Gastrointestinal - Pathology (2) Flashcards
(25 cards)
1
Q
Cirrhosis and portal hypertension (360)
- Cirrhosis
- Etiologies
- Portosystemic shunts
A
-
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
Q
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
A
- 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
Q
Reye syndrome
- Definition
- Findings
- Mechanism
A
- 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
Q
Alcoholic liver disease
- Hepatic steatosis
- Alcoholic hepatitis
- Alcoholic cirrhosis
A
-
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
Q
Non-alcoholic fatty liver disease
A
- Metabolic syndrome (insulin resistance) –> fatty infiltration of hepatocytes –> cellular “ballooning” and eventual necrosis.
- May cause cirrhosis and HCC.
- Independent of alcohol use.
- ALT > AST (Lipids)
6
Q
Hepatic encephalopathy
- Cirrhosis –>
- Triggers
- Treatment
A
- Cirrhosis –> portosystemic shunts –> decreased NH3 metabolism –> 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
Q
Hepatocellular carcinoma/hepatoma
- Definition
- Findings
- Diagnosis
A
- 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
Q
Other liver tumors
- Cavernous hemangioma
- Hepatic adenoma
- Angiosarcoma
A
-
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
Q
Nutmeg liver
A
- 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
Q
Budd-Chiari syndrome
A
- 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
Q
α1-antitrypsin deficiency
A
- Misfolded gene product protein aggregates in hepatocellular ER –> cirrhosis with PAS (+) globules in liver.
- Codominant trait.
- In lungs, decreased a1-antitrypsin –> uninhibited elastase in alveoli –> decreased elastic tissue –> panacinar emphysema.
12
Q
Jaundice
- Definition
- Physiologic neonatal jaundice
A
- 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 –> unconjugated hyperbilirubinemia –> jaundice/ kernicterus.
- Treatment: phototherapy (converts unconjugated bilirubin to water-soluble form).
13
Q
Hyperbilirubinemia
- For each
- Urine urobilinogen (increased/decreased)
- Diseases
- Unconjugated (indirect) hyperbilirubinemia
- Conjugated (direct) hyperbilirubinemia
- Mixed (direct and indirect) hyperbilirubinemia
A
- 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
Q
Hereditary hyperbilirubinemias
- Gilbert syndrome
- Crigler-Najjar syndrome, type I
- Dubin-Johnson syndrome
- Rotor syndrome
A
- Gilbert syndrome [1]
-
Problem with bilirubin uptake –> 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.
-
Problem with bilirubin uptake –> unconjugated bilirubinemia
- Crigler-Najjar syndrome, type I [2]
-
Problem with bilirubin conjugation –> 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.
-
Problem with bilirubin conjugation –> unconjugated bilirubinemia
- Dubin-Johnson syndrome [3]
-
Problem with excretion of conjugated bilirubin –> conjugated bilirubinemia
- Conjugated hyperbilirubinemia due to defective liver excretion.
- Grossly black liver.
- Benign.
-
Problem with excretion of conjugated bilirubin –> conjugated bilirubinemia
- Rotor syndrome [4]
- Mild conjugated hyperbilirubinemia
- Similar to but even milder than Dubin-Johnson syndrome
- Does not cause black liver.
15
Q
Wilson disease (hepatolenticular degeneration)
- Definition
- Characterized by
- Treatment
A
- 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
Q
Hemochromatosis
- Hemosiderosis
- Hemochromatosis
- Definition
- Can cause…
- Primary hemochromatosis
- Treatment of hereditary hemochromatosis
A
- 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 –> “bronze” diabetes.
- Results in CHF, testicular atrophy, and increased risk of HCC.
- Increased ferritin, increased iron, decreased TIBC –> 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.
- Definition
17
Q
Biliary tract disease:
Secondary biliary cirrhosis
- Pathophysiology / pathology
- Presentation
- Labs
- Additional information
A
- Pathophysiology / pathology
- Extrahepatic biliary obstruction (gallstone, biliary stricture, chronic pancreatitis, carcinoma of the pancreatic head)
- –> increased pressure in intrahepatic ducts
- –> 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
Q
Biliary tract disease:
Primary biliary cirrhosis
- Pathophysiology / pathology
- Presentation
- Labs
- Additional information
A
- Pathophysiology / pathology
- Autoimmune reaction
- –> lymphocytic infiltrate + granulomas
- –> 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
Q
Biliary tract disease:
Primary sclerosing cholangitis
- Pathophysiology / pathology
- Presentation
- Labs
- Additional information
A
- Pathophysiology / pathology
- Unknown cause of concentric “onion skin” bile duct fibrosis
- –> 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
Q
Gallstones (cholelithiasis)
- Definition
- 2 types of stones:
- Cholesterol stones
- Pigment stones
- Causes…
- Diagnosis
- Treatment
A
- 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.
- Cholesterol stones
- 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 –> gallstone ileus.
- Most often causes cholecystitis
- Diagnosis
- Diagnose with ultrasound [B].
- Treatment
- Treat with cholecystectomy if symptomatic.
21
Q
Cholecystitis
- Definition
- Diagnosis
A
- Definition
- Acute or chronic inflammation of gallbladder.
- Usually from cholelithiasis (gallstones [A])
- Most commonly blocking the cystic duct –> 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
Q
Porcelain gallbladder
- Definition
- Treatment
A
- Definition
- Calcified gallbladder due to chronic cholecystitis
- Usually found incidentally on imaging [A].
- Treatment
- Prophylactic cholecystectomy due to high rates of gallbladder carcinoma.
23
Q
Acute pancreatitis
- Definition
- Causes
- Clinical presentation
- Labs
- Complication
A
- 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
Q
Chronic pancreatitis
- Definition
- Causes
- Can lead to…
- Labs
A
- Definition
- Chronic inflammation, atrophy, calcification of the pancreas [A].
- Major causes
- Alcohol abuse
- Idiopathic.
- Can lead to…
- Pancreatic insufficiency –> 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] (--\> 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
* Weight loss (due to malabsorption and anorexia)
* Migratory thrombophlebitis—redness and tenderness on palpation of extremities (**Trousseau syndrome**)
* Obstructive jaundice with palpable, nontender gallbladder (Courvoisier sign)
* Treatment
* Whipple procedure, chemotherapy, radiation therapy.
