Liver pathology Tuesday objectives

Question 1

Define jaundice, icterus, and cholestasis.

Answer 1

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

Question 2

List the steps involved in bilirubin metabolism

Answer 2

hemoglobin –> bilirubin
bilirubin in blood –> liver
gluconuryl transferase puts 2 UDP glucuronates on it.
bacteria turn it to urobilins

Question 3

Which form of bilirubin is toxic to tissues?

Answer 3

Unconjugated

water insoluble

Question 4

list some of the causes of conjugated hyperbilirubinemia.

Answer 4

Biliary obstruction
- tumor, stone, pancreatitis, strictures, certain parasites
Intrahepatic
- hepatitis, cirrhosis, sarcoid/amylodosis

Question 5

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?

Answer 5

Increased production
 - hemolysis
decreased clearance
 - Crigler-Najjar syndrome
 - Gilbert's syndrome
increased intrahepatic circulation
 - intestinal obstruction

Brain. leads to encephalopathy or kernicterus.

Question 6

Define Gilbert’s syndrome and describe the typical laboratory findings.

Answer 6

decreased glucuronyltransferase activity (UGT1A1 30% of normal).
Increased unconjugated bilirubin (

Question 7

Describe the morphologic findings of hepatocellular cholestasis, canalicular cholestasis, and acute cholangitis

Answer 7

hepatocellular cholestasis
- brownish deposits in hepatocytes

canalicular cholestasis
- brownish deposits in the canals

acute cholangitis
- inflammation around the bile duct

Question 8

For all of the viral hepatitis types described, make sure you can describe the possible clinical consequences (e.g. which can cause chronic disease).

Answer 8

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.

Question 9

describe how viral hepatitis infection is diagnosed.

Answer 9

serology.

Question 10

Describe the possible clinical presentations of acute viral hepatitis. When is an acute viral hepatitis defined as a chronic viral hepatitis?

Answer 10

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

Question 11

describe the pathologic findings seen in acute viral hepatitis. Is acute viral hepatitis frequently biopsied?

Answer 11

nah, no biopsy.
Swelling, focal necrosis/apoptosis (councilman bodies).
big ole’ kupffer cells.
lymphocytes
hepatocellular and canalicular cholestasis

Question 12

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?

Answer 12

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

Question 13

Describe the pathologic clue that can be seen on liver biopsy that would suggest that someone may have chronic HBV infection.

Answer 13

ground glass hepatocytes in chronic HBV,

Question 14

Describe some of the causes of acute massive hepatic necrosis. If these patients survive, do they always get cirrhosis?

Answer 14

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).

Question 15

List the tests used to screen blood to avoid transfusion transmitted hepatitis. Describe how perinatally acquired HBV is prevented.

Answer 15

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

Question 16

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.

Answer 16

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

Question 17

Define cirrhosis, and state the most common cause of cirrhosis. List the 3 main complications associated with cirrhosis (see slide #75).

Answer 17

widely distributed (diffuse, not focal) interconnecting fibrous scars with nodular parenchymal regeneration

vast majority of cases caused by specifically wine coolers

Question 18

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.

Answer 18

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

Question 19

Define Reye’s syndrome, and the typical patient population. How is Reye’s syndrome avoided? What is the finding on liver biopsy?

Answer 19

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

Question 20

State the most common cause of portal hypertension, and state the four main complications (see slide #80).

Answer 20

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

Question 21

Describe, using just a few sentences, the causes and complications of portal vein thrombosis

Answer 21

Extra hepatic causes:

1. Intra-abdominal sepsis and pylephlebitis (septic thrombophlebitis of the portal vein, often caused by acute appendicitis, acute diverticulitis, or other intrabdominal infection).
2. hypercoagulability
3. trauma
4. pancreatitis or pancreatic cancer

Intrahepatic causes:

1. Cirrhosis
2. 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

Question 22

list some of the causes of unconjugated hyperbilirubinemia.

Answer 22

increased production
- hemolysis
impaired hepatic uptake
- heart failure, gilbert’s syndrome, rifampin
impaired conjugation
- gilbert’s again, neonates, hyperthyroidism, wilson disease.