ChemPath: Liver Disease Flashcards
How may the causes of high bilirubin be categorized?
- Pre-hepatic -usually due to haemolysis
- Hepatic - liver dysfunction
- Post-hepatic - usually due to bile duct obstruction
Where is bilirubin conjugated?
The liver
How do you measure conjugated and unconjugated bilirubin?
Van de Bergh Reaction
A direct reaction measures conjugated bilirubin
An indirect reaction measures unconjugated bilirubin
When may paediatric jaundice be normal and when may it be pathological?
Depends on time
<24 hours after birth - pathological
24 hours to 2 weeks after birth - physiological
>2 weeks after birth - pathological
How is jaundice treated in neonates?
Depends on transcutaenous bilirubin measurement
- Moderate hyperbilirubinaemia - phototherapy
- Severe hyperbilirubinaemia - exchange transfusion
What type of inheritance pattern does Gilberts syndrome have?
Recessive
How prevalent is Gilbert’s syndrome?
About 6% of people will have it (1 in 20) 50% carry the gene.
What would you expect to see on LFTs for Gilberts?
Normal LFTs and high (unconjugated) bilirubin. No need for liver biopsy.
What may exacerbate a high bilirubin level in Gilberts?
- Fasting
- Illness
- Dehydration
- Alcohol consumption
Describe the pathophysiology of Gilberts.
UDP glucuronyl transferase activity reduced to 30%. This causes a slightly raised unconjugated bilirubin but this does not enter the urine and cause bilirubinurea.
What does it mean if you have urobilinogen in the urine?
That the enterohepatic circulation is intact. Urobilinogen is always present in the urine of normal people. It comes from the entero-hepatic circulation. If you have a normal GIT, the bilirubin that you make goes into the biliary tree, into the bowel, then bacteria in the bowel converts a small amount of bilirubin into stercobilinogen which is the same as urobilinogen and is reabsorbed and you pee it out.
What does a lack of urobilinogen in the urine suggest?
Blockage of the biliary tree. If you block the biliary tree then the bacteria cannot see the bilirubin, you get pale stools, don’t make any urobilinogen which means urine becomes negative. If urine is negative for urobilinogen but they are jaundice, suggests physical obstruction to biliary tree.
What is the best measure of Liver Function?
- Prothrombin time (clotting factors PT, PTTK)
- Albumin
- Bilirubin
What do raised levels of all liver enzymes suggest?
Hepatitis
What does a high AST and ALT suggest?
Hepatocyte damage
What would an extremely high ALP suggest?
- Obstructive Jaundice
- Obstructive jaundice normally causes ALP to rise a lot. ALP will increase by the greatest of the enzymes with obstructive jaundice.
What are prehepatic causes of hyperbilirubinaemia?
- Gilberts
- Haemolysis
What are hepatic causes of hyperbilirubinaemia?
- Viral hepatitis
- Alcoholic hepatitis
- Cirrhosis
What are post-hepatic causes of hyperbilirubinaemia?
- Gallstones
- Cancer of the head of the pancreas
What are 3 main causes of hepatitis?
- Viral - check viral titres
- Autoimmune
- Alcoholic
Describe Hepatitis A serology.
IgM - acute infection
IgG - resolved infection or vaccination
What are the two main antigens measured in Hepatitis B?
- Hepatitis B e antigen
- Hepatitis B s antigen
Describe the serology of acute, chronic, cleared, and vaccinated hepatitis B in terms of
- HBsAg
- Anti-HBc IgM
- Anti-HBc IgG
- Anti-HBs
- HBeAg
What else is used to monitor hepatitis B in addition to serology
Viral DNA
What antigen does the Hep B vaccine contain?
Hepatitis B s antigen
What are defining histology features of Alcoholic Hepatitis?
- Liver cell damage:
- Ballooning degeneration
- Mallory-Denk bodies
- Inflammatory cell infiltrate
- Fibrosis
What is the management of alcoholic hepatitis?
Supportive
- Stop drinking
- Nutritional support
- Adequate caloric intake
- Replace vitamins (B1, thiamine)
Ocassionally steroids (in severe cases)
What diseases do deficiencies in these cause?
- Vitamin D
- Vitamin C
- Vitamin B12
- Vitamin B1
- Vitamin B3
- Folic acid
- Vitamin D - rickets, osteomalacia
- Vitamin C - scurvy
- Vitamin B12 - pernicious anaemia, neuropathy
- Vitamin B1 - beri-beri
- Vitamin B3 - pellagra
- Folic acid - neural tube defects, megaloblastic anaemia
What are clinical signs of chronic stable liver disease?
- Spider naevi
- Dupuytren’s contracture
- Palmar erythema
- Gynaecomastia
What are 3 clinical signs of portal hypertension?
- Visible veins (caput medusae)
- Splenomegaly
- Ascites
What causes a liver flap?
Hepatic encephalopathy
What are the consequences of liver failure?
- Failed clotting factor and albumin synthesis - bleeding
- Failed clearance of bilirubin - jaundice
- Failed clearance of ammonia - encephalopathy
- Portal hypertension - varices and haemorrhage
What is the management of liver failure?
Supportive
- Treat cause (e.g. antivirals in hepatitis)
- Treat complications (e.g. variceal banding)
- Liver transplant in only cure for cirrhosis
What is intra-hepatic shunting of blood?
Extensive fibrosis leads to abnormal connections between portal vein and hepatic vein, bypassing sinusoids and hepatocytes. This means blood is not filtered
What is a porto-systemic anastomoses? What can happen at these places in chronic liver diease
Where portal veins join to systemic veins. These are sites of varices in liver disease
Where are the possible sites of porto-systemic anastamoses?
- Lower oesophagus
- Rectum
- Umbilicus
- Retro-peritoneal
What does scratching with jaundice suggest?
A post-hepatic cause (bile salts)
What 2 things make up bile?
Bilirubin and bile salts
What is the role of bile salts?
Bile salts emulsify fats to aid digestion and absorption
What causes itching in post-hepatic jaundice?
Bile salts or bile acids. Both not in the blood stream usually but appear when you block the bile duct.
What is Courvoisier’s sign?
Jaundice with an enlarged but painless gallbladder is unlikely to be caused by gallstones. Suggests biliary tree malignancy
Signs of obstructive jaundice
- Pale stools, dark urine
- Pruritus
- Raised ALP
