Feb22 M1,2-Hepatic Function Liver Disease Flashcards
true liver function tests
- total serum protein and albumin
- total bilirubin
- prothrombin time (PT, INR)
fake LFTs
- ALT
- AST
- AP
ALT charact
released when liver cells damaged
normal 5-40
AST charact
can come from liver but also heart muscle intestine pancreas
normal 8-20
AST:ALT ratio in alcoholics
2:1 AST:ALT
AP charact
normal 20-70. found in liver (can frac or do isoenzymes to check if not from bone)
marker of OBSTRUCTION or infiltrative disease (cholestatic disease)
how to check if AP shows cholestatic liver injury (bile not emptying properly)
GGT (gamma GT) must be elevated too
(EXAM) bilirubin source and 2 types
indirect (unconjugated): from old RBCs.
conjugated (direct): after liver adds glucuronic acid to make it water soluble for excretion
(EXAM) bilirubin excretion
stool (makes it brown)
urine (high bilirubin = black urine)
(EXAM) normal total bilirubin
0.3-1.0 mg per dL
(EXAM) direct bilirubin tells what
amount of bilirubin liver was able to manage
(EXAM) how bilirubin made from heme
IN MACROPHAGES:
- heme oxygenase transforms open alpha group on heme: makes biliverdin
- biliverdin reduced by biliverdin reductase to make bilirubin
(EXAM) what happens to bilirubin in hepatocytes
conjugated to form bilirubin diglucuronide (DIRECT) by UDP-glucuronyl transferase
(EXAM) what happens to bilirubin diglucuronide in bacteria of the gut
transformed in urobilinogen (which is what goes to urine) and stercobilinogen (in the stool)
3 types of jaundice (also called icterus)
(jaundice = serum bilirubin over 3 mg per dL)
prehaptic, intrahepatic, posthepatic
prehepatic jaundice
hemolytic anemia, increased load of bilirubin
intrahepatic jaundice
problem inside liver in making direct bilirubin (infection, chemical, drug, genetics, autoimmune, neonatal)
posthepatic jaundice
intrahepatic bile ducts (drug, PBC, cholangitis)
extrahepatic bile ducts (gallstones, pancreatic tumor, cholangiocarcinoma)
2 types of drug injuries to the liver
- predictable (tylenol): we know the quantity
- by chance
elevated bilirubin and jaundice: which is up direct or indirect?
both. DIRECT is the most of it. (bc still transforming to direct, it’s a clearance problem)
LFTs in liver problem
direct bilirubin up
indirect bilirubin up
albumin down
INR up
steps in determining what kind of jaundice is present
- check the conjugated bilirubin (is normal in pre, but is high in intra and post)
- ask for color of stools (are light colored if extrahepatic)
other way to distinguish posthepatic jaundice
high ALP (AP) and NO urine urobilinogen
(IMPORTANT)extrahepatic causes of biliary obstruction + most common of these
- choledocholithiasis
- malignancy (cholangio, PANCREATIC IS MOST COMMON, GB, ampullary)
- PSC
- AIDS cholangiopathy
(IMPORTANT) causes of intrahepatic biliary obstruction
- TPN (total parenteral nutrition)
- sepsis
- PSC
- PBC
- intrahepatic mass
main things that kill the liver
- fat
- alcohol
- autoimmune (PSC and PBC)
- viruses
- drugs
…
how to dx the etiology of liver disease using the fake LFTs (liver enzyme tests)
- enzymes less 300 = alcohol, cirrhosis, obstruction (AST:ALT 2:1 for alcohol
- enzymes 500-1000 = ACUTE biliary obstruction
- enzymes over 1000 = ischemia, toxin, virus/
6 causes of fulminant hepatic failure (mnemonic ABCDEF)
A: acetaminophen B: hepB C: hepC, cryptogenic D: hepD, drugs E: esoteric (Wilson's Budd-Chiari) F: fatty infiltration (acute fatty liver of pregnancy, Reye's)
ddx of ascites + main one
-PORTAL HTN (85%)
-malignancy
-infection
-renal
-endocrine
…
(EXAM) what to do to investigate ascites
measure serum-ascites albumin gradient (SAAG): more than 11 is high
(EXAM) meaning of SAAG
- high SAAG = transudative process = LIVER CAUSE
- low SAAG = exudative process = PERITONEUM CAUSE (peritoneal carcinomatosis, peritonitis, pancreatic ascites, bile leak, nephrotic syndrome,.._
(imp?) when ascites associated with portal htn
when SAAG over 1.1
(EXAM) main pathophgy of ascites (2)
- Na retention secondary to splanchnic and systemic vasodilation (dereased arterial volume led to Na retaining mechanisms)
- extrahepatic: CHF, constrictive pericarditis, Budd Chiari syndrome)
(EXAM) portal htn def and value
portal system branches into sinusoids (and then these will drain in hepatic venous system).
**portal htn = portal vein P over 11
(EXAM) prehepatic causes of portal htn
- congenital atresia or stenosis (portal vein)
- thrombosis of portal vein
- splenic vein thrombosis
- extrinsic compression (tumor)
(EXAM) intrahepatic causes of portal htn
- cirrhosis (sinusoidal obstruction)
- bilharzial periportal fibrosis
- sinusoidal obstruction syndrome (chemo)
(EXAM) posthepatic causes of portal htn
- Budd Chiari (hepatic vein thrombosis)
- cardiac disease (valvular disease or constrictive pericarditis)
- right heart failure
(EXAM) cirrhosis pathophgy of ascites and other pathophgies
- increased intrahepatic resist due to fibrosis, regenerative nodules, hepatic venular vasoconstriction = sinusoidal htn
- lymph leakage in sinusoids
- TB
- peritoneal lymph leakage
- bile ascites
- pancreatic ascites
most important risk factor for liver disease + 2nd most important
alcohol
2nd is obesity (fat)
ALT of 70 (normal below 35) approach
means nothing. repeat the test
AST 55 (normal <30), ALT 70 (normal <35), ALP 70 (normal <90) conclusion
- NOT alcohol bc AST:ALT not 2:1
- statistically, more likely cause is fat (NASH)
(IMPORTANT) when liver enzymes and bilirubin go up
- ALT and AST up acutely bc hepatocytes destroyed
- AP and bilirubin up after days bc have to be manufactured and excreted
liver zones and fct
1 = near portal triad (duct, arteriole, venule): FA oxydation, glucose synthesis
zone 2 = in between
zone 3 = near central vein (glycogen synthesis and glycolysis + coag factors synth)
injuries where in liver and meaning
- usually zone 1
- zone 3 = toxic (get high INR, low glucose)
UC patient with high enzymes and bilirubin
PSC
high INR patient high bilirubin
zone 3 injured: toxic = fulminant (acute) liver failure
acute vs chronic hepatitis
acute = 10 fold elevation of ALT chronic = 1.5-10 fold elevation of ALT
high AP and GGT, normal INR, jaundice, palmar erythema, spider angiomata, splenomegaly (signs of portal htn) dx
PBC
all normal except bilirubin of 56 dx
Gilbert’s syndrome
how to check liver problem cause with bilirubin
bilirubin < 250 = obstruction
bilirubin > 250 not obstruction
end stage of any chronic liver disease
cirrhosis: regenerative nodules, fibrous septation
2 stages: compensated and decompensated
(EXAM) pathophgy of portal htn in cirrhosis
distorted sinusoidal architecture leads to increased resistance. backup in porto-caval anastomoses
