Liver pathology Tuesday objectives Flashcards
(22 cards)
Define jaundice, icterus, and cholestasis.
Jaundice: yellow discoloration of the skin due to retention of bilirubin.
Icterus: yellow discoloration of the sclera due to retention of bilirubin.
Cholestasis = impaired secretion of bile
List the steps involved in bilirubin metabolism
hemoglobin –> bilirubin
bilirubin in blood –> liver
gluconuryl transferase puts 2 UDP glucuronates on it.
bacteria turn it to urobilins
Which form of bilirubin is toxic to tissues?
Unconjugated
water insoluble
list some of the causes of conjugated hyperbilirubinemia.
Biliary obstruction
- tumor, stone, pancreatitis, strictures, certain parasites
Intrahepatic
- hepatitis, cirrhosis, sarcoid/amylodosis
In your own words, describe the causes and significance of increased unconjugated hyperbililrubinemia in the neonate. What organ system can be affected if bilirubin levels are too high, and what is the treatment?
Increased production - hemolysis decreased clearance - Crigler-Najjar syndrome - Gilbert's syndrome increased intrahepatic circulation - intestinal obstruction
Brain. leads to encephalopathy or kernicterus.
Define Gilbert’s syndrome and describe the typical laboratory findings.
decreased glucuronyltransferase activity (UGT1A1 30% of normal).
Increased unconjugated bilirubin (
Describe the morphologic findings of hepatocellular cholestasis, canalicular cholestasis, and acute cholangitis
hepatocellular cholestasis
- brownish deposits in hepatocytes
canalicular cholestasis
- brownish deposits in the canals
acute cholangitis
- inflammation around the bile duct
For all of the viral hepatitis types described, make sure you can describe the possible clinical consequences (e.g. which can cause chronic disease).
HAV - not chronic, mostly asymptomatic/subclinical. prevent by vaccine. injury is from CD8 response (that pertains to all of these)
HBV - can be chronic, it’s transferred from boning. also has a vaccine. slide 33 shows outcomes
HCV - from the drugs and the sex time. 20% get acute hep. 80% get chronic )’: it is 50% of the liver disease in USA.
HDV - D for dumb, needs hep B to function and spread. Mostly in IV drug users. Vaccinate against Hep B and you’re golden. can be chronic.
HEV - rare in US of A. Not chronic(vowels A and E are not chronic). Mostly bad in pregnant women.
describe how viral hepatitis infection is diagnosed.
serology.
Describe the possible clinical presentations of acute viral hepatitis. When is an acute viral hepatitis defined as a chronic viral hepatitis?
You’re sick with raise AST and ALT, but no jaundice. Then you get jaundice and/or icterus and dark pee pee.
chronic = over 6 months
describe the pathologic findings seen in acute viral hepatitis. Is acute viral hepatitis frequently biopsied?
nah, no biopsy.
Swelling, focal necrosis/apoptosis (councilman bodies).
big ole’ kupffer cells.
lymphocytes
hepatocellular and canalicular cholestasis
describe the pathologic findings that can be present in a patient with chronic viral hepatitis with ongoing necroinflammatory changes. Why is it sometimes necessary to perform liver biopsy in these patients?
from periportal hepatitis with piecemeal necrosis (zone 1), to bridging necrosis and progressive fibrosis leading to cirrhosis in severe cases.
Clinically, it’s pretty variable, which is why a biopsy is used to see severity
Describe the pathologic clue that can be seen on liver biopsy that would suggest that someone may have chronic HBV infection.
ground glass hepatocytes in chronic HBV,
Describe some of the causes of acute massive hepatic necrosis. If these patients survive, do they always get cirrhosis?
causes: acute viral hepatitis, drug or toxin induced hepatitis (acetaminophen overdose causes 50%), vascular liver diseases, autoimmune hepatitis, Wilson’s disease.
if the patient survives, they may not get cirrhosis (the acute toxic agent causes no fibrosis, and as the reticulin framework of the liver is intact, the liver can regenerate without much architectural distortion).
List the tests used to screen blood to avoid transfusion transmitted hepatitis. Describe how perinatally acquired HBV is prevented.
tests: HBsAg anti-HBc (total) HBV DNA anti-HCV HCV RNA
Treatment of newborns born to HBsAg positive mothers is done with with hepatitis B immune globulin (HBIG) and hepatitis B vaccine. 85-95% effective
Define autoimmune hepatitis (AIH), and describe the key antibodies used in diagnosis. Describe what feature seen on liver biopsy may suggest the diagnosis. Contrast the treatment of AIH with that of chronic viral hepatitis.
T-cell-mediated autoimmune pathogenesis
Type 1 is defined by ***anti-nuclear (ANA), anti-smooth muscle actin (SMA)***, and anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) antibodies. Type 2 is defined by anti-liver/kidney microsome-1 (anti-ALKM-1) and/or antibodies to a liver cytosol antigen (ALC-1).
Type 1 is usually seen in middle age females, type 2 is usually seen in children and adolescents. Type 1 is the most common type seen in the USA, and is associated with HLA DR3
Define cirrhosis, and state the most common cause of cirrhosis. List the 3 main complications associated with cirrhosis (see slide #75).
widely distributed (diffuse, not focal) interconnecting fibrous scars with nodular parenchymal regeneration
vast majority of cases caused by specifically wine coolers
List the key causes of acute and chronic hepatic failure. While the list of clinical manifestations of hepatic failure is too long to memorize, be able to define and describe the manifestations in your own words.
chronic failure more common
Acute liver failure is typically secondary to massive hepatic necrosis (usually acute viral hepatitis A or B, drug, toxin, AIH). Acute liver failure may also occur without overt necrosis (Reye’s syndrome, acute fatty liver of pregnancy). Most common cause of acute liver failure is acetaminophen overdose (50% of cases).
chronic - cirrhosis
slide 77 for all manifestations
asterixis - flapping tremor assc with ammonia neurotox
Define Reye’s syndrome, and the typical patient population. How is Reye’s syndrome avoided? What is the finding on liver biopsy?
you know what it is
NO, NOT SILENTO
Liver injury (on biopsy you see microvesicular steatosis with small lipid vacuoles within the hepatocytes) and encephalopathy
just don’t take the aspirin you dwingle fuck
State the most common cause of portal hypertension, and state the four main complications (see slide #80).
Cirrhosis is most common
MOTHER FUCKING MANIFESTATIONS FUCK
Portosystemic shunts, occurring in areas where systemic and portal circulation share similar capillary beds (e.g. bleeding ESOPHAGEAL VARICES)
ASCITES (fluid in peritoneal cavity, most common cause is cirrhosis)
SPLENOMEGALY (congestive)
HEPATIC ENCEPHALOPATHY
EVA-SHE has portal hypertension
Describe, using just a few sentences, the causes and complications of portal vein thrombosis
Extra hepatic causes:
- Intra-abdominal sepsis and pylephlebitis (septic thrombophlebitis of the portal vein, often caused by acute appendicitis, acute diverticulitis, or other intrabdominal infection).
- hypercoagulability
- trauma
- pancreatitis or pancreatic cancer
Intrahepatic causes:
- Cirrhosis
- invasion of portal vein by hepatocellular carcinoma
Complications: portal hypertension. if obstruction is presunusoidal (before the liver, and it often is) then ascites does not typically occur
list some of the causes of unconjugated hyperbilirubinemia.
increased production
- hemolysis
impaired hepatic uptake
- heart failure, gilbert’s syndrome, rifampin
impaired conjugation
- gilbert’s again, neonates, hyperthyroidism, wilson disease.
