EXAM #2: REVIEW Flashcards
What is causing the dark urine seen in patients with extravascular hemolysis?
Urobilinogen
What labs differentiate Dubin-Johnson Syndrome and Rotor Syndrome?
Dubin-Johnson=
- Normal urine coproporphyrinogen
- Elevated isomer I
Rotor Syndrome=
- Elevated urine coproporphyrinogen
- Normal isomer I
What are the five normal components of bile?
1) Bile salts
2) Bilirubin
3) Bicarbonate
4) Cholesterol
5) Lecithin
What defect is seen in PFIC-1?
Defect in the canalicular ATPase
What defect is seen in PFIC-2?
Defect in the Bile Salt Export Pump
What defect is seen in PFIC-3?
Defect in the MDR-3 transporter, impairing phosphatidylcholine transport
List five clinical features of the PFICs.
1) Cholestasis
2) Fat malabsorption
3) Fat soluble vitamin deficiency
4) Osteopenia
5) Liver failure
List seven clinical manifestations of bile duct obstruction.
1) Jaundice
2) Steatorrhea
3) Dark urine
4) Xanthomas
5) Pruritis
6) Osteoporosis
7) Bleeding
List the lab findings in bile duct obstruction.
1) Elevated conjugated bilirubin
2) Decreased urine urobilinogen
3) Elevated: ALP, 5’-NT, and GGT
4) Hyperlipidemia
What diseases is macronodular cirrhosis associated with?
Viral hepatitis
Alpha-1 antitrypsin
Wilson’s Disease
What are the three general manifestations of portal HTN?
1) Ascites
2) Congestive splenomegaly
3) Portosystemic shunts
What is acute liver failure?
Liver failure that occurs within 4 weeks of initial symptoms of liver dysfunction
List four clinical signs of hepatorenal syndrome.
1) Oliguria/anuria
2) Increased BUN/Creatinine
3) Low urinary Na+
4) Normal urinary sediment
What are the extrahepatic manifestations of Hepatitis C?
1) Cryoglobulinemia
2) Thyroiditis
3) Glomerulonephritis
4) Thrombocytopenia
What four factors will increase the likelihood of HCV infection leading to HCC?
1) Alcoholism
2) Cirrhosis
3) Male
4) Old age
What are the microscopic features of acute viral hepatitis?
- Swelling of hepatocytes
- Cholestasis
- Lobular disarray
What are the microscopic features of chronic viral hepatitis?
- Piecemeal necrosis
- Bridging fibrosis
- Nodular cirrhosis
What microscopic feature is associated with HCV infection?
Lymphoid aggregates in portal tracts
List the clinical manifestations of acute hepatitis.
- Mixed jaundice
- Dark urine
- Fever
- Malaise
- Nausea
- Elevated liver enzymes
I.e. flu-like illness with mixed jaundice, dark urine, and elevated liver enzymes.
What is an alternate name for Primary Biliary Cirrhosis?
Granulomatous cholangitis
What antibody is associated with PBC?
Anti-mitochondrial antibody (AMA)
List all of the lab findings associated with PBC.
1) Elevated antibodies: AMA, anti-M2, and anti PDH-E2
2) Elevated IgM
3) Elevated ALP/ 5’-NT, and GGT
4) Elevated cholesterol
What are the lab findings associated with PSC?
1) Elevated transaminases
2) Elevated ALP, 5’NT, and GGT
What antibody is most specific to PSC?
p-ANCA
What antibodies are specific to autoimmune hepatitis?
ANA
ASMA
ALKM
What are the features of Type I autoimmune hepatitis?
- Most common
- 10 y/o to elderly affected
- SMA and ANA positive
What are the features of Type II autoimmune hepatitis?
- Less common
- 2-14 y/o effected
- ALKM antibody
- Poor prognosis
What is Type III autoimmune hepatitis?
- Less common
- Effects 30-50 year olds
- Anti-SLA positive
What type of liver injury is seen with Tetracycline?
Microsteatosis
What type of liver injury is seen with Amiodarone?
Fibrosis
What type of liver injury is seen with steroids?
Cholestasis
What are Mallory Bodies?
Damaged intermediate filaments or “alcoholic hyaline” seen in alcoholic hepatitis
What are the clinical features of Alcoholic Steatohepatitis?
1) Fever
2) Leukocytosis
3) Jaundice
4) AST/ elevatopm
What are the four most common causes of death in chronic alcoholism?
1) Hepatic coma
2) Massive GI hemorrhage (esophageal varice)
3) Infection
4) Hepatorenal syndrome
What can cause Nonalcoholic Steatohepatitis?
1) Metabolic Syndrome
2) Drug hepatotoxicity
3) Pregnancy
What two drugs are notorious for inducing Steatohepatitis?
Tamoxifen
Nifedipine
Name four causes of a hepatic infarct. How does a liver infarct present?
1) Liver transplant
2) Chemoembolism–chemo delivery into the liver
3) Polyarteritis nodosium
4) Surgery
Presents with RUQ pain, fever, and jaundice.
What causes ischemic hepatitis/ shock liver/ hypoxic hepatitis?
This is when there is occlusion of the HEPATIC ARTERY (branch of the celiac trunk)
1) Left sided heart failure
2) Heart surgery
3) Shock
What are the clinical manifestations of ischemic hepatitis?
- Centrilobular coagulative necrosis
- AST/ALT elevation
- Jaundice
Not enough oxygenated blood is feeding the liver via the hepatic artery
What are the extra-hepatic etiologies of Portal Vein Thrombosis?
This is an issue with the PORTAL VEIN OUTSIDE OF THE LIVER:
1) Abdominal infection
- Appendicitis
- Diverticulitis
- Pancreatitis
2) Hypercoaguability
3) Surgery
What are the intrahepatic etiologies of Portal Vein Thrombosis?
These are all problems with the BRANCHES OF THE PORTAL VEIN, in the liver i.e. intra-hepatic:
1) Cirrhosis
2) Malignancy
3) Stasis
4) Pregnancy
5) Idiopathic
Note that this will result in INFARCTS OF ZAHN
What are the clinical manifestations of portal vein thrombosis?
1) Abdominal pain
2) Portal HTN causing:
- Esophageal varices
- Splenomegaly
- Ascites
3) Bowel Infarction
What causes Hepatic Vein Obstruction?
1) Right heart failure causing backflow of blood into the liver via the HEPATIC VEIN
2) Budd-Chiari Syndrome
What causes Hepatic Passive Congestion?
1) Right heart failure
2) Constrictive pericarditis
3) Congenital heart disease
What is Budd-Chiari Syndrome?
Thrombosis of the hepatic vein or IVC–prevents the liver from draining
What are the etiologies of Budd-Chiari Syndrome?
1) HCC
2) Abdominal cancer
3) Myeloproliferative disorder
4) PNH
5) Hypercoagulability
6) Pregnancy
7) Contraceptives
What are the clinical features of acute Budd-Chiari Syndrome?
- Abdominal pain
- Hepatomegaly
- Ascites
- Jaundice
- Liver failure
What are the clinical features of chronic Budd-Chiari Syndrome?
- Portal HTN
- Cirrhosis
- Obliterative Hepatocavopathy
What is an Obliterative Hepatocavopathy?
IVC obstruction at its hepatic portion caused by the development of fibromembranous webs causing:
- Edema of the abdominal wall
- Tortuous abdominal venous pattern
- Edema of the legs
*Note that this is endemic in Nepal and is suspected to have an infectious etiology
What is Veno-Occlusive Disease of the liver?
Complication following bone marrow transplant or ingestion of plant alkaloids (Jamaican)
- Vasculitis causes sinusoid obstruction
What is the link between transferrin, hepcidin, and iron absorption?
- HFE gene codes for a membrane product that regulates Hepcidin
- Hepcidin normally prevents iron absorption from the gut by breaking down ferroportin
- HFE mutation= decreased hepcidin and increased iron absorption
The membrane product coded for by HFE alters the relationship between transferrin receptors and transferrin; the liver thinks the body needs more iron; consequently Hepcidin goes down
What pathologic change is seen in early Hemochromatosis? Late?
Early= Fe++ deposition in periportal hepatocytes
Late= Fe++ deposition in kupffer cells, bile duct epithelium, and fibrous septa
Really, iron deposition occurs all over the body
List six complications of Hemochromatosis.
1) DM
2) Cardiomyopathy
3) Hypogonadism
4) Skin pigmentation changes (i.e. gray color)
5) Pseudo-gout
6) Cirrhosis
*Note that these complications are seen at roughly 40 years-old.
In secondary hemochromatosis, where is iron loaded?
Kupffer cells i.e. liver macrophages
List five roles that copper plays in the body.
1) Pigment formation
2) Neurotransmitter production
3) Peptide formation
4) Connective tissue biosynthesis
5) Antioxidant defense
What organs are most affected in Wilson’s Disease?
Brain, liver, and kidneys
What gene is mutated in Wilson’s Disease? What is the result?
ATP7B copper transporter
*Copper cannot be excreted into bile canaliculi
List the clinical manifestations of Wilson’s Disease.
1) Degeneration of the basal ganglia–> PD-like syndrome–adults
2) Hepatitis–kids
3) Cirrhosis
What is the normal function of alpha-1 antitrypsin?
This is an enzyme that prevents action of trypsin/proteases
What causes the hepatic symptoms of alpha-1 antitrypsin disease?
Misfolded/nonfunctional PiZ accumulates in hepatocytes and can’t get out of the liver to do its job
*PiZZ genotype
How does alpha-1 antitrypsin deficiency present in kids?Adults?
Kids= Hepatitis/ cholestasis Adults= Chronic hepatitis/ cirrhosis
What is Focal Nodular Hyperplasia of the liver?
- Benign tumor of the liver
- More common in women
- Asymptomatic–does NOT require treatment
What is the morphological appearance of Focal Nodular Hyperplasia?
Solitary mass on the liver with a central scar
What is Nodular Regenerative Hyperplasia?
Diffuse nodular transformation of the liver WITHOUT fibrosis
Think of regeneration gone awry*
What is Nodular Regenerative Hyperplasia commonly confused with?
Cirrhosis
Note that on Trichrome stain, you don’t see the outline of the nodules like you do with cirrhosis*
What is the most common complication of Nodular Regenerative Hyperplasia?
Noncirrhotic portal hypertension
What is the surgical treatment for Nodular Regenerative Hyperplasia?
Transjugular Intrahepatic Portal Shunt i.e. TIPS
What is Nodular Regenerative Hyperplasia associated with?
Transplantation
Chemotherapy
Vasculitis
What is the most common benign hepatic tumor?
Hemangioma
What patient population are Hemangiomas more common in?
Women on oral contraceptives
What do you need to remember about the diagnosis of a Hemangioma?
Do NOT biopsy; it will hemorrhage
What is a Liver Cell Adenoma?
Glandular tumor of the liver
What patient populations are Liver Cell Adenomas more common in?
- Young women on oral contraceptives
- GSD (I and III)
What is the most feared complication of a Liver Cell Adenoma?
Rupture during pregnancy
What is the most common primary malignant liver tumor?
Hepatocellular Carcinoma
Geographically, where is HCC most common?
Asia
Africa
What is the biggest risk factor for HCC?
Cirrhosis and the other disorders that lead to cirrhosis
List the risk factors for HCC.
1) Chronic hepatitis (HBV and HCV)
2) Cirrhosis
- Alcohol
- NAFLD
- Hemochromatosis
- Wilson’s
- A1AT
3) Aflatoxin and Tyrosinemia
What genetic change is associated with progression to HCC?
p53
Note that Aspergillus/ aflatoxin causes p53 mutations
How does HBV lead to HCC?
- HBV is dsDNA virus
- Integrates into host
- Activates proto-oncogenes
What are the clinical manifestations of HCC?
1) Painful hepatomegaly
2) Abdominal mass
3) Weight loss
4) Portal/hepatic vein thrombosis
5) Hemorrhagic ascites
6) Hepatic Failure
7) Massive bleeding
What lab elevation is associated with HCC?
AFP greater than 1,000
What subtype of HCC has the best prognosis?
Fibrolamellar HCC –thick fibrous bands within the tumors
What is the primary malignant tumor of the bile duct epithelium?
Cholangiocarcinoma
What are the risk factors for Cholangiocarcinoma?
1) Primary Sclerosing Cholangitis
2) Thorotrast
3) Caroli Disease
4) Liver Flukes
What is the most common primary malignant hepatic tumor in children?
Hepatoblastoma
What lab is associated with Hepatoblastoma?
Very elevated AFP
What is an angiosarcoma?
This is a cancer of the inner lining of blood vessels associated with:
- Thorotrast
- Steroids
*V. poor prognosis
What is the most common malignant tumor of the liver?
Metastases
Where are the primary tumors of liver metastases commonly located?
- GI
- Breast
- Lung
- Pancreas
- Melanoma
