Diseases of the liver and pancreas Flashcards
Which organelle conjugates bilirubin?
Smooth endoplasmic reticulum
What are the functions of the liver?
Carbohydrates
- Glycogen storage & synthesis
- Glycolysis & gluconeogenesis
Proteins
- Synthesis & catabolism
- Clotting factors
- Amino acid metabolism &urea synthesis
Lipids
- Lipoprotein & cholesterol synthesis
- Fatty acid metabolism
- Bile acid synthesis
Excretion & detoxification
- Bile acid & bilirubin excretion
- Drug detoxification & excretion
- Steroid hormone inactivation & excretion
Miscellaneous
- Iron storage
- Vitamin A, D, E & B12 storage & metabolism
What is measured by LFTs?
Alkaline phosphatase
ALT (alanine aminotransferase)
AST (aspartate transaminase)
Bilirubin
Albumin
Total protein
GGT (glutamyl transferase)
What tests might be used for specific liver functions?
Carbohydrate metabolism
- glucose
Protein metabolism
- albumin
- urea
- prothrombin (clotting factors)
Lipid metabolism
- cholesterol
- triglycerides
- bile acids
Excretion and detoxification
- bilirubin
- drugs
- steroid hormones
Misc
- Ferritin (iron storage)
- Prothrombin time (Vit K)
What tests give an indication of hepatocyte damage?
Aminotransferases
- Alanine/ALT
- Aspartate/AST
- Found in the cell and only released by cellular damage.
ALT is more specific for liver than AST
AST also found in muscle and red blood cells
Tumour markers – α-fetoprotein (primary hepatocellular carcinoma)
What tests give an indication of biliary tract damage?
Impaired excretory function
- Increased Conjugated bilirubin
Increased synthesis of enzymes by cells lining the bile canaliculi
- ALP
- γGT
What might be the causes of increased ALP in biliary tract damage?
Cholestasis (intra- or extrahepatic)
Infiltrative diseases
Space-occupying lesions (tumours)
Cirrhosis
Which organs also secrete ALP isoenzymes?
Liver
Bone
Intestine
Placenta
If γGT and ALP are raised, what might this mean?
A raised γGT supports a liver source of ALP (as opposed to any other isoenzyme).
Elevated due to structural damage
What can cause biliary tract damage?
alcohol
enzyme inducing agents
- e.g. anti-epileptics
fatty liver
- e.g. due to alcohol, diabetes or obesity
heart failure
prostatic disease
pancreatic disease
- acute & chronic pancreatitis, cancer
kidney damage
- ARF, nephrotic syndrome, rejection
What are the biochemical markers of fibrosis?
ELF score
- PIIINP
- TIMP-1
- Hyaluronic acid
What is bilibrubin a measure of?
Excretory capacity of the liver and free flow of bile.
What is bilirubin measured as?
Total
Unconjugated
- Pre-hepatic & Hepatic
Conjugated
- Post-hepatic (Obstructive) & Hepatic
What serum level of bilirubin is considered to be jaundice?
> 40-50 μmol/L
What happens to bilirubin in the liver?
It is conjugated to bilirubin glucuronide by glucuronyl transferase.
What protein is bilirubin bound to in the blood?
Albumin
What are the pre-hepatic causes of jaundice?
Haemolysis
- e.g. Rhesus incompatibility
Ineffective erythropoiesis
- e.g. spherocytosis
What are the post-hepatic (obstructive) causes of jaundice?
Gallstones
Biliary Stricture
Cancer
- i.e. cholangiocarcinoma, head of pancreas
Cholangitis
What are the hepatic causes of jaundice?
Unconjugated
- Pre-microsomal
- Microsomal
- Inherited disorders of conjugation e.g. Gilberts, Crigler-Najjar
Conjugated
- Post-microsomal/impaired excretion
- Intrahepatic obstruction
- Inherited disorders of excretion e.g. Dubin-Johnson, Rotor.
What are the inborn errors of bilirubin metabolism?
Decreased activity of UDP glucuronyl transferase
- Gilbert’s
- Crigler-Najjar
Reduced ability to excrete bilirubin glucuronide
- Dubin-Johnson
- ROTOR
What is the pathway from haemoglobin to bilirubin glucuronide?
Haemoglobin -> bilirubin albumin-bound bilirubin -> bilirubin -> bilirubin glucuronide -> bile duct
The patient is jaundiced, their AST/ALT is elevated and their ALP is normal. What will are they likely to have?
Approx 90% of these patients will have hepatitis
The patient is jaundiced, their AST/ALT is normal and their ALP is elevated. What will are they likely to have?
Approx 90% will have obstructive jaundice
What will urine tests show in prehepatic jaundice?
Unconjugated bilirubin - no urinary bilirubin
