Acute liver failure pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]
Overview
Acute liver failure results from loss of normal function of hepatic tissue. When this damage occurs in a short period of time this results in multiple effects like disturbed alertness of the patient, hemodynamic instability and multisystem failure.
Pathophysiology
Acute liver failure is caused due to extensive damage to the liver tissue, causing severe compromise of its function. The effects of acute liver failure are due to loss of its metabolic, secretory and regulatory effects. This results in accumulation of toxic substances and causes deleterious effects. The major cause of morbidity and mortality in patients of liver failure is due to the development of cerebral edema which causes altered sensorium and increased intracranial pressure.
Cerebral edema is mediated due to damage to blood brain barrier. Acute liver failure causes increased ammonia concentrations due to failure of detoxification system. This increased ammonia with glutamate of astrocytes of brain gets converted to glutamine with the help of enzyme glutamine synthetase. This accumulation of glutamine in high concentrations causes cerebral edema.
In acute liver failure there is increase in levels of nitric oxide in circulation. This nitric oxide is a potent vasodilator causing disruption of cerebral blood. This disrupts cerebral auto regulation.
Another consequences of liver failure is multiorgan failure due to severe hypotension caused by decreased systemic vascular resistance.
Specific Conditions
Acetaminophen Toxicity
- Acetaminophen is the leading cause of acute liver failure.
- Acetaminophen causes dose related toxicity.
- Toxic doses can be as low as 3-4 g/day but most toxic ingestion's are of >10 g/day.
Other Drugs
- Drugs other than acetaminophen also cause acute liver failure.
- These constitute 13% of cases of acute liver failure in US. [1]
- They cause idiosyncratic drug hepatotoxicity.
- They usually present within six months of drug initiation.
Mushroom Poisoning
- It is mainly caused by the genus Amanita (Amanita phalloides).[2]
- Presentations may vary from case to case and it constitutes to a medical emergency.
- Patients may be recovering from traditional medical treatment to as severe as requiring transplantation.
Viral Hepatitis
- Hepatitis viruses A, B, D( associated with B) and E (in endemic countries) causes acute liver failure.
- Viral hepatitis (Hepatitis A & B) constitutes 12% of cases of acute liver failure in US.[1]
- Hepatitis C alone doesn't seem to cause acute liver failure.[3]
- There is a difference in survival of patients of acute liver failure with A and B, this cannot be explained by the severity of dysfunction but may rather be an inherent feature of the infections.[3]
Autoimmune Hepatitis
- Autoimmune hepatitis may be unrecognized coexistent condition.
- Autoantibodies are helpful in diagnosis of the condition. In cases of negative autoantibody biopsy may be required.
- Few patients may need transplantation along with steroid therapy.
Ischemic Injury
- This condition is called as shock liver.
- Shock liver results from severe hypotension due to any cause like heart failure, severe vaso-constriction due to drugs like niacin and cocaine.
- Early recovery is frequent but long term outcome depends on the underlying cause of the ischemia.
HELLP Syndrome
Malignancy
Pathology
In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease[4].
References
- ↑ 1.0 1.1 Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Annals of Internal Medicine. 137 (12): 947–54. PMID 12484709. Retrieved 2012-10-27. Unknown parameter
|month=ignored (help) - ↑ Catalina MV, Núñez O, Ponferrada A, Menchén L, Matilla A, Clemente G, Bañares R (2003). "[Liver failure due to mushroom poisoning: clinical course and new treatment perspectives]". Gastroenterología Y Hepatología (in Spanish; Castilian). 26 (7): 417–20. PMID 12887855. Retrieved 2012-10-27.
- ↑ 3.0 3.1 Schiødt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM (2003). "Viral hepatitis-related acute liver failure". The American Journal of Gastroenterology. 98 (2): 448–53. doi:10.1111/j.1572-0241.2003.t01-1-07223.x. PMID 12591067. Retrieved 2012-10-27. Unknown parameter
|month=ignored (help) - ↑ Boyer JL, Klatskin G (1970). "Pattern of necrosis in acute viral hepatitis. Prognostic value of bridging (subacute hepatic necrosis)". N. Engl. J. Med. 283 (20): 1063–71. PMID 4319402.