Pathology of Anemia I

Question 1

Hematopoiesis

Answer 1

Series of events in which pluripotent stem cells mature into functional blood cells

Question 2

What is the precursor for blood cells lines?

Answer 2

Pluripotent stem cell is precursor of all blood cell lines: red blood cells (RBCs), white blood cells (WBCs), platelets

Question 3

What is the shape of the RBC?

Answer 3

Biconcave disc

Question 4

Reticulocyte

Answer 4

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

Question 5

Describe the red blood cell membrane, including the importance of integral proteins and the membrane cytoskeleton.

Answer 5

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).

Question 6

What are the 2 biosynthetic pathways involved in Hb synthesis?

Answer 6

– Synthesis of heme

– Synthesis of globin chains

Question 7

What is the most abundant Hb in adults?

Answer 7

HbA

Question 8

Catabolism of RBCs

Answer 8

Aging RBCs are largely removed by mononuclear phagocytic engulfment in the spleen

Question 9

What is the definition of anemia?

Answer 9

Reduced oxygen carrying capacity of blood
– Reduction below normal in volume of packed cells (hematocrit)
– Reduction in hemoglobin concentration of blood

Question 10

What are the 3 general causes of anemia?

Answer 10

􏰀Blood loss – acute and chronic
􏰀Increased rate of destruction (hemolytic anemias)
􏰀Impaired red cell production (diminished erythropoiesis)

Question 11

What are 2 causes of increased rate of RBC destruction?

Answer 11

– Intrinsic (intracorpuscular) abnormalities of RBCs

– Extrinsic (extracorpuscular) abnormalities of RBCs

Question 12

What are the 3 groups of anemia classified based on MCV?

Answer 12

1. Microcytic Anemia (MCV 100fL): Megaloblastic anemia (Vitamin B12/folate deficiency)
2. Normocytic Anemia (MCV 80-100fL)

Question 13

What are some of the characteristics of hemolytic anemia?

Answer 13

– 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

Question 14

Intravascular Hemolysis

Answer 14

– RBCs are destroyed within the vascular compartment resulting in hemoglobinemia, hemoglobinuria, and hemosiderinuria (hemosiderin is a byproduct of iron metabolism)

Question 15

What does low haptoglobin tell you?

Answer 15

Test for anemia is to look for haptoglobin - if it is low then
there must be hemolytic anemia.

Haptoglobin will bind with free Hb

Question 16

Extravascular Hemolysis

Answer 16

RBCs are destroyed primarily by tissue macrophages (as in normal RBC catabolism, but exaggerated) and there will be splenomegaly - more common

Question 17

What happens to RBCs in Hereditary Spherocytosis?

Answer 17

􏰀Intrinsic defect in RBC membrane that makes the RBCs spheroidal, less deformable, vulnerable to splenic sequestration and destruction

Question 18

What is the general inheritance pattern of Hereditary Spherocytosis?

Answer 18

Autosomal Dominant

Question 19

What does the autosomal dominant form of Hereditary Spherocytosis affect?

Answer 19

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.

Question 20

How does Hereditary Spherocytosis lead to spherical RBCs?

Answer 20

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.

Question 21

Why do spherocytes get degrade more?

Answer 21

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

Question 22

What is seen on a blood smear of Hereditary Spherocytosis?

Answer 22

Small RBCs without the central zone of pallor

Question 23

Why is jaundice seen in Hereditary Spherocytosis?

Answer 23

Jaundice due to increased bilirubin from RBC catabolism

Question 24

What are the clinical signs of Hereditary Sphercytosis?

Answer 24

􏰀Anemia
􏰀Splenomegaly 􏰀
Jaundice

Question 25

What is Aplastic Anemia and when does it occur in Hereditary Spherocytosis?

Answer 25

Infection will cause a cessation of RBC production which is highly dangerous in combination with hemolytic anemia

Question 26

What is laboratory evidence of increased osmotic fragility?

Answer 26

Hereditary Spherocytosis cells will explode faster when they take up water

Question 27

What is the inheritance of G6PD deficiency?

Answer 27

X-linked

Question 28

When do the symptoms of G6PD deficiency occur?

Answer 28

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

Question 29

What is the main mechanism with which the RBC deals with oxidative stress?

Answer 29

Glutathione

Question 30

What is necessary for the function of the glutathione system?

Answer 30

NADPH. NADPH is regenerated by G6PD

Question 31

What happens if there is G6PD deficiency with oxidative stress?

Answer 31

If enough NADPH is not available to regenerate reduced glutathione, H2O2 accumulates, oxidizing sulfhydryl groups of globin chains

Question 32

What is the characteristic finding of G6PD deficiency?

Answer 32

Hemoglobin denatures, forming precipitates known as Heinz bodies which attach to the RBC membrane, causing membrane damage and decreasing deformability

Question 33

What are bite cells?

Answer 33

Macrophages bite out Heinz bodies, with ensuing loss of membrane (“bite cells”) and formation of spherocytes

Question 34

What is Sickle Cell Anemia?

Answer 34

Disorder of hemoglobin synthesis, producing a structurally abnormal hemoglobin

Question 35

What is the common population for SCA?

Answer 35

African Americans

Question 36

What is the pathogenesis of SCA?

Answer 36

Results from point mutation leading to substitution of valine for glutamic acid at the sixth position of the 􏰂-globin gene, resulting in HbS

Question 37

What is seen on smear of SCA?

Answer 37

Sickling of cells

Question 38

What are the 2 major clinical consequences of SCA?

Answer 38

Major 2 clinical consequences of sickling are chronic hemolytic anemia and occlusion of small blood vessels

Question 39

What types of hemolysis occur with SCA?

Answer 39

Both.
-􏰀 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

Question 40

What happens to the spleen with SCA?

Answer 40

-􏰀 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”

Question 41

What symptoms are usually seen with sickle cell TRAIT?

Answer 41

Patients with sickle cell trait usually have an uneventful clinical course