Flashcards in Anemia Deck (27):
1. What is macrocytic, microcytic and normocytic RBC anemia usually associated with??
Macrocytic → vit B12 or folic acid deficiency
Microcytic → iron deficiency anemia
Normocytic → acute blood loss
2. Discuss the transport and storage of iron in the body.
Ferritin – in intestinal mucosa, liver and heart until body needs it
Transferrin – transporter of iron
3. What are the causes of iron deficiency anemia?
1. acute or chronic blood loss
2. insufficient intake during periods of accelerated growth in children
3. heavily menstruating or pregnant women
4. Describe the type of anemia caused by iron deficiency.
Hypochromic microcytic anemia
5. How is iron deficiency anemia treated?
Oral or parenteral iron preparations
Oral iron therapy → ferrous iron is the most efficiently absorbed therefore ONLY ferrous salts should be used [ferrous sulfate, ferrous gluconate, ferrous fumarate]
Parenteral iron therapy → should be reserved for pts unable to tolerate or absorb oral iron or pts with severe chronic anemia that cannot be maintained with oral iron alone
6. What are the adverse effects of oral iron therapy?
2. epigastric discomfort
3. abdominal cramps
7. What is acute iron toxicity?
Acute iron toxicity is usually seen in young children who accidently ingest iron tablets. Iron poisoning leads to: necrotizing gastroenteritis, vomiting, abdominal pain, bloody diarrhea leading to shock, metabolic acidosis, coma and death.
8. What is the treatment for acute iron toxicity?
Deferoxamine → this is an iron-chelator that binds iron that has already been absorbed to promote its excretion in urine and feces
9. What is chronic iron toxicity?
Excess iron is deposited in the heart, liver, pancreas and other organs leading to organ failure and death. This most commonly occurs in patients with inherited hemochromatosis (excessive iron absorption) or pts with repeated transfusions (ex. thalassemia major).
10. What is the treatment for chronic iron toxicity?
Phlebotomy OR Deferoxamine or Deferasirox [chelation therapy] may be needed with pts with thalassemia major to stop the accumulation of iron
11. What are the active forms and forms found in food of vitamin B12 (cobalamin)?
Active form → deoxyadenosylcobalamin and methylcobalamin
Food form that is converted to active form → cyanocobalamin and hydroxocobalamin (what is also given via vitamin B12 parenteral injection)
*B12 is not synthesized by animals or plants therefore we need to get it from food (meats, eggs, dairy products that have microbially derived vitamin B12). Once consumed, vitamin B12 is stored primarily in the liver.
12. How much Vit B12 is needed in the diet?
Only 2 micrograms of Vitamin B12 daily is required in the diet, but the average diet contains 5-30 micrograms of Vitamin B12 daily. The average adult has a total of 3000-5000 micrograms in the total vitamin B12 storage. Because so much more than what is needed is consumed, it would take 5 years for all the stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if B12 absorption were stopped. Although we store so much B12, most vitamin B12 deficiencies in humans result from malabsorption due to lack of intrinsic factor to transporter malfunction. Strict vegetarians who do not eat meat, eggs or dairy products are the ones after many years end up with this vit B12 deficiency.
13. Discuss the absorption of vitamin B12.
Vitamin B12 is absorbed only after it complexes with intrinsic factor (glycoprotein secreted by the parietal cells in the gastric mucosa). The IF-vit B12 complex is absorbed in the distal ileum by a receptor-mediated transport system.
14. What are the causes of vitamin B12 deficiency?
1. pernicious anemia – defective secretion of intrinsic factor [treatment of B12 needs to be given via IV and not orally in these pts if they cannot absorb it]
3. Malabsorption syndrome
5. Small bowel resection
15. What enzymatic reactions in the body require vitamin B12?
1. Homocysteine → methionine via ______
*Methylcobalamin transfers a methyl group from N5-MTHF to homocysteine. [cobalamin → methylcobalamin via release of methyl group from N5-MTHF to THF – this is a precursor of folate cofactors] Without vitamin B12 the conversion of N5-MTHF (dietary folate) → THF (storage folate) cannot happen
2. Methylmalonyl-CoA →Succinyl-CoA via methylmalonyl-CoA mutase
16. What is the methylfolate trap?
With a vitamin B12 deficiency, there is an accumulation of folate as N5-MTHF as it cannot be converted to THF therefore depleting THF and treating it as a deficiency, even though it is there – just not accessible. Depletion of THF prevents synthesis of dTMP and purine required for DNA synthesis.
17. Why are neurological problems seen with Vitamin B12 deficiency and not Folate deficiency?
Disruption of methionine synthesis and accumulation of homocysteine leads to neurologic problems. Administration of folic acid in the presence of vitamin B12 deficiency corrects the anemia, but does not prevent neurologic manifestation – it masks the hematalogic vit B12 deficiency making the neurological problems even worse. If megaloblastic anemia is noted, treatment of both folate AND vit B12 should be administered until underlying cause is determined.
18. What is folic acid deficiency?
Folate deficiency is not uncommon and can be easily corrected by the administration of folic acid. During pregnancy, folate deficiency can lead to congenital malformations (fetal neural tube defects) or plays a role in vascular disease. These deficiencies go beyond anemia. Although the body’s stores folate are low, the daily requirements are high. Deficiency and megaloblastic anemia can develop within 1-6 months after folic acid intake stops. Unlike vitamin B12 deficiency, folate deficiency does not cause neurologic syndromes.
19. What reactions is folate used for?
Folate is the cofactor of THF producing dTMP needed for DNA synthesis (de novo synthesis of purines).
20. What drugs can lead to folic acid deficiency?
*all of these drugs inhibit dihydrofolate reductase leads to megaloblastic anemia
21. What growth factors have been produced by recombinant DNA technology and approved by the FDA to treat pts with blood cell deficiencies?
2. Myeloid growth factor – Filgrastim, Sargramostin
3. Megakaryocyte growth factor – Interleukin-11
22. What is the role of recombinant Erythropoietin?
Exogenous EPO → Darbepoetin [Darbepoetin has two extra carbohydrate chains compared to EPO and a 3 times longer half life]
Erythropoietin binds erythropoietin receptors (JAK/STAT) stimulating erythroid proliferation. Endogenous erythropoietin is produced by the kidney in response to hypoxia.
*All hemoglobin levels fall, erythropoietin levels rise – production of erythropoietin helps to correct for the anemia [this relationship does not hold for anemia or chronic renal failure]
**Give exogenous EPO to pts with renal failure and anemia!
23. What are the adverse effects of EPO?
HTN and thrombotic complications
24. What is the role of myeloid growth factors? Give examples.
Filgrastim and Sargramostin
Myeloid growth factors stimulate the production and function of neutrophils. This is used to accelerate recovery of neutrophils after cancer chemotherapy.
25. What is the role of Interleukin-11 administration?
Interleukin is a megakaryocyte growth factor used to increase the number of peripheral platelets in pts undergoing cancer chemo. This reduces the need for platelet transfusions.
26. What is the drug used to treat sickle-cell disease?
Hydroxyurea – increases HbF thereby diluting HbS – this change over takes severe months but helps relieve the pts of the painful sickle cell disease course.