liver Flashcards by L W

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)

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portal triad

portal vein
hepatic artery
bile ductule

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blood supply to liver

portal vein (from mesenteric veins, gastric vein): toxins + nutrition from GI
hepatic artery: O2 blood

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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

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zone affected first by ischemia + hypotension

zone 3: pericentral vein zone (farthest from O2 blood source - hepatic artery)

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zone affected first by viral hepatitis

zone 1: periportal zone (next to portal vein)

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zone most sensitive to metabolic toxins (acetaminophen overdose, site of alcoholic hepatitis)

zone 3: pericentral vein zone

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zone with highest concentration of P450 enzymes

zone 3: pericentral vein zone

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examples of proteins made by liver

coag factors
complement
albumin
apolipoproteins: lipid transport
transferrin: iron transport
ceruloplasmin: copper transport
others:
cholesterol
phosopholipids

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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)

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storage role of liver

glucose as glycogen
store cholesterol with TG in liver (esp VLDL)
iron bound to ferritin
B12, ADEK

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role of bile

breakdown fats

carrier for excretion of bilirubin

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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

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neuro effects of excess unconjugated bilirubin in newborn (occur in hrs-days)

bilirubin is neurotoxic:
lethargy
hypotonia

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prevent kernicterus

phototherapy: convert bilirubin to isomer that can excrete

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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

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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

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treatment of type 1 crigler-najjar syndrome

phototherapy
plasmaphoresis - remove unconjugated bilribubin bound to albumin
definitive: liver transplant (makes UDP-GT)

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mutated UDP-glucoronyltransferase enzyme

jaundice + ↑ INDIRECT bilirubin in first few days of life (but less than type I)

type II crigler-najjar syndrome

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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!)

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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

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milder form of dubin-johnson syndrome
mild elevation in DIRECT bilirubin
liver DOESN’T turn black

rotor syndrome

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stages of alcoholic liver disease

steatosis (fatty liver)
alcoholic hepatitis
alcoholic cirrhosis

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fat droplets in cytosol of hepatocytes seen in HEAVY drinks

REVERSIBLE if stop drinking

steatosis: fatty liver

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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

liver Flashcards

(71 cards)