Chronic diarrhea pathophysiology
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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
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.[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. For example, cholera is caused by secretion and altered motility[2] whereas pseudomembranous colitis is said to be associated with secretion, inflammation, and motility[3].
Thus, diarrhea is a condition of altered intestinal water and electrolyte transport. The pathophysiologic mechanisms of diarrhea include osmotic, secretory, inflammatory, altered motility or iatrogenic.
- Osmotic chronic diarrhea; involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients. Examples of chronic diarrhea due to an osmotic cause include malabsorption states such as celiac disease, bacterial overgrowth, osmotic laxatives and maldigestion as occurs commonly in disaccharidase deficiency, and pancreatic exocrine insufficiency. 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.[4]
- Secretory chronic diarrhea results from disordered electrolyte transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion. Examples of 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. Secretoty 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]
- Inflammatory chronic diarrhea cause diarrhea with exudative, secretory, or malabsorptive components. 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. Typically, bowel imaging and tissue biopsies provide the diagnosis of the condition. Anti-inflammatory agents, including bismuth subsalicylate or other more potent anti-inflammatory medications, appear to benefit patients with microscopic or collagenous colitis, other data in the literature suggest that simply slowing down transit through the bowel with loperamide results in an equivalent therapeutic benefit. [6]
- Motility disorders causing chronic diarrhea; both rapid transit time and a slow transit time can be associated with chronic diarrhea. A rapid transit time delivers fluid secreted during digestion to the distal small bowel or colon, this prevents reabsorption of normally secreted fluid in the small bowel thereby overwhelming the reabsorptive capacity of the colon. On the other hand, 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. Experimentally osmotic laxatives results in acceleration of transit through the bowel, and this is associated with up to 14 g of fat in the stool, on the other hand, the 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.[7]
- Iatrogenic causes of chronic diarrhea; chronic diarrhea might follow abdominal surgery. After cholecystectomy, about 5%–10% of patients develop diarrhea. In many cases the diarrhea will resolve or significantly improve over the course of weeks to months. The diarrhea is related to excessive bile acids entering the colon.[8][9] In the absence of a gallbladder, bile drains directly and more continuously into the small bowel, which may overcome the terminal ileum's reabsorptive capacity. The increased bile acids in the colon lead to diarrhea (cholerheic diarrhea) Some other iatrogenic causes of chronic diarrhea might result from vagal injury and ileal resection.
However, from a pathophysiologic perspective, no single cause of diarrhea is truly unifactorial.
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.
- ↑ Goyal RK, Hirano I (1996). "The enteric nervous system". N Engl J Med. 334 (17): 1106–15. doi:10.1056/NEJM199604253341707. PMID 8598871.
- ↑ Kurose I, Pothoulakis C, LaMont JT, Anderson DC, Paulson JC, Miyasaka M; et al. (1994). "Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine". J Clin Invest. 94 (5): 1919–26. doi:10.1172/JCI117542. PMC 294602. PMID 7962537.
- ↑ 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.