Erythrocytes Flashcards
What are 5 general characteristics of RBCs?
- Function to transport oxygen and CO2
- Containers of hemoglobin
- Membrane provides strength and flexibility
- Metabolic apparatus provides energy and protection from environmental insults
- Shape provides deformability
Why do men have higher levels affiliated with RBCs than women?
Testosterone increases erythrocyte development
What are normal hematocrit levels in men and women?
Men = 39-49% Women = 33-43%
What are normal hemoglobin levels in men and women?
Men = 13.6-17.2 Women = 12.0-15.0
What are the main membrane proteins involved in anchoring the RBC cytoskeleton?
Spectrin anchors the actin filaments within the RBC
Ankyrin binds to spectrin and binds to the membrane via band 3
How might cells appear if they have problems with their cytoskeletal proteins?
If there is a problem with dimerization, the cells will appear as an elliptocyte; if there is a problem with the proteins themselves, they will appear as spherocytes without biconvacity
What three nutritional factors are necessary for maintained red blood cell populations?
Iron
Folate
Vitamin B12
Where is iron absorbed and by what proteins?
In the duodenum; hepcidin allows iron to get into enterocytes
What compound carries iron in the blood? How do cells acquire iron from it?
Ferritin; it is endocytosed, cleaved from its iron and then excreted back into the blood stream
How is iron recycled after red blood cells die?
Macrophages consume red blood cells and cleave iron from hemoglobin
Where is iron stored? How would deficiency be diagnosed?
The liver; low serum Fe, high transferrin levels, or low ferritin will indicate anemia
Why are Vitamin B12 and folate necessary? How would deficiencies appear?
They are involved in DNA synthesis and methionine resynthesis; erythrocyte precursors divide rapidly and absorb them quickly. A deficiency would present as a patient with macrocytic anemia and hypersegmented neutrophils
What are the components that make up hemoglobin?
Globin groups, protoporphyrin, and iron. Iron and protoporphyrin combine to make heme
What are the steps involved in the production of protoporphyrin?
succinyl CoA and delta-ALA are transformed in the cytosol to porphobilinogen–>uroporphytinogen–>coproporphyrinogen-
–>proporphyrin (in mitochondria)
What are the two most common forms of hemoglobin in adults and their components? What is the most common form in a fetus and its components?
Hemoglobin A (2 alpha and 2 beta) and A2 (2 alpha and 2 delta) -Hemoglobin F (2 alpha and 2 gamma)
What are the two main types of hemoglobin abnormalities? What are their etiologies?
1) Structural variants
2) Thalassemias
- -Most are genetic point mutations, of which there are over 400
What is the mechanism of a hemoglobin structural variant?
Alter globin polypeptide without affecting its rate of
synthesis
What is the mechanism of a thalassemia?
Decreased synthesis of one or more of the globin chains
Resulting in imbalance in relative amounts of the α & β chains
As a result, the normal chain propagates in excess and precipitates in the cell, ultimately lysing the cell
What are the genetic bases of alpha and beta thalassemias?
Alpha tend to be gene deletions
Beta tend to be missense deletions or spice mutations and often manifest as more severe anemias
How will most genetic mutations in glycolysis affect red blood cells and why?
Since RBCs do not have any alternate machinery to generate energy, mutations in glycolysis enzymes or in the hexose shunt (which regenerates glutathione) will typically manifest as hemolytic anemia
What is the purpose of the Methemoglobin reductase pathway?
It uses NADH to regenerate ferrous iron from ferric iron (Fe++ from Fe+++)
What is the purpose of the Luebering-Rappaport pathway?
It draws 1,3 BPG from the glycolysis pathway and transforms it into 2,3 BPG, which is needed for oxygen offloading
What is the fate of porphyrin after red blood cell lysis?
It is converted to bilirubin and carbon monoxide and conjugated in the liver to make bile (unconjugated bilirubin is a signal of RBC lysis)
What are the N-terminal sugars that determine the ABO antigens?
A- (N-acetylgalactosamine)
B-(D‐galactose)
O-(fucose alone)
Why are people incompatible from birth to A or B (or both) antigens?
IgM antibodies to the incompatible blood types are made readily without exposure to blood as those sugars exist as antigens on bacterial and viral substances
What are the antigens of the Rhesus factor?
D <—this is the predominant one
Cc,
Ee
What are the clinical implications of a Rh incompatibility?
After an Rh negative person is exposed to an Rh+ blood supply, they will readily produce IgG antibodies to it. This can affect transfusions. More commonly presents as hemolytic disease of the newborn where an Rh negative mother is carrying an Rh positive fetus
