List the functions of the liver (60% marks).
Discuss the metabolism of paracetamol in toxicity and the pharmacologic management of this overdose (40% marks).
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.