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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.<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> The causes of chronic diarrhea include [[inflammatory]], [[osmotic]], secretory, [[iatrogenic]], [[motility]], and functional diseases. In general, no single cause of chronic diarrhea is truly unifactorial from a perspective of pathophysiology.
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.<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> The causes of chronic diarrhea include [[inflammatory]], [[osmotic]], secretory, [[iatrogenic]], [[motility]], and functional diseases. In general, no single cause of chronic diarrhea is truly unifactorial from a perspective of pathophysiology.


==Pathophysiology==
==Pathophysiology==
Diarrhea is a condition of altered intestinal water and [[electrolyte]] transport. The physiological mechanisms of diarrhea include [[osmotic]], secretory, [[inflammatory]], altered motility or [[iatrogenic]].
Diarrhea is a condition of altered intestinal water and [[electrolyte]] transport. The physiological mechanisms of diarrhea include [[osmotic]], secretory, [[inflammatory]], altered motility or [[iatrogenic]].


*'''Osmotic chronic diarrhea:''' It involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients.  
*'''Osmotic chronic diarrhea:''' It involves an unabsorbed substance that draws water from the [[plasma]] into the intestinal lumen along osmotic gradients.  
**Chronic diarrhea due to an osmotic cause include osmotic laxatives such as [[lactose intolerance]] [[Antacid|antacids]], [[fructose]], [[lactulose]], [[laxatives]] [[magnesium]], [[phosphate]], and [[sorbitol]].  
**Chronic diarrhea due to an osmotic cause include osmotic [[laxatives]] such as [[lactose intolerance]] [[Antacid|antacids]], [[fructose]], [[lactulose]], [[laxatives]] [[magnesium]], [[phosphate]], and [[sorbitol]].  
**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''' 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 exchange in the [[ileum]] results in the loss of [[chloride]] into the [[stool]].  
**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]].  
**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]].  
**Secretoty 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]].  
**Examples 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>
**Examples 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'''  cause diarrhea with [[exudative]], secretory, or malabsorptive components.   
*'''Inflammatory chronic diarrhea'''  cause diarrhea with [[exudative]], secretory, or [[Malabsorption|malabsorptive]] components.   
**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'''; both rapid transit time and a slow transit time can be associated with chronic diarrhea.  
*'''Motility disorders causing chronic diarrhea'''; both rapid transit time and a slow transit time can be associated with 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]].  
**Reduced motility leading to slow transit might result in bacterial overgrowth with bile acid deconjugation, poor [[micelle]] formation, and [[steatorrhea]].  
**Reduced motility leading to slow transit might result 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 might suggest 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 might suggest 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>


*'''Iatrogenic causes of chronic diarrhea'''; After abdominal surgeries such as [[cholecystectomy]] about 5%–10% of patients develop chronic diarrhea.  
*'''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.  
**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 intestines.<ref name="pmid3731987">{{cite journal| author=Breuer NF, Jaekel S, Dommes P, Goebell H| title=Fecal bile acid excretion pattern in cholecystectomized patients. | journal=Dig Dis Sci | year= 1986 | volume= 31 | issue= 9 | pages= 953-60 | pmid=3731987 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3731987  }} </ref><ref name="pmid3606289">{{cite journal| author=Arlow FL, Dekovich AA, Priest RJ, Beher WT| title=Bile acid-mediated postcholecystectomy diarrhea. | journal=Arch Intern Med | year= 1987 | volume= 147 | issue= 7 | pages= 1327-9 | pmid=3606289 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3606289  }} </ref>
**[[Iatrogenic]] diarrhea is related to excessive [[Bile acid|bile acids]] being delivered into the [[intestine]].<ref name="pmid3731987">{{cite journal| author=Breuer NF, Jaekel S, Dommes P, Goebell H| title=Fecal bile acid excretion pattern in cholecystectomized patients. | journal=Dig Dis Sci | year= 1986 | volume= 31 | issue= 9 | pages= 953-60 | pmid=3731987 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3731987  }} </ref><ref name="pmid3606289">{{cite journal| author=Arlow FL, Dekovich AA, Priest RJ, Beher WT| title=Bile acid-mediated postcholecystectomy diarrhea. | journal=Arch Intern Med | year= 1987 | volume= 147 | issue= 7 | pages= 1327-9 | pmid=3606289 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3606289  }} </ref>
**After a cholecystectomy, bile is delivered directly into the small bowel, overcomeing the [[terminal ileum]]'s ability to reabsorb adequately leading to cholerheic diarrhea.  
**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 [[Ileum|ileal]] resection.
**Some other [[iatrogenic]] causes of chronic diarrhea might result from [[vagal]] injury and [[Ileum|ileal]] resection.



Revision as of 18:20, 5 July 2017

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Case #1

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.[1] The causes of chronic diarrhea include inflammatory, osmotic, secretory, iatrogenic, motility, and functional diseases. In general, no single cause of chronic diarrhea is truly unifactorial from a perspective of pathophysiology.

Pathophysiology

Diarrhea is a condition of altered intestinal water and electrolyte transport. The physiological mechanisms of diarrhea include osmotic, secretory, inflammatory, altered motility or iatrogenic.

  • Motility disorders causing chronic diarrhea; both rapid transit time and a slow transit time can be associated with 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.
    • Reduced motility leading to slow transit might result 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 might suggest the presence of bacterial overgrowth or associated disease such as celiac disease.[5]
  • 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.[6][7]
    • 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.

References

  1. 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.
  2. Morris AI, Turnberg LA (1979). "Surreptitious laxative abuse". Gastroenterology. 77 (4 Pt 1): 780–6. PMID 467934.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Arlow FL, Dekovich AA, Priest RJ, Beher WT (1987). "Bile acid-mediated postcholecystectomy diarrhea". Arch Intern Med. 147 (7): 1327–9. PMID 3606289.


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