Pathology - S2B3 - Liver 2

Front 1

List the Hereditary & Congenital Hyperbilirubinemias that have UNCONJUGATED Bilirubin

Back 1

1. Hemolytic anemia
2. Gilbert Syndrome
3. Crigler-Najjar Syndrome
4. Physiologic jaundice of neonates

Front 2

Hereditary & Congenital Hyperbilirubinemias that have CONJUGATED Hyperbilirubinemias

Back 2

1. Dubin-Johnson Syndrome
2. Rotor Syndrome
3. Biliary obstruction: atresia, cysts, AAT deficiency

Front 3

What is the cause of Gilbert Syndrome?

Back 3

Autosomal Dominant condition in which there is a mutation in the gene encoding UDP-glucuronyl transferase (UGT) activity along with decreased bilirubin uptake
-results in decreased UGT activity and a resultant Unconjugated Hyperbilirubinemia

Front 4

Syndrome that is associated with jaundice that appears with minor stress, exercise, or fasting; usually asymptomatic & no treatment is required

Back 4

Gilbert Syndrome = decreased UGT activity & decreased Bilirubin uptake by Liver

Front 5

What is the ONLY Hereditary Hyperbilirubinemia that causes Liver changes

Back 5

Dubin-Johnson Syndrome -> Black Liver

Front 6

Describe Crigler-Najjar Syndrome Type 1

Back 6

Autosomal recessive condition resulting in absent UGT activity & Unconjugated Hyperbilirubinemia
-early death from Kernicterus, damage to the Basal Ganglia

Front 7

Describe Crigler-Najjar Syndrome Type 2

What is the treatment?

Back 7

AUtosomal dominant condition resulting in decreased UGT activity & Unconjugated Bilirubinemia
-milder than Type 1; jaundice

Phenobarbitol

Front 8

Explain Physiologic Jaundice of Neonates

Back 8

Transient Unconjugated Hyperbilirubinemia due to immaturity of the liver
-due to increased Bilirubin production & a relative deficiency of Glucuronyl Transferase in the immature liver

Front 9

What is the cause of Dubin-Johnson Syndrome?

Back 9

Autosomal recessive condition resulting from defective bilirubin TRANSPORT protein out of the liver

Front 10

What are the clinical manifestations of Dubin-Johnson Syndrome?

Back 10

1. Intermittent Jaundice
2. RUQ & epigastric pain
3. CONJUGATED HYPERBILIRUBINEMIA
4. mildly elevated LFT's
5. BLACK LIVER

Front 11

Conjugated Hyperbilirubinemia + Black Liver

Back 11

Dubin-Johnson Syndrome

Front 12

Syndrome that is similar to Dubin-Johnson Syndrome but abnormal black pigment is not present

Back 12

Rotor Syndrome

Front 13

Dubin-Johnson Syndrome = causes Black Liver

Back 13

What Hereditary Hyperbilirubinemia caused this?

Front 14

After what % of Liver functional capacity is lost do symptoms of Hepatic Failure appear?

Back 14

80-90%

Front 15

What is the difference between Acute & Chronic Liver Failure?

Back 15

Acute = sudden onset that may cause death in a few days or weeks; associated with massive hepatic necrosis following viral infection, adverse drug reaction, or ingestion of toxins

Chronic = develops over a period of years & is typically associated with Cirrhosis

Front 16

Describe "Hepatorenal Syndrome"

Back 16

-sudden functional renal failure (w/out underlying kidney disease) in a patient with end-stage liver failure
-renal failure is caused by hypoperfusion of the kidneys
-if patient dies, kidneys can be transplanted into another person & will function normally

Front 17

Describe Hepatic Encephalopathy

Back 17

-due to entry of AMMONIA from the portal vein into the systemic circulation
-under normal circumstances the substances generated by the nitrogen-producing bacteria in the intestine are removed from the Portal Venous blood by the liver
-In patients with Cirrhosis, the venous blood from Portal System bypasses liver and enter Systemic Circulation
-Ammonia gets to brain -> Coma

Front 18

What are the signs/symptoms of Hepatorenal Syndrome?

Back 18

1. Oliguria
2. increased BUN
3. increased Creatinie
4. concentrated Urine & Hyperosmolar
5. unresponsive to Diuretic therapy

Front 19

Define Cirrhosis

Back 19

End-stage liver disease characterized by:
1. loss of normal architecture
2. widespread fibrosis, bridging from portal to portal or Centrolobular to Portal zones, and encircling parts of liver parenchyma
3. Nodular transformation of the parenchyma

Front 20

List 7 causes of Cirrhosis

Back 20

1. Alcohol
2. Viral Hepatitis
3. Biliary diseases
4. Hemochromatosis
5. AAT deficiency
6. Wilson Disease
7. Cryptogenic cirrhosis (15%)

Front 21

What are the clinical manifestations of Cirrhosis?

Back 21

1. Portan HTN = Ascites, Splenomegaly, Varices (esophageal & hemorrhoidal)
2. Metabolic disorders
3. Bleeding tendency
4. Hepatic encephalopaty = due to ammonia
5. Hepatorenal Syndrome = due to decrease kidney perfusion

Front 22

What are the lab findings in Cirrhosis?

Back 22

1. prolonged PT
2. Hypoalbuminemia
3. Hyperbilirubinemia
4. increased ALT, AST, ALP

Front 23

What is a complication of Cirrhosis?

Back 23

Liver Cell Carcinoma = Hepatocellular Carcinoma

Front 24

What is the mechanism of fibrosis in Cirrhosis?

Back 24

produced by Ito cells (Stellate cells)

Front 25

Cirrhosis

Back 25

What is this picture showing?

Front 26

Cirrhosis
-nodularity

Back 26

What is this picture showing?

Front 27

Cirrhosis
-nodularity

Back 27

What is this picture showing?

Front 28

What is the definition of Ascites?

Back 28

Accumulation of fluid in the abdominal cavity

Front 29

When is Ascites detectable?

Back 29

> 500 ml

Front 30

Discuss the pathogenesis of Ascites in Cirrhosis

Back 30

1. Portal HTN = increase in portal vein hydrostatic pressure
2. Hypoalbuminemia = liver does not synthesize albumin = decreased oncotic pressure
3. Secondary Hyperaldosteronism = decreased CO activates renin-angiotensin-aldosterone system; liver is unable to metabolize Aldosterone

Front 31

What does it mean if PMN's are found in the serous fluid in Ascites? What if RBC's are found?

Back 31

PMN = infection

RBC = tumor (hepatocellular carcinoma, ovarian CA, pancreas)

Front 32

List the virus families associated with each of the Hepatitis Viruses

Back 32

A = PicornAvirus
B = Hepadnavirus
C = Flavivirus
E = Calicivirus

Front 33

Aside from Hepatotrophic viruses, what other viruses can cause Viral Hepatitis?

Back 33

Yellow Fever

Epstein-Barr virus

Herpes Simplex

Cytomegalovirus

Front 34

What Viral Hepatitis' are transmitted fecal-orally?

Back 34

A & E

Front 35

What Viral Hepatitis' are blood-borne viruses?

Back 35

B, C, D

Front 36

Hepatitis virus that causes a "ground-glass" appearance

Back 36

HBV

Front 37

Hepatitis viruses associated with Hepatocellular Carcinoma

Back 37

B & C

Front 38

What are the microscopid changes associated with Acute Viral Hepatitis?

Back 38

Liver cells = hydropic change, bile stasis, apoptosis, necrosis & regeneration

Kupffer cells = reactive changes, increase in number

Inflammatory cells = Macrophage, Lymphocytes in portal tracts and lobules

Front 39

Acute Hepatitis

Back 39

What is seen here?

Front 40

Acute Viral Hepatitis
-lobular disarray
-hepatocyte swelling
-apoptotic hepatocytes
-lympocytes in portal tracts & lobule

Back 40

What is seen here?

Front 41

What are the microscopid finding in Chronic Hepatitis?

Back 41

Persistent signs of Acute Hepatitis
-lobular disarray, reactive changes, inflammation

INFLAMMATION SPILLS INTO THE PARENCHYMA CAUSING "INTERFACE HEPATITIS" = piecemeal necrosis of limiting plate

Portal fibrosis -> Bridging Fibrosis -> Cirrhosis

Front 42

Chronic Active Hepatitis = inflammation has spilled into the Parenchyma

Back 42

What is seen here?

Front 43

Chronic Persistent Hepatitis = confined to the Portal Tracts

Back 43

What is this?

Front 44

Chronic Hepatitis
-Lymphocyte aggregates

Back 44

What is seen here?

Front 45

Chronic Active Hepatitis
-Interface Hepatitis = Piecemeal necrosis of LImiting plate

Back 45

What is seen here?

Front 46

Define Fulminant Hepatitis

Back 46

Hepatic Failure with Encephalopathy within 2-3 weeks of onset

Front 47

What causes Fulminant Hepatitis 60% of the time? 30%?

List 4 rare causes

Back 47

60% = Viral Hepatitis = HBV & HCV

30% = Drug-induced & chemical = Tylenol

1. Ischemic necrosis
2. Hepatic Vein obstruction
3. Steatosis syndrome (eg. pregnancy)
4. Malignant tumors

Front 48

Fulminant Hepatitis

Back 48

What is seen here?

Front 49

Describe Bacterial infections of the liver via the Arterial route

Back 49

Bacteria reach the liver via the Hepatic Artery during SEPSIS or in SEPTIC THROMBOEMBOLI in bacterial endocarditis
-Streptococcus
-Staphylococcus aureus
-Salmonella

Front 50

Describe Bacterial infections of the liver via Portal Vein route

Back 50

from Appendicitis, Diverticulosis, or Mucosal abscesses
-E. coli
-Enteric saprophytes

Front 51

Describe Bacterial infections of the liver via the Ascending Biliary route

Back 51

Bacteria ascending into the liver from the Duodenum are most often Gram Negative
-usually occur in patients who have bile stones or other diseases of the biliary tract

Front 52

Describe Direct Invasion of the liver of Bacterial infections

Back 52

-bacterial infection of the gallbladder may extend to the liver
-transdiaphragmatic infection from the infected peritoneum is a rare complication of severe infection & is usually found in terminally ill patients or those who had extensive surgery

Front 53

Bacterial infection of the liver

Back 53

What is seen here?

Front 54

Protozoa that causes "flask-shaped" ulcers in the Colon & right lobe liver abscesses

Back 54

Entamoeba Histolytica

Front 55

Trematode (fluke) that is contracted by ingesting fish; causes inflammation of the Biliary Tract & may cause Cholangiocarcinoma

Back 55

Clonorchis sinensis

Front 56

Trematode with snails as their host, cercariae penetrate skin of humans; causes granulomas, fibrosis, & inflammation of the Portal Vein

Back 56

Schistosoma mansoni & japonicum

Front 57

This tapeworm is ingested from the excreta of Dogs & Sheep; causes cysts in the liver; rupture of cysts can cause anaphylaxis

Back 57

Echinococcis granulosus

Front 58

What drug induces Fatty Change?

Back 58

Tetracycline

Front 59

What drug induces Centrolobular Necrosis?

Back 59

Acetaminophen (Tylenol)

Front 60

What drug causes massive necrosis of the liver?

Back 60

Halothane

Front 61

What drugs cause Hepatitis-like changes in the liver?

Back 61

Isoniazid

Methyldopa

Front 62

What drug causes Fibrosis of the liver?

Back 62

Methotrexate

Front 63

What 2 drugs cause Cholestasis?

Back 63

Chlorpromazine = anti-emetic

Oral Contraceptives

Front 64

What drugs cause Veno-occlusive disease of the liver?

Back 64

Cytotoxic drugs

Pyrrolizidine

Front 65

What drugs cause Thrombosis (Portal or Hepatic vein)?

Back 65

Oral Contraceptives

Estrogens

Cytotoxic drugs

Front 66

What drugs cause Peliosis Hepatis (blood-filled cavities in the liver)?

Back 66

Anabolic steroids

Oral Contraceptives

Front 67

List the types of liver disease associated with Alcohol

Back 67

1. Fatty change = >80%; usually asymptomatic, reversible

2. Alcoholic hepatitis = 10-15%; after acute bout of drinking; may be reversible or progress to cirrhosis

3. Cirrhosis = 0-15%; irreversible & lethal if liver is not replaced

Front 68

Explain why Fatty Change occurs with alcohol consumption

Back 68

Substrates of alcohol metabolism are used to synthesize liver Triglyceride (glycerol + 3 fatty acids)

Front 69

What are the microscopic changes associated with Alcoholic Hepatitis?

Back 69

1. Hepatocyte swelling
2. MALLORY BODIES
3. EVENTUAL FIBROSIS AROUND THE CENTRAL VEIN (TERMINAL HEPATIC VEIN)

Front 70

Steatosis due to alcohol consumption

Tender hepatomegaly WITHOUT fever or neutrophilic leukocytosis

Back 70

What is this?

What would be the clinical manifestation?

Front 71

Alcoholic Hepatitis
-Mallory Hyaline
-Neutrophils
-Necrosis of hepatocytes
-collagen deposition
-Fatty change

Back 71

What is the cause of this?

Front 72

Alcoholic hepatitis
-hepatocyte swelling
-Mallory Hyaline
-Neutrophilic infiltration of hepatocytes

Back 72

What is shown here?

Front 73

Cirrhosis
-"hobnail" liver appearance

Back 73

What is this showing?

Front 74

Cirrhosis

Alcohol

Acetaldehyde stimulates Ito cell to produce fibrous tissue

Back 74

What is seen here? What is the most common cause? What is the mechanism?