Chronic diarrhea pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The fundamental pathophysiology of all diarrhea is incomplete [[absorption]] of water from the [[lumen]] either because of a reduced rate of net water absorption (related to impaired [[electrolyte]] absorption or excessive electrolyte secretion) or because of osmotic retention of water intraluminally. The causes of chronic diarrhea include [[inflammatory]], [[osmotic]], [[Secretory component|secretory]], [[iatrogenic]], [[motility]], and functional diseases. In general, the causes of chronic diarrhea are multi factorial. | The fundamental [[pathophysiology]] of all diarrhea is incomplete [[absorption]] of water from the [[lumen]] either because of a reduced rate of net water [[absorption]] (related to impaired [[electrolyte]] absorption or excessive [[electrolyte]] secretion) or because of [[osmotic]] retention of water intraluminally. The causes of chronic diarrhea include [[inflammatory]], [[osmotic]], [[Secretory component|secretory]], [[iatrogenic]], [[motility]], and functional [[Disease|diseases]]. In general, the causes of chronic [[diarrhea]] are multi factorial. | ||
==Pathogenesis== | ==Pathogenesis== | ||
Diarrhea is a condition of altered intestinal water and [[electrolyte]] transport. The physiological mechanisms of diarrhea include [[osmotic]], secretory, [[inflammatory]], altered motility or [[iatrogenic]].<ref name="pmid22677080">{{cite journal| author=Sweetser S| title=Evaluating the patient with diarrhea: a case-based approach. | journal=Mayo Clin Proc | year= 2012 | volume= 87 | issue= 6 | pages= 596-602 | pmid=22677080 | doi=10.1016/j.mayocp.2012.02.015 | pmc=3538472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22677080 }} </ref> | [[Diarrhea]] is a condition of altered [[intestinal]] water and [[electrolyte]] transport. The physiological mechanisms of [[diarrhea]] include [[osmotic]], secretory, [[inflammatory]], altered motility or [[iatrogenic]].<ref name="pmid22677080">{{cite journal| author=Sweetser S| title=Evaluating the patient with diarrhea: a case-based approach. | journal=Mayo Clin Proc | year= 2012 | volume= 87 | issue= 6 | pages= 596-602 | pmid=22677080 | doi=10.1016/j.mayocp.2012.02.015 | pmc=3538472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22677080 }} </ref> | ||
===Osmotic chronic diarrhea=== | ===Osmotic chronic diarrhea=== | ||
Osmotic chronic diarrhea involves an unabsorbed substance that draws water from the [[plasma]] into the intestinal lumen along osmotic gradients. If excessive amounts of unabsorbed substance are retained in the intestinal lumen, water will not be absorbed and diarrhea will result. | [[Osmotic]] chronic [[diarrhea]] involves an unabsorbed substance that draws water from the [[plasma]] into the [[intestinal]] lumen along [[osmotic]] gradients. If excessive amounts of unabsorbed substance are retained in the [[intestinal]] lumen, water will not be absorbed and [[diarrhea]] will result. | ||
*Chronic diarrhea due to an osmotic cause include osmotic [[laxatives]] such as [[lactose intolerance]] [[Antacid|antacids]], [[fructose]], [[lactulose]], [[laxatives]] [[magnesium]], [[phosphate]], and [[sorbitol]].<ref name="pmid7776987">{{cite journal| author=Suarez FL, Savaiano DA, Levitt MD| title=A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 1 | pages= 1-4 | pmid=7776987 | doi=10.1056/NEJM199507063330101 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7776987 }} </ref> | *Chronic [[diarrhea]] due to an [[osmotic]] cause include osmotic [[laxatives]] such as [[lactose intolerance]] [[Antacid|antacids]], [[fructose]], [[lactulose]], [[laxatives]] [[magnesium]], [[phosphate]], and [[sorbitol]].<ref name="pmid7776987">{{cite journal| author=Suarez FL, Savaiano DA, Levitt MD| title=A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 1 | pages= 1-4 | pmid=7776987 | doi=10.1056/NEJM199507063330101 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7776987 }} </ref> | ||
*[[Maldigestion]] syndromes such as [[disaccharidase]] deficiency and [[Pancreatic insufficiency|pancreatic exocrine insufficiency]] can also result in [[osmotic]] chronic diarrhea. | *[[Maldigestion]] [[syndromes]] such as [[disaccharidase]] deficiency and [[Pancreatic insufficiency|pancreatic exocrine insufficiency]] can also result in [[osmotic]] chronic [[diarrhea]]. | ||
*[[Osmotic]] diarrheas might result in [[steatorrhea]] and [[azotorrhea]] (passage of fat and nitrogenous substances into the stool), but typically they do not cause any [[rectal bleeding]].<ref name="pmid467934">{{cite journal| author=Morris AI, Turnberg LA| title=Surreptitious laxative abuse. | journal=Gastroenterology | year= 1979 | volume= 77 | issue= 4 Pt 1 | pages= 780-6 | pmid=467934 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=467934 }} </ref> | *[[Osmotic]] diarrheas might result in [[steatorrhea]] and [[azotorrhea]] (passage of [[fat]] and nitrogenous substances into the stool), but typically they do not cause any [[rectal bleeding]].<ref name="pmid467934">{{cite journal| author=Morris AI, Turnberg LA| title=Surreptitious laxative abuse. | journal=Gastroenterology | year= 1979 | volume= 77 | issue= 4 Pt 1 | pages= 780-6 | pmid=467934 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=467934 }} </ref> | ||
===Secretory chronic diarrhea=== | ===Secretory chronic diarrhea=== | ||
Secretory chronic diarrhea results from disordered [[electrolyte]] transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion. | Secretory chronic [[diarrhea]] results from disordered [[electrolyte]] transport and, despite the term, is more commonly caused by decreased [[absorption]] rather than net [[secretion]]. | ||
*Secretory diarrheas include congenital abnormalities such as congenital chloridorrhea, in which an abnormality in the genetic control of [[Chloride-bicarbonate exchanger|chloride-bicarbonate exchange]] in the [[ileum]] results in the loss of [[chloride]] into the [[stool]]. | *Secretory [[Diarrhea|diarrheas]] include [[congenital]] abnormalities such as [[congenital]] chloridorrhea, in which an abnormality in the [[genetic]] control of [[Chloride-bicarbonate exchanger|chloride-bicarbonate exchange]] in the [[ileum]] results in the loss of [[chloride]] into the [[stool]]. | ||
*Another example is the loss of α2-adrenergic function in [[enterocytes]] of patients with [[autonomic neuropathy]] caused by [[diabetes mellitus]]. | *Another example is the loss of α2-adrenergic function in [[enterocytes]] of patients with [[autonomic neuropathy]] caused by [[diabetes mellitus]]. | ||
*The typical features of secretory diarrhea include the persistence of the diarrhea with fasting and the absence of [[steatorrhea]], [[azotorrhea]], or [[Rectal bleeding|blood per rectum]]. | *The typical features of secretory [[diarrhea]] include the persistence of the [[diarrhea]] with fasting and the absence of [[steatorrhea]], [[azotorrhea]], or [[Rectal bleeding|blood per rectum]]. | ||
*Secretory diarrheas caused by [[neuroendocrine tumors]] has been identified by measurement of [[plasma]] levels of the [[hormone]] or its [[metabolite]] in the [[urine]]. | *Secretory diarrheas caused by [[neuroendocrine tumors]] has been identified by measurement of [[plasma]] levels of the [[hormone]] or its [[metabolite]] in the [[urine]]. | ||
*Investigations include measurements of [[VIP]], [[gastrin]], or [[calcitonin]] in [[plasma]] or 24-hour collections of urine for [[5-Hydroxyindoleacetic acid|5-hydroxyindoleacetic acid]].<ref name="pmid8371728">{{cite journal| author=von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM| title=Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea. | journal=N Engl J Med | year= 1993 | volume= 329 | issue= 15 | pages= 1073-8 | pmid=8371728 | doi=10.1056/NEJM199310073291503 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8371728 }} </ref> | *Investigations include measurements of [[VIP]], [[gastrin]], or [[calcitonin]] in [[plasma]] or 24-hour collections of urine for [[5-Hydroxyindoleacetic acid|5-hydroxyindoleacetic acid]].<ref name="pmid8371728">{{cite journal| author=von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM| title=Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea. | journal=N Engl J Med | year= 1993 | volume= 329 | issue= 15 | pages= 1073-8 | pmid=8371728 | doi=10.1056/NEJM199310073291503 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8371728 }} </ref> | ||
===Inflammatory chronic diarrhea=== | ===Inflammatory chronic diarrhea=== | ||
Disruption of the normal colonic epithelial barrier by microorganisms is mainly responsible for inflammatory | Disruption of the normal colonic epithelial barrier by microorganisms is mainly responsible for inflammatory chronic [[diarrhea]]. This disruption can lead to exudative, secretory or malabsorptive components of inflammatory chronic [[diarrhea]]. | ||
*[[Inflammatory]] causes of chronic diarrhea might present with features that suggest [[malabsorption]] or [[rectal bleeding]]. | *[[Inflammatory]] causes of chronic [[diarrhea]] might present with features that suggest [[malabsorption]] or [[rectal bleeding]]. | ||
*The nature of the [[malabsorption]] depends on the regions affected (e.g., [[proximal]] vs. distal small bowel), and [[rectal bleeding]] is usually a manifestation of colonic or rectal [[ulcerations]]. | *The nature of the [[malabsorption]] depends on the regions affected (e.g., [[proximal]] vs. distal small bowel), and [[rectal bleeding]] is usually a manifestation of colonic or rectal [[ulcerations]]. | ||
*Anti-inflammatory agents, including [[bismuth subsalicylate]] or other more potent anti-inflammatory medications, appear to benefit patients with microscopic or [[collagenous colitis]].<ref name="pmid12003412">{{cite journal| author=Pardi DS, Smyrk TC, Tremaine WJ, Sandborn WJ| title=Microscopic colitis: a review. | journal=Am J Gastroenterol | year= 2002 | volume= 97 | issue= 4 | pages= 794-802 | pmid=12003412 | doi=10.1111/j.1572-0241.2002.05595.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12003412 }} </ref> | *Anti-inflammatory agents, including [[bismuth subsalicylate]] or other more potent anti-inflammatory medications, appear to benefit patients with microscopic or [[collagenous colitis]].<ref name="pmid12003412">{{cite journal| author=Pardi DS, Smyrk TC, Tremaine WJ, Sandborn WJ| title=Microscopic colitis: a review. | journal=Am J Gastroenterol | year= 2002 | volume= 97 | issue= 4 | pages= 794-802 | pmid=12003412 | doi=10.1111/j.1572-0241.2002.05595.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12003412 }} </ref> | ||
===Motility disorders causing chronic diarrhea=== | ===Motility disorders causing chronic diarrhea=== | ||
Both rapid transit time and a slow transit time are associated with motility disorders causing chronic diarrhea. | Both rapid transit time and a slow transit time are associated with motility disorders causing chronic [[diarrhea]]. | ||
*Rapid transit time delivers [[fluid]] secreted during digestion to the distal [[small bowel]] or [[colon]], this prevents re absorption of normally secreted fluid in the [[small bowel]] thereby overwhelming the re absorptive capacity of the [[colon]]. | *Rapid transit time delivers [[fluid]] secreted during digestion to the distal [[small bowel]] or [[colon]], this prevents re absorption of normally secreted fluid in the [[small bowel]] thereby overwhelming the re absorptive capacity of the [[colon]]. | ||
*Slow transit time results in [[bacterial overgrowth]] with [[bile acid]] deconjugation, poor [[micelle]] formation, and [[steatorrhea]]. | *Slow transit time results in [[bacterial overgrowth]] with [[bile acid]] deconjugation, poor [[micelle]] formation, and [[steatorrhea]]. | ||
*The clinical manifestations of chronic diarrhea caused by motility disorders include [[steatorrhea]], usually up to 14 g per day. | *The clinical manifestations of chronic [[diarrhea]] caused by motility disorders include [[steatorrhea]], usually up to 14 g per day. | ||
*Osmotic [[laxatives]] results in acceleration of transit through the [[bowel]], and this is associated with up to 14 g of fat in the [[stool]]. | *Osmotic [[laxatives]] results in acceleration of transit through the [[bowel]], and this is associated with up to 14 g of fat in the [[stool]]. | ||
*Presence of more than 14 g per day of [[fat]] in the stool suggests the presence of [[bacterial overgrowth]] or associated [[disease]] such as [[celiac disease]].<ref name="pmid2794043">{{cite journal| author=Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS| title=Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. | journal=J Clin Invest | year= 1989 | volume= 84 | issue= 4 | pages= 1056-62 | pmid=2794043 | doi=10.1172/JCI114267 | pmc=329760 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2794043 }} </ref> | *Presence of more than 14 g per day of [[fat]] in the stool suggests the presence of [[bacterial overgrowth]] or associated [[disease]] such as [[celiac disease]].<ref name="pmid2794043">{{cite journal| author=Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS| title=Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. | journal=J Clin Invest | year= 1989 | volume= 84 | issue= 4 | pages= 1056-62 | pmid=2794043 | doi=10.1172/JCI114267 | pmc=329760 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2794043 }} </ref> | ||
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==Genetics, Associated conditions, Gross pathology and Microscopic pathology== | ==Genetics, Associated conditions, Gross pathology and Microscopic pathology== | ||
For the details of the genetics, associated conditions, gross and microscopic pathology of the following causes of chronic diarrhea, click the link bellow. | For the details of the [[genetics]], associated conditions, [[Gross examination|gross]] and [[microscopic]] [[pathology]] of the following causes of chronic [[diarrhea]], click the link bellow. | ||
*[[Ulcerative colitis pathophysiology#Pathphysiology|Ulcerative colitis]] | *[[Ulcerative colitis pathophysiology#Pathphysiology|Ulcerative colitis]] | ||
*[[Crohn's disease pathophysiology#Pathophysiology|Crohn's disease]] | *[[Crohn's disease pathophysiology#Pathophysiology|Crohn's disease]] | ||
Revision as of 16:29, 28 July 2017
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Chronic diarrhea Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]
Overview
The fundamental pathophysiology of all diarrhea is incomplete absorption of water from the lumen either because of a reduced rate of net water absorption (related to impaired electrolyte absorption or excessive electrolyte secretion) or because of osmotic retention of water intraluminally. The causes of chronic diarrhea include inflammatory, osmotic, secretory, iatrogenic, motility, and functional diseases. In general, the causes of chronic diarrhea are multi factorial.
Pathogenesis
Diarrhea is a condition of altered intestinal water and electrolyte transport. The physiological mechanisms of diarrhea include osmotic, secretory, inflammatory, altered motility or iatrogenic.[1]
Osmotic chronic diarrhea
Osmotic chronic diarrhea involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients. If excessive amounts of unabsorbed substance are retained in the intestinal lumen, water will not be absorbed and diarrhea will result.
- Chronic diarrhea due to an osmotic cause include osmotic laxatives such as lactose intolerance antacids, fructose, lactulose, laxatives magnesium, phosphate, and sorbitol.[2]
- Maldigestion syndromes such as disaccharidase deficiency and pancreatic exocrine insufficiency can also result in osmotic chronic diarrhea.
- Osmotic diarrheas might result in steatorrhea and azotorrhea (passage of fat and nitrogenous substances into the stool), but typically they do not cause any rectal bleeding.[3]
Secretory chronic diarrhea
Secretory chronic diarrhea results from disordered electrolyte transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion.
- Secretory diarrheas include congenital abnormalities such as congenital chloridorrhea, in which an abnormality in the genetic control of chloride-bicarbonate exchange in the ileum results in the loss of chloride into the stool.
- Another example is the loss of α2-adrenergic function in enterocytes of patients with autonomic neuropathy caused by diabetes mellitus.
- The typical features of secretory diarrhea include the persistence of the diarrhea with fasting and the absence of steatorrhea, azotorrhea, or blood per rectum.
- Secretory diarrheas caused by neuroendocrine tumors has been identified by measurement of plasma levels of the hormone or its metabolite in the urine.
- Investigations include measurements of VIP, gastrin, or calcitonin in plasma or 24-hour collections of urine for 5-hydroxyindoleacetic acid.[4]
Inflammatory chronic diarrhea
Disruption of the normal colonic epithelial barrier by microorganisms is mainly responsible for inflammatory chronic diarrhea. This disruption can lead to exudative, secretory or malabsorptive components of inflammatory chronic diarrhea.
- Inflammatory causes of chronic diarrhea might present with features that suggest malabsorption or rectal bleeding.
- The nature of the malabsorption depends on the regions affected (e.g., proximal vs. distal small bowel), and rectal bleeding is usually a manifestation of colonic or rectal ulcerations.
- Anti-inflammatory agents, including bismuth subsalicylate or other more potent anti-inflammatory medications, appear to benefit patients with microscopic or collagenous colitis.[5]
Motility disorders causing chronic diarrhea
Both rapid transit time and a slow transit time are associated with motility disorders causing chronic diarrhea.
- Rapid transit time delivers fluid secreted during digestion to the distal small bowel or colon, this prevents re absorption of normally secreted fluid in the small bowel thereby overwhelming the re absorptive capacity of the colon.
- Slow transit time results in bacterial overgrowth with bile acid deconjugation, poor micelle formation, and steatorrhea.
- The clinical manifestations of chronic diarrhea caused by motility disorders include steatorrhea, usually up to 14 g per day.
- Osmotic laxatives results in acceleration of transit through the bowel, and this is associated with up to 14 g of fat in the stool.
- Presence of more than 14 g per day of fat in the stool suggests the presence of bacterial overgrowth or associated disease such as celiac disease.[6]
Iatrogenic causes of chronic diarrhea
After abdominal surgeries such as cholecystectomy about 5%–10% of patients develop chronic diarrhea.
- Most of these cases resolve completely or significantly improve within a couple of months.
- Iatrogenic diarrhea is related to excessive bile acids being delivered into the intestine.[7][8]
- After a cholecystectomy, bile is delivered directly into the small bowel, overcoming the terminal ileum's ability to reabsorb adequately leading to cholerheic diarrhea.
- Some other iatrogenic causes of chronic diarrhea might result from vagal injury and ileal resection.
Genetics, Associated conditions, Gross pathology and Microscopic pathology
For the details of the genetics, associated conditions, gross and microscopic pathology of the following causes of chronic diarrhea, click the link bellow.
- Ulcerative colitis
- Crohn's disease
- Lactose intolerance
- Celiac disease
- Chronic pancreatitis
- Cholera
- Microsporidiosis
- Giardiasis
- Cryptosporidiosis
- Hyperthyroidism pathophysiology#PathophysiologyHyperthyroidism
References
- ↑ Sweetser S (2012). "Evaluating the patient with diarrhea: a case-based approach". Mayo Clin Proc. 87 (6): 596–602. doi:10.1016/j.mayocp.2012.02.015. PMC 3538472. PMID 22677080.
- ↑ Suarez FL, Savaiano DA, Levitt MD (1995). "A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance". N Engl J Med. 333 (1): 1–4. doi:10.1056/NEJM199507063330101. PMID 7776987.
- ↑ Morris AI, Turnberg LA (1979). "Surreptitious laxative abuse". Gastroenterology. 77 (4 Pt 1): 780–6. PMID 467934.
- ↑ von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM (1993). "Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea". N Engl J Med. 329 (15): 1073–8. doi:10.1056/NEJM199310073291503. PMID 8371728.
- ↑ Pardi DS, Smyrk TC, Tremaine WJ, Sandborn WJ (2002). "Microscopic colitis: a review". Am J Gastroenterol. 97 (4): 794–802. doi:10.1111/j.1572-0241.2002.05595.x. PMID 12003412.
- ↑ Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS (1989). "Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose". J Clin Invest. 84 (4): 1056–62. doi:10.1172/JCI114267. PMC 329760. PMID 2794043.
- ↑ Breuer NF, Jaekel S, Dommes P, Goebell H (1986). "Fecal bile acid excretion pattern in cholecystectomized patients". Dig Dis Sci. 31 (9): 953–60. PMID 3731987.
- ↑ Arlow FL, Dekovich AA, Priest RJ, Beher WT (1987). "Bile acid-mediated postcholecystectomy diarrhea". Arch Intern Med. 147 (7): 1327–9. PMID 3606289.