liver Flashcards
role of fetal liver
major site of hematopoiesis in fetus: mesodermal hematopoietic stem cells migrate from mesonephros → to liver at 3 wk GA (source of fetal blood cell until BM at 28 wks GA)
portal triad
portal vein
hepatic artery
bile ductule
blood supply to liver
portal vein (from mesenteric veins, gastric vein): toxins + nutrition from GI hepatic artery: O2 blood
hepatocytes role
make proteins energy, vitamin, mineral storage metabolize drugs/toxins make bile → dump bile into bile canaliculi (opposite flow to sinusoid flow → bile ductule → hepatic duct → common hepatic duct...) excrete bilirubin
zone affected first by ischemia + hypotension
zone 3: pericentral vein zone (farthest from O2 blood source - hepatic artery)
zone affected first by viral hepatitis
zone 1: periportal zone (next to portal vein)
zone most sensitive to metabolic toxins (acetaminophen overdose, site of alcoholic hepatitis)
zone 3: pericentral vein zone
zone with highest concentration of P450 enzymes
zone 3: pericentral vein zone
examples of proteins made by liver
coag factors complement albumin apolipoproteins: lipid transport transferrin: iron transport ceruloplasmin: copper transport others: cholesterol phosopholipids
examples of drug + toxin metabolism of liver
P450 enzymes
UDP glucoronyl transferase
ALT and AST: transaminases
steroid hormones → inactive metabolites (need for breakdown of estrogen, progesterone, testosterone, vitamin D, cortisol, thyroid hormone)
storage role of liver
glucose as glycogen
store cholesterol with TG in liver (esp VLDL)
iron bound to ferritin
B12, ADEK
role of bile
breakdown fats
carrier for excretion of bilirubin
complication of excess unconjugated bilirubin for several months in newborn
kernicterus: unconjugated bilirubin in brain → chorea cerebral palsy hearing loss gaze abnormalities brain damage → death
neuro effects of excess unconjugated bilirubin in newborn (occur in hrs-days)
bilirubin is neurotoxic:
lethargy
hypotonia
prevent kernicterus
phototherapy: convert bilirubin to isomer that can excrete
AR mutation in promotor for UDP-glucoronyltransferase gene →↓ amounts of UDP-glucoronyltransferase enzyme
conjugate bilirubin more slowly → slight elevation of INDIRECT bilirubin
benign and asymptomatic unless infection or alcohol (incidental finding)
Gilbert syndrome
complete absence of UDP-glucoronyltransferase enzyme
can’t conjugate bilirubin and excrete it into the bile
jaundice + ↑ INDIRECT bilirubin in first few days of life
may have NEURO sx
if no treatment: kernicterous (die in a couple years)
type I crigler-najjar syndrome
treatment of type 1 crigler-najjar syndrome
phototherapy
plasmaphoresis - remove unconjugated bilribubin bound to albumin
definitive: liver transplant (makes UDP-GT)
mutated UDP-glucoronyltransferase enzyme
jaundice + ↑ INDIRECT bilirubin in first few days of life (but less than type I)
type II crigler-najjar syndrome
distinguish type I vs type II crigler-najjar syndrome
give phenobarbital (barbiturate): induces liver enzyme production (even UDP-GT) type II pr Gilbert: ↓ bilirubin type I: no change (no UDP-GT in liver!)
problem putting conjugated bilirubin back into bile → conjugated bilirubin trapped in hepatocytes → turns liver BLACK
↑ DIRECT serum bilirubin
benign - no treatment necessary
dubin-johnson syndrome
milder form of dubin-johnson syndrome
mild elevation in DIRECT bilirubin
liver DOESN’T turn black
rotor syndrome
stages of alcoholic liver disease
steatosis (fatty liver)
alcoholic hepatitis
alcoholic cirrhosis
fat droplets in cytosol of hepatocytes seen in HEAVY drinks
REVERSIBLE if stop drinking
steatosis: fatty liver
inflammation + steatosis
swollen necrotic hepatocytes
neutrophils in liver parenchyma
MALLORY bodies: intracytoplasmic eosinophilic inclusions of keratin
alcoholic hepatitis
RUQ pain anorexia jaundice low-grade fever ↑AST>ALT (AST >2x the ALT, A Scotch and Tonic = AST) enlarged, swollen liver
alcoholic hepatitis
IRREVERSIBLE
scarring + fibrosis
palpate hard, nodular liver edge
enlarged OR shrunken liver
AST/ALT: may be high, normal, low (trashed liver)
residual nodules of hepatocytse with collagen + sclerosis (blue on trichrome stain) surrounding them (replaced necrotic hepatocytes)
sclerosis located around central vein (zone 3)
alcoholic cirrhosis
complications of cirrhosis
liver failure: no hepatocytes
portal HTN: blood can’t flow through sinusoids (causes hepatosplenomegaly) → portal vein
coagulopathy: ↑PT, PTT (need vitamin K)
bleeding/bruising
↓osmotic pressure → peripheral edema, ascites
no metabolism of ammonia → hepatic encephalopathy (confusion, delerium, hypersomnia, coma, death, asterixis, fetor hepaticus (musty odor of breath)
↑estradiol levels: testicular atrophy, gynecomastia, spider telangiectasia on chest, palmar erythema
↑ unconjugated bilriubin: jaundice, slceral icterus
↓LDL and HDL (liver not making)
liver failure
hepatosplenomegaly (blood backs up in these organs, can cause enlarged liver even though cirrhotic)
fluid leaks from liver due to back up of blood → ascites
caput medusa: umbilica veins dilated
anorectal varices: tortuous, dilated vein
esophageal varices (if active bleed → hematemesis, melena)
portal hypertension
complication of ascites
spontaneous bacterial peritonitis (SBP)
treatment of active esophogeal variceal bleed
↓ splanchnic circulation: octreotide (somatostatin analog)
B blocker: propranolol, nadolol
prevent esophageal varicel bleeding
endoscopic banding
transjugular intrahepatic portosystemic shunt (TIPS) - create shunt from portal vein → systemic circulation to bypass liver →↓ portal HTN, ↓ variceal blood flow, ↑ hepatic encephalopathy
treatment of hepatic encephalopathy
lactulose: trap ammonia in gut so excreted in stool →↓ serum ammonia levels
cirrhosis (alcohol, hep viral infection, hemachromatosis) is risk factor for
hepatocellular carcinoma
cocktail of meds for severe cirrhosis
diuretics
B blocker: nadolol, propranol
vitamin K: make clotting factors
lactulose: encephalopathy
aminotransferase (AST, ALT, liver enzymes) can suggest
viral hepatitis: ALT = or > AST
alcoholic hepatitis: AST > ALT (AST >2x)
gamma-glutamyl transpeptidase (GGT)
↑ in following:
liver + biliary tract diseases
excessive alcohol
akaline phosphatase
↑ in following:
biliary obstruction: gallstones, cancer
active bone formation: children (normal), Paget disease of bone, bone cancer
HCC
R sided heart failure or Budd-Chiari syndrome→ back up of blood into liver → nutmeg liver → if persists, centrilobular congestion + necrosis → cardiac cirrhosis
nutmeg liver (speckled)
occlusion of IVC or hepatic veins → congested liver
hepatomegaly
ascites
ab pain
portal HTN → esophageal varices, caput medusae
NO JVD
budd-chiari syndrome
congested liver
JVD
right sided heart failure
liver disease associated with: hypercoagulable states pregnancy polycythemia HCC
budd-chiari syndrome
children receiving aspirin for viral infection → aspirin metabolites inhibit mitochondrial enzymes →↓ B oxidation →
hepatoencephalopathy:
rash, vomit, headache, confusion → hypoglycemia, stupor, coma, death
reye syndrome
AR ATP7B enzyme defect:
1) inadequate copper excretion into bile → copper accumulates in:
liver, brain, cornea, kidneys, joints
2) impaired conversion of copper to ceruloplasmin (need for transport in blood) →↓ serum ceruloplasmin
wilson disease
features of wilson disease
cirrhosis of liver Kayser-Fleischer rings: corneal deposits ↓ serum ceruloplasmin basal ganglia degeneration: parkinsonian sx asterixis, dyskinesia, dysarthria hemolytic anemia hepatic encephalopathy → dementia fanconi syndrome: PT dysfunction in kidney ↑ risk HCC
Kayser-Fleischer rings: golden corneal deposits near edge of eye
wilson’s disease
complication of wilson disease
↑ risk HCC
treatment of wilson disease
penicillamine (copper penny)
excess iron deposition triad: cirrhosis diabetes mellitus skin pigmentation other complications: congestive heart failure testicular atrophy ↑ risk HCC
hemachromatosis
called “bronze diabetes”
hematochromatosis
causes of hematochromatosis
AR disease
secondary: excessive transfusion (chronic anemia states: B thalasemia, SCD)
↑ ferritin (complex of iron in apoferritin- primary cellular storage of iron): screening test
↑ total serum iron
↓ total iron binding capacity
↑ transferrin saturation (binds iron and transports it through plasma)
hemachromatosis
treatment of hematochromatosis
phlebotomy (iron is in RBCs - DOC) subq: deFEroxamine (for Fe): chelating agent oral agents: deferiprone deferasirox
panacinar emphysema and liver cirrhosis in young person or non-smoker
α1 antitrypsin deficiency
autosomal codominant disease
↑ elastase activity → break down elastic tissue in lungs →
panacinar emphysema
mutated form of α1 antitrypsin made in liver and polymerizes → accumulates in liver →cirrhosis: jaundice, ↑ LFT
α1 antitrypsin deficiency
role of α1 antitrypsin
inhibit elastase (breaks down elastin)
female 20-40 yo
asymptomatic (incidental on imaging) or RUQ pain
associated with OCP use, anabolic steroids, glycogen storage disease type I and III
hepatic adenoma
complication of hepatic adenoma
malignant transformation to HCC in 10%
treatment of hepatic adenoma
stop OCP
serial imaging
check AFP to ensure not getting HCC
resect if > 5cm
malignant endothelial neoplasm of liver
hepatic angiosarcoma
risk factors of hepatic angiosarcoma
vinyl chloride
arsenic
liver disease with elevated α fetoprotein
HCC
risk factors for HCC
hep B/C wilson disease hemachromatosis α1 antitrypsin deficiency hepatic adenoma alcoholic cirrhosis carcinogen exposure (aflatoxin from aspergillus)
jaundice tender hepatomegaly ascites polycythemia due to ↑ epo hypoglycemia
HCC
serum marker for HCC
AFP
risk factors for hepatitis
IVDU (Hep B + C)
alcoholism (alcoholic hepatitis)
travel to developing countries/poor sanitation (fecal oral route: Hep A + E)
asymptomatic (but can transfer via sexual contact) symptoms: malaise arthralgias fatigue N/V RUQ pain jaundice/scleral icterus tender hepatosplenomegaly LAD
hepatitis
labs: bilirubinuria ↑AST + ALT (ALT higher or equal to AST in viral, AST higher in alcohol) ↑ serum bilirubin ↑ serum alk phosphatase
hepatitis labs
resolves with absitence
fatty liver disease
due to binge drinking
alcoholic hepatitis
