Hematopoietic Growth Factors Flashcards
How early do anemic individuals show a response to iron sulfate?
Response within a week
How long until anemic individuals’ hemoglobin levels return to normal following iron sulfate therapy?
1-3 months
Adverse effects of oral ferrous sulfate
GI distress; black stool may obscure recognition of GI bleeding
How to avoid GI distress with iron therapy
Take with meals
What does parenteral iron consist of, and how is parenteral iron administered?
Iron dextran, IV or IM
Indications of IV iron (3)
Post-gastrectomy/small bowel resection
Malabsorption syndromes
Intolerance of oral preps
Indications of oral iron
Prevention or treatment of iron deficiency anemia (microcytic hypochromic anemia)
Adverse effects of parenteral iron
Adverse effects: local pain and tissue staining with i.m., headache, fever, nausea, vomiting, back pain, arthralgias, urticaria, bronchospasm, anaphylaxis/death (rare)
What causes acute iron toxicity?
Accidental ingestion of iron tablets
What are the clinical features seen in acute iron toxicity? In what age group could it be fatal?
Necrotizing gastroenteritis
After short improvement, metabolic acidosis, coma and death
Children
Treatment of acute iron toxicity (2)?
Would activated charcoal be effective?
(a) Gastric aspiration, lavage with phosphate or carbonate solution (get stomach pumped)
(b) Deferoxamine, a potent iron chelating substance, i.m. or i.v.
Activated charcoal is not effective
Which patients show iron overload (chronic iron toxicity)?
Seen in an inherited disorder, hemochromatosis
Patients receiving repeated red cell transfusions
Clinical features of iron overload?
Excess iron deposited in heart, liver and pancreas leading to organ failure
Treatment of chronic iron toxicity (2)?
If no anemia, intermittent phlebotomy
Iron chelation via deferoxamine (parenteral) or deferasirox (oral)
3 main causes of iron-deficiency anemia
Increased requirements
(1) Frequently present in premature infants
(2) Children during rapid growth period
(3) Pregnant and lactating women
Inadequate absorption: post-gastrectomy or severe small bowel disease
Blood loss
(1) Menstruation
(2) Occult gastrointestinal bleeding
How do heme iron and non-heme iron enter the mucosal cell?
(1) Heme iron is absorbed intact from duodenum and jejunum
(2) Non-heme iron must be reduced to ferrous iron (Fe2+)
(3) The ferrous form is the absorbed through DMT1 by active transport
How is the ferrous ion acted upon in the mucosal cell and how does it leave the mucosal cell?
(4) Within mucosal cell, ferrous iron is converted to ferric (Fe3+)
(5) Iron leaves the mucosal cell by passing through ferroportin
(6) Hepcidin downregulates ferroportin and regulates iron absorption
Effects of iron deficiency and overload on transferrin and ferritin
In iron deficiency anemia, transferrin increases and ferritin decreases
In iron overload, transferrin decreases and ferritin increases
Remember, ferritin = liver and spleen stores, and plasma ferritin can approximate liver + spleen ferritin
Transferrin = hunts for for iron, transport to the bone marrow
Active forms of B12
Is supplemental B12 given in its active forms?
Deoxyadenosylcobalamin and methylcobalamin are the active forms
No, cyanocobalamin and hydroxycobalamin (therapeutic drugs) are converted to the active forms. They are prodrugs.
Absorption of B12
Distribution of B12
Storage of B12
Distal ileum, requires intrinsic factor
Bound to transcobalamin II
Liver, 3-5 mg
Indications of B12 or folic acid
Vitamin B12 and folic acid used only for prevention or treatment of deficiencies. Need to differentiate to prevent nerve damage from B12.
Time course of response (Return to normal) for B12 and folate deficiency
1-2 months, however if B12 deficiency is caused by malabsorption (loss of IF), usually requires lifelong parenteral injection.
Absorption and storage of folic acid
Polyglutamate forms must be hydrolyzed to monoglutamate. Monoglutamate form inters bloodstream by active and passive transport
5-20 mg of folates are stored in liver and other tissues. Folates are excreted and destroyed by catabolism.
Since normal daily requirements are ~ 50 μg, diminished intake will result in deficiency and anemia within 1-6 months
Function of EPO
Where is it produced
When does it increase
Stimulates proliferation and differentiation of erythroid cells
Promotes release of reticulocytes from bone marrow
Produced by the kidney
Increases in anemia, with the exception of anemia secondary to chronic renal failure
