different observed rates of post-GBS symptomatic gallstones requiring cholecystectomies in various studies. Of note, post-operative ursodiol (ursodeoxycholic acid) may also reduce the incidence of post-GBS cholelithiasis (5,11). 
References

1. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med 1993;119(10):1029–35. https://www.ncbi.nlm.nih.gov/pubmed/8214980
2. Wudel LJ, Wright JK, Debelak JP, Allos TM, Shyr Y, Chapman WC. Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: Results of a randomized controlled pilot study. J Surg Res 2002;102(1):50–6. https://www.ncbi.nlm.nih.gov/pubmed/11792152
3. Manatsathit W, Leelasincharoen P, Al-Hamid H, Szpunar S, Hawasli A. The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study. Int J Surg [Internet] 2016;30:13–8. Available from: http://dx.doi.org/10.1016/j.ijsu.2016.03.060 https://www.ncbi.nlm.nih.gov/pubmed/27063855
4. Shiffman M, Sugerman H, Kellum J, Brewer W, Moore E. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991;(86):1000–5. https://www.ncbi.nlm.nih.gov/pubmed/1858735
5. Sugerman H, Brewer W, Shiffman M, et al. A Multicenter, Placebo-Controlled, Randomized, Double-Blind, Prospective Trial of Prophylactic Ursodiol for the Prevention of Gallstone Formation Rapid Weight Loss. Am Jourmal Surg 1995;169(January):91–7. https://www.ncbi.nlm.nih.gov/pubmed/7818005

6. de Oliverira CIB, Chaim EA, da Silva BB. Impact of rapid weight reduction on risk of cholelithiasis after bariatric surgery. Obesity Surgery 2003;13:625-8.
7. Tarantino I, Warschkow R, Steffen T, Bisang P, Schultes B, Thurnheer M. Is routine cholecystectomy justified in severely obese patients undergoing a laparoscopic Roux-en-Y gastric bypass procedure? A comparative cohort study. Obes Surg 2011;21(12):1870–8. https://reference.medscape.com/medline/abstract/21863228
8. Amstutz S, Michel JM, Kopp S, Egger B. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg 2015;25(11):2054–60. https://link.springer.com/article/10.1007%2Fs11695-015-1650-6
9. Karadeniz M, Gorgun M, Kara C. The evaluation of gallstone formation in patients undergoing Roux-en -Y gastric bypass due to morbid obesity. Turkish J Surg 2014;30(2):76–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379817/
10. D’Hondt M, Sergeant G, Deylgat B, Devriendt D, Van Rooy F, Vansteenkiste F. Prophylactic Cholecystectomy, a Mandatory Step in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass? J Gastrointest Surg 2011;15(9):1532–6. https://www.ncbi.nlm.nih.gov/pubmed/21751078
11. Miller K, Hell E, Lang B, Lengauer E. Gallstone Formation Prophylaxis after Gastric Restrictive Procedures for Weight Loss: A Randomized Double-Blind Placebo-Controlled Trial. Ann Surg 2003;238(5):697–702. https://www.ncbi.nlm.nih.gov/pubmed/14578732

Contributed by Kim Schaefer, Harvard medical student, Boston, MA. 

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My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

Is my hospitalized patient with possible pneumonia at risk of Clostridium difficile-associated disease after only 1-3 days of empiric antibiotic therapy?

Yes! Even relatively brief duration of antibiotic therapy may increase the risk of Clostridium difficile-associated disease (CDAD) in a susceptible host.
In a study of hospitalized patients with new-onset diarrhea, prior exposure to levofloxacin and cefazolin was significantly associated with CDAD with the median duration of therapy for levofloxacin of 3 days (range 1-18 days), and for cefazolin 2 days (range 1-3 days) (1). Similarly, a study in hospitalized patients during a CDAD epidemic found a significantly increased risk of CDAD among patients who received fluoroquinolones for only 1-3 days (hazard ratio 2.4) with a 95% confidence interval (1.6-3.6) that overlapped 4-6 days and ≥ 7 days treatment groups (2). Yet another study found no significant difference in the risk of CDAD between those on antibiotic for < 4 days vs 4-7 days of antibiotics (3). CDAD following a single dose of cefazolin has also been reported (4).
Of interest, laboratory studies in mice have shown a profound alteration of intestinal microbiota following a single dose of clindamycin, resulting in increased susceptibility to C. difficile colitis (5).
So although duration of antibiotic therapy is an important factor in CDAD (3, 6) and we should minimize the duration of antibiotic therapy whenever possible, not starting antibiotics in the absence of clear indication is even better!

References
1. Manian FA, Aradhyula S, Greisnauer S, et al. Is it Clostridium difficile infection or something else? A case-control study of 352 hospitalized patients with new-onset diarrhea. S Med J 2007;100:782-786. https://www.ncbi.nlm.nih.gov/pubmed/17713303
2. Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254-60. https://www.ncbi.nlm.nih.gov/pubmed/16206099
3. Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011;53:42-48. https://www.ncbi.nlm.nih.gov/pubmed/21653301
4. Mcneeley SG, Anderson GD, Sibai BM. Clostridium difficile colitis associated with single dose cefazolin prophylaxis. Ob Gynecol 1985;66:737-8. https://www.ncbi.nlm.nih.gov/pubmed/4058831
5. Buffie CG, Jarchum I, Equinda M, et al. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect Immun 2011;80: 62-73. https://www.ncbi.nlm.nih.gov/pubmed/22006564
6. Chalmers JD, Akram AR, Sinanayagam A, et al. Risk factors for Clostridium difficile infection in hospitalized patients with community-acquired pneumonia. J Infect 2016;73:45-53. https://www.ncbi.nlm.nih.gov/pubmed/27105657

Disclosure: The contributor of this post was a coinvestigator of a cited study (ref. 1).

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Is my hospitalized patient with possible pneumonia at risk of Clostridium difficile-associated disease after only 1-3 days of empiric antibiotic therapy?

My patient with cirrhosis now has an upper gastrointestinal bleed (UGIB) with hepatic encephalopathy (HE). What’s the connection between UGIB and HE?

Hepatic encephalopathy (HE) may be precipitated by a variety of factors including infection, hypovolemia, electrolyte imbalance (eg, hyponatremia, hypokalemia), metabolic alkalosis, sedatives, and of course UGIB. 1-3

Ammonia is often considered to play a central role in the the pathogenesis of HE, particularly when associated with UGIB. The ammoniagenic potential of UGIB is primarily attributed to the presence of hemoglobin protein in the intestinal tract. One-half of the ammoniagenesis originates from amino acid metabolism (mainly glutamine) in the mucosa of the small bowel, while the other half is due to the splitting of urea by the resident bacteria in the colon (eg, Proteus spp., Enterobacteriaceae, and anerobes).1,2

A large protein load in the GI tract, as occurs in UGIB, may result in hyperammonemia in patients with cirrhosis due to the limited capacity of the liver to convert ammonia to urea through the urea cycle as well as by the shunting of blood around hepatic sinusoids. Recent studies, however, also implicate the kidneys as an important source of ammonia in this setting, further compounding HE.3

It’s important to stress that ammonia is not likely to be the only mediator of HE. Enhanced production of cytokines due to infection or other inflammatory states, neurosteroids, endogenous benzodiazepines, and other bacterial byproducts may also play an important role in precipitating HE.2,4-6  So stay tuned!

Bonus pearl: Did you know that proinflammatory cytokines tumor necrosis factor-alpha and inerleukin-6 increase ammonia permeability across central nervous system-derived endothelial cells? 7

 

References

  1. Olde Damink SWM, Jalan R, Deutz NEP, et al. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. Hepatology 2003;37:1277-85.
  2. Frederick RT. Current concepts in the pathophysiology and management of hepatic encephalopathy. Gastroenterol Hepatol 2011;7:222-233.
  3. Tapper EB, Jiang ZG, Patwardhan VR. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy. Mayo Clin Proc 2015;90:646-58.
  4. Shawcross DL, Davies NA, Williams R, et al. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 2004;40:247-254.
  5. Shawcross DL, Sharifi Y, Canavan JB, et al. Infection and systemic inflammation, not ammonia, are associated with grade ¾ hepatic encephalopathy, but not mortality in controls. J Hepatol 2011;54:640-49.
  6. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation.Cell Mol Life Sci 2005;62:2295-2304.
  7. Duchini A, Govindarajan S, Santucci M, et al. Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J Investig Med 1996;44:474-82.

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My patient with cirrhosis now has an upper gastrointestinal bleed (UGIB) with hepatic encephalopathy (HE). What’s the connection between UGIB and HE?

Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

There are at least 2 reasons for considering pneumococcal vaccination in hospitalized patients with ulcerative colitis flare.

First, these patients are often on immunosuppressants (eg, glucocorticoids) or biological agents (eg, infliximab) that qualifies them for both 13-valent conjugate (PCV13) and 23-valent polysaccharide (PPSV23) pneumococcal vaccines under the Advisory Committee on Immunization Practices (ACIP) Guidelines’ “Immunocompromised persons” risk group.1-4

Another reason is the possibility of  UC patients having coexisting hyposplenism, a major risk factor for pneumococcal disease. Although this association has been described several times in the literature since 1970s, it is relatively less well known.  In a study of patients with UC, hyposplenism (either by the presence of Howell-Jolly bodies in the peripheral blood smear or prolongation of clearance from blood of injected radioactively labelled heat-damaged red blood cells) was found in over one-third with some developing life-threatening septicemia in the early postcolectomy period.5

Another study found the majority of patients with UC having slow clearance of heat damaged RBCs despite absence of Howell-Jolly bodies in the peripheral smear.6 Fulminant and fatal pneumococcal sepsis has also been reported in patients with UC.7

Although the immunological response to pneumococcal vaccination may be lower among immunosuppressed patients in general, including those with UC, it should still be administered to this population given its potential benefit in reducing the risk of serious pneumococcal disease. 2,3  

References

  1. CDC. Intervals between PCV13 and PSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2015;64:944-47. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm
  2. Carrera E, Manzano r, Garrido. Efficacy of the vaccination in inflammatory bowel disease. World J Gastroenterol 2013;19:1349-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602493/
  3. Reich J, Wasan S, Farraye FA. Vaccinating patients with inflammatory bowel disease. Gastroenterol Hepatol 2016;12:540-46. http://www.gastroenterologyandhepatology.net/archives/september-2016/vaccinating-patients-with-inflammatory-bowel-disease/
  4. Chaudrey K, Salvaggio M, Ahmed A, et al. Updates in vaccination: recommendations for adult inflammatory bowel disease patients. World J Gastroenterol 2015;21:3184-96. https://www.ncbi.nlm.nih.gov/pubmed/25805924
  5. Ryan FP, Smart RC, Holdworth CD, et al. Hyposplenism in inflammatory bowel disease. Gut 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411782/
  6. Jewell DP, Berney JJ, Pettit JE. Splenic phagocytic function in patients with inflammatory bowel disease. Pathology 1981;13:717-23. https://www.ncbi.nlm.nih.gov/pubmed/7335378
  7. Van der Hoeven JG, de Koning J, Masclee AM et al. Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infec Dis 1996;22:860-1. https://www.ncbi.nlm.nih.gov/pubmed/8722951

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Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

Should I avoid intravenous furosemide for management of ascites in my patient with cirrhosis?

Generally, yes! IV furosemide for treatment of ascites in patients with cirrhosis should be avoided for couple of reasons.

First, in contrast to patients with congestive heart failure in whom the absorption of oral furosemide may be impaired due to bowel wall edema, patients with cirrhosis and ascites appear to absorb oral furosemide efficiently, similarly to that of control patients.1   Another reason for avoiding IV furosemide in this setting is the possibility of a significant drop in the GFR with its attendant rise in BUN and serum creatinine, clinically resembling a picture of hepatorenal syndrome.2

Although the mechanism of the adverse effect of IV furosemide on the renal function of patients with cirrhosis is not totally clear, furosemide-induced vasoconstriction, not intrasvascular volume depletion due to sodium wasting, seems to play an important role.3

Nevertheless, certain situations may necessitate the use of IV furosemide in patients with cirrhosis and ascites, such as in single doses to help identify patients who will be responsive to diuretics, and in patients in need of prompt diuresis such as those with concurrent pulmonary edema. In a somewhat reassuring study, a single dose of 80 mg IV furosemide reliably identified cirrhotic patients with ascites responsive to diuretics, without a significant risk of deteriorating renal function.3

 

References

  1. Sawhney VK, Gregory PB, Swezey SE, et al. Furosemide disposition in cirrhotic patients. Gastroenterology 1981; 81: 1012-16. https://www.ncbi.nlm.nih.gov/pubmed/7286579
  2. Daskalopoulos G, Laffi G, Morgan T, et al. Immediate effects of furosemide on renal hemodynamics in chronic liver disease with ascites. Gastroenterology 1987;92:1859-1863. https://www.ncbi.nlm.nih.gov/pubmed/3569760
  3. Spahr, L., Villeneuve, J., Tran, H. K., & Pomier-Layrargues, G. Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites. Hepatology 2001;33:28-31. https://www.ncbi.nlm.nih.gov/pubmed/11124817

 

Contributed by Sam Miller, MD, Mass General Hospital, Boston, MA.

 

Should I avoid intravenous furosemide for management of ascites in my patient with cirrhosis?

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.

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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?