Ch 32 RBCs, anemia, polycythemia Flashcards
Where are RBCs produced in the early and mid embryo vs late fetus?
Embryo: early in the yolk sac
Mid trimester: liver, spleen, lymph nodes
Fetus: bone marrow
Where are RBCs produced in the adult?
Membranous bones: sternum, vertebrae, ribs, ilia
Which interleukin promotes growth/repro of all types of committed stem cells?
Interleukin-3
What is a committed stem cell ?
Also called colony forming units, they are the early version of each cell type but can only produce that type.
What promotes the differentiation of different blood cell types?
Differentiation inducers: proteins that cause one type of committed stem cell to differentiate one or more steps toward a final adult cell. Examples are
Hypoxemia> RBC
Infectious dz > WBCs
What controls formation of the growth inducers?
Outside stimulation: low O2 stimulates RBCs, infectious disease induces WBC growth and differentiation
Name the stages of erythrocyte development in order of ascending maturity
Proerythroblast, basophil erythroblast, polychromatophil erythroblast, orthochromatic erythroblast, reticulocyte, erythrocyte
How long does it take a reticulocyte to develop into an adult cell?
1-2 days. They exit bone marrow by diapedesis
What is the most potent stimulator of red blood cell production?
Tissue oxygenation
How do erythropoietin and hypoxia work together to stimulate RBC production?
- Oxygenation decreases via low blood volume, anemia, low Hb, poor perfusion, or pulmonary disease
- Tissue oxygenation falls
- Low O2 stimulates erythropoietin production from the kidneys
- EPO stimulates RBC production and speeds their maturation
- Continues until tissues are oxygenated enough
Specifically, how does hypoxia stimulate EPO production?
Renal tissue hypoxia > increased tissue levels of transciption factor “hypoxia inducible factor 1” (HIF-1)»_space; HIF-1 binds hypoxia response element to induce EPO synthesis
What role(s) does vitamin B12 and folic acid play in RBC maturation?
B12 = cyanocobalamin
-Both: DNA synthesis via thymidine triphosphate formation
Needed for RBC nuclear maturation and cell division. Resultant RBCs are large and flimsy.
***Deficiency causes maturation failure
What is pernicious anemia? Be specific
-Failure to absorb vit B12 caused by atrophic gastric mucosa that fails to produce intrinsic factor. Intrinsic factor is essential for enabling B12 absorption.
Takes 3-4 years to become obvious
What is sprue?
GI absorption abnormalities or lack of fresh vegetables causes difficulty absorbing folic acid and B12
Which bonds in hemoglobin does oxygen bind to?
the coordination bonds of the Fe atom
How is iron transported and stored in the blood?
- GI-absorbed iron binds with apotransferrin to form transferrin in plasma
- Excess iron goes to the liver
- In the cell cytoplasm, Fe combines with apoferritin to form ferrtin. Iron can combine in clusters this way.
- Ferritin is “storage iron”
a. some iron is in insoluble form of Hemosiderin in cells - Stored iron in the ferritin pool is removed and transported to area of need when levels are low, and transferrin binds esp strongly to receptors on the erythroblasts in the bone marrow.
What is the lifespan of an RBC?
120 days-ish
How is iron excreted?
In the feces
How is iron absorbed from the GIT?
*all parts of SI, but mostly as…
1. Liver secretes apotransferrin in bile
2. Apotransferrin binds to free iron, Hb, and myoglobin in the duodenum to form transferrin
3. Binds SI epithelial cells, pinocytosis, and released in blood as plasma transferrin
How are total body iron stores regulated?
By altering rate of absorption
What are the 4 roles of cytoplasmic enzymes in RBCs?
- Keep the cell membrane pliable
- Membrane transport of ions
- Keep iron in ferrous form
- Prevent protein oxidation
How are old RBCs dealt with and “upcycled”?
- Hb from burst cells is phagocytosed by macrophages
- Iron is released back into the blood from the hemoglobin
- Porphyrin portion of hemoglobin is converted by macrophages into bilirubin and released into blood for secretion into bile
How long does it take to replenish plasma vs red blood cells after rapid hemorrhage?
Plasma: 1-3 days
RBCs: 3-6 weeks
How does anemia affect cardiac output?
Anemia leads to reduced blood viscosity, lowering peripheral resistance. Also, the associated hypoxia also causes peripheral vasodilation and increases cardiac output by increasing venous return.
Major results= increased cardiac output and pumping workload on the heart
What are the four main types of anemia?
- Blood loss anemia: either acute or chronic. Chronic shows up as microcytic, hypochromic
- Aplastic anemia: via bone marrow aplasia (lupus, idiopathic, chemotherapeutics, toxins)
- Megaloblastic anemia: B12 and folic acid deficiency
- Hemolytic anemia: spherocytosis, immune mediated (self or from the dam), sickle cell
