Flashcards in Pathology of Anemia I Deck (41):
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?
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.
1. Phospholipid bilayer combined with glycolipids and cholesterol; integral proteins span the bilayer (act as sites for RBC antigen formation).
2. 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?
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?
1. Microcytic Anemia (MCV 100fL): Megaloblastic anemia (Vitamin B12/folate deficiency)
3. 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
– 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
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?
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?
What is Aplastic Anemia and when does it occur in Hereditary Spherocytosis?
Infection will cause a cessation of RBC production which is highly dangerous in combination with hemolytic anemia
What is laboratory evidence of increased osmotic fragility?
Hereditary Spherocytosis cells will explode faster when they take up water
What is the inheritance of G6PD deficiency?
When do the symptoms of G6PD deficiency occur?
Usually no symptoms unless red cells are subjected to oxidant injury following exposure to offending drugs or toxins:
– drugs, such as antimalarials, sulfonamides, nitrofurantoin, and others
– infections, probably acting by generation of oxidant free radicals in macrophages
What is the main mechanism with which the RBC deals with oxidative stress?
What is necessary for the function of the glutathione system?
NADPH. NADPH is regenerated by G6PD
What happens if there is G6PD deficiency with oxidative stress?
If enough NADPH is not available to regenerate reduced glutathione, H2O2 accumulates, oxidizing sulfhydryl groups of globin chains
What is the characteristic finding of G6PD deficiency?
Hemoglobin denatures, forming precipitates known as Heinz bodies which attach to the RBC membrane, causing membrane damage and decreasing deformability
What are bite cells?
Macrophages bite out Heinz bodies, with ensuing loss of membrane (“bite cells”) and formation of spherocytes
What is Sickle Cell Anemia?
Disorder of hemoglobin synthesis, producing a structurally abnormal hemoglobin
What is the common population for SCA?
What is the pathogenesis of SCA?
Results from point mutation leading to substitution of valine for glutamic acid at the sixth position of the -globin gene, resulting in HbS
What is seen on smear of SCA?
Sickling of cells
What are the 2 major clinical consequences of SCA?
Major 2 clinical consequences of sickling are chronic hemolytic anemia and occlusion of small blood vessels
What types of hemolysis occur with SCA?
- Intravascular hemolysis may occur due to increased mechanical fragility of severely damaged RBCs
- Extravascular hemolysis occurs from rigid sickled RBCs becoming sequestered in the spleen
What happens to the spleen with SCA?
- Children may have moderate splenomegaly caused by the red pulp congestion
- Over time, hypoxic tissue damage occurs and the spleen becomes small and fibrotic: “functional splenectomy”