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Normal Development of Blood Cells

Chapter 13 - Red Blood Cell and Bleeding Disorders

Jon C. Aster MD, PhD

The organs and tissues involved in hematopoiesis have been traditionally divided into myeloid tissue, which includes the bone marrow and the cells derived from it (e.g., erythrocytes,

platelets, granulocytes, and monocytes), and lymphoid tissue, consisting of thymus, lymph nodes, and spleen. This subdivision is artificial with respect to both the normal physiology of

hematopoietic cells and the diseases affecting them. For example, although bone marrow is not where most mature lymphoid cells are found, it is the source of lymphoid stem cells.

Similarly, myeloid leukemias, neoplastic disorders of myeloid stem cells, originate in the bone marrow but secondarily involve the spleen and (to a lesser degree) lymph nodes. Some red

cell disorders (hemolytic anemias) result from the formation of autoantibodies, signifying a primary disorder of lymphocytes. Thus, it is not possible to draw neat lines between diseases

involving the myeloid and lymphoid tissues. Recognizing this difficulty, we somewhat arbitrarily divide diseases of the hematopoietic tissues into two chapters. In the first, we consider

diseases of red cells and those affecting hemostasis. In the second, we discuss white cell diseases and disorders affecting primarily the spleen and thymus.

Normal

A complete discussion of normal hematopoiesis is beyond our scope, but certain features are helpful to an understanding of the diseases of blood.

Normal Development of Blood Cells

Blood cells first appear during the third week of fetal embryonic development in the yolk sac, but these cells are generated from a primitive stem cell population restricted to the production

of myeloid cells. The origin of definitive hematopoietic stem cells that give rise to lymphoid and myeloid cells is still unsettled. Most studies suggest they arise in the mesoderm of the

intraembryonic aorta/gonad/mesonephros (AGM) region,[1] but evidence also exists for an origin within a small subset of yolk sac-derived cells. By the third month of embryogenesis, stem

cells derived from the AGM and/or yolk sac migrate to the liver, which is the chief site of blood cell formation until shortly before birth. Beginning in the fourth month of development,

stem cells migrate to the bone marrow to commence hematopoiesis at this site. By birth, marrow throughout the skeleton is hematopoietically active and virtually the sole source of blood

cells. In fullterm infants, hepatic hematopoiesis dwindles to a trickle, persisting only in widely scattered small foci that become inactive soon after birth. Up to the age of puberty, marrow

throughout the skeleton remains red and hematopoietically active. By age 18 only the vertebrae, ribs, sternum, skull, pelvis, and proximal epiphyseal regions of the humerus and femur

retain red marrow, the remaining marrow becoming yellow, fatty, and inactive. Thus, in adults, only about half of the marrow space is active in hematopoiesis.



Several features of this normal sequence should be emphasized. By birth, the bone marrow is virtually the sole source of all forms of blood cells, including lymphocyte precursors. In the

premature infant, foci of hematopoiesis are frequently evident in the liver and, rarely, in the spleen, lymph nodes, or thymus. Significant postembryonic extramedullary hematopoiesis is

abnormal in the full-term infant. With an increased demand for blood cells in the adult, the fatty marrow can transform to red, active marrow. For example, in the face of red cell deficiency

(anemia), the marrow can increase red cell production (erythropoiesis) as much as eight-fold. If the marrow stem cells and microenvironment are normal and the necessary nutrients are

available (e.g., adequate amounts of iron, protein, requisite vitamins), premature loss of red cells (as occurs in hemolytic disorders) produces anemia only when marrow compensatory

mechanisms are outstripped. Under these circumstances, extramedullary hematopoiesis can reappear within the spleen, liver, and even lymph nodes.


Date: 2016-04-22; view: 688


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