BASIC OF LIFE: BLOOD PART 4- Haemopoiesis

Haemopoiesis

Haemopoiesis is the production of the formed elements of blood. Haemopoietic tissues refer to the tissues that produce blood. The earliest haemopoietic tissue to develop is the yolk sac, which also functions in the transfer of yolk nutrients of the embryo. In the foetus, blood cells are produced by the bone marrow, liver, spleen and thymus. This changes during and after birth. The liver stops producing blood cells around the time of birth, while the spleen stops producing them soon after birth but continues to produce lymphocytes for life. From infancy onwards, all formed elements are produced in the red bone marrow. Lymphocytes are additionally produced in lymphoid tissues and organs widely distributed in the body, including the thymus, tonsils, lymph nodes, spleen and patches of lymphoid tissues in the intestine.

Erythropoesis

Erythropoiesis refers specifically to the production of erythrocytes or red blood cells (RBCs). These are formed through the following sequence of cell transformations:

The proerythroblast has receptors for the hormone erythropoietin (EPO). Once EPO receptors are in place, the cell is committed to exclusively producing RBCs. The erythroblasts then multiply and synthesise haemoglobin (Hb), which is a red oxygen transport protein. The nucleus from the erythroblasts is then discarded, giving rise to cells named reticulocytes. The overall transformation from haemocytoblast to reticulocytes involves a reduction in cell size, an increase in cell number, the synthesis of haemoglobin, and the loss of the cell nucleus. These reticulocytes leave the bone marrow and enter the bloodstream where they mature into erythrocytes when their endoplasmic reticulum disappears.

Leukopoiesis

Leukopoiesis refers to the production of leukocytes (WBCs). It begins when some types of haemocytoblasts differentiate into three types of committed cells:

    B progenitors, which are destined to become B lymphocytes

    T progenitors, which become T lymphocytes

    Granulocyte-macrophage colony-forming units, which become granulocytes and monocytes

These cells have receptors for colony-stimulating factors (CSFs). Each CSF stimulates a different WBC type to develop in response to specific needs. Mature lymphocytes and macrophages secrete several types of CSFs in response to infections and other immune challenges. The red bone marrow stores granulocytes and monocytes until they are needed in the bloodstream. However, circulating leukocytes do not stay in the blood for very long. Granulocytes circulate for 4-8 hours and then migrate into the tissues where they live for another 4-5 days. Monocytes travel in the blood for 10-20 hours, then migrate into the tissues and transform into a variety of macrophages which can live as long as a few years. Lymphocytes are responsible for long-tern immunity and can survive from a few weeks to decades. They are continually recycled from blood to tissue fluid to lymph and finally back to the blood.

Thrombopoiesis

Thrombopoiesis refers to the production of platelets in the blood, because platelets used to be called thrombocytes. This starts when a haemocytoblast develops receptors for the hormone thrombopoietin which is produced by the liver and kidneys. When these receptors are in place, the haemocytoblast becomes a committed cell called a megakaryoblast. This replicates its DNA, producing a large cell called a megakaryocyte, which breaks up into tiny fragments that enter the bloodstream. About 25-40% of the platelets are stored in the spleen and released as needed. The remainder circulate freely in the blood are live for about 10 days.

Ageing changes in the blood

The properties of blood change as we grow older. It is thought that these changes might contribute to the increased incident of clot formation and atherosclerosis in older people. Some of the most prominent findings on these changes include:

* Rise in fibrinogen

* Rise in blood viscosity

* Rise in plasma viscosity

* Increased red blood cell rigidity

* Increased formation of fibrin degradation products

* Earlier activation of the coagulation system

The increased level of plasma fibrinogen is thought to be due to either its rapid production or slower degradation. As age progresses, fibrinogen and plasma viscosity tend to be positively correlated, with the rise in plasma viscosity being largely attributed to the rise in fibrinogen.

The viscosity of blood depends on factors such as shear rate, haemocrit, red cell deformability, plasma viscosity and red cell aggregation.

 Although there are many factors involved, hyperviscosity syndrome can be generated by a rise in only one factor. A state of hyperviscosity causes sluggish blood flow and reduced oxygen supply to the tissue.

An age-dependent increase in various coagulation factors, a positive correlation with fibrinogen and a negative correlation with plasma albumin has also been found. Both platelet and red cell aggregation increase with age, with red cell aggregation appearing to be the primary factor responsible for a rise in blood viscosity at low shear rates.

The decrease in red cell deformability (increase in rigidity) refers to its ability to deform under flow forces. Less deformable cells offer more resistance to flow in the microcirculation, which influences the delivery of oxygen to the tissues. Studies have found that older people have less fluid membranes in their red cells.

Blood H+ has also been found to be positively correlated with age, making the blood slightly more acidic as we age. This results in a swelling of the cell, making the red cells less deformable. This sets up a cycle for further increase in blood viscosity and worsening of blood flow parameters.

Since ageing causes a reduction in total body water, blood volume decreases due to less fluid being present in the bloodstream. The number of red blood cells, and the corresponding haemoglobin and haemocrit levels, are reduced which contributes to fatigue in the individual. Most of the white blood cells stay at their original levels, although there is a decrease in lymphocyte number and ability to fight off bacteria, leading to a reduced ability to resist infection.

Overall, the rise in fibrinogen is the most common and significant change in blood during ageing because it contributes to a rise in plasma viscosity, red blood cell aggregation and a rise in blood viscosity at low shear rates. Increased age is associated with a state of hypercoagulation of blood, making older people more susceptible to clot formation and atherosclerosis.