13The blood

LEARNING OBJECTIVES

After reading this chapter you should understand:

• the composition of blood

• the formation of blood cells

• the formation of red blood cells

• the process of blood clotting

• the functions of blood

• blood groups and the Rhesus (Rh) factor

The circulatory system is the transport system of the body by whichfood, oxygen, water and all other essentials are carried to the tissue cellsand their waste products are carried away. It consists of three parts:

1. the blood– the fluid inwhichmaterials are carried to and fromthe tissues2. the heart – the driving force, which propels the blood3. the blood vessels – the routes by which the blood travels to and

through the tissues, and back to the heart.

The blood is a thick red fluid; it is bright red in the arteries, where it isoxygenated, and a dark purplish-red in the veins, where it is deoxygen-ated, having given up some of its oxygen to the tissues – the cause of thecolour change – and received waste products taken in from them. It isslightly alkaline; the pH varies very little during life as the cells of thebody can live only if the pH is normal. It forms about 5% of the bodyweight, hence the average volume is 3–4 L.

Composition of the blood

Although apparently fluid, blood actually consists of a fluid and a solidpart. When examined under the microscope, large numbers of smallround bodies, known as the blood corpuscles or cells, can be seen. These

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form the solid part, while the liquid in which they float is the fluid partor plasma. The cells form 45% and the plasma 55% of the total volume.

Plasma

The plasma (the fluid part of the blood) is a clear, straw-coloured,watery fluid similar to the fluid found in an ordinary blister. It is com-posed of the following:

• water, which forms over 90% of the whole• mineral salts – these include chlorides, phosphates and carbonates of

sodium, potassium and calcium. The chief salt present is sodiumchloride. The correct balance of the various salts is necessary for thenormal functioning of the body tissues, and there is a total of 0.9%inorganic substances

• plasma proteins – albumin, globulin, fibrinogen, prothrombin andheparin

• foodstuffs in their simplest forms – glucose, amino acids, fatty acidsand glycerol, and vitamins

• gases in solution – oxygen, carbon dioxide and nitrogen• waste products from the tissues – urea, uric acid and creatinine• antibodies and antitoxins – these protect the body against bacterial

infection• hormones – from the ductless glands• enzymes.

The water in plasma provides fresh water to supply the fluid that bathesall the body cells and renews the water within the cells; 60% of bodyweight is water and in an average person weighing 70 kg this wouldbe approximately 46 L. Of these 46 L, approximately 29 L are withinthe cells (intracellular fluid) and 17 L are outside the cells (extracellularfluid). The extracellular fluid is divided between the blood vessels(3 L) and the fluid bathing the cells, called the interstitial fluid (14 L).

The salts in the plasma are necessary for the building of protoplasm andthey act as buffer substances neutralizing acids or alkali in the body andmaintaining the correct pH of the blood. Blood is always slightly alkalinein health and has a pH of 7.4. In plasma there are approximately155 mmol/L of positively charged ions, chiefly sodium, balanced by155 mmol/L of negatively charged ions, mainly chloride and bicarbonate.This is referred to as the electrolyte balance and is similar in the interstitialfluid. In the intracellular fluid, potassium replaces sodium as the positivelycharged ions, and phosphate ions and proteins replace chloride as the neg-atively charged ions.

The proteins that plasma contains give the blood the sticky consis-tency, called viscosity, which is necessary to prevent too much fluid

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passing through the capillary walls into the tissues. If there is a defi-ciency of protein, as in kidney disease, when protein is constantly lostas albumin in the urine, the osmotic pressure of the plasma is loweredand excess fluid escapes into the tissues. This excess fluid is calledoedema. The viscosity of the blood also assists in the maintenance ofthe blood pressure. Albumin is made in the liver and globulin is derivedfrom the group of white blood cells called lymphocytes. Fibrinogen andprothrombin are produced in the liver and are both necessary for themechanism of the clotting of blood. Plasma without fibrinogen is calledserum; this can be seen as the yellow fluid that oozes from a cut aftera clot has formed. Heparin is also formed in the liver and prevents bloodclotting in the vessels.

Foodstuffs, in the form of glucose, amino acids, fatty acids and glyc-erol, are absorbed from the alimentary tract into the blood. They arethe end products of carbohydrate, protein and fat metabolism.

Urea, uric acid and creatinine are the waste products from proteinmetabolism. They are made in the liver and are carried by the bloodfor excretion by the kidneys.

Antibodies and antitoxins are complex protein substances providingprotection against infection and neutralizing the poisonous bacterial toxins.

Enzymes, which are all protein molecules, produce chemical changesin other substances without themselves entering into the reaction.

The blood cells

The cells are of three types: red blood cells (erythrocytes), white bloodcells (leukocytes) and platelets (thrombocytes).

The formation of blood cells

The formation of blood cells takes place in the bone marrow and themature products are released into the blood stream. Eight different cellsare formed and all are formed from one type of pluripotent stem cell,which gives rise to five different lines of cells (Fig. 13.1). The myeloblastline gives rise to three types of granulocyte cells and the monoblast andlymphoblast lines give rise to the agranulocyte cells. The erythrocytes(red cells) and the platelets are formed from their own specific cell lines.

Red cells

The red cells (erythrocytes) are disc-shaped bodies, concave onboth sides (Fig. 13.2). They are very numerous, numbering about5 000 000 per cubic millimetre (mm3) of blood. They have a diameter

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of 7.2 micrometres (1 micrometre ¼ 1/1000 mm, abbreviated to mm).They have no nucleus but contain a special protein known as haemoglo-bin. This is a yellow pigment but the massed effect of these numerousyellow bodies is to make the blood appear red. Haemoglobin containsa little iron, which is essential to normal health, though the total amountin the whole body is said to be only sufficient to make a 5-cm (2-in) nail.Haemoglobin has a great affinity for oxygen. As the red cells passthough the lungs the haemoglobin combines with oxygen from the air

Pluripotent stem cell

Proerythroblast Myeloblast Monoblast Lymphoblast Megakaryoblast

Erythrocyteprecursors

Granulocyteprecursors

Monocytes

Lymphocyteprecursors

Megakaryocyte

Eosinophils Neutrophils Basophils

T-lymphocytes B-lymphocytes

Platelets

Fig. 13.1 Summary of the formation of blood cells.

(a) (b)

(c)

(d)

Fig. 13.2 Red cells. (a) In rouleaux, as seen in shed blood under the microscope.(b)–(d) Three views of a single cell.

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(forming oxyhaemoglobin) and becomes bright in colour – this makesthe oxygenated blood bright red. As the red cells pass through the tis-sues oxygen is given off from the blood and the haemoglobin becomesa dull colour (reduced haemoglobin), making the blood a darkpurplish-red. The haemoglobin is measured in grams per 100 mL; thenormal figure is 14–16 g/100 mL.

The function of the red cells is to carry oxygen to the tissues from thelungs and to carry away some carbon dioxide. This is their sole function,and is dependent on the amount of haemoglobin they contain. If there isa lack of haemoglobin, either because red cells are reduced in number orbecause each one does not contain the normal quantity of haemoglobin,the individual suffers from anaemia.

The red cells are produced in the red bone marrow of spongy bone,which is found in the extremities of long bones and in flat and irregularbones. In childhood the red bone marrow also extends throughout theshaft of the long bones, as children have a greater need for the produc-tion of red cells.

Red cells pass through various stages of development in the bonemarrow. Erythroblasts are large cells containing nuclei and a smallquantity of haemoglobin. These develop into normoblasts, which aresmaller cells with more haemoglobin and smaller nuclei. The nucleusthen disintegrates and disappears, and the cytoplasm contains finethreads, at which stage the cells are called reticulocytes. Finally, thethreads disappear and the fully mature erythrocyte passes into the bloodstream. In health, almost all red cells in the blood should be erythro-cytes, with only an occasional reticulocyte. Many factors are necessaryfor the normal formation of red blood cells. The overproduction of redcells, which may occur at high altitudes, is called polycythaemia.

Protein is required for the manufacture of protoplasm.Iron is needed for the haemoglobin. Very little iron is excreted. As

the red cells are broken down the iron is stored and used again but acertain amount of iron must be taken in the diet. A man requires about10 mg of iron per day but women require about 15 mg to replenish themenstrual loss and the depletion of iron reserves that occurs duringpregnancy, labour and lactation. Iron-containing foods include redmeat, egg yolk, green vegetables (such as lettuce and cabbage), peas,beans and lentils.

Vitamin B12 (cyanocobalamin) is necessary for the maturation of redblood cells and is usually found in adequate quantities in the diet intemperate climates. It can be absorbed from the small intestine onlywhen it has been combined with the intrinsic factor, which is secretedby the stomach. Together these two substances are known as the antia-naemic factor (or haemopoietic factor), which is stored in the liver andpassed to the bone marrow as necessary. Vitamin B12 is also known asthe extrinsic factor.

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Other necessary factors, even if only in small quantities, are vitaminC, folic acid (one of the vitamin B complex), the hormone thyroxineand traces of copper and manganese.

Red blood cells live in the circulation for about 120 days after whichthey are ingested by the cells of the monocyte/macrophage system inthe spleen and lymph nodes. Here the haemoglobin is broken down intoits component parts, which are carried to the liver. The globin is returnedto the protein stores or is excreted in the urine after further breakingdown. The haem is further split into iron, which is stored and used again,and pigment, which is converted by the liver into bile pigments andis excreted in the faeces. Red cell production and breakdown usuallyproceed at the same rate so that the number of cells remains constant.

White cells

The white cells (leukocytes) are larger than the red cells, measuringabout 10 mm in diameter, and they are less numerous. There are7–10 � 109 per litre of blood, though this increases considerably to30 � 109 per litre when infection is present. This increase is knownas leukocytosis. The leukocytes are of three different types (Fig. 13.3),as follows.

Polymorphonuclear leukocytes

Polymorphonuclear leukocytes are also known as granulocytes becauseof the granular appearance of the cytoplasm. The nucleus graduallydevelops several lobes, hence the name (poly ¼ many; morph ¼ form).These cells make up about 75% of the total white cells. They are madein the red bone marrow and survive for about 21 days. Granulocytescan be further classified according to their staining properties:

1. Neutrophils (70%) absorb both acid and alkaline dyes. They are ableto ingest small particles, e.g. bacteria and cell debris. This ability is

(a) (b) (c)

Fig. 13.3 White cells. (a) A polymorphonuclear leukocyte. (b) A lymphocyte.

(c) A monocyte.

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called phagocytosis and they are sometimes known as phagocytes.A decrease in the production of these cells is called agranulocytosisand this may occur as a result of exposure to radiation. They haveamoeboid movements and can pass out of the blood stream throughthe capillary walls to accumulate where there is infection.

2. Eosinophils (4%) absorb acid dyes and stain red. An increase in theirnumber occurs during allergic states such as asthma, and duringinfestation with worms.

3. Basophils (1% or less) absorb alkaline or basic dyes and stain blue.They contain heparin and histamine.

Lymphocytes

Lymphocytes make up approximately 20% of the total white cell count.They are made in the lymph nodes and in the lymphatic tissue, which ispresent in the spleen, liver and other organs. They show some amoeboidmovement but are not actively phagocytic. They are concerned with theproduction of antibodies.

Monocytes

Monocytes make up approximately 5% of the total white cell count.They are the largest of the white blood cells and have a horseshoe-shaped nucleus. They show both amoeboid movement and are phago-cytic, and are part of the monocyte/macrophage system.

An overproduction of immature leukocytes leads to the condition ofleukaemia. There are several types of leukaemia; all are fatal if nottreated and some forms are more responsive to treatment, usually bychemotherapy, than others.

Platelets

Platelets (thrombocytes) are even smaller than red blood cells and aremade in the bone marrow. There are about 250 � 109 per litre of blood.They are necessary for the clotting of blood.

The clotting of blood

The process whereby blood loss from the body is prevented following acut is called haemostasis and involves three stages, which work together:

1. vascular spasm – narrowing of the lumen of the cut blood vessels toslow down the loss of blood

2. formation of a platelet plug – to stop the flow of blood from the cut

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3. clotting of fibrin around the plug and retraction of fibrin – to seal thecut and pull its edges together.

The clotting process (Fig. 13.4) is very complex and involves many fac-tors. The endpoint in the process is the formation of an insoluble fibrinclot from soluble fibrinogen and this process is stimulated by the for-mation of thrombin. The formation of thrombin is stimulated by theformation of prothrombin activator and there are two systems wherebythis is achieved – the extrinsic and the intrinsic systems. The extrinsicsystem is stimulated by damaged tissue and quickly forms a very smallamount of fibrin to form a clot. The intrinsic system takes a few min-utes to work but leads to the formation of a relatively large amountof fibrin to complete the formation of the clot. As soon as the clot isformed it is broken down by the action of an enzyme called plasmin.This allows the clot to be removed in order to begin the process ofwound healing (see Chapter 23).

Extrinsicsystem

Intrinsicsystem

Formation ofprothrombin activator

Prothrombin Thrombin

Fibrinogen Fibrin � platelets

Clot

Fig. 13.4 The clotting process.

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Factors affecting clotting

Prothrombin is made in the liver and vitamin K is necessary for its man-ufacture. Vitamin K is present in green vegetables (e.g. lettuce and cab-bage) and is also manufactured in the intestines by bacterial action. Itcan be absorbed from the intestines into the blood only in the presenceof bile. If bile is not present, as in some forms of jaundice, prothrombinmay be lacking and the tendency to bleed is increased. There are a groupof genetic disorders known as the haemophilias in which individuals failto produce particular protein factors essential for clotting. These disor-ders lead to prolonged bleeding and also bleeding in deep tissues inthe body from very minor injuries. These conditions can only be treatedby replacing the missing clotting factors.

Heparin is a protein normally present in blood and is formed in theliver. It prevents blood clotting in the vessels and is therefore ananticoagulant.

The functions of blood

The functions of blood are to:

• carry nutrients to the tissues• carry oxygen to the tissues in oxyhaemoglobin• carry water to the tissues• carry away waste products to the organs that excrete them• fight bacterial infection through the white cells and antibodies• provide the materials from which glands make their secretions• distribute the secretions of ductless glands and enzymes• distribute heat evenly throughout the body and so regulate the body

temperature• arrest haemorrhage through clotting.

Blood groups

Blood from one individual cannot always be safely mixed with that ofanother. This fact became evident with the introduction of blood transfu-sion, which at first sometimes cured but sometimes killed the patient.This was due to the fact that blood is of four basic groups. If blood of dif-fering groups is mixed, the red corpuscles may become sticky and formclumps. This is termed agglutination and is fatal as the clumps of redcells block the blood vessels and obstruct the circulation, and thekidneys are severely damaged by excretion of excessive quantities ofpigment from destroyed red cells.

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When a blood transfusion is required, it is necessary first to findwhich group the person belongs to and then to find a donor belongingto the same group. Blood groups are named according to the presenceor absence of substances called agglutinogens, which are present in thered blood cells. There are two agglutinogens, A and B. If A is presentthe blood group is called group A; if B, group B. If both A and B arepresent the blood group is called group AB, and if neither is presentit is group O. Having found to which group the patient belongs(Table 13.1) and found blood donated by a person belonging to thesame basic group, a sample of red blood cells from the donor’s bloodis mixed with some plasma from the patient who is to receive the trans-fusion (now called the recipient). This is because plasma contains sub-stances called agglutinins, which cause agglutination of the red cells ifincompatible blood groups are mixed. Agglutinins are called anti-Aand anti-B, and plasma contains all those agglutinins that will notaffect its own red cells. Therefore the plasma of group A containsanti-B agglutinin, the plasma of group B contains anti-A agglutinin,the plasma of group AB contains no agglutinins, and the plasma ofgroup O contains both anti-A and anti-B agglutinins. When the donor’sred cells are mixed with the recipient’s plasma in the laboratory, it canbe seen under the microscope whether agglutination occurs. It will benoticed that group AB has no agglutinins in the plasma and thereforecannot cause any red cells to agglutinate – this means that a patientwith blood belonging to this group will probably be able to receiveblood from any other group and the group is therefore known as theuniversal recipient. Group O contains no agglutinogens in the red cellsand therefore they cannot be made to agglutinate by the agglutinins inany plasma. Blood belonging to this group can therefore be given to apatient belonging to any group and it is known as the universal donor.In practice the compatibility of blood is always checked very carefullybefore it is given to a patient.

Table 13.1 Blood groups

Blood Agglutinogen Agglutinin Transfusion group

in red cells in plasma possible

A A Anti-B Groups A and O

B B Anti-A Groups B and O

AB A and B Neither Any group

O None Anti-A and anti-B Group O only

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Rhesus factor

In addition to the ABO grouping there is an additional factor presentin the blood of approximately 85% of the population. It is an agglutino-gen called the Rhesus factor. Those who possess this factor are calledRhesus-positive (Rhþ) and the remaining 15% are Rhesus-negative(Rh–). If a Rh– person receives the blood of a Rhþ donor, the agglutino-gen stimulates the production of anti-Rh agglutinins called anti-D. Ifa second Rhþ transfusion were given later, the transfused cells wouldbe agglutinated and destroyed (haemolysed), with serious or fatalresults to the recipient. This factor can also cause difficulty during preg-nancy. If a Rh– mother is carrying a Rhþ fetus, the mother may begin toproduce anti-Rh agglutinins, which may then destroy the baby’s redcells. The baby may overcome this spontaneously or may requireexchange transfusion.

Self-test questions

• What is the major constituent of blood?• How many different types of blood cell are there?• Describe an erythrocyte.• Compare and contrast the intrinsic and extrinsic systems of blood

clotting.• What is the blood group of a universal donor and a universal

recipient?

Clinical focus

Check the websites provided to learn more about conditions related tothe blood:

Anaemia: http://www.nhs.uk/conditions/anaemia-iron-deficiency-/pages/introduction.aspx

Leukemia (acute and chronic): http://www.nhs.uk/Conditions/Leukaemia-acute/Pages/Introduction.aspx; http://www.nhs.uk/Conditions/Leukaemia-chronic/Pages/Introduction.aspx

Sickle cell anaemia: http://www.nhs.uk/conditions/sickle-cell-anaemia/pages/introduction.aspx

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