Inherited Liver Dz Flashcards
Iron absorption from the gut exclusively occurs where
Duodenum…about 60mg/ day
Iron is absorbed and stored as what
Ferritin
Iron released into the circulation at the rate of
1-2 mg per day
Iron in the circulation is bound to
Tranferrin…This iron is taken up by hepatocytes where it is again stored in ferritin
If iron in the circulation is not taken up by the hepatocytes and stored in ferritin, it is involved in RBC synthesis
ok
Anything that disrupts iron absorption can lead to
iron overload
What is the principle iron regulatory hormone?
Hepcidin
Regulation of hepcidin release is the central mechanism in the pathogenesis of
Hereditary Hemochromatosis
Hepcidins job is to downregulate iron release
ok
Hepcidin levels are increased when?
There is excess iron or inflammation
Mutations in the HFE gene lead to what
Decreased Hepcidin expression leading to increased intestinal absorption of Fe via ferroportin
What is the most common genetic disorder affecting caucasians?
Hemochromatosis
Type 1 Hemochromatosis
HFE mutations
Net result of HC?
too much iron….it accumulates in tissues,,,,oxidative stress and tissue damage
90% of HC related to
HFE mutation
Most common HFE gene mutation
C282Y….G to A missense
When do hemochromatosis pts generally present?
men= over 40, women= over 50
General symptoms of hemochromatosis
Fatigue, aches and pain, arthritis
Liver findings in Hemochromatosis
Cirrhosis
Heart
Restrictive cardiomyopathy
Bronze diabetes is a common finding
ok
Arthritis generally located where
2nd and 3rd metacarpal
classic triad of hemochromatosis?
Micronodular cirrhosis, Diabetes Mellitus, and skin pigmentation
Pts may also develop gonadal atrophy and high risk of hepatocellular carcinoma
Type II hemochromatosis
Lack of hepcidin due to a mutation at the Genes encodine HAMP and HJV. Age of onset is 10-15 years. More cardiac involvement
Type III HC
Transferrin receptor mutation
Type IV HC
Ferroportin mutation
Liver disease mostly seen in which types
I and III
Cardiomyopathy and heart failure seen in which types
Type II
Endocrine disorders seen in which types
II and III
First step in diagnosis of HC is documenting the excess Iron. How do you do this
Divide Serum iron by serum transferrin. If Serum transferrin is over 45% saturated then you suspect iron overload
Excess iron stoarage suspected. Measure serum ferritin
ok
Next step
HFE gene mutation
MRI shows
Liver will be much darker (less signal intensity than the spleen)
Screening for HFE….If someone is identified who has HFE mutation, all first degree relatives should also be checked
ok….check ferritn saturations and also check for the C282Y gene mutation
Hemochromatosis treatment
The focus is on removing excess Iron
Phlebotomy is really the only option for each type
Phlebotomy needs to be performed until —– is less than —
Ferritin is less than 50ng/ml
What other dietary measures need to be taken by someone with hemochromatosis?
Avoid Vitamin C, Decrease alcohol intake, Decrease Iron intake
It is important to initiate treatment as early as possible. Survival improves if you can start treating them prior to onset of cirrhosis/diabetes
ok
Hypogonadism, arthropathy and cirrhosis are irreversible
ok
What is Wilson’s disease
Excessive copper deposition
Target organs in Wilson’s disease?
Liver, Brain, Kidneys
Where is copper absorbed?
Duodenum
95% of plasma copper is bound to?
Ceruloplasmin…this copper can be taken up and used for various processes in different organs
Wilson’s disease presents when?
Early in life
Neurologic manifestations in wilson’s disease are
behavioral changes, dementia, chorea, parkinsonian like symptoms, etc…
Know fulminant liver failure signs
they will die if you do not transplant them
When to suspect wilsons
any pt under 40 with high AST/ALT
Neuropsychiatric disease with liver disease
Any young pt with liver disease
Labs for wilsons
high urinary copper, low ceruloplasmin, high copper on liver biopsy
Know Kayser Fleischer rings
USually present in thse with psychological symptoms…sometimes low in others
Genertic testing in Wilsons
Usually not advised…too many possibilities
Alpha 1 Antitrypsin is what
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)
To have a functional alpha 1 antitrypisn, which phenotype do you need
MM
Two zz’s
bad news. protein cant be secreted
hen to suspect
cirrhosis of undetermined cause
emphysema and cirrhosis
Emphysema in a non-smoker (uncontrolled elastase)
