Overview RBC

=Objectives=

Be able to identify the principal sites of hematopoiesis in the human embryo, fetus, infant, and adult
Human Embryo and Fetus: Initially, the yolk sac is the major hematopoeitic site in the embryo. This is roughly for the first 2.5 months. After about six weeks, the liver starts to kick in. It is the major hematopoietic site from about 10 weeks until about 28 weeks, roughly correlating with the transition from embryo to fetus. From week 28 onwards, the bone marrow becomes the major hematopoietic site. The spleen also plays a minor role in hematopoiesis in the fetus from about 10 weeks until about week 28.

Human Infant: In the infant, hematopoiesis occurs in the vertebrae, pelvis, sternum, ribs, and the long bones (tibias and femurs).

Human Adult: From the teenage years through the mid-twenties, hematopoiesis in the long bones drops off sharply. By age 25, the majority of hematopoiesis occurs in the following sites in the following order: vertebrae and pelvis, sternum, ribs, and a small contribution from femurs and then tibias.

Be able to diagram the erythroid differentiation pathway from pluripotent stem cell to mature red cells. Your diagram should include four progenitor cell classes which precede the pronormoblast
PHSC: Pluripotent Hematopoietic Stem Cell Myeloid stem cell CFU-GEMM: Colony forming unit - Granulocyte, Erythrocyte, Monocyte, Megakaryocyte BFU-E: Burst forming unit-erythroid lineage CFU-E: Colony forming unit-erythroid lineage Pro-normoblast

==Be able to diagram the feedback loop which regulates red blood cell production and list five factors which affect oxygen delivery to the tissues. Be able to identify the portion of the loop which is most often the cause of anemia in patients with renal disease.==

Be able to describe the globin chain composition of Hb A, Hb F, Hb A2 and the relative proportions of each hemoglobin in normal adult red cells.
==Be able to draw a normal hemoglobin oxygen dissociation curve, identify P50 on the curve, and show the direction of shift of the curve elicited by increases or decreases of pH, 2,3-DPG concentration, HbF, increased temperature, and HbS.== ==Be able to list five disorders associated with increased erythropoietin production and two disorders associated with absolute or relative erythropoietin deficiency. Be able to list two disorders associated with abnormalities of erythropoietin receptor function.== Deficiency: -Renal failure -anemia of chronic disease Increased Epo -hypoxia(lung disease, congenital heart disease, obstructive sleep apnea) -high altitude -EPO secreting tumors from kidney or liver (rare)

==Be able to list the main clinical indication for the use of recombinant human erythropoietin as well as five diseases in which recombinant human erythropoietin may be indicated for the treatment of symptomatic anemia.== Clinical indications Absolute or relative deficiency of EPO -renal failure pre-dialysis -anemia of chronic disease Diseases Chronic renal failure Patients undergoing surgery HIV+ patients being treated with AZT Anemia secondary to chemotherapy Anemia of chronic disease Low risk myelodysplasia Aim for hemoglobin level at 12g/dL

Be able to diagram or briefly describe the Bohr effect. Be able to describe how CO2 and pH levels in the tissue and alveoli modify Hb O2 affinity.
==Be able to briefly describe or diagram the main components of the normal red blood cell membrane and associated cytoskeleton. You will be asked to identify those proteins which are deficient in hereditary spherocytosis and hereditary eliptocytosis.== ==Be able to briefly describe the Embden-Meyerhof pathway. In particular you will need to know 1) how the pathway helps regulate the reduction of methemoglobin back to hemoglobin, 2) how the pathway relates to 2,3-DPG production, and 3) how the pathway interacts with the hexose monophosphate shunt.== ==Be able to briefly diagram or describe the function of the hexose monophosphate shunt and how this helps protect red cells from oxidant stress. Be able to identify or diagram the defective step in patients with G-6-PD deficiency.==