Intro to Anemias Pt I Flashcards
Define anemia
Reduction in number and/or function of RBCs. This leads to hypoxia
What are two main causes of anemia?
- Increased RBC loss (hemolysis, excessive blood loss)
- Decreased production of RBC
Lab evidence of RBC destruction?
- Schistocytes
- Increased bilirubin
- Splenomegaly
- Pappenheimers
- Hemosiderin
- Reduced haptoglobin
DAT
Direct anti-globulin test
Tests if anemia is caused by Ab attaching to RBCs
____ of total body iron is find in Hgb
2/3
T/F: Body Fe is repeatedly recycled. Small amount lost, replaced by diet
So true
What is daily iron requirement affected by?
- Menstruation
- Pregnancy
- Growth
- Additional blood loss
Most dietary Fe is in what state?
Ferric (Fe3+). It gets converted to Ferrous (Fe2+) state by reductase enzymes such as Duodenal Cytochrome B (DCYTB) for optimal absorption. Optimal pH < 4.0
Ferrous iron is carried into enterocyte by which enzyme?
Divalent Metal Transporter 1
What does copper-dependent enzyme hephaestin do in the enterocyte?
It converts ferrous iron to ferric state so that it can be stored as ferritin
Function of enterocytes in context of iron?
- Store iron as ferritin
- Export Fe out to rest of body
Which enzyme exports iron? To which cells does it carry iron?
Ferroportin 1 (FPN1). It carries iron from enterocytes, macrophages, and hepatocytes into the bloodstream
Describe FPN1 regulation
- Regulated by hepcidin, which binds/inactivates FPN1
- If body Fe stores good, then liver increases hepcidin production, which reduces Fe absorption/cellular release
- If body Fe stores low, then less hepcidin made, which increases Fe absorption/cellular release
What do enterocytes, macrophages, and hepatocytes do with iron?
- Enterocytes are involved in iron absorption/storage
- Macrophages recycle iron
- Hepatocytes store iron
Describe hepcidin regulation
- Not fully understood
- Hemochromatosis gene (HFE) allows hepcidin production when Fe levels are good
- EPO stimulates rubriblast-derived erythroferrone (ERFE) to suppress hepcidin
Once Fe3+ is released from the enterocyte into circulation, what happens?
It is picked up by apoferritin, becoming transferrin (carries 2 ferric atoms), and then carried to the BM for RBC production and storage in BM, liver, and spleen. Maintains solubility
Function of Transferrin Receptor 1 (TfR1) in BM?
- It brings in transferrin into nRBCs and reticulocytes (this is a surface protein) through an endosome, which acidifies and allows iron to convert to ferrous state and moved to the cytoplasm by DMT1.
- DMT1 shuttles iron to mitochondria and ferritin
- Last step is heme synthesis by adding ferrous iron into protoporphyrin IX by ferrochelatase
What’s special about measuring TfR1 ?
When iron stores in the RBC is enough, TfR1 production declines and the existing proteins slough off and can be measured to see how your body’s iron stores are doing
What happens to TfR1 production when iron stores are low?
Production increases
What happens to senescent RBCs?
They are broken down by macrophages and their iron is recycled
Why must iron be sequestered by a protein, such as apoferritin?
Free iron is toxic
Solubility of apoferritin?
Water soluble - so easily mobilized for use
Describe ferritin and TfR1 levels when iron is high or low
- Iron high: Increased ferritin and decreased TfR1
- Iron Low: Decreased ferritin and increased TfR1
Describe hemosiderin traits
- It’s a breakdown product of ferritin that is principally found in the reticuloendothelial system (RES) of the liver, spleen, and BM
- NOT water soluble
- Prussian blue used to visualize granules
- Less readily available than ferritin
Describe serum iron evaluation of iron status (what does it measure…etc)
- Measures transferrin-bound iron
- Fluctuates so must use with other labs
Describe Total iron binding capacity (TIBC) (what it measures…etc)
- Measures total amount of Fe that can be bound to transferrin in serum or plasma
- Binding capacity normally 1/3 saturated
- Values increase in IDA and decrease in iron overload
Describe transferrin saturation (what does it measure etc…)
- Measures percent saturation of transferrin aka max amount of iron that is bound in plasma/serum
- % Transferrin sat = (serum iron/TIBC) X 100%
Describe serum ferritin (what it measures…etc)
- Measures serum ferritin, which is directly proportional to amount of iron stored
- Better measure of body storage iron than serum iron and TIBC
Ferritin levels during inflammation
Increased, so acute phase reactant
Describe soluble transferrin receptor (sTfR) lab test
- Measures sloughed off TfRs in serum, which is inversely proportional to amount of body iron
Describe hepcidin level lab test
Measures hepcidin levels to assess quality of iron stores
Describe Free Erythrocyte Protoporphyrin (FEP) or Zinc Protoporphyrin (ZPP)
- FEP is the heme without iron inserted
- ZPP is heme with zinc inserted instead of iron
- Both inversely correlated to ferritin (stored iron) level
Describe retic count and Reticulocyte Corpuscular Hgb (CHr) lab test
- Retic number decreases with diminished/ineffective erythropoiesis
- CHr is an early indicator of iron deficient erythropoiesis (good indicator of patient’s response to iron therapy). Measures Hgb content in retics
Describe BM iron lab evaluation
- Prussian blue
- Rarely justifiable except in possible case of sideroblastic anemia, myelodysplastic syndrome, or other complex case
