Body Fluids and Circulation

Blood is a connective tissue. That sounds odd the first time you hear it, because blood does not connect anything the way a ligament does. The reason is structural: every connective tissue is made of cells scattered in a matrix, and blood follows exactly that plan. Its matrix simply happens to be a liquid. The liquid part is called plasma and the cells and cell fragments suspended in it are called the formed elements. If you take blood into a tube with an anticoagulant and spin it in a centrifuge, the plasma rises as a pale straw-coloured layer taking up roughly 55 per cent of the volume, and the formed elements are packed into the lower 45 per cent. A healthy adult carries about 5 to 5.5 litres of blood in all.

Plasma is 90 to 92 per cent water. Only about 6 to 8 per cent of it is protein, but those proteins do a lot of work. Fibrinogen is the raw material of a blood clot. Globulins are largely the defence proteins, the antibodies. Albumins are the most abundant plasma protein and they hold water inside the blood vessels by maintaining the osmotic balance, which is why a shortage of albumin makes fluid leak into the tissues. Plasma also carries dissolved minerals such as Na⁺, Ca²⁺, Mg²⁺, Cl^- and HCO₃^-, along with glucose, amino acids and lipids that are being transported, and the clotting factors, which float about in an inactive form until an injury switches them on. One distinction is worth fixing now: plasma from which the clotting factors have been removed is called serum. Plasma clots in a tube, serum does not.

The erythrocytes, or red blood cells, are the most abundant cells in blood. A healthy adult has about 5 to 5.5 million of them in every cubic millimetre of blood. They are made in the red bone marrow of the adult, and as they mature in nearly all mammals they throw out the nucleus, which leaves a flexible biconcave disc with more room inside for pigment. Birds, reptiles, amphibians and fishes are different: their mature red cells keep the nucleus. The pigment is haemoglobin, present at about 12 to 16 grams in every 100 millilitres of blood, and it is what binds and carries oxygen. A red cell survives roughly 120 days and is then broken down in the spleen, which is why the spleen is nicknamed the graveyard of red blood cells.

The leucocytes, or white blood cells, are colourless because they have no haemoglobin, they keep their nucleus, and there are far fewer of them, about 6000 to 8000 per cubic millimetre. Most are short lived. They fall into two groups by whether their cytoplasm carries visible granules. The granulocytes are neutrophils, eosinophils and basophils. Neutrophils are the most abundant white cell at 60 to 65 per cent of the total and they are phagocytic, that is, they engulf and destroy invading germs. Eosinophils form only 2 to 3 per cent and are linked with resisting infections and with allergic reactions. Basophils are the rarest at 0.5 to 1 per cent and they secrete histamine, serotonin and heparin, so they are involved in inflammation. The agranulocytes are lymphocytes and monocytes. Lymphocytes make up 20 to 25 per cent and come in two kinds, B cells and T cells, which between them run the immune responses. Monocytes are 6 to 8 per cent, are the largest of the white cells, and are phagocytic like neutrophils.

The platelets, also called thrombocytes, are not whole cells at all. They are fragments pinched off from giant cells in the bone marrow called megakaryocytes, and blood holds about 1.5 to 3.5 lakh of them per cubic millimetre, that is, 1,50,000 to 3,50,000. Their job is to release the factors that start clotting, so a fall in platelet number shows up as bleeding that does not stop easily.

The surface of a red blood cell carries certain proteins and sugars that act as antigens, meaning the immune system of another person can recognise them as foreign. Two antigens, called A and B, decide the ABO grouping. The plasma of the same person carries antibodies against whichever of these antigens the person does not have, and this pairing is the whole logic of the system. A person of group A has antigen A on the red cells and anti-B antibody in the plasma. A person of group B has antigen B and anti-A antibody. A person of group AB has both antigens and, because neither is foreign to them, no anti-A or anti-B antibody at all. A person of group O has neither antigen on the cells but both antibodies in the plasma.

Compatibility follows from one rule: the donor cells must not meet an antibody in the recipient that matches their antigen. If they do, the antibody bridges the donated cells together and they agglutinate, that is, they clump into masses that block small vessels and then break down, which can be fatal. Because group O red cells carry neither A nor B antigen, they meet no matching antibody in any recipient, so group O is loosely called the universal donor. Because group AB plasma contains neither anti-A nor anti-B, it will not attack any donated red cell, so group AB is loosely called the universal recipient. In real transfusion practice the group is matched exactly wherever possible, because donor plasma antibodies and other antigen systems also matter.

A second, independent system is the Rh grouping. An antigen very like one first observed in the rhesus monkey is present on the red cells of about 80 per cent of people, and such people are written as Rh positive. Those who lack it are Rh negative. Unlike the ABO system, an Rh negative person does not already carry anti-Rh antibodies. They only make them after they have been exposed to Rh positive blood. So a first mismatched transfusion may pass off quietly while sensitising the person, and a second one produces a severe reaction.

The same sensitisation explains Rh incompatibility in pregnancy. Trouble arises in only one combination: an Rh negative mother carrying an Rh positive foetus. During pregnancy the two blood streams do not mix, because the placenta keeps them apart, so the first such pregnancy is usually normal. At the time of delivery, however, some foetal Rh positive blood can leak across into the mother, and her immune system responds by making anti-Rh antibodies. In a later pregnancy with another Rh positive foetus, those maternal antibodies can cross the placenta into the foetal circulation and destroy the foetal red blood cells. The result is a severe anaemia and jaundice in the baby known as erythroblastosis foetalis. It is prevented by giving the mother anti-Rh antibodies immediately after the delivery of the first Rh positive child, which removes the escaped foetal cells before she can be sensitised by them.

When a blood vessel is cut, the body has to plug the leak within seconds, but it must not form clots inside intact vessels. It solves this by keeping the clotting machinery in an inactive form and switching it on only where there is damage. The end product, the clot or coagulum, is a dense network of threads of a protein called fibrin, in which the dead and damaged formed elements of blood are trapped. What you see as a dark red scab is that fibrin mesh with red cells caught in it.

The switching on happens as a cascade, a chain in which each activated factor activates the next, so a small trigger produces a large, fast response. Damaged tissue and the platelets that gather at the wound release factors that begin the chain. Several plasma clotting factors, which are normally present in an inactive state, are activated one after another and finally produce an enzyme complex called thrombokinase, also written as prothrombinase. Thrombokinase converts the inactive plasma protein prothrombin into the active enzyme thrombin. Thrombin in turn catalyses the change of soluble fibrinogen into insoluble fibrin, and the fibrin threads knit into the mesh. Learn the order as a two step conversion: thrombokinase acts on prothrombin, thrombin acts on fibrinogen. Calcium ions are needed at several steps of this cascade, which is why a laboratory can stop a blood sample from clotting simply by binding up its calcium. The liver needs vitamin K to make prothrombin, and heparin, released by basophils, acts as a natural anticoagulant that keeps blood fluid inside healthy vessels.

Blood itself never touches most body cells. At the capillaries, blood pressure pushes part of the plasma out through the thin capillary wall into the spaces between cells. What comes out is called tissue fluid or interstitial fluid. It has almost the same mineral composition as plasma, but very little protein and no formed elements, because the large plasma proteins and the cells are too big to pass. Every exchange between blood and a body cell, of glucose, oxygen, carbon dioxide, hormones or waste, goes through this fluid. Most of it seeps back into the capillary at the far end, but not all.

The part that does not return directly is collected by a separate set of blind ending vessels called lymph capillaries, and once inside them the fluid is called lymph. Lymph is a colourless fluid, poor in protein and free of red blood cells, but rich in the lymphocytes that carry out immune responses, which it picks up as it passes through the lymph nodes. Lymph capillaries join into larger lymph vessels which finally empty the lymph back into the large veins near the base of the neck, so the fluid rejoins the blood. This drainage does three things: it returns fluid and any leaked protein to the circulation, it filters the fluid through lymph nodes where germs can be trapped and destroyed, and it transports the fats absorbed from the small intestine, which enter special lymph vessels called lacteals inside the intestinal villi. If lymph drainage from a limb is blocked, the tissue fluid piles up and the limb swells.

The human heart is about the size of a clenched fist and lies in the thoracic cavity between the two lungs, tilted a little towards the left. It is enclosed in a double walled membranous bag called the pericardium, and the thin layer of pericardial fluid between the two walls cushions the heart and lets it move without friction. Its wall is mostly cardiac muscle, and the muscle of the left ventricle is much thicker than that of the right, because the left ventricle has to push blood around the entire body while the right ventricle only pushes it as far as the lungs.

There are four chambers. The two upper chambers are the atria, right and left, and the two lower ones are the ventricles. A thin partition called the interatrial septum separates the two atria, a thick muscular interventricular septum separates the two ventricles, and a thick fibrous atrioventricular septum separates the atria above from the ventricles below. This complete separation is what keeps oxygenated and deoxygenated blood from mixing.

Openings between the chambers are guarded by valves that let blood pass one way only. The opening from the right atrium into the right ventricle is guarded by the tricuspid valve, which has three flaps. The opening from the left atrium into the left ventricle is guarded by the bicuspid valve, also called the mitral valve, which has two flaps. Where each ventricle opens into its great artery there is a semilunar valve, made of three half moon shaped pockets, one at the mouth of the pulmonary artery and one at the mouth of the aorta. Together these valves force blood to move from atria to ventricles and from ventricles to the arteries, and they prevent any backflow.

Now trace the blood. Deoxygenated blood returns from the whole body through the superior and inferior vena cava into the right atrium, passes the tricuspid valve into the right ventricle, and is pumped out through the pulmonary artery to the lungs. In the lungs it loses carbon dioxide and picks up oxygen, and it comes back through the pulmonary veins into the left atrium, passes the bicuspid valve into the left ventricle, and leaves through the aorta to be distributed to every tissue in the body. Note the pair of exceptions to the usual rule about arteries and veins: the pulmonary artery is the one artery that carries deoxygenated blood, and the pulmonary veins are the veins that carry oxygenated blood.

This arrangement is called double circulation, because a given portion of blood passes through the heart twice in one complete round of the body. The right side drives the pulmonary circulation, from right ventricle to lungs to left atrium, which is the short circuit that reloads oxygen. The left side drives the systemic circulation, from left ventricle through the aorta to the tissues and back through the venae cavae to the right atrium, which is the long circuit that delivers oxygen and nutrients and collects carbon dioxide and wastes. Two special arrangements sit inside the systemic circuit. The hepatic portal system is a vein that carries blood from the intestine to the liver before that blood is returned to the general circulation, so the liver gets first look at absorbed material. The coronary system is a set of vessels that exists only to supply the heart muscle itself, since the blood rushing through the chambers cannot feed the thick muscular wall.

The human heart is myogenic: the signal that starts each beat is generated inside the heart itself, not sent down a nerve from the brain. It comes from patches of specialised cardiac muscle called nodal tissue, which is autoexcitable, meaning it can produce action potentials without any outside stimulus.

Follow the impulse through the conducting system in order. It starts at the sinoatrial node, a small mass of nodal tissue in the upper right corner of the right atrium, close to where the superior vena cava enters. This node generates roughly 70 to 75 action potentials per minute, which is why a resting heart beats about 72 times a minute, and because it fires faster than any other part of the nodal tissue it sets the pace for the whole heart. That is why it is called the pacemaker. The impulse spreads across both atria and reaches the atrioventricular node, a second mass of nodal tissue in the lower left corner of the right atrium, just above the atrioventricular septum. Conduction slows briefly here, which gives the atria time to finish emptying before the ventricles start. From the atrioventricular node a bundle of conducting fibres called the bundle of His runs downward and pierces the atrioventricular septum, the only electrical doorway between atria and ventricles. On the other side it splits into a right and a left bundle branch that travel down either face of the interventricular septum towards the tip of the heart, and there they break up into fine Purkinje fibres that fan upward through the muscular walls of both ventricles. Because the ventricles are wired from the tip upward, they squeeze from the bottom up and push blood towards the arteries that leave at the top.

All the events of one heartbeat together make the cardiac cycle. Begin at joint diastole, when all four chambers are relaxed, the tricuspid and bicuspid valves are open and the semilunar valves are shut, so blood flows in from the venae cavae and pulmonary veins, through the atria and straight into the ventricles. The sinoatrial node then fires and the atria contract, which is atrial systole, and this squeezes about 30 per cent more blood into the ventricles. The impulse now reaches the ventricles and ventricular systole begins while the atria relax. Rising ventricular pressure slams the tricuspid and bicuspid valves shut, and that closure produces the first heart sound, heard as a low lubb. Pressure keeps climbing until it exceeds the pressure in the aorta and pulmonary artery, the semilunar valves are pushed open, and blood is ejected. Then the ventricles relax in ventricular diastole, pressure inside falls below that in the great arteries, and the semilunar valves snap shut, giving the second heart sound, a sharper dup. Pressure falls further, the atrioventricular valves open again and the cycle repeats. At 72 beats per minute one cycle lasts about 0.8 second, usually divided as 0.1 second of atrial systole, 0.3 second of ventricular systole and 0.4 second of joint diastole. Notice that the heart muscle spends more of each cycle resting than working, which is how it keeps going for a lifetime.

Each ventricle pushes out about 70 mL of blood per beat, and that volume is the stroke volume. The volume pumped out by each ventricle in one minute is the cardiac output, and it is simply cardiac output = stroke volume x heart rate. For a resting adult that is about 70 mL x 72 = 5040 mL, so roughly 5 litres per minute. A trained athlete can raise cardiac output to five or six times the resting value during exercise. The heart adjusts this on demand under the control of a neural centre in the medulla oblongata: sympathetic nerves increase the rate of the heartbeat, the strength of ventricular contraction and therefore the cardiac output, while parasympathetic nerves slow the heart down. Adrenal medullary hormones such as adrenaline also raise cardiac output.

An electrocardiograph is a machine that records the electrical activity of the heart from the surface of the body, and the tracing it produces is an electrocardiogram, or ECG. For a standard ECG the person is connected to the machine by three electrical leads, one to each wrist and one to the left ankle. It is important to be clear about what is being recorded: the ECG shows the electrical events that trigger the beat, not the mechanical squeezing itself. Each normal beat gives the same repeating pattern of three features, and each one has a name.

The P wave is a small upward bump that represents the electrical excitation, or depolarisation, of the atria. It is what leads to the contraction of both atria a moment later. The QRS complex is the tall spike, and it represents the depolarisation of the ventricles. Ventricular contraction begins shortly after the Q point, so the start of the QRS complex marks the beginning of ventricular systole. The repolarisation of the atria happens at the same time as the QRS complex and is hidden inside that large spike, which is why there is no separate wave for it. The T wave is the rounded wave that follows and it represents the return of the ventricles from their excited state to normal, that is, ventricular repolarisation. The end of the T wave marks the end of ventricular systole. Since every beat produces exactly one QRS complex, counting the QRS complexes in a measured length of tracing gives the heart rate. Any change in the shape, size or spacing of these waves from the normal pattern points to an abnormality in the heart, which is why ECG is such a widely used clinical test.

The chapter also lists four disorders. Hypertension means high blood pressure. Normal blood pressure is about 120/80 mm Hg, where 120 is the systolic or pumping pressure produced when the ventricles contract and 80 is the diastolic or resting pressure between beats. If repeated measurements show a pressure of 140/90 mm Hg or higher, the condition is called hypertension. Sustained high pressure makes the heart work harder and damages vital organs such as the brain and the kidney.

Coronary artery disease, often called atherosclerosis, affects the vessels that supply blood to the heart muscle. Deposits of calcium, fat, cholesterol and fibrous tissue build up in the wall of these arteries and make the lumen narrower, so less blood reaches the cardiac muscle. Angina, also called angina pectoris, is the acute chest pain that appears when not enough oxygen is reaching the heart muscle. It can occur in men and women of any age but is more common among the middle aged and the elderly, and it appears whenever a condition reduces the flow of blood to the heart muscle. Heart failure is the state in which the heart is not pumping blood effectively enough to meet the needs of the body. It is sometimes called congestive heart failure because congestion of the lungs is one of its main features. Keep three terms apart here, because they are routinely mixed up: heart failure is the heart pumping too weakly, cardiac arrest is the heart stopping altogether, and a heart attack is the sudden damage to heart muscle caused when its blood supply is cut off.