Ch 32 RBCs, anemia, polycythemia

Question 1

Where are RBCs produced in the early and mid embryo vs late fetus?

Answer 1

Embryo: early in the yolk sac
Mid trimester: liver, spleen, lymph nodes
Fetus: bone marrow

Question 2

Where are RBCs produced in the adult?

Answer 2

Membranous bones: sternum, vertebrae, ribs, ilia

Question 3

Which interleukin promotes growth/repro of all types of committed stem cells?

Answer 3

Interleukin-3

Question 4

What is a committed stem cell ?

Answer 4

Also called colony forming units, they are the early version of each cell type but can only produce that type.

Question 5

What promotes the differentiation of different blood cell types?

Answer 5

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

Question 6

What controls formation of the growth inducers?

Answer 6

Outside stimulation: low O2 stimulates RBCs, infectious disease induces WBC growth and differentiation

Question 7

Name the stages of erythrocyte development in order of ascending maturity

Answer 7

Proerythroblast, basophil erythroblast, polychromatophil erythroblast, orthochromatic erythroblast, reticulocyte, erythrocyte

Question 8

How long does it take a reticulocyte to develop into an adult cell?

Answer 8

1-2 days. They exit bone marrow by diapedesis

Question 9

What is the most potent stimulator of red blood cell production?

Answer 9

Tissue oxygenation

Question 10

How do erythropoietin and hypoxia work together to stimulate RBC production?

Answer 10

1. Oxygenation decreases via low blood volume, anemia, low Hb, poor perfusion, or pulmonary disease
2. Tissue oxygenation falls
3. Low O2 stimulates erythropoietin production from the kidneys
4. EPO stimulates RBC production and speeds their maturation
5. Continues until tissues are oxygenated enough

Question 11

Specifically, how does hypoxia stimulate EPO production?

Answer 11

Renal tissue hypoxia > increased tissue levels of transciption factor “hypoxia inducible factor 1” (HIF-1)&raquo_space; HIF-1 binds hypoxia response element to induce EPO synthesis

Question 12

What role(s) does vitamin B12 and folic acid play in RBC maturation?

Answer 12

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

Question 13

What is pernicious anemia? Be specific

Answer 13

-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

Question 14

What is sprue?

Answer 14

GI absorption abnormalities or lack of fresh vegetables causes difficulty absorbing folic acid and B12

Question 15

Which bonds in hemoglobin does oxygen bind to?

Answer 15

the coordination bonds of the Fe atom

Question 16

How is iron transported and stored in the blood?

Answer 16

1. GI-absorbed iron binds with apotransferrin to form transferrin in plasma
2. Excess iron goes to the liver
3. In the cell cytoplasm, Fe combines with apoferritin to form ferrtin. Iron can combine in clusters this way.
4. Ferritin is “storage iron”
   a. some iron is in insoluble form of Hemosiderin in cells
5. 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.

Question 17

What is the lifespan of an RBC?

Answer 17

120 days-ish

Question 18

How is iron excreted?

Answer 18

In the feces

Question 19

How is iron absorbed from the GIT?

Answer 19

*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

Question 20

How are total body iron stores regulated?

Answer 20

By altering rate of absorption

Question 21

What are the 4 roles of cytoplasmic enzymes in RBCs?

Answer 21

1. Keep the cell membrane pliable
2. Membrane transport of ions
3. Keep iron in ferrous form
4. Prevent protein oxidation

Question 22

How are old RBCs dealt with and “upcycled”?

Answer 22

1. Hb from burst cells is phagocytosed by macrophages
2. Iron is released back into the blood from the hemoglobin
3. Porphyrin portion of hemoglobin is converted by macrophages into bilirubin and released into blood for secretion into bile

Question 23

How long does it take to replenish plasma vs red blood cells after rapid hemorrhage?

Answer 23

Plasma: 1-3 days
RBCs: 3-6 weeks

Question 24

How does anemia affect cardiac output?

Answer 24

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

Question 25

What are the four main types of anemia?

Answer 25

1. Blood loss anemia: either acute or chronic. Chronic shows up as microcytic, hypochromic
2. Aplastic anemia: via bone marrow aplasia (lupus, idiopathic, chemotherapeutics, toxins)
3. Megaloblastic anemia: B12 and folic acid deficiency
4. Hemolytic anemia: spherocytosis, immune mediated (self or from the dam), sickle cell