Microcytic Anemias Flashcards
1
Q
How does anemia present? How do we test for it? How are the anemias classified?
A
- anemia presents as hypoxia; weakness, fatigue, dyspnea, pale conjunctiva, headache, light-headedness (can present as angina/claudication in patients with CAD and atherosclerosis)
- tested for with Hb, hematocrit, and RBC count
- anemia is a Hb less than 13.5 g/dL in males (less than 12.5 in females)
- classified based on mean corpuscular volume (MCV): microcytic is less than 80, normocytic is between 80 and 100, macrocytic is greater than 100
2
Q
What general principle is involved in the case of microcytic anemia? What are the four types?
A
- microcytic anemia is due to a decreased production of Hb; erythroblasts essentially undergo an extra division (hence the smaller size) in order to attempt to maintain the Hb concentration of each RBC
- a decrease in any component of Hb can cause this: heme (iron and protoporphyrin) and globin
- iron deficiency anemia (low iron); MC
- anemia of chronic disease (low iron)
- sideroblastic anemia (low protoporphyrin)
- thalassemia (low globin)
3
Q
How is iron normally acquired by the body? How is it transferred and where is it stored? How is iron excreted/regulated?
A
- iron is obtained in the diet; it is absorbed in the duodenum (5% is obtained in diet, 95% is recycled from already made Hb)
- the enterocytes absorb iron and pump it into the blood via ferroportin; in the blood, iron travels bound to transferrin and heads to liver hepatocytes and bone marrow macrophages where it is stored as ferritin (the macrophages eventually give the iron to the developing erythroblasts, which have transferrin receptors)
- iron is essentially unable to be excreted! therefore, regulation occurs at the level of the enterocyte and whether or not the cell will pump the iron into the blood via ferroportin (regulated by hepcidin: decreases ferroportin)
4
Q
What four lab measurements are used to determine a patient’s iron status?
A
- serum iron: the amount of iron in the blood (this iron will be bound to transferrin); (N is 100 micrograms/dL)
- TIBC: total iron binding capacity: the amount of transferrin in the blood; (N is 300 micrograms/dL)
- percent saturation: the amount of transferrin bound to iron (N is 33%; 1 of every 3 transferrin molecules is bound to iron); greater than 45% indicates hemochromatosis
- serum ferritin: the amount of iron stored in cells (N is about 100-300)
- (note that when ferritin decreases, TIBC will increase and vice versa)
5
Q
What is the most common type of anemia overall? What are the major causes of this anemia in infants, children, adults, and the elderly? How do we treat it?
A
- iron deficiency anemia is the most common anemia overall
- infants: breast-feeding (low iron content) and high demand
- children: poor diet (high demand in adolescents)
- adults: peptic ulcer disease/GI disease, malignancy, menorrhagia, pregnancy (increased demand)
- elderly: colon polyps/carcinoma (Western world), hookworm infection (third world)
- others: gastric surgery (achlorhydria delays reduction of non-heme iron)
- treat with ferrous sulfate (simply increasing dietary intake is not enough)
6
Q
What are the four stages of iron deficiency (ie, how does the deficiency progress)?
A
- 1) depletion of stored iron (ferritin decreases; TIBC will increase as a result)
- 2) depletion of serum iron (serum iron and percent saturation decrease)
- *3) NORMOCYTIC anemia develops
- 4) microcytic anemia develops
7
Q
What clinical and lab findings are associated with iron deficiency anemia?
A
- microcytic hypochromic anemia
- pica (urge to chew/eat abnormal things), koilonychia, angular stomatitis/chelitis, pale conjunctiva
- elevated RDW (RBC distribution width; the spectrum of RBC size; in iron deficiency anemia, both normocytic and microcytic anemia occur, increasing the spectrum)
- decreased ferritin to less than 50 (and increased TIBC)
- decreased serum iron and percent saturation
- elevated FEP (free erythrocyte protoporphyrin; because there is no iron for it to bind to in the RBC to form heme)
8
Q
What syndrome involves iron deficiency anemia? What are the features of this syndrome?
A
- Plummer-Vinson syndrome
- iron deficiency anemia, esophageal web (dysphagia), atrophic glossitis (beefy red tongue)
9
Q
What is the most common type of anemia in hospitalized patients? How do we treat it?
A
- anemia of chronic disease is the most common type of anemia in hospitalized patients
- it is associated with chronic inflammation, cancer, alcoholism, etc.
- treat the underlying cause; can give exogenous EPO in some cases
10
Q
What is the pathophysiology of anemia of chronic disease?
A
- in chronic disease, acute phase reactants are chronically altered: ferritin and hepcidin are elevated and transferrin is decreased
- these all act to sequester iron from the assumed microbial pathogens; major player is hepcidin, which locks iron in its stored state as ferritin and also suppresses renal EPO prodution
- the resulting decrease in readily available iron results in anemia of chronic disease
11
Q
What findings are associated with anemia of chronic disease?
A
- microcytic hypochromic anemia (initially it’s normocytic)
- increased ferritin (and decreased TIBC)
- decreased serum iron
- decreased percent saturation
- normal or increased RDW (RBC distribution width)
- increased FEP (free erythroctye protoporphyrin because iron is sequestered and not used)
12
Q
What is sideroblastic anemia? What are the most common causes?
A
- sideroblastic anemia is a microcytic anemia due to defective protoporphyrin synthesis in the erythroblast, leading to decreased Hb production
- MC congenital cause: X-linked defect in ALA-S enzyme (catalyzes the 1st step of protoporphyrin synthesis)
- acquired causes: alcoholism (MCC overall; damage to mitochondria, where the final steps of synthesis take place), lead poisoning (Pb denatures ALA-D and ferrochelatase), vitamin B6/pyridoxine deficiency (cofactor for ALA-S; isoniazid)
13
Q
What is the role of ALA-S, ALA-D, and ferrochelatase in protoporphyrin synthesis?
A
- ALA-S (aminolevulinic acid synthase) catalyzes the 1st step: converts succinyl-CoA into ALA; the RLS; major cofactor is vitamin B6/pyridoxine
- ALA-D (ALA-dehydrogenase) catalyzes the 2nd step: converts ALA into prophobullinogen; it is denatured in lead poisoning
- (prophobullinogen is eventually made into protoporphyrin)
- ferrochelatase is involved in the final step and binds protoporphyrin to iron in the mitochondria to form Hb; it is denatured in lead poisoning
14
Q
What findings are associated with sideroblastic anemia?
A
- microcytic hypochromatic anemia
- increased ferritin (iron isn’t being used to bind to protoporphyrin); decreased TIBC
- increased serum iron
- increased percent saturation
- low protoporphyrin (FEP)
- histo reveals ringed sideroblasts: iron-loaded mitochondria (because not enough protoporphyrin to form Hb) form a ring around the nucleus in these erythroblasts; seen with Prussian blue
15
Q
What is thalassemia? This anemia is usually due to an inherited mutation - what are carriers of this mutation protected against?
A
- thalassemia is a microcytic anemia due to the decreased synthesis of globin chains, resulting in decreased production of Hb
- carriers of these mutations are protected against malaria via Plasmodium falciporum
