Liver Function

Question 1

Functions of liver

Answer 1

Nitrogen excretion
Protein biosynthesis: aIbumin, etc.
Drugs & alcohol metabolism
Bile formation: composed of phospholipids, bilirubin, bile salts & cholesterol. Digests & absorbs fats.

Liver recieves 70% of blood from portal vein, which supplies it with metabolic substrates first so that liver can detoxify any toxins or pathogens that may be ingested.

Question 2

Bilirubin transport

Answer 2

Hb broken down in spleen.
Bilirubin transported to liver bound to albumin.
Becomes conjugated in liver and transported to large intestine.
Converted to urobilinogen, then urobilin, then excreted.

Question 3

Jaundice

Answer 3

Abnormally high bilirubin >21PMol/L.
Excess urobilinogen leaves large intestine and enters kidney via portal vein.
Excreted in urine.

Question 4

Prehepatic Jaundice

Answer 4

A condition that causes elevated unconjugated bilirubin in blood.
Doesn’t primarily involve the liver but affects it indirectly.
Use Erlich’s reagent to detect urobilinogen in urine.

Question 5

Hepatocellular damage

Answer 5

Direct damage to liver.
Caused by: viruses (Hepatitis A, B & C), poisons & drugs, alcohol, conditions like non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH).
NAFLD: fatty liver without inflammation & fibrosis.
NASH: fatty liver with inflammation & fibrosis.
Can lead to cirrhosis.

Question 6

Cirrhosis

Answer 6

Long-term damage causes scarring of liver.
Portal blood flow blocked.
Causes cell death & lack of regeneration.
Cirrhotic liver has nodular surface and yellow/green colour.

Question 7

Alanine aminotransferase

Answer 7

Levels increase sharply when liver is damaged, but low normally.
Although highest activity is in liver, also present in other tissues (cardiac & skeletal muscle).
Can be increased in myocardial infarction.

Question 8

Aspartate aminotransferase

Answer 8

Levels increase in liver disease, but less than ALT.
Not specific as found in other tissues (cardiac, skeletal, kidney).

Question 9

Gamma glutamyl transferase

Answer 9

Primarily found in liver & biliary tract, and in lower levels in kidneys, pancreas & heart.
Levels increase in most diseases that result in damage to liver or bile products, so not specific.
Normally concentration is low, but increases quickly after liver damage.
Enzyme-inducing drugs (e.g., phenytoin, carbamazepine) and alcohol increase GGT levels.
Good marker for hepatocellular damage & cirrhosis.

Question 10

Albumin

Answer 10

Exclusively produced by liver, so shows livers ability to synthesise proteins.
Several functions include maintenance of oncotic pressure & transport of bilirubin, hormones & drugs.
Low levels indicate chronic liver dysfunction.
Low levels could also be caused by malnutrition, inflammation, and conditions that cause protein loss by kidneys.

Question 11

Test for Hep B infection

Answer 11

Hep B antigens increase after 1 and a 1/2 months after infection.
Damage is already occuring.
ALT increase after 1 and a 1/2 months.
Use ELISA to detect HepB surface antigen.
Use PCR test to detect viral DNA.
Detects trace amounts of DNA early on in infection.
Amplify & fluorescently tag target gene.
Correlate amount of fluorescence to infection stage.

Question 12

Non-biochemical tests for liver

Answer 12

Biopsy to confirm cirrhosis.
Ultrasound to confirm fatty liver.

Question 13

Cholestatic liver disease

Answer 13

Reduced bile flow caused by impaired secretion from hepatocytes or obstruction within the bile ducts.
Can be caused by obstruction (gallstones or pancreatic carcinoma), drugs, primary biliary cirrhosis (chronic autoimmune condition where bile duct is attacked by immune system, preventing bile secretion) or primary sclerosing cholangitis (where bile duct becomes inflamed, thickened, scarred and obstructed).

Question 14

Alkaline phosphatase (ALP)

Answer 14

Functions in intestinal homeostasis & protection, by dephosphorylating toxins and inflammatory microbiome ligands.
Although it’s concentrated in liver & bile duct, it’s present in all tissues, including bone, placenta & kidney.
Increased ALP levels can occur due to any obstruction of bile ducts but can also arise due to bone disease.
Autoanalysers detect the total ALP levels without differentiating the various isoforms. Thus, the liver -specific isoform levels cannot be measured.
Requires specialised techniques, including electrophoresis and isoenzyme-specific assays.

Question 15

Bilirubin in cholestatic liver disease

Answer 15

Due to obstruction of bile duct, conjugated bilirubin accumulates in liver.
As conjugated bilirubin is water soluble, it’s filtered into urine.
Use a dipstick test to detect bilirubin in urine.
If obstruction continues to occur, bacteria in large intestine can’t ferment conjugated bilirubin into urobilinogen or urobilin, causing faeces to become paler.
Due to bile duct impairment, fats aren’t emulsified & so are excreted. High fat content in faeces.

Question 16

Wilson’s disease

Answer 16

Caused by mutations in ATP7B gene, which prevents incorporation of copper into ceruloplasmin (Rodriguez -Castro et al., 2015).
This leads to accumulation of copper in hepatocytes, which generates oxidative stress and causes cellular damage.
This results in inflammation, necrosis & fibrosis.
This condition can cause acute liver failure when large amounts of copper are released into the blood.

Rodriguez-Castro, K. I., Hevia-Urrutia, F. J., Sturniolo, G. C. (2015) Wilson’s disease: A review of what we have learned. World journal of hepatology, 7(29), 2859–2870.