Bone Marrow

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Myeloid tissues

Back 1

Blood forming tissues identified as the red marrow of bones

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Lymphoid tissues

Back 2

Some lymphocytes of peripheral blood arise from proliferation within lymphoid tissues

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Mesoblastic phase of hematopoiesis

Back 3

Extends from two weeks to two months - hematopoiesis begins in the yolk sac wall as small cell nests (blood islands)

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Hepatic & splenic phases of hematopoiesis

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Islands of blood cell development occur in the liver parenchyma from 6 weeks gestation to birth. Also occurs at lesser intensity in the spleen

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Myeloid phase

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Bone hematopoiesis begins in the clavicle at about 2.5 months gestation and continues to spread through the bones

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Hematopoiesis after birth

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Hematopoesis begins to reside exclusively in the red marrow of the axial skeleton - limbs begin to contain more yellow marrow

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Pleuripotent hematopoietic stem cell

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All blood cells differentiate from this common, self-renewing source

Present in red marrow and have a CD34+/CD38-/CD90+/Lin- surface marker

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Common Myeloid Progenitor

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Leads to monocytes, platelets, erythrocytes, granulocytes

(CFU-GEMM signals lead to CFU-MegE/-GM, CFU-E/-G/-M/-Meg)

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Common Lymphoid Progenitor

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Leads to lymphocytes

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Colony Stimulating Factors

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Cytokines, typically glycoproteins, that sequentially stimulate differentiation and hyperplasia of stem cells into more differentiated progenitor cells

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IL-3

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CSF released by CD4+ T lymphocytes that stimulates multiple lineages

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Signals to differentiate

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erythropoietin (CSF-E)
Thrombopoietin (CFU-Meg)
Neutrophils CSF-GM and -G
Monocytes - CSF-M from CSF-GM

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Erythropoiesis

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Involves 16-32 cell divisions and takes about a week

Under the control of IL-e and erythropoietin from the kidney (released in response to anemia and decreased pO2)

Requires vitamin B12 and folic acid

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Proerythroblast

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15-20 microns

Large spherical nuclues with granular chromatin and 1-2 nucleioli

Mildly basophilic cytoplasm

Undergoes mitosis

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Basophilic erythroblast

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Slightly smaller than pro. 10-16 microns. Blue jean cytoplasm due to free ribosomes. Smaller nucleus with coarsely clumped chromatin. Has nucleoli. Undergoes mitosis. Blue beer

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Polychromatic erythroblast

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Smaller than baso. 9-12 microns. Stains eosinophilic due to hemoglobin and basophilic due to ribosomes. Smaller, more condensed nucleus. Mottled nucleus - pepperoni pizza. Undergoes mitosis

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Orthochromatic erythroblast

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Smaller than poly, about the same size nucleus as RBC. 8-10 microns. Mostly eosinophliic cytoplasm - lavender. Fully condensed chromatin, deeply stained nucleus.

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Reticulocyte

Back 18

Slightly larger than RBC: 8-10 microns. No nucleus. Slightly lavender cytoplasm.

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Erythrocyte

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7-8 microns with agranular eosionophilic cytoplasm. No nucleus or organelles. When phagocytosed, the remaining heme is degraded to bilirubin and bound to albumin in blood, then excreted.

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Granulopoiesis

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Formation of granulocytes stimulated by IL-e as well and CSF-GM released by many cells, then more specifically by CSF-G.

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Myeloblast

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15-20 microns. Basophilic cytoplasm. No granules. Nucleus round and euchromatic. Multiple nucleoli. Undergoes mitosis.

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Promyelocyte

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Still a large cell: 15-24 mircons. Blue-grey cytoplasm with primary azurophilic granules (lysosomes). Large, spherical euchromatic nucleus with multiple nucleoli. Undergoes mitosis

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Myelocyte

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Smaller: 12-18 microns. Three cell lines become apparent: must use proper descriptors. Fat Texan: round/ovoid nucleus, more condensed nucleus. Secondary specific granules in cytoplasm. Last stage undergoing mitosis

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Metamyelocyte

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Cytoplasm less basophilic and specific granules. Indented nucleus - Middle thicker than ends. American reality.

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Band

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Cytoplasm granules same as metamylocytes. American dream: Ends bigger than the middle. 1-5% of circulating granulocytes

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Segmented mature granulocyte

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Cytoplasm granules same as band. Multi-lobed polymorphonuclear nucleus. French model.

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Thrombopoiesis

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Stimulated by thrombopoietin and IL-3. Endomitoses yield polyploid cells from which membrane bound cytoplasmic fragments bud off

Mediated by indirect feedback loop from thrombopoietin receptor

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Megakaryoblast

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Large cells: 15+ microns. Last stage undergoing mitosis.

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Promegakaryocyte

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Endomitosis. 35+ micron cell with large, multiploid nucleus (4-8n)

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Megakaryocyte

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Gigantic cell (50-70 microns) with large polyploid nucleus. Cell fragments bud into capillary sinus via invaginations of plasmalemma.

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Thrombocyte

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Anuclear, cell fragment much smaller than erythrocyte.

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Macrophages in Blood Marrow

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Function in Phagocytosis and Iron storage.

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Lymphopoiesis

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Retain capacity for further mitosis