Primary biliary cirrhosis pathophysiology: Difference between revisions

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Revision as of 21:16, 11 August 2017

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

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Pathogenesis

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
The progression to [disease name] usually involves the [molecular pathway].
The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

[Disease name] is transmitted in [mode of genetic transmission] pattern.
Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
The development of [disease name] is the result of multiple genetic mutations.

Associated Conditions

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Histopathology

References

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+__NOTOC__
+{{Primary biliary cirrhosis}}
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-__NOTOC__
-{{Primary biliary cirrhosis}}
 {{CMG}}; {{AE}}
+==Overview==
+The exact pathogenesis of [disease name] is not fully understood.
+OR
+It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
+OR
+[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
+OR
+Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
+OR
+[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
+OR
+The progression to [disease name] usually involves the [molecular pathway].
-{{PleaseHelp}}
+OR
-==Overview==
+The pathophysiology of [disease/malignancy] depends on the histological subtype.
 ==Pathophysiology==
-The pathogenesis of the disease is unknown at this time, but research indicates that there is an [[Immunology|immunological]] basis for the [[disease]], making it an [[autoimmune disorder]].  Most of the patients (>90%) seem to have anti-mitochondrial antibodies (AMAs) against [[pyruvate dehydrogenase complex]]  (PDC-E2), an enzyme complex that is found in the [[mitochondria]].
-In addition, a more specific test to confirm this disease from a bone disorder such as Paget's (disease of bone) which also has increases in alkaline phosphatase is the [[Gamma glutamyl transpeptidase|gamma-glutamyl trans peptidase]] test (GGTP). An increase in GGTP could indicate presence of primary biliary cirrhosis.
-% of patients with acute liver failure have [[anti-transglutaminase antibodies]]<ref name="pmid17657817">{{cite journal | author = Leung PS, Rossaro L, Davis PA, ''et al'' | title = Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis | journal = | volume = | issue = | pages = | year = 2007 | pmid = 17657817 | doi = 10.1002/hep.21828}}</ref>  suggesting a role of [[gluten sensitivity]] in primary biliary cirrhosis, and primary biliary cirrhosis is considerable more common in [[Gluten-sensitive enteropathy associated conditions#Diseases of the pancreas.2C gall bladder.2C bile duct|gluten sensitive enteropathy]] than the normal population.<ref name="pmid74661">{{cite journal | author = Logan RF, Ferguson A, Finlayson ND, Weir DG | title = Primary biliary cirrhosis and coeliac disease: an association? | journal = Lancet | volume = 1 | issue = 8058 | pages = 230-3 | year = 1978 | pmid = 74661 | doi = }}</ref><ref name="pmid12385447">{{cite journal | author = Volta U, Rodrigo L, Granito A, ''et al'' | title = Celiac disease in autoimmune cholestatic liver disorders | journal = Am. J. Gastroenterol. | volume = 97 | issue = 10 | pages = 2609-13 | year = 2002 | pmid = 12385447 | doi = }}</ref>
+===Pathogenesis===
+*The exact pathogenesis of [disease name] is not fully understood.
+OR
+*It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
+*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
+*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
+*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
+*The progression to [disease name] usually involves the [molecular pathway].
+*The pathophysiology of [disease/malignancy] depends on the histological subtype.
-In some cases of disease, protein expression may cause an [[immune tolerance]] failure, as might be the case with [[nucleoporin 210kDa| gp210]] and [[nucleoporin 62|p62]], nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients.<ref name="pmid16337775">{{cite journal | author = Nakamura M, Takii Y, Ito M, ''et al'' | title = Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis | journal = J. Autoimmun. | volume = 26 | issue = 2 | pages = 138-45 | year = 2006 | pmid = 16337775 | doi = 10.1016/j.jaut.2005.10.007}}</ref> Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.
+==Genetics==
+*[Disease name] is transmitted in [mode of genetic transmission] pattern.
+*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
+*The development of [disease name] is the result of multiple genetic mutations.
+==Associated Conditions==
-In 2003 it was reported that an environmental gram negative alphabacterium — ''[[Novosphingobium aromaticivorans]]''<ref name=Selmi2003>{{cite journal |author=Selmi C, Balkwill DL, Invernizzi P, ''et al.'' |title=Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium |journal=Hepatology |volume=38 |issue=5 |pages=1250–7 |year=2003 |month=November |pmid=14578864 |doi=10.1053/jhep.2003.50446 }}</ref> was strongly associated with this disease. Subsequent reports appear to have confirmed this finding suggesting an aetiological role for this organism.<ref name=Mohammed2009>{{cite journal |author=Mohammed JP, Mattner J |title=Autoimmune disease triggered by infection with alphaproteobacteria |journal=Expert Rev Clin Immunol |volume=5 |issue=4 |pages=369–379 |year=2009 |month=July |pmid=20161124 |pmc=2742979 |doi=10.1586/ECI.09.23 }}</ref><ref name=Kaplan2004>{{cite journal |author=Kaplan MM |title=''Novosphingobium aromaticivorans'': a potential initiator of primary biliary cirrhosis |journal=Am. J. Gastroenterol. |volume=99 |issue=11 |pages=2147–9 |year=2004 |month=November |pmid=15554995 |doi=10.1111/j.1572-0241.2004.41121.x }}</ref><ref name=Selmi2004>{{cite journal |author=Selmi C, Gershwin ME |title=Bacteria and human autoimmunity: the case of primary biliary cirrhosis |journal=Curr Opin Rheumatol |volume=16 |issue=4 |pages=406–10 |year=2004 |month=July |pmid=15201604 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1040-8711&volume=16&issue=4&spage=406}}</ref> The mechanism appears to be a cross reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells.<ref name=Mattner2008>{{cite journal |author=Mattner J, Savage PB, Leung P, ''et al.'' |title=Liver autoimmunity triggered by microbial activation of natural killer T cells |journal=Cell Host Microbe |volume=3 |issue=5 |pages=304–15 |year=2008 |month=May |pmid=18474357 |pmc=2453520 |doi=10.1016/j.chom.2008.03.009 |url=http://linkinghub.elsevier.com/retrieve/pii/S1931-3128(08)00120-0}}</ref> The gene encoding [[cluster of differentiation 101|CD101]] may also play a role in host susceptibility to this disease.<ref name=Mohammed2003>{{cite journal |author=Mohammed JP, Fusakio ME, Rainbow DB, ''et al.'' |title=Identification of Cd101 as a susceptibility gene for ''Novosphingobium aromaticivorans''-induced liver autoimmunity |journal=J. Immunol. |volume=187 |issue=1 |pages=337–49 |year=2011 |month=July |pmid=21613619 |pmc=3134939 |doi=10.4049/jimmunol.1003525 |url=http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21613619}}</ref>
+==Gross Pathology==
+*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
-===Genetics===
+==Microscopic Pathology==
-A genetic predisposition to disease has been thought important for some time, as evident by cases of PBC in family members, concordance in identical twins, and clustering of autoimmune diseases.  In 2009 a Canadian led group of investigators reported in the New England Journal of Medicine results from the first genome scan of PBC patients.<ref>{{cite journal |author=Hirschfield GM, Liu X, Xu C, ''et al.'' |title=Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants |journal=N. Engl. J. Med. |volume=360 |issue=24 |pages=2544–55 |year=2009 |month=June |pmid=19458352 |pmc=2857316 |doi=10.1056/NEJMoa0810440 |url=http://content.nejm.org/cgi/content/full/NEJMoa0810440}}</ref><ref>http://www.torontoliver.ca</ref>  This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the etiology of the disease in addition to the HLA region, suggesting future therapeutic targets.
+*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 ===Histopathology===