Microbiology 435Hematopoiesis |
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Blood"A few nights working in a trauma center would tend to convince one that the body is just a huge bag of blood. In fact, an "average" 70 liter human body contains only about 5 liters of blood, or 7% by volume. In the normal state, blood has no business anywhere except in the confines of the heart and blood vessels and in the sinusoids of the marrow, liver, and spleen. Of the average 5 L of blood, only 2.25 L, or 45% consists of cells. The rest is plasma, which itself consists of 93% water (by weight) and 7% solids (mostly proteins, the greatest proportion of which is albumin). Of the 2.25 L of cells, only 0.037 L (1.6%) are leukocytes. The entire circulating leukocyte population, if purified, would fit in a bartender’s jigger. The total circulating platelet volume is even less — about 0.0065 L — or a little over one teaspoonful." Dr. Edward O. Uthman
Hematopoiesis is the formation and development of blood cells. A steady blood cell population is maintained by production of new cells and destruction of old cells. The Blood Cells
Hematopoiesis in a fetus The first blood cells formed are RBCs. At 2 to 8 weeks primitive nucleated erythroid cells are found in the yolk sac; they contain hemoglobin but don’t mature to fully developed RBCs. During the 2nd month extramedullary hematopoiesis develops; yolk sac cells migrate to the liver. Granulocytes also appear in the liver during the 2nd month and all adult organs are recognizable. The spleen also contributes to hematopoiesis at this point.. During the 4th month medullary hematopoiesis develops when the bone marrow begins to contribute to hematopoiesis. During the 5th month bone marrow takes over as chief production site and continues throughout life. Hematopoiesis after birth At birth the liver and spleen have ceased production of blood cells and hematopoiesis is occurring in the red bone marrow of almost every bone (axial and appendicular skeletons). As a child develops and matures (beginning at 4 years) the hematopoietic activity begins to move to the axial skeleton (flat bones, skull, ribs, sternum, clavicle, vertebrae, pelvic bones) and proximal ends of long bones (humerus and femur). This move is completed by age 18 Remaining marrow cavities are replaced with fat (yellow bone marrow). By age 40 the marrow in sternum, ribs, pelvis and vertebrae is composed of equal amounts of hematopoietic tissue and fat. In times of great demand the marrow in the long bone shafts may become hematopoietic again. Extramedullary hematopoiesis may occur under two conditions:
When extramedullary hematopoiesis occurs, the liver and spleen will become enlarged. Blood cell development in adults All blood cells develop from pluripotent stem cells that are found in the red bone marrow. Stem cells make up 10% of cord blood cells and <1% of all adult blood cells. Stem cells are able to proliferate as well as differentiate into the different types of blood cells. They are also able to renew themselves. The pluripotent stem cell is the progenitor of two multipotential stem cell lines: the myeloid and the lymphoid lines. Myeloid stem cells are precursors of granulocytes, monocyte, RBCs and platelets; lymphoid stem cells are precursor of lymphocytes. Myeloid cell line The myeloid stem cell becomes the CFU-GEMM (colony forming unit, granulocyte-erythrocyte-monocyte-megakaryocyte). CFU terminology comes from tissue culture of cells where marrow cells were injected and colonies of cells would appear. CFU-GEMM leads to formation of:
Using routine hematology laboratory analysis, we cannot identify the cells up to this point by morphology alone. They are identified by surface receptor analysis. All this formation and development of cells is under control of growth factors and inhibitors, and the microenvironment.
Lymphoid cell line Cells that develop along this line become the pre-B lymphocyte and pre-T lymphocyte (prothymocyte) cells. Pools of hematopoietic activity (where are all these cells?) 1. Bone marrow Stem cell pool - comprised of multipotential stem cells and unipotential committed colony-forming units (CFUs), all of which are morphologically unidentifiable. Proliferating pool - cells are capable of DNA synthesis and are undergoing mitosis. Storage pool - mature cells that are stored for later release into the peripheral blood and cells that are maturing. They are no longer capable of mitosis. 2. Peripheral blood Circulating pool - functioning cells in circulation, in transit to tissues. The blood we draw for evaluation comes from this pool. The circulating pool is found more towards the center of the tubular blood vessel. Marginating pool – Primarily a term used for white blood cells. The cells are adhered to walls of blood vessels and are ready to move through into the tissues (diapedesis). There is constant movement between the circulating and marginating pools. At a given time the ratio of cells in the circulating pool to the cells in the marginating pool is 50:50. Neutrophils move freely between the two pools.
The two pools of circulation in peripheral blood
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