2196
The functional unit for erythropoiesis is the bone marrow is the erythroblastic island, a multicellular structure composed of a central macrophage with surrounding erythroblasts in development.
The contact of the macrophage and the erythroblast supports growth, survival, and differentiation of the early red blood cells and allows for phagocytosis of the extruded nucleus of the erythroblast.
During fetal life erythropoiesis occurs in both the liver and spleen and becomes restricted to the bone marrow after birth.
Initially a cohort of embryonic red blood cells originate in the blood islands of the yolk sac.
Hematopoietic stem cells (HSCs) persist throughout fetal and adult life emerge from the ventral wall of the dorsal aorta, migrating to the fetal liver, and by 60 days of gestation fetal cells are released into the circulation replacing embryonic RBCs.
During fetal development HSCs migrate to the bone marrow, the site of erythropoiesis for the rest of adult life.
Early in postnatal life adult RBCs from the marrow replace fetal cells.
The process begins with the commitment the hematopoetic stem cells to a hierarchy of progenitors, including the common myeloid progenitor, the megakaryocyte-erythrocyte progenitor and the erythroid lineage specific burst forming units and colony forming units.
Colony forming units mature through a program in which hemoglobin protein accumulates and organelles such as mitochondria and the nucleus are lost, resulting in a terminally differentiated red blood cell that enters the bloodstream and transport oxygen.
Red cell production is regulated by a negative feedback loop.
Hypoxia is detected by proteins in specialized cells in the kidney, resulting in the production of the cytokine erythropoietin, which then docks with its receptor on the cell surface of the early erythroblast.
This process triggers involvement of the cytoplasmic proteins Janus Kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), the latter of which translocates to the nucleus.
The oxygen sensing pathway involves the proteins, prolly hydroxylase domain containing protein 2(PHD 2) hypoxia inducible factor 2 alpha (HIF-two alpha), and von Hippel-Lindau tumor suppressor (VHL).
At the nucleus, it activates genes that cause the erythroblast to differentiate into a red blood cell.
The above process is switched off by the attachment of a protein (SHP1) to the erythropoietin receptor, dislodging erythropoietin, and shutting down signaling.
Hemoglobin is produced in different stages by switching to distict genes in the embryo, fetus, and adults
Daily production of 200 billion new red blood cells daily to compensate for the daily destruction of senescent erythrocytes by tissue macrophages.
RBCs rapidly mature, and once the stem cell differentiates into the erythroid cell line a cell matures through the nucleated cells pages in for or five days.
Control dependent on erythropoietin production by the kidney and on the availability of plasma iron.
Substances needed for erythropoiesis include amino acids, iron, vitamin B12, vitamin B6, folate acid, trace minerals, cobalt and nickel.
Daily requirement of 20 mg of elemental iron, which mostly comes from recycled senescent red cells from macrophage-phagocytic system with only one-2 mg of daily iron derived from intestinal absorption.
Abnormal erythropoiesis can result from deficiencies of any of the required substances.
Cell divisions that accompany terminal erythroid differentiation or controlled by cell cycle regulators and disruption of these terminal divisions results in erythroid cell apoptosis.
At the polychromatophilic erythroblast stage, erythroid cells do not divide but undergo maturation.
Androgens and thyroid hormones also stimulate erythropoiesis.