Fa: Gastrointestinal - Pathology - 6

Front 1

What are the characteristics of Hepatic Steatosis?

Back 1

- First stage in alcoholic liver disease
- Reversible change with moderate alcohol intake
- Macrovesicular fatty changes that may be reversible with alcohol cessation

Front 2

What are the characteristics of Alcoholic Hepatitis?

Back 2

- Second stage in alcoholic liver disease
- Requires sustained, long-term consumption of alcohol
- Swollen and necrotic hepatocytes with neutrophilic infiltration
- Mallory bodies (intracytoplasmic eosinophilic inclusions) are present
- AST > ALT (ratio usually >1.5)

Front 3

What are the characteristics of Alcoholic Cirrhosis?

Back 3

- Final stage of alcoholic liver disease
- Irreversible changes
- Micronodular, irregularly shrunken liver with "hobnail" appearance
- Sclerosis around central vein (zone III)
- Has manifestations of chronic liver disease (eg, jaundice, hypoalbuminemia)

Front 4

When might you see macrovesicular fatty change in the liver?

Back 4

Macrovesicular fatty change is a sign of hepatic steatosis (stage 1 of alcoholic liver disease); reversible with alcohol cessation

Front 5

When might you see swollen and necrotic hepatocytes with neutrophilic infiltration and Mallory bodies?

Back 5

Alcoholic Heptitis (stage 2 of alcoholic liver disease)
- Mallory Bodies: intracytoplasmic eosinophilic inclusions

Front 6

When might you see a micronodular with a "hobnail" appearance?

Back 6

Alcoholic cirrhosis (stage 3 of alcoholic liver disease); irreversible and final form

Front 7

Where is there sclerosis in the liver with alcoholic cirrhosis?

Back 7

Around the central vein (zone III)

Front 8

What causes non-alcoholic fatty liver disease? What changes happen?

Back 8

Metabolic syndrome (insulin resistance) → fatty infiltration of hepatocytes → cellular "ballooning" and eventual necrosis

ALT > AST (lipids)
(independent of alcohol use)

Front 9

What can non-alcoholic fatty liver disease lead to?

Back 9

May cause cirrhosis and hepatocellular carcinoma

Front 10

What causes hepatic encephalopathy?

Back 10

Cirrhosis → portosystemic shunts → ↓ NH3 metabolism → neuropsychiatric dysfunction

Front 11

How severe is hepatic encephalopathy?

Back 11

Spectrum from disorientation / asterixis (mild) to difficult arousal or coma (severe)

Front 12

What an trigger hepatic encephalopathy?

Back 12

- ↑ NH3 production: dietary protein, GI bleed, constipation, infection
- ↓ NH3 removal: renal failure, diuretics, post-TIPS

Front 13

What can lead to ↑ NH3 production? Implications?

Back 13

- Dietary protein
- GI bleed
- Constipation
- Infection

- Can be a trigger for hepatic encephalopathy

Front 14

What can lead to ↓ NH3 removal? Implications?

Back 14

- Renal failure
- Diuretics
- Post-TIPS (Transjugular Intrahepatic Portosystemic Shunt)

Front 15

How do you treat patients with hepatic encephalopathy?

Back 15

- Lactulose (removes NH3 by converting to NH4+)
- Low protein diet
- Rifaximin (kills intestinal bacteria)

Front 16

What is the most common 1° malignant tumor of the liver in adults?

Back 16

Hepatocellular Carcinoma (HCC)

Front 17

What is Hepatocellular Carcinoma (HCC) associated with?

Back 17

- Hepatitis B & C
- Wilson disease
- Hemochromatosis
- α1-antitrypsin deficiency
- Alcoholic cirrhosis
- Aflatoxin from Aspergillus (carcinogen)

Front 18

What can Hepatocellular Carcinoma (HCC) lead to?

Back 18

Budd-Chiari Syndrome

- Caused by occlusion of the hepatic veins that drain the liver
- Presents with the classical triad of abdominal pain, ascites and hepatomegaly

Front 19

What are the findings in patients with Hepatocellular Carcinoma?

Back 19

- Jaundice
- Tender hepatomegaly
- Ascites
- Anorexia
- May lead to Budd-Chiari Syndrome

Front 20

How do you diagnose Hepatocellular Carcinoma (HCC)?

Back 20

- ↑ α-Fetoprotein
- Ultrasound
- Contrast CT (enhancing heterogenous mass)

Front 21

How does Hepatocellular Carcinoma (HCC) spread?

Back 21

Hematogenously

Front 22

What are the liver tumors?

Back 22

- Hepatocellular Carcinoma (most common)
- Cavernous Hemangioma
- Hepatic Adenoma
- Angiosarcoma

Front 23

What is the common, benign liver tumor that typically occurs at age 30-50 years?

Back 23

Cavernous Hemangioma

Front 24

What is the rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use?

Back 24

Hepatic Adenoma

Front 25

What is the malignant liver tumor of endothelial origin associated with exposure to arsenic and vinyl chloride?

Back 25

Angiosarcoma

Front 26

What are the characteristics of Cavernous Hemangioma?

Back 26

- Common, benign liver tumor
- Typically occurs at age 30-50 years
- Biopsy contraindicated because of a risk of hemorrhage

Front 27

What are the characteristics of Hepatic Adenoma?

Back 27

- Rare, benign liver tumor
- Often related to oral contraceptive or anabolic steroid use
- May regress spontaneously or rupture (abdominal pain and shock)

Front 28

What are the characteristics of Angiosarcoma?

Back 28

- Malignant tumor of endothelial organ
- Associated with exposure to arsenic and vinyl chloride

Front 29

What causes the liver to have a "nutmeg" appearance?

Back 29

- Backup of blood into liver
- Commonly caused by R-sided heart failure and Budd-Chiari Syndrome
- Appears mottled by a nutmeg

Front 30

What can nutmeg liver progress to?

Back 30

If the condition persists, centrilobular congestion and necrosis can result in cardiac cirrhosis

Front 31

What causes Budd-Chiari Syndrome?

Back 31

Occlusion of IVC or hepatic vein with centrilobular congestion and necrosis

Front 32

What does Budd-Chiari Syndrome lead to?

Back 32

- Congestive liver disease → hepatomegaly, ascites, abdominal pain, and eventual live failure
- May develop varices
- May have visible abdominal and back veins

Front 33

What is Budd-Chiari Syndrome associated with?

Back 33

- Hypercoagulable states
- Polycythemia vera
- Pregnancy
- Hepatocellular Carcinoma (HCC)
- Absence of JVD

Front 34

How does α1-antitrypsin deficiency cause liver damage?

Back 34

Misfolded gene product protein aggregates in hepatocellular ER → cirrhosis

Front 35

What is the histologic finding of α1-antitrypsin deficiency in the liver?

Back 35

Cirrhosis with PAS (+) globules (made of aggregations of misfolded gene product)

Front 36

How do you inherit α1-antitrypsin deficiency?

Back 36

Codominant trait

Front 37

How does α1-antitrypsin deficiency affect other organs besides the liver?

Back 37

In lungs, ↓ α1-antitrypsin → uninhibited elastase in alveoli → ↓ elastic tissue → panacinar emphysema

Front 38

What causes jaundice?

Back 38

- Bilirubin deposition in the skin and/or sclera causing yellowing
- Occurs at high bilirubin levels (>2.5 mg/dL) in the blood 2° to ↑ production or defective metabolism

Front 39

How high does bilirubin need to be to cause jaundice?

Back 39

>2.5 mg/dL in blood

Front 40

What are the types of hyperbilirubinemia?

Back 40

- Unconjugated (indirect) hyperbilirubinemia
- Conjugated (direct) hyperbilirubinemia
- Mixed (direct and indirect) hyperbilirubinemia

Front 41

What is the level of urine urobilinogen in unconjugated (indirect) hyperbilirubinemia? What diseases have this finding?

Back 41

- Increased urine urobilinogen
- Diseases: hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome

Front 42

What is the level of urine urobilinogen in conjugated (direct) hyperbilirubinemia? What diseases have this finding?

Back 42

- Decreased urine urobilinogen

Diseases:
- Biliary tract obstruction: gallstones, pancreatic liver cancer, liver fluke
- Biliary tract disease: 1° sclerosing cholangitis and 1° biliary cirrhosis
- Excretion defect: Dubin-Johnson syndrome, Rotor syndrome

Front 43

What is the level of urine urobilinogen in mixed (direct and indirect) hyperbilirubinemia? What diseases have this finding?

Back 43

- Normal or ↑
- Diseases: hepatitis or cirrhosis

Front 44

What type of hyperbilirubinemia is seen in patients with hemolysis?

Back 44

Unconjugated (indirect) hyperbilirubinemia
- ↑ urine urobilinogen

Front 45

What type of hyperbilirubinemia is seen in newborns?

Back 45

Physiologic (don't have enzymes to convert to conjugated form)
- Unconjugated (indirect) hyperbilirubinemia
- ↑ urine urobilinogen

Front 46

What type of hyperbilirubinemia is seen in patients with Crigler-Najjar syndrome?

Back 46

Unconjugated (indirect) hyperbilirubinemia
- ↑ urine urobilinogen

Front 47

What type of hyperbilirubinemia is seen in patients with Gilbert syndrome?

Back 47

Unconjugated (indirect) hyperbilirubinemia
- ↑ urine urobilinogen

Front 48

What type of hyperbilirubinemia is seen in patients with a biliary tract obstruction? What can cause this?

Back 48

Causes of biliary tract obstruction:
- Gallstones
- Pancreatic liver cancer
- Liver fluke

Conjugated (direct) hyperbilirubinemia
- ↓ urine urobilinogen

Front 49

What type of hyperbilirubinemia is seen in patients with a biliary tract disease? What can cause this?

Back 49

Causes of biliary tract disease:
- 1° sclerosing cholangitis
- 1° biliary cirrhosis

Conjugated (direct) hyperbilirubinemia
- ↓ urine urobilinogen

Front 50

What type of hyperbilirubinemia is seen in patients with an excretion defect? What can cause this?

Back 50

- Dubin-Johnson Syndrome
- Rotor Syndrome

Conjugated (direct) hyperbilirubinemia
- ↓ urine urobilinogen

Front 51

What type of hyperbilirubinemia is seen in patients with hepatitis and cirrhosis?

Back 51

Mixed (direct and indirect) hyperbilirubinemia
- Normal or ↑ urine urobilinogen

Front 52

What is the most common cause of jaundice in a neonate?

Back 52

Physiologic Neonatal Jaundice
- At birth, immature UDP-glucuronosyltrasnferase --> unconjugated hyperbilirubinemia --> jaundice / kernicterus

Front 53

How do you treat a neonate with physiologic jaundice?

Back 53

Phototherapy (converts unconjugated bilirubin to water-soluble form

Front 54

Which hereditary hyperbilirubinemia is associated with mildly DECREASED UDP-glucuronosyltransferase conjugation activity? What does this lead to?

Back 54

Gilbert Syndrome
- Decreased bilirubin uptake by hepatocytes
- Asymptomatic or mild jaundice (no clinical consequences)
- Elevated unconjugated bilirubin without overt hemolysis
- Bilirubin increases with fasting and stress

Front 55

Which hereditary hyperbilirubinemia is associated with ABSENT UDP-glucuronosyltransferase conjugation activity? What does this lead to?

Back 55

Crigler-Najjar Syndrome (type I)
- Presents early in life, patients die within a few years
- Causes jaundice, kernicterus (bilirubin depostion in brain), and ↑ unconjugated bilirubin

Front 56

Which hereditary hyperbilirubinemia is associated with a black liver? Why?

Back 56

Dubin-Johnson Syndrome
- Conjugated hyperbilirubinemia is due to defective liver excretion
- Benign

Front 57

Which hereditary hyperbilirubinemia causes a mild conjugated hyperbilirubinemia but without turning th eliver black?

Back 57

Rotor Syndrome

Front 58

Which syndrome causes bilirubin to increase with fasting or stress? Consequences?

Back 58

Gilbert Syndrome

- Mildly ↓ UDP-glucuronosyltransferase conjugation activity
- Leads to ↓ bilirubin uptake by hepatocytes
- Can be asymptomatic or cause mild jaundice
- Elevated unconjugated bilirubin without overt hemolysis

Front 59

What is wrong in Gilbert Syndrome? Symptoms? Other characteristics?

Back 59

- Very common, no clinical consequences
- Mildly ↓ UDP-glucuronosyltransferase conjugation activity
- Leads to ↓ bilirubin uptake by hepatocytes
- Can be asymptomatic or cause mild jaundice
- Elevated unconjugated bilirubin without overt hemolysis
- Bilirubin ↑ with fasting and stress

Front 60

What is wrong in Crigler-Najjar Syndrome, type 1? Symptoms? Other characteristics?

Back 60

- Absent UDP-glucuronosyltransferase
- Presents early in life, patients die within a few years
- Findings: jaundice, kernicterus (bilirubin deposition in brain), ↑ unconjugated bilirubin
- Treat with plasmapheresis and phototherapy

Front 61

What is wrong in Crigler-Najjar Syndrome, type 2? Symptoms? Other characteristics?

Back 61

- Type 2 is less severe
- Responds to phenobarbital which ↑ liver enzyme synthesis

Front 62

What is wrong in Dubin-Johnson Syndrome? Symptoms? Other characteristics?

Back 62

- Conjugated hyperbilirubinemia
- Due to defective liver excretion
- Grossly black liver
- Benign

Front 63

What is wrong in Rotor Syndrome? Symptoms? Other characteristics?

Back 63

- Similar to Dubin-Johnson Syndrome (problem with liver excretion of bilirubin)
- Mild conjugated hyperbilirubinemia
- Even milder, and doesn't cause black liver

Front 64

What does hemoglobin get converted to during its destruction? Where?

Back 64

Bilirubin - takes place in hepatic sinussoid

Front 65

Which hereditary syndromes cause a problem with bilirubin uptake and conjugation (1)? Leads to?

Back 65

Gilbert Syndrome
- Leads to unconjugated bilirubinemia

Front 66

Which hereditary syndromes cause a problem with bilirubin conjugation (2)? Leads to?

Back 66

Crigler-Najjar Syndrome
- Leads to unconjugated bilirubinemia

Front 67

Which hereditary syndromes cause a problem with conjugated bilirubin excretion (3) and (4)? Leads to?

Back 67

Dubin-Johnson Syndrome
- Leads to conjugated hyperbilirubinemia

Rotor Syndrome
- Leads to MILD conjugated hyperbilirubinemia