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
- The pathogenesis is multifactorial:
- Alcoholic Hepatitis is caused by interplay between ethanol 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 along with lipogenesis.[2]Closing
</ref>missing for<ref>tag - Endotoxin binds to lipopolysacchride and translocate from intestine to hepatocytes.[3]
- In hepotocytes, lipopolysacchride bindes to CD14 molecule on surface of Kupffer cells which activates Kupffer cells.[3]
- This activation release tumor necrosis factor-alpha (TNF alpha), interleukin-8, monocyte chemotactic protein 1 (MCP-1), and platelet-derived growth factor (PDGF) which are responsible for characterized symptoms including malaise, fever, and peripheral neutrophil leukocytosis. [4] [5]
- Diffuse focal liver cell necrosis with polymorphonuclear, mononuclear, fatty infiltration. Neutrophilic infiltration in particular is unusual for other forms of hepatitis.
- Mallory bodies
- Perinuclear eosinophilic inclusions from intermediate filaments found in alcohol liver disease that can also be seen in fatty liver, primary biliary cirrhosis, hepatitis C, obesity.
- Perivenular inflammation
- “Ballooning” of hepatocytes results from the accumulation of fat and water.
- Swollen hepatocytes and collagen deposition leads to increased sinusoidal pressures, and perhaps portal hypertension.
- Perisinusoidal fat cells transform into fibroblasts.
- Other non-essential changes that might be present include bridging necrosis, bile duct proliferation, and cholestasis.
Some signs and pathological changes in liver histology include:
- Mallory's Hyaline - 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
- ↑ . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check
|doi=value (help). Missing or empty|title=(help) - ↑ . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check
|doi=value (help). Missing or empty|title=(help) - ↑ 3.0 3.1 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.
- ↑ 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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