11.5: Anemia I Flashcards
What is a pluripotent stem cell?
Precursor of all blood cell lines: RBC, WBC, platelet
What is hematopoiesis?
- Series of events in which pluripotent stem cells mature into functional blood cells
- Occurs in marrow
RBC characteristics?
- Anucleate
- Bi concave
- Make up majority of blood cells
What is blood smear?
- Allows visualization of formed blood elements
- Drop of blood on glass then stained
How do you see if there is issue with hematopoiesis?
Bone marrow aspirate and biopsy
What is a reticulocyte?
- First stage or RBC released from marrow into periphary
- Cytoplasm may be blueish bind from residual RNA
Life span of RBC?
120 Days
What is the structure of RBC membrane? How is it different from other cells?
- **Membrane skeleton controlling bi concave shape and cell malleability: Allows for microcirculation transit
- Otherwise is phospholipid bilayer with membrane proteins, glycolipids and cholesterol just like other cells
What is hemoglobin?
- Functional protein in RBC allowing for O2 transport
2 Biosynthetic pathways involved in hemoglobin synthesis?
- Synthesis of HEME
2. Synthesis of globin chains
What is heme?
- 4 pyrrole groups joined in a ring
- Ferrous iron is incorporated in center
What are globin chains?
- 150 aa protein with heme binding site
- 2 Globin dimers form hemoglobin
- Hemoglobin A comprises 95% of globin in adults
What is hemoglobin A?
- Makes of 95% of adult hemoglobin
- Composed of 2 alpha and 2 beta chains
How are aging RBCs removed?
- Mononuclear phagocytes in spleen responsible for removal of aged RBCs
- Heme is divided into iron which is recycled, and porphyrin rings: removed as bilirubin
- Globin is dismantled into amino acids
What are porphyrin rings?
- Byproduct of heme degradation
- Eliminated as bilirubin
Term for accelerated RBC destruction?
Hemolysis
What is anemia?
- Reduced oxygen carrying capacity of the blood
- Reduction in red cell mass
3 Classes of anemia?
- Blood loss
- Hemolytic: increased rate of destruction
- Diminished production
Intrinsic factors leading to increased hemolysis?
- Spherocytosis
- G6PD deficiency
- Sickle Cell anemia
- Thalassemia
- PNH (Acquired)
3 types of disturbances in differentiation?
- Iron deficiency anemia
- Megaloblastic anemia: B12/folate
- Anemia of chronic disease
What is MCV?
“Mean cell volume”
- Reading from CBC
What is MCH?
“Mean cell Hemoglobin”
- Reading from CBC
What is MCHC?
“Mean cell Hemoglobin concentration”
- Reading from CBC
What is RDW?
“Red cell distribution width”
- Measures anisocytosis
- Variation in RBC volume
What is anisocytosis?
Variation in RBC size
Examples of MICROcytic anemia?
- Iron deficiency
- Thalassemias
- Anemia of chronic disease
Examples of MACROcytic anemia?
- Megaloblastic anemia: B12 / Folate deficiency
Characteristics of hemolytic anemias?
- Shortened RBC lifespan
- Accumulation of products of RBC metabolism
- Increase in erythropoiesis from bone marrow
Where does extravascular hemolysis occur?
Spleen
Where does intravascular anemia occur and what does in cause?
Occurs in vascular compartment causing:
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria: byproduct of iron metabolism
What happens to free hemoglobin in the blood?
- Binds to haptoglobin and is removed by liver
- Low haptoglobin means hemolytic anemia
What does low haptoglobin mean?
- Hemolytic anemia
- It is binding the hemoglobin to remove it from serum
What is extravascular hemolysis?
- Accelerated destruction of RBCs in spleen by macs
- More common than intravascular
- Don’t see same products in serum
- Hyperactive reticular system leads to splenomegaly
What is hereditary spherocytosis?
- Intrinsic deficiency in RBC spectrin or ankyrin
- Spheroid RBCs, less malleable
- More vulnerable to splenic destruction/sequestration
- Autosomal dominant
What is spectrin?
- Main protein in membrane skeleton of RBC
- Deficiency leads to spherocytosis
What is ankyrin?
- Protein that anchors spektrin to membrane proteins
- Deficient in autosomal dominant Spherocytosis
- Recessive is spectrin deficiency
Pathophysiology of spherocytosis?
- Decreased interaction w/ skeleton and lipids layer
- Reduced membrane stability and loss of fragments
- Decreased surface are to volume ratio causing spherical shape
What does biconcave shape of RBC allow for?
- Deformation allowing it to squeeze through tight spaces in spleen and other areas
- If you are spherical, takes longer to get through spleen and macs eat you
What can improve spherocytosis?
- Splenectomy
- Prevents destruction of RBCs in spleen
- Still have disease by symptoms are better
What are RBCs w/o central pallor in smear indicative of?
Spherocytosis
Clinical findings in spherocytosis?
- Jaundice
- Anemia
- Splenomegaly
- Increased osmotic fragility
- Increased MCHC
What are anemia, jaundice, and splenomegaly consistent with?
Spherocytosis
What is Aplastic crisis?
- Occurs in hemolytic anemia
- Bone marrow ramps up and is maxed out
- If infection occurs, marrow cannot respond with WBCs
What is increased MCHC characteristic of?
Spherocytosis
How is G6PD deficiency inherited?
- X linked
- Higher incidence in males than females
When does G6PD deficiency manifest?
- Usually there are no symptoms
- When there is oxidative stress on RBC from stress or infection
What is the glutathione system?
- Manner in which RBCs deal with oxidative stress
- Glutathione is oxidized by stress to protect RBC
- NADPH reduces Glutathione so it can be used again becoming NADP in process
- G6PD responsible for converting back into NADPH
How does oxidative stress damage RBC?
- H2O2 oxidizes sulfhydryl groups of globin chains
- Hemoglobin denatures and precipitates forming Heinz bodies
- Heinz bodies attach to RBC membrane decreasing maleability
What are Heinz bodies?
- Denatured hemoglobin from oxidative stress
- Bind to RBC decreasing maleability
- Causes intravascular hemolysis
- Macs also bit off Heinz bodies leading to spherocytes
Clinical course of G6PD deficiency?
- Intravascular hemolysis
- Hemoglobinemia
- Hemoglobinuria
- Decreased hematocrit
- Bone marrow produces more RBCs to compensate
What is Sickle Cell disease?
- Structurally abnormal hemoglobin synthesis
- Most common form of familial hemolytic anemia
- Defective HbS
- You must be homozygous to show symptoms
What is the most common form of hemolytic anemia?
Sickle cell Disease
What is HbS?
- Responsible for sickle cell trait
Pathophys of sickle cell?
- Point mutation of valine for glutamic acid in B globin
- Forms HbS molecules that aggregate and polymerize
- Red cell distorts into sickle shape
3 things sickling of cells dependant on?
- Fall in PH
- Amount of HbS
- High MCHC
Clinical consequences of sickling?
- Hemolytic anemia
- Occlusion of small vessels
- Splenomegaly in kids
- Hypoxic damage to spleen leading to fibrosis
- Vaso Occlusive / painful crises
- Aplastic crises
- Increased susceptibility to infection
- Ischemic damage from occlusion
What happens in sickle cell trait?
- Usually not clinical appearance
