Gastrointestinal - Pathology (2)

Question 1

Cirrhosis and portal hypertension (360)

• Cirrhosis
• Etiologies
• Portosystemic shunts

Answer 1

• Cirrhosis
  
  • Diffuse fibrosis and nodular regeneration destroys normal architecture of liver [A] [B]
  • Increased risk for hepatocellular carcinoma (HCC).
• Etiologies
  
  • Alcohol (60–70%), viral hepatitis, biliary disease, hemochromatosis.
• Portosystemic shunts partially alleviate portal hypertension:
  
  • Esophageal varices
  • Caput medusae

Question 2

Serum markers of liver and pancreas pathology:
Major diagnostic uses of these serum markers

• Alkaline phosphatase (ALP)
• Aminotransferases (AST and ALT)
• Amylase
• Ceruloplasmin
• γ-glutamyl transpeptidase (GGT)
• Lipase

Answer 2

• Alkaline phosphatase (ALP)
  
  • Obstructive hepatobiliary disease, HCC, bone disease
• Aminotransferases (AST and ALT) (often called “liver enzymes”)
  
  • Viral hepatitis (ALT > AST)
  • Alcoholic hepatitis (AST > ALT)
• Amylase
  
  • Acute pancreatitis, mumps
• Ceruloplasmin
  
  • Decreased in Wilson disease
• γ-glutamyl transpeptidase (GGT)
  
  • Increased in various liver and biliary diseases (just as ALP can), but not in bone disease
  • Associated with alcohol use
• Lipase
  
  • Acute pancreatitis (most specific)

Question 3

Reye syndrome

• Definition
• Findings
• Mechanism

Answer 3

• Definition
  
  • Rare, often fatal childhood hepatoencephalopathy.
  • Associated with viral infection (especially VZV and influenza B) that has been treated with aspirin.
• Findings
  
  • Mitochondrial abnormalities, fatty liver (microvesicular fatty change), hypoglycemia, vomiting, hepatomegaly, coma.
• Mechanism
  
  • Aspirin metabolites decrease β-oxidation by reversible inhibition of mitochondrial enzyme.
  • Avoid aspirin in children, except in those with Kawasaki disease.

Question 4

Alcoholic liver disease

• Hepatic steatosis
• Alcoholic hepatitis
• Alcoholic cirrhosis

Answer 4

• Hepatic steatosis
  
  • Reversible change with moderate alcohol intake.
  • Macrovesicular fatty change [A] that may be reversible with alcohol cessation.
• Alcoholic hepatitis
  
  • Requires sustained, long-term consumption.
  • Swollen and necrotic hepatocytes with neutrophilic infiltration.
  • Mallory bodies (intracytoplasmic eosinophilic inclusions) are present.
  • Make a toAST** with alcohol: AST > ALT (ratio usually > 1.5).**
• Alcoholic cirrhosis
  
  • Final and irreversible form.
  • Micronodular, irregularly shrunken liver with “hobnail” appearance.
  • Sclerosis around central vein (zone III).
  • Has manifestations of chronic liver disease (e.g., jaundice, hypoalbuminemia).

Question 5

Non-alcoholic fatty liver disease

Answer 5

• Metabolic syndrome (insulin resistance) –>Ž fatty infiltration of hepatocytes –> cellular “ballooning” and eventual necrosis.
• May cause cirrhosis and HCC.
• Independent of alcohol use.
• ALT > AST (Lipids)

Question 6

Hepatic encephalopathy

• Cirrhosis –>
• Triggers
• Treatment

Answer 6

• Cirrhosis –>Ž portosystemic shunts Ž–> decreased NH3 metabolism –>Ž neuropsychiatric dysfunction.
  
  • Spectrum from disorientation/asterixis (mild) to difficult arousal or coma (severe).
• Triggers
  
  • Increased NH3 production (due to dietary protein, GI bleed, constipation, infection).
  • Decreased NH3 removal (due to renal failure, diuretics, post-TIPS).
• Treatment
  
  • Lactulose (increased NH4+ generation)
  • Low-protein diet
  • Rifaximin (kills intestinal bacteria).

Question 7

Hepatocellular carcinoma/hepatoma

• Definition
• Findings
• Diagnosis

Answer 7

• Definition
  
  • Most common 1° malignant tumor of the liver in adults [A].
  • Associated with hepatitis B and C, Wilson disease, hemochromatosis, α1-antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (e.g., aflatoxin from Aspergillus).
  • May lead to Budd-Chiari syndrome.
• Findings
  
  • Jaundice, tender hepatomegaly [B], ascites, and anorexia.
  • Spreads hematogenously.
• Diagnosis
  
  • Increased α-fetoprotein
  • Ultrasound or contrast CT.

Question 8

Other liver tumors

• Cavernous hemangioma
• Hepatic adenoma
• Angiosarcoma

Answer 8

• Cavernous hemangioma
  
  • Common, benign liver tumor
  • Typically occurs at age 30–50 years.
  • Biopsy contraindicated because of risk of hemorrhage.
• Hepatic adenoma
  
  • Rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use
  • May regress spontaneously or rupture (abdominal pain and shock).
• Angiosarcoma
  
  • Malignant tumor of endothelial origin
  • Associated with exposure to arsenic, vinyl chloride.

Question 9

Nutmeg liver

Answer 9

• Due to backup of blood into liver.
• Commonly caused by right-sided heart failure and Budd-Chiari syndrome.
• The liver appears mottled like a nutmeg.
• If the condition persists, centrilobular congestion and necrosis can result in cardiac cirrhosis.

Question 10

Budd-Chiari syndrome

Answer 10

• Occlusion of IVC or hepatic veins with centrilobular congestion and necrosis, leading to congestive liver disease (hepatomegaly, ascites, abdominal pain, and eventual liver failure).
• May develop varices and have visible abdominal and back veins.
• Absence of JVD.
• Associated with hypercoagulable states, polycythemia vera, pregnancy, and HCC.

Question 11

α1-antitrypsin deficiency

Answer 11

• Misfolded gene product protein aggregates in hepatocellular ER Ž–> cirrhosis with PAS (+) globules in liver.
• Codominant trait.
• In lungs, decreased a1-antitrypsin –> uninhibited elastase in alveoli Ž–> decreased elastic tissue –>Ž panacinar emphysema.

Question 12

Jaundice

• Definition
• Physiologic neonatal jaundice

Answer 12

• Definition
  
  • Abnormal yellowing of the skin and/or sclera [A] due to bilirubin deposition.
  • Occurs at high bilirubin levels (> 2.5 mg/dL) in the blood 2° to increased production or defective metabolism.
• Physiologic neonatal jaundice
  
  • At birth, immature UDP-glucuronosyltransferase –>Ž unconjugated hyperbilirubinemia –> jaundice/ kernicterus.
  • Treatment: phototherapy (converts unconjugated bilirubin to water-soluble form).

Question 13

Hyperbilirubinemia

• For each
  
  • Urine urobilinogen (increased/decreased)
  • Diseases
• Unconjugated (indirect) hyperbilirubinemia
• Conjugated (direct) hyperbilirubinemia
• Mixed (direct and indirect) hyperbilirubinemia

Answer 13

• Unconjugated (indirect) hyperbilirubinemia
  
  • Urine urobilinogen: Increased
  • Diseases: Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome
• Conjugated (direct) hyperbilirubinemia
  
  • Urine urobilinogen: Decreased
  • Diseases:
    
    • Biliary tract obstruction: gallstones, pancreatic liver cancer, liver fluke
    • Biliary tract disease: 1° sclerosing cholangitis, 1° biliary cirrhosis
    • Excretion defect: Dubin-Johnson syndrome, Rotor syndrome
• Mixed (direct and indirect) hyperbilirubinemia
  
  • Urine urobilinogen: Normal / increased
  • Diseases: Hepatitis, cirrhosis

Question 14

Hereditary hyperbilirubinemias

• Gilbert syndrome
• Crigler-Najjar syndrome, type I
• Dubin-Johnson syndrome
• Rotor syndrome

Answer 14

• Gilbert syndrome [1]
  
  • Problem with bilirubin uptake –>Ž unconjugated bilirubinemia
    
    • Mildly decreased UDP-glucuronosyltransferase conjugation activity –> decreased bilirubin uptake by hepatocytes.
    • Elevated unconjugated bilirubin without overt hemolysis.
  • Asymptomatic or mild jaundice.
  • Bilirubin increased with fasting and stress.
  • Very common.
  • No clinical consequences.
• Crigler-Najjar syndrome, type I [2]
  
  • Problem with bilirubin conjugation –>Ž unconjugated bilirubinemia
    
    • Absent UDP-glucuronosyltransferase.
  • Presents early in life; patients die within a few years.
  • Findings: jaundice, kernicterus (bilirubin deposition in brain), increased unconjugated bilirubin.
  • Treatment: plasmapheresis and phototherapy.
  • Type II is less severe and responds to phenobarbital, which increases liver enzyme synthesis.
• Dubin-Johnson syndrome [3]
  
  • Problem with excretion of conjugated bilirubin –>Ž conjugated bilirubinemia
    
    • Conjugated hyperbilirubinemia due to defective liver excretion.
  • Grossly black liver.
  • Benign.
• Rotor syndrome [4]
  
  • Mild conjugated hyperbilirubinemia
  • Similar to but even milder than Dubin-Johnson syndrome
  • Does not cause black liver.

Question 15

Wilson disease (hepatolenticular degeneration)

• Definition
• Characterized by
• Treatment

Answer 15

• Definition
  
  • Inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmin.
  • Leads to copper accumulation, especially in liver, brain, cornea, kidneys, and joints.
  • Copper is normally excreted into bile by hepatocyte copper transporting ATPase (ATP7B gene).
  • Autosomal recessive inheritance (chromosome 13).
• Characterized by: (“Copper is Hella BAD.”)
  
  • Decreased Ceruloplasmin, Cirrhosis, Corneal deposits (Kayser-Fleischer rings) [A], Copper accumulation, Carcinoma (hepatocellular)
  • Hemolytic anemia
  • Basal ganglia degeneration (parkinsonian symptoms)
  • Asterixis
  • Dementia, Dyskinesia, Dysarthria
• Treatment
  
  • Treat with penicillamine or trientine.

Question 16

Hemochromatosis

• Hemosiderosis
• Hemochromatosis
  
  • Definition
  • Can cause…
  • Primary hemochromatosis
  • Treatment of hereditary hemochromatosis

Answer 16

• Hemosiderosis
  
  • The deposition of hemosiderin (iron)
• Hemochromatosis
  
  • Definition
    
    • The disease caused by the deposition of hemosiderin (iron).
    • Disease may be 1° (autosomal recessive) or 2° to chronic transfusion therapy (e.g., β-thalassemia major).
    • Total body iron may reach 50 g, enough to set off metal detectors at airports.
    • Iron loss through menstruation slows progression in women.
  • Hemochromatosis Can Cause Deposits
    
    • ​Classic triad of micronodular Cirrhosis, Diabetes mellitus, and skin pigmentation –>Ž “bronze” diabetes.
    • Results in CHF, testicular atrophy, and increased risk of HCC.
    • Increased ferritin, increased iron, decreased TIBC Ž–> increased transferrin saturation.
  • Primary hemochromatosis
    
    • Due to C282Y or H63D mutation on HFE gene.
    • Associated with HLA-A3.
  • Treatment of hereditary hemochromatosis
    
    • Repeated phlebotomy, deferasirox, deferoxamine.

Question 17

Biliary tract disease:
Secondary biliary cirrhosis

• Pathophysiology / pathology
• Presentation
• Labs
• Additional information

Answer 17

• Pathophysiology / pathology
  
  • ​Extrahepatic biliary obstruction (gallstone, biliary stricture, chronic pancreatitis, carcinoma of the pancreatic head)
  • –> increased pressure in intrahepatic ducts
  • –>Ž injury / fibrosis and bile stasis.
• Presentation
  
  • ​Pruritus, jaundice, dark urine, light stools, hepatosplenomegaly.
• Labs
  
  • ​Increased conjugated bilirubin
  • Increased cholesterol
  • Increased ALP.
• Additional information
  
  • _​_Complicated by ascending cholangitis.

Question 18

Biliary tract disease:
Primary biliary cirrhosis

• Pathophysiology / pathology
• Presentation
• Labs
• Additional information

Answer 18

• Pathophysiology / pathology
  
  • Autoimmune reaction
  • –>Ž lymphocytic infiltrate + granulomas
  • –>Ž destruction of intralobular bile ducts.
• Presentation
  
  • Pruritus, jaundice, dark urine, light stools, hepatosplenomegaly.
• Labs
  
  • Increased conjugated bilirubin
  • Increased cholesterol
  • Increased ALP
• Additional information
  
  • Increased serum mitochondrial antibodies, including IgM.
  • Associated with other autoimmune conditions (e.g., CREST, Sjögren syndrome, rheumatoid arthritis, celiac disease).

Question 19

Biliary tract disease:
Primary sclerosing cholangitis

• Pathophysiology / pathology
• Presentation
• Labs
• Additional information

Answer 19

• Pathophysiology / pathology
  
  • ​Unknown cause of concentric “onion skin” bile duct fibrosis
  • –>Ž alternating strictures and dilation with “beading” of intra- and extrahepatic bile ducts on ERCP.
• Presentation
  
  • ​Pruritus, jaundice, dark urine, light stools, hepatosplenomegaly.
• Labs
  
  • ​Increased conjugated bilirubin
  • Increased cholesterol
  • Increased ALP
• Additional information
  
  • Hypergammaglobulinemia (IgM).
  • Associated with ulcerative colitis.
  • Can lead to 2° biliary cirrhosis and cholangiocarcinoma.

Question 20

Gallstones (cholelithiasis)

• Definition
• 2 types of stones:
  
  • Cholesterol stones
  • Pigment stones
• Causes…
• Diagnosis
• Treatment

Answer 20

• Definition
  
  • Increased cholesterol and/or bilirubin, decreased bile salts, and gallbladder stasis all cause stones [A].
• 2 types of stones:
  
  • Cholesterol stones
    
    • Radiolucent with 10–20% opaque due to calcifications
    • 80% of stones.
    • Associated with obesity, Crohn disease, cystic fibrosis, advanced age, clofibrate, estrogen therapy, multiparity, rapid weight loss, and Native American origin.
  • Pigment stones
    
    • Black = radiopaque, hemolysis
    • Brown = radiolucent, infection
    • Seen in patients with chronic hemolysis, alcoholic cirrhosis, advanced age, and biliary infection.
• Causes…
  
  • Most often causes cholecystitis
    
    • Also ascending cholangitis, acute pancreatitis, bile stasis.
  • Can also lead to biliary colic
    
    • Neurohormonal activation (e.g., by CCK after a fatty meal) triggers contraction of the gallbladder, forcing a stone into the cystic duct.
    • May present without pain (e.g., in diabetics).
  • Can cause fistula between gallbladder and small intestine, leading to air in the biliary tree.
    
    • Gallstone may obstruct ileocecal valve –>Ž gallstone ileus.
• Diagnosis
  
  • Diagnose with ultrasound [B].
• Treatment
  
  • Treat with cholecystectomy if symptomatic.

Question 21

Cholecystitis

• Definition
• Diagnosis

Answer 21

• Definition
  
  • Acute or chronic inflammation of gallbladder.
  • Usually from cholelithiasis (gallstones [A])
  • Most commonly blocking the cystic duct Ž–> 2° infection
    
    • Rarely ischemia or 1° infection (CMV).
• Diagnosis
  
  • Murphy sign (+)—inspiratory arrest on RUQ palpation due to pain.
  • Increased ALP if bile duct becomes involved (e.g., ascending cholangitis).
  • Diagnose with ultrasound or HIDA.

Question 22

Porcelain gallbladder

• Definition
• Treatment

Answer 22

• Definition
  
  • Calcified gallbladder due to chronic cholecystitis
  • Usually found incidentally on imaging [A].
• Treatment
  
  • Prophylactic cholecystectomy due to high rates of gallbladder carcinoma.

Question 23

Acute pancreatitis

• Definition
• Causes
• Clinical presentation
• Labs
• Complication

Answer 23

• Definition
  
  • Autodigestion of pancreas by pancreatic enzymes [A].
• Causes
  
  • PANCREATITIS
  • hyperParathyroidism –> hypercalcemia
  • Alcohol
  • Neoplasm / autoimmune disease
  • Cholelithiasis (gallstones)
  • Rx (HIV drugs [NRTIs, protease inhibitor ritonavir], sulfa drugs, steroids)
  • ERCP
  • Abdominal surgery
  • hyperTriglyceridemia (> 1000 mg/dL)
  • Infection (mumps)
  • Trauma
  • Idiopathic
  • Scorpion sting
• Clinical presentation
  
  • Epigastric abdominal pain radiating to back, anorexia, nausea.
  • Can lead to DIC, ARDS, diffuse fat necrosis, hypocalcemia (Ca2+ collects in pancreatic calcium soap deposits), pseudocyst formation, hemorrhage, infection, and multiorgan failure.
• Labs
  
  • Increased amylase, lipase (higher specificity).
• Complication
  
  • Pancreatic pseudocyst (lined by granulation tissue, not epithelium; can rupture and hemorrhage).

Question 24

Chronic pancreatitis

• Definition
• Causes
• Can lead to…
• Labs

Answer 24

• Definition
  
  • Chronic inflammation, atrophy, calcification of the pancreas [A].
• Major causes
  
  • Alcohol abuse
  • Idiopathic.
• Can lead to…
  
  • Pancreatic insufficiency –>Ž steatorrhea
  • Fat-soluble vitamin deficiency
  • Diabetes mellitus
  • Increased risk of pancreatic adenocarcinoma.
• Labs
  
  • Amylase and lipase may or may not be elevated (almost always elevated in acute pancreatitis).

Question 25

Pancreatic adenocarcinoma * Definition * Risk factors * Often presents with... * Treatment

Answer 25

* Definition * Prognosis averages 1 year * Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration [A]) * Already metastasized at presentation * Tumors more common in pancreatic head [B] (--\>Ž obstructive jaundice). * Associated with CA-19-9 tumor marker (also CEA, less specific). * Risk factors * Tobacco use * Chronic pancreatitis (especially \> 20 years) * Diabetes * Age \> 50 years * Jewish and African-American males * Often presents with... * Abdominal pain radiating to back * ƒƒWeight loss (due to malabsorption and anorexia) * ƒƒMigratory thrombophlebitis—redness and tenderness on palpation of extremities (**Trousseau syndrome**) * ƒƒObstructive jaundice with palpable, nontender gallbladder (Courvoisier sign) * Treatment * Whipple procedure, chemotherapy, radiation therapy.