Steatorrhea pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(6 intermediate revisions by 3 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Steatorrhea}}
{{Steatorrhea}}
{{CMG}}; {{AE}}{{SKA}}
{{CMG}} ; {{AE}} {{SKA}}
 
 


==Overview==
==Overview==
Stearorhea is loss of fatty undigested fecal material in stools. The processes invokes defect if the digestive tract. It may involve defect of synthesis or secretion or function of enzymes of GI tract which are needed to metabolize fatty content of food. It can also be due to defect in anatomical structures of GI tract.
Steatrorhea can be defined as loss of undigested fat in [[stools]]. The processes can be invoked by either defect of the normal architecture of [[Gastrointestinal tract|digestive tract]] or it may involve defect of [[synthesis]] or [[secretion]] of [[enzymes]] of GI tract which are needed to metabolize fatty content of food.


==Pathophysiology==
==Pathophysiology==


===Normal Fat malabsorption===
===Normal Fat absorption===
To understanf the pathophysiology of fat malabsoption we need to understand follwoing points:.<ref name="pmid29085272">{{cite journal| author=Kumar R, Bhargava A, Jaiswal G| title=A case report on total pancreatic lipomatosis: An unusual entity. | journal=Int J Health Sci (Qassim) | year= 2017 | volume= 11 | issue= 4 | pages= 71-73 | pmid=29085272 | doi= | pmc=5654180 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29085272  }}</ref><ref name="pmid28698280">{{cite journal| author=Previti E, Salinari S, Bertuzzi A, Capristo E, Bornstein S, Mingrone G| title=Glycemic control after metabolic surgery: a Granger causality and graph analysis. | journal=Am J Physiol Endocrinol Metab | year= 2017 | volume= 313 | issue= 5 | pages= E622-E630 | pmid=28698280 | doi=10.1152/ajpendo.00042.2017 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28698280  }}</ref><ref name="pmid28281512">{{cite journal| author=Vakhrushev YM, Lukashevich AP| title=[Specific features of impaired intestinal digestion, absorption, and microbiocenosis in patients with cholelithiasis]. | journal=Ter Arkh | year= 2017 | volume= 89 | issue= 2 | pages= 28-32 | pmid=28281512 | doi=10.17116/terarkh201789228-32 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28281512  }}</ref><ref name="pmid27825371">{{cite journal| author=Scarpignato C, Gatta L, Zullo A, Blandizzi C, SIF-AIGO-FIMMG Group. Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners| title=Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. | journal=BMC Med | year= 2016 | volume= 14 | issue= 1 | pages= 179 | pmid=27825371 | doi=10.1186/s12916-016-0718-z | pmc=5101793 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27825371  }}</ref><ref name="pmid26769182">{{cite journal| author=Podboy A, Anderson BW, Sweetser S| title=61-Year-Old Man With Chronic Diarrhea. | journal=Mayo Clin Proc | year= 2016 | volume= 91 | issue= 2 | pages= e23-8 | pmid=26769182 | doi=10.1016/j.mayocp.2015.07.033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26769182  }}</ref>
To understand the [[pathophysiology]] of fat malabsoption we need to understand normal physiology of fat metabolization:<ref name="pmid29085272">{{cite journal| author=Kumar R, Bhargava A, Jaiswal G| title=A case report on total pancreatic lipomatosis: An unusual entity. | journal=Int J Health Sci (Qassim) | year= 2017 | volume= 11 | issue= 4 | pages= 71-73 | pmid=29085272 | doi= | pmc=5654180 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29085272  }}</ref><ref name="pmid28698280">{{cite journal| author=Previti E, Salinari S, Bertuzzi A, Capristo E, Bornstein S, Mingrone G| title=Glycemic control after metabolic surgery: a Granger causality and graph analysis. | journal=Am J Physiol Endocrinol Metab | year= 2017 | volume= 313 | issue= 5 | pages= E622-E630 | pmid=28698280 | doi=10.1152/ajpendo.00042.2017 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28698280  }}</ref><ref name="pmid28281512">{{cite journal| author=Vakhrushev YM, Lukashevich AP| title=[Specific features of impaired intestinal digestion, absorption, and microbiocenosis in patients with cholelithiasis]. | journal=Ter Arkh | year= 2017 | volume= 89 | issue= 2 | pages= 28-32 | pmid=28281512 | doi=10.17116/terarkh201789228-32 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28281512  }}</ref><ref name="pmid27825371">{{cite journal| author=Scarpignato C, Gatta L, Zullo A, Blandizzi C, SIF-AIGO-FIMMG Group. Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners| title=Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. | journal=BMC Med | year= 2016 | volume= 14 | issue= 1 | pages= 179 | pmid=27825371 | doi=10.1186/s12916-016-0718-z | pmc=5101793 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27825371  }}</ref><ref name="pmid26769182">{{cite journal| author=Podboy A, Anderson BW, Sweetser S| title=61-Year-Old Man With Chronic Diarrhea. | journal=Mayo Clin Proc | year= 2016 | volume= 91 | issue= 2 | pages= e23-8 | pmid=26769182 | doi=10.1016/j.mayocp.2015.07.033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26769182  }}</ref><ref name="pmid26086616">{{cite journal| author=Burnett JR, Hooper AJ| title=Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. | journal=Free Radic Biol Med | year= 2015 | volume= 88 | issue= Pt A | pages= 59-62 | pmid=26086616 | doi=10.1016/j.freeradbiomed.2015.05.044 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26086616 }}</ref><ref name="pmid25502918">{{cite journal| author=Valenzise M, Alessi L, Bruno E, Cama V, Costanzo D, Genovese C et al.| title=APECED syndrome in childhood: clinical spectrum is enlarging. | journal=Minerva Pediatr | year= 2016 | volume= 68 | issue= 3 | pages= 226-9 | pmid=25502918 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25502918  }}</ref><ref name="pmid24602022">{{cite journal| author=Wilcox C, Turner J, Green J| title=Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. | journal=Aliment Pharmacol Ther | year= 2014 | volume= 39 | issue= 9 | pages= 923-39 | pmid=24602022 | doi=10.1111/apt.12684 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24602022  }}</ref>
* Normal fat absorption involves a complex mixture of digestive enzymes, bile salts, and an intact intestinal mucosa to enable uptake of these hydrophobic complexes.
* Absorption of fat requires a complex interaction of
* After ingestion, dietary lipids are initially emulsified in the stomach and then hydrolyzed by the action of gastric and pancreatic lipase and colipase.  
** [[Digestive enzymes]]
* The hydrolyzed lipids are then aggregated into micelles or liposomes with the addition of bile salts in the duodenum and jejunum.   
** [[Bile salts]] 
* These micelles are absorbed across the intact intestinal villi by both active and passive processes. Finally, they are packaged into chylomicrons within intestinal epithelial cells and transported to the circulation via the lymphatic system
** An intact [[intestinal mucosa]]
* More than 90% of daily dietary fat is absorbed into the general circulation, but any defects in the processes can reduce this uptake and lead to fatty diarrhea/ steatorrhea.  
* Ingested fats are initially [[Emulsification|emulsified]] in the [[stomach]].  
* The bulk of dietary lipid is neutral fat or triglyceride, composed of a glycerol backbone with each carbon linked to a fatty acid.  
* By the action of [[digestive enzymes]] emulsified [[lipids]] are [[Hydrolysis|hydrolyzed]] subsequently.  
* Foodstuffs typically also contain phospholipids, sterols like cholesterol and many minor lipids, including fat-soluble vitamins.  
* Once [[hydrolyzed]], they aggregate to form [[micelles]] with the help of [[bile salts]].  
* Finally, small intestinal contents contain lipids from sloughed epithelial cells and considerable cholesterol delivered in bile.  
* These [[micelles]] are absorbed across the intact [[intestinal villi]] of proximal [[small intestine]].  
 
* After absorption, micelles are packaged into chylomicrons within intestinal epithelial cells and transported to the circulation via the lymphatic system.  
===== '''Emulsification, Hydrolysis and Micelle Formation''': =====
* Bile acids play their first critical role in lipid assimilation by promoting emulsification.
* As derivatives of cholesterol, bile acids have both hydrophilic and hydrophobic domains (i.e. they are amphipathic).
* On exposure to a large aggregate of triglyceride, the hydrophobic portions of bile acids intercalate into the lipid, with the hydrophilic domains remaining at the surface. 
* Such coating with bile acids aids in breakdown of large aggregates or droplets into smaller and smaller droplets.
* Hydrolysis of triglyceride into monoglyceride and free fatty acids is accomplished predominantly by pancreatic lipase.
* The activity of this enzyme is to clip the fatty acids at positions 1 and 3 of the triglyceride, leaving two free fatty acids and a 2-monoglyceride.
* The drug orlistat (Xenical) that is promoted for treatment of obesity works by inhibiting pancreatic lipase, thereby reducing the digestion and absorption of fat in the small intestine.
* Lipase is a water-soluble enzyme, and with a little imagination, it's easy to understand why emulsification is a necessary prelude to its efficient activity. 
* Shortly after a meal, lipase is present within the small intestine in rather huge quantities, but can act only on the surface of triglyeride droplets.
* For a given volume of lipid, the smaller the droplet size, the greater the surface area, which means more lipase molecules can get to work.
* As monoglycerides and fatty acids are liberated through the action of lipase, they retain their association with bile acids and complex with other lipids to form structures called '''micelles'''. 
* Micelles are essentially small aggregates (4-8 nm in diameter) of mixed lipids and bile acids suspended within the ingesta.
* As the ingesta is mixed, micelles bump into the brush border of small intestinal enterocytes, and the lipids, including monoglyceride and fatty acids, are taken up into the epithelial cells.


===== '''Absorption and Transport into Blood''': =====
=== Pathogenesis ===
* The major products of lipid digestion - fatty acids and 2-monoglycerides - enter the enterocyte by simple diffusion across the plasma membrane.
Any disturbance in the normal physiology results in decreased [[absorption]] of the [[fats]].  
* A considerable fraction of the fatty acids also enter the enterocyte via a specific fatty acid transporter protein in the membrane.
* '''<u>Disturbance in intact intestinal mucosa</u>'''
* Lipids are transported from the enterocyte into blood by a mechanism distinctly different from what we've seen for monosaccharides and amino acids.
** Marked acceleration of intestinal transit can increase nutrient malabsorption and induce symptoms due to:
* Once inside the enterocyte, fatty acids and monoglyceride are transported into the endoplasmic reticulum, where they are used to synthesize triglyeride.
*** [[Osmosis|High osmotic load]]
* Beginning in the endoplasmic reticulum and continuing in the Golgi, triglyceride is packaged with cholesterol, lipoproteins and other lipids into particles called '''chylomicrons'''. ''Remember where this is occurring - in the absorptive enterocyte of the small intestine.''
*** Increased bacterial [[metabolism]] in the [[colon]]
* Chylomicrons are extruded from the Golgi into exocytotic vesicles, which are transported to the basolateral aspect of the enterocyte.
** Delayed intestinal transit may promote [[small intestinal bacterial overgrowth]].
* The vesicles fuse with the plasma membrane and undergo exocytosis, dumping the chylomicrons into the space outside the cells.
** This bacterial overgrowth also causes [[malnutrition]] by consuming ingested [[nutrients]].
* Because chylomicrons are particles, virtually all steps in this pathway can be visualized using an electron microscope, as the montage of images to the right demonstrates.
** In addition, [[Conjugation|de-conjugation]] of [[Bile acid|bile acids]] also sets in by the action of bacterial enzymes
* Transport of lipids into the circulation is also different from what occurs with sugars and amino acids.
*** Compromises bile acid absorption in the terminal [[ileum]]
* Instead of being absorbed directly into capillary blood, chylomicrons are transported first into the lymphatic vessel that penetrates into each villus. 
*** Depletes the [[bile acid]] pool
* Chylomicron-rich lymph then drains into the system lymphatic system, which rapidly flows into blood. Blood-borne chylomicrons are rapidly disassembled and their constitutent lipids utilized throughout the body.
*** Disturb lipid [[absorption]]
* When large numbers of chylomicrons are being absorbed, the lymph draining from the small intestine appears milky and the lymphatics are easy to see.
* In the image below, of abdominal contents from a coyote, the fine white lines (arrows) are intestinal lymphatics packed with chylomicrons. That lymph passes through mesenteric lymph nodes (LN) and then into larger lymphatics.
* Another lipid of importance that is absorbed in the small intestine is cholesterol. 
* Cholesterol homeostatis results from a balance of cholestrol synthesis, absorption of dietary cholesterol, and elimination of cholesterol by excretion in bile. 
*  Years ago it was shown that cholesterol, but not plant sterols, is readily absorbed in the intestine. More recently, a specific transport protein (NPC1L1) has been identified that ferries cholesterol from the intestinal lumen into the enterocyte. 
* From there, a bulk of the cholesterol is esterified, incorporated into chylomicrons and shuttled into blood by the mechanisms described above.


* '''<u>Impaired Bile Acid Synthesis and Secretion</u>'''
** Bile acids support the [[emulsification]] of [[Triglyceride|triglycerides]] and form [[micelles]] with [[fatty acids]] and [[monoglycerides]] to enable [[absorption]] from the intestinal [[lumen]].
** Thus, decreased luminal availability may result in or contribute to steatorrhea.
** While there are rare inborn errors of [[bile acid]] synthesis and transport
*** Interruption of the [[enterohepatic circulation]] is the clinically most important pathomechanism which leads to decreased luminal availability of bile acids and lipid [[malabsorption]].


==Genetics:==
==Genetics:==
Following are the causes of fat malabsorption which are have genetic defect. Patients having these defects are affected because of decreased production of enzymes required in that are required to digest the the fatty food.
The development of steatorrhea is the result of multiple genetic mutations. Common genetic conditions associated with steatorrhea include:
* Cystic fibrosis
* [[Cystic fibrosis]]
* Crohn’s disease  
* [[Crohn's disease|Crohn’s disease]]
* Ulcerative colitis
* [[Ulcerative colitis]]
* Abetalipoproteinemia 
* [[Abetalipoproteinemia]] 


==Gross pathology==
==Gross pathology==
On Gross pathology the GIT looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.
On gross pathology the gastro-intestinal tract looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.


==Microscopic pathology==
==Microscopic pathology==

Latest revision as of 15:24, 20 February 2018

Steatorrhea Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Steatorrhea from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Steatorrhea pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Steatorrhea pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Steatorrhea pathophysiology

CDC on Steatorrhea pathophysiology

Steatorrhea pathophysiology in the news

Blogs on Steatorrhea pathophysiology

Directions to Hospitals Treating Steatorrhea

Risk calculators and risk factors for Steatorrhea pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Sunny Kumar MD [2]

Overview

Steatrorhea can be defined as loss of undigested fat in stools. The processes can be invoked by either defect of the normal architecture of digestive tract or it may involve defect of synthesis or secretion of enzymes of GI tract which are needed to metabolize fatty content of food.

Pathophysiology

Normal Fat absorption

To understand the pathophysiology of fat malabsoption we need to understand normal physiology of fat metabolization:[1][2][3][4][5][6][7][8]

Pathogenesis

Any disturbance in the normal physiology results in decreased absorption of the fats.

Genetics:

The development of steatorrhea is the result of multiple genetic mutations. Common genetic conditions associated with steatorrhea include:

Gross pathology

On gross pathology the gastro-intestinal tract looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.

Microscopic pathology

On microscopy the GIT looks normal in conditions which involves enzyme deficiencies. However in condition which involves obstruction of ducts involved in secretion of enzymes will look narrowed. The luminal causes which damage the luman of GIT and does not allow the absoption of faty products will also look ulcerated.

References

  1. ↑ Kumar R, Bhargava A, Jaiswal G (2017). "A case report on total pancreatic lipomatosis: An unusual entity". Int J Health Sci (Qassim). 11 (4): 71–73. PMC 5654180. PMID 29085272.
  2. ↑ Previti E, Salinari S, Bertuzzi A, Capristo E, Bornstein S, Mingrone G (2017). "Glycemic control after metabolic surgery: a Granger causality and graph analysis". Am J Physiol Endocrinol Metab. 313 (5): E622–E630. doi:10.1152/ajpendo.00042.2017. PMID 28698280.
  3. ↑ Vakhrushev YM, Lukashevich AP (2017). "[Specific features of impaired intestinal digestion, absorption, and microbiocenosis in patients with cholelithiasis]". Ter Arkh. 89 (2): 28–32. doi:10.17116/terarkh201789228-32. PMID 28281512.
  4. ↑ Scarpignato C, Gatta L, Zullo A, Blandizzi C, SIF-AIGO-FIMMG Group. Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners (2016). "Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression". BMC Med. 14 (1): 179. doi:10.1186/s12916-016-0718-z. PMC 5101793. PMID 27825371.
  5. ↑ Podboy A, Anderson BW, Sweetser S (2016). "61-Year-Old Man With Chronic Diarrhea". Mayo Clin Proc. 91 (2): e23–8. doi:10.1016/j.mayocp.2015.07.033. PMID 26769182.
  6. ↑ Burnett JR, Hooper AJ (2015). "Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia". Free Radic Biol Med. 88 (Pt A): 59–62. doi:10.1016/j.freeradbiomed.2015.05.044. PMID 26086616.
  7. ↑ Valenzise M, Alessi L, Bruno E, Cama V, Costanzo D, Genovese C; et al. (2016). "APECED syndrome in childhood: clinical spectrum is enlarging". Minerva Pediatr. 68 (3): 226–9. PMID 25502918.
  8. ↑ Wilcox C, Turner J, Green J (2014). "Systematic review: the management of chronic diarrhoea due to bile acid malabsorption". Aliment Pharmacol Ther. 39 (9): 923–39. doi:10.1111/apt.12684. PMID 24602022.

Template:WS Template:WH

Retrieved from "https://www.wikidoc.org/index.php?title=Steatorrhea_pathophysiology&oldid=1446361"