Theories on Blood Cell Formation A. MONOPHYLETIC THEORY All blood cells come from one origin stem cell the HEMOCYTOBLAST REC B. POLYPHYLETIC THEORY Also known as Dualistic Theory which suggests different groups of blood cells originate from different stem cells.- RBC,WBC, platelets – Hemohistioblast- Monocytes, lymphocytes & plasma cells – Tissue hemohistioblast
Stages of Hematopoiesis Mesoblastic stage – first month of embryonic life where cells are formed outside the embryo in the mesenchyme of the yolk sac. Hepatic stage – by the 6th week Medullary stage – by the 5th month blood cell formation occurs in the bone marrow. - Marrow – primitive stem cells & committed progenitor cells are confined - Spleen & lymph nodes – 2ndary lymphoid tissue for lymphocyte development and differentiation.
Principles in Normal Cell Maturation CELL SIZE – immature cells are much bigger than more mature cells CYTOPLASMIC DIFFERENTIATION - amount of cytoplasm - color (basophilia) - presence of granules (WBC) NUCLEAR MATURATION - presence, size (nucleus:cytoplasm ratio) - nucleolus presence & lobes or indentation
ERYTHROPOIESIS Governed by a hormone produced by the kidneys called ERYTHROPOIETIN Begins with the multipotential stem CFU-S. By the action of microenvironmental factors the CFU- S differentiates forming a committed erythroid progenitor cell.
Pronormoblast (Rubriblast) First recognizable RBC precursor First Hemoglobin-synthesizing cell Approximately 20 um Moderate amount of cytoplasm Basophilic cytoplasm with 1-3 nuclei Prominent nuclear membrane Shows active mitotic division
Basophilic normoblast(prorubricyte) Slightly smaller than the rubriblast Cytoplasm is moderate in amount with deep basophilia due to high amounts of cytoplamsic RNA Nucleoli are present though not always visible Active mitotic division noted
Prorubricyte (Basophilic normoblast)
Polychromatic erythroblast(rubricyte) Cytoplasm stains various shades of gray due to mixture of RNA and hemoglobin Nuclear volume occupies half of the cell area May undergo 1 or mitotic division in which after the last division the nucleus become small & condensed
Rubricyte (polychomatic erythroblast)
Orthochromic normoblast(metarubricyte) Last nucleated stage in RBC series First non-mitotic stage Slight polychromasia Abundant or full hemoglobinization
Metarubricyte (orthochromic normoblast)
Reticulocyte Non-nucleated immature RBC Appears polychromatic due to remaining RNA responsible for the bluish-gray color on air-dried smears Larger than mature erythrocyte Released into the circulation after 2 days of maturation in the marrow Synthesize Hemoglobin for approximately 1 day after leaving the bone marrow
Reticulocyte (poychromatophilic erythrocyte)
Reticulocyte (supravital stain)
Mature Erythrocyte Appears as a biconcave disc with a concavity on each side – “Discocyte” Average size 7.2 um
Cells of the WBC series Myeloblast Promyelocyte Myelocyte Metamyelocyte Band or stab Segmenter
Myeloblast Earliest cell in the WBC series Nucleus:cytoplasm ratio of 4:1 Large, round nucleus with 2-5 visible nucleoli Deeply basophilic cytoplasm No granules noted
Promyelocyte Slightly smaller than myeloblast Basophilic cytoplasm N:C ratio of 2:1 with visible nucleoli Presence of azurophilic granules
Myelocyte Appearance of the specific granules or also known as secondary granules Specific granules will determine the functional destiny of the WBC giving rise to eosinophil, basophil or neutrophil. N:C ratio 1:1 with almost invisible nucleoli. Cytoplasm show mixture of basophilic and acidophilic staining
Metamyelocyte Also known as the JUVENILE Differentiated from the myelocyte because of the presence of indentation of its nucleus N:C ratio 1:1 and smaller than the myelocyte
Band or Stab Also known as the STAFF Measures 12-13 um Nucleus is sausage-shaped, elongated or horse-shoe shaped in appearance there is no lobulation or segmentation noted.
Band / Stab / Staff
Segmenter Most mature stage of the WBC N:C ratio of 1:2 Nucleus shows lobulation or segments Differentiated based on the appearance of its granules as follows:- Eosinophil – reddish-orange granules- Basophil – blue-black granules- Neutrophil – pink-tan granules