Lecture 19: Hematopoisis Flashcards
Define hematopoiesis (hemopoiesis).
The process through which formed elements of the blood are produced
Elements:
▪ Erythrocytes
▪ Leukocytes
▪ Platelets
List the 3 major organs involved in hematopoiesis before birth.
1) Yolk - sac phase
- 3rd week gestation
- “Blood Islands”
2) Hepatic phase
- 2nd trimester
3) Bone marrow phase
- 2nd trimester
List the sites where hematopoiesis is predominant as age advances
After birth:
-Bone marrow
Elderly:
-Most in vertebral and pelvis > sternum > ribs > Lmyph > Femur > Tibia
Describe the histological features of various hematopoietic sites in the body as age progresses
HISTO SLIDE
Describe the characteristics of a stem cell:
Cell plasticity
1) Cell plasticity
- Ability of stem cells to form specialized cell types of other tissues
Hematopoietic stem cells – Neurons & glial cells – Skeletal muscle cells – Cardiac muscle cells – Liver cells
• Bone marrow stromal cells
– Cardiac muscle cells
– Skeletal muscle cells
• Neural stem cells
– Blood cells
– Skeletal muscle cells
Define totipotent, pluripotent and multipotent stem cells
1) Totipotent:
-Ability to develop into all
tissues
(Embryonic germ layers,
Extra-embryonic: Placental, amnion, chorion)
2) Pluripotent:
- Ability to develop into all cells and tissues of the body
- Capable of all blood cell lineages & self – renewal
3) Multipotent:
-Ability to develop into a small
number of different cell types
Define and describe hematopoietic stem cell (HSC)
Function: -Gives rise to multiple colonies of progenitor stem cells ➢Fibroblasts ➢Adipocytes ➢Endothelial cells ➢Osteoblasts
Location:
-Bone marrow (cavity of long & axial bones, surrounded by stroma=support)
Define and describe hematopoietic stem cell niches (Endosteal niche)
A stem cell niche Def:
-A spatial structure (microenvironment) in which
Hematopoietic stem cells are housed
Function:
• Storage of quiescent stem cells
• Self renewal
• Inhibition of differentiation
Location:
-Epiphyseal areas (spongy
bone or “cancellous bone”)
Describe the myeloid and lymphoid lineages
Myeloid Lineage:
Start: Pluripotent Stem cell –> Myeloid Stem cell –> (Diff paths to create the following)
1) CFU-E –> Proerythroblast –> Reticulocyte –> RBC (erythrocyte)
2) CFU-Meg –> Megakaryoblast –> Megakaryocyte –> Platelets (Thrombocytes)
3) Eosinophilic myeloblast –> Basophil (Granular leukocyte)
4) Basophilic myeoblast –> Basophil (Granular leukocyte)
5) CFU-GM –> Myeoblast –> Neutrophil
6) CFU-GM –> Monoblast –> Monocyte –> Macrophages
(Agranular leukocytes)
Lymphoid Lineage:
Pluripotent Stem cell –> Lymphoid Stem cell –> T and B lymphoblasts –> T and B lymphocytes –> B –> Plasma cell
(Agranular leukocytes)
Describe the cellular organization, vascularity and functions of bone marrow
Structure Bone marrow:
1) Reticular fibers, veins, arteries, sinusoids
2) Red bone marrow:
- Active hematopoiesis
3) Yellow bone marrow:
- Fat, capillaries, reticular cells, inactive hematopoiesis
-Hematopoietic stem cells mature they move from endosteal niche (end of bone) to vascular niche (middle of the bone to conduct) hematopoisesis –>
Then do the following:
-Support and promote the differentiation & maturation of progenitors into formed elements of the blood .
-Secretion of growth factors by stromal cells
Describe the role of growth factors, cytokines and hormones involved in hematopoiesis
Role:
-Proliferate and mature progenitor cells (Hematopoietic cells would die without it)
Growth Factors:
1) Erythropoietin (EPO)
- Produced by the kidneys increase erythrocyte precursors
2) Thrombopoietin (TPO)
- Hormone from liver stimulates thrombocyte formation
3) Cytokines are local hormones of bone marrow
-Produced by some marrow cells to stimulate proliferation in other marrow cells
-Colony-stimulating factor (CSF) & interleukin stimulate leukocyte
production
Describe the process of erythropoiesis
- Erthropoiesis:
- Location: Red bone marrow
1) Reduced oxygen levels= Hypoxia occurs (stimulus)
2) Kidneys release Erythropoietin
3) Erythropoietin acts on bone marrow and increases number RBC produced
List & identify the stages of erythrocyte differentiation
1) Proerythroblast
- No hemoglobin
2) Basophilic (early) erythroblast:
- Some hemoglobin
- Nucleus condenses
3) Polychromatophilic erythroblast:
- “Muddy” cytoplasm
4) Orthochromatophilic (late) erythroblast (normoblast):
- Increased hemoglobin
- Nucleus condenses
5) Reticulocyte:
- No nucleus
- Some ribosomes
6) Erythrocyte
- Only hemoglobin
- No ribosomes
Describe the process of thrombopoiesis
Thrombopoiesis:
-Formation of thrombocytes ( platelets)
1) Controlled by thrombopoietin
2) Megakaryoblast
3) Megakaryocyte:
4) Platelets formed by fragments Megakaryocytes
Identify and describe the structure and function of megakaryocytes and formation of platelets
Structure:
(Histo slides)
-Platelets fragmenting off
-Muli-nuclei
Function:
-Forms Platelets from their fragments
Describe the process of granulopoiesis
- Formation of granulocytes
- Controlled by cytokines (11 days)
1) Myeloblast:
- No granules
2) Promyelocyte:
- Large nucleus
- Azurophilic granules
-Starts to differentiate into Neutrophilic, Eosinophilic, basophilic
3) Myelocyte:
- Specific granules for cell first appear!
4) Metamyelocyte:
-Kidney shaped nucleus
(Still has specific granules)
5) Band:
-C-shaped nucleus
(Still has specific granules)
6) Mature formation of the corresponding cell
Identify reticulocytes, band cells and megakaryocytes in the normal development of erythrocytes, granulocytes and platelets respectively
Look at Histo slide
Describe the process of bone marrow aspiration & biopsy techniques and the clinical significance
1) Aspiration
- Uses aspiration needle
- Channel into the bone cavity and aspirate
- Common locations –> Iliac crest
2) Biopsy
- Get a chunk of the bone
-Helps make a diagnosis of a disease
Compare normal bone marrow vs. aplastic anemia and leukemia in a peripheral smear
Look at Histo slide
1) Aplastic anemia:
- Adipose tissue (white)
2) Leukemia:
- Increase in cells
Describe the effects of renal failure on erythropoiesis
Kidneys wouldn’t be able to release Erythropoietin, so they can’t act on bone marrow –> Decreasing number RBC produced
