Liver Function 11/11

Question 1

What are the 2 types of liver cells?

Answer 1

Hepatocytes and Kuppfer cells

Question 2

What is the function of hepatocytes?

Answer 2

Protein synthesis

Question 3

What is the function of Kupffer Cells?

Answer 3

Macrophages lining sinusoids that act as phagocytes and engulf bacteria, toxins and debris

Question 4

What are the 5 major functions of the liver?

Answer 4

1. Metabolism
2. Synthesis
3. Storage
4. Detoxification
5. Excretion/digestion

Question 5

Describe the metabolic function of the liver.

Answer 5

Carbohydrate metabolism (storage of glycogen/release of glucose)
Protein metabolism
Lipid/cholesterol metabolism

Question 6

Describe the synthesis function of the liver.

Answer 6

The liver synthesises plasma proteins such as albumin, clotting factors and c-reactive proteins

Question 7

Describe the storage function of the liver.

Answer 7

Stores iron, glycogen, amino acids, some vitamins (A, D, B12), temporary lipid storage

Question 8

Describe the detoxification function of the liver.

Answer 8

Detoxifies alcohol, paracetemol, drugs, GIT metabolites

Question 9

Describe the excretory/digestive function of the liver.

Answer 9

Removes waste eg degrades bilirubin and excretes excess cholesterol in bile

Question 10

Define jaundice.

Answer 10

A clinical condition associated with increased serum bilirubin and its deposition in the skin, mucous membranes and white of the eye (sclera) giving a characteristic yellow colouring known as icterus

= problems with heme degredation

Question 11

What causes prehepatic jaundice?

Answer 11

anything which causes an increased rate of haemolysis (breakdown of red blood cells) (eg malaria, sickle cell disease, haemolytic disease of the newborn)

Question 12

What biochemical changes will you see in prehepatic jaundice?

Answer 12

Increase in unconjugated bilirubin
Increase in plasma total bilirubin
Increase in urine urobilinogen

Question 13

What are the 3 types of hepatic/intrahepatic jaundice?

Answer 13

1. Hepatocellular damage
2. Disorders of bilirubin metabolism and transport
3. Transient immaturity of the liver - neonatal physiological jaundice

Question 14

What are the 4 different causes of hepatocellular damage?

Answer 14

1. Hepatitis
2. Drug induced hepatic damage
3. Wilson’s disease
4. Liver tumors

Question 15

Describe Wilson’s disease.

Answer 15

Low levels of caeruloplasmin (copper transport protein) resulting in deposition of copper in the liver causing cirrhotic damage (scarring of liver cells)

Question 16

What biochemical changes will you see in hepatic/intrahepatic jaundice?

Answer 16

Increased conjugated bilirubin
Increased total plasma bilirubin
Increased urine bilirubin
Decreased urine urobilinogen
Increased plasma AST and ALT

Question 17

What are the 3 disorders of bilirubin metabolism and transport?

Answer 17

1. Gilbert’s disease
2. Crigler-Najjar disease
3. Dublin-johnson syndrome

Question 18

Describe Gilbert’s disease.

Answer 18

Defective transport of bilirubin into the hepatocytes = causes an increase in unconjugated bilirubin

Question 19

Describe Crigler-Najjar disease.

Answer 19

Hereditary deficiency of the UDPG-transferase enzyme (can’t convert unconjugated bilirubin to conjugated)

Question 20

Describe Dublin-Johnson syndrome.

Answer 20

Deficiency of canalicular multidrug transporter protein = defective removal of conjugated bilirubin = accumulation in blood

Question 21

Describe transient immaturity of the liver - neonatal physiological jaundice

Answer 21

Short term delay in the ability to produce UDPG-transferase enzyme resulting in rapid buildup of unconjugated bilirubin

Question 22

What are the possible treatment options for neonatal physiological jaundice?

Answer 22

Phototherapy (UV light) to isomerise bilirubin into a non-toxic form
Exchange blood transfusion to prevent damage to the brain (kernicterus)

Question 23

What causes posthepatic jaundice?

Answer 23

Partial or complete obstruction of the biliary tree that prevents flow of conjugated bilirubin into the bile canaliculi (stools become clay coloured since it doesn’t reach the gut)

e.g gall stones or pancreatic cancer

Question 24

What biochemical changes will you see in posthepatic jaundice?

Answer 24

Increased conjugated bilirubin
Increased total plasma bilirubin
Positive urine bilirubin
Decreased urine urobilinogen
Increased plasma GGT and ALP

Question 25

What are the 3 types of liver function tests?

Answer 25

1. Tests measuring synthetic ability 2. Tests measuring nitrogen metabolism 3. Tests measuring bilirubin metabolism

Question 26

What are the 3 things you could measure when testing for synthetic ability of the liver?

Answer 26

1. Albumin - major plasma protein produced by the liver, decreased in chronic liver disease 2. Prothrombonin time - commonly increases in liver disease due to inadequate production of clotting factors and inadequate absorption of vitamin K from intestine due to disrupted bile flow 3. Lipids - hepatic disorders cause derangements in lipoproteins metabolism but this is not specific for liver

Question 27

Why is albumin testing not useful for acute liver disease?

Answer 27

Because it has a long half life there will still be albumin levels circulating

Question 28

Describe tests measuring nitrogen metabolism.

Answer 28

Protein metabolism produces ammonia NH4+ which is toxic so is converted to urea by the liver In liver failure plasma ammonia levels are increased and are responsible for neurological signs of hepatic encephalopathy (decline in brain function), transient hyperammonaemia in newborn due to liver immaturity, or urea cycle enzyme deficiencies

Question 29

What are the 3 main types of liver function tests (broad)?

Answer 29

1. Liver function 2. Liver damage tests 3. Cholestasis

Question 30

What do tests measuring bilirubin metabolism measure for?

Answer 30

Total plasma bilirubin Conjugated/unconjugated bilirubin Urine bilirubin Urine urobilinogen

Question 31

What enzymes are measured in liver damage tests and why?

Answer 31

Plasma AST and ALT - released into circulation after an injury that results in cytolysis or necrosis

Question 32

What is measuring AST and ALT used for?

Answer 32

Used to differentiate hepatocelluar damage from obstructive liver disease

Question 33

Where is AST produced?

Answer 33

By hepatocytes and many other tissues such as cardiac muscle, skeletal muscle and erythrocytes

Question 34

Where is ALT produced?

Answer 34

Primarily by hepatocytes (more specific than AST)

Question 35

In acute hepatitis, what biochemical response would you see?

Answer 35

Early and dramatic rise in AST and ALT

Question 36

In hepatic necrosis why would you see a sudden decrease in AST and ALT?

Answer 36

Due to total liver cell destruction - bad prognostic sign

Question 37

In chronic hepatits what levels of AST and ALT would you see?

Answer 37

Mildly elevated levels of AST and ALT

Question 38

From alcohol, drugs, cirrhosis, what levels of AST and ALT would you see.

Answer 38

AST higher than ALT

Question 39

What is cholestasis?

Answer 39

Blockage of the bile duct = no bile can flow from the liver to the intestine

Question 40

What causes intrahepatic cholestasis?

Answer 40

Liver cancer, biliary cirrhosis

Question 41

What causes extrahepatic cholestasis?

Answer 41

Gallstone or tumor blocking

Question 42

What enzyme is more specific to blockage of bile duct?

Answer 42

GGT ALP is produced by hepatocytes but also bone, intestine and placenta

Question 43

How are GGT levels used to monitor alcohol intake?

Answer 43

Levels decline with abstention of alcohol intake

Question 44

What is the limitation of liver enzymes in acute disease?

Answer 44

They don't correlate with severity/prognosis

Question 45

What is the limitation of liver enzymes in chronic liver disease?

Answer 45

They can only tell us something is wrong with the liver - not useful in addressing severity or progression