Liver (Jaundice + Cirrhosis + Tumors) - Pathoma

Question 1

What is the earliest sign of jaundice?

Answer 1

Scleral Icterus

Question 2

Why does extravascular hemolysis or ineffective erythropoiesis result in jaundice?

Answer 2

• Excessive destruction of RBCs leads to high levels of unconjugated bilirubin
  
  • overwhelms the conjugating ability of the liver
  • unconjugated bilirubin spills over into the blood until the liver is able to conjugate it

Question 3

What are the clinical features in extravascular hemolysis or ineffective erythropoeisis?

Answer 3

• dark urine
  
  • due to increase in urine urobilinogen
  • UCB is not water soluble and thus is absent from the urine
• increased risk for pigmented bilirubin gallstones

Question 4

What is physiologic jaundice of the newborn due to?

Answer 4

• Newborn liver has transiently low UGT activity
  
  • (UGT= uridine glucuronyl transferase)

Question 5

What is the potential complication of neonatal jaundice? How does it happen?

Answer 5

• Kernicterus
  
  • unconjugated bilirubin is fat soluble and can deposit in the basal ganglia

Question 6

Why does phototherapy work to treat physiologic jaundice of the newborn?

Answer 6

it makes unconjugated bilirubin water-soluble

can then leak out in the urine

Question 7

What syndrome results in jaundice due to autosomal recessive inheritance of mildly lowered UGT activity?

Answer 7

Gilbert Syndrome

Question 8

When is jaundice most prevalent in patients with Gilbert Syndrome?

Answer 8

• During stress
  
  • severe infection

Question 9

What syndrome is characterized by a severe decrease or abscence of UGT?

Answer 9

Crigler-Najjar Sydrome

Question 10

What causes death in Crigler-Najjar Syndrome?

Answer 10

Kernicterus

Question 11

What syndrome is characterized by an autosomal recessive inherited deficiency of bilirubin canalicular transport proteins?

Answer 11

Dubin-Johnson Syndrome

Question 12

What are the clinical features of Dubin-Johnson Syndrome?

Answer 12

Dark liver → grossly black (benign)

increased Conjugated Bilirubin

Question 13

What jaundice-causing disease is associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and liver flukes?

Answer 13

Biliary Tract Obstruction

(a.k.a. obstructive jaundice)

Question 14

What are the laboratory findings in Biliary Tract Obstruction/Obstructive Jaundice?

Answer 14

• Increased conjugated bilirubin
• Decreased urine urobilinogen
• Increased alkaline phosphatase

Question 15

What are the clinical features of Biliary Tract Obstruction/Obstructive Jaundice?

Answer 15

• Dark urine
  
  • due to bilirubinuria (conjugated bilirubin is water soluble)
• Pale stool
  
  • can’t get bile into the stool
• Pruritis
  
  • due to increased plasma bile acids
• Hypercholesterolemia with xanthomas
• Steatorrhea with malabsorption of fat-soluble vitamins

Question 16

What jaundice-causing disease results in increased conjugated and unconjugated bilirubin in the blood and results in dark urine?

Answer 16

Viral hepatitis

(inflammation damages both the hepatocytes (UB) and small bile ductules (CB))

Question 17

What is cirrhosis?

Answer 17

• End-stage liver damage
• Characterized by disruption of normal hepatic parenchyma by
  
  • broad bands of fibrosis
  • regenerative nodules of hepatocytes

Question 18

What is the fibrosis in cirrhosis mediated by?

Answer 18

• Stellate cells
  
  • fibrosis is mediated by TGF-beta from stellate cells
  • lie beneath the endothelial cells that line the sinusoids

Question 19

What four sequelae are due to portal hypertension in cirrhosis?

Answer 19

• Ascites
• Congestive splenomegaly/hypersplenism
  
  • consumes RBCs and platelets
• Portosystemic shunts
  
  • esophageal varices
  • caput medusae
• Hepatorenal syndrome

Question 20

What sequelae are due to decreased detoxification in cirrhosis?

Answer 20

• Mental status changes, asterixis, and coma
• Gynecomastia, Spider angiomata, Palmar erythema
  
  • liver cannot remove estrogen from blood
• Jaundice

Question 21

What three sequelae are due to decreased protein synthesis in cirrhosis?

Answer 21

• Hypoalbuminemia
• Edema
• Coagulopathy
  
  • both PT and PTT increased

Question 22

What are the three classic patterns of injury in Alcohol-Related Liver Disease?

Answer 22

• Fatty liver
  
  • reversible heavy, greasy liver
• Alcoholic hepatitis
  
  • direct chemical injury to hepatocytes mediated by acetaldehyde
• Cirrhosis
  
  • chronic alcohol-induced liver damage

Question 23

In what disease are Mallory Bodies found? What are they?

Answer 23

• Found in Alcoholic Hepatitis
  
  • consist of damaged intermediate filaments within the hepatocytes

Question 24

What is the helpful laboratory finding in Non-Alcoholic Fatty Liver Disease?

Answer 24

ALT > AST

Question 25

What iron-related disease can lead to cirrhosis?

Answer 25

Hemochromatosis

Question 26

What is primary hemochromatosis due to?

Answer 26

mutations in the HFE gene | (most commonly C282Y \> H63D)

Question 27

What is secondary hemochromatosis due to?

Answer 27

* Complication of chronic transfusion therapy * iron constantly recycled * no way to get rid of excess iron * builds up in tissues → hemosiderosis

Question 28

What is the symptom triad of Secondary Hemochromatosis?

Answer 28

cirrhosis + 2° diabetes mellitus + bronze skin (cardiac arrhythmia and gonadal dysfunction also possible)

Question 29

What is the key finding on biopsy in Hemochromatosis?

Answer 29

Brown pigment in hepatocytes (Prussian blue stain distinguishes iron (blue) from lipofuscin)

Question 30

What is Wilson Disease?

Answer 30

* Autosomal recessive defect in *ATP7**B** gene* that involved in ATP-mediated hepatocyte copper transport * Results in lack of copper transport into bile and lack of copper incorporation into ceruloplasm

Question 31

What is the clinical manifestation of Wilson Disease?

Answer 31

* Presents in childhood or before age 40 * Cirrhosis * Neurologic manifestations (like psychopathy in House) * Kayser-Fleisher rings in cornea * Increased risk of hepatocellular carcinoma

Question 32

What cirrhosis-causing disease involves autoimmune granulomatous destruction of intrahepatic bile ducts and usually arises in women around age 40 who present with obstructive jaundice?

Answer 32

Primary Biliary Cirrhosis

Question 33

What antibody is present in Primary Biliary Cirrhosis?

Answer 33

Anti-Mitochondrial Antibody

Question 34

What disease is characterized by inflammation and fibrosis of intrahepatic and extrahepatic bile ducts resulting in periductal fibrosis with an "onion-skin" appearance?

Answer 34

Primary Sclerosing Cholangitis

Question 35

What is Primary Sclerosing Cholangitis associated with?

Answer 35

* Ulcerative colitis * (+) p-ANCA * middle-aged men * increased risk for cholangiocarcinoma

Question 36

What kind of damage is seen in Reye Syndrome?

Answer 36

* Fulminant liver failure and encephalopathy * likely related to **mitochondrial** damage of hepatocytes

Question 37

Is a hepatic adenoma benign or malignant?

Answer 37

Benign tumor of hepatocytes

Question 38

Hepatic adenomas are associated with the use of what two things?

Answer 38

* Oral contraceptives * Anabolic steroids

Question 39

What is the risk/complication with hepatic adenomas?

Answer 39

Rupture and intraperitoneal hemorrhage | (especially during pregnancy)

Question 40

What are the risk factors for Hepatocellular Carcinoma?

Answer 40

* Chronic hepatitis * Cirrhosis * Aflatoxins related to Aspergillus * induce p53 mutations

Question 41

What syndrome is presents with painful hepatomegaly and ascites, and is characterized by liver infarction secondary to hepatic vein obstruction (HCC, hypercoagulopathy, postpartum states, etc.)?

Answer 41

Budd-Chiari Syndrome

Question 42

What is a helpful serum tumor marker in HCC

Answer 42

Alpha-fetoprotein