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;
43 Cards in this Set
- Front
- Back
|
What is Hirschprung disease?
|
Congenital absence of intrinsic ganglion cells in the myenteric and submucosal plexuses of the GI tract.
|
|
|
What are the 2 main forms of Hirschprung?
|
Short-segment=aganglionic segment does not extend beyond upper sigmoid.
Long-segment= aganglionic segment extends proximal to the sigmoid. |
|
|
What is the clinical presentation of Hirschprung?
|
Intestinal obstruction, colon distension and associated with downs, bardet bidl and cartilage-hair hypoplasia syndromes.
|
|
|
RET gene is expressed in what type of cells?
|
Neural crest cells
|
|
|
Hirschprung disease is what type of mutation in the RET gene, gain of function or loss of function mutation?
|
Loss of function
|
|
|
What is iron bound and transported with in the body?
|
Transferrin
|
|
|
What are the 2 methods of iron overload?
|
Too much is absorbed and too many erythrocytes are destroyed.
|
|
|
When too much iron is absorbed, where is it deposited?
|
Liver, heart and some endocrine tissues.
|
|
|
When too many erythrocytes are destroyed, where does iron accumulate?
|
In reticuloendothelial macrophages first then tissue parenchyma
|
|
|
What are mutations in HFE gene responsible for?
|
Responsible for most common form of iron-overload: hemochromatosis.
|
|
|
Mutations in HJV are responsible for?
|
Most cases of juvenile hemochromatosis.
|
|
|
Mutations in TRF2 are responsible for what condition?
|
Similar clinical presentation to HFE mutations, hemochromatosis.
|
|
|
What protein does HAMP encode for?
|
Hepcidin, which is central in amount of iron available.
|
|
|
Transferrin and HFE compete for binding sites at what receptor?
|
TFR1
|
|
|
Which binds to TFR1 better, Transferrin or HFE?
|
Transferrin
|
|
|
Unbound HFE elevated on cell surface stimulates the expression of what protein?
|
Hepcidin
|
|
|
What is the effect of too much FE on the TFR receptors?
|
More TFR2 is produced than TFR1 which means more transferrin binds to TRF2.
|
|
|
What does Hepcidin down regulate?
|
Transport of iron out of enterocytes.
|
|
|
What effect does elevated iron and hepcidin have on the amounts of iron in the body?
|
Decreases iron transfer to body.
|
|
|
What are the effects of too little HFE?
|
Decrease unbound HFE leads to decreased TFR2, resulting in decreased HAMP expression, leading to increased iron transfer out of enterocytes.
|
|
|
What are the characteristics of hemochromatosis?
|
Late onset--40-50s in males
Non-specific early symptoms Hepatosplenomegaly Liver fibrosis/cirrhosis Increasing liver damage leading to carcinoma Endocrinopathies Increased infection with decreased hepcidin |
|
|
What do intracellular iron lead to?
|
Leads to increased free radical production and peroxidation of phospholipids of organelles.
|
|
|
What leads to the liver fibrosis and cirrhosis found in hemochromatosis?
|
Increased collagen synthesis
|
|
|
What are the 2 mutated genes seen in hemochromatosis?
|
C282Y and H63D
|
|
|
What are the 2 genetic ways HH may occur?
|
Homozygous condition or as a compound heterozygous condition
|
|
|
Where is copper absorbed and how does it travel to the liver?
|
Absorbed in stomach and duodenum and bound to albumin for transportation to liver.
|
|
|
What 2 genes are involved in copper homeostasis and where are they expressed?
|
ATP7A expressed in most cells
ATP7B expressed in liver, brain, kidney, and placenta |
|
|
Copper is the rate limiting step in what conversion?
|
The conversion of apoceruloplasmin to yield ceruloplasmin.
|
|
|
Most copper is bound to what?
|
Ceruloplasmin
|
|
|
Increased levels of ceruloplasmin is seen in what conditions?
|
Inflammation, infection, and trauma required.
|
|
|
What effect does reduced copper have on iron transport?
|
Reduced copper leads to reduced iron transport that leads to an increased attempt to increase iron absorption.
|
|
|
What 2 proteins are important for copper absorption at the brush border of intestinal cells?
|
DMT1 and CRT1
|
|
|
Copper metabolism and excretion is controlled by what organ?
|
Liver
|
|
|
What is the normal function of ATP7A?
|
Move copper from intestinal mucosa into blood.
|
|
|
What syndrome is associated with ATP7A and what does a mutation at this gene lead to?
|
Menkes Syndrome
Uptake is impaired, copper deficiency occurs and co-factor deficiency and inefficient reactions. |
|
|
What is the clinical presentation of Menkes in infants?
|
Healthy until 2-3 months
Loss of developmental milestones, hypotonia, seizures, and failure to thrive. |
|
|
How is diagnosis of Menkes usually made?
|
Suspected when infants exhibit typical neurologic changes and concomitant characteristic changes of the hair.
|
|
|
Describe the Hair changes seen in Menkes.
|
Scalp and eyebrow hair is short, sparse, coarse, twisted and often lightly pigmented. Shorter and thinner on sides and back of head.
|
|
|
Tortuous intracranial and extracranial vessels is characteristic of what syndrome?
|
Menkes
|
|
|
Mutations in ATP7B is associated with what disease?
|
Wilson Disease
|
|
|
What is the effect on copper when Mutations in ATP7B gene occur?
|
Prevents copper release from hepatocytes, apoceruloplasmin is degraded, ceruloplasmin levels decrease, iron levels affected.
|
|
|
What is the clinical presentation of Wilson disease?
|
Progressive lenticular degeneration, bilateral softening of the lenticular nucleus and liver cirrhosis.
Neurologic symptoms (movement disorders and rigid dystonia) Psychiatric cymptoms |
|
|
What are Kayser-Fleischer rings and what are they seen in?
|
Copper deposition in Descemet's membrane of the cornea, reflects high degree of copper storage, seen in Wilson disease.
|
