Primary biliary cirrhosis pathophysiology
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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 |
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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
- [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
Conditions associated with primary biliary cirrhosis include:[6][7]
- 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, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis.
Histopathology
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.
- ↑ 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.