Liver Flashcards
Zones of liver lobule and susceptibility
Zone 1: highest O2 content, includes the portal triad
-Viral hepatitis
Zone 2: middle
Zone 3: closest to Central v.
-furthest from oxygenated blood - highest risk of ischemia
-toxic injury
highest p450 concentration
Hepatocyte protein production
coagulation factors complement albumin apolipoproteins CRP antiotensinogen transferrin ceruloplasmin
Synthesis of cholesterol and phospholipids (non protein)
Hepatocyte drug/toxin metabolism
CYP450 enzymes
UDP-glucuronyltransferase
ALT and AST
Steroids –> inactive metabolites
Hepatocyte storage
glucose - glycogen
Chloesterol and TGs - VLDL particles
Minerals
Vit B12, A, D, E, K
Hepatocyte bile function
breakdown fats
carrier for excretion of bilirubin
UDP-glucuronyl transferase
transfers glucuronyl group to bilirubin
- conjugation –> direct bilirubin aka conjugated bilirubin
Low in newborns:
decreased bilirubin conjugation
causes physiologic jaundice (indirect bili)
Kernicterus
bilirubin buildup in the brain –> neurotoxicity
Chorea
cerebral palsy
hearing loss
gaze abnormalities
Tx: phototherapy - blue lights
Gilbert Syndrome
AR - UDT1A1 mutation in promoter region of UDP-GT gene
Not much produced –> slow conjugation
Slight elevation of indirect bilirubin
benign, asx unless under stress –> mild jaundice
Crigler Najjar Sn type I
complete absence of UDP-GT
unable to conjugate bilirubin and excrete it
Jaundice and elevated indirect bilirubin in first few days
w/o tx –> kernicteris –> death in couple years
Tx: phototherapy, plasmapheresis
Cure via liver transplant
Crigler Najjar Sn type II
mutated UDP-GT - not as effective
Less severe, clinically like Gilbert Sn
Phenobarbital test for neonatal jaundice
induces production of hepatic enzymes
-distinguishes types
Crigler Najjar Type I - no change - no gene to induce
Crigler Najjar Type II reduced indirect bilirubin
Gilbert Sn reduced indirect bilirubin
Dubin-Johnson Syndrome
Cannot excrete conjugated bilirubin in bile
elevated direct bilirubin
liver turns black (dark)
D’s - Dubin, direct up, dark liver
Rotor Syndrome
like Dubin Johnson - elevated direct bili
no black liver
Stages of Alcoholic liver disease
1: steatosis - fat droplets w/in liver cells
- reversible if stop drinking
2: alcoholic hepatitis - inflammation w/ fatty depostis
3: Cirrhosis - irreversible
Alcoholic hepatitis
inflammation with fatty deposits
hepatocytes swollen and necrotic
neutrophils invade parenchyma
Mallory bodies - eosinophilic squiggly blobs
RUQ pain, anorexia, jaundice
low grade fever
>2:1 AST: ALT
-ALT low d/t B6 deficiency
Cirrhosis
irreversible
scarring and fibrosis
nodular surface
hard and nodular on palpation if palpable
-shrunken and contracted
liver enzymes may be high, normal, or low - trashed hepatocytes
Hepatocytes pink and blue collagen (scarring /fibrosis)
necrotic
Sclerosis centralized around central v in zone 3 of lobule
Liver failure effects
Coagulopathy - increased PT and PTT
-bleeding and bruising
Decreased albumin production = lower osmotic pressure
-edema, ascites
Can’t metabolize ammonia –> hepatic encephalopathy
- confusion, delirium, hypersomnia
- -> coma and death
- asterixis
- Fetor hepaticus (musty odor to breath)
High estradiol - can’t metabolize steroids
- -> testicular atrophy, gynecomastia
- spider telangectasias (spider angiomas)
- Palmar erythema
Jaundice
low LDL and HDL
Portal hypertension
HSM
Ascites –> paracentesis
-risk spontaneous bacterial peritonitis (potentially deadly)
Portosystemic anastomases dilate, become varicosed
- caput medusae - abdominal wall veins
- anorectal varices - rectal v.
- esophageal varices
- renal varices
- paravertebral varices
Treatment of esophageal variceal bleeding
Octreotide - somatostatin analog
propranolol, nadolol to prevent
endoscopic banding
Transjugular intrahepatic portosystemic shunt (TIPS)
-worsen risk of hepatic encephalopathy, bypass liver
Medications used in cirrhosis
diuretics - decrease ascites and edema
beta blocker - prevent esophageal varices bleeding
Vit K - maximize clotting potential
Laculose - trap ammonia in gut, excreted in stool
- decrease serum ammonium levels
- tx hepatic encephalopathy
Aminotransferases
AST, ALT
ALT >= AST - viral hepatitis
AST > ALT - alcohol
Hepatocytes
Gamma-glutamyl transpeptidase (GGT)
liver pathology
excess etOH
biliary tree disease
Alkaline phophatase
biliary obstruction - gallstones, cancer
Active bone formation - kids, Paget dz of bone, bone cancer
Nutmeg liver
back up of blood into liver d/t right sided HF
JVD
speckled liver section
can be due to Budd Chiari Syndrome
Long time –> central lobular congestion and necrosis
–> fibrosis (aka cardiac cirrhosis)
Budd-Chiari
Obstruction of IVC and hepatic vs
Central lobular congestion and necrosis –> congestive liver disease
- hepatomegaly
- ascites
- abdominal pain
- Portal HTN –> esophageal varices, caput medusa
NO JVD
Assoc w/: hyper coagulable stages pregnancy polycythemia hepatocellular carcinoma
Reye Syndrome
Potentially fatal
children w/ aspirin for viral infections
hepatoencephalopathy
Early: rash, V, HA, confusion
–> hypoglycemia, stupor, coma, death
Damage to cellular mitochondria –> decreased beta-oxidation
-aspirin metabolites reversible inhibitor of enzymes
Aspirin only okay in kids w/ Kawasaki disease
Wilson disease
AR Defect in ATP7B Inadequate copper excretion into bile Impaired conversion of copper to ceruloplasmin -low ceruloplasmin in serum
Copper accumulates in liver, brain, cornea, kidneys, joints -Kayser-Fleischer rings -Cirrhosis --> increased risk of HCC hemolytic anemia Basal ganglia degeneration Parkinson like sx Hepaticencephalopathy --> dementia Fanconi syndrome : proximal tubule dysfunction in kidney, decreased reabsorption
Tx: penicilliamine “copper penny”
Hemochromatosis
excess iron deposition
Triad: cirrhosis, bronze DM, skin pigmentation
Other:
CHF
Testicular atrophy
increased risk of HCC
Labs: high ferritin (cellular storage of Fe), high total serum Fe, decreased total iron binding capacity (TIBC - all used up, can’t bind more), high transferrin saturation
Primary - AR
Secondary - excessive transfusions d/t chronic anemia
Tx: phlebotomy
Deferexamine - SQ
Oral: deferiprone, deferasirox
Alpha1-antitrypsin deficiency
Autosomal codominant
Panacinar emphysema: too much elastase activity
Cirrhosis - mutated form of protein accumulates in liver cell, toxic
Early onset
Hepatic adenoma
Females 20-44 yo - OCP years
Risk: OCP use, anabolic steroids, glycogen storage disease type I and III
Sx:
RUQ pain, usually asx
10% transform to HCC
Tx: dc OCP, serial imaging and AFP, +/- resection (esp over 5 cm)
Hepatic angiosarcoma
Malignant endothelial neoplasm in liver
Risk: vinyl chloride, arsenic exposure
Hepatocellular carcinoma
MC primary liver tumor
Risk: HBV, HCV Wilson dz Hemochromatosis a1-antitrypsin deficiency alcoholic cirrhosis Aflatoxin from aspergillus
Sx: Jaundice tender hepatomegaly ascites polycythemia hypoglycemia
Marker: AFP - check serially
General hepatitis
asx - transmit infection w/o knowing
Sx: malaise, arthralgias, fatigue, N/V, RUQ pain, scleral icteris, HSM, LAD
Labs: high ALT and AST High serum bilirubin high alk phos high urine bilirubin
Causes: viral infections, chronic alcohol use, toxins
Micro:
Councilman bodies
Mallory bodies (more common in etoh liver dz)
Hepatitis A
ssRNA
Fecal/oral route, poor sanitation
30 d incubation
risk: international travel (Mexico, S. America)
labs:
HepA IgM during illness
HepA IgG after resolution or vaccination (1 dose 12 mo - 18 yrs, 1 booster 1 yr later)
Tx: supportive - self limited
Hepatitis E
ssRNA
Fecal oral/route, contaminated water
more likely to cause fulminant hepatic failure in pregnant
Labs: PCR, HepE IgM
tx: supportive
Fecal-oral transmitted hepatitis
“vowels come from the bowels”
HAV, HEV
Hepatitis D
ssRNA
Delta virus, defective pathogen
Infections in presence of HBV
Transmission MC blood, sexual contact
20% mortality (highest)
Tx: pegylated IFN-a for 1 yr
prevention - HBV vaccine
Hepatitis C
ssRNA
50-85% chronic infection; 5-35% –> cirrhosis
Increased risk of hepatocellular carcinoma - u/s q6mo for surveillance
Extrahepatic manifestations: membranoproliferative glomerulonephritis, essential mixed cryoglobinemia, lymphoma, thyroiditis, porphyria cutanea tarda, lichen planus, DM
Transmission: MC blood, sexual contact (rare)
Dx: HepC Ab, RNA
Tx:
Ledipasvir - sofosbuvir
Ombitasvir-paritaprevir-ritonavir + dasabuvir
Hepatitis B characteristics
dsDNA!!!
Transmission: perinatally, sex MC, blood
Chronic infection
- less than 5% acquire as adult
- 90% acquire perinatally
Extrahepatic manifestations - d/t circulating immune complexes
-polyarteritis nodosa, membranous nephropathy, aplastic anemia
Increased risk of HCC - U/S every 6 mo, +/- AFP (high false +)
-more than HCV
Significance of HBsAg
active disease
Significance of HBsAb
recovery from active infection or immunization
HBcAb significance
Hx of infection - IgM early; IgG late
HBeAg significance
active viral replication = high transmissibility
HBeAb significance
low transmissibility
HBV DNA
active viral replicaiton
tx indicated when high and high LFTs
HBsAg+ HBsAb - HBcAb + IgM HBeAg + HBeAb - HBV DNA high
Active HBV infection
HBsAg- HBsAb- HBcAb+ IgM HBeAg HBeAb HBV DNA high/low
Acute infection - Window period
- Abs neutralize Ag
- on the way to recovery
HBsAg- HBsAb+ HBcAb+ IgG HBeAg- HBeAb+ HBV DNA -
Past infection - recovered
HBsAg - HBsAb+ HBcAb- HBeAg- HBeAb- HBV DNA-
vaccine
HBsAg+ HBsAb- HBcAb+IgG HBeAg+ HBeAb HBV DNA high
Chronic infection - immune tolerance
still active HBV, little liver damage
HBsAg+ HBsAb HBcAb+ IgG HBeAg + --> - HBeAb HBV DNA high --> low
Chronic infection - immune clearance
high LFTs, damage happening
Likely to clear and respond to treatment
HBsAg+ HBsAb HBcAb+ IgG HBeAg- HBeAb HBV DNA Low
Chronic infection - inactive carrier
normal LFT
20-30% can reactivate
treatment of HBV
MC: tenofovir
entecavir, telbivudine, lamivudine, adefovir
Pregnant women: if HBV DNA elevated w/ active liver involvement - lamivudine
-Give baby HBV vaccine and HBV immune globulin w/in 12 hours of birth
Autoimmune hepatitis
elevated AST and ALT
Type 1: ANA, anti-smooth muscle Ab
Type 2: anti-liver-kidney microsomal Ab, anti-liver cytosol Ab
Other disease w/ autoimmune features: hemolytic anemia T1DM thyroiditis celiac sprue UC
