Approach to Anemias Flashcards
How can you tell if an erythrocyte is newly produced?
Do a DNA staining and look for granules containing DNA (which will still exist in young denucleated erythrocytes for 1-2 days after ejection from bone marrow). These classify the erythrocyte as a reticulocyte.
Daily turnover of erythrocytes
~1-2% destroyed by the spleen per day, ~1-2% produced by bone marrow per day
Stress reticulocytes
Tend to be pushed out of the bone marrow early in times of hemorrhage or hemolytic anemia. Still blue from high RNA density, you don’t even need a special stain to see them.
High numbers of ‘bluish red cells’ is termed polychromatophilia.
Anemias of erythrocyte loss
Hemoltyic or hemorrhagic
In hemolytic anemia, markers of erythrocyte and heme catabolism will be apparent in blood. This is not true for hemorrhagic anemia, but rather in hemorrhagic anemia iron is often scarce.
Haptoglobin
Free hemoglobin scavenger. Binds up free hemoglobin in plasma and brings it to macrophages for catabolism.
As a consequence, during hemolytic anemic processes, haptoglobin levels fall.
Classic pattern of hemolysis
- Anemia
- Increased reticulocytes
- Elevated LDH and indirect bilirubin
- Decreased haptoglobin
If hemolytic anemia persists chronically, the patient may develop. . .
. . . a folate deficiency and bilirubin gallstones. These bilirubin gallstones may also impair secretion, leading to direct bilirubinemia on top of the pre-existing indirect bilirubinemia.
Intravascular hemolysis
When hemolysis takes place within the ciruclatory system. In these cases, large amounts of hemoglobin will be secreted into plasma and haptoglobin will be completely consumed.
When haptoglobin cannot handle the hemoglobin load, as in intravascular hemolytic processes, . . .
. . . the remaining hemoglobin is filtered in the kidney, then reabsorbed and re-packaged as hemosiderin.
Chronically, hemoglobin and hemosiderin may be lost in urine, and in this case iron losses become significant.
Extravascular hemolysis
Mediated primarily by macrophages
Acute and chronic hemolysis summary
Reasons one might have an erythrocyte production problem
- Not enough EPO (renal failure)
- Thalassemia (disorder of hemoglobin production)
- Iron deficiency (iron deficiency anemia)
- Folate or B12 deficiency (megaloblastic anemia)
- Not enough stem cells (aplastic or hypoplastic anemia)
- Fibrosis of marrow
- Myeloma/leukemia/lymphoma/metastatic marrow cancer
- Granulomas in marrow
Normocytic anemia
Fewer erythrocytes, but erythrocytes look normal. Low BUN and creatinine levels indicating renal failure.
Results in insufficient EPO production, leading to anemia.
Microcytic anemia
When hemoglobin synthesis is compromised or there is not sufficient iron available for synthesis (iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia). Red cells are made smaller to preserve the concentration of hemoglobin within each cell.
Megaloblastic anemia
Affects myeloid and erythroid precursors. Precursors exhibit poor nuclear development and a high nuclear to cytoplasmic ratio. Erythrocytes are macrocytic and more ovular.PMNs with 6 lobes may also be seen in these anemias.
Caused by B12 or folate deficiency, or drug-induced.