BLOOD SYSTEM

Blood & CVS

Blood is circulated around the body within the cardiovascular system, transporting O2, necessary metabolic substrates and hormones to the cells of the body, while removing CO2 and waste products.

BLOOD FUNCTIONS • (I) It helps the process of respiration by

transporting O2 to the tissues and CO2 to the lungs.

• (II) It is responsible for distributing various nutrients to all parts of the body.

• (III) It helps the process of excretion by transporting the waste materials to the organs of excretion.

• (IV) It is the transport medium for various hormones, chemicals, essential elements, vitamins and also for the drugs we take.

• (V) It helps to maintain the acid-base balance of the body by the different buffers present in it.

BLOOD FUNCTIONS • (VI) The blood is responsible for carrying heat away

from the body core to the periphery or from a hotter region of the body to a cooler region and thus helps in maintenance of body temperature.

• (VII) The blood protects the body by neutrophils, monocytes and by the immune mechanism. The antibodies present in blood provide readymade immunity.

• (VIII) The blood also acts as a storehouse of different materials like water, electrolyte and nutrients for the cells of the body.

• (IX) The blood is responsible for haemostasis which prevents blood loss from an injury.

BLOOD VOLUME AND CONSTITUENTS

• Blood volume averages about 70 ml/kg body weight, giving a total of approximately 5 litres in an adult.

• This consists of a suspension of the formed elements: red cells, white cells and platelets - in plasma.

BLOOD VOLUME AND CONSTITUENTS

• Centrifuging a sample of blood separates the formed elements from the plasma and the ratio of the volume of the packed red cells to the total blood volume is referred to as the haematocrit or packed cell volume, which is normally about 0.45 or 45%.

• A thin layer of white cells and platelets can also be identified at the interface between the red cells and the plasma (the buffy coat). Plasma comprises 55% of total blood volume (about 3 litres in an adult).

PLASMA CONSTITUENTSPLASMA has the same ionic composition as the rest of the extracellular fluid but also contains plasma proteins (total concentration of about 60 g /L), with a range of important functions:

• ALBUMIN (synthesized by the liver) is the protein in highest concentration and so it makes the greatest contribution to the colloid osmotic pressure of plasma. It also acts as a nonspecific transport protein for a number of substances with a low solubility in water (e.g. bilirubin).

• GLOBULINS include specific transport proteins (e.g. transferrin for iron), clotting factors, the complement system and inactive precursors of certain hormones (e.g. angiotensinogen).One subtype, known as gamma globulins, or immunoglobulins, act as circulating antibodies important in specific immune responses.

• FIBRINOGEN is converted to fibrin during clotting.

FUNCTIONS OF PLASMA PROTEINS

• (1) The colloidal osmotic tension (COT) of plasma is about 25 mm Hg and plasma proteins are mostly responsible for it. Albumin (highest amount of particles with lowest molecular weight) contributes 80% of the COT. When the COT of plasma decreases (e.g., due to decreased albumin concentration), fluid leaves to the tissue spaces and oedema results.

• (2) The important function of the plasma proteins is transport (transport medium of the body). They transport hormones, metals, drugs and various metabolites. Plasma proteins also transport some CO2 as carbamino compounds.

• (3) Fibrinogen, prothrombin and other proteins which act as clotting factors are responsible for coagulation of blood.

• (4) Plasma proteins are good buffers. They can donate or accept H and help in maintenance of pH.

FUNCTIONS OF PLASMA PROTEINS

• (5) The plasma proteins are responsible for viscosity of plasma and help to maintain blood pressure.

• (6) Fibrinogen is most important in this regard due to its asymmetrical shape. They have role in rouleaux formation and thus in erythrocyte sedimentation rate (ESR).

• (7) The plasma proteins act as protein store for the tissues and also provide precursors of hormones like erythropoietin, angiotensin, etc.

• (8) Antibodies are the gama-globulins, which provide readymade immunity and protect the body.

• (9) The plasma proteins help in the formation of lipoproteins and thus keep the blood lipids in solution.

ERYTHROCYTES

• Red blood cells, or erythrocytes, have several functions but are particularly important as O2 delivery systems.

• This reflects the O2 transport characteristics of haemoglobin, which is packaged inside erythrocytes so that it does not leak out of capillaries.

HAEMOGLOBIN

• Haemoglobin consists of four peptide chains (the globin structure) each linked to a haem molecule consisting of a porphyrin ring structure encircling a ferrous iron ion (Fe2).

• The reversible binding of O2 to these ions, accounts for 97% of the normal O2-carrying capacity of blood.

• Normal haemoglobin values are in the range of 14-16 g/dl in men and 12-14 g/dl in women.

• A low blood haemoglobin concentration is referred to as anaemia.

ERYTHROCYTE DEVELOPMENT

• The process of red cell production, or erythropoiesis, begins in the embryonic yolk sac and is continued in the liver, spleen and lymph nodes in the maturing fetus.

• By the end of pregnancy and after birth, however, the process is restricted to bone marrow.

• As time progresses, the contribution from long bones decreases and in adult life only the marrow of membranous bones, such as the vertebrae, ribs and pelvis, is involved.

STAGES IN ERYTHROCYTE DEVELOPMENT

• Pluripotential stem cells, which have the potential to produce any type of blood cell, divide and develop into erythroid stem cells committed to form erythrocytes.

• These divide further and mature, synthesizing haemoglobin and eventually forming normoblasts. Nuclear material is extruded and the endoplasmic reticulum resorbed, producing first a reticulocyte, containing a few remnants of endoplasmic reticulum, and then an erythrocyte.

• Normally only these last two cell types are found in the circulation, with reticulocytes making up less than 2% of the total. This percentage rises during periods of rapid erythrocyte synthesis, when more immature cells enter the circulation.

Development of RBC & Hb

1) Pronormoblast

2) Early normoblast

3) Intermediate normoblast

4) Late normoblast

5) Reticulocyte

6) Matured RBC

NORMAL RED CELL COUNT

Mature red cells take the form of biconcave discs, which deform easily within the narrow capillaries. The normal red cell count in blood is (in one microliter of blood):4.7 to 6.1 million(male)4.2 to 5.4 million (female)

ERYTHROCYTE DESTRUCTION

• Ageing erythrocytes are destroyed, often in the spleen, after an average life span of 120 days.

• The phagocytic cells of the reticuloendofhelial system degrade the haemoglobin released, with iron from the haem and amino acids from the globin molecules being recycled.

• The porphyrin ring is converted to bilirubin, which is further metabolized by the liver and then excreted in bile.

CONTROL OF ERYTHROCYTE PRODUCTION

• Erythropoiesis is controlled by the kidney, which releases a hormone known as erythropoietin if the delivery of O2 to renal cells falls below normal. This will occur if the concentration of circulating haemoglobin is reduced (i.e. during anaemia).

• The bone marrow responds by increasing red cell production, thus increasing the haemoglobin content back to normal.

• This is seen at high altitudes, where the partial pressures of O2 in the lungs and blood are reduced. Over a period of weeks at high altitudes, erythropoietin stimulates an increase in the haemoglobin concentration, with a rise in haematocrit and red cell count (compensatory polycythaemia).

NUTRITIONAL REQUIREMENTS FOR RED CELL PRODUCTION

Erythropoiesis and haemoglobin synthesis require adequate supplies of the vitamins B12

(cyanocobalamin) and folic acid, as well as the mineral iron. Deficiencies of these may cause anaemia.

VITAMIN B12 & FOLATE

• If B12 or folate levels are reduced, cell division and maturation are adversely affected. This is particularly important at sites of rapid cell turnover, such as the bone marrow.

• There is a reduction in the red cell count so that the overall haemoglobin concentration falls. The erythrocytes, which do form are abnormally large (macrocytes), so this is known as a macrocytes or megaloblastic anaemia.

• There is no problem with haemoglobin synthesis within the developing cells; there are just too few red cells produced.

IRON• If the supply of iron is inadequate,

haemoglobin synthesis is restricted.• This leads to an anaemia in which

erythrocytes contain less haemoglobin than normal (they are hypochromic) and are, as a result, smaller than normal (microcytic).

• Iron-deficiency anaemia can occur whenever iron demand exceeds supply.

• That may be because of reduced iron intake or increased iron loss, e.g. because of chronic bleeding (men normally lose approximately 1 mg of iron daily; in menstruating women, this can rise to 2 mg or more).

HAEMOLYSIS

• Haemolysis is a destruction of the RBC membrane with the release of Hb into plasma. If exposed to hypotonic solution, a RBC undergoes swelling followed by osmotic haemolysis. The normal RBC are haemolysed by half in 0.43% NaCI, while in 0.34% NaCI all RBC are destroyed.

• Osmotic haemolysis can also occur in isotonic solutions of the compounds that are able to permeate through RBC membranes (e.g. urea).

• Fat soluble substances like chloroform or aether wash out the lipids in the RBC membranes with subsequent chemical haemolysis.

• Mechanical haemolysis is usually due to strong mechanical subjection of the blood (e.g. shaking the container of the blood).

• Thermal haemolysis is evident under freezing or defrosting the blood.

• Biological haemolysis occurs in transfusing incompatible blood or a snakebite.

OSMOTIC HAEMOLYSIS

ERYTHROCYTE SEDIMENTATION RATE (ESR)

• In an undisturbed vertical column of anticoagulated blood, erythrocytes slowly settle out, leaving a clear column of plasma above them. This rate of sedimentation increases in certain disease states and the erythrocyte sedimentation rate (ESR) is a widely used clinical investigation.

• Normal values lie in the range 5-10 mm/h but may be higher during pregnancy. Abnormally high ESR values are often associated with an increase in immunoglobulins. This favours aggregation of red cells into stacks called rouleaux, which sediment more rapidly than single cells.

ESR CLINICAL SIGNIFICANT

• As the specific gravity of RBC (1,096) is higher than gravity of plasma (1,027), sedimentation of RBC takes place (plasma with the anticoagulants, preventing blood coagulation).

• The normal erythrocyte sedimentation rate (ESR) is:– 1 to 10 mm/h in male – 2 to 15 mm/h in female.

• Inflammations of whatever origin, tumours cause an increase in ESR due to the aggregation of cells. ESR is affected by the protein blood levels: an elevation of blood albumin level leads to ESR decrease, whereas a rise in fibrinogen concentration results in ESR increase

• If the blood viscosity falls, as a consequence of diminished RBC count, ESR becomes higher and vice versa.

BLOOD GROUPS • The ability to replace blood lost following trauma or

surgery is a vital aspect of the medicine. This relies on an understanding of immune reactions against red blood cells, since these may be fatal and must be avoided if blood from one person (the donor) is to be safely transfused into another (the recipient).

• Whenever antigens on the surface of erythrocytes (aggluitinogens) come into contact with specific antibodies directed against them (agglutinins), the cells clump together or agglutinate.

• By testing for agglutination of red cells with known antibodies, the erythrocyte antigens can be identified and this defines the blood group. A variety of different antigen types have been identified but those of the ABO and Rhesus systems are the most common.

ABO system• There are two main antigens in this system, A

and B, and these give rise to four different blood groups. Of these, blood groups O and A are almost equally common and together account for over 85% of the population.

• The plasma always contains preformed antibodies (IgM class) against A or B antigens which are not already present on our own erythrocytes, whether we have been sensitized by exposure to foreign red cells or not.

• We are all exposed to A and B antigens from another source, e.g. intestinal bacteria, and only become tolerant to the antigens also present on our erythrocytes.

BLOOD TYPE

ABO system• Blood group O (or blood group zero in some

countries) individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains IgM anti-A antibodies and anti-B antibodies against the A and B blood group antigens. Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (A, B, O or AB).

• Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals of groups A or AB.

ABO system• Blood group B individuals have the B antigen on the

surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals of groups B or AB.

• Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but can donate blood only to another group AB individual.

RHESUS (Rh) FACTOR

• Blood is either Rh positive or Rh negative depending on whether red cells carry one of the Rh antigens or not. There are three main Rh antigens, C, D and E, but D is the most common. Over 85% of the population are Rh positive.

• There is unlikely to be any Rh-dependent agglutination following an initial transfusion with Rh-positive blood. This exposure sensitizes the immune system to the Rh antigen, however, so that subsequent mismatched transfusions can lead to prompt agglutination and haemolysis of the donor cells.

RHESUS (Rh) FACTOR

• Rhesus sensitization can also occur when a Rh-negative mother gives birth to a Rh-positive baby. Fetal red cells, normally separated from the maternal circulation by the placenta, may enter the mother's blood during delivery as the placenta is sheared off the uterine wall. This stimulates production of anti-Rh antibodies by the mother.

• If there is a subsequent Rh-positive pregnancy, these antibodies (IgG class) cross into the fetal circulation, leading to haemolysis. The resulting jaundice, anaemia and heart failure may threaten the baby's life.

• These problems of the ”Rhesus baby” have largely been eradicated by injecting all D-negative mothers with anti-D antibodies shortly after the birth of each baby.

TRANSFUSIONSAND CROSS MATCHING

• The terms universal donor (blood group O, Rh negative) and universal recipient (blood group AB, Rh positive) are sometimes used to indicate conditions in which transfusions may be attempted without knowing the blood group of both donor and recipient.

• The reasoning is that the red cells of the universal donor carry no antigens and so cannot be agglutinated, while the plasma of the universal recipient contains no antibodies and could not agglutinate donor cells, regardless of their group.

• Possible agglutination of recipient cells is regarded as unlikely, since agglutinins in the donor plasma will be diluted following transfusion.

TRANSFUSIONSAND CROSS MATCHING

• Use of O, Rh negative blood for a patient of unknown blood group is reserved for life-threatening emergencies, however, and donor and recipient blood groups should normally match.

• The existence of a wide range of rarer erythrocyte antigens means that blood of the appropriate group should actually be tested against samples of the patient's cells and plasma before being transfused.

• Donor cells are mixed with recipient plasma, while recipient cells are mixed with donor plasma; there should be no agglutination in either case. This is referred to as cross matching.

HEMATOPOIETIC STEM CELL

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