Microcytic Anemia Flashcards
What does the CBC of someone with iron deficiency look like?
Decreased: RBC, Hgb, Hct, MCV, and Reticulocytes
Increased: RDW and Platelets
Dietary iron is of what charge?
Fe3+
To be taken in by gut enterocytes what charge must iron be?
Fe2+
What are the two transporters on either side of gut enterocytes?
DTM-1 (lumen side)
Ferroportin (basolateral surface)
To bind to transferrin, what charge must iron be?
Fe3+
Iron bound to transferrin has what 2 fates?
Use (transferrin binds to TfR on surface of bone marrow RBCs to make new RBCs)
Store (in macrophages in the liver, spleen, and bone marrow bound to ferritin)
What molecule controls ferroportin activity?
Hepcidin has a negative effect on ferroportin activity
If iron levels decrease, what happens to hepcidin?
it decreases (allows ferroportin to take in iron from gut enterocytes and release iron from stores)
How do you diagnose an iron deficiency?
Check serum ferritin (because serum ferritin is proportional to body stores of iron).
- Low ferritin
- Increased TIBC
- Decreased Serum Ferritin
What are two major reasons for iron deficiency?
- Malabsorption (duodenum)
- Blood loss (ex. menorrhagia, colon cancer)
- Hookworm
- Picca
What are the three main medications you use to treat iron deficiency?
1) Ferrous Sulfate (oral)
2) Ferrous gluconate (oral)
3) Iron dextran (parenteral–if patient’s problem is uptake)
What happens/what should you do if someone overdoses on iron?
- Necrotizing gastrointeritis, abdominal pain, bloody diarrhea, shock, lethargy, dyspnea
- Give Deferoxamine (iron chelator)
If you have an infection or chronic inflammation, what happens to hepcidin?
- levels of IL-1, IL-6, and TNF-alpha increase
- Liver makes acute phase reactants (including hepcidin)
- Hepcidin blocks ferroportin activity (so no intake of iron and no mobilizaiton of iron)
What is a ‘functional iron deficiency’?
Occurs in ACD, because you have enough iron, you just cannot take it up or mobilize it!
What diseases can lead to ACD?
RA, Lupus, Tb, cancer, sarcoidosis, AIIDS
What do iron studies show for ACD?
Ferritin normal or increased
Serum Fe is decreased
TIBC is decreased
What stain is diagnostic of ACD? What do you see?
Prussian blue stain of bone marrow shows lots of blue iron present in macrophages.
Thalassemias prevent the proper production of what component of Hgb?
alpha globin (ch. 16) beta globin (ch. 11)
What will the major difference of a CBC between iron problems/ACD and thalassemias be?
you have a normal to increased number of RBCs
Alpha Thal is seen in what groups of people?
Blacks and Asians
Beta Thal is seen in what groups of people?
Mediterranean
What thalassemia is associated with a gene deletion?
alpha
What thalassemia is associated with a mutation?
beta
What is unique about the MCVs of thalassemias?
They will usually be below 70 fL (VERY low)
If a patient presents with mild microcytic anemia, what type of alpha thalassemia could he have?
Alpha thalassemia 2 trait (two deletions)
What is hemoglobin H?
a functional tetramer of beta globulins
How do you diagnose alpha thalassemia?
Severe anemia, splenomegaly, and high HgH (cannot be detected with Hgb Electrophoresis, so use PCR to probe)
Will NOT see “hair on end” because you have intravascular hemolysis due to beta hemochromes (not as severe).
What would a peripheral smear of someone with alpha thalassemia look like?
target cells
hypochromia
some “golf-ball cells” due to beta precipitation
What is hemoglobin bart’s?
- all defective alpha chains, so gamma chains form tetramers that damage RBCs
- FATAL in fetus
What is the difference between beta thalassemia major and minor?
beta thalassemia minor has only one beta mutation while major has both beta mutations
What leads to the symptoms assoicated with beta thalassemia?
increased alpha chains make “inclusion bodies” that the spleen must remove or else they aggregate and harm RBCs (extravascular hemolysis) and cause defective erythropoiesis
Why do people with thalassemias have increased levels of iron?
1) GDF-15 is released by messed up erythroblasts and inhibits hepcidin (so increased iron uptake and mobilization)
2) Tons of transfusions
What would you expect to see in a Hgb electrophoresis of beta thal?
Increased Hgb A2 (alpha2, delta2)
Increased Hgb F (alpha2, gamma2)
What leads to the “chipmunk faces” and “crewcut” seen in people with beta thalassemia? What other two symptoms can be seen with beta thal?
extramedullary hematopoiesis caused by alpha hemochromes (increase in EPO) causes blood production to be performed elsewhere (like bones of face!)
Hypercoagulation and Endocrinopathies
What does a peripheral smear look like in someone with beta-thal major?
target cells
nRBCs
Basophilic stippling
What virus is devastating for someone with beta thal major?
Parvovirus B19 of erythroid precursors can lead to an aplastic crisis.
What is protoporphyrin? What type of anemia does it relate to?
- it is a component of heme that is generated from succinyl CoA and glycine
- Sideroblastic anemia
What are the major players needed to generate protoporphyrin?
ALA-S (enzyme)
Vitamin B6 (cofactor)
Ferrochelatase (what couples iron with protoporphyrin)
What are the 4 major causes of siderobastic anemia?
Lead poisoning Alcoholism Hereditary B6 Deficiency (he also said myelodysplasia)
How does lead poisoning cause sideroblastic anemia?
denatures ferrochelatase, so you cannot couple iron with protoporphryin to make heme
How does alcoholism cause sideroblastic anemia?
mitochondrial toxin
What is the hereditary cause of sideroblastic anemia?
ALA-S mutation on X chromosome prevents the first step of protoporphyrin synthesis
How does a B6 deficiency cause sideroblastic anemia?
Cofactor for ALA-S reaction, so cannot make protoporphyrin
What does a peripheral smear look like in a sideroblastic anemia patient?
ringed sideroblasts, becasue iron gets deposited in mitochondria forming “rings” around the nucleus
What do iron studies show for sideroblatic anemia?
Serum iron increased Ferritin increased (iron overload)
