Case of the yellow eyed woman Flashcards
LIVER ARCHITECTURE
i) what lies between the hepatocytes?
ii) what is bilirubin produced from?
iii) what implication does damaged hepatocytes have on bilirubin? how does this lead to jaundice
iv) damage to what other structure can cause jaundice?
v) what can compression of the larger bile ducts cause?
i) bile ductules > become bigger as they progress
ii) breakdown of RBC > liver > conjugated
iii) damaged hepatos > cant excrete bilirubin into the bile ductules
- bilirubin regurgitates into the blood/circ > jaundice
iv) damage to the bile ductules > cant get bilirubin out therefore back into the circ and causes jaundice
v) extra hepatic biliary obstruction
- inability of hepatos or bile ductules to normally excrete bilirubin > cholestasis and jaundice (intra hepatic cholestasis)
BILE PRODUCTION
i) what are RBC first broken down into? then what? then bilirubin
ii) where does bilirubin then go to and what happens? what enzyme controls it and what happens if this enzyme goes wrong
iii) what does the MRP2 gene control? what happens if it goes wrong?which duct does it enter to get to the gall bladder? where does it go to after the GB?
iv) which breakdown product gives urine its colour? which gives faeces its brown colour?
v) what happens if there is any obstruction in the liver?
i) RBC broken down into heme then biliverdin then bilirubin
ii) active transport to the liver where it gets conjugated - controled by UGT enzyme
- doesnt work - get high levels of unconj bilirubin > crigler najjar syndrome - need transplant immed
- milder syndrome if UGT doesnt work = Gilberts syndrome (benign condition)
iii) MRP2 controls transport from liver > conjugated bilirubinaemia = dublin johnson syndrome
- common bile duct then gall bladder
- from GB > sphincter of oddi to the bowel
iv) bdown to urobillogen in the bowel > urobilin gives urine colour
- stercobilin gives poo brown colour
v) bilirubin cant pass and regurgitates into the blood > jaundice
APPROACH TO ABNORMAL LFT
i) what are the three patterns of liver injury?
ii) what three time durations?
iii) what do you need to ask if present
i) hepatitic, cholestatic and cholestatic hepatitic (mixed)
ii) acute, sub acute or chronic
iii) is liver failure present and what is the underlying cause
LFTS
i) what enzymes go up in hepatitic problems? (2)
ii) what go up in cholestatic (2)
iii) what albumin levels are expected to be seen in liver injury?
iv) which two other measures test the clotting factors? which pathway?
v) which two liver tests have prognostic value?
i) transaminases eg AST and ALT
ii) ALP and GGT
iii) low
iv) PT and INR - measures extrinsic coagulation pathway ( factors II, V, VII, X and fibrinogen)
v) bilirubin and INR
- for these to go up > there has been a major hit to the liver
CAUSES OF ABNORMAL LFTS
i) name three things that can cause a hepatitic pattern
ii) name three drugs that can cause drug induced liver injury
iii) name four intrahepatic causes of a cholestatic picture
iv) name three causes of extrahepatic cholestasis
i) viral hepatitis (A,B,C,E), drug induced liver injury (paracetamol and abx), autoimmune hepatitis, wilsons disease (young)
ii) paracetamol, antibiotics, statins, check point inhibitors, anti epileptics
iii) viral hepatitis (eg A can start off as hepatitic > progress to cholestatic), drugs, autoimmune
- genetic conds - primary biliary cholangitis (AI destruc of small interlob bile ducts), genetic syndromes, sepsis
iv) affects bigger bile ducts > stones, strictures, primary sclerosing cholangitis, tumour eg cholangiocarcinoma
DURATION OF INJURY IN ABNORMAL LFTS
i) up to how many weeks is an injury classed as acute? name three causes of acute injury
ii) how many weeks is sub acute? name four causes
iii) how many weeks is chronic? name three key causes?
i) <6 weeks - viral hep, drug induced, AI heptitis, wilsons disease
ii) sub acute is 6-26 weeks
- viral hep ABCDE, AI hep, drug induced, wilsons disease
iii) chronic = abnormal liver tests for >26wks (6 month)
- NAFLD, alcohol, viral hepatitis
- also AI hep, wilsons, haemochromotosis, A1 anti tryp defic
CIRRHOSIS
i) what happens to an intial liver injury if it is not treated?
ii) what is cirrhosis? is it reversible?
iii) what is an essential pre requiste for cirrhosis?
iv) name three tests for hepatic fibrosis? what remains gold standard?
i) progresses from initial inflammation to scarring/fibrosis that is reversible then leads to cirrhosis
ii) cirrhosis is replacement of liver architecture with fibrotic nodules
- generally not reversible
iii) all patients with cirhhosis have chronic liver disease
(but not all those with CLD have cirrhosis)
- CLD is abnormal liver for >6m
iv) AST/ALT ratio, FIB-4 test (AST, ALT, plats), fibroscan (non invasive scan of liver)
- liver biopsy remains gold standard
PORTAL HYPERTENSION
i) which two veins join to make the portal vein
ii) what does scarring in the liver cause in relation to portal circ?
i) sup mesenteric and splenic vein
ii) destruction of portal venous areas that leads to raised pressure in the portal circ > portal HTN (UL mech of may sequale of cirrhosis)
COMPENSATED VS DECOMPENSATED CIRRHOSIS
i) what are the three most common causes of cirrhosis?
ii) what happens to portal pressure once somebody has cirrhosis?
iii) at what level do sequale of portal HTN appear? name three sequale?
iv) what marks transition from compensated to decompensated phase
v) what is avg life expectancy for compensated cirrhosis? what is it for decompensated?
i) irreversible scarring of liver - NAFLD, alcohol, viral hepatitis
ii) portal pressure goes up > portal HTN
iii) Portal pressures > 11
- ascites (most common), variceal bleeding, hepatic encephalopathy and jaundice
iv) once a person develops any of the above sequale
v) compensated 12-15yrs
- decomp - 2 years > evaluate for transplantation
LIVER FAILURE
i) what are two things that are a pre requisite for liver failure?
ii) what are the three types
iii) what defines acute liver failure? what are two causes? is it better for enceph to start quicker or slower
iv) what is acute on chronic liver failure? what can it be regarded as
v) what bilirubin level is acute on chronic liver failure?
i) hepatic encephalopathy (confusion) and coagulopathy (INR >2)
ii) acute, sub acute and acute on chronic
iii) no pre existing liver disease > acute insult then jaundice then within 4 weeks > encephalopathy
- paracetamol and viral hepatitis
- better prognosis if enceph starts earlier
iv) organ fail (hep enceph + coagulopathy) in the presence of underlying liver disease
- can be regarded as a more severe form of hepatic decompensation
v) bilirubin 12x UL normal with jaundice > ACLF
LIVER SCREEN
i) name four things tested for in a hepatitis serology/viral screen?
ii) name three auto antibodies to screen for in auto immune hepatitis
iii) which condition is positive for anti mito antibody M2?
iv) name three genetic conditions that can cause abnormal LFTs
v) what needs to be ruled out if someone is jaundiced?
i) hep A IgM, hep B surface antigen, Hep C antibody, Hep E IgM
ii) anti nuc antibody, anti smooth muscle antibody, liver kidney microsomal antibody
iii) primary biliary cholangitis
iv) wilsons disease, alpha 1 antitrypsin, genetic haemochromotosis
v) rule out biliary obstruction
AUTOIMMUNE HEPATITIS
i) what is it? is it more common in men or women?
ii) name two auto antibodies that may be seen? which two HLA associations?
iii) what does it have excellent response to
iv) which cells are implicated
i) chronic immune mediated condition of unknown cause
- more common in women
ii) ANA, SMA, LKM
- HLA DRB1, DRb3
iii) good response to immunosuppression (steroids) to supress the antigen specific effector T cells
iv) loss of T regulatory cells
PRIMARY BILIARY CHOLANGITIS
i) what are 90% of the affected people?
ii) name two symptoms? what picture is seen on liver tests
iii) which antibody is positive?
iv) what is seen on biopsy?
v) what is the treatment?
i) women between 40-50yrs
ii) asymp or itchy
- see cholestatic picture
iii) AMA M2 positive
iv) see granulomatous hepatitis
v) ursodeoxycholic acid (obetacholic acid second line)
PRIMARY SCLEROSING CHOLANGITIS
i) are men or women more affected? which bile ducts does it affect
ii) what do 75% of patients also have? how is this thought to lead to PSC
iii) what is seen on biopsy?
iv) what cancer is there increased risk of
v) what happens to the bile ducts
i) men are more affected
- affects larger bile ducts (intra and extra hepatic) - cholestatic pattern
ii) 75% also have IBD > bacteria enters the portal circ through an inflamed intestine
iii) concetric fibrosis around bile ducts
iv) cholangiocarcinoma - transplant is difficult
v) narrowing and stricturing
GENETIC CHOLESTATSIS SYNDROMES
i) what are the severe versions called? who is it generally seen in
ii) what is the milder version
i) PFIC - children and neonates
ii) BRIC
