Chronic diarrhea pathophysiology: Difference between revisions

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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:''' It involves an unabsorbed substance that draws water from the [[plasma]] into the intestinal lumen along osmotic gradients.  
===Osmotic chronic diarrhea===
**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>   
It involves an unabsorbed substance that draws water from the [[plasma]] into the intestinal lumen along osmotic gradients.  
**[[Maldigestion]] syndromes such as [[disaccharidase]] deficiency and [[Pancreatic insufficiency|pancreatic exocrine insufficiency]] can also result in [[osmotic]] chronic diarrhea.  
*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>   
**[[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>
*[[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>


*'''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===
**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 chronic diarrhea results from disordered [[electrolyte]] transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion.  
**Another example is the loss of α2-adrenergic function in [[enterocytes]] of patients with [[autonomic neuropathy]] caused by [[diabetes mellitus]].  
*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]].  
**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]].  
*Another example is the loss of α2-adrenergic function in [[enterocytes]] of patients with [[autonomic neuropathy]] caused by [[diabetes mellitus]].  
**Secretory diarrheas caused by [[neuroendocrine tumors]] has been identified by measurement of [[plasma]] levels of the [[hormone]] or its [[metabolite]] in the [[urine]].  
*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]].  
**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>
*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>


*'''Inflammatory chronic diarrhea'''  cause diarrhea with [[exudative]], secretory, or [[Malabsorption|malabsorptive]] components.  
===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'''; both rapid transit time and a slow transit time can be associated with chronic diarrhea.  
===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]].  
Both rapid transit time and a slow transit time are associated with motility disorders causing chronic diarrhea.  
**Reduced motility leading to slow transit might result in [[bacterial overgrowth]] with [[bile acid]] deconjugation, poor [[micelle]] formation, and [[steatorrhea]].  
*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]].  
**The clinical manifestations of chronic diarrhea caused by motility disorders include [[steatorrhea]], usually up to 14 g per day.  
*Slow transit time results in [[bacterial overgrowth]] with [[bile acid]] deconjugation, poor [[micelle]] formation, and [[steatorrhea]].  
**Osmotic [[laxatives]] results in acceleration of transit through the [[bowel]], and this is associated with up to 14 g of fat in the [[stool]].
*The clinical manifestations of chronic diarrhea caused by motility disorders include [[steatorrhea]], usually up to 14 g per day.  
**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>
*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>


*'''Iatrogenic causes of chronic diarrhea'''; After [[abdominal]] surgeries such as [[cholecystectomy]] about 5%–10% of patients develop chronic diarrhea.  
===Iatrogenic causes of chronic diarrhea===
**Most of these cases resolve completely or significantly improve within a couple of months.  
After [[abdominal]] surgeries such as [[cholecystectomy]] about 5%–10% of patients develop chronic diarrhea.  
**[[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>
*Most of these cases resolve completely or significantly improve within a couple of months.  
**After a [[cholecystectomy]], bile is delivered directly into the [[small bowel]], overcoming the [[terminal ileum]]'s ability to reabsorb adequately leading to cholerheic diarrhea.  
*[[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>
**Some other [[iatrogenic]] causes of chronic diarrhea might result from [[vagal]] [[injury]] and [[Ileum|ileal]] resection.
*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.


==Genetics, Associated conditions, Gross pathology and Microscopic pathology==
==Genetics, Associated conditions, Gross pathology and Microscopic pathology==

Revision as of 18:08, 25 July 2017

Chronic diarrhea Microchapters

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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. 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

It involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients.

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.

Inflammatory chronic diarrhea

Motility disorders causing chronic diarrhea

Both rapid transit time and a slow transit time are associated with motility disorders causing chronic diarrhea.

Iatrogenic causes of chronic diarrhea

After abdominal surgeries such as cholecystectomy about 5%–10% of patients develop chronic diarrhea.

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.

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. 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.
  3. Morris AI, Turnberg LA (1979). "Surreptitious laxative abuse". Gastroenterology. 77 (4 Pt 1): 780–6. PMID 467934.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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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