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74 Cards in this Set

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List the Hereditary & Congenital Hyperbilirubinemias that have UNCONJUGATED Bilirubin
1. Hemolytic anemia
2. Gilbert Syndrome
3. Crigler-Najjar Syndrome
4. Physiologic jaundice of neonates
Hereditary & Congenital Hyperbilirubinemias that have CONJUGATED Hyperbilirubinemias
1. Dubin-Johnson Syndrome
2. Rotor Syndrome
3. Biliary obstruction: atresia, cysts, AAT deficiency
What is the cause of Gilbert Syndrome?
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
Syndrome that is associated with jaundice that appears with minor stress, exercise, or fasting; usually asymptomatic & no treatment is required
Gilbert Syndrome = decreased UGT activity & decreased Bilirubin uptake by Liver
What is the ONLY Hereditary Hyperbilirubinemia that causes Liver changes
Dubin-Johnson Syndrome -> Black Liver
Describe Crigler-Najjar Syndrome Type 1
Autosomal recessive condition resulting in absent UGT activity & Unconjugated Hyperbilirubinemia
-early death from Kernicterus, damage to the Basal Ganglia
Describe Crigler-Najjar Syndrome Type 2

What is the treatment?
AUtosomal dominant condition resulting in decreased UGT activity & Unconjugated Bilirubinemia
-milder than Type 1; jaundice

Phenobarbitol
Explain Physiologic Jaundice of Neonates
Transient Unconjugated Hyperbilirubinemia due to immaturity of the liver
-due to increased Bilirubin production & a relative deficiency of Glucuronyl Transferase in the immature liver
What is the cause of Dubin-Johnson Syndrome?
Autosomal recessive condition resulting from defective bilirubin TRANSPORT protein out of the liver
What are the clinical manifestations of Dubin-Johnson Syndrome?
1. Intermittent Jaundice
2. RUQ & epigastric pain
3. CONJUGATED HYPERBILIRUBINEMIA
4. mildly elevated LFT's
5. BLACK LIVER
Conjugated Hyperbilirubinemia + Black Liver
Dubin-Johnson Syndrome
Syndrome that is similar to Dubin-Johnson Syndrome but abnormal black pigment is not present
Rotor Syndrome
Dubin-Johnson Syndrome = causes Black Liver
What Hereditary Hyperbilirubinemia caused this?
After what % of Liver functional capacity is lost do symptoms of Hepatic Failure appear?
80-90%
What is the difference between Acute & Chronic Liver Failure?
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
Describe "Hepatorenal Syndrome"
-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
Describe Hepatic Encephalopathy
-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
What are the signs/symptoms of Hepatorenal Syndrome?
1. Oliguria
2. increased BUN
3. increased Creatinie
4. concentrated Urine & Hyperosmolar
5. unresponsive to Diuretic therapy
Define Cirrhosis
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
List 7 causes of Cirrhosis
1. Alcohol
2. Viral Hepatitis
3. Biliary diseases
4. Hemochromatosis
5. AAT deficiency
6. Wilson Disease
7. Cryptogenic cirrhosis (15%)
What are the clinical manifestations of Cirrhosis?
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
What are the lab findings in Cirrhosis?
1. prolonged PT
2. Hypoalbuminemia
3. Hyperbilirubinemia
4. increased ALT, AST, ALP
What is a complication of Cirrhosis?
Liver Cell Carcinoma = Hepatocellular Carcinoma
What is the mechanism of fibrosis in Cirrhosis?
produced by Ito cells (Stellate cells)
Cirrhosis
What is this picture showing?
Cirrhosis
-nodularity
What is this picture showing?
Cirrhosis
-nodularity
What is this picture showing?
What is the definition of Ascites?
Accumulation of fluid in the abdominal cavity
When is Ascites detectable?
> 500 ml
Discuss the pathogenesis of Ascites in Cirrhosis
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
What does it mean if PMN's are found in the serous fluid in Ascites? What if RBC's are found?
PMN = infection

RBC = tumor (hepatocellular carcinoma, ovarian CA, pancreas)
List the virus families associated with each of the Hepatitis Viruses
A = PicornAvirus
B = Hepadnavirus
C = Flavivirus
E = Calicivirus
Aside from Hepatotrophic viruses, what other viruses can cause Viral Hepatitis?
Yellow Fever

Epstein-Barr virus

Herpes Simplex

Cytomegalovirus
What Viral Hepatitis' are transmitted fecal-orally?
A & E
What Viral Hepatitis' are blood-borne viruses?
B, C, D
Hepatitis virus that causes a "ground-glass" appearance
HBV
Hepatitis viruses associated with Hepatocellular Carcinoma
B & C
What are the microscopid changes associated with Acute Viral Hepatitis?
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
Acute Hepatitis
What is seen here?
Acute Viral Hepatitis
-lobular disarray
-hepatocyte swelling
-apoptotic hepatocytes
-lympocytes in portal tracts & lobule
What is seen here?
What are the microscopid finding in Chronic Hepatitis?
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
Chronic Active Hepatitis = inflammation has spilled into the Parenchyma
What is seen here?
Chronic Persistent Hepatitis = confined to the Portal Tracts
What is this?
Chronic Hepatitis
-Lymphocyte aggregates
What is seen here?
Chronic Active Hepatitis
-Interface Hepatitis = Piecemeal necrosis of LImiting plate
What is seen here?
Define Fulminant Hepatitis
Hepatic Failure with Encephalopathy within 2-3 weeks of onset
What causes Fulminant Hepatitis 60% of the time? 30%?

List 4 rare causes
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
Fulminant Hepatitis
What is seen here?
Describe Bacterial infections of the liver via the Arterial route
Bacteria reach the liver via the Hepatic Artery during SEPSIS or in SEPTIC THROMBOEMBOLI in bacterial endocarditis
-Streptococcus
-Staphylococcus aureus
-Salmonella
Describe Bacterial infections of the liver via Portal Vein route
from Appendicitis, Diverticulosis, or Mucosal abscesses
-E. coli
-Enteric saprophytes
Describe Bacterial infections of the liver via the Ascending Biliary route
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
Describe Direct Invasion of the liver of Bacterial infections
-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
Bacterial infection of the liver
What is seen here?
Protozoa that causes "flask-shaped" ulcers in the Colon & right lobe liver abscesses
Entamoeba Histolytica
Trematode (fluke) that is contracted by ingesting fish; causes inflammation of the Biliary Tract & may cause Cholangiocarcinoma
Clonorchis sinensis
Trematode with snails as their host, cercariae penetrate skin of humans; causes granulomas, fibrosis, & inflammation of the Portal Vein
Schistosoma mansoni & japonicum
This tapeworm is ingested from the excreta of Dogs & Sheep; causes cysts in the liver; rupture of cysts can cause anaphylaxis
Echinococcis granulosus
What drug induces Fatty Change?
Tetracycline
What drug induces Centrolobular Necrosis?
Acetaminophen (Tylenol)
What drug causes massive necrosis of the liver?
Halothane
What drugs cause Hepatitis-like changes in the liver?
Isoniazid

Methyldopa
What drug causes Fibrosis of the liver?
Methotrexate
What 2 drugs cause Cholestasis?
Chlorpromazine = anti-emetic

Oral Contraceptives
What drugs cause Veno-occlusive disease of the liver?
Cytotoxic drugs

Pyrrolizidine
What drugs cause Thrombosis (Portal or Hepatic vein)?
Oral Contraceptives

Estrogens

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

Oral Contraceptives
List the types of liver disease associated with Alcohol
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
Explain why Fatty Change occurs with alcohol consumption
Substrates of alcohol metabolism are used to synthesize liver Triglyceride (glycerol + 3 fatty acids)
What are the microscopic changes associated with Alcoholic Hepatitis?
1. Hepatocyte swelling
2. MALLORY BODIES
3. EVENTUAL FIBROSIS AROUND THE CENTRAL VEIN (TERMINAL HEPATIC VEIN)
Steatosis due to alcohol consumption

Tender hepatomegaly WITHOUT fever or neutrophilic leukocytosis
What is this?

What would be the clinical manifestation?
Alcoholic Hepatitis
-Mallory Hyaline
-Neutrophils
-Necrosis of hepatocytes
-collagen deposition
-Fatty change
What is the cause of this?
Alcoholic hepatitis
-hepatocyte swelling
-Mallory Hyaline
-Neutrophilic infiltration of hepatocytes
What is shown here?
Cirrhosis
-"hobnail" liver appearance
What is this showing?
Cirrhosis

Alcohol

Acetaldehyde stimulates Ito cell to produce fibrous tissue
What is seen here? What is the most common cause? What is the mechanism?