Blood is rightfully considered the vital fluid, as every organ system depends on the normal function of blood. Blood delivers oxygen and other essential substances throughout the body, removes waste products of metabolism, transports hormones from their origin to site of action, signals and defends against threatened infection, promotes healing via the inflammatory response and maintains the vascular integrity of the circulatory system. It also contains the central compartment of classical pharmacokinetics, and thereby comes into direct contact with virtually every systemic toxin that acts on the organism.162 The ease and frequency with which blood is assayed, its central role in functions vital to the organism, and the ability to analyze its characteristics, at first by light microscopy and more recently with molecular techniques, have enabled a detailed understanding of blood that has advanced the frontier of molecular medicine.
In addition to transporting xenobiotics throughout the body, blood and the blood-forming organs can at times be directly affected by these same xenobiotics. For example, decreased blood cell production, increased blood cell destruction, alteration of hemoglobin, and impairment of coagulation can all result from exposure to many xenobiotics. The response in many cases depends on the nature and quantity of the xenobiotic, and the capacity of the system to respond to the insult. In other cases, no clear and predictable dose–response relationship can be determined, especially when the interaction involves the immune system. These latter reactions are often termed idiosyncratic, reflecting an incomplete understanding of their causative mechanism. In general, such reactions can often be reclassified when advancing knowledge identifies the characteristics which render the individual vulnerable.
Hematopoiesis is the development of the cellular elements of blood. The majority of the cells of the blood system may be classified as either lymphoid (B, T, and natural-killer lymphocytes) or myeloid (erythrocytes, megakaryocytes, granulocytes, and macrophages). All of these cells are descended from a small common pool of totipotent cells called hematopoietic stem cells.182 Indeed, the study of this process and its regulation has provided fundamental insight into embryogenesis, stem cell pluripotency, and complex cell-to-cell signaling and interaction.
Marrow spaces within bone begin to form in humans at about the 5th fetal month and become the sole site of granulocyte and megakaryocyte proliferation. Erythropoiesis moves from the liver to the marrow by the end of the last trimester. At birth, all marrow contributes to blood cell formation and is red, containing very few fat cells. By adulthood, the same volume of hematopoietic marrow is normally restricted to the sternum, ribs, pelvis, upper sacrum, proximal femora and humeri, skull, vertebrae, clavicles and scapulae. So-called extramedullary hematopoiesis in the liver and spleen may reemerge as a compensatory mechanism under severe stimulation.
Progenitor cells must interact with a supportive microenvironment to sustain hematopoiesis. The hematopoietic stroma consists of macrophages, fibroblasts, adipocytes, and endothelial cells. The extracellular matrix is produced by the stromal ...