List the functions of the liver (60% marks).

Discuss the metabolism of paracetamol in toxicity and the pharmacologic management of this overdose (40% marks). 

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College Answer

A good response to this question required an ordered and well structured response. There are 
numerous important functions that the liver undertakes (eg bile formation, immunological, protein, 
lipid, glucose metabolism, storage, endocrine, etc), yet most candidates could not generate a 
sufficient list. In relation to paracetomol toxicity, a good response required candidates to mention 
that normal conjugating reactions in the liver are saturated and metabolism diverts to mixed 
function oxidases, which generate toxic metabolites. These in turn are inactivated by conjugation 
with glutathione. However when glutathione is depleted, toxic metabolites react with cellular 
nuclear material, thus causing liver necrosis. Toxic compound depletes sulphydril groups and 
also causes direct damage via lipid peroxidation. Regeneration of sulphydril groups and 
glutathione depends on availability of cysteine, thus the need to administer acetylcysteine.