Gastrointestinal - Pathology (2) Flashcards Preview

First Aid > Gastrointestinal - Pathology (2) > Flashcards

Flashcards in Gastrointestinal - Pathology (2) Deck (25):
1

Cirrhosis and portal hypertension (360)

  • Cirrhosis
  • Etiologies
  • Portosystemic shunts

  • 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

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

  • 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)

3

Reye syndrome

  • Definition
  • Findings
  • Mechanism

  • 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.

4

Alcoholic liver disease

  • Hepatic steatosis
  • Alcoholic hepatitis
  • Alcoholic cirrhosis

  • 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).

5

Non-alcoholic fatty liver disease

  • 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)

6

Hepatic encephalopathy

  • Cirrhosis -->
  • Triggers
  • Treatment

  • 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).

7

Hepatocellular carcinoma/hepatoma

  • Definition
  • Findings
  • Diagnosis

  • 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.

8

Other liver tumors

  • Cavernous hemangioma
  • Hepatic adenoma
  • Angiosarcoma 

  • 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.

9

Nutmeg liver

  • 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.

10

Budd-Chiari syndrome

  • 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.

11

α1-antitrypsin deficiency

  • 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.

12

Jaundice

  • Definition
  • Physiologic neonatal jaundice

  • 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).

13

Hyperbilirubinemia

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

  • 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

14

Hereditary hyperbilirubinemias

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

  • 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.

15

Wilson disease (hepatolenticular degeneration)

  • Definition
  • Characterized by
  • Treatment

  • 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.

16

Hemochromatosis

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

  • 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.

17

Biliary tract disease:
Secondary biliary cirrhosis

  • Pathophysiology / pathology
  • Presentation
  • Labs
  • Additional information

  • 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.

18

Biliary tract disease:
Primary biliary cirrhosis

  • Pathophysiology / pathology
  • Presentation
  • Labs
  • Additional information

  • 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).

19

Biliary tract disease:
Primary sclerosing cholangitis

  • Pathophysiology / pathology
  • Presentation
  • Labs
  • Additional information

  • 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.

20

Gallstones (cholelithiasis)

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

  • 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.

21

Cholecystitis

  • Definition
  • Diagnosis

  • 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.

22

Porcelain gallbladder

  • Definition
  • Treatment

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

23

Acute pancreatitis

  • Definition
  • Causes
  • Clinical presentation
  • Labs
  • Complication

  • 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).

24

Chronic pancreatitis

  • Definition
  • Causes
  • Can lead to...
  • Labs

  • 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).

25

Pancreatic adenocarcinoma

  • Definition
  • Risk factors
  • Often presents with...
  • Treatment

  • 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.

Decks in First Aid Class (92):