Pathology of Anemia I Flashcards
Hematopoiesis
Series of events in which pluripotent stem cells mature into functional blood cells
What is the precursor for blood cells lines?
Pluripotent stem cell is precursor of all blood cell lines: red blood cells (RBCs), white blood cells (WBCs), platelets
What is the shape of the RBC?
Biconcave disc
Reticulocyte
Reticulocyte is usually the first stage of the RBC released from marrow into peripheral blood; cytoplasm may be slightly bluish-pink due to residual RNA
Describe the red blood cell membrane, including the importance of integral proteins and the membrane cytoskeleton.
- Phospholipid bilayer combined with glycolipids and cholesterol; integral proteins span the bilayer (act as sites for RBC antigen formation).
- Membrane cytoskeleton controls biconcave shape of cell deformability (qualities essential for travel through microcircualtion).
What are the 2 biosynthetic pathways involved in Hb synthesis?
– Synthesis of heme
– Synthesis of globin chains
What is the most abundant Hb in adults?
HbA
Catabolism of RBCs
Aging RBCs are largely removed by mononuclear phagocytic engulfment in the spleen
What is the definition of anemia?
Reduced oxygen carrying capacity of blood
– Reduction below normal in volume of packed cells (hematocrit)
– Reduction in hemoglobin concentration of blood
What are the 3 general causes of anemia?
Blood loss – acute and chronic
Increased rate of destruction (hemolytic anemias)
Impaired red cell production (diminished erythropoiesis)
What are 2 causes of increased rate of RBC destruction?
– Intrinsic (intracorpuscular) abnormalities of RBCs
– Extrinsic (extracorpuscular) abnormalities of RBCs
What are the 3 groups of anemia classified based on MCV?
- Microcytic Anemia (MCV 100fL): Megaloblastic anemia (Vitamin B12/folate deficiency)
- Normocytic Anemia (MCV 80-100fL)
What are some of the characteristics of hemolytic anemia?
– Shortening of normal RBC life span (premature destruction of RBCs)
– Accumulation of products of hemoglobin catabolism
– Marked compensatory increase in erythropoiesis within the bone marrow
Intravascular Hemolysis
– RBCs are destroyed within the vascular compartment resulting in hemoglobinemia, hemoglobinuria, and hemosiderinuria (hemosiderin is a byproduct of iron metabolism)
What does low haptoglobin tell you?
Test for anemia is to look for haptoglobin - if it is low then
there must be hemolytic anemia.
Haptoglobin will bind with free Hb
Extravascular Hemolysis
RBCs are destroyed primarily by tissue macrophages (as in normal RBC catabolism, but exaggerated) and there will be splenomegaly - more common
What happens to RBCs in Hereditary Spherocytosis?
Intrinsic defect in RBC membrane that makes the RBCs spheroidal, less deformable, vulnerable to splenic sequestration and destruction
What is the general inheritance pattern of Hereditary Spherocytosis?
Autosomal Dominant
What does the autosomal dominant form of Hereditary Spherocytosis affect?
Most frequent is a mutation in the ankyrin gene, resulting in reduced synthesis of ankyrin, and a secondary reduction in spectrin assembly as spectrin is no longer anchored and more easily degraded.
How does Hereditary Spherocytosis lead to spherical RBCs?
Diminish interactions between the membrane cytoskeleton and the overlying lipid bilayer which results in reduced membrane stability and loss of membrane fragments.
Reduction in cell surface to volume ratio causes the cells to assume the smallest possible diameter for a given volume: a sphere.
Why do spherocytes get degrade more?
In the splenic sinus, normal RBCs are deformable and can squeeze through spaces while the spherocytes remain in the splenic sinus longer, allowing macrophages to engulf them
What is seen on a blood smear of Hereditary Spherocytosis?
Small RBCs without the central zone of pallor
Why is jaundice seen in Hereditary Spherocytosis?
Jaundice due to increased bilirubin from RBC catabolism
What are the clinical signs of Hereditary Sphercytosis?
Anemia
Splenomegaly
Jaundice
