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GI Week 5 - WLB > Liver Pathology #1 - Nelson > Flashcards

Liver Pathology #1 - Nelson Flashcards

1
Q

Define jaundice.

A

yellow discoloration of the skin due to retention of bilirubin

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2
Q

Define icterus.

A

yellow discoloration of the sclera due to retention of bilirubin

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3
Q

Define cholestasis.

A

Impaired secretion of bile = cholestasis

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4
Q

What are the steps involved in bilirubin metabolism?

A
  • Reticuloendothelial cells convert heme to bilirubin
    • (85% from breakdown of senescent RBCs, 15% from hepatic heme or marrow RBC precursors)
  • Bilirubin is transported to the liver complexed to albumin (unconjugated bilirubin).
  • Bilirubin is conjugated with glucuronic acid in liver cells (conjugated bilirubin).
  • Conjugated bilirubin is excreted in bile (brown stools).
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5
Q

What are some of the causes of unconjugated and conjugated hyperbilirubinemia?

A
  • Unconjugated hyperbilirubinemia
    • Increased bilirubin production
      • extravascular hemolysis
      • dyserythropoiesis
    • Impaired hepatic bilirubin uptake
      • heart failure
    • Impaired bilirubin conjugation
      • Crigler-Najjar syndrome
      • Gilbert’s syndrome
  • Conjugated hyperbilirubinemia
    • Extrahepatic cholestasis
      • Choledocholithiasis
      • Acute/Chronic pancreatitis
    • Intrahepatic cholestasis
      • Hepatitis
      • Pregnancy
      • Infiltrative diseases (e.g. sarcoidosis, amyloidosis, Tb, lymphoma)
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6
Q

Which form of bilirubin is toxic to tissues?

A

Unconjugated bilirubin

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7
Q

What are the causes of increased unconjugated hyperbililrubinemia in the neonate?

A
  • Causes:
    • exaggeration of mechanisms that cause neonatal jaundice or by pathologic conditions that increase bilirubin production
      • decrease bilirubin clearance
      • increase the enterohepatic circulation
    • Such causes include:
      • immune-mediated hemolysis (ABO or Rh(D) incompatibility)
      • inherited RBC membrane or enzyme defects
      • sepsis
      • inherited defects in UGT1A1 activity (e.g. Crigler-Najjar syndrome
      • Gilbert’s syndrome)
      • breast milk jaundice
      • intestinal obstruction
      • breastfeeding failure jaundice (last three causing increased enterohepatic circulation)
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8
Q

What is the significance of increased unconjugated hyperbililrubinemia in the neonate?

A

Infants with severe hyperbilirubinemia (TB >25 to 30 mg/dl are at risk for bilirubin-induced neurologic dysfunction (BIND), presenting acutely as acute bilirubin encephalopathy (ABE) and, if inadequately treated, long-term neurologic sequelae or kernicterus.

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9
Q

What organ system can be affected if bilirubin levels are too high, and what is the treatment?

A
  • If bilirubin levels are too high → damage to CNS/brain (kernicterus)
  • Tx: Phototherapy
    • light converts bilirubin into water soluble isomers
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10
Q

What is Gilbert’s syndrome?

A
  • Benign hyperbilirubinemia disorder
    • Common (3-10%); autosomal recessive or autosomal dominant inheritance
    • Due to decreased glucuronyltransferase activity (UGT1A1 30% of normal).
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11
Q

What are the typical laboratory findings in Gilbert’s Syndrome?

A

Increased unconjugated bilirubin ( <6 mg/dl )

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12
Q

What are the morphologic findings of hepatocellular cholestasis?

A
  • Intrahepatic cholestasis:
    • Bile within hepatocytes
    • Canalicular bile stasis
    • Feathery degeneration of hepatocytes
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13
Q

What are the morphologic findings of canalicular cholestasis and acute cholangitis?

A
  • Extrahepatic cholestasis (extrahepatic biliary obstruction):
    • Canalicular bile stasis
    • Feathery degeneration of hepatocytes
    • Bile within distended bile ducts, and occasionally “bile lakes”
    • Portal tract edema
    • Bile duct proliferation within portal tracts
    • Extrahepatic biliary obstruction may promote the development of ascending cholangitis, a secondary bacterial infection of the biliary tree
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14
Q

What are the possible clinical consequences of Hepatitis A virus?

A
  • HAV infection does not cause chronic hepatitis.
  • The viremia (virus in the blood) is transient, and because of this, blood products are rarely at risk and donor screening for HAV is not performed (fecal-oral transmission).
  • Majority of infections are subclinical (asymptomatic).
  • Some present clinically with acute hepatitis
    • 0.1% will develop fulminant hepatitis (acute liver failure) and may die
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15
Q

What are the possible clinical consequences of Hepatitis B virus?

A
  • HBV infection has the potential to cause chronic hepatitis.
  • Majority of patients (70%) have asymptomatic infection (subclinical disease)
  • 30% develop clinical acute hepatitis.
  • Approximately 5% of exposed adults will develop chronic hepatitis
    • some will develop non-progressive chronic hepatitis B
    • some will develop progressive disease leading to cirrhosis
    • some will develop hepatocellular carcinoma
    • Some individuals (particularly those exposed at childbirth) will develop an asymptomatic “healthy” carrier state.
  • 0.1-0.5% develop acute fulminant hepatitis with liver failure and may die.
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16
Q

What are the possible clinical consequences of Delta Hepatitis Virus (HDV)?

A
  • Acute coinfection of HBV and HDV results in acute hepatitis B + D
    • increased risk of acute liver failure, particularly in IV drug users (3-4%, compared to 0.1-0.5% with HBV alone)
  • HDV superinfection may:
    • (1) convert mild chronic HBV hepatitis into acute liver failure (7-10%)
    • (2) cause acute hepatitis to erupt in a healthy, inactive HBV carrier
    • (3) lead to chronic hepatitis (80%, compared to 4% with HBV alone)
    • An inactive HDV/HBV carrier state also exists.
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17
Q

What are the possible clinical consequences of Hepatitis C Virus (HCV)?

A
  • Acute liver failure is rare
    • develops in only 0.2%
  • 20% will develop acute hepatitis
    • which is usually asymptomatic, that resolves
  • Unfortunately, 80% will develop chronic hepatitis
    • with 20-30% developing cirrhosis if untreated
  • Chronic HCV infection accounts for almost half of all chronic liver disease in the USA
    • the number of cases are expected to triple in the next 20 years
    • Most patients with chronic viral hepatitis C are asymptomatic, and 30% may have a normal serum ALT.
  • Some patients develop extrahepatic autoimmune manifestations/syndromes (cryoglobulinemia, membranoproliferative glomerulonephritis, thyroiditis).
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18
Q

What are the possible clinical consequences of Hepatitis E Virus (HEV)?

A
  • HEV does not cause chronic hepatitis or a carrier state
  • While acute viral hepatitis E is generally self-limited, 0.5-3% develop acute liver failure.
    • For reasons that are unknown, pregnant women have high mortality (20%).
    • acute hepatitis also possible
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19
Q

What forms of Viral Hepatitis cause Chronic Hepatitis?

A
  • B
  • C
  • D

(remember, the viral hepatitis that are “vowels”, A and E, do not cause chronic hepatitis)

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20
Q

What are the possible clinical presentations of acute viral hepatitis?

A
  • Preicteric prodrome:
    • nonspecific constitutional symptoms (malaise, fatigue, nausea, loss of appetite, arthralgias etc.)
    • elevated serum levels of liver enzymes
  • Icteric (jaundice) phase:
    • jaundice is not always present (anicteric hepatitis)
    • conjugated hyperbilirubinemia mainly
    • dark urine (bilirubinuria)
  • Convalescence (recovery) vs. acute liver failure vs. chronic hepatitis (with or without progression to cirrhosis) vs. “healthy” carrier.
21
Q

When is an acute viral hepatitis defined as a chronic viral hepatitis?

A

Hepatitis lasting more than 6 months is defined as chronic hepatitis.

22
Q

What are the pathologic findings seen in acute viral hepatitis?

A
  • Major finding is that of lobular hepatitis, which includes:
    • Diffuse liver cell degeneration (cellular swelling - ballooning degeneration)
      • with focal hepatocellular necrosis and apoptosis (apotosis → councilman bodies, and with necrosis → loss and disappearance of hepatocytes, so called “dropout necrosis”)
      • In severe cases, confluent necrosis can be seen.
    • Kupffer cell hyperplasia and hepatocellular regeneration.
    • Mononuclear inflammation (predominantly lymphocytes) within portal tracts and lobules (hence the term lobular hepatitis).
    • “Lobular disarray”
    • Variable hepatocellular and canalicular cholestasis.
23
Q

Is acute viral hepatitis frequently biopsied?

A

NO

Patients with acute viral hepatitis seldom undergo liver biopsy.

24
Q

What are the pathologic findings that can be present in a patient with chronic viral hepatitis with ongoing necroinflammatory changes?

A
  • spectrum of possible findings can occur, ranging from:
    • periportal hepatitis (also known as interface hepatitis) with piecemeal necrosis
    • bridging necrosis and progressive fibrosis leading to cirrhosis in severe cases
25
Q

Why is it sometimes necessary to perform liver biopsy in chronic viral hepatitis patients?

A

Clinical findings of chronic viral hepatitis are highly variable, and thus liver biopsy is often required for assessing the degree of liver damage.

26
Q

What is the pathologic clue that can be seen on liver biopsy that would suggest that someone may have chronic HBV infection?

A

ground glass hepatocytes

27
Q

What are some of the causes of acute massive hepatic necrosis?

A
  • acute viral hepatitis
  • drug or toxin induced hepatitis (acetaminophen overdose causes 50%)
  • vascular liver diseases
  • autoimmune hepatitis
  • Wilson’s disease
28
Q

If patients with acute massive hepatic necrosis survive, do they always get cirrhosis?

A
  • they may not get cirrhosis
    • the acute toxic agent causes no fibrosis
    • as the reticulin framework of the liver is intact → the liver can regenerate without much architectural distortion
29
Q

What are the tests used to screen blood to avoid transfusion transmitted hepatitis?

A
  • Blood donor screening to prevent transfusion transmitted viral hepatitis:
    • HBsAg
    • anti-HBc (total)
    • HBV DNA
    • anti-HCV
    • HCV RNA
30
Q

How is perinatally acquired HBV is prevented?

A
  • Treatment of newborns born to HBsAg positive mothers:
    • hepatitis B immune globulin (HBIG)
    • hepatitis B vaccine
  • 85-95% effective in preventing the development of the HBV chronic carrier state when administered within 2-12 hours after birth
31
Q

What is autoimmune hepatitis (AIH)?

A

Liver injury due to a T-cell-mediated autoimmune pathogenesis

32
Q

What antibodies are used to diagnose autoimmune hepatitis (AIH)?

A
  • Type 1 is defined by:
    • anti-nuclear (ANA)
    • anti-smooth muscle actin (SMA)
    • 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).
33
Q

What feature seen on liver biopsy may suggest the diagnosis of Autoimmune Hepatitis (AIH)?

A

chronic hepatitis with increased plasma cells in the periportal lymphocytic inflammatory infiltrate along with lobular inflammation

34
Q

How does the treatment of AIH compare/contrast with that of chronic viral hepatitis?

A
  • Treatment of autoimmune hepatitis is with immunosuppressive agents (e.g. steroids).
  • Treatment regimens are in flux (continuously changing) for chronic viral hepatitis
    • based on the genotype
35
Q

Define cirrhosis.

A

Hepatic disease of varied etiology characterized by widely distributed (diffuse, not focal) interconnecting fibrous scars with nodular parenchymal regeneration.

36
Q

What are the most common causes of cirrhosis?

A
  • Alcoholic liver disease (60-70%)
  • Viral hepatitis (B, D, C) (10%)
  • Biliary diseases (5-10%)
  • Hereditary hemochromatosis (5%)
  • Wilson’s disease, A1AT def. (rare)
  • Cryptogenic cirrhosis (Non-Alcoholic Fatty Liver Disease) (10-15%)
37
Q

What are the 3 main complications associated with cirrhosis?

A
  1. Hepatic failure
  2. Portal hypertension
  3. Hepatocellular carcinoma
38
Q

What are the key causes of acute and chronic hepatic failure?

A
  • Acute:
    • Acetaminophen overdose
  • Chronic:
    • chronic liver disease associated with cirrhosis
39
Q

What are some clinical manifestations of hepatic failure?

A
  • Jaundice
  • Hypoalbuminemia
  • Bleeding tendencies (coagulopathy - reduced factors II, V, VII, IX, X)
  • Hyperammonemia (urea cycle defects)
  • Fetor hepaticus (sweet and sour odor of breath)
  • Increased liver transaminases (may be normal in cirrhosis)
  • Hypoglycemia (impaired storage of glycogen)
  • Endocrine changes (hyperestrogenism: spider angiomas, palmar erythema, gynecomastia, hypogonadism)
  • Hepatorenal syndrome (acute renal failure in absence of intrinsic or functional renal disease)
  • Hepatic encephalopathy and coma, asterixis (ammonia neurotoxicity)
  • Hepatopulmonary syndrome (HPS - chronic liver disease, hypoxemia, and intrapulmonary vascular dilations)
  • Portopulmonary HTN (pulmonary arterial hypertension)
  • Portal HTN (increased resistance to portal blood flow, typically associated with cirrhosis)
  • Decreased metabolism of drugs
40
Q

What is Reye’s syndrome?

A

a rare acute postviral illness characterized by liver injury (microvesicular steatosis) and encephalopathy

41
Q

What is the typical patient population affected by Reye’s syndrome?

A

usually children and teenagers following a viral infection, with 90-95% having received salicylates (aspirin)

42
Q

How is Reye’s syndrome avoided?

A

discontinuation of aspirin for febrile illness

43
Q

What is the finding on liver biopsy in Reye’s syndrome?

A
  • Microvesicular steatosis
    • with small lipid vacuoles within the hepatocytes
  • Widespread mitochondrial injury is also present
44
Q

What is the most common cause of portal hypertension?

A

Cirrhosis

45
Q

What are the four main complications of portal hypertension?

A
  1. Ascites (fluid in peritoneal cavity, most common cause is cirrhosis)
  2. Portosystemic shunts, occurring in areas where systemic and portal circulation share similar capillary beds (e.g. bleeding Esophageal Varices)
  3. Splenomegaly (congestive)
  4. Hepatic Encephalopathy
46
Q

What are the Extrahepatic causes of portal vein thrombosis?

A
  • Extrahepatic causes:
    • Intra-abdominal sepsis leading to pylephlebitis (septic thrombophlebitis of the portal vein, often caused by acute appendicitis, acute diverticulitis, or other intrabdominal infection).
    • Inherited or acquired hypercoagulable disorders (e.g. post surgical thrombosis, myeloproliferative syndromes).
    • Trauma
    • Pancreatitis or pancreatic cancer (propagation of splenic vein thrombosis).
47
Q

What are the Intrahepatic causes of portal vein thrombosis?

A
  • Cirrhosis
  • Invasion of portal vein by hepatocellular carcinoma
48
Q

What are the complications of portal vein thrombosis?

A
  • Complications of portal vein thrombosis include:
    • portal hypertension.

(As the obstruction is often presinusoidal (i.e. before the liver), ascites does not typically occur.)

GI Week 5 - WLB (16 decks)

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