Jaundice Flashcards
What type of jaundice is seen classically with the following bloods:
Hb 153, Plts 75, WCC 6.4, ALT 90, Alk Phos 132, Bili 40, PT 24
Hepatocellular
A raised ALT, an Alk Phos within the upper limits of normal, with low platelets and high INR, this is most likely to be hepatocellular in nature (most commonly alcoholic liver disease)
A patient is admitted with RUQ pain and blood tests showing a post-hepatic jaundice, the patient otherwise well and stable. What is the most appropriate initial investigation?
US abdomen
What are the bilirubin levels for the jaundice to occur?
Bilirubin levels >50µmol/L
What is the jaundice result of?
High level of bilirubin in the blood
Bilirubin pathway
- Bilirubin is the normal breakdown product from the catabolism of haem (destruction of RBCs)
- bilirubin undergoes conjugation within the liver, making it water-soluble
- It is then excreted via the bile into the GI tract, the majority of which egested in the faeces as urobilinogen
- Around 10% is reabsorbed into the bloodstream and excreted through the kidneys
Jaundice occurs when this pathway is disrupted.
Pre-hepatic jaundice
- what happens in overall?
- what happens to bilirubin?
Pre-hepatic jaundice
- Happens as a result of excessive breakdown of RBCs
- the liver cannot cope with excess bilirubin -> cannot conjugate it all -> unconjugated bilirubin
- unconjugated bilirubin = jaundice
*some bilirubin can manage to be conjugated and to be excreted normally. It’s only an unconjugated bilirubin that remains in the bloodstream and appear as a jaundice
Hepatocellular jaundice
- what happens?
- what picture of jaundice can be seen and why?
Hepatocellular/ intracellular
- liver loses its ability to conjugate bilirubin (due to liver damage/ impairment)
- mixed picture jaundice may occur because, example:
- liver cirrhosis may compress on the hepetic portion of biliary duct -> conjugated bilirubin
- liver damage -> cannot conjugate -> unconjugated bilirubin
Post-hepatic jaundice
- what happens
- type of jaundice
Post-hepatic
- bilirubin cannot be excreted from a biliary tract due to obstruction
- as bilirubin was conjugated by the liver -> conjugated hyperbilirubinaemia
Pre- hepatic causes of jaundice
Name some specific conditions
- *Pre-Hepatic**
- Haemolytic anaemia
- Gilbert’s syndrome or Criggler-Najjar syndrome
Hepatocellular jaundice causes
(specific conditions)
Hepatocellular jaundice
- Alcoholic liver disease
- Viral hepatitis
- Medication
- Hereditary haemochromatosis
- Autoimmune hepatitis
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Hepatocellular carcinoma
Post-hepatic jaundice causes
- specific conditions
Post-hepatic jaundice
- Intra-luminal causes, such as gallstones
- Mural causes, such as cholangiocarcinoma, strictures, or drug-induced cholestasis
- Extra-mural causes, such as pancreatic cancer or abdominal masses (e.g. lymphomas)
Colour of urine and type of jaundice
Conjugated bilirubin (as per normal pathway) may be excreted in the urine
- dark, coca-cola urine -> in conjugated, mixed-type jaundice
- normal urine -> in unconjugated
Investigations for jaundice (bloods) + rationale
FBC -> anaemia, raised MCV, thrombocytopaenia - seen in all liver diseases
LFTs-> to look for a degree of jaundice, hepatocellular injury
U&Es
Coagulation studies -> PT may be raised in liver dysfunction (due to impaired synthesis of clotting factors)
LFTs in testing for jaundice
(explain each component of the blood test)
- Bilirubin -> to assess the degree of jaundice
- Albumin -> marker of liver synthesis function
- AST and ALT -> marker of hepatocellular injury
- Alkaline Phosphatase -> raised in a biliary obstruction (or in bone injury)
- Gamma-GT -> raised in biliary obstruction
*Gamma-GT is not a part of standard LFTs - requested separately if ALP is raised
What conditions are the ratios suggesting of:
- AST:ALT ratio of >2
- AST:ALT ratio of around 1
- AST:ALT ratio of >2 -> likely alcohol liver disease
- AST:ALT ratio of around 1 -> likely viral hepatitis
When to perform liver screen?
What are the main two categories looked at in the liver screen?
If unsure of what is causing a liver dysfunction
Categories:
A. Acute Liver Injury
B. Chronic liver injury
*both looking at viral serology and non-infective markers
Components of the liver screen in acute liver injury
- viral serology
- non- infective markers
Components of the liver screen in chronic liver injury:
- viral serology
- non-infective markers
Autoantibodies screened for in the liver screen for chronic liver injury
Chronic liver injury, non-infective causes markers - autoantibodies:
- AMA anti-mitochondrial antibody
- Anti-SMA anti-smooth muscle antibody
- ANA anti-nuclear antibody
*these are used to identify variety of autoimmune conditions e.g. primary sclerosing cholangitis
Imaging in the investigation of jaundice
- abdominal USS -> to identify obstructive causes or gross liver pathology
- MRCP -> to visualise biliary tree*
*MRCP is typically performed if obstructive jaundice is suspected, but USS abdomen was inconclusive
Examples for definitive treatment for jaundice
Depends on underlying cause, e.g.
obstructive - removal of gallstone through ERCP, open surgery, cholecystectomy, stenting of the common bile dugt
Symptomatic treatment of itching in obstructive jaundice
Itching (due to hyperbilirubinaemia)
- cholestyramine - to improve biliary drainage
*MoA of cholestyramine: it is a bile acid sequestrant; combines with bile acids in the intestine -> forms an insoluble complex that is excreted in the faeces
- antihistamines
Possible complications of liver failure (monitoring and management)
Coagulopathy/ bleeding -> vitamin K, Fresh Frozen Plasma (FFP)
Hypoglecaemia -> oral Rx (when possible) or 5% dexterose
Confusion (from hepatic encephalopathy):
- laxatives (lactulose or senna)*
- neomycin or rifaximin (*to reduce the number of ammonia-producing bacteria in the bowel)
* neomycin - aminoglycoside antibiotic
* rifaximin - semi-synthetic antibiotics (used in travellers diarrhoea and hepatic encephalopathy)
Gilbert’s syndrome
- What is this
- Pathology and genetics
Gilbert’s syndrome
- It is a mild liver disorder - unable to fully process bilirubin
-
Mutation in UGT1A1 gene -> decreased function of bilirubin uridine diphosphate glucuronosyntransferate enzyme
- usually inherited in AR pattern
- rarely inherited in AD pattern - depends on type of mutation
Gilbert syndrome
- Symptoms and presentation
- Diagnosis
Gilbert syndrome
-
Symptoms
- occasional yellowing of the skin or sclera
- weakness/ fatigue
- abdominal pain
* episodes of jaundice may be triggered by stress, exercise, menstruation, starvation
- Diagnosis:
higher levels of unconjugated bilirubin in the blood without signs or liver problems or RBCs breakdown
Gilbert syndrome
Treatment
Gilbert syndrome
- usually, no treatment is needed
- significant jaundice -> phenobarbital
*phenobarbital is barbiturate; in jaundice, it works by increasing liver metabolism (so it will conjugate more bilirubin)
Crigler - Najjar syndrome
- What is this and complications
- Pathology and genetics
Crigler-Najjar syndrome
- disorder of bilirubin metabolism
- manifests in infancy
- for od non-haemolytic jaundice
- accumulation of bilirubin -> brain damage in infants
Genetics:
AR manner of inheritance
Pathology: uridine diphosphogluconurate glucuronosyltransferase (UGT1A1) enzyme dysfunction -> bilirubin cannot be conjugated
Crigler-Najjar syndrome
What’s seen and what’s not seen on the investigation
Crigler-Najjar
- liver function and hepatic histology -> are usually normal = no evidence of liver damage
- no evidence of haemolysis
Treatment in Crigler- Najjar syndrome
- plasmapheresis
- phototherapy
- liver transplant - curative
Dubin - Johnson syndrome
- pathology and genetics
AR benign disorder -> increased conjugated bilirubin in the serum
Pathology: hepatocytes unable to secrete conjugated bilirubin into the bile (instead it goes into the serum/blood)
Dubin - Johnson syndrome
- the appearance of the liver
Dubin-Johnson
- liver would be black or pink - due to the accumulation of pigment
Dubin - Johnson syndrome
- diagnosis
Unusual ratio between the byproducts of heme biosynthesis:
- normally, coproporphyrin III to coproporphyrin I ratio around 3–4:1.
- in Dubin–Johnson syndrome, this ratio is inverted, with coproporphyrin I being 3–4 times higher than coproporphyrin III
For the first two days of life, healthy neonates have ratios of urinary coproporphyrin similar to those seen in patients with Dubin–Johnson syndrome; by 10 days of life, however, these levels convert to the normal adult ratio
Dubin-Johnson syndrome
treatment
The condition is benign and usually, no treatment is needed as most patients are asymptomatic
*it is important to recognise it so it is not confused with other disorders associated with hyperbilirubinaemia (jaundice)
