Lecture 25: Hematopoiesis Flashcards
Where does hematopoiesis occur during the first trimester? What is the product?
Yolk sac: primordial eryhtroblasts
Where does hematopoiesis occur during the second trimester? What is the product?
Liver, spleen, and thymus: precursor granulocytes, megakaryocytes, and definitive erythroblasts
What do we call hematopoiesis during the second trimester?
Hepato-spleno-thymic phase
Where does hematopoiesis occur during the third trimester? What is the product?
Bone marrow of distal long bones and lymph nodes: all cell types
Where does hematopoiesis occur in adults? What is the product?
Axial skeleton > distal long bones: all cell types
What does “ontogeny follows philogeny” mean? When do we use this phrase? Explain in detail.
During fetal development: the developmental stages a fetus goes through illustrates the evolutionary stages of its ancestors
- Primitive vertebrates: hematopoiesis in gut associated lymphoid tissue (GALT) = non-encapsulated lymphoid tissue
- Jawed vertebrates: hematopoiesis in thymus and spleen = encapsulated lymphoid tissue
- Terrestrial vertebrates:hematopoiesis in bone marrow
What is GALT
Gut Associated Lymphoid Tissue: lymphoid tissue underneath the lining of the GI tract
From where do we do bone marrow biopsies in children? Why?
Tibial shaft because the tibia is the largest bone we can access
From where do we do bone marrow biopsies in adults? (PASS)
Axial bones:
- Posterior superior iliac spine
- Anterior superior iliac spine
- Sternum
- Spinous processes of vertebrae
What is the common precursor to all blood cell types? Is it pluripotent or totipotent?
Pluripotent hemocytoblast (stem cell)
What lineages does the hemocytoblast give rise to?
- Multipotential lymphoid stem cell lineage
2. Multipotential myeloid stem cell lineage
What cells does the multipotential lymphoid stem cell lineage give rise to?
Lymphocytes
What cells does the multipotential myeloid stem cell lineage give rise to? 4 of them
RBCs, platelets, granulocytes, and monocytes
What is the order in hematopoiesis?
Pluripotent stem cells –> multipotent stem cells –> progenitor cells –> precursor cells –> mature cells
Do we have a lot of pluripotent cells? Why or why not?
No because they either reproduce themselves or give rise to multipotent stem cells
Which cell lineage is highly mitotic in hematopoiesis?
Progenitor cells
Can you tell multipotent and progenitor cells apart in histology?
NOPE
Which cell lineages are most sensitive to growth factor in hematopoiesis?
Progenitor cells and precursor cells
Which cell lineage is capable of self-renewal in hematopoiesis?
Pluripotent and multipotential stem cells
What is another name for progenitor cells?
Blasts
Which cell lineage is morphologically distinct in hematopoiesis?
Progenitor cells
How does potentiality change throughout hematopoiesis? Why?
It decreases because cells become more differentiated
How does self-renewing ability change throughout hematopoiesis? Why?
It decreases because cells lose them stem cell character
How does mitotic activity change throughout hematopoiesis? Until when?
It increases until the end of the precursor stage and stops entirely before reaching the mature cell stage
When do typical morphological characteristics and differentiated functionality appear during hematopoiesis?
Mature cell stage
Which cell stages in hematopoiesis involve leukemias and lymphomas? Explain.
Progenitor and precursor cell stages leading to a deficit of functional product
What color is bone marrow in young people? Why? What is it called
Red because it’s very vascularized and hematopoietically active = hematogenous bone marrow
What color is bone marrow in old people? Why?
Yellow because it’s replaced with adipose tissue and is hematopoietically inactive
Why does immunological activity decrease with age?
Because the cellular components of immune organs are replaced with adipose tissue
Describe the structure of hematopoietically active bone marrow.
Encapsulated by bone with vasculature to allow entry of nutrients (through peiosteal capillaries) and exit of hematopoiesis products (through vena comitans)
Where are stromal cells located? What is their function? What do they create?
They line the sinusoidal cavities in red bone marrow and secrete growth factors for the sustenance and viability of the hematopoietic components = create hematopoietic inductive microenvironment
How do we get rid of the hematopoietic components that have not formed properly?
Macrophages eat them up!
What is bone marrow a crazy reservoir for? Why is this cool?
DNA
Can help understand how animals are related to each other and help in criminal cases
How is erythropoiesis regulated?
More RBCs = more O2 in system = negative feedback on kidneys (on renal interstitial peritubular cells) to lower RBC production and stop preventing apoptosis
Describe the 7 stages of erythropoiesis.
- Erythroblast
- Proerythroblast (EPO stimulated)
- Basophilic erythroblast: begins producing hemoglobin
- Polychromatophilic erythroblast: last mitotic stage
- Normoblast: nucleus condenses (very small) and is on one side of the cell
- Reticulocyte: normoblast ejects its nucleus (but RNA remnants) and reticulocyte is ejected into vasculature - looks like an empty cell
- RBC after RNA breaks down
How can you tell a basophilic erythroblast has started producing hemoglobin?
It has a large heterochromatic nucleus
What color is the cytoplasm of basophilic erythroblasts?
Purple
What color is the polychromatophilic erythroblast? Why?
Pink because of increased hemoglobin and blue
What is another name for a normoblast?
Orthochromatophilic erythroblast
What stage of erythropoiesis are we at if blue-staining squiggles are seen? Why? What is the blue stain?
Reticulocyte because of RNA remnants
Supravital stain = brilliant cresyl blue
What stages of erythropoiesis are mitotic?
1, 2, 3, and 4
How does the size of the erythrocyte change during erythropoiesis?
Decreases
How does the concentration of RNA/mitochondria change during erythropoiesis?
Decreases
How does the hemoglobin concentration of the erythrocyte change during erythropoiesis?
Increases
Where does erythropoiesis occur in the bone marrow? Why
In an erythroblastic island = around a macrophage that phagocytoses the ejected nucleus (=pyknotic nucleus) and recycles its components
What % of RBCs are actually reticulocytes?
1%
What does elevated reticulocyte concentration mean?
Increase in erythropoiesis
What are the 6 stages of granulopoiesis?
- Myeloblasts: contains no granules
- Promyelocytes: contain non-specific granules (blue) and round/oval nucleus
- Myelocytes: neutrophilic, eosinophilic, or basophilic with specific granules (pink) and round/oval nucleus
- Metamyelocytes: lobulation begins and kidney bean shaped nucleus
- Band cells: horseshoe shaped nucleus
- Final mature product (lobulated nucleus)
What does the accumulation of band cells (granulocytes) correspond to? How come?
Immune response against bacterial infection, sometimes they are released into the vasculature (or maybe even leukemia)
What does a monocyte differentiate into?
Macrophage
What are macrophages called in the liver?
Kupffer cells
What are macrophages called in the bone?
Osteoclasts
What are macrophages called in the brain?
Glial cells
What is thrombopoiesis?
Production of platelets from megakaryocytes
What stimulates thrombopoiesis?
Thrombopoietin (TPO)
What is special about megakaryocytes?
They are polyploid meaning they duplicate their DNA but do not divide
How does platelet formation happen?
A megakaryocyte reaches a sinusoidal cavity (without entering) and sheds platelets on the inside of the bone marrow
What is Hodgkin’s lymphoma characterized by?
The presence of giant Reed-Sternberg cells (RS)
What are lymphomas?
Cancers of lymphatic tissue
What are leukemias?
Cancers of leukocytes and precursors (all blood cells except for lymphocytes)
What are the 2 types of leukemias? Explain each.
Acute: cancer of earlier stages of hematopoiesis = replication of immature cells, worse prognosis, rapid progression
Chronic: cancer of later stages of hematopoiesis = replication of mature cells, better prognosis, less agressive
What is myelogenous leukemia?
Cancer where tumor cells replace hematopoietic tissue in the bone marrow
How is myelogenous leukemia classified?
Based on type of precursor: erythrocytic, granulocytic, monocytic
What are the 2 types of myelogenous leukemias? Explain each.
Acute: early stage = replication of immature cells, worse prognosis, rapid progression
Chronic: later stages = replication of mature cells, better prognosis, less agressive
What treatment against chronic myelogenous leukemia has doubled the 5 year survival rate?
Gleevec which targets BCR-Abl tyrosine kinase
Is it easier to treat a liquid tumor or a solid tumor? Why?
Liquid because drug can easily reach them and because there is a certain threshold of drug you can give for solid tumors (because other normal cells attached to it)
What do we call macrophages in the skin?
Langerhans cells
What do we call hematopoiesis during the third trimester?
Medullo-lymphatic phase
Why would we do a biopsy of bone barrow?
If we suspect leukemia or lymphoma
What lines the sinusoidal lumen? Why?
Epithelial cells because bone marrow is a type of blood vessel
Which stages of erythropoiesis are RNA-rich?
- Proerythroblast
2. Basophilic erythroblast
Where are megakaryocytes?
Always in the bone marrow (not the sinusoidal cavity)
Are myelogenous leukemias liquid or solid?
Liquid
How to recognize leukemia after bone marrow biopsy (on a slide)?
Leukemia: density of hematopoitic cells is much larger, stains darker
What is the latest stage of erythropoiesis where restablishing the lineage would be possible? Why?
Polychromatic erythroblasts because they are the last mitotic stage
