Question 12

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. 

Discussion

You have a maximum of six minutes to list all the functions of the liver, which is probably why "most candidates could not generate a sufficient list". Considering that the highest possible rate of writing legible handwritten characters is approximately 190 characters per minute (by a 1980s police interviewer, a group widely held to be the fastest handwriters in the universe), this limits the list to a maximum of 1,140 characters, excluding blank spaces. Working within this framework, the absolutely maximally comprehensive answer to the first part of this question should look something like this:

Storage functions:

• Glycogen (75g, 400kcal)
• Fat (75g, 600 kcal)
• Vitamins (A, D, E, K, and B12)
• Trace elements: iron, copper, sink, selenium
• Blood reservoir: up to 27% of total blood volume

Synthetic functions:

• Blood proteins (albumin, clotting factors, complement)
• Regulatory molecules (thrombopoietin, angiotensinogen)
• Nutrients: glucose (gluconeogenesis), ketones, lipids (VLDL), cholesterol, non-essential amino acids
• Bile acids: from cholesterol
• Urea: from ammonia
• Bilirubin

Metabolic functions:

• Carbohydrates: conversion of glucose to and from glycogen
• Lipids: transformation into ketones or triglycerides
• Proteins: deamination or transamination of amino acids
• Ammonia: metabolism (into urea)
• Lactate: metabolism (into glucose)

Immunological functions:

• Production of complement proteins
• Decreased iron transport proteins to hinder infection
• Reduced synthesis of negative acute phase reactants
• Filtration of antigens by Kupffer cells

Excretory functions:

• Bile acids (though 95% undergo reabsorption)
• Cholesterol in the bile (800-1200mg/day)
• Conjugated bilirubin in the bile
• Drugs (ceftriaxone, apixaban, digoxin)
• Heavy metals (lead, arsenic, mercury, cadmium)

That's 146 words, or 1,140 characters. Now: to paracetamol.

Kuntz, Erwin, and Hans-Dieter Kuntz. "Biochemistry and functions of the liver." Hepatology Textbook and Atlas: History· Morphology Biochemistry· Diagnostics Clinic· Therapy (2008): 35-76.

Ozougwu, Jevas C. "Physiology of the liver." International Journal of Research in Pharmacy and Biosciences 4.8 (2017): 13-24.