Hemolysis Flashcards
What are the 3 ways to become anemic?
- lose RBCs
- don’t make enough RBCs
- both
What are 2 ways to lose RBCs?
- hemorrhage
2. hemolysis
What are the mechanisms of hemolysis?
- intravascular rupture of RBCs
- uptake of RBCs into macrophages in either the spleen or liver (reticuloendothelial system)
What lab values can detect hemolytic anemia?
- free hemoglobin in plasma and/or urine - not filtered by kidneys if overwhelmed by severe hemolysis
- LDH - lots released from lysed RBCs (*could also be due to lysis of other cells)
- unconjugated bilirubin - this end product of heme catabolism is normally removed by liver; turns serum yellow
- Haptoglobin - the hemoglobin recycler; it will be reduced (busy) when free Hgb levels are up
- Reticulocyte count - elevated due to compensatory increased red cell production
What findings on peripheral blood smear are indicative of compensatory RBC production?
- polychromasia
- nucleated RBCs
- increased reticulocytes
What structural proteins, if mutated or defective, could result in loss of integrity of the RBC membrane and lead to hemolysis?
- anchors: Band 3
- cables: spectrin
- associated proteins: ankyrin
What are spherocytes and what test is done to diagnose?
spherocytes are RBCs that are sphere shaped instead of biconcave disc shaped because a genetic defect in structural proteins that results in the default most surface tension efficient shape; diagnosed by the osmotic fragility test
Describe the osmotic fragility test.
place RBCs in hypotonic solution and measure how many survive; if a high proportion burst (because they couldn’t withstand the swelling) then the diagnosis is hereditary spherocytosis (or thalassemia)
Describe Hemoglobin crystallization. What disease is this significant in and how’s it diagnosed?
RBCs have evolved to carry as much Hgb as possible–that is, very close to the crystallization concentration. Minor changes in Hgb can cause crystallization and RBC instability.
Disease = Hgb C disease
Diagnosis = Hgb electrophoresis
Describe polychromasia and what it indicates.
bluish discoloration of immature RBCs that are either reticulocytes or nucleated (nRBCs). Indicates that immature RBCs are being released from bone marrow which has increased production to compensate for anemia/rapid RBC loss
Describe the process and consequences of pyruvate kinase deficiency.
Without pyruvate kinase the RBC can’t run glycolysis to make ATP which is needed for transporting Na+ out of / K+ into the cell to maintain the osmotic gradient. Upsetting the osmotic gradient will cause build up of Na+ within the cell, osmosis of water, and swelling/rupture of the RBC. (hence, anemia)
Describe G6PD deficiency.
Glutathione cleans up oxidative damage in RBCs by reducing oxidized proteins (like Hgb) and peroxide. To regenerate glutathione, NADPH must oxidize it. To generate NADPH the cell runs the pentose phosphate shunt pathway. G6PD is one of the first enzymes in this pathway. Without G6PD to run the pathway, NADPH can’t be made and glutathione can’t be regenerated; therefore the RBC dies of oxidative damage.
How does an individual usually first detect their G6PD deficiency?
hemolysis is observed following certain food intakes - especially fava beans
What are Heinz bodies?
precipitates of oxidized Hgb within RBCs that stain blue with methylene blue. They are there in patients with G6PD deficiency (because oxidized Hgb can’t be repaired in such patients)
What is methemoglobinemia?
excessive oxidation of heme iron; can occur (along with hemolysis) in G6PD deficiency