Overview of Hematopoiesis: Strom

Question 1

What are the characteristics of pluripotent Stem cells?

Answer 1

Pluripotent stem cells are (1) rare (1 in 20 million), (2) can’t be clearly ID’d by morphology, (3) express receptors of growth factors

Question 2

What are burst forming units and colony forming units?

Answer 2

Burst forming unit is a precursor to erythroid cells and colony forming units are the precursors for thrombocytes and granulocytes. They express specific receptors for different growth factors.

Question 3

What four growth factors can be given therapeutically?

Answer 3

Erythropoietin, thrombopoietin, G-CSF, and GM-CSF

Question 4

What is myelopoiesis?

Answer 4

Myelopoiesis is the production of granulocytes and monocytes in the bone marrow (accounts for 60-70% of all blood cell formation

Question 5

What is erythropoiesis?

Answer 5

Erythropoiesis is the production of Red blood cells by stem cells. (accounts for 20-30% of blood cell formation)

Question 6

What is thrombopoiesis?

Answer 6

Thrombopoiesis is the production of thrombocytes by stem cells

Question 7

What are the morphological characteristics of blasts?

Answer 7

Blasts have immature (smudgy) chromatin, large nucleus to cytoplasm ratio, and prominent nucleoli.

Question 8

What is the lineage of neutrophils?

Answer 8

Blasts –> promyelocytes (blue granules) –> myelocytes (prominent golgi) –> Metamyelocytes (kidney shaped nucleus) –> Bands/neutrophils

Question 9

Where is granulopoiesis regulated?

Answer 9

The formation of promyelocytes from blasts and the formation of myelocytes from promyelocytes is regulated by G-CSF.

Question 10

How is thrombopoiesis regulated?

Answer 10

The liver and throbocytes release thrombopoietin steadily to stimulate thrombopoiesis.

Question 11

What is the lineage of thrombocytes?

Answer 11

Blasts –> Immature megakarycytes –> Mature megakaryocytes

Question 12

What is the lineage of erythrocytes?

Answer 12

Blast –> pronormoblast –> Basophilic erythroblast –> Polychromatophilic erythroblast –> Normochromic erythroblast

Question 13

What happens to bone marrow as we age?

Answer 13

More bone marrow is converted to fat as we age. age 5: 80% red marrow. Age 35: 40% red marrow.

Question 14

What is unique about megakaryocytes?

Answer 14

Megakaryocytes are polyploid.

Question 15

What are the 4 requirements for erythropoiesis?

Answer 15

Erythropoiesis require (1) heme synthesis, (2) globin synthesis, (3) DNA synthesis, (4) regulation.

Question 16

What is required for Heme synthesis?

Answer 16

Heme synthesis requires (1) iron, (2) Vit B6, (3) Succinyl CoA, (4) Glycine (5) B12, (6) Folate

Question 17

What is required for Globin synthesis?

Answer 17

Globin synthesis requires normal Globin genes (alpha and Beta) (2) amino acids.

Question 18

What is required for DNA synthesis?

Answer 18

DNA synthesis requires (1) deoxynucleoside tirphosphates, (2) ribonucleotide reductase, (3) Thymidine, (4) B12, (5) Folate

Question 19

What is required for regulation of erythropoiesis?

Answer 19

Regulation of erythropoiesis requires erythrpoietin, which requires (1) normal kidneys, and (2) normal bone marrow microenvironment.

Question 20

What are the three ways to become anemic?

Answer 20

To become anemic a patient either is losing to much heme/red cells, not making enough heme/red cells, or a combination of both.

Question 21

What happens in Iron deficiency anemia?

Answer 21

In iron deficiency small (microcytic) red blood cells lacking normal levels of hemeglobin (hypochromic) are observed.
Additionally RBCs haver variable size (anisocytosis) and shape (poikilocytosis).

Question 22

How must iron be altered before it is absorbed?

Answer 22

Iron must be converted from the dietary Fe3+ (ferric) form to the Fe2+ (ferrous) form. Ascorbate (vit C) is involved in this process.

Question 23

How must the iron be altered before it can be released to the blood?

Answer 23

Before iron can be released to the blood it must be reconverted from the Fe2+ ferrous form to the Fe3+ ferric form.

Question 24

What iron management proteins can measured in the blood?

Answer 24

(1) transferrin
(2) transferrin receptor
(3) Ferritin
Additionally serum iron and TIBC can be measured.

Question 25

What happens in iron deficiency to iron management proteins?

Answer 25

In iron deficiency (1) serum iron is decreased. (2) Serum transferrin is increased, (3) transferrin receptor is increased. (4) ferritin is decreased.

Question 26

What are lab findings in iron deficiency due to hemorrhage?

Answer 26

(1) reduced serum iron
(2) increased TIBC
(3) increased serum transferrin receptor
(4) reduced serum ferritin
(5) Absent bone marrow iron stores
(6) Normal hemoglobin.

Question 27

What are the disorders of globin synthesis?

Answer 27

Thalassemias are the disorders of globin synthesis.

Question 28

What are the morphological characteristics of beta thalassemia?

Answer 28

Beta thalassemia exhibits

1) microcytosis
(2) Hypochromia
(3) Target cells (abnormally pale cells

Question 29

What lab values are often altered in thalassemia?

Answer 29

(1) RBC count is normal
(2) Hgb is decreased
(3) Hct is decreased
(4) MCV is decreased.(microcytosis)

Question 30

How is thalassemia diagnosis confirmed?

Answer 30

Thalassemia is confirmed by hemaglobin electrophoresis.

Question 31

What is the structure of normal hemoglobin?

Answer 31

Normal hemaglobin is composed of 2 alpha and 2 beta. There are traces of hemaglobin present that are 2alpha2delta.

Question 32

What is the structure of alternate hemoglobins?

Answer 32

There is alpha2delta2 (HgA2) and there is alpha2gamma2 (HgF).

Question 33

What is alpha thalassemia trait 1?

Answer 33

One defective alpha gene results in thalassemia alpha trait 1. (usually clinically normal).

Question 34

What is alpha thalassemia trait 2?

Answer 34

2 defective alleles causes thalassemia trait 2.

(1) mild microcytic anemia
(2) Excess Hgb Gamma4 (barts) at birth.
(3) Normal Hgb as adults.
(4) 3% of african americans.

Question 35

What is alpha thalassemia trait 3?

Answer 35

Alpha thalassemia trait 3 is characterized by HgbH (beta4),

(1) variable microcytic anemia
(2) 15-30% HgbH

Question 36

What is alpha thalassemia trait 4?

Answer 36

Alpha thalassemia trait 4 has 4 defective alleles (is lethal in utero or soon after birth)

Question 37

What are the characteristics of impaired DNA synthesis during erythropoiesis?

Answer 37

(1) fewer cells produced
(2) Normal/enhanced maturation of cytoplasm
(3) Impaired nuclear maturation.

Question 38

What is Megaloblastic anemia?

Answer 38

Anemia caused by impaired DNA synthesis leading to cells with large mature cytoplasm and immature nuclei.

Question 39

What causes megaloblastic anemia?

Answer 39

(1) impaired B12 uptake (pernicious anemia)
(2) Impaired folate upatake
(3) Nucleoside inhibitors, ribonucleotide reductase inhibitors.
(4) Bone marrow dysfunction (myelodysplastic syndromes).

Question 40

Where is EPO made?

Answer 40

EPO is made in the peritubular cells of the kidney.

Question 41

What is the function of hepcidin?

Answer 41

Hepcidin impairs the release of iron from macrophages by downregulating ferroportin

Question 42

Why is hepcidin upregulated by acute phase reactions?

Answer 42

To protect iron stores form bacteria.

Question 43

What happens to TIBC and Transferrin in chronic inflammation?

Answer 43

In chronic inflammation TIBC and serum iron are both decreased.

Question 44

What happens to ferritin and bone marrow iron during chronic inflammation?

Answer 44

Ferritin and bone marrow iron are both increased in chronic inflammation.