Hematology Flashcards
Erythropoietin is formed by which organs?
90% made by the kidney
10 % Liver
What stimulates renal production of EPO?
Hypoxia
How does EPO exert its effects?
Triggers hematopoietic stem cells to produce more proerythroblasts
What is the result of vitamin B12 or folic acid deficiency?
Maturation failure during the process of erythropoiesis.
Final maturation of RBCs requires what?
(2 factors)
Vitamin B12
Folic Acid
What is pernicious anemia?
Atrophic gastric mucosa (GI defect) leads to decreased B12 absorption.
What is intrinsic factor?
Glycoprotein that binds to Vit B12 and protects B12 from digestion. Then the intrinsic factor-B12 complex is absorbed by pinocitosis in the ileum.
What cells produce intrinsic factor?
The parietal cells of the gastric glands
At what RBC cell stage does the process of hemoglobin synthesis start?
A the proerythroblast stage
What are the components of hemoglobin?
Heme - molecule
Globin - long polypeptide
What is the total iron distribution in the body?
Hemoglobin - 65%
Ferretin - 15-30%
Myoglobin - 4%
Compounds of intracellular oxidation - 1 %
Transferrin - 0.1%
How is iron absorbed in the GI?
Iron combines with apotransferrin in the small intestine.
Apotransferrin is converted to transferrin.
Transferrin transports Iron in plasma.
How is iron (transferrin form) is distributed and stored in the cell?
Transferrin circulates iron and deposits it in:
Liver and reticuloendothelial cells of bone marrow
Once inside the cell - iron combines with apoferritin to form ferritin.
What happens when iron plasma levels decrease?
Iron dissociates from ferritin in the cells and then it is recirculated to where it is needed (via transferrin)
How is Iron stored in the cell?
Via ferritin
How is iron transported in the blood?
Transferrin
Where does transferrin bind particularly strongly?
Receptors of erythroblasts and bone marrow (cells that need large amounts of iron)
Transferrin is endocytosed and it delivers iron directly to the mitochondria.
What receptor does transferrin use to bring iron into the cell? How is it brought into the cell?
- Transferrin receptor 1 (TFR1) - outside of the cell
- Once transferrin is bound to TFR1 - endosome is formed.
- DMT1 receptor is within endosome - Is proton pump that brings iron into cytoplasm
What are the two main receptors involved in cellular uptake of Iron?
Transferrin receptor 1 (TFR1) - Outside cell > stimulates endosome
Divalent metal transporter 1 (DMT1) - Within endosome > brings it into cytoplasm
What is the primary regulator of iron homeostasis?
Hepcidin
What organ produces hepcidin?
Liver mainly
Some is produced by monocytes/macrophages
In what part of the small intestine is iron mostly absorbed?
Duodenum
What is the major effect of hepcidin?
Inhibits iron export from cells
Causes iron retention in the cells
What triggers hepcidin expression?
Iron overload
Inflammation
Hypoxia
Anemia
What is aplastic anemia?
Anemia from nonfunctioning bone marrow (e.g. cancer, radiation, toxicity)
What is megaloblastic anemia?
Results from lack of B12 (e.g. pernicious anemia), folic acid or intrinsic factor.
=Slow RBC production = erythrocytes grow into large megaloblasts
What are the types of polycythemia
- Physiologic polycythemia - High altitude, R-L shunt, chronic hypoxia
- Polycythemia vera - Genetic defect in RBC line
What is the effect of hepcidin in the GI?
Decreased iron absorption by the duodenum
What are the signs of acute iron toxicity?
Early - GI signs
Followed by circulatory collapse
Last stage - Pulmonary edema, hepatic failure, cyanosis, coma, death
In which condition would you expect development of microcytosis before hypochromia?
Iron deficiency anemia - RBC progressively get smaller (MVC), then decrease in color (MCHC)