GI - Pathology (Wilson disease, Hemochromatosis, & Biliary tract disease)

Question 1

What is another name for Wilson’s disease?

Answer 1

Wilson disease (hepatolenticular degeneration)

Question 2

What is (are) the defect(s) in Wilson’s disease? What effect does this have, and especially in what 5 organs?

Answer 2

Inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmin; Leads to copper accumulation, especially in liver, brain, cornea, kidneys, and joints

Question 3

What 11 clinical signs/symptoms characterize Wilson disease (hepatolenticular degneration)?

Answer 3

Characterized by: (1) low Ceruloplasmin, (2) Cirrhosis, (3) Corneal deposits (Kayser-Fleischer rings), (4) Copper accumulation, (5) Carcinoma (hepatocellular) (6) Hemolytic anemia, (7) Basal ganglia degeneration (parkinsonian symptoms), (8) Asterixis, (9) Dementia, (10) Dyskinesia, (11) Dysarthria; Think: “Copper is Hella BAD”

Question 4

With what disease are Kayser-Fleischer rings associated? What are they, and how do they appear?

Answer 4

Wilson disease (hepatolenticular degeneration); Corneal deposits (Kayser-Fleischer rings); Golden brown corneal ring

Question 5

What are 2 treatment options for Wilson disease (hepatolenticular degeneration)?

Answer 5

Treat with penicillamine or trientine

Question 6

What is the mode of inheritance of Wilson disease (hepatolenticular degeneration), and with what chromosome is it associated?

Answer 6

Autosomal recessive inheritance (chromosome 13)

Question 7

What normally excretes copper into bile? Give the protein and its gene name.

Answer 7

Copper is normally excrete into bile by hepatocyte copper transporting ATPase (ATP7B gene)

Question 8

What is hemosiderosis versus hemachromatosis?

Answer 8

Hemosiderosis is the deposition of hemosiderin (iron); Hemochromatosis is the disease caused by this iron deposition

Question 9

What is the classic triad of hemochromatosis? What is a nickname associated with this?

Answer 9

Classic triad of (1) micronodular Cirrhosis, (2) Diabetes mellitus, and (3) skin pigmentation => “bronze “ diabetes

Question 10

What are 3 conditions/risks that result from hemochromatosis?

Answer 10

Results in CHF, testicular atrophy, and increased risk of HCC

Question 11

What are the 2 types/causes of hemachromatosis?

Answer 11

Disease may be primary (autosomal recessive) or secondary to chronic transfusion therapy (e.g., Beta-thalassemia major)

Question 12

What the iron studies clinical lab findings associated with hemochromatosis?

Answer 12

Increased ferritin, increased iron, low TIBC => increased transferrin saturation

Question 13

What is a way to remember 3 presenting signs/symptoms and 1 complication of Hemochromatosis?

Answer 13

Think: “Hemochromatosis Can Cause (Corneal/Copper) Deposits”; CCD = Cirrhosis & Diabetes mellitus as signs/symptoms and CHF as a complication

Question 14

What amount can total body iron reach, and what social effect may this have?

Answer 14

Total body iron may reach 50g, enough to set off metal detectors at airports

Question 15

What is the gene associated with primary hemachromatosis, and what are 2 of its relevant mutations?

Answer 15

Primary hemachromatosis due to C282Y or H63D mutation on HFE gene.

Question 16

With what HLA marker is Hemochromatosis associated?

Answer 16

Associated with HLA-A3

Question 17

What is unique about hemachromatosis in women?

Answer 17

Iron loss through menustration slows progression in women

Question 18

What are the 3 treatments for hereditary hemochromatosis?

Answer 18

Treatment of hereditary hemochromatosis: repeated phlebotomy, deferasirox, deferoxamine.

Question 19

What are 3 kinds of biliary tract disease?

Answer 19

(1) Secondary biliary cirrhosis (2) Primary biliary cirrhosis (3) Primary sclerosing cholangitis

Question 20

What is the pathophysiology/pathology of secondary biliary cirrhosis?

Answer 20

Extrahepatic biliary obstruction (gallstone, biliary stricture, chronic pancreatitis, carcinoma of the pancreatic head) => increased pressure in intrahepatic ducts => injury/fibrosis and bile stasis

Question 21

What is the pathophysiology/pathology of primary biliary cirrhosis?

Answer 21

Autoimmune reaction => lymphocytic infiltrate + granulomas => destruction of intralobular bile ducts

Question 22

What is the pathophysiology/pathology of primary sclerosing cholangitis?

Answer 22

Unknown cause of concentric “onion skin” bile duct fibrosis => alternating strictures and dilation with “beading” of intra- and extrahepatic bile ducts on ERCP

Question 23

What 5 signs/symptoms characterize the presentation of secondary biliary cirrhosis? How does this compare/contrast to primary biliary cirrhosis? How does this compare/contrast to primary sclerosing cholangitis?

Answer 23

Pruritus, jaundice, dark urine, light stools, hepatosplenomegaly; Same; Same

Question 24

What 3 lab findings characterize secondary biliary cirrhosis? How does this compare/contrast to primary biliary cirrhosis? How does this compare/contrast to primary sclerosing cholangitis?

Answer 24

High conjugated bilirubin, High cholesterol, High ALP; Same; Same

Question 25

What is a complication of secondary biliary cirrhosis?

Answer 25

Complicated by ascending cholangitis

Question 26

What is a key marker to associate with primary biliary cirrhosis?

Answer 26

Increased serum mitochondrial antibodies, including IgM

Question 27

With what type of conditions is primary biliary cirrhosis associated? Give 4 examples of such conditions.

Answer 27

Associated with other autoimmune conditions (e.g., CREST, Sjogren syndrome, rheumatoid arthritis, celiac disease)

Question 28

What key blood lab finding is associated with primary sclerosing cholangitis?

Answer 28

Hypergammaglobinemia (IgM)

Question 29

With what condition is primary sclerosing cholangitis associated?

Answer 29

Associated with ulcerative colitis

Question 30

What are 2 conditions/complications that may result from primary sclerosing cholangitis?

Answer 30

Can lead to secondary biliary cirrhosis and cholangiocarcinoma