Diagnostics in Paracetamol Overdosage Cases Coursework

Introduction

A liver function test (LFTs or LFs) is used to identify the degree of hepatotoxicity or liver damage. In LFTs, the levels of various enzymes and compounds like Alanine aminotransferase (ALT), Aspartate aminotransferase, Creatine kinase, Albumin, Alkaline phosphatase, Bilirubin are measured to ensure the state of the liver.

Abnormal Liver function test result

Based on the case study test results, elevated levels of the two Aminotransferases can be correlated to paracetamol overdose, especially elevated ALT which is more specific for liver cell damage. Alkaline phosphatase remains in the range of 70-350U/L in growing children which is considered normal.

Blood Collection for Paracetamol Test

The patient’s blood is collected every two hours for the Paracetamol Test as the level of paracetamol in plasma will give an assessment of the risk of liver damage. “As there are chances of continuing absorption and distribution of the drug, plasma concentrations after four hours from the time of overdose is generally taken into consideration” (Guideline for the management of acute paracetamol overdosage [updated 2007]). So, it will be important to know from the patient the exact time of intake of the paracetamol overdosage in order to calculate the interval in which the paracetamol test must be taken. Paracetamol concentration below 1000 units after 4 hours is considered safe for the patient.

Role of Parvolex and Liver’s Detoxification Mechanism

“In paracetamol overdose, hepatic centrilobular necrosis occurs. Studies have revealed that cytochrome P450 enzymes convert Paracetamol into a reactive metabolite called N-acetyl-p-benzoquinone imine (NAPQI), which depletes glutathione (GSH) and covalently binds to proteins leading to the destruction of the cell” (James et al. 2003). Glutathione is an antioxidant known to protect cells against toxic reactive oxygen species which are mainly free radicals and peroxides. “Parvolex is known to have a sulphydryl(SH) group donor which seems to play a potential role in restoring depleted hepatic concentrations of reduced glutathione levels or can act as an alternative substrate to the toxic metabolite NAPQI, thereby saving the cell from high toxicity.” (Paw, Park). “Liver is known to carry out detoxification of a wide variety of organic compounds by a system of oxygen transferring enzymes (oxygenases). These enzymes lack substrate specificity and oxidize hydrophobic compounds to hydrophilic nature which can be easily excreted” (Karp 2002).

Elevated Transaminases

The two transaminases are mainly intracellular enzymes, but normal levels of these enzymes are found in the blood due to cell turnover. The elevated levels of these enzymes in blood signify cellular damage due to paracetamol-induced hepatotoxicity as pertaining to this case study.

Indications of Elevated Bilirubin Level

“Elevated bilirubin levels are usually related to its increased production (breakdown of haem), deficiencies in bilirubin excretion and hepatobiliary diseases. Bilirubin levels remain in the normal range at initial stages of liver damage” (Lester 1983).

“Liver Function Test” a Misnomer

Liver Function Test is considered a misnomer because the test does not provide information of total liver function as such. “The test uses measurements of various enzymes and other components to determine the degree of liver damage, biliary obstruction, possible liver disease and its causes monitor the progress of the disease and treatment responses” (Liver function tests (LFTs) [updated 2010 Apr 9]).

Parvolex – An Antidote in Paracetamol Overdose

If parvolex was not administered in the first 12 hours it could have led to severe hepatic centrilobular necrosis due to depletion of glutathione (GSH) caused by a high dosage of paracetamol. This breakdown of liver cells leads to an increase in levels of both aminotransferases in blood from their normal concentrations (35U/L for ALT and 40U/L for AST) to high concentrations of 1000U/L for both the enzymes in severe drug toxicity. The levels of Alkaline phosphatase can also climb above the normal range (70-350U/L in growing children). Gamma Glutamyl Transferase (GGT) levels remain normal (< 30U/L) in the early stages of liver cell necrosis but will increase in due course, the same scenario of GGT can be applied to bilirubin in hepatic cell damage. Failure in the administration of parvolex can be fatal, as the detoxification process of the body fails due to liver damage caused by paracetamol toxicity.

Conclusion

In case of paracetamol overdose, Liver Function tests and Paracetamol blood levels are checked to measure the severity of damage to the liver. These tests can help in outlining the mode of treatment for the patient. Administration of parvolex is the most effective treatment currently used in paracetamol overdosage cases.

Bibliography

Guideline for the management of acute paracetamol overdosage [Internet]. Paracetamol Information Center; Web.

James LP, Mayeu, PR, Hinson J A. 2003. Acetaminophen-induced hepatotoxicity. Drug metabolism and disposition. 31. p.1499–1506.

Karp G. 2002. Cell and molecular biology: Concepts and experiments. Von Hoffman Press: John Wiley & Sons. p.288.

Lester RN. 1983. Engl J Med. 309. p.183-185.

Liver function tests (LFTs). [Internet]. 2010. VirtualMedicalCenter.com; Web.

Paw HGW, Park GR. Drugs: An A-Z guide. [internet]. Cambridge University Press; 2010. Web.