Lecture 23: Autoimmune/Metabolic Liver Diseases

Question 1

Primary biliary cirrhosis (PBC): gender; pathogenesis

Answer 1

F:M 9:1; susceptibility –> trigger –> immune mediated –> bile duct injury, fibrosis, cirrhosis

Question 2

PBC affects mostly the…

Answer 2

Bile duct cell

Question 3

PBC: external triggers

Answer 3

Unknown, maybe env’t (chemicals), or infectious

Question 4

PBC: dx (tests and name)

Answer 4

Elevated Alk Phos/GGTP, anti-mitochondrial Abs, elevated total serum IgM, “Florid duct lesion”

Question 5

PBC: histology

Answer 5

Florid duct lesion = inflammation around bile duct –> obliterated bile ducts –> cirrhosis

Question 6

PBC: presentation

Answer 6

Starts w/ abnormal liver biochemistries, may have pruritis (bile salts under skin), fatigue, and eventually signs/symptoms of liver disease (xanthomas, butterfly hyperpigmentation)

Question 7

PBC: survival hinges on…

Answer 7

Cirrhosis development (survival drops off)

Question 8

Autoimmune patients tend to do how with transplants?

Answer 8

Fairly well

Question 9

Primary sclerosing cholangitis (PSC): gender, pathogenesis, presentation

Answer 9

M:F 3:1, pathogenesis is UNKNOWN (immune perhaps?, infection), elevated cholestatic tests with cholangitis sx (fever, chills, RUQ pain, jaundice)

Question 10

Are there secondary causes of sclerosing cholangitis?

Answer 10

Yes! due to a variety of causes

Question 11

PSC: long-term complication

Answer 11

Cholangicarcinoma/cirrhosis

Question 12

PSC: dx (tests, imaging, and term)

Answer 12

Elevated Alk Phos/GGTP, 75% w/ pANCA, effects intra AND extrahepatic duct sclerosis = ONION SKIN FIBROSIS with strictures in ducts on imaging

Question 13

pANCA spelled out

Answer 13

Perinuclear anti-neutrophil cytoplasmic antibodies

Question 14

PSC: histo

Answer 14

Onion skin and loss of bile ducts in triad

Question 15

Majority of people with PSC have…

Answer 15

IBD

Question 16

PSC: complications

Answer 16

Cholangitis, end stage liver disease, cholangiocarcinoma (10% risk), higher risk of colon cancer

Question 17

PSC: tx

Answer 17

Resection, dilate strictures in ducts, medication (ursodeoxycholic acid –> maybe not good), transplant

Question 18

Autoimmune hepatitis (AiH): gender, age, presentation

Answer 18

F:M 8:1, young and perimenopausal, can be acute hepatitis or insidious

Question 19

AiH: dx

Answer 19

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

Question 20

AiH: tx

Answer 20

Immunosuppression (steroids)

Question 21

Wilson Disease: inheritance, describe, gene

Answer 21

Autosomal recessive disease of copper metabolism due to ATP7B on chrom 13

Question 22

What does ATP7B do?

Answer 22

Encodes for a copper transporting ATPase needed to excrete copper in bile and blood

Question 23

Wilson Disease: pathophys

Answer 23

Accumulation of copper –> hepatocyte death –> Cu accum in brain, kidneys, cornea

Question 24

Wilson Disease: histo

Answer 24

Rhodamine stain –> Cu deposition

Question 25

Copper metabolism

Answer 25

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

Question 26

Copper metabolism: Wilson and dx test

Answer 26

Ceruloplasmin not made (low in serum = TEST) AND no secretion in bile = build-up in hepatocyte

Question 27

Wilson disease: presentation

Answer 27

Hepatic (occasional FHF, hepatitis, cirrhosis), neurologic (PD), hematologic (hemolytic anemia), psychiatric (PSYCHOSIS)

Question 28

Wilson disease: characteristic finding

Answer 28

Kayser Fleischer Ring

Question 29

Wilson disease: dx

Answer 29

Low serum ceruplasmin, Kayser Fleisher ring, biopsy, genetic testing

Question 30

Wilson disease: tx

Answer 30

Chelating agents, oral Zinc (blocks intestinal copper), avoid mushrooms, nuts, dried fruit, transplant

Question 31

Hereditary Hemochromatosis: two types

Answer 31

HFE-related and non HFE related

Question 32

Hereditary hemochromatosis HFE: inheritance, rare?, presentation, gene

Answer 32

AR, fairly common, presents late, HFE gene on chrom 6, generally due to biallele C282Y mutation

Question 33

HFE HHC: pathogenesis

Answer 33

Mutation causes altered HFE protein –> impaired iron sensing in GI tract –> excess iron absorption –> deposition in liver, heart, pituitary, thyroid, pancreas, gonad

Question 34

Iron homeostasis

Answer 34

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

Question 35

Iron in hemochromatosis

Answer 35

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

Question 36

HFE HHC: triad

Answer 36

Cirrhosis, bronze skin, diabetes (= Bronze Diabetes)

Question 37

HFE HHC: dx (mention stain)

Answer 37

Fasting transferrin saturation over 50% or high ferritin, gene testing, MRI with liver quantification, biopsy (Prussian blue stain)

Question 38

HFE HHC: tx

Answer 38

Phlebotomize blood to deplete iron stores (note: women require less due to menstruaton)

Question 39

HFE HHC: survival

Answer 39

If phlebotomy is initiated BEFORE cirrhosis, they survive as normal population