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| | ==Physical examination== |
| | ==References== |
| | {{reflist|2}} |
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| | {{WH}} |
| | {{WS}} |
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| | ==References== |
| | {{Reflist|2}} |
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| ===Pathophysiology prev=== | | ===Pathophysiology prev=== |
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| {{CMG}} {{AE}} | | {{CMG}} {{AE}} |
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| ==Overview==
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| Cirrhosis occurs due to long term [[liver]] injury which causes an imbalance between [[matrix]] production and degradation. Early disruption of the normal hepatic matrix results in its replacement by [[scar tissue]], which in turn has deleterious effects on cell function.
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| ==Pathophysiology== | | ===Pathophysiology prev=== |
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| | | {| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;" |
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| Pathology
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| * There are four stages of Cirrhosis as it progresses:
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| ** Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
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| ** Development of biliary stasis and fibrosis
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| *Periportal fibrosis progresses to bridging fibrosis
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| *Increased proliferation of smaller bile ductules leading to regenerative nodule formation.
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| ==Associated Conditions== | |
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| {{family tree/start}}
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| {{family tree| | | | | | | | | | | A01 | | | | | | | | | |A01='''Portal Hypertension'''<br>associated conditions}}
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| {{family tree| | | | | | | | | | | |!| | | | | | | | | | |}}
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| {{family tree| | | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| | | |}}
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| {{family tree| | | B01 | | B02 | | B03 | | B04 | | B05 | | |B01='''''Immunological disorders'''''|B02='''''Infections'''''|B03='''''Medication and toxins'''''|B04='''''Genetic disorders'''''|B05='''''Prothrombotic conditions'''''}}
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| {{family tree| | | |!| | | |!| | | |!| | | |!| | | |!| | | |}}
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| {{family tree|boxstyle=text-align: left; | | | B01 | | B02 | | B03 | | B04 | | B05 | | |B01=• [[Common variable immunodeficiency|Common variable immunodeficiency syndrome]]<ref name="pmid23420139">{{cite journal |vauthors=Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L, Raffeld M, Kleiner DE, Heller T, Strober W |title=Nodular regenerative hyperplasia in common variable immunodeficiency |journal=J. Clin. Immunol. |volume=33 |issue=4 |pages=748–58 |year=2013 |pmid=23420139 |pmc=3731765 |doi=10.1007/s10875-013-9873-6 |url=}}</ref><br>• [[Connective tissue disease|Connective tissue diseases]]<ref name="pmid21393872">{{cite journal |vauthors=Vaiphei K, Bhatia A, Sinha SK |title=Liver pathology in collagen vascular disorders highlighting the vascular changes within portal tracts |journal=Indian J Pathol Microbiol |volume=54 |issue=1 |pages=25–31 |year=2011 |pmid=21393872 |doi=10.4103/0377-4929.77319 |url=}}</ref><br>• [[Crohn’s disease]]<ref name="pmid18415755">{{cite journal |vauthors=De Boer NK, Tuynman H, Bloemena E, Westerga J, Van Der Peet DL, Mulder CJ, Cuesta MA, Meuwissen SG, Van Nieuwkerk CM, Van Bodegraven AA |title=Histopathology of liver biopsies from a thiopurine-naïve inflammatory bowel disease cohort: prevalence of nodular regenerative hyperplasia |journal=Scand. J. Gastroenterol. |volume=43 |issue=5 |pages=604–8 |year=2008 |pmid=18415755 |doi=10.1080/00365520701800266 |url=}}</ref><br>• [[Organ transplant|Solid organ transplant]]<br>•• [[Renal transplantation]]<ref name="pmid1438671">{{cite journal |vauthors=Allison MC, Mowat A, McCruden EA, McGregor E, Burt AD, Briggs JD, Junor BJ, Follett EA, MacSween RN, Mills PR |title=The spectrum of chronic liver disease in renal transplant recipients |journal=Q. J. Med. |volume=83 |issue=301 |pages=355–67 |year=1992 |pmid=1438671 |doi= |url=}}</ref><br>•• [[Liver transplantation]]<ref name="pmid8020909">{{cite journal |vauthors=Gane E, Portmann B, Saxena R, Wong P, Ramage J, Williams R |title=Nodular regenerative hyperplasia of the liver graft after liver transplantation |journal=Hepatology |volume=20 |issue=1 Pt 1 |pages=88–94 |year=1994 |pmid=8020909 |doi= |url=}}</ref><br>• [[Hashimoto's thyroiditis]]<ref name="pmid2944377">{{cite journal |vauthors=Imai Y, Minami Y, Miyoshi S, Kawata S, Saito R, Noda S, Tamura S, Nishikawa M, Tajima K, Tarui S |title=Idiopathic portal hypertension associated with Hashimoto's disease: report of three cases |journal=Am. J. Gastroenterol. |volume=81 |issue=9 |pages=791–5 |year=1986 |pmid=2944377 |doi= |url=}}</ref><br>• [[Autoimmune disease]]<ref name="pmid11831999">{{cite journal |vauthors=Li X, Gao W, Chen J, Tang W |title=[Non-cirrhotic portal hypertension associated with autoimmune disease] |language=Chinese |journal=Zhonghua Wai Ke Za Zhi |volume=38 |issue=2 |pages=101–3 |year=2000 |pmid=11831999 |doi= |url=}}</ref>
| |
| |B02=• [[Bacterial]] intestinal [[Infection|infections]]<br>• Recurrent [[Escherichia coli|E.coli]] infection<ref name="pmid3276575">{{cite journal |vauthors=Kono K, Ohnishi K, Omata M, Saito M, Nakayama T, Hatano H, Nakajima Y, Sugita S, Okuda K |title=Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits |journal=Gastroenterology |volume=94 |issue=3 |pages=787–96 |year=1988 |pmid=3276575 |doi= |url=}}</ref><br>• [[Human Immunodeficiency Virus (HIV)|Human immunodeficiency virus (HIV) infection]]<ref name="pmid24155091">{{cite journal |vauthors=Siramolpiwat S, Seijo S, Miquel R, Berzigotti A, Garcia-Criado A, Darnell A, Turon F, Hernandez-Gea V, Bosch J, Garcia-Pagán JC |title=Idiopathic portal hypertension: natural history and long-term outcome |journal=Hepatology |volume=59 |issue=6 |pages=2276–85 |year=2014 |pmid=24155091 |doi=10.1002/hep.26904 |url=}}</ref><br>• [[AIDS antiretroviral drugs|Antiretroviral therapy]]<ref name="pmid18389904">{{cite journal |vauthors=Maida I, Garcia-Gasco P, Sotgiu G, Rios MJ, Vispo ME, Martin-Carbonero L, Barreiro P, Mura MS, Babudieri S, Albertos S, Garcia-Samaniego J, Soriano V |title=Antiretroviral-associated portal hypertension: a new clinical condition? Prevalence, predictors and outcome |journal=Antivir. Ther. (Lond.) |volume=13 |issue=1 |pages=103–7 |year=2008 |pmid=18389904 |doi= |url=}}</ref>|B03=• [[Thiopurine|Thiopurine derivatives]]<br>•• [[Didanosine]]<br>•• [[Azathioprine]]<ref name="pmid17504943">{{cite journal |vauthors=Vernier-Massouille G, Cosnes J, Lemann M, Marteau P, Reinisch W, Laharie D, Cadiot G, Bouhnik Y, De Vos M, Boureille A, Duclos B, Seksik P, Mary JY, Colombel JF |title=Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine |journal=Gut |volume=56 |issue=10 |pages=1404–9 |year=2007 |pmid=17504943 |pmc=2000290 |doi=10.1136/gut.2006.114363 |url=}}</ref><br>•• [[Thioguanine|Cis-thioguanine]]<ref name="pmid21272804">{{cite journal |vauthors=Calabrese E, Hanauer SB |title=Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease |journal=J Crohns Colitis |volume=5 |issue=1 |pages=48–53 |year=2011 |pmid=21272804 |doi=10.1016/j.crohns.2010.08.007 |url=}}</ref> <br>• [[Arsenicals]]<ref name="pmid2398270">{{cite journal |vauthors=Nevens F, Fevery J, Van Steenbergen W, Sciot R, Desmet V, De Groote J |title=Arsenic and non-cirrhotic portal hypertension. A report of eight cases |journal=J. Hepatol. |volume=11 |issue=1 |pages=80–5 |year=1990 |pmid=2398270 |doi= |url=}}</ref><br>• [[Vitamin A]]<ref name="pmid2019375">{{cite journal |vauthors=Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C |title=Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases |journal=Gastroenterology |volume=100 |issue=6 |pages=1701–9 |year=1991 |pmid=2019375 |doi= |url=}}</ref>|B04=• Adams-Olivier syndrome<ref name="pmid15832360">{{cite journal |vauthors=Girard M, Amiel J, Fabre M, Pariente D, Lyonnet S, Jacquemin E |title=Adams-Oliver syndrome and hepatoportal sclerosis: occasional association or common mechanism? |journal=Am. J. Med. Genet. A |volume=135 |issue=2 |pages=186–9 |year=2005 |pmid=15832360 |doi=10.1002/ajmg.a.30724 |url=}}</ref><br>• [[Turner syndrome]]<ref name="pmid23121401">{{cite journal |vauthors=Roulot D |title=Liver involvement in Turner syndrome |journal=Liver Int. |volume=33 |issue=1 |pages=24–30 |year=2013 |pmid=23121401 |doi=10.1111/liv.12007 |url=}}</ref><br>• Phosphomannose isomerase deficiency<ref name="pmid19101627">{{cite journal |vauthors=de Lonlay P, Seta N |title=The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib |journal=Biochim. Biophys. Acta |volume=1792 |issue=9 |pages=841–3 |year=2009 |pmid=19101627 |doi=10.1016/j.bbadis.2008.11.012 |url=}}</ref><br>• Familial cases<ref name="pmid3499813">{{cite journal |vauthors=Sarin SK, Mehra NK, Agarwal A, Malhotra V, Anand BS, Taneja V |title=Familial aggregation in noncirrhotic portal fibrosis: a report of four families |journal=Am. J. Gastroenterol. |volume=82 |issue=11 |pages=1130–3 |year=1987 |pmid=3499813 |doi= |url=}}</ref>
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| |B05=• [[Inherited thrombophilia|Inherited thrombophilias]] <ref name="pmid18685811">{{cite journal |vauthors=Bayan K, Tüzün Y, Yilmaz S, Canoruc N, Dursun M |title=Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension |journal=J. Thromb. Thrombolysis |volume=28 |issue=1 |pages=57–62 |year=2009 |pmid=18685811 |doi=10.1007/s11239-008-0244-8 |url=}}</ref><br>• [[Myeloproliferative neoplasm]]<ref name="pmid18685811" /><br>• [[Antiphospholipid syndrome]]<ref name="pmid18685811" /><br>• [[Sickle cell disease]]<ref name="pmid17558079">{{cite journal |vauthors=Kumar S, Joshi R, Jain AP |title=Portal hypertension associated with sickle cell disease |journal=Indian J Gastroenterol |volume=26 |issue=2 |pages=94 |year=2007 |pmid=17558079 |doi= |url=}}</ref>}}
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| {{family tree/end}}
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| ===Gross Pathology===
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| Macroscopically, the liver may initially be enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and the color is often yellow (if associates [[steatosis]]). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis.
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| * In the micronodular form ([[René Laennec|Laennec]]'s cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm.
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| * In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm.
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| * The mixed cirrhosis consists of a variety of nodules with different sizes.
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| ==Gross Pathology==
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| {| class="wikitable"
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| | colspan="3" |
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| *On [[gross pathology]], [[Cirrhosis|cirrhotic liver]], [[splenomegaly]], and [[esophageal varices]] are characteristic findings in portal hypertension.
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| |- | | |- |
| | | | | {{#ev:youtube|https://https://www.youtube.com/watch?v=5szNmKtyBW4|350}} |
| === Cirrhosis ===
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| On [[gross pathology]] there are two types of [[cirrhosis]]:
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| * Micronodular [[cirrhosis]] which is uniform and diffuse, mostly due to [[alcohol]].
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| * Macronodular [[cirrhosis]] which is irregular, mostly due to [[viral hepatitis]].
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| [[image:Cirrosi micronodular.1427.jpg|thumb|200px|Micronodular cirrhosis - By Amadalvarez (Own work), via Wikimedia Commons<ref><CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)></ref>]]
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| [[image:Fig78x.jpg|thumb|200px|Macronodular cirrhosis<ref name="urlwww.meddean.luc.edu">{{cite web |url=http://www.meddean.luc.edu/lumen/MedEd/orfpath/images/fig78x.jpg |title=www.meddean.luc.edu |format= |work= |accessdate=}}</ref>]]
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| |- | | |- |
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| === Splenomegaly ===
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| On [[gross pathology]], diffuse enlargement and [[congestion]] of the [[spleen]] are characteristic findings of [[splenomegaly]].
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| | colspan="2" |
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| [[image:Esplenomegalia i hiperplasia linfoide folicular reactiva. IMG 2865.jpg|thumb|200px|center|Splenomegaly - By Amadalvarez (Own work), via Wikimedia Commons<ref>Amadalvarez - <span class="int-own-work" lang="en">Own work</span>, <"https://creativecommons.org/licenses/by-sa/4.0" title="Creative Commons Attribution-Share Alike 4.0">CC BY-SA 4.0, <"https://commons.wikimedia.org/w/index.php?curid=49669333">Link</ref>]]
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| === Esophageal Varices ===
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| On gross pathology, prominent, congested, and tortoise [[veins]] in the lower parts of [[esophagus]] are characteristic findings of [[esophageal varices]].
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| | colspan="2" |
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| [[image:F21. Venous enlargement in hepatic cirrhosis. Alfred Kast Wellcome L0074357.jpg|thumb|200px|center|Esophageal varices<ref><http://wellcomeimages.org/indexplus/obf_images/29/b4/13f38971164f946a97f9d32ddd93.jpg>Gallery: <"http://wellcomeimages.org/indexplus/image/L0074357.html"><"http://creativecommons.org/licenses/by/4.0> CC BY 4.0, <"https://commons.wikimedia.org/w/index.php?curid=36297209"></ref>]]
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| |} | | |} |
| | __NOTOC__ |
| | {{Cirrhosis}} |
| | {{CMG}} {{AE}} |
|
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| [http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
| | == History and Symptoms == |
| <gallery>
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| Image:Cirrhosis 001.jpg|Cirrhosis: Gross, external view of micronodular cirrhosis
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| Image:Cirrhosis 002.jpg|Cirrhosis: Gross, cut section of previous one (an excellent example)
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| Image:Cirrhosis 003.jpg|Cirrhosis: Gross, close-up image
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| Image:Cirrhosis 004.jpg|Macronodular cirrhosis and hepatoma
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| </gallery>
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|
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|
| <gallery>
| | * History should include: |
| Image:Cirrhosis 005.jpg|Cirrhosis: Gross, close-up, natural color (an excellent example)
| | ** Appearance of bowel movements |
| Image:Cirrhosis 006.jpg|Cirrhosis: Gross, close-up (an excellent example)
| | ** Travel history |
| Image:Cirrhosis 007.jpg|Cirrhosis: Gross, close-up view
| | ** Associated symptoms |
| Image:Cirrhosis 008.jpg|Micronodular cirrhosis: Gross, external view (an excellent example)
| | ** Immune status |
| </gallery>
| | ** Woodland exposure |
| | ==References== |
| | {{reflist|2}} |
|
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|
| <gallery>
| | {{WH}} |
| Image:Cirrhosis 009.jpg|Micronodular cirrhosis: Gross, close-up image
| | {{WS}} |
| Image:Cirrhosis 010.jpg|Micronodular cirrhosis: Gross (an excellent example)
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| Image:Cirrhosis 011.jpg|Macronodular cirrhosis: Gross, natural color (perfect color for cirrhosis), close-up, an excellent example
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| Image:Cirrhosis 012.jpg|Cirrhosis with portocaval shunt: Gross, severe cirrhosis with extensive liver necrosis due to thrombosis of portocaval shunt (well shown)
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| </gallery>
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|
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|
| <gallery>
| | ==Other Imaging Findings== |
| Image:Cirrhosis 013.jpg|Endstage cirrhosis: Gross, natural color, close-up (an excellent example)
| | * [[Endoscopy]] |
| Image:Cirrhosis 014.jpg|Endstage cirrhosis: Gross, natural color, close-up view is an excellent example for nodules of yellow-orange liver tissue and broad irregular bands of fibrosis
| | * [[Barium enema]] |
| Image:Cirrhosis 015.jpg|Endstage cirrhosis: Gross, natural color, close-up cut surface, very well shown nodules of yellow and necrotic opaque liver tissue with broad and irregular bands of fibrosis (an excellent example)
| | * [[Colonoscopy]] |
| Image:Cirrhosis 016.jpg|Macronodular cirrhosis: Gross, natural color, external view of liver and very enlarged spleen (liver has variable size nodules up to about 2 cm)
| | * [[Sigmoidoscopy]] |
| </gallery>
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|
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|
| <gallery>
| | ==Other diagnostic studies== |
| Image:Cirrhosis 017.jpg|Macronodular cirrhosis: Gross, natural color, cut surface, large irregular bands of fibrosis with variable size liver cell nodules up to about 8 mm and all necrotic appears to be an end stage liver disease.
| | == Other Diagnostic Studies == |
| Image:Cirrhosis 018.jpg|Macronodular cirrhosis: Gross, natural color view of frontal sections of liver and spleen showing a contracted macronodular liver and an enlarged spleen as large as the liver
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| Image:Cirrhosis 019.jpg|Macronodular cirrhosis: Gross, natural color slab of liver
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| Image:Cirrhosis 020.jpg|Fatty change and early cirrhosis: Gross, natural color, rather close-up image showing typical fatty color, and in lighting at lower right of micrography micronodularity is evident (quite good example)
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| </gallery>
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|
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|
| <gallery>
| | * Breath hydrogen test |
| Image:Cirrhosis 021.jpg|Cirrhosis with portal vein thrombosis: Gross, natural color, sectioned liver with portal vein exposed and filled with red thrombus. A good example of end stage cirrhosis.
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| Image:Cirrhosis 022.jpg|Endstage cirrhosis with lobular necrosis: Gross, natural color, very close-up view (an excellent example of alcoholic cirrhosis)
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| Image:Cirrhosis 023.jpg|Micronodular cirrhosis: Gross, natural color view of whole liver through capsule with obvious cirrhosis (note to quite large liver)
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| Image:Cirrhosis 024.jpg|Micronodular cirrhosis: Gross, natural color, view of whole liver showing external surface typical cirrhotic liver (history of alcoholism)
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| </gallery>
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|
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|
| <gallery>
| | * [[HIV test]]ing for those patients suspected of having HIV |
| Image:Cirrhosis 025.jpg|Lung: Idiopathic Interstitial Fibrosis: Gross, natural color, an excellent photo of lung cirrhosis (close-up view)
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| Image:Cirrhosis 026.jpg|Endstage cirrhosis: Gross, natural color, slice of liver. Portal vein is opened to show size and patency.
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| Image:Cirrhosis 027.jpg|Endstage cirrhosis: Gross, natural color, severe cirrhosis with bile stasis
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| Image:Cirrhosis 028.jpg|Portal Vein Thrombosis with cirrhosis: Gross, close-up, micronodular cirrhosis with portal vein thrombosis
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| </gallery>
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|
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|
| <gallery>
| | == |
| Image:Cirrhosis 029.jpg|Lung: Hematite: Gross, natural color, external view of "pulmonary cirrhosis" with typical hematite color
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| Image:Cirrhosis 030.jpg|Gross, natural color of liver and stomach view from external surfaces, micronodular cirrhosis and hemorrhagic gastritis (as the surgeon would see these in natural color)
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| </gallery>
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|
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|
| ===Microscopic Pathology=== | | ==Overview== |
| Microscopically, cirrhosis is characterized by regeneration nodules surrounded by fibrous septa. In these nodules, regenerating [[hepatocyte]]s are disorderly disposed. Portal tracts, [[central vein]]s and the radial pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate ([[lymphocyte]]s, [[macrophage]]s). If it is a [[secondary biliary cirrhosis]], biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appears as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes".<ref>[http://www.pathologyatlas.ro/Cirrhosis.html Pathology atlas], "cirrhosis".</ref>
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| ==Microscopic Pathology==
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| {| class="wikitable"
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| | colspan="2" |
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| *The main microscopic [[histopathological]] findings in portal hypertension are related to [[Cirrhosis (patient information)|cirrhosis]], [[esophageal varices]], [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]], and congestive [[hepatopathy]] due to [[heart failure]] or [[Budd-Chiari syndrome]].
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| |-
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| === Cirrhosis ===
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| Robbins definition of microscopic [[histopathological]] findings in cirrhosis includes (all three is needed for diagnosis):<ref>{{cite book | last = Mitchell | first = Richard | title = Pocket companion to Robbins and Cotran pathologic basis of disease | publisher = Elsevier Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416054542 }}</ref>
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| * Bridging [[fibrosis]]
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| * [[Nodule]] formation
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| * Disruption of the [[hepatic]] architecture
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| [[image:Cirrhosis.jpg|thumb|200px|Cirrhosis with bridging fibrosis (yellow arrow) and nodule (black arrow) - By Nephron, via Librepathology.org<ref name="urlFile:Cirrhosis high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Cirrhosis_high_mag.jpg#filelinks |title=File:Cirrhosis high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
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| |-
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| === Esophageal varices ===
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| The main microscopic [[histopathological]] findings in [[esophageal varices]] are:
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| * Large dilated submucosal [[veins]] ('''key feature''')
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| * [[Blood]] (fresh)
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| * [[Hemosiderin]]-laden [[macrophages]].
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| [[image:Eso-varices.jpg|thumb|200px|Esophageal varices with submucosal vein (black arrow), via Librepathology.org<ref name="urlEsophageal varices - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/Esophageal_varices#cite_note-3 |title=Esophageal varices - Libre Pathology |format= |work= |accessdate=}}</ref>]]
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| |-
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| === Hepatic amyloidosis ===
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| The main microscopic [[histopathological]] findings in [[Hepatic amyloidosis with intrahepatic cholestasis|hepatic amyloidosis]] is amorphous extracellular pink stuff on H&E staining.
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| [[image:Amyloidosis - high mag.jpg|thumb|200px|Hepatic amyloidosis with amorphous amyloids (black arrow) and normal hepatocytes (blue arrow), via Librepathology.org<ref name="urlFile:Hepatic amyloidosis - high mag.jpg - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:Hepatic_amyloidosis_-_high_mag.jpg |title=File:Hepatic amyloidosis - high mag.jpg - Libre Pathology |format= |work= |accessdate=}}</ref>]]
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| === Congestive hepatopathy ===
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| The main microscopic [[histopathological]] findings in congestive [[hepatopathy]] (due to [[heart failure]] or [[Budd-Chiari syndrome]]) are:
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| * [[Atrophy]] of zone III
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| * Distension of portal [[venule]] ([[central vein]])
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| * Perisinusoidal [[fibrosis]] which may progress to centrilobular [[fibrosis]] and then diffuse [[fibrosis]]
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| * [[Sinusoidal]] dilation in ''all'' zone III areas ('''key feature)'''
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| [[image:Congestive hepatopathy.jpg|thumb|200px|Congestive hepatopathy with central vein (yellow arrowhead), inflammatory cells, Councilman body (green arrowhead), and hepatocyte with mitotic figure (red arrowhead), via Librepathology.org<ref name="urlFile:2 CEN NEC 1 680x512px.tif - Libre Pathology">{{cite web |url=https://librepathology.org/wiki/File:2_CEN_NEC_1_680x512px.tif |title=File:2 CEN NEC 1 680x512px.tif - Libre Pathology |format= |work= |accessdate=}}</ref>]]
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| |}
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| ===Chronic active hepatitis - Cirrhosis===
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| {{#ev:youtube|CzKGvWZrUpU}}
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| ===Micronodular cirrhosis===
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| {{#ev:youtube|CV8OYeIUXko}}
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| ===Primary biliary cirrhosis===
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| {{#ev:youtube|Jj8ozr_IttM}}
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|
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|
| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
|
| |
|
| [[Category:Gastroenterology]]
| | {{WH}} |
| [[Category:Hepatology]]
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| [[Category:Disease]]
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| {{WS}} | | {{WS}} |
| {{WH}}
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| ===the end===
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| -
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| ==== Portal HTN results from the combination of the following: ====
| |
| * Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
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| * Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.
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| Pathogenesis of Cirrhosis due to Alcohol:
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| * More than 66 percent of all American adults consume alcohol.
| |
| * Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
| |
| * Mechanisms of alcohol-induced damage include:
| |
| ** Impaired protein synthesis, secretion, glycosylation
| |
| * Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
| |
| ** Lipoprotein secretion
| |
| ** Decreased fatty acid oxidation
| |
| ** Increased fatty acid uptake
| |
| * Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
| |
| * Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
| |
| ** Trafficking of hepatic proteins
| |
| ** Interrupting microtubule formation
| |
| ** Interfering with enzyme activities
| |
| * Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.<ref name="pmid11984538">{{cite journal |vauthors=Arthur MJ |title=Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C |journal=Gastroenterology |volume=122 |issue=5 |pages=1525–8 |year=2002 |pmid=11984538 |doi= |url=}}</ref>
| |
| *Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
| |
| *Stellate cell activation leads to the production of extracellular matrix and collagen.
| |
| * Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
| |
| * Shrinkage of the liver occurs over years due to repeated insults that lead to:
| |
| ** Loss of hepatocytes
| |
| ** Increased production and deposition of collagen
| |
|
| |
|
| | | ===Pathophysiology prev=== |
| Pathology
| | <div style="-webkit-user-select: none;"> |
| * There are four stages of Cirrhosis as it progresses:
| | {| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;" |
| ** Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
| |
| ** Development of biliary stasis and fibrosis
| |
| *Periportal fibrosis progresses to bridging fibrosis
| |
| *Increased proliferation of smaller bile ductules leading to regenerative nodule formation.
| |
| | |
| | |
| | |
| ===Causes=== | |
| {| class="wikitable"
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Drugs and Toxins
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Infections
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Autoimmune
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Metabolic
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Biliary obstruction(Secondary bilary cirrhosis)
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Vascular
| |
| ! style="background:#4479BA; color: #FFFFFF;" align="center" + |Miscellaneous
| |
| |- | | |- |
| |Alcohol | | | {{#ev:youtube|https://https://www.youtube.com/watch?v=5szNmKtyBW4|350}} |
| |Hepatitis B | |
| |Primary Biliary Cirrhosis
| |
| |Wilson's disease
| |
| |Cystic fibrosis
| |
| |Chronic RHF
| |
| |Sarcoidosis
| |
| |-
| |
| |Methotrexate
| |
| |Hepatitis C
| |
| |Autoimmune hepatitis
| |
| |Hemochromatosis
| |
| |Biliary atresia
| |
| |Budd-Chiari syndrome
| |
| |Intestinal
| |
| | |
| bypass operations for obesity
| |
| |-
| |
| |Isoniazid
| |
| |Schistosoma japonicum
| |
| |Primary Sclerosing Cholangitis
| |
| |Alpha-1 antitrypsin deficiency
| |
| |Bile duct strictures
| |
| |Veno-occlusive disease | |
| |Cryptogenic: unknown
| |
| |- | | |- |
| |Methyldopa
| |
| |
| |
| |
| |
| |Porphyria
| |
| |Gallstones
| |
| |
| |
| |
| |
| |-
| |
| |
| |
| |
| |
| |
| |
| |Glycogen storage diseases (such as Galactosaemia, Abetalipoproteinaemia)
| |
| |
| |
| |
| |
| |
| |
| |} | | |} |
| | | __NOTOC__ |
| ===Cirrhosis===
| | {{Cirrhosis}} |
| | | {{CMG}} {{AE}} |
| Pathophysiology <ref name="pmid7932316">{{cite journal |vauthors=Arthur MJ, Iredale JP |title=Hepatic lipocytes, TIMP-1 and liver fibrosis |journal=J R Coll Physicians Lond |volume=28 |issue=3 |pages=200–8 |year=1994 |pmid=7932316 |doi= |url=}}</ref><ref name="pmid8502273">{{cite journal |vauthors=Friedman SL |title=Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies |journal=N. Engl. J. Med. |volume=328 |issue=25 |pages=1828–35 |year=1993 |pmid=8502273 |doi=10.1056/NEJM199306243282508 |url=}}</ref><ref name="pmid8682489">{{cite journal |vauthors=Iredale JP |title=Matrix turnover in fibrogenesis |journal=Hepatogastroenterology |volume=43 |issue=7 |pages=56–71 |year=1996 |pmid=8682489 |doi= |url=}}</ref><ref name="pmid7959178">{{cite journal |vauthors=Gressner AM |title=Perisinusoidal lipocytes and fibrogenesis |journal=Gut |volume=35 |issue=10 |pages=1331–3 |year=1994 |pmid=7959178 |pmc=1374996 |doi= |url=}}</ref><ref name="pmid17332881">{{cite journal |vauthors=Iredale JP |title=Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ |journal=J. Clin. Invest. |volume=117 |issue=3 |pages=539–48 |year=2007 |pmid=17332881 |pmc=1804370 |doi=10.1172/JCI30542 |url=}}</ref><ref name="pmid11984538">{{cite journal |vauthors=Arthur MJ |title=Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C |journal=Gastroenterology |volume=122 |issue=5 |pages=1525–8 |year=2002 |pmid=11984538 |doi= |url=}}</ref>
| |
| * When an injured issue is replaced by a collagenous scar, it is termed as fibrosis.
| |
| * When fibrosis of the liver reaches an advanced stage where distortion of the hepatic vasculature also occurs, it is termed as cirrhosis of the liver.
| |
| * The cellular mechanisms responsible for cirrhosis are similar regardless of the type of initial insult and site of injury within the liver lobule.
| |
| * Viral hepatitis involves the periportal region, whereas involvement in alcoholic liver disease is largely pericentral.
| |
| * If the damage progresses, panlobular cirrhosis may result.
| |
| * Cirrhosis involves the following steps: <ref name="pmid7737629">{{cite journal |vauthors=Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G |title=Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension |journal=Hepatology |volume=21 |issue=5 |pages=1238–47 |year=1995 |pmid=7737629 |doi= |url=}}</ref>
| |
| ** Inflammation
| |
| ** Hepatic stellate cell activation
| |
| ** Angiogenesis
| |
| ** Fibrogenesis
| |
| * Kupffer cells are hepatic macrophages responsible for Hepatic Stellate cell activation during injury.
| |
| * The hepatic stellate cell (also known as the perisinusoidal cell or Ito cell) plays a key role in the pathogenesis of liver fibrosis/cirrhosis.
| |
| * Hepatic stellate cells(HSC) are usually located in the subendothelial space of Disse and become activated to a myofibroblast-like phenotype in areas of liver injury.
| |
| * Collagen and non collagenous matrix proteins responsible for fibrosis are produced by the activated Hepatic Stellate Cells(HSC).
| |
| * Hepatocyte damage causes the release of lipid peroxidases from injured cell membranes leading to necrosis of parenchymal cells.
| |
| * Activated HSC produce numerous cytokines and their receptors, such as PDGF and TGF-f31 which are responsible for fibrogenesis.
| |
| * The matrix formed due to HSC activation is deposited in the space of Disse and leads to loss of fenestrations of endothelial cells, which is a process called capillarization.
| |
| * Cirrhosis leads to hepatic microvascular changes characterised by <ref name="pmid19157625">{{cite journal |vauthors=Fernández M, Semela D, Bruix J, Colle I, Pinzani M, Bosch J |title=Angiogenesis in liver disease |journal=J. Hepatol. |volume=50 |issue=3 |pages=604–20 |year=2009 |pmid=19157625 |doi=10.1016/j.jhep.2008.12.011 |url=}}</ref>
| |
| ** formation of intra hepatic shunts (due to angiogenesis and loss of parenchymal cells)
| |
| ** hepatic endothelial dysfunction
| |
| * The endothelial dysfunction is characterised by <ref name="pmid22504334">{{cite journal |vauthors=García-Pagán JC, Gracia-Sancho J, Bosch J |title=Functional aspects on the pathophysiology of portal hypertension in cirrhosis |journal=J. Hepatol. |volume=57 |issue=2 |pages=458–61 |year=2012 |pmid=22504334 |doi=10.1016/j.jhep.2012.03.007 |url=}}</ref>
| |
| ** insufficient release of vasodilators, such as nitric oxide due to oxidative stress
| |
| ** increased production of vasoconstrictors (mainly adrenergic stimulation and activation of endothelins and RAAS)
| |
| * Fibrosis eventually leads to formation of septae that grossly distort the liver architecture which includes both the liver parenchyma and the vasculature. A cirrhotic liver compromises hepatic sinusoidal exchange by shunting arterial and portal blood directly into the central veins (hepatic outflow). Vascularized fibrous septa connect central veins with portal tracts leading to islands of hepatocytes surrounded by fibrous bands without central veins.<ref name="pmid18328931">{{cite journal |vauthors=Schuppan D, Afdhal NH |title=Liver cirrhosis |journal=Lancet |volume=371 |issue=9615 |pages=838–51 |year=2008 |pmid=18328931 |pmc=2271178 |doi=10.1016/S0140-6736(08)60383-9 |url=}}</ref><ref name="pmid15094237">{{cite journal |vauthors=Desmet VJ, Roskams T |title=Cirrhosis reversal: a duel between dogma and myth |journal=J. Hepatol. |volume=40 |issue=5 |pages=860–7 |year=2004 |pmid=15094237 |doi=10.1016/j.jhep.2004.03.007 |url=}}</ref><ref name="pmid11079009">{{cite journal |vauthors=Wanless IR, Nakashima E, Sherman M |title=Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis |journal=Arch. Pathol. Lab. Med. |volume=124 |issue=11 |pages=1599–607 |year=2000 |pmid=11079009 |doi=10.1043/0003-9985(2000)124<1599:ROHC>2.0.CO;2 |url=}}</ref>
| |
| * The formation of fibrotic bands is accompanied by regenerative nodule formation in the hepatic parenchyma.
| |
| * Advancement of cirrhosis may lead to parenchymal dysfunction and development of portal hypertension.
| |
| * Portal HTN results from the combination of the following:
| |
| ** Structural disturbances associated with advanced liver disease account for 70% of total hepatic vascular resistance.
| |
| ** Functional abnormalities such as endothelial dysfunction and increased hepatic vascular tone account for 30% of total hepatic vascular resistance.
| |
| | |
| Pathogenesis of Cirrhosis due to Alcohol:
| |
| * More than 66 percent of all American adults consume alcohol.
| |
| * Cirrhosis due to alcohol accounts for approximately forty percent of mortality rates due to cirrhosis.
| |
| * Mechanisms of alcohol-induced damage include:
| |
| ** Impaired protein synthesis, secretion, glycosylation
| |
| * Ethanol intake leads to elevated accumulation of intracellular triglycerides by:
| |
| ** Lipoprotein secretion
| |
| ** Decreased fatty acid oxidation
| |
| ** Increased fatty acid uptake
| |
| * Alcohol is converted by Alcohol dehydrogenase to acetaldehyde.
| |
| * Due to the high reactivity of acetaldehyde, it forms acetaldehyde-protein adducts which cause damage to cells by:
| |
| ** Trafficking of hepatic proteins
| |
| ** Interrupting microtubule formation
| |
| ** Interfering with enzyme activities
| |
| * Damage of hepatocytes leads to the formation of reactive oxygen species that activate Kupffer cells.<ref name="pmid11984538">{{cite journal |vauthors=Arthur MJ |title=Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C |journal=Gastroenterology |volume=122 |issue=5 |pages=1525–8 |year=2002 |pmid=11984538 |doi= |url=}}</ref>
| |
| *Kupffer cell activation leads to the production of profibrogenic cytokines that stimulates stellate cells.
| |
| *Stellate cell activation leads to the production of extracellular matrix and collagen.
| |
| * Portal triads develop connections with central veins due to connective tissue formation in pericentral and periportal zones, leading to the formation of regenerative nodules.
| |
| * Shrinkage of the liver occurs over years due to repeated insults that lead to:
| |
| ** Loss of hepatocytes
| |
| ** Increased production and deposition of collagen
| |
| | |
| | |
| Pathology
| |
| * There are four stages of Cirrhosis as it progresses:
| |
| ** Chronic nonsuppurative destructive cholangitis - inflammation and necrosis of portal tracts with lymphocyte infiltration leading to the destruction of the bile ducts.
| |
| ** Development of biliary stasis and fibrosis
| |
| *Periportal fibrosis progresses to bridging fibrosis
| |
| *Increased proliferation of smaller bile ductules leading to regenerative nodule formation. __NOTOC__
| |
|
| |
|
| ==Video codes== | | ==Video codes== |
| Line 352: |
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| ===Normal video=== | | ===Normal video=== |
| {{#ev:youtube|x6e9Pk6inYI}} | | {{#ev:youtube|x6e9Pk6inYI}} |
| | {{#ev:youtube|4uSSvD1BAHg}} |
| | {{#ev:youtube|PQXb5D-5UZw}} |
| | {{#ev:youtube|UVJYQlUm2A8}} |
|
| |
|
| ===Video in table=== | | ===Video in table=== |
| Line 383: |
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| ===Image and text to the right=== | | ===Image and text to the right=== |
|
| |
|
| <figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline>[[File:Global distribution of leptospirosis.jpg|577x577px]]</figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline> Recent out break of leptospirosis is reported in Bronx, New York and found 3 cases in the months January and February, 2017. | | <figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline><figure-inline>[[File:Global distribution of leptospirosis.jpg|577x577px]]</figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline> Recent out break of leptospirosis is reported in Bronx, New York and found 3 cases in the months January and February, 2017. |
|
| |
|
| ===Gallery=== | | ===Gallery=== |
| Line 398: |
Line 134: |
| ==References== | | ==References== |
| {{Reflist|2}} | | {{Reflist|2}} |
|
| |
| [[Category:Gastroenterology]]
| |
| [[Category:Hepatology]]
| |
| [[Category:Disease]]
| |
|
| |
| {{WS}} | | {{WS}} |
| {{WH}} | | {{WH}} |
| Line 409: |
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| REFERENCES | | REFERENCES |
| <references /> | | <references /> |
| | |
| | [[Category:Gastroenterology]] |
| | [[Category:Needs overview]] |
| | [[Category:Hepatology]] |
| | [[Category:Disease]] |
</figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline></figure-inline> Recent out break of leptospirosis is reported in Bronx, New York and found 3 cases in the months January and February, 2017.
![Histopathology of a pancreatic endocrine tumor (insulinoma). Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/images/2/2f/Pancreatic_insulinoma_histology_2.JPG)
![Histopathology of a pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/images/a/a3/Pancreatic_insulinoma_histopathology_3.JPG)
![Histopathology of a pancreatic endocrine tumor (insulinoma). Insulin immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/images/d/d5/Pancreatic_insulinoma_histology_4.JPG)
![Histopathology of a pancreatic endocrine tumor (insulinoma). Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/index.php/File:Pancreatic_insulinoma_histology_2.JPG)
![Histopathology of a pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/index.php/File:Pancreatic_insulinoma_histopathology_3.JPG)
![Histopathology of a pancreatic endocrine tumor (insulinoma). Insulin immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas[1]](/index.php/File:Pancreatic_insulinoma_histology_4.JPG)