Karius Flashcards
Erythropoieitin - production location, stimulation, action
- Produced in kidney and liver
- Stimulated by tissue hypoxia, resulting in HIF not being destructed and accumulating in cell, then acting as a transcription factor for genes like EPO and increased Fe absorption/transport
- EPO acts on HSC to increase erythroid lineage and speed RBC maturation.
Granulocyte Colony Stimulating Factor - production location, action
- Produced by endothelium, macrophages, other mature immune cells. Regulated by TNF-alpha and IL-1alpha
- Factor acts on HSC to promote differentiation and development of various WBC lineages (also activates mature WBC)
Thrombopoietin - production location and regulation
i. Produced continually by liver and kidney
ii. Regulation via binding to mpl-receptor on circulating platelets, then TPO is internalized and degraded
Correlation between platelet number and free TPO
Inversely proportional to platelets
- Low platelet number correlates with increased free TPO and increased production of platelets
- High platelet number correlates with decreased free TPO due to binding, internalization, and consequent TPO destruction.
What protein maintains RBC shape, allowing for what?
spectrin maintains biconcave shape, allowing for deformation through small capillaries and splenic sinusoids
Location of hematopoiesis - childhood v. adulthood
i. Childhood – long bones of legs
ii. Adulthood – sternum and vertebra
First identifiable RBC precursor
Proerythroblast
Two nutrient/vitamin requirements for maturation of RBC
Vitamin B12 and Folic Acid
Deficiency in Vitamin B12 - usually due to what, and leads to what?
Due to intrinsic factor deficiency=decreased absorption.
B12 deficiency leads to pernicious anemia
Deficiency in Folate - usually due to what
heat, alcohol, intestinal absorption
Steps in hemoglobin production
- Succinyl-CoA + glycine = pyrrole
- Four pyrroles = protoporphyrin 9
- Protoporphyrin 9 + iron = heme
- Heme + peptide chain (alpha or Beta) = hemoglobin chain
- Four hemoglobin chains = one hemoglobin molecule
Type of hemoglobin chains in: . a. Adult hemoglobin
b. Fetal hemoglobin
c. Sickle cell hemoglobin
a. Adult hemoglobin: 2 alpha + 2 beta
b. Fetal hemoglobin: 2 alpha + 2 gamma
c. Sickle cell hemoglobin: 2 beta with amino acid substitution, valine replaces glutamic acid
What is the major limitation to hemoglobin production?
iron availability
What does protein does the liver add to bile to increase iron availability?
apotransferrin added to bile so that hemoglobin can bind (making transferrin), which is released into blood
What is the liver storage protein for iron?
apoferritin