Hematopoiesis and Thrombopoiesis

hematopoiesis during each trimester of fetal development

*1st trimester*: yolk sac surrounding the embryo produces blood cells (mostly RBCs) *2nd trimester*: liver has developed and produces blood cells, spleen begins to develop and contributes to WBC production *3rd trimester*: bones have developed and the bulk of blood cells are produced in the bone marrow (this is the case from now on, though newborns possess only red blood marrow whereas adults have red and yellow blood cells due to the presence of fat cells)

erythropoiesis initiation, phases (3) and general morphological changes

driven by erythropoietin, a hormone released from the kidney in response to low oxygen, anemia, etc. *phase 1*: ribosome synthesis *phase 2*: hemoglobin accumulation *phase 3*: nuclear ejection throughout this process, the cell shrinks and RNA content decreases linearly while hemoglobin content rises exponentially changes involving the nucleus may or may not occur synchronously with those involving the cytoplasm

properties of hematopoietic cells during differentiation

hematopoietic stem cells are self renewing and have unlimited potentiality (can become any type of blood cell) progenitor cells have more limited potentiality and less ability to self renew precursor cells are unipotent and cannot self renew, but are actively mitotic and are undergoing morphological differentiation mature cells are terminally differentiated such that they are unipotent, cannot self renew, and are not mitotic, but can undergo morphological differentiation to achieve functional specification

cell stages of erythropoiesis (9)

hematopoietic stem cells become myeloid stem cells which become erythroblasts pro-eryhroblasts become basophilic erythroblasts which become polychromatophilic erythroblasts at this point, mitosis arrests to yield orthochromatophilic erythroblasts, which eject their nuclei to become reticulocytes, which eject their ribosomes to become mature RBCs

bone marrow definition, composition, and vascularization

semi-fluid connective tissue that resides in the spaces of spongy bone much more heterogeneous than blood, consisting of a stroma (framework of reticular connective tissue that contains unique compounds like hemonectin), islands of developing and mature blood cells, megakaryocytes, fat cells, macrophages, fibroblasts, etc. dense vasculature including a nutrient artery that gives off nutrient arterioles and is connected to a central longitudinal vein by sinusoids (discontinuous capillaries)

bone marrow functions (5)

stores mature blood cells develops new blood cells in the spaces between sinusoids (non-motile cells develop near the sinusoids while motile WBCs can develop far from them) releases new blood cells into the sinusoids upon release factor signaling destroys old RBCs stores iron from displaced hemoglobin

regulation of hematopoiesis and thrombopoiesis

these processes are driven by cytokines in the bone marrow known as colony stimulating factors (CSFs) WBC development is much more complicated than the development of RBCs and platelets, which are driven by erythropoietin and thromopoietin respectively

thrombopoiesis

platelets arise from megakaryocytes, giant cells (50-100 microns) that reside in bone marrow and consist of a large multi-lobed nucleus and a "sandy" cytosol that breaks off to release platelets (look like tiny basophilic dots) megakaryocytes become so large due to endo-mitosis, the process of serial mitotic divisions without cell division which leads to the development of a large cytoplasm full of dense and alpha granules and an extensive demarcation membrane system that allows for the release of platelets megakaryocytes reside near the sinusoids and project demarcated platelets into the sinusoid lumen where shear forces carry the platelets into circulation hematopoietic stem cells become myeloid stem cells which become megakaryoblasts which become pro-megakaryocytes which become megakaryocytes

general overview of hematopoiesis

pluripotent stem cells, also known as hematopoietic stem cells, in the bone marrow become progenitor cells, also known as colony forming units, at which point mitosis is initiated progenitor cells become precursor cells, also known as blast cells, at which point mitosis is at its maximum rate once mitosis arrests, the cells become mature (some cells, like granulocytes, first enter an immature cell state and undergo further morphological differentiation first)

erythroblast development from a morphological/histological perspective

pro-eryhroblasts look like stem cells, which are large, nucleated with active nucleoli, and have a relatively basophilic cytoplasm basophilic erythroblasts have a much more basophilic cytoplasm due to ribosome synthesis and some acidophilic spots due to hemoglobin synthesis polychromatophilic erythroblasts have a heterogeneous cytoplasm and with both acidic and basic regions and a round granular nucleus due to arrest of mitosis orthochromatophilic erythroblasts have a strongly basophilic nucleus due to DNA condensation with a strongly acidophilic cytoplasm due to hemoglobin accumulation reticulocytes lack a nucleus due to nuclear ejection but still possess cytosolic ribosomes mature RBCs are completely acidophilic due to the presence of hemoglobin and the lack of nucleic acid

erythropoiesis vs. granulopoiesis

process is the same up to the blast stage and the transition from mitotic to post-mitotic stage can be seen in both as the point at which nucleus changes size or shape RBC mitotic phase is less than a week and ends at the polychromatophilic erythroblast stage and post-mitotic phase is about a day granulocyte mitotic phase is about a week and ends at the myelocyte stage and post-mitotic phase is about a week

granulopoiesis cell stages (7) and morphological/histological characteristics of each

hematopoietic stem cells become myeloid stem cells which become myeloblasts, which lack cytoplasmic granules (all large, nucleated with active nucleoli, and have a relatively basophilic cytoplasm) myeloblasts become promyelocytes, which contain azure granules (lysosomes), rough ER, and a Golgi apparatus (begin to see dark spots in the cytoplasm) promyelocytes become myelocytes, which contain specific granules (differ by type of granulocyte) produced by the rough ER and Golgi (big, round, active nucleus with acidic, neutral, or basic granules in the cytoplasm) myelocytes become metamyelocytes, which contain an indented nucleus due to the arrest of mitosis, many specific granules, and few azure granules (looks like a monocyte with granules) metamyelocytes become mature granulocytes, which contain a lobed nucleus

blood cell lineages

hematopoietic stem cells give rise to either myeloid or lymphoid stem cells myeloid stem cells give rise to RBCs, platelets, or myeloblasts, which give rise to granulocytes (eosinophils, basophils, and neutrophils) lymphoid stem cells give rise to lymphoblasts, which give rise to B cells, T cells, and NK cells

monocyte development cell stages (4) and timeline

monoblasts become pro-monocytes which becomes a monocyte which eventually becomes a macrophage or dendritic cell about half are fast growing (to make baseline levels of macrophages) and about half are slow growing (act as a reserve) entire process takes about a day and a half