Hematopoiesis

1. Erythropoiesis
2. thrombopoiesis
3. leukopoiesis

Hematopoiesis

The formation of blood cells (hematopoiesis) occurs in the bone marrow. In neonates, most of the skeleton contains active bone marrow, but in adults it is usually found only in the vertebrae, ribs, skull, pelvis, and the proximal femurs.

Blood cells are derived from stem cells in the bone marrow and are produced after several stages of cell division and differentiation. Erythropoiesis is the process of red blood cell formation; thrombopoiesis is the process of platelet production; and leukopoiesis is a general term describing white blood cell production. The final differentiation of lymphocytes occurs in peripheral lymphoid tissues .

1. Erythropoiesis

The production of red blood cells is regulated to provide an adequate O2 - carrying capacity in blood. The hormone erythropoietin (EPO) is the primary regulator of erythropoiesis, and is released from the kidney when O2 tension in the renal parenchyma is reduced. Committed erythroid stem cells in the bone marrow are responsive to EPO, which increases the rate of cell division and the differentiation into mature red cells.

There are several general features of the process of stem cell differentiation into mature red cells: 

• Cells decrease in size. 
• Hemoglobin is produced, which fills the cytoplasm and causes the characteristic red coloration. 
• The number of cell organelles decreases; all organelles eventually disappear from red cells. 
• The nucleus gradually condenses and disappears.

In the final stage of differentiation, immature red cells are called reticulocytes, which are characterized by the presence of organelle remnants. There is normally less than 1% of circulating red blood cells in the immature reticulocyte stage.

Mature erythrocytes are diskshaped anucleate cells, approximately 7–8 μm in diameter. The extensive cytoskeleton of red cells causes them to be extremely pliable and allows them to pass through the microcirculation.

When red cells leave the bone marrow, they contain several key cytoplasmic proteins:

• Hemoglobin is the major protein present in red blood cells, and is responsible for the large O2 -carrying capacity of blood. 
• Glycolytic enzymes are needed because red cells have no mitochondria and must synthesize adenosine triphosphate (ATP) via glycolysis. 
• Carbonic anhydrase is used to catalyze the following equilibrium reaction, which is essential for CO2 carriage in blood: H2O + CO2↔ H2 CO3↔ HCO3 -+ H+

The normal lifespan of a red blood cell in the circulation is approximately 100–120 days. Erythropoiesis must therefore replace approximately 0.8% to 1.0% of the circulating red cells daily to maintain a stable red cell mass. Aging red blood cells become progressively more fragile and are ultimately removed from the circulation by scavenging macrophages, particularly in the spleen. 

The end product of hemoglobin breakdown in macrophages is bilirubin, which is conjugated in the liver and excreted in the bile and in the urine. 

2. Thrombopoiesis

Platelets are small diskshaped cell fragments without a nucleus. The cytoplasm contains an extensive cytoskeleton, which allows the shape of a platelet to change upon activation. There are also many secretory granules containing factors that regulate hemostasis (blood clothing). Thrombopoiesisis activated during the stress. 

Platelet production (thrombopoiesis) occurs in the bone marrow by the cytoplasmic fragmentation of megakaryocytes .

The rate of platelet formation is regulated by the cytokine thrombopoietin (note: the term “cytokine” is used to describe peptide hormones that regulate cell differentiation or immune functions). 

Thrombopoietin is constitutively secreted by the liver and kidneys, although the plasma concentration of TPO is mostly determined by the number of platelets in circulation.

3. Leukopoiesis

White cells play a defensive role in destroying infecting organisms and in the removal of damaged tissue. 

Limphopoiesis 

The development of lymphoid progenitor cells in bone marrow yields only primitive precursor cells. The final differentiation of lymphocytes occurs in peripheral lymphoid tissues as part of a specific immune response: T lymphocytes are differentiated in the thymus gland, and B lymphocytes are mainly differentiated in the lymph nodes. 

Neutrophilopoiesis, eosinophilopoiesis, and basophilopoiesis 

The granular white blood cells (i.e., neutrophils, eosinophils, and basophils) are released from the bone marrow as mature cells. In the case of neutrophils, a large pool of cells is maintained in the bone marrow and can be rapidly mobilized in response to an infection. 

Monocytopoiesis 

Monocytes leave the bone marrow soon after their formation. In contrast to neutrophils, there is no pool of mature monocytes in the bone marrow. Monocytes typically spend 2–3 days in the circulation before entering the tissues to become macrophages. 

Types of White Blood Cells

 Cell Type

 Relative Abundance (%)

 Characteristic Feature(s)

 Major Function(s)

 Neutrophils 

 50–70

• Multilobed nucleus 
• Cytoplasmic granules containing antibacterial, digestive, and proinflammatory agents

• Ingest and destroy invading microorganisms (phagocytosis), mediating cellular immunity
• Coordination of the early phase of acute inflammation

 Eosinophils 

 5

Acidophilic granules in cytoplasm

Phagocytosis of toxins, especially against parasitic infestation , products of allergic reactions and oncotic processes

 Monocytes 

 1–5

Large cell with 

• Respond chemotactically to invading microorganisms and sites of inflammation
• Part of a cell network, called the monocytemacrophage system; called macrophages when outside the vascular system

 Lymphocytes 

 20–40

Small cells with variable morphology

• Generate specific immune responses
• B lymphocytes become plasma cells and secrete antibodies, mediating humoral immunity
• T cells provide cellmediated immunity (e.g., destruction of virally infected cells)

 

The bacterial infections are usually associated with an increased proportion of neutrophils and monocytes, whereas viral infections increase the proportion of lymphocytes.