11.5 - Liver - Cirrhosis & Tumors Flashcards
What cell mediates the fibrosis in cirrhosis? What factor?
- Stellate cells (lie beneath endothelial cells that line the sinusoids)
- TGF-beta
clinical feature of cirrhosis?
-Portal HTN =ascites =congestive splenomegaly and hypersplenism =portosystemic shunts =hepatorenal system
Result decreased detox due to cirrhosis?
- mental status changes (ammonia). asterixis, coma
- Due to excess estrogen: gynecomastia, spider angiomas, and palmar erythema
- jaundice
Results of decreased protein synthesis?
- hypoalbuminemia
- coagulogpathy (use PT and PTT to measure cirrhosis)
Alcohol liver diseases: manifestations:
1) fatty liver: accumulation of fat in liver - resolves with abstinence - greasy-shiny-yellow liver on gross examination
2) alcoholic hepatitis: chemical injury to hepatocytes DUE TO ACETALDEHYDE (binge drinking) -swelling and ballooning of hepatocyte
- mallory bodies=damaged intermediate filaments (hyaline?)
3) cirrhosis - chronic alcohol induced liver damage
Presentation of alcoholic liver disease?
- painful hepatomegaly
- elevated AST and ALT (*AST>ALT in 2:1 ratio)
S.T for scotch and tonic
Non-alcoholic fatty liver disease
- what is it?
- How develops?
- common association?
- Faty change, hepatitis &/or cirrhosis
- develops without exposure to alcohol or other known insult
- usually due to metabolic syndrome/obesity
non-alcoholic fatty liver disease
-Diagnostic finding that is golden?
Diagnosis of exclusion: ALT>AST!
Why is AST higher in alcohol related damage?
- AST is found throughout the body and especially mitochondria
- alcohol is especially toxic to mitochondria = more AST
(aLt - L for Liver - is more liver specific than AST)
hemochromatosis
- what is it?
- how is damage caused?
- excess body iron leading to deposition in tissues and organ damage
- damage is mediated by generation of free radicals (FENTEN REATION)
Hemosiderosis vs Hemochromatosis
Sid=just accumulation in tissues
chrom=actual damage occuring
Secondary hemochromatosis causes:
THALAS
- T=transfusions
- H=hemochromatosis/neonatal
- A=alimentary - from diet
- L=liver disease
- A=anemia
- S=sideroblastic anemia
Primary hemochromatosis is due to?
- mutations in HFR gene
- C282Y and H63D
- Mechanism for iron uptake:
- Mechanism for hemochromatosis?
- GI enterocytes pretty much take up all iron from diet
- they only release it into the blood when there is a need.. otherwise they hold onto it (KEY REGULATORY MECH FOR IRON)
-so in hemochromatosis this regulatory mech isnt working (HFE gene mutation) and the enterocytes pretty much dump all the iron into the blood
Presentation of hemochromatosis:
Late adulthood - iron takes time to accumulate in body
Complications of hemochromatosis:
Classic triad:
- cirrhosis
- secondary diabetes mellitus
- bronze skin
Others:
- cardiac arrhythmia
- gonadal dysfunction
Hemochromatosis - labs
- INC ferritin
- DEC TIBC
- INC serum iron
- INC % saturation
Biopsy of hemochromatosis liver:
- Brown pigment in hepatocytes
- prussian blue stain makes iron blue
Tx for hemochromatosis?
Inc risk for?
- phlebotomy
- HCC risk
Wilsons disease
- how do you get this disease?
- what ahppens?
- autosomal recessive defect in ATP7B gene which is ATPmediated hypatocyte copper transport
- lack of copper transport into bile and lack of copper incorporation into ceruloplasmin
Issues with Wilsons disease?
- copper builds up in hepatocytes –> leaks into serum –> deposits into tissues
- Copper produces free radicals = tissue damage
When does Wilsons present?
Symtpoms in patient?
Inc risk?
TX?
-childhood
- neurologic manifestations
- Kayser-Fleisher rings in cornea
- HCC risk increased
- Tx with D-penicillamine (copper chelating agent
Wilsons disease- LABS
- INC urinary copper
- DEC serum ceruloplasmin
- INC copper deposit on liver biopsy
Primary biliary cirrhosis (PBC)
- what is it?
- classic patient?
- autoimmune granulomatous destruction of intrahepatic bile ducts (SMALL DUCTS)
- middle aged women most common
