Gastro: Jaundice Flashcards
definition of jaundice
yellow discolouration of the skin, sclerae and other tissues due to excess circulating bilirubin
what is the clinical definition of jaundice?
conjugated/unconjugated concentration higher than 34umol/L
where is bilirubin metabolised?
- red cell
- plasma
- hepatocyte
- bile canaliculi
- colonic bacterial gluronidases
- intestine
what happens at the red cell?
haemoglobin is catabolised
what happens at the plasma?
unconjugated bilirubin bound to albumin, since this is lipid-soluble
what happens at the hepatocyte?
bilirubin conjugation - defective in Gilbert’s and Criggler Najjer
what happens at the bile canaliculi?
ATP-dependent biliary excretion of conjugated bilirubin; defective in Dubin-Johnson syndrome
what happens at colonic bacterial glucuronidases?
hydrolyse the conjugated bilirubin to form urobilinogen and urobilin which are excreted
what happens at the intestine?
absorption of urobilinogen which is re-excreted by liver and kidneys. renal component important in liver disease
how can you classify jaundice?
- unconjugated
- conjugated
examples of conditions that cause unconjugated jaundice
- haemolysis
- gilbert’s
- criggler najjar
what can cause conjugated jaundice?
- hepatocyte failure
- cholestasis
things that can cause cholestasis
- small duct disease
- large duct obstruction
- reduced canalicular excretion in hepatocytes
how can jaundice be classified by cause?
- hepatic (prehepatic, hepatic, posthepatic)
- cholestatic
what is the problem in jaundice where the problem is cholestasis?
the conjugated bilirubin cannot be excreted
what can cause hepatocyte failure?
- acute or chronic liver failure
- viral
- alcohol
- drugs
- autoimmune
clinical picture in haemolysis
- increase bilirubin load
- unconjugated hyperbilirubinaemia
- normal liver enzymes
- no bilirubinuria
- check CBC and reticulocyte count
clinical picture in Gilbert’s syndrome
- hereditary failure of bilirubin conjugation
- isolated unconjugated hyperbilirubinaemia
- normal liver enzymes
- no bilirubinuria
- bilirubin levels increase on fasting
- no treatment required
clinical picture of Crigler-Najjer syndrome
- hereditary failure of bilirubin conjugation
- normal liver enzymes
- phenobarbitone improve jaundice
2 types of Crigler-Najjer syndrome
Type 1: neonates die of kernicterus
Type 2: unconjugated hyperbilirubinaemia between Type 1 and Gilbert’s
what is kernicterus
brain damage found in newborns caused by jaundice
what is the cutoff between acute and chronic hepatic conditions?
6 months
clinical picture in hepatic causes of jaundice?
- prolonged INR
- low albumin
- conjugated hyperbilirubinaemia
- maintained levels of uridine diphosphate glucuronosyl transferase
causes of acute hepatitis causing liver failure
- alcohol excess
- drugs: NSAIDs, TB drugs, antiepileptics, paracetamol OD
- infections: Hep viruses, EBV, toxoplasma, rickettsaie
- autoimmune chronic active hepatitis
- autoimmune diseases like SLE and RA
- haemochromatosis
- Wilson’s disease
- liver infarction
what do the criteria consider for the diagnosis of AICAH?
- ANA
- SMA
- LKMA
- SLA
- IgG
- liver histology
score 6=probable AICAH
score 7 or higher=definite
treatment regiments for AICAH
- prednisolone
- azathioprine
what is cholestasis?
interference of bile flow or formation
symptoms of cholestasis
- jaundice
- fatigue
- pruritis
- pale stools
- dark urine
how can you classify different types of cholestasis?
- intrahepatic (hepatocyte/cholangiocyte or small duct disease)
- extrahepatic (dilatation of the bile ducts)
causes of bile duct dilatation
- obstruction
- no obstruction
obstructive causes of bile duct dilatation
- strictures
- stones
causes of strictures within the bile duct system
- neoplasms (cholangiocarcinoma, gallbladder adenocarcinoma, pancreatic adenocarcinoma)
- postinflammatory (pancreatitis, post-radio/chemotherapy)
- inflammatory (AIDS cholangiopathy, biliary parasites, primary sclerosing cholangitis)
non-obstructive causes of bile duct dilatation
- caroli disease
- choledochal cyst
- recurrent pyogenic cholangitis
- primary sclerosing cholangitis
investigations in large duct obstruction
- trans-thoracic US
- cross sectional imaging (CT/MRCP)
- endoscopic US
- ERCP and brush cytology (this is more therapeutic rather than diagnostic)
management of a patient with biliary dilatation, obstruction and is septic?
emergency ERCP and stenting
management of a patient with no obstruction
CS imaging and follow up
classify according to the liver biopsy
- disorder of the bile ducts
- disorders with spare the bile ducts
- no disorders
conditions that can cause bile duct involvement
- AMA negative PBC
- primart/secondary sclerosing cholangitis
- congenital disorders
- sarcoidosis
- idiopathic ductopenia
- prolonged drug induced cholestasis
- developmental abnormalities
- cholangitis associated with malignancies
- IgG4 associated cholangitis (autoimmune disease)
- cystic fibrosis
- graft vs host disease
histological features of PBC
- granulomatous changes
- dense lymphocytic infiltrate
- ruptured interlobular bile duct
- epitheloid granuloma
- FLORID DUCT LESION (focal duct obliteration with granuloma formation)
treatment of PBC
- ursodeoxycholic acid
how does ursodeoxycholic acid work in PBC?
protects injured cholangiocytes from toxic bile acids in the early stages; stimulates secretion from impaired hepatocytes in advanced cholestasis
things to note about ursodeoxycholic acid
- does not have an effect on pruritis or fatigue
- improves bilirubin levels, enzyme levels and IgM levels
histological features of PSC
- moderately dense inflammatory infiltrate
- onion skin fibrosis
which dose of UDCA has been shown to have benefits?
15-20mg/kg/day
what kind of benefits does UDCA have
- improves LFTs
- improves histological findings
interventional treatment for PSC
- ERCP (balloon dilatation, stenting)
- liver tranplantation
surgical interventions for PSC
- resection of the extrahepatic biliary tree
- Roux-en-Y choledochojejunostomy (indicated in advanced cirrhosis, failed ERCP stricture management)
which are abnormalities causing jaundice which do not involve the bile ducts?
- malignant infiltration
- benign infiltration (amyloidosis/sarcoidosis)
- peliosis hepatis
- cirrhosis
- congenital hepatic fibrosis
- sinusoidal dilatation: Budd Chiari, veno-occlusive disease, congestive heart failure
what is peliosis hepatis?
- large blood filled spaces which may not be lined with sinusoidal cells
- associated with drugs such as tamoxifen, OCP, androgenic steroids, danazol
- seen in renal transplant recipients
what is sinusoidal dilatation associated with?
acute right heart failure
what is benign recurrent intrahepatic cholestasis
- inherited condition
- presents in adolescents/adults
- acute episodes of cholestasis with jaundice and pruritis
- can resolve in weeks/months but they may recur after
- BRIC 1 - pancreatitis
- BRIC-2 - gall stones
- may have liver fibrosis
drug treatment for pruritis
- UDCA
- cholestryramine
- rifampicin
- naltrexone
- sertraline
which drugs are not recommended for treating pruritis
- anti-histamines
- ondansetron
- phenobarbitone
supportive care
- pruritis
- fatigue
- fat-soluble vitamins
- osteoporosis
