Alcoholic hepatitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S
Pathophysiology
Pathogenesis
- The pathogenesis of Alcoholic Hepatitis is multifactorial.
- Alcoholic Hepatitis is caused by interplay between alcohol metabolism, inflammation and innate immunity. [1]
- The Alcohol metabolism leads to a reduced ratio of the nicotinamide adenine dinucleotide (NAD) to NADH. The NAD depletion inhibit fatty acid oxidation and causes fat accumulation in hepatocytes associated with lipogenesis. [1]
- Due to increased intestinal permeability in patients with Alcoholic Hepatitis, high levels of Endotoxemia is recognized.[1]
- Endotoxin binds to lipopolysaccharide and translocate from intestine to hepatocytes.[2]
- In hepatocytes, lipopolysaccharide bindes to CD14 molecule and toll-like receptor 4 on surface of Kupffer cells.[3]
- These bindings activate Kupffer cells to release reactive oxygen species.[2]
- This activation release tumor necrosis factor-alpha (TNF alpha), interleukin-8, monocyte chemotactic protein 1 (MCP-1), andplatelet-derived growth factor (PDGF) which are responsible for characterized symptoms including malaise, fever, and peripheral neutrophil leukocytosis. [4] [5]
Histologic Findings
- Mallory body - a condition where pre-keratin filaments accumulate in hepatocytes. This sign is not limited to alcoholic liver disease, but is often characteristic.[6]
- Ballooning degeneration - hepatocytes in the setting of alcoholic change often swell up with excess fat, water and protein; normally these proteins are exported into the bloodstream. Accompanied with ballooning, there is necrotic damage. The swelling is capable of blocking nearby biliary ducts, leading to diffuse cholestasis.[6]
- Inflammation - Neutrophilic invasion is triggered by the necrotic changes and presence of cellular debris within the lobules. Ordinarily the amount of debris is removed by Kupffer cells, although in the setting of inflammation they become overloaded, allowing other white cells to spill into the parenchyma. These cells are particularly attracted to hepatocytes with Mallory bodies.[6]
If chronic liver disease is also present:
References
- ↑ 1.0 1.1 1.2 Gao, Bin; Bataller, Ramon (2011). "Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets". Gastroenterology. 141 (5): 1572–1585. doi:10.1053/j.gastro.2011.09.002. ISSN 0016-5085.
- ↑ 2.0 2.1 Bautista, Abraham P (2001). "Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease". Journal of Gastroenterology and Hepatology. 15 (4): 349–356. doi:10.1046/j.1440-1746.2000.02174.x. ISSN 0815-9319.
- ↑ Suraweera DB, Weeratunga AN, Hu RW, Pandol SJ, Hu R (2015). "Alcoholic hepatitis: The pivotal role of Kupffer cells". World J Gastrointest Pathophysiol. 6 (4): 90–8. doi:10.4291/wjgp.v6.i4.90. PMC 4644891. PMID 26600966.
- ↑ Bird G (1994). "Interleukin-8 in alcoholic liver disease". Acta Gastroenterol Belg. 57 (3–4): 255–9. PMID 7810274.
- ↑ Laso FJ, Lapeña P, Madruga JI, San Miguel JF, Orfao A, Iglesias MC; et al. (1997). "Alterations in tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 production by natural killer cell-enriched peripheral blood mononuclear cells in chronic alcoholism: relationship with liver disease and ethanol intake". Alcohol Clin Exp Res. 21 (7): 1226–31. PMID 9347083.
- ↑ 6.0 6.1 6.2 Cotran. Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. 0-7216-7335-X. Unknown parameter
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