Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
20 Cards in this Set
- Front
- Back
|
What disorders are liver AAT deficiencies?
|
Hereditary/secondary hemochromatosis
- Wilson and Menkes syndrome |
|
|
AKA mega colon
name disease and explain two types... |
Hirschprung
Short‐segment form, (approximately 80% of cases) aganglionic segment does not extend beyond the upper sigmoid, – Long‐segment form (L‐HSCR) • aganglionosis extends proximal to the sigmoid – Total colonic aganglionosis and total intestinal HSCR also occur ‐‐‐ very rare. |
|
|
This is the gene associated with Hirschprung?
Whaat is MOA? |
RET, AD, Chr 10q11.2 tyrosine kinase receptor
can not bind properly to ligand and therefore enteric system does not develop currectly |
|
|
Where is RET expressed?
What might it cause? |
expressed in neural crest cells
responsible for MEN syndromes gain of function mutation (MEN2A, MEN2B, FMTC) - loss of function mutation- Hirschprung |
|
|
Mutation in HFE you think?
|
def. iron problem most likely Hemachromotosis
|
|
|
What is responsible for most causes of juvenile hemochromatosis? (what type is this?)
What gene may present similar but less common? (what type?) |
HJV and HAMP (hepcidin is central in iron amount available) (HFE-2)
- TFR2 (HFE-3) |
|
|
HAMP gene associate with what?
|
hepcidin is central in iron amount available- seen in juvenile hemachromatosis (types HFE-2-A/B)
|
|
|
Describe how Fe2+ is regulated use terms HFE, TFR1, and hepcidin
|
Fe2+ transported to liver by transferrin and binds to TFR1 (but has to compete for site with HFE)
- HFE unbound is then increased in # on cell surface, so it then sends signal to stimulate hepcidin expression (which down regulates transport of Fe2+ out of enterocytes) |
|
|
What happens normally to iron regulation with too much Fe2+?
|
- cause more TFR2 to be produced for TFR1
- TFR2 stimulates hepcidin expression |
|
|
Describe clinical presentation of hemochromatosis in...
a. males b. female |
Non‐specific early symptoms
– Fatigue – Arthralgia – Erectile dysfunction – Increased pigmentation Progresses to hepatosplenomegaly • Liver fibrosis and cirrhosis • Increasing liver damage leading to carcinoma • Endocrinopathies (diabetes, hypopituitarism, hypogonadism, hypoparathyroidism) a. 40‐50s in males b. Later onset in females |
|
|
What are the two types of mutations/genes for hereditary hemochromatosis?
|
C282Y – 90% of HH
– CYS to TYR mutation at residue 282 • H63D – HIS to ASP mutation at residue 63 |
|
|
Why might Hereditary hemochromatosis might not show with a homozygous
What are heterozygous carriers of HH? What is incidence with northern European ancestry? |
due to 2 different types of mutation... could have "compound heterozygous" w/o complete penetrance
+/C282Y • +/H63D • C282Y/H63D = compound heterozygote - 1:250 |
|
|
With Wilson's and Menkes syndrome what is cofactor problem?
What genes are involved in copper homeostasis *Which cause wilson/Menkes? |
copper
- ATP7A (menkes enterocyte), ATP7B (wilson, hepatocyte) |
|
|
90% of copper in body is bound to ______?
What increases its levels? |
ceruloplasmin- increased during inflammation, infection, and trauma
|
|
|
What two proteins at brush border of intestinal cells does copper absorption occur?
|
DMT1
CRT1 |
|
|
Explain the difference between Menkes and Wilsons?
|
Menkes- uptake of copper is impaired in enterocyte, due to ATP7A mutation
Wilsons- ATP7B mutation prevents copper release from hepatocytes |
|
|
Presents concomitant characteristic changes of the hair (short, sparse, coarse, twisted, often lightly pigmented).
|
Menkes
|
|
|
Disease shows on Three dimensional MR angiography shows markedly tortuous intracranial and extracranial vessels, which are characteristics of Menkes disease.
|
Menkes
|
|
|
copper deposition in Descemet's membrane of the cornea
|
Kayser-Fleischer rings (shown in Wilson's)
|
|
|
How does treatment of Menkes vs Wilsons differ?
What are the lab findings in a. Menkes b. Wilson's |
Wilsons- copper chelation
Menkes- copper/histidine injections a. decreased serum copper, decreased liver copper, intestinal/kidney copper b. decreased serum copper, increased liver copper, increased urinary copper |
