Lec 22 Autoimmune

Question 1

Who gets primary biliary cirrhosis?

Answer 1

• women more than men

- mean age 50 yo

Question 2

What is pathogenesis of primary biliary cirrhosis?

Answer 2

• have external trigger [environment or infectious] and underlying susceptibility
• causes autoimmune attack and destriuction of intralobular bile ducts

Question 3

What diseases are associated with primary biliary cirrhosis?

Answer 3

• celiac
• sjogren
• rheumatoid arthritis
• thyroid
• scleroderma

Question 4

What lab values can you use to diagnose biliary cirrhosis?

Answer 4

• high alk phos/GGTP
• high cholesterol
• high conjugated bilirubin
• anti-mitochondiral antibody [AMA]
• high serum IgM

Question 5

What disease is associated with anti mitochondrial antibody?

Answer 5

primary biliary cirrhosis

Question 6

What do you see on histology in primary biliary cirrhosis?

Answer 6

florid duct lesion = lymphocytic infiltration and attack of bile duct

Question 7

What are symptoms of primary biliary cirrhosis?

Answer 7

• pruritis
• jaundice
• dark urine
• light stools
• hepatosplenomegaly

Question 8

What is prognosis of primary biliary cirrhosis?

Answer 8

slowly progressive

good prognosis

Question 9

Who gets primary sclerosing cholangitis?

Answer 9

• men

- onset 24-25 yo

Question 10

What is pathogenesis of primary sclerosing cholangitis?

Answer 10

• unknown cause

- may be hypersentivity; or immune mediated; or assocaited wtih infection

Question 11

How does primary sclerosing cholangtis present?

Answer 11

• elevation of LFTs
• pruritis
• cholangitis –> fever, chills, RUQ pain, jaundice

Question 12

What labs do you see in PSC?

Answer 12

• 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]

Question 13

What histo/imaging findings with primary sclerosing cholangtiis?

Answer 13

• onion skin fibrosis around bile duct

- alternating strictures and dilations with beading of intra and extra hepatic bile ducts

Question 14

What diseases associated with primary sclerosing cholangitis?

Answer 14

IBD [ulcerative colitis > crohns]

cholangiocarcinoma

Question 15

What are 2 complications of primary sclerosing cholangitis?

Answer 15

secondary biliary cirrhosis
cholangiocarcinoma
colon cancer risk increased 10x

Question 16

What is treatment for primary sclerosing cholangitis?

Answer 16

• dilation of dominant stricture

- ursodeoxycholic acid to increase bile flow

Question 17

Who gets autoimmune hepatitis?

Answer 17

adolescent or post menopausal women

Question 18

How does autoimmune hepatitis present?

Answer 18

can be acute: RUQ pain, fever, chills, jaundice

or can be insidious with abnormal LFTs, fatigue, aches

Question 19

What are diagnostic criteria for autoimmune hepatitis?

Answer 19

• 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

Question 20

What is treatment of autoimmune hepatitis?

Answer 20

long term immunosuppression: prednisone

Question 21

What is prognosis of autoimmune hepatitis?

Answer 21

75% mortality if untreated; good pronosis if treated

Question 22

What is the target for autoimmune hepatitis?

Answer 22

hepatocytes

Question 23

What is genetics of wilson disease?

Answer 23

• autosomal recessive

- mutation in chr 13 ATP7B gene responsible for excretion of copper into the bile

Question 24

What is pathogenesis of wilson disease?

Answer 24

• have accumulation of copper in hepatocytes –> causes mitochondrial damage and lipid oxidation –> hepatocellular death and release of unbound copper into blood

Question 25

Where does copper deposit in wilsons?

Answer 25

- brain - kidneys - cornea

Question 26

What stain to test for copper deposition in the liver?

Answer 26

rhodamine stain

Question 27

What do you see in liver in wilson disease?

Answer 27

- elevated ALT/AST - chronic hepatitis - liver failure - cirrhosis - can lead to hepatocellular carcinoma

Question 28

What neuro signs do you see in wilsons?

Answer 28

progressive movement disorder - mildtremor, speech/writing problems, basal ganglia degerneration leading to parkinsonian symptoms - dimentia, dyskinesia

Question 29

What heme signs of wilsons?

Answer 29

hemolytic anemia

Question 30

How do you diagnose wilson disease?

Answer 30

- kayser fleisher rings = copper deposited in cornea - urinary copper - low serum ceruloplasmin - liver biopsy containing copper

Question 31

What is treatment for wilson disease?

Answer 31

- copper chelator = penicillamine - zinc = blocks intestinal copper absorption - low copper diet

Question 32

What foods should you avoid in wilsons disease?

Answer 32

mushrooms, nuts, chocolate, dried fruit, liver, shellfish

Question 33

What is genetic cause of hemochromatosis? What HLA type associated?

Answer 33

- mutation in C282Y or H63D of HFE gene on chr 6 | - associated with HLA-A3

Question 34

What is pathogenesis of hemochromatosis?

Answer 34

- mutation in HFE gene --> impaired iron sensing and absorption have excess iron absorbed from GI tract

Question 35

Where does iron deposit in hemochromatosis?

Answer 35

- liver - heart - pituiary and thyroid - pancreas - joints - gonad

Question 36

What is action of HFE normally?

Answer 36

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

Question 37

What levl of hepcidin in hemochromatosis?

Answer 37

low hepcidin b/c of defect in HFE

Question 38

What is classic triad of hemochromatosis?

Answer 38

- cirrhosis - bronze skin - diabetes

Question 39

What lab levels in hemochromatosis?

Answer 39

- high fasting transferrin sat > 50% - ferritin > 1000 - high irin - low TIBC