Jaundice Flashcards
Differentiate obstructive vs cholestatic jaundice
Obstructive jaundice: this refers to jaundice caused by the lack of bile flow into the gut, which manifests as pale faeces (lack of urobilin/stercobilin) and dark urine (conjugated bilirubin). The obstruction can be anywhere in the biliary system (in the bile canaliculi inside the liver, or after the liver), but some clinicans use it to refer specifically to obstructions affecting the biliary system outside the liver
Cholestatic: jaundice caused by bilirubin not flowing out via the common bile duct, can be due to obstruction or due to paralysis of the common bile duct peristalsis
Cause of paralysis of common bile duct peristalsis- is this obstructive?
Paralysis of common bile duct peristalsis is NOT obstuctive, it is cholestatic.
It can be drug induced
What might be the cause of
i. Darker urine
ii. Black urine
Dark urine:
When there is obstructive jaundice, no conjugated bilirbin can get into the gut, therefore it cannot be metabolised into stercobilinogen (so in complete obstructio there is not a trace of stercobilinogen in the urine). The unconjugated bilirubin backing up into the bloodstream and then into the urine is what makes the urine darker in this case. In a healthy person, the urobilin makes urine yellow.
Black urine:
There is intravascular haemolysis, so the free haemoglobin is degraded via an alternative pathway into haemosiderin which is very dark but water soluble. You would find schistocytes on blood film
T/F reduced bilirubin conjugation is commonly due to hepatocyte damage
F…. it is rarely due to hepatocyte damage because the hepatocytes need to be VERY DAMAGED before they stop conjugating- so damaged that jaundice would be the least of one’s problems
Reasons for decreased conjugation of bilirubin
Enzyme problem (Gilbert’s… UDP-glucuronosyltransferase, UGT deficiency) or reduced hepatic uptake of bilirubin (cholecystographic contrast agents/portosystemic shunts to bypass a cirrhotic liver)
Or reduced hepatic uptake (due to cholecystographic contast agens/porti-systemic shunts to bypass a cirrhotic liver)
Medications causing jaundice: the 4 mechanisms with examples
- Intravascular haemolysis- sulphonamides and aspirin in those with G6PD
- Autoimmune, extravascular haemolysis (methyldopa)
- Hepatitis (e.g. paracetemol overdose)
- Cholestasis (e.g. co-amoxiclav)
Drugs can cause jaundice by reducing the excretion of bilirubin (e.g. alcohol abuse, paracetamol overdose, valproate, rifampicin)
Others can induce a paralysis (ileus) of the biliary system (e.g. co-amoxiclav, nitrofurantoin, oral contraceptive pill).
What can cause jaundice in pregnancy
Acute fatty liver of pregnancy
HELLP
Intrahepatic cholestasis of pregnancy
Pre-eclampsia
What is the relevance of the following conditions to jaundice:
- Haemophilia
- Ulcerative colitis
- Diabetes mellitus
- Emphysema
- May have received blood products contaminated with hep C
- Strong association between UC and PSC
- Seen in haemochromatosis
- Associated with a1- antitrypsin deficiency
What percentage of conjugated bilirubin as a percetnage of total bilirubin in the blood indicates an obstructive problem
As long as the conjugated bilirubin is greater than 20%
What does a rased AST and ALT
AST and ALT normally means that there is hepatocyte damage. They are very high in acute viral hepatitis.
Elevation of AST>ALT suggests excessive alcohol intake, but ALT>AST suggests viral hepatitis.
Levels of AST/ALT in the thousands is seen when
Viral hepatitis, paracetemol and ischaemic hepatitis
Where is ALP and GGT released from. When are the tests useful
Useful is bile flow obstruction suspected
ALP is released from damaged biliary epithelial cells, bones with high turnover, and/or a placenta (remember that she might be pregnant!).
GGT is expressed almost exclusively by biliary epithelial cells.
Consequently, a raised ALP and raised GGT suggest bile duct pathology (e.g. obstruction), whereas a raised ALP but normal GGT suggests increased bone turnover (e.g. malignant bone metastases, primary hyperparathyroidism) or pregnancy.
When is a raised GGT seen in isolation
After recent alcohol consumption
T/F bilirubin in the urine is always pathological
True.
Urobilinogen can be in the urine in some people, so a normal urine urobilinogen is sometimes positive and sometimes negative
A normal urine bilirubin is negative. An example of a disease process resulting in bilirubin in the urine is in posthepatic obstructive jaundice, when there is not a trace of uribilinogen in the urine because the bilirubin cannot flow into the gut. Then unconjugated bilirubin is found in the urine.
NOTE THAT IN HAEMOLYTIC DISEASE, BILIRUBIN IS NEGATIVE. In conditions which increase bilirubin production, the normal liver cannot cope with the additional bilirubin. But this additional unconjugated ubilirubin doesn’t make it into the urine because it is insoluble
What are you looking for in a haemolysis screen
- Haptoglobins (reduces in haemolysis because it binds all the free haem released from the haemolysed RBCs)
- Lactate dehydrogenase (released by haemolysed RBCs)
- Direct antiglobulin test (DAT) for autoimmune haemolysis and
- A blood film allows you to look for schistocytes, sickle cells, target cells (thal), sperocytes or malaria
