Primary biliary cirrhosis pathophysiology: Difference between revisions
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==Microscopic Pathology== | ==Microscopic Pathology== | ||
*On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis. | *On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis. | ||
*Prinary biliary cirrhosis can be classified into four stages according to histological classification of Ludwig. According to Ludwig classification, all four stages may be present on a single liver biopsy.<ref name="pmid19554543">{{cite journal| author=Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ et al.| title=Primary biliary cirrhosis. | journal=Hepatology | year= 2009 | volume= 50 | issue= 1 | pages= 291-308 | pmid=19554543 | doi=10.1002/hep.22906 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19554543 }} </ref><ref name="pmid150690">{{cite journal| author=Ludwig J, Dickson ER, McDonald GS| title=Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). | journal=Virchows Arch A Pathol Anat Histol | year= 1978 | volume= 379 | issue= 2 | pages= 103-12 | pmid=150690 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=150690 }} </ref> | |||
=== | * It can also be classified into four stages according to the histological classification of P. Scheuer.<ref name="pmid6066569">{{cite journal| author=Scheuer P| title=Primary biliary cirrhosis. | journal=Proc R Soc Med | year= 1967 | volume= 60 | issue= 12 | pages= 1257-60 | pmid=6066569 | doi= | pmc=1901478 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6066569 }}</ref> | ||
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! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + | Classification of Primary biliary cirrhosis on the basis of histology | |||
|- | |||
! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Stage | |||
! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + | Histologic appearance | |||
|- | |||
! style="background:#7d7d7d; color: #FFFFFF;" align="center" + |Ludwig classification | |||
! style="background:#7d7d7d; color: #FFFFFF;" align="center" + |Scheuer's classification | |||
|- | |||
| style="background:#DCDCDC;" align="center" + |Stage 1 | |||
| style="background:#F5F5F5;" + |Portal inflammation | |||
| style="background:#F5F5F5;" + |Florid duct lesion or chronic non-suppurative destructive cholangitis | |||
|- | |||
| style="background:#DCDCDC;" align="center" + |Stage 2 | |||
| style="background:#F5F5F5;" + |Extension of inflammation beyond portal tracts into surrounding parenchyma with or without ductal loss | |||
| style="background:#F5F5F5;" + |Proliferation of the small bile ductules | |||
|- | |||
| style="background:#DCDCDC;" align="center" + |Stage 3 | |||
| style="background:#F5F5F5;" + |Presence of fibrous septa linking adjacent portal tracts | |||
| style="background:#F5F5F5;" + |Fibrosis or scarring | |||
|- | |||
| style="background:#DCDCDC;" align="center" + |Stage 4 | |||
| style="background:#F5F5F5;" + |Cirrhosis | |||
| style="background:#F5F5F5;" + |Cirrhosis | |||
|} | |||
==References== | ==References== | ||
Revision as of 17:55, 6 February 2018
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Primary Biliary Cirrhosis Microchapters |
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Differentiating Primary Biliary Cirrhosis from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Primary biliary cirrhosis pathophysiology On the Web |
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American Roentgen Ray Society Images of Primary biliary cirrhosis pathophysiology |
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Risk calculators and risk factors for Primary biliary cirrhosis pathophysiology |
| https://https://www.youtube.com/watch?v=CQtHOMzLzwU%7C350}} |
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 primary biliary cirrhosis is not fully understood.
- It is thought that primary biliary cirrhosis is the result of antimitochondrial antibodies (AMAs), directed to the E2 component of the pyruvate dehydrogenase complex (PDC-E2).[1]
| Biliary epithelial cells (BEC) | |||||||||||||||||||||||||||||||||||||||||||||||||
| Overexpression of Bcl-2 in small apoptotic BEC | Cell lineage specific lack of glutathione | ||||||||||||||||||||||||||||||||||||||||||||||||
| Inhibition of PDC-E2 glutathiolation | |||||||||||||||||||||||||||||||||||||||||||||||||
| Prevents loss of immunogenicity after apoptpsis of BEC | |||||||||||||||||||||||||||||||||||||||||||||||||
| PDC-E2 component remains intact and antigenic in apoptotic blebs of BEC | |||||||||||||||||||||||||||||||||||||||||||||||||
| Antigenic PDC-E2 are engulfed by intrahepaticc dendritic cells | |||||||||||||||||||||||||||||||||||||||||||||||||
| Dendritic cells transfer antigenic PDC-E2 to regional lymph nodes | |||||||||||||||||||||||||||||||||||||||||||||||||
| Antigenic PDC-E2 is recognized by MHC class I restricted CD8+ T cells | |||||||||||||||||||||||||||||||||||||||||||||||||
| Initiates autoimmunity | |||||||||||||||||||||||||||||||||||||||||||||||||
| Primary biliary cirrhosis | |||||||||||||||||||||||||||||||||||||||||||||||||
Genetics
- Primary biliary cirrhosis may be familial and is related to factors inherited maternally.[6]
- Primary biliary cirrhosis tends to present at an earlier age in the second generation.
Associated Conditions
Conditions associated with primary biliary cirrhosis include:[7][8][9]
- Addison's disease
- Autoimmune thrombocytopenic purpura
- Celiac disease
- CREST syndrome
- Crohn's disease
- Dermatomyositis
- Diabetes mellitus type 1
- Gallstones
- Glomerulonephritis
- Grave's disease
- Hashimoto's thyroiditis
- Lichen planus
- Mixed connective tissue disorder
- Myasthenia gravis
- Pemphigoid
- Pernicious anemia
- Polymyositis
- Psoriasis
- Pulmonary fibrosis
- Raynaud's disease
- Rheumatoid arthritis
- Sarcoidosis
- Scleroderma
- Sjogren's syndrome
- Systemic lupus erythematosus
- Ulcerative colitis
Gross Pathology
- On gross pathology, characteristic findings of primary biliary cirrhosis include:[7]
- Hepatomegaly
- Splenomegaly
- Cirrhosis (late stages)
Microscopic Pathology
- On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis.
- Prinary biliary cirrhosis can be classified into four stages according to histological classification of Ludwig. According to Ludwig classification, all four stages may be present on a single liver biopsy.[10][11]
- It can also be classified into four stages according to the histological classification of P. Scheuer.[12]
| Classification of Primary biliary cirrhosis on the basis of histology | ||
|---|---|---|
| Stage | Histologic appearance | |
| Ludwig classification | Scheuer's classification | |
| Stage 1 | Portal inflammation | Florid duct lesion or chronic non-suppurative destructive cholangitis |
| Stage 2 | Extension of inflammation beyond portal tracts into surrounding parenchyma with or without ductal loss | Proliferation of the small bile ductules |
| Stage 3 | Presence of fibrous septa linking adjacent portal tracts | Fibrosis or scarring |
| Stage 4 | Cirrhosis | Cirrhosis |
References
- ↑ Matsumura S, Van De Water J, Leung P, Odin JA, Yamamoto K, Gores GJ; et al. (2004). "Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis". Hepatology. 39 (5): 1415–22. doi:10.1002/hep.20175. PMID 15122771.
- ↑ Lleo A, Selmi C, Invernizzi P, Podda M, Coppel RL, Mackay IR; et al. (2009). "Apotopes and the biliary specificity of primary biliary cirrhosis". Hepatology. 49 (3): 871–9. doi:10.1002/hep.22736. PMC 2665925. PMID 19185000.
- ↑ Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A (2001). "Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis". J Clin Invest. 108 (2): 223–32. doi:10.1172/JCI10716. PMC 203018. PMID 11457875.
- ↑ Charlotte F, L'Herminé A, Martin N, Geleyn Y, Nollet M, Gaulard P; et al. (1994). "Immunohistochemical detection of bcl-2 protein in normal and pathological human liver". Am J Pathol. 144 (3): 460–5. PMC 1887102. PMID 8129031.
- ↑ Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A; et al. (2008). "Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells". Hepatology. 47 (3): 958–65. doi:10.1002/hep.22102. PMID 18181218.
- ↑ Brind AM, Bray GP, Portmann BC, Williams R (1995). "Prevalence and pattern of familial disease in primary biliary cirrhosis". Gut. 36 (4): 615–7. PMC 1382507. PMID 7737573.
- ↑ 7.0 7.1 Kumagi T, Heathcote EJ (2008). "Primary biliary cirrhosis". Orphanet J Rare Dis. 3: 1. doi:10.1186/1750-1172-3-1. PMC 2266722. PMID 18215315.
- ↑ Watt FE, James OF, Jones DE (2004). "Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study". QJM. 97 (7): 397–406. PMID 15208427.
- ↑ Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF; et al. (1990). "Sjögren's syndrome in patients with primary biliary cirrhosis". Hepatology. 11 (5): 730–4. PMID 2347546.
- ↑ Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; et al. (2009). "Primary biliary cirrhosis". Hepatology. 50 (1): 291–308. doi:10.1002/hep.22906. PMID 19554543.
- ↑ Ludwig J, Dickson ER, McDonald GS (1978). "Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)". Virchows Arch A Pathol Anat Histol. 379 (2): 103–12. PMID 150690.
- ↑ Scheuer P (1967). "Primary biliary cirrhosis". Proc R Soc Med. 60 (12): 1257–60. PMC 1901478. PMID 6066569.