Lec 22 Autoimmune Flashcards
Who gets primary biliary cirrhosis?
- women more than men
- mean age 50 yo
What is pathogenesis of primary biliary cirrhosis?
- have external trigger [environment or infectious] and underlying susceptibility
- causes autoimmune attack and destriuction of intralobular bile ducts
What diseases are associated with primary biliary cirrhosis?
- celiac
- sjogren
- rheumatoid arthritis
- thyroid
- scleroderma
What lab values can you use to diagnose biliary cirrhosis?
- high alk phos/GGTP
- high cholesterol
- high conjugated bilirubin
- anti-mitochondiral antibody [AMA]
- high serum IgM
What disease is associated with anti mitochondrial antibody?
primary biliary cirrhosis
What do you see on histology in primary biliary cirrhosis?
florid duct lesion = lymphocytic infiltration and attack of bile duct
What are symptoms of primary biliary cirrhosis?
- pruritis
- jaundice
- dark urine
- light stools
- hepatosplenomegaly
What is prognosis of primary biliary cirrhosis?
slowly progressive
good prognosis
Who gets primary sclerosing cholangitis?
- men
- onset 24-25 yo
What is pathogenesis of primary sclerosing cholangitis?
- unknown cause
- may be hypersentivity; or immune mediated; or assocaited wtih infection
How does primary sclerosing cholangtis present?
- elevation of LFTs
- pruritis
- cholangitis –> fever, chills, RUQ pain, jaundice
What labs do you see in PSC?
- high alk phos/GTP
- high conjugated bilirubin
- high cholesterol
- no specific antibody tests –> can be pANCA [anti neutrophil cytoplasmic antibody] OR anti-SMA [anti-smooth muscle] or ANA [anti nuclear]
What histo/imaging findings with primary sclerosing cholangtiis?
- onion skin fibrosis around bile duct
- alternating strictures and dilations with beading of intra and extra hepatic bile ducts
What diseases associated with primary sclerosing cholangitis?
IBD [ulcerative colitis > crohns]
cholangiocarcinoma
What are 2 complications of primary sclerosing cholangitis?
secondary biliary cirrhosis
cholangiocarcinoma
colon cancer risk increased 10x
What is treatment for primary sclerosing cholangitis?
- dilation of dominant stricture
- ursodeoxycholic acid to increase bile flow
Who gets autoimmune hepatitis?
adolescent or post menopausal women
How does autoimmune hepatitis present?
can be acute: RUQ pain, fever, chills, jaundice
or can be insidious with abnormal LFTs, fatigue, aches
What are diagnostic criteria for autoimmune hepatitis?
- positive antinuclear antibody [ANA] or smooth muscle antibody [SMA] or LKM1 [liver kidney muscle antibody]
- high total IgG
- high ALT/AST
- liver biopsy to rule out other causes
What is treatment of autoimmune hepatitis?
long term immunosuppression: prednisone
What is prognosis of autoimmune hepatitis?
75% mortality if untreated; good pronosis if treated
What is the target for autoimmune hepatitis?
hepatocytes
What is genetics of wilson disease?
- autosomal recessive
- mutation in chr 13 ATP7B gene responsible for excretion of copper into the bile
What is pathogenesis of wilson disease?
- have accumulation of copper in hepatocytes –> causes mitochondrial damage and lipid oxidation –> hepatocellular death and release of unbound copper into blood
Where does copper deposit in wilsons?
- brain
- kidneys
- cornea
What stain to test for copper deposition in the liver?
rhodamine stain
What do you see in liver in wilson disease?
- elevated ALT/AST
- chronic hepatitis
- liver failure
- cirrhosis
- can lead to hepatocellular carcinoma
What neuro signs do you see in wilsons?
progressive movement disorder
- mildtremor, speech/writing problems, basal ganglia degerneration leading to parkinsonian symptoms
- dimentia, dyskinesia
What heme signs of wilsons?
hemolytic anemia
How do you diagnose wilson disease?
- kayser fleisher rings = copper deposited in cornea
- urinary copper
- low serum ceruloplasmin
- liver biopsy containing copper
What is treatment for wilson disease?
- copper chelator = penicillamine
- zinc = blocks intestinal copper absorption
- low copper diet
What foods should you avoid in wilsons disease?
mushrooms, nuts, chocolate, dried fruit, liver, shellfish
What is genetic cause of hemochromatosis? What HLA type associated?
- mutation in C282Y or H63D of HFE gene on chr 6
- associated with HLA-A3
What is pathogenesis of hemochromatosis?
- mutation in HFE gene –> impaired iron sensing and absorption
have excess iron absorbed from GI tract
Where does iron deposit in hemochromatosis?
- liver
- heart
- pituiary and thyroid
- pancreas
- joints
- gonad
What is action of HFE normally?
liver cells sense plasma iron and absorb iron via HFE
HFE regulates synthesis of hepcidin
hepcidin inhibits iron secretion by duodenum and tells macrophages of GI to stop taking up iron
What levl of hepcidin in hemochromatosis?
low hepcidin b/c of defect in HFE
What is classic triad of hemochromatosis?
- cirrhosis
- bronze skin
- diabetes
What lab levels in hemochromatosis?
- high fasting transferrin sat > 50%
- ferritin > 1000
- high irin
- low TIBC
