Flashcards in 11.5: Anemia I Deck (57):
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
- 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?
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?
1. 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?
What is anemia?
- Reduced oxygen carrying capacity of the blood
- Reduction in red cell mass
3 Classes of anemia?
1. Blood loss
2. Hemolytic: increased rate of destruction
3. Diminished production
Intrinsic factors leading to increased hemolysis?
2. G6PD deficiency
3. Sickle Cell anemia
5. PNH (Acquired)
3 types of disturbances in differentiation?
1. Iron deficiency anemia
2. Megaloblastic anemia: B12/folate
3. 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?
1. Iron deficiency
3. Anemia of chronic disease
Examples of MACROcytic anemia?
1. Megaloblastic anemia: B12 / Folate deficiency
Characteristics of hemolytic anemias?
1. Shortened RBC lifespan
2. Accumulation of products of RBC metabolism
3. Increase in erythropoiesis from bone marrow
Where does extravascular hemolysis occur?
Where does intravascular anemia occur and what does in cause?
Occurs in vascular compartment causing:
3. 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?
- Prevents destruction of RBCs in spleen
- Still have disease by symptoms are better
What are RBCs w/o central pallor in smear indicative of?
Clinical findings in spherocytosis?
4. Increased osmotic fragility
5. Increased MCHC
What are anemia, jaundice, and splenomegaly consistent with?
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?
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
- 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?
1. Fall in PH
2. Amount of HbS
3. High MCHC
Clinical consequences of sickling?
1. Hemolytic anemia
2. Occlusion of small vessels
3. Splenomegaly in kids
4. Hypoxic damage to spleen leading to fibrosis
5. Vaso Occlusive / painful crises
6. Aplastic crises
7. Increased susceptibility to infection
8. Ischemic damage from occlusion