Alcoholic hepatitis pathophysiology: Difference between revisions

Jump to navigation Jump to search
Line 17: Line 17:
*Endotoxin binds to lipopolysacchride and translocate from intestine to hepatocytes.<ref name="Bautista2001">{{cite journal|last1=Bautista|first1=Abraham P|title=Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease|journal=Journal of Gastroenterology and Hepatology|volume=15|issue=4|year=2001|pages=349–356|issn=0815-9319|doi=10.1046/j.1440-1746.2000.02174.x}}</ref>
*Endotoxin binds to lipopolysacchride and translocate from intestine to hepatocytes.<ref name="Bautista2001">{{cite journal|last1=Bautista|first1=Abraham P|title=Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease|journal=Journal of Gastroenterology and Hepatology|volume=15|issue=4|year=2001|pages=349–356|issn=0815-9319|doi=10.1046/j.1440-1746.2000.02174.x}}</ref>
* In hepotocytes, lipopolysacchride bindes to CD14 molecule on surface of Kupffer cells which activates Kupffer cells.<ref name="Bautista2001">{{cite journal|last1=Bautista|first1=Abraham P|title=Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease|journal=Journal of Gastroenterology and Hepatology|volume=15|issue=4|year=2001|pages=349–356|issn=0815-9319|doi=10.1046/j.1440-1746.2000.02174.x}}</ref>
* In hepotocytes, lipopolysacchride bindes to CD14 molecule on surface of Kupffer cells which activates Kupffer cells.<ref name="Bautista2001">{{cite journal|last1=Bautista|first1=Abraham P|title=Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease|journal=Journal of Gastroenterology and Hepatology|volume=15|issue=4|year=2001|pages=349–356|issn=0815-9319|doi=10.1046/j.1440-1746.2000.02174.x}}</ref>
* 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 {{cite journal |vauthors=Laso FJ, Lapeña P, Madruga JI, San Miguel JF, Orfao A, Iglesias MC, Alvarez-Mon M |title=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 |journal=Alcohol Clin Exp Res |volume=21 |issue=7 |pages=1226–31 |date=October 1997 |pmid=9347083 |doi= |url=}}{{cite journal |vauthors=Bird G |title=Interleukin-8 in alcoholic liver disease |journal=Acta Gastroenterol Belg |volume=57 |issue=3-4 |pages=255–9 |date=1994 |pmid=7810274 |doi= |url=}}
* 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. {{cite web |url=https://pubmed.ncbi.nlm.nih.gov/7810274/ |title=Interleukin-8 in alcoholic liver disease - PubMed |format= |work= |accessdate=}}
 
 





Revision as of 21:52, 29 July 2021

https://https://www.youtube.com/watch?v=RudR2_VVoaw%7C350}}

Alcoholic hepatitis Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Alcoholic hepatitis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Ultrasound

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Alcoholic hepatitis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Alcoholic hepatitis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Alcoholic hepatitis pathophysiology

CDC on Alcoholic hepatitis pathophysiology

Alcoholic hepatitis pathophysiology in the news

Blogs on Alcoholic hepatitis pathophysiology

Directions to Hospitals Treating Alcoholic hepatitis

Risk calculators and risk factors for Alcoholic hepatitis pathophysiology

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.[1]
  • Alcoholic Hepatitis is caused by interplay between alcohol metabolism, inflammation and innate immunity.[2]
  • The Alcohol metabolism leads to a reduced ratio of the nicotinamide adenine dinucleotide (NAD) to NADH."Alcoholic Hepatitis - StatPearls - NCBI Bookshelf".
  • The NAD depletion inhibit fatty acid oxidation; therefore, it cause fat accumulation in hepatocytes and lipogenesis.[3]
  • Due to increased intestinal permeability in patients with Alcoholic Hepatitis, high levels of Endotoxemia is recognized.[4]
  • Endotoxin binds to lipopolysacchride and translocate from intestine to hepatocytes.[5]
  • In hepotocytes, lipopolysacchride bindes to CD14 molecule on surface of Kupffer cells which activates Kupffer cells.[5]
  • 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. "Interleukin-8 in alcoholic liver disease - PubMed".



  • The amount and duration of alcohol (EtOH) necessary to damage the liver is variable and relates to host factors.
  • Most patients with established liver disease continuously consume 60-80 g/day of ETOH (about 8 beers, one liter of wine, or half a pint of liquor) for 10 to 20 years. After 20 years of such behavior, most will have fatty changes, but only half will have cirrhosis.
    • Cirrhosis occurs in women at ~40gm EtOH/day for >10 years
    • Cirrhosis occurs in men at ~80gm EtOH/day for >10 years
  • Diffuse focal liver cell necrosis with polymorphonuclear, mononuclear, fatty infiltration. Neutrophilic infiltration in particular is unusual for other forms of hepatitis.
  • Mallory bodies
  • 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.

Molecular Biology

Potential mechanisms of alcohol associated liver disease include:

  • ETOH generates excess NADH, which slows gluconeogenesis, increasing lactate production, and leading to fatty acid accumulation.
  • Acetaldehyde is a toxic metabolite that can impair hepatocyte function
  • Alcohol metabolism consumes oxygen and contributes to centrilobular hypoxia
  • Neutrophil infiltration – perhaps in association with reactive oxygen species
  • Other minor pathways of alcohol metabolism are upregulated in alcoholics, which may produce more dangerous oxygen intermediates. A microsomal pathway has been called the microsomal enzyme oxidation system (MEOS). Polymorphisms of enzymes in this system (P4502E1 in particular) may contribute to the predisposition of some individuals to alcohol associated liver damage. P4502E1 also appears to increase acetominophen metabolism to toxic metabolites, and may play a role in acetominophen associated liver disease in patients who drink alcohol.
  • Inflammation and collagen deposition in the perivenular (zone 3) region of the hepatic sinusoids and the space of Disse, impede flow, increasing pressure. Perivenular cell necrosis may be found.

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:

  • Fibrosis
  • Cirrhosis - a progressive and permanent type of fibrotic degeneration of liver tissue.

References

  1. . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check |doi= value (help). Missing or empty |title= (help)
  2. . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check |doi= value (help). Missing or empty |title= (help)
  3. . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check |doi= value (help). Missing or empty |title= (help)
  4. . doi:10.1053/j.gastro.2011.09.002. Epub 2011 Sep 12. Check |doi= value (help). Missing or empty |title= (help)
  5. 5.0 5.1 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.
  6. 6.0 6.1 6.2 Cotran. Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. 0-7216-7335-X. Unknown parameter |coauthors= ignored (help)

Template:WH Template:WS