Overview of Hematopoiesis: Strom Flashcards
What are the characteristics of pluripotent Stem cells?
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
What are burst forming units and colony forming units?
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.
What four growth factors can be given therapeutically?
Erythropoietin, thrombopoietin, G-CSF, and GM-CSF
What is myelopoiesis?
Myelopoiesis is the production of granulocytes and monocytes in the bone marrow (accounts for 60-70% of all blood cell formation
What is erythropoiesis?
Erythropoiesis is the production of Red blood cells by stem cells. (accounts for 20-30% of blood cell formation)
What is thrombopoiesis?
Thrombopoiesis is the production of thrombocytes by stem cells
What are the morphological characteristics of blasts?
Blasts have immature (smudgy) chromatin, large nucleus to cytoplasm ratio, and prominent nucleoli.
What is the lineage of neutrophils?
Blasts –> promyelocytes (blue granules) –> myelocytes (prominent golgi) –> Metamyelocytes (kidney shaped nucleus) –> Bands/neutrophils
Where is granulopoiesis regulated?
The formation of promyelocytes from blasts and the formation of myelocytes from promyelocytes is regulated by G-CSF.
How is thrombopoiesis regulated?
The liver and throbocytes release thrombopoietin steadily to stimulate thrombopoiesis.
What is the lineage of thrombocytes?
Blasts –> Immature megakarycytes –> Mature megakaryocytes
What is the lineage of erythrocytes?
Blast –> pronormoblast –> Basophilic erythroblast –> Polychromatophilic erythroblast –> Normochromic erythroblast
What happens to bone marrow as we age?
More bone marrow is converted to fat as we age. age 5: 80% red marrow. Age 35: 40% red marrow.
What is unique about megakaryocytes?
Megakaryocytes are polyploid.
What are the 4 requirements for erythropoiesis?
Erythropoiesis require (1) heme synthesis, (2) globin synthesis, (3) DNA synthesis, (4) regulation.
What is required for Heme synthesis?
Heme synthesis requires (1) iron, (2) Vit B6, (3) Succinyl CoA, (4) Glycine (5) B12, (6) Folate
What is required for Globin synthesis?
Globin synthesis requires normal Globin genes (alpha and Beta) (2) amino acids.
What is required for DNA synthesis?
DNA synthesis requires (1) deoxynucleoside tirphosphates, (2) ribonucleotide reductase, (3) Thymidine, (4) B12, (5) Folate
What is required for regulation of erythropoiesis?
Regulation of erythropoiesis requires erythrpoietin, which requires (1) normal kidneys, and (2) normal bone marrow microenvironment.
What are the three ways to become anemic?
To become anemic a patient either is losing to much heme/red cells, not making enough heme/red cells, or a combination of both.
What happens in Iron deficiency anemia?
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).
How must iron be altered before it is absorbed?
Iron must be converted from the dietary Fe3+ (ferric) form to the Fe2+ (ferrous) form. Ascorbate (vit C) is involved in this process.
How must the iron be altered before it can be released to the blood?
Before iron can be released to the blood it must be reconverted from the Fe2+ ferrous form to the Fe3+ ferric form.
What iron management proteins can measured in the blood?
(1) transferrin
(2) transferrin receptor
(3) Ferritin
Additionally serum iron and TIBC can be measured.
What happens in iron deficiency to iron management proteins?
In iron deficiency (1) serum iron is decreased. (2) Serum transferrin is increased, (3) transferrin receptor is increased. (4) ferritin is decreased.
What are lab findings in iron deficiency due to hemorrhage?
(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.
What are the disorders of globin synthesis?
Thalassemias are the disorders of globin synthesis.
What are the morphological characteristics of beta thalassemia?
Beta thalassemia exhibits
1) microcytosis
(2) Hypochromia
(3) Target cells (abnormally pale cells
What lab values are often altered in thalassemia?
(1) RBC count is normal
(2) Hgb is decreased
(3) Hct is decreased
(4) MCV is decreased.(microcytosis)
How is thalassemia diagnosis confirmed?
Thalassemia is confirmed by hemaglobin electrophoresis.
What is the structure of normal hemoglobin?
Normal hemaglobin is composed of 2 alpha and 2 beta. There are traces of hemaglobin present that are 2alpha2delta.
What is the structure of alternate hemoglobins?
There is alpha2delta2 (HgA2) and there is alpha2gamma2 (HgF).
What is alpha thalassemia trait 1?
One defective alpha gene results in thalassemia alpha trait 1. (usually clinically normal).
What is alpha thalassemia trait 2?
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.
What is alpha thalassemia trait 3?
Alpha thalassemia trait 3 is characterized by HgbH (beta4),
(1) variable microcytic anemia
(2) 15-30% HgbH
What is alpha thalassemia trait 4?
Alpha thalassemia trait 4 has 4 defective alleles (is lethal in utero or soon after birth)
What are the characteristics of impaired DNA synthesis during erythropoiesis?
(1) fewer cells produced
(2) Normal/enhanced maturation of cytoplasm
(3) Impaired nuclear maturation.
What is Megaloblastic anemia?
Anemia caused by impaired DNA synthesis leading to cells with large mature cytoplasm and immature nuclei.
What causes megaloblastic anemia?
(1) impaired B12 uptake (pernicious anemia)
(2) Impaired folate upatake
(3) Nucleoside inhibitors, ribonucleotide reductase inhibitors.
(4) Bone marrow dysfunction (myelodysplastic syndromes).
Where is EPO made?
EPO is made in the peritubular cells of the kidney.
What is the function of hepcidin?
Hepcidin impairs the release of iron from macrophages by downregulating ferroportin
Why is hepcidin upregulated by acute phase reactions?
To protect iron stores form bacteria.
What happens to TIBC and Transferrin in chronic inflammation?
In chronic inflammation TIBC and serum iron are both decreased.
What happens to ferritin and bone marrow iron during chronic inflammation?
Ferritin and bone marrow iron are both increased in chronic inflammation.
