Lecture 23: Autoimmune/Metabolic Liver Diseases Flashcards
Primary biliary cirrhosis (PBC): gender; pathogenesis
F:M 9:1; susceptibility –> trigger –> immune mediated –> bile duct injury, fibrosis, cirrhosis
PBC affects mostly the…
Bile duct cell
PBC: external triggers
Unknown, maybe env’t (chemicals), or infectious
PBC: dx (tests and name)
Elevated Alk Phos/GGTP, anti-mitochondrial Abs, elevated total serum IgM, “Florid duct lesion”
PBC: histology
Florid duct lesion = inflammation around bile duct –> obliterated bile ducts –> cirrhosis
PBC: presentation
Starts w/ abnormal liver biochemistries, may have pruritis (bile salts under skin), fatigue, and eventually signs/symptoms of liver disease (xanthomas, butterfly hyperpigmentation)
PBC: survival hinges on…
Cirrhosis development (survival drops off)
Autoimmune patients tend to do how with transplants?
Fairly well
Primary sclerosing cholangitis (PSC): gender, pathogenesis, presentation
M:F 3:1, pathogenesis is UNKNOWN (immune perhaps?, infection), elevated cholestatic tests with cholangitis sx (fever, chills, RUQ pain, jaundice)
Are there secondary causes of sclerosing cholangitis?
Yes! due to a variety of causes
PSC: long-term complication
Cholangicarcinoma/cirrhosis
PSC: dx (tests, imaging, and term)
Elevated Alk Phos/GGTP, 75% w/ pANCA, effects intra AND extrahepatic duct sclerosis = ONION SKIN FIBROSIS with strictures in ducts on imaging
pANCA spelled out
Perinuclear anti-neutrophil cytoplasmic antibodies
PSC: histo
Onion skin and loss of bile ducts in triad
Majority of people with PSC have…
IBD
PSC: complications
Cholangitis, end stage liver disease, cholangiocarcinoma (10% risk), higher risk of colon cancer
PSC: tx
Resection, dilate strictures in ducts, medication (ursodeoxycholic acid –> maybe not good), transplant
Autoimmune hepatitis (AiH): gender, age, presentation
F:M 8:1, young and perimenopausal, can be acute hepatitis or insidious
AiH: dx
DIAGNOSIS OF EXCLUSION with some serologies: abnormal serum aminotransferase, high gamma globulin (IgG), and other positive serologies (SMA/ANA), with liver biopsy to rule out other lesions
AiH: tx
Immunosuppression (steroids)
Wilson Disease: inheritance, describe, gene
Autosomal recessive disease of copper metabolism due to ATP7B on chrom 13
What does ATP7B do?
Encodes for a copper transporting ATPase needed to excrete copper in bile and blood
Wilson Disease: pathophys
Accumulation of copper –> hepatocyte death –> Cu accum in brain, kidneys, cornea
Wilson Disease: histo
Rhodamine stain –> Cu deposition
Copper metabolism
Copper absorbed by SI and transported to liver; hepatocytes incorporate copper into apocerloplasmin to produce ceruplasmin which gets secreted into blood; also secretes Cu in bile
Copper metabolism: Wilson and dx test
Ceruloplasmin not made (low in serum = TEST) AND no secretion in bile = build-up in hepatocyte
Wilson disease: presentation
Hepatic (occasional FHF, hepatitis, cirrhosis), neurologic (PD), hematologic (hemolytic anemia), psychiatric (PSYCHOSIS)
Wilson disease: characteristic finding
Kayser Fleischer Ring
Wilson disease: dx
Low serum ceruplasmin, Kayser Fleisher ring, biopsy, genetic testing
Wilson disease: tx
Chelating agents, oral Zinc (blocks intestinal copper), avoid mushrooms, nuts, dried fruit, transplant
Hereditary Hemochromatosis: two types
HFE-related and non HFE related
Hereditary hemochromatosis HFE: inheritance, rare?, presentation, gene
AR, fairly common, presents late, HFE gene on chrom 6, generally due to biallele C282Y mutation
HFE HHC: pathogenesis
Mutation causes altered HFE protein –> impaired iron sensing in GI tract –> excess iron absorption –> deposition in liver, heart, pituitary, thyroid, pancreas, gonad
Iron homeostasis
Dietary iron absorbed by duodenum AND secreted by macrophages –> blood via ferroportin , iron circulates bound to transferrin, liver senses plasmin iron and absorbs it via HFE and turns on hepcidin protein which is secreted into circulation and inhibits ferroportin via duodenum and secretion via macrophages
Iron in hemochromatosis
Defective HFE = less hepcidin production so more iron is absorbed by gut and secreted by macrophages –> more iron stored by gut and transported to other organs
HFE HHC: triad
Cirrhosis, bronze skin, diabetes (= Bronze Diabetes)
HFE HHC: dx (mention stain)
Fasting transferrin saturation over 50% or high ferritin, gene testing, MRI with liver quantification, biopsy (Prussian blue stain)
HFE HHC: tx
Phlebotomize blood to deplete iron stores (note: women require less due to menstruaton)
HFE HHC: survival
If phlebotomy is initiated BEFORE cirrhosis, they survive as normal population
