Outline how the measurement of the following can be used in the assessment of liver function
(25% marks of each):
- Albumin
- Prothrombin time
- Glucose
- Ammonia
College Answer
This was a new question and overall, most candidates provided some detail on each component as requested. Those answers that used a simple template for each section generally scored better than those who wrote in a paragraph style for each section. Areas expected to be covered included the following; a definition of the variable to provide context, a normal value and the range of influences that effect the variable both related to liver function and or extrinsic to the liver (attempting to introduce the concepts of sensitivity and specificity for each test). Stronger answers provided some context as to whether the variable was sensitive to acute or chronic changes in liver function and which synthetic/metabolic component of the liver the variable represented.
Discussion
Though the magnanimous examiners present us with a clear breakdown of the structure they expected, it feels like something that should have been articulated more clearly at the stem of the question, instead of waiting to reveal it after the exam. One can imagine how some high quality candidates with excellent understanding of the subject might have failed only because they settled on a paragraph structure for their answer. Anyway: what follows is an attempt to answer in the secret "proper" format.
Albumin
- Ubiquitous protein produced almost exclusively by the liver
- Normal value is 35-40 g/L
- Depressed albumin levels can a failure of synthetic function
- Albumin can also be depressed in other circumstances (starvation, protein malnutrition, stress, critical illness, protein loss via nephrotic syndrome)
- A long half life means albumin levels can remain normal for some days even as hepatic synthesis has stopped
Prothrombin time
- Definition: test of extrinsic and final common clotting pathway
- Normal value: 11-15 seconds
- Test of synthetic liver function (Factors II, VII and X produced by the liver)
- Chronic liver failure typically results in the loss of clotting protein synthesis and a high PT
- Hyperacute liver failure may present with residually normal clotting function
- Extrinsic influences on PT include synthesis inhibitors (eg. warfarin), other anticoagulants, protein loss (nephrotic syndrome) and consumption (eg. DIC)
Glucose
- Glucose is the dominant form of metabolic fuel in human cellular energy production
- Normal value is 5mmol/L, up to 10 following a meal
- The liver stores glucose as glycogen and triglycerides, and is able to mobilise glucose into the bloodstream as needed
- Hypoglycaemia is often associated with acute liver failure - blood glucose can drop over hours or minutes
- In chronic liver failure, hyperglycaemia is often seen, due to decreased hepatic insulin clearance and increased peripheral insulin resistance
- Extrahepatic influences on glucose include nutrition (eg. glucagon depleted in starvation), diabetes, medications (eg. insulin, exogenous IV glucose), skeletal muscle glycogen and renal gluconeogenesis.
Ammonia
- Ammonia is the product of amino acid catabolism and a substrate for the urea cycle enzymes which reside in the liver
- Normal value is 11 to 32 µmol/L
- A raised ammonia level suggests poor metabolic liver function or a dysfunction of hepatic urea cycle enzymes
- Acute liver failure can result in a rapid rise of ammonia (over hours)
- Extrahepatic causes can include increased protein turnover or increased dietary protein intake, increased production by altered populations of gut organisms, or congenital impairment of urea cycle enzymes in the presence of an otherwise healthy liver.