Week 1/2 - F - Liver Function Tests- A.L.T/A.S.T (hepatocellular injury), A.L.P/G.G.T (cholestasis), Bilirubin/Prothrombin time/Albumin

Question 1

There is a difference between a liver screen and liver function tests A ‘liver screen’ is a batch of investigations focused on ruling underlying causes of liver disease in or out. What is the purpose of carrying out liver function tests?

Answer 1

Live function tests have two purposes * To confirm clinical suspicion of potential liver injury or disease * To distinguish between hepatocellular injury (intrahepatic jaundice) and cholestasis (post-hepatic or obstructive jaundice)

Question 2

The left shows the different blood tests carried out in a typical liver screen What are the blood tests carried out when ordering a liver function test?

Answer 2

Liver function tests measure * Serum transaminase - alanine transaminase (ALT) * Serum transaminase - aspartate transaminase (AST) * Alkaline phosphatase (ALP) * Gamma glutamyl transpeptidase (GGT) * Albumin * Prothrombin time/INR * Bilirubin

Question 3

Functions of the liver include protein synthesis, detoxification, and metabolic processes. What are the main synthetic functions of the liver? Which tests can be used to assess the liver’s synthetic function?

Answer 3

The liver’s main synthetic functions include: * Conjugation and elimination of bilirubin * Synthesis of albumin * Synthesis of clotting factors * Gluconeogenesis - one of the last to be impaired
Investigations that can be used to assess synthetic liver function include: * Serum bilirubin * Serum albumin * Prothrombin time (PT) * (Serum blood glucose)

Question 4

What are the transaminases?

Answer 4

The serum transaminases are hepatic enzymes that catalyses amino acid group transfers They are usually intracellular in hepatocutes however are released from the hepatocytes in the context of injury

Question 5

Which serum transaminase is more specific? Which organ(s) are both found in?

Answer 5

ALT is found in high concentrations predominantly within hepatocytes and enters the blood following hepatocellular injury. * It is, therefore, a useful marker of hepatocellular injury (also found in kidney and muscle) * - it is more sensitive and specific than AST AST is present in many different organs eg liver, heart, skeletal muscle, pancreas, RBCs

Question 6

The ALT/AST ratio can be used to determine the likely cause of LFT derangement: Which would be greater in: * Chronic liver disease * Liver cirrhosis * Alcoholic liver disease

Answer 6

ALT >AST chronic liver disease AST > ALT in liver cirrhosis and alcoholic liver disease * wASTed - or AST: Alcohol gets you STeaming

Question 7

What is ALP? Where is it found?

Answer 7

ALP stands for alkaline phosphatase It is an enzyme that catalyses a number of phosphate esters It is found particularly in the liver, biliary cells (bile ducts) bone and placenta

Question 8

What liver pathology causes a raised ALP and therefore what is it a useful marker in?

Answer 8

Biliary cholestasis (eg due to a gallstone obstructing bile flow) causes enhanced synthesis and release of ALP and it is therefore a useful marker for cholestasis

Question 9

If there is a rise in ALP, what enzyme is important to review?

Answer 9

If there is a raise in ALP, it is important to review the level of gamma glutamyl transpeptidase (GGT) (aka gamma glutamyl transferase)

Question 10

Why is it important to review GGT if there is a rise in ALP? * think, where are both produced * what is a raise in both highly suspcious of * what is a raise of ALP in the absence of raised GGT make you think

Answer 10

ALP is produced in the liver, bile cells, bone and pancreas GGT is produced in the cell membranes of the liver bile ducts, kidneys, pancreas, drugs * A markedly raised ALP with a raised GGT is highly suggestive of cholestasis * A raised ALP in the absence of a raised GGT should raise suspicion of non-hepatobilliary pathology - usually bone disease

Question 11

GGT levels can be raised with different drugs What are some examples here?

Answer 11

Drugs which GGT levels are particularly * Anticonvulsants eg phenytoin * Tricyclic antidepressants * Paracetamol * Alcohol

Question 12

If ALT (and AST) levels are markedly raised in comparison to ALP, what do you think? If ALP levels (and GGT) are markedly raised in comparison to ALT (and AST) levels, what do you think?

Answer 12

If ALT is raised markedly compared to the ALP, this is primarily a hepatocellular pattern of injury. If ALP is raised markedly compared to ALT, this is primarily a cholestatic pattern of injury.

Question 13

Where is bilirubin broken down and how is it transported to the liver? What happens to it in the liver? Where is it excreted?

Answer 13

Bilirubin is a breakdown product of heme Unconjugated bilirubin is transported to the liver bound to albumin (produced in the liver) once reaching the liver, it undergoes conjugation It is then excreted via urine/faeces

Question 14

What happens to the conjugated bilirubin?

Answer 14

Conjugated bilirubin makes up part of the bile Bacterial modification converts it to urobilinogen Urobilinogen is then either Excreted via faeces as stercoblin - majority Excreted via the urine as urobilin Re-enters enterohepatic circulation

Question 15

The combination of the colour of urine and stools can give an indication as to the cause of jaundice: This is because of the effects of unconjugated and conjugated bilirubin on these colours State the combination of the colour of urine and stools seen in * Pre-hepatic causes of jaundice * Hepatic causes of jaundice * Post-hepatic causes of jaundice

Answer 15

Unconjugated bilirubin is water-insoluble and therefore doesn’t affect the colour of the patient’s urine. Conjugated bilirubin, however, can pass into the urine as urobilinogen, causing the urine to become darker. Normal urine + normal stools = pre-hepatic cause Dark urine + normal stools = hepatic cause Dark urine + pale stools = post-hepatic cause (obstructive)

Question 16

The liver is responsible for the synthesis of most clotting factors Which clotting factors is it responsible for? What can be measured here?

Answer 16

The liver is responsible for producing clotting factors I (fibrinogen) II (prothrombin) V, VII, IX, X, XII, XIII Prothrombin time measures the conversion time from prothrombin –> thrombin

Question 17

What are other causes of an increased prothrombin time?

Answer 17

Other secondary causes such as Anticoagulant drug use eg warfarin Vitamin K deficiency (malabsorption of bile) Consumptive coagulopathies

Question 18

Albumin is synthesised in the liver and helps to bind water, cations, fatty acids and bilirubin. It also plays a key role in maintaining the oncotic pressure of blood. What can cause albumin levels to fall? (albumin levels changing is difficult to use in isolation)

Answer 18

Albumin levels can fall due to Liver cirrhosis Inflammation of liver triggering an acute phase response which temporarily decreases albumin Excessive loss of albumin due to eg nephrotic syndrome

Question 19

Acute hepatocellular injury can be due to many different causes What AST:ALT ratio would be suggestive of alcohol injury? What else would be raised?

Answer 19

AST and ALT both raised in acute hepatocellular injury AST:ALT ratio however is normally >2 in alcoholic liver disease GGT is also often raised in alcoholic liver disease

Question 20

What are different causes of acute hepatocellular injury?

Answer 20

Acute hepatocellular injury causes * Poisoning eg paracetamol overdose * Infection - hepatitis A and B * Liver ischaemia * Autoimmune hepaititis

Question 21

What are different causes of chronic hepatocellular injury? (both common and rare)

Answer 21

Chronic hepatocellular injuries * Common - AFLD, NAFLD, Chronic infection (Hep B or C), primary biliary cirrhosis * Rarer causes - alpha-1-antitrypsin deficinecy, Wilson’s disease (copper), haemochromatosis (iron)

Question 22

State the likely pathology causing the outlined LFTs

Answer 22

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