Inherited Liver Dz

Question 1

Iron absorption from the gut exclusively occurs where

Answer 1

Duodenum…about 60mg/ day

Question 2

Iron is absorbed and stored as what

Answer 2

Ferritin

Question 3

Iron released into the circulation at the rate of

Answer 3

1-2 mg per day

Question 4

Iron in the circulation is bound to

Answer 4

Tranferrin…This iron is taken up by hepatocytes where it is again stored in ferritin

Question 5

If iron in the circulation is not taken up by the hepatocytes and stored in ferritin, it is involved in RBC synthesis

Answer 5

ok

Question 6

Anything that disrupts iron absorption can lead to

Answer 6

iron overload

Question 7

What is the principle iron regulatory hormone?

Answer 7

Hepcidin

Question 8

Regulation of hepcidin release is the central mechanism in the pathogenesis of

Answer 8

Hereditary Hemochromatosis

Question 9

Hepcidins job is to downregulate iron release

Answer 9

ok

Question 10

Hepcidin levels are increased when?

Answer 10

There is excess iron or inflammation

Question 11

Mutations in the HFE gene lead to what

Answer 11

Decreased Hepcidin expression leading to increased intestinal absorption of Fe via ferroportin

Question 12

What is the most common genetic disorder affecting caucasians?

Answer 12

Hemochromatosis

Question 13

Type 1 Hemochromatosis

Answer 13

HFE mutations

Question 14

Net result of HC?

Answer 14

too much iron….it accumulates in tissues,,,,oxidative stress and tissue damage

Question 15

90% of HC related to

Answer 15

HFE mutation

Question 16

Most common HFE gene mutation

Answer 16

C282Y….G to A missense

Question 17

When do hemochromatosis pts generally present?

Answer 17

men= over 40, women= over 50

Question 18

General symptoms of hemochromatosis

Answer 18

Fatigue, aches and pain, arthritis

Question 19

Liver findings in Hemochromatosis

Answer 19

Cirrhosis

Question 20

Heart

Answer 20

Restrictive cardiomyopathy

Question 21

Bronze diabetes is a common finding

Answer 21

ok

Question 22

Arthritis generally located where

Answer 22

2nd and 3rd metacarpal

Question 23

classic triad of hemochromatosis?

Answer 23

Micronodular cirrhosis, Diabetes Mellitus, and skin pigmentation

Pts may also develop gonadal atrophy and high risk of hepatocellular carcinoma

Question 24

Type II hemochromatosis

Answer 24

Lack of hepcidin due to a mutation at the Genes encodine HAMP and HJV. Age of onset is 10-15 years. More cardiac involvement

Question 25

Type III HC

Answer 25

Transferrin receptor mutation

Question 26

Type IV HC

Answer 26

Ferroportin mutation

Question 27

Liver disease mostly seen in which types

Answer 27

I and III

Question 28

Cardiomyopathy and heart failure seen in which types

Answer 28

Type II

Question 29

Endocrine disorders seen in which types

Answer 29

II and III

Question 30

First step in diagnosis of HC is documenting the excess Iron. How do you do this

Answer 30

Divide Serum iron by serum transferrin. If Serum transferrin is over 45% saturated then you suspect iron overload

Question 31

Excess iron stoarage suspected. Measure serum ferritin

Answer 31

ok

Question 32

Next step

Answer 32

HFE gene mutation

Question 33

MRI shows

Answer 33

Liver will be much darker (less signal intensity than the spleen)

Question 34

Screening for HFE....If someone is identified who has HFE mutation, all first degree relatives should also be checked

Answer 34

ok....check ferritn saturations and also check for the C282Y gene mutation

Question 35

Hemochromatosis treatment

Answer 35

The focus is on removing excess Iron Phlebotomy is really the only option for each type

Question 36

Phlebotomy needs to be performed until ----- is less than ---

Answer 36

Ferritin is less than 50ng/ml

Question 37

What other dietary measures need to be taken by someone with hemochromatosis?

Answer 37

Avoid Vitamin C, Decrease alcohol intake, Decrease Iron intake

Question 38

It is important to initiate treatment as early as possible. Survival improves if you can start treating them prior to onset of cirrhosis/diabetes

Answer 38

ok

Question 39

Hypogonadism, arthropathy and cirrhosis are irreversible

Answer 39

ok

Question 40

What is Wilson's disease

Answer 40

Excessive copper deposition

Question 41

Target organs in Wilson's disease?

Answer 41

Liver, Brain, Kidneys

Question 42

Where is copper absorbed?

Answer 42

Duodenum

Question 43

95% of plasma copper is bound to?

Answer 43

Ceruloplasmin...this copper can be taken up and used for various processes in different organs

Question 44

Wilson's disease presents when?

Answer 44

Early in life

Question 45

Neurologic manifestations in wilson's disease are

Answer 45

behavioral changes, dementia, chorea, parkinsonian like symptoms, etc...

Question 46

Know fulminant liver failure signs

Answer 46

they will die if you do not transplant them

Question 47

When to suspect wilsons

Answer 47

any pt under 40 with high AST/ALT Neuropsychiatric disease with liver disease Any young pt with liver disease

Question 48

Labs for wilsons

Answer 48

high urinary copper, low ceruloplasmin, high copper on liver biopsy

Question 49

Know Kayser Fleischer rings

Answer 49

USually present in thse with psychological symptoms...sometimes low in others

Question 50

Genertic testing in Wilsons

Answer 50

Usually not advised...too many possibilities

Question 51

Alpha 1 Antitrypsin is what

Answer 51

a protein produced by the liver who's main function is to neutralize neutrophil elastase (produced by macrophages...if it increases it can have a proteolytic effects and cut up proetins like elastin...becomes problematic in the lungs and other tissues)

Question 52

To have a functional alpha 1 antitrypisn, which phenotype do you need

Answer 52

MM

Question 53

Two zz's

Answer 53

bad news. protein cant be secreted

Question 54

hen to suspect

Answer 54

cirrhosis of undetermined cause emphysema and cirrhosis Emphysema in a non-smoker (uncontrolled elastase)