Hematopoietic Growth Factors Flashcards
What are 3 main growth factors for erythrocytes?
- IL-1, IL-6, IL-3
- G-CSF
- GM-CSF
- **Epoetin **
What is the best source of dietary iron?
meat (heme iron)
*Vegetables not as good. Non-heme iron in foods must be reduced to ferrous iron: usually ascorbate aids this *
Which form of iron is absorbed?
Only the ferrous (Fe+2) form is absorbed.
Both vitamin C and HCl will increase absorption.
What determines the body’s iron content?
Absorption
Storage = ferritin
Transferrin transports iron from mucosal cell to the tissues. Duodenum and prox. jejunum.
How is iron eliminated?
No excretion mechanisms
Regulation of iron balance is achieved by changing absorption and storage of iron.
What happens if body iron stores are high ?
stored as ferritin
What happens if body iron stores are low?
iron is transported to bone marrow for hemoglobin production.
What happens with apoferritin if free iron is low?
synthesis is inhibited and iron binding shifts to transferrin
What happens with apoferritin if free iron is hi?
synthesis is stimulated and iron is sequestered as ferritin and organs are protected from iron’s toxic effects.
What happens in acute iron toxicity?
Necrotizing gastroenteritis
Treatment = bowel irrigation, Deferoximine- to chelate iron that has been absorbed and to promote excretion, Supportive care
Chronic toxicity
Treated with phlebotomy or chelation therapy
What is the most common form of iron?
Ferrous sulfate is the most common, but most GI side effects. Ferrous gluconate is less.
When is iron dextran given?
Reserved for patients that cannot tolerate oral iron or cannot absorb it. Give IV or IM
Function of vitamin B12
Dietary folate is absorbed. A methyl group gets removed by vit. B 12. It donates it to methionine, an important AA to be a methyl donor and essential aa . . . which then gets metabolized to S adenosyl (makes norepi from epi).
N5/N10 methyeleneTHF, catalyzes dUMP, dTMP which goes on to DNA synthesis. If you can’t make DNA, you can’t make cells (RBCs)
How is B 12 transported?
Transported bound to transcobalamin II; excess vitamin stored in liver
Correcting a B12 anemia with folic acid
Large amounts of folic acid can correct the anemia due to Vitamin B12. **BUT it Cannot correct the neurologic damage. **
How is vit B12 administered?
Given by parenteral injection usually as hydroxycobalamin- remains in the circulation longer.
- To replenish stores given daily
- Maintenance dose- once per month for lifetime
- Hematologic response is rapid: marrow returns to normal within 48 h.
What’s the recommended intake for folic acid?
400 mcg per day
Pregnant or lactating women 500-600 mcg, Prevention of neural tube defects 400 mcg per day
How soon can anemia develop with folic acid deficiency?
Anemia can develop in 1-6 mo after dietary intake has diminished
How is folate absorbed?
Reduced methylated monoglutamates are absorbed. Stored in cells as the **polyglutamate **
Folates in pills
Folic acid = Pteroylglutamic acid
Folinic acid- 5- formyltetrahydrofolate = Leucovorin-rescue from high dose methotrexate therapy
What is the dosage for folic acid deficiency?
1 mg per day
reversal of deficiency within 1-2 months
Epoetin Alpha
Glycosylation patterns in the recombinant protein is different from that produced by body and can be distinguished using modern assay methods.
**Not cleared by dialysis
Liver major site of degradation **
List 4 functions of Epoetin alpha
- Made in response to tissue hypoxia
- Target cells- CFU-E
- Stimulates erythroid proliferation and differentiation
- Induces release of reticulocytes from marrow
