Chapter 7 — Coordination in Life Processes

A textbook has to describe the digestive system in one chapter and the respiratory system in another, but the body does not divide its work that way. Every life process depends on the others and is timed to fit them. Digestion needs the circulatory system to carry away what is absorbed, the respiratory system to supply the energy for the muscles and glands of the gut, and the excretory system to remove the urea made from the protein that was digested. Respiration needs the circulation to carry oxygen, and the circulation needs the nervous system to set the pace of the heart. None of this happens by chance; it is coordinated, and the coordination is done by the two linking systems studied in the previous chapter: the nervous system, acting quickly through nerve impulses, and the endocrine system, acting more slowly through hormones in the blood.

Consider one ordinary event, a meal. Before the meal we feel hungry; the feeling is produced by the brain in response to signals from the stomach and the blood. We see or smell food and the mouth waters, before a morsel has been touched. We put food in the mouth; the tongue tastes it, the jaws chew it in a rhythm set by the brain stem, saliva flows, and at the right moment the tongue pushes the bolus back and a reflex closes the windpipe and opens the gullet. Peristalsis carries the food down without any attention from us. The arrival of food in the stomach releases a hormone that switches on the gastric glands; the arrival of acid chyme in the duodenum releases other hormones that switch on the pancreas and gall bladder and slow the emptying of the stomach. Blood is diverted to the intestine so that absorption can proceed; the liver adjusts what enters the general circulation; insulin is released to deal with the glucose. Later, the water taken with the meal is regulated by the kidney under the control of ADH, and the urea from its proteins is excreted. Every step was signalled by a nerve or a hormone, and every step was timed to the one before.

This chapter takes such everyday events one by one, hunger, eating, digestion, absorption, water balance, urination, exercise and temperature, and asks in each case what the stimulus is, which receptor detects it, how the message travels, and what the response is. The pattern of the previous chapter, stimulus → receptor → coordinating system → effector → response, applies throughout, but now the responses are the life processes themselves.

Two ideas will recur. One is the reflex: many of the actions of the gut, the bladder and the breathing muscles are reflexes carried out by the spinal cord or brain stem, so fast and automatic that we are unaware of them. The other is negative feedback: a change in some quantity, blood glucose, water content, carbon dioxide, temperature, sets in motion a response that reverses the change and so keeps the quantity steady. Together they make the body a self-regulating system, which is what homeostasis means.

Hunger is the sensation that makes us seek and eat food. It is not the same as appetite, which is the desire for a particular food and can exist without need, nor the same as the emptiness of the stomach, though that is part of it. Hunger is produced in the brain, in the hypothalamus, which contains a feeding centre that drives eating and a satiety centre that stops it. The hypothalamus receives three main signals.

The stomach. An empty stomach, two to four hours after a meal, begins to contract rhythmically in waves that are stronger and longer than the mixing contractions of a full stomach. These hunger contractions are felt as pangs, and they squeeze the air and juices in the stomach so that it rumbles. Stretch receptors in the stomach wall report the state of the stomach to the brain through the vagus nerve: a stretched stomach signals fullness, an empty contracting one signals hunger. The empty stomach also secretes a hormone, ghrelin, into the blood, which acts on the hypothalamus and increases the feeling of hunger before meals; its level rises before eating and falls after.

The blood. The level of glucose in the blood is monitored by cells in the hypothalamus and in the liver. As the glucose absorbed from the last meal is used up and the level falls, the feeding centre is stimulated and we feel hungry; after a meal the rising glucose, together with insulin, stimulates the satiety centre and hunger disappears. This is why hunger passes for a while if a sweet is eaten, and why a diabetic whose cells cannot take up glucose feels constantly hungry although the blood is full of it. The levels of amino acids and fatty acids in the blood, and the hormone leptin secreted by fat tissue, which tells the hypothalamus how much fat is stored, also influence the centres over longer periods.

The senses and habit. The sight, smell or even thought of food, and the arrival of the usual meal time, stimulate the hypothalamus through the cerebral cortex, so that hunger is felt at noon even when the body is not short of fuel. Hunger is thus partly a conditioned response, and it can be increased by the sight of a laden table or destroyed by fear, illness or grief.

The feeling of hunger is the coordinating signal for the whole digestive system. It sets the animal looking for food, and it prepares the system for the food: the flow of saliva and gastric juice begins in anticipation, before a mouthful is taken. In this sense hunger is to nutrition what thirst is to water balance and breathlessness is to respiration: a sensation produced by the brain from internal signals that drives a behaviour to correct a deficit. When the meal has been eaten and the stomach is stretched, the glucose is rising and the gut hormones are flowing, the satiety centre switches hunger off, and the body has closed the feedback loop.

The sight or smell of a favourite dish makes the mouth water, and a person who is hungry can salivate at the mere mention of a mango. Salivation is the first act of digestion, and it is coordinated by the nervous system in three stages.

Before food enters the mouth. Impulses from the eyes, the nose and the memory of past meals reach the cerebral cortex, which sends impulses through the salivary centre in the medulla oblongata and along the parasympathetic nerves (the facial and glossopharyngeal cranial nerves) to the three pairs of salivary glands. The glands secrete a watery saliva before any food arrives. This is a conditioned reflex, learned by experience: a newborn does not salivate at the sight of food, but a child soon does. It was this reflex that Pavlov used in his famous experiments with dogs, in which salivation was measured through a tube from the salivary duct. The same anticipatory signals reach the stomach through the vagus nerve and start the secretion of gastric juice, so that the stomach too is ready before the food arrives; this is called the cephalic (head) phase of gastric secretion. A meal that looks and smells good is therefore genuinely better digested, and food eaten in anxiety or haste, when the sympathetic system suppresses the glands, sits heavily.

When food is in the mouth. The taste buds of the tongue, the touch receptors of the mouth lining and the pressure receptors of the teeth and jaws are stimulated by the food. Impulses travel along sensory nerves to the salivary centre in the medulla, and the centre sends motor impulses back to the glands. This is an unconditioned reflex, present from birth, and it adjusts the saliva to the food: dry food such as biscuit brings a large flow of watery saliva, sour food such as tamarind or lemon brings the greatest flow of all, since acid is the strongest stimulus, and milk brings only a little. The flow continues as long as the food is being chewed, so that the food is moistened, tasted, lubricated and, if it contains starch, partly digested by salivary amylase. A thoroughly chewed mouthful is easier to swallow and easier for the stomach.

Taste as a guide. Taste is part of the coordination in another way: it tells the brain what has been eaten and whether to accept it. Sweet and salt tastes, which signal energy and minerals, are accepted; strong bitter and sour tastes, which often signal poisons and spoiled food, produce the reflex of spitting out and, if swallowed, may produce vomiting. Flavour combines taste with smell reaching the nose from the back of the mouth, and it is smell that distinguishes a thousand flavours from five tastes.

Saliva flows at about 1 to 1.5 litres a day, most of it at meals, with a slow basal trickle between meals that keeps the mouth moist and clean. In fear the sympathetic nerves stop the flow, which is why the mouth goes dry before a speech or an examination, and why the ancient ordeal of chewing dry rice detected the guilty by their dry mouths.

Chewing (mastication). Chewing is a rhythmic movement of the lower jaw produced by the powerful jaw muscles, coordinated by a centre in the brain stem. It can be started and stopped at will, but once started it runs on its own: the pressure of food on the teeth and gums triggers a reflex that relaxes the jaw muscles, the jaw drops, the stretch of the muscles then triggers their contraction, the jaw closes on the food, and the cycle repeats. Meanwhile the tongue and cheeks, also under reflex control, keep pushing the food back between the teeth and away from the cheeks. The receptors in the teeth measure the hardness of the food and adjust the force of the bite, which is why we bite gently on a nut we expect to be soft and hard on one we expect to be tough, and why an unexpected stone in the rice is felt so sharply. The food is broken into small pieces, mixed with saliva, tasted, and rolled by the tongue into a soft ball, the bolus. Thorough chewing prepares the food for the stomach and gives the brain time to register what is being eaten.

Swallowing (deglutition). Swallowing begins voluntarily and finishes as a reflex. In the first, voluntary stage the tongue presses upward against the palate and pushes the bolus back into the pharynx. As soon as the bolus touches the receptors in the walls of the pharynx, the swallowing reflex takes over, controlled by the swallowing centre in the medulla, and it cannot be stopped. In less than a second a precisely timed sequence occurs: the soft palate is lifted to close the passage into the nose, so that food does not go up into the nasal cavity; breathing is briefly stopped; the larynx is pulled upward, which can be felt as the bobbing of the Adam's apple, and the epiglottis folds back over the opening of the larynx, so that food cannot enter the windpipe; the vocal cords close as a second barrier; and the muscles of the pharynx contract in a wave that pushes the bolus into the oesophagus, whose upper sphincter relaxes to receive it. Then the airway reopens and breathing resumes. The whole sequence is coordinated by about twenty muscles acting through five cranial nerves, and it happens about 600 times a day, mostly without our noticing, including during sleep as saliva is swallowed.

If the coordination fails, food enters the larynx. This is what happens when we talk or laugh while swallowing, since speech requires the airway to be open and the vocal cords apart at the very moment the swallowing reflex needs them closed. The touch of food on the larynx at once triggers the cough reflex, a violent expulsion of air that throws the food out; this is the choking and spluttering that follows eating too fast. If a large piece lodges in the larynx and blocks it, coughing may fail and the person cannot breathe; a sharp upward thrust on the abdomen below the ribs (the Heimlich manoeuvre) forces air from the lungs and expels the piece. Old people, patients after a stroke, and drunk persons, in whom the reflex is slow, are at particular risk, and food entering the lungs causes pneumonia.

Chewing and swallowing thus show two types of coordination in one act: a voluntary movement handed over to a reflex, and a reflex that protects one system, respiration, while serving another, nutrition.

Once the bolus has entered the oesophagus it is beyond the reach of the will. From here to the anus, a distance of about eight metres, food is moved and mixed by the smooth muscle of the gut wall, controlled by the autonomic nervous system and by a network of nerve cells within the wall itself, sometimes called the gut's own brain.

Peristalsis. The wall of the alimentary canal has two layers of smooth muscle, an inner circular layer and an outer longitudinal layer. When a bolus stretches a part of the tube, the stretch receptors there trigger a local reflex: the circular muscle just behind the bolus contracts and the muscle just ahead relaxes, so the bolus is squeezed forward; the stretched region ahead then repeats the response, and a wave of contraction travels along the tube, carrying the food with it. This wave is peristalsis, and it moves food down the oesophagus in about six to eight seconds, whether the person is sitting, lying or standing on the head. In the stomach, peristaltic waves starting near the top sweep down towards the pyloric end every twenty seconds, churning the food with gastric juice and pushing small squirts of chyme through the pyloric sphincter. In the small intestine, peristalsis is combined with segmentation, in which rings of circular muscle contract at intervals and then relax while the rings between them contract, chopping the contents back and forth to mix them with the juices and bring them against the villi. In the large intestine slow waves move the residue along, and two or three times a day, usually after a meal, a strong mass movement pushes the contents into the rectum.

Control. The gut can carry out these movements on its own, because of the plexus of nerve cells in its wall, and a piece of intestine removed from the body continues to show peristalsis in warm salt solution. But the rate and force are regulated by the autonomic nerves. The parasympathetic supply, mainly through the vagus nerve, increases peristalsis and the secretion of juices, and it is active during and after a meal, in the rest-and-digest state. The sympathetic supply slows the gut, reduces its blood supply and closes its sphincters, and it takes over in fear, anger, pain and exertion, in the fight-or-flight state, when digestion can wait. This is why a frightened animal stops feeding, why food eaten during anxiety is not digested well, and why a heavy meal before a race is a mistake. The sphincters, rings of circular muscle at the junctions, are also coordinated: the cardiac sphincter relaxes as a peristaltic wave reaches it and closes again to prevent reflux; the pyloric sphincter opens only when the stomach contents are fluid enough and the duodenum is ready; the ileo-caecal valve passes residue into the large intestine when the stomach fills again (the gastro-colic reflex, the reason a meal often prompts a visit to the toilet); and the anal sphincters are described later.

When the coordination is disturbed. Reversed peristalsis, from the intestine and stomach up the oesophagus, is vomiting, a protective reflex controlled by a centre in the medulla, triggered by irritation of the stomach by spoiled food or poison, by the motion of a vehicle acting on the balance organs, by certain smells, or by pain and emotion. Peristalsis that is too fast, in infection or anxiety, gives diarrhoea; too slow, in a fibre-poor diet or inactivity, gives constipation.

The digestive glands do not secrete continuously; that would waste enzymes and damage the gut. They are switched on when food is present and switched off when it has passed. The switching is done partly by nerves, as already seen for the cephalic phase, but mainly by hormones secreted by the gut wall itself, which detect the food at one point and signal the glands that will be needed at the next. These were the first hormones ever discovered: secretin, found by Bayliss and Starling in 1902, gave the word hormone to science.

Gastrin and the stomach. When food, especially protein, enters the stomach and stretches its wall, cells in the lining of the pyloric region release the hormone gastrin into the blood. Gastrin is carried round the circulation and back to the stomach, where it stimulates the gastric glands to secrete hydrochloric acid and pepsinogen and increases the churning movements. This gastric phase keeps the juice flowing for the three or four hours that the meal remains in the stomach. It is self-limiting: when the acid in the stomach becomes strong enough, it inhibits the release of gastrin, a negative feedback that prevents over-secretion. A stomach that has been empty for hours has stopped secreting; the cephalic and gastric phases start it again at the next meal.

Secretin and the pancreas. When the acid chyme squirts through the pyloric sphincter into the duodenum, the acid stimulates cells in the duodenal wall to release secretin. Secretin travels in the blood to the pancreas and makes it pour out a watery juice rich in sodium bicarbonate, which neutralises the acid and provides the alkaline medium that the pancreatic and intestinal enzymes need. Secretin also stimulates the liver to secrete more bile and slows the emptying of the stomach, so that the duodenum is not overwhelmed. The neutralisation of the acid in turn stops the release of secretin, another feedback loop.

Cholecystokinin, the gall bladder and enzymes. The presence of fats and partly digested proteins in the duodenum releases a second duodenal hormone, cholecystokinin (CCK). It has two actions: it makes the gall bladder contract and squirt stored bile through the bile duct into the duodenum, exactly when fat has arrived to be emulsified; and it makes the pancreas secrete a juice rich in enzymes, trypsin, amylase and lipase, to digest the meal. CCK also slows the stomach and, acting on the brain, contributes to the feeling of fullness that ends the meal.

The three hormones thus form a relay: gastrin from the stomach, secretin and CCK from the duodenum, each released by the food itself and each preparing the next stage. The system needs no thought and no nerve; a piece of intestine with its blood supply will respond to acid by making the pancreas secrete even when all nerves have been cut, which is how Bayliss and Starling proved that a chemical messenger was at work. Other gut hormones inhibit the stomach when fat arrives (enterogastrone) and increase insulin release when glucose is absorbed, so that the pancreas anticipates the rise in blood sugar. When the meal has passed and the stimuli are gone, the hormones fall, secretion stops, and the gut rests until the next meal.

Digestion is useless unless its products are carried away, and here the digestive and circulatory systems are coordinated so closely that they behave as one.

Blood flow to the gut. At rest about a quarter of the blood pumped by the heart goes to the digestive organs. After a meal the parasympathetic nerves and the gut hormones dilate the arterioles of the intestine and its blood flow roughly doubles, so that the capillaries of the villi are flushed with fresh blood that carries away the absorbed glucose and amino acids as fast as they enter and keeps the concentration gradient steep. The same signals increase the flow of lymph in the lacteals, which carry the absorbed fat. This diversion of blood to the gut is one reason for drowsiness after a heavy meal and for the old advice not to swim or run immediately after eating: exercise makes the sympathetic system divert blood to the muscles instead, digestion slows, and cramps may follow. The villi themselves move, swaying and shortening, under the control of the gut's nerve plexus and a hormone, villikinin, to stir the contents against their surface.

The hepatic portal system. The blood leaving the capillaries of the stomach, intestine, pancreas and spleen does not return directly to the heart; it is collected into the hepatic portal vein and taken first to the liver. This arrangement, a vein between two capillary beds, ensures that everything absorbed from the gut passes through the liver before it reaches the general circulation. In the liver, excess glucose is removed and stored as glycogen, so that the blood glucose leaving the liver stays within narrow limits however sweet the meal; amino acids are taken for protein synthesis, and those in excess are deaminated, their nitrogen becoming urea; harmful substances absorbed with the food, alcohol, drugs, bacterial toxins, are broken down or made harmless; and vitamins A, D and B₁₂ and iron are stored. Between meals the liver reverses the process, breaking down glycogen to release glucose into the blood, so that the brain, which can burn nothing else, is never without fuel. The liver is thus the coordinating organ between absorption and the needs of the body, the buffer between the irregular arrival of food and the steady requirement of the cells.

Insulin and glucagon. The storage and release of glucose by the liver are governed by the two hormones of the pancreatic islets. As glucose is absorbed and its level in the blood rises, the islets release insulin, which makes the liver, muscles and fat cells take up glucose and the liver store it as glycogen; the blood glucose falls back to about 90 mg per 100 mL within two hours of a meal. When the level falls below normal, between meals or during exercise, the islets release glucagon, which makes the liver break down glycogen and release glucose. The two hormones act in opposite directions on the same store, a perfect example of negative feedback, and in diabetes, where insulin is lacking, the coordination breaks down and glucose floods the blood and the urine while the cells starve.

Water and the large intestine. The water taken with the meal and the eight litres of digestive juices secreted each day are almost all reabsorbed in the small and large intestine, coordinated with the body's water needs; in cholera the toxin makes the intestinal cells pump salt and water out instead, and the patient can lose ten litres in a day. Oral rehydration solution works because glucose and sodium absorbed together drag water with them even in the diseased gut, a piece of physiology that has saved millions of children.

The body is about 60 to 70 percent water, and its cells work only if the concentration of the fluid around them stays within narrow limits. Water is lost continuously in urine, sweat, breath and faeces, about 2.5 litres a day and much more in heat or exercise, and it is replaced irregularly at meals and drinks. The coordination of this balance involves the brain, the pituitary, the kidneys, the skin and a sensation, thirst.

Detecting the deficit. When the body loses more water than it takes in, the blood becomes slightly more concentrated (its osmotic pressure rises) and its volume falls. Special cells in the hypothalamus, the osmoreceptors, shrink slightly as they lose water to the concentrated blood, and this is the signal. Receptors in the large veins and the heart also report the fall in blood volume, and the kidneys, sensing the fall in pressure, release an enzyme that leads to the hormone angiotensin, which also acts on the hypothalamus. Dryness of the mouth, from reduced saliva, adds a further signal but is not the main one; a person can be thirsty with a wet mouth and can quench thirst with a drink that has not yet been absorbed, because the stretch of the stomach and the wetting of the throat signal the brain that water is on the way.

Two responses. The hypothalamus responds in two ways at once. First, it produces the sensation of thirst, a behavioural response: the person seeks and drinks water, the only way the deficit can actually be made good. Thirst is felt when about half a litre has been lost, and it becomes intense and painful with greater loss; a person deprived of water dies in a few days, long before starving. Second, the hypothalamus makes the posterior pituitary release antidiuretic hormone (ADH), a physiological response that reduces further loss: ADH makes the collecting ducts of the kidney reabsorb water, so the urine becomes scanty and dark and water is saved. The sympathetic nerves at the same time reduce the flow of saliva and, in severe dehydration, of sweat. When water has been drunk and absorbed, the blood dilutes, the osmoreceptors swell, thirst disappears, ADH secretion stops, and the kidney passes the surplus as pale dilute urine. The whole loop, deficit → hypothalamus → thirst and ADH → intake and retention → correction, is one of the clearest examples of homeostasis by negative feedback.

Salt and volume. The balance of salt is coordinated with that of water. Sweat carries salt, and heavy sweating without salt replacement dilutes the blood, so that thirst is quenched too early and the person remains short of water; this is the danger of heat exhaustion in field workers and athletes, and the reason for adding a pinch of salt and sugar to their drink. When the blood volume falls, the adrenal cortex is stimulated through the angiotensin system to secrete aldosterone, which makes the kidney retain sodium, and water follows the sodium. A craving for salt appears in salt-depleted animals and people.

When the coordination fails. Infants and old people feel thirst less keenly and become dehydrated in diarrhoea or hot weather without asking for water; they must be given fluids without waiting for them to ask. Alcohol suppresses ADH, so a drinker passes more urine than he drinks and wakes dehydrated. In the rare disease diabetes insipidus ADH is absent and the person drinks and passes ten to twenty litres a day. Drinking far too much water too fast, as in some endurance events, can dilute the blood dangerously before the kidney catches up.

The kidneys make urine continuously, about a millilitre a minute, and it trickles down the ureters into the bladder all day. Passing it out, however, is an event, timed and controlled, and the control of urination (micturition) is a good example of a reflex brought under the command of the will.

The bladder and its sphincters. The urinary bladder is a bag of smooth muscle whose wall relaxes to accommodate urine as it collects; the pressure inside hardly rises until about 200 to 300 mL have gathered. At its outlet are two rings of muscle: the internal sphincter of smooth muscle, which is involuntary, and below it the external sphincter of skeletal muscle, which is under voluntary control. Both are normally closed.

The micturition reflex. As the bladder fills to about 300 mL, stretch receptors in its wall send impulses along sensory nerves to the sacral part of the spinal cord. There a reflex is set off: parasympathetic motor impulses return to the bladder wall and make it contract, and the internal sphincter relaxes. In an infant this is the whole story: the reflex empties the bladder as soon as it is full, without awareness or control, which is why babies wet themselves. The reflex centre in the spinal cord also sends the information up to the brain, and it is from this that the sensation of a full bladder and the desire to urinate arise.

Voluntary control. From the age of about two, as the nervous system matures, the cerebral cortex learns to control the reflex. It does so in two ways. It can keep the external sphincter, a skeletal muscle, contracted by voluntary motor impulses, so that even when the bladder contracts the urine is held; and it can send inhibitory impulses down the spinal cord that suppress the reflex contraction of the bladder itself, so that the sensation fades for a while and the bladder goes on filling. When the time and place are suitable, the cortex withdraws the inhibition, relaxes the external sphincter, and the reflex proceeds: the bladder contracts, both sphincters open, and the urine is passed, helped by contraction of the abdominal muscles. Toilet training is the learning of this control, and it depends on the maturation of the nerve pathways, which is why it cannot be hurried. The bladder can be held to 500 mL or more, but with rising discomfort, and beyond a point the reflex overrides the will.

When control is lost. Injury to the spinal cord above the sacral region cuts the pathway from the brain: the reflex still works, since its centre is intact, but the person can neither feel the bladder nor control it, and it empties automatically as in an infant. Damage to the sacral cord or its nerves abolishes the reflex, the bladder overfills and dribbles. In old age, after childbirth, in infection of the bladder and in prostate enlargement, control weakens in different ways: the bladder becomes irritable and contracts too soon, or the sphincters are weak, or the outlet is obstructed. Bed-wetting in older children is usually a delay in maturation of the control and passes with time. Emptying of the rectum, defaecation, is coordinated in exactly the same way: a reflex set off by the stretching of the rectum, held in check by the voluntary external anal sphincter until convenient, and released by the will; the internal anal sphincter is involuntary.

Breathing goes on without attention, awake or asleep, at about 15 breaths a minute at rest, and it speeds up or slows down exactly as the body's need for oxygen and its production of carbon dioxide change. This adjustment is a coordination between the respiratory, circulatory and nervous systems.

The respiratory centre. The rhythm of breathing is set by a group of neurons in the medulla oblongata, with a helping centre in the pons. The centre sends bursts of impulses down the phrenic nerves to the diaphragm and the intercostal nerves to the rib muscles; each burst produces an inspiration, and when the burst stops the muscles relax and expiration follows. Stretch receptors in the lungs signal when the lungs are full and cut short the inspiration, so that they are not over-inflated. The centre works automatically, but it can be overridden for a time by the cerebral cortex, for speech, singing, blowing, swimming under water or holding the breath, and it is modified by reflexes such as coughing, sneezing, yawning and hiccups.

Carbon dioxide as the signal. The chief stimulus that adjusts the rate is not shortage of oxygen but excess of carbon dioxide. Carbon dioxide dissolved in the blood forms carbonic acid, and the resulting rise in acidity is detected by chemoreceptors on the surface of the medulla, and to a smaller extent by chemoreceptors in the walls of the aorta and carotid arteries, which also respond to a fall in oxygen. A rise in carbon dioxide of only a few percent doubles the rate and depth of breathing; the extra ventilation blows off the carbon dioxide, the blood acidity returns to normal, and breathing settles again. This is negative feedback and it is extremely sensitive. It explains why a person cannot hold the breath to the point of harm: the rising carbon dioxide forces a breath. It explains the danger of breathing pure oxygen from a cylinder in a closed space, or of a diver who over-breathes before a dive to wash out carbon dioxide and then loses consciousness under water from lack of oxygen before the carbon dioxide signal returns. And it explains hyperventilation, in which rapid anxious breathing drives carbon dioxide so low that the person feels dizzy and tingly and may faint, a condition relieved by breathing into a paper bag.

During exercise. When we run, the muscles produce carbon dioxide and lactic acid at many times the resting rate. The rising carbon dioxide and acidity stimulate the respiratory centre, and the rate of breathing rises from 15 to 40 or 50 a minute and the depth from half a litre to three or four litres, so that the ventilation of the lungs increases twenty-fold. Signals from the moving joints and muscles, and impulses from the motor cortex as it commands the muscles, begin the increase even before the carbon dioxide rises, so that the first breaths of exercise are anticipatory. At the same time the sympathetic nerves and adrenaline dilate the bronchioles to reduce the resistance to air flow. After exercise the breathing stays fast until the oxygen debt is repaid and the lactic acid is cleared. Coordination with the circulation completes the picture: the heart's output rises in step with the ventilation, so that the extra oxygen taken in is carried away, and the two are matched so well that the oxygen content of arterial blood hardly changes during hard exercise.

Other adjustments. At high altitude the low oxygen stimulates the carotid chemoreceptors and breathing deepens; over days the kidney adjusts the blood acidity and over weeks more red cells are made. In sleep the centre becomes less sensitive and breathing slows; in fever it quickens. Emotion changes breathing through the hypothalamus, giving the sigh of relief, the gasp of surprise and the panting of fear.

The heart beats on its own, driven by its pacemaker, at about 70 to 75 times a minute, but the rate and force of the beat and the distribution of the blood are constantly adjusted to what the body is doing. This coordination is carried out by the cardiovascular centre in the medulla, the autonomic nerves, and the hormone adrenaline.

Adjusting the rate. The pacemaker, the sinoatrial node, receives fibres from both divisions of the autonomic system. The vagus (parasympathetic) nerve releases acetylcholine and slows the node; it is active at rest, and without it the heart would beat at about 100 a minute, which is what happens in a transplanted heart that has no nerves. The sympathetic nerves release noradrenaline and speed the node and strengthen the contraction of the ventricles. The balance between the two is set by the cardiovascular centre in the medulla, which receives information from several receptors. Baroreceptors (pressure receptors) in the walls of the aorta and carotid arteries report the blood pressure: if it rises, the centre increases vagal activity and the heart slows and the vessels relax; if it falls, as on standing up suddenly or after bleeding, the centre increases sympathetic activity and the heart speeds up and the vessels narrow, so that the pressure is restored. This is why one feels faint on jumping up from bed, before the reflex catches up. Chemoreceptors report carbon dioxide and oxygen, and receptors in the muscles and joints report movement. The hypothalamus, which handles emotion and temperature, and the cortex also send signals, so the heart races at a fright or a shout.

During exercise. When exercise begins, impulses from the motor cortex and from the moving limbs reach the cardiovascular centre, the vagus is withdrawn and the sympathetic nerves fire; the rate rises within seconds from 70 to 120 and, in hard exercise, to 180 or more, and the stroke volume increases from 70 to over 100 mL, so the output of the heart rises from 5 to 20 or 25 litres a minute. Adrenaline from the adrenal medulla reinforces this and keeps it going. The rise is coordinated with the rise in breathing, so that the extra oxygen taken in is delivered. At the same time the arterioles of the working muscles dilate, partly under sympathetic control and mostly because the carbon dioxide, acid and heat they produce relax their walls, so that they receive up to twenty times their resting flow; the arterioles of the skin dilate to lose heat; and the arterioles of the intestine, kidney and inactive muscles constrict, so that blood is diverted from the organs that can wait to the ones that cannot. The muscles pumping on the veins and the deeper breathing return blood to the heart faster. After exercise the reverse occurs over some minutes, and a trained athlete's rate falls faster than an untrained person's.

At rest and after meals. During sleep the vagus dominates, the rate falls to 50 or 60, and the pressure falls. After a meal blood is diverted to the gut, and the heart works a little harder to maintain the pressure. In fever the rate rises about ten beats for each degree. In shock from loss of blood the sympathetic system narrows the vessels of the skin, gut and kidneys to keep the brain and heart supplied, which is why the patient is pale and cold and passes no urine.

The circulation thus coordinates all the other processes: it delivers to each organ the blood it needs at that moment, reading the needs from the pressure, gases and activity of the body, and it is itself coordinated by the medulla, the autonomic nerves and adrenaline.

Humans keep their internal temperature close to 37 °C whether the air is 5 °C or 45 °C. This constancy, called homeothermy, lets the enzymes of every cell work at their best rate all the time, and it is achieved by coordinating heat production, which is a by-product of respiration and muscular work, with heat loss, which takes place mostly through the skin. The thermostat is in the hypothalamus, which has heat-sensitive cells of its own that measure the temperature of the blood flowing through it, and which receives impulses from the cold and warm receptors of the skin that warn of changes outside before the core temperature has moved. The hypothalamus then acts through the autonomic nerves, the hormones and behaviour.

When the body is too hot, after exercise, in fever or in a hot climate, the hypothalamus increases heat loss. The arterioles of the skin dilate (vasodilation), so that warm blood flows close to the surface and heat radiates and is conducted away; the skin becomes flushed and red. The sweat glands are stimulated through the sympathetic nerves and pour out sweat, whose evaporation takes heat from the skin, about 2.4 kJ for every gram of water evaporated; this is the main cooling mechanism in heat and during exercise, when sweating may exceed a litre an hour. Sweating fails when the air is very humid, since evaporation slows, which is why a humid 35 °C on the coast is more oppressive than a dry 42 °C inland. Heat production is reduced by lassitude and by the lowering of thyroxine over weeks, and behaviour does the rest: we seek shade, remove clothing, drink and stop working. Because sweating loses water and salt, temperature regulation is coordinated with water balance: heavy sweating provokes thirst and ADH, and a dehydrated person stops sweating and is in danger of heat stroke, in which the temperature climbs above 41 °C and the hypothalamus itself fails; the victim must be cooled at once with water and fanning.

When the body is too cold, the hypothalamus reduces loss and increases production. The skin arterioles constrict (vasoconstriction), keeping warm blood in the core and away from the surface, so that the skin becomes pale and the fingers and toes go numb; sweating stops; the tiny muscles at the base of the hairs contract, raising them (goose-flesh), which traps a layer of air in furry animals and is a useless relic in us. Heat production is increased by shivering, rhythmic involuntary contractions of the skeletal muscles that can raise heat output five-fold, by the release of adrenaline and, in prolonged cold, of thyroxine, which raise the metabolic rate, and by voluntary activity, stamping and rubbing. Behaviour again completes the response: we put on clothes, huddle, seek the sun or a fire, and eat more. In infants, in the elderly and in the drunk the responses are weak, and prolonged cold produces hypothermia, a falling core temperature that ends in unconsciousness and death, a real danger in the Himalayan cold and to newborns in winter.

Fever. During an infection, substances released by white cells act on the hypothalamus and reset its thermostat to a higher level, say 39 °C. The body then behaves as if too cold: the patient shivers and feels chilled while the temperature climbs, until the new level is reached. The higher temperature slows many germs and speeds the immune response, so moderate fever is useful. When the infection subsides the thermostat is reset to 37 °C, the body behaves as if too hot, and the patient sweats profusely as the fever breaks. Paracetamol lowers the setting, which is why it produces a sweat. Temperature regulation thus draws on the circulation, the skin, the muscles, the endocrine glands and the water balance, all coordinated by the hypothalamus, and it shows in one system how closely all the life processes are linked.

Having followed the coordination of each process, it is worth stepping back to see the pattern that connects them. Each of the earlier chapters described a system; this chapter has shown that the systems form a single network, and that the network is held together by three kinds of link.

Material links. The systems supply one another. Nutrition provides glucose for respiration, amino acids for the proteins of every organ, and the water and salts that circulation and excretion handle. Respiration provides the ATP that drives the muscles of the gut, the pumping of the heart, the active transport of the kidney tubules and the impulses of the nerves; without it nothing else works for more than a minute. Circulation carries every material between every pair of systems: oxygen from lungs to cells, carbon dioxide back, nutrients from gut to liver to tissues, urea from liver to kidney, hormones from glands to targets, heat from muscles to skin. Excretion removes what the others produce and keeps the internal environment in which they work. Coordination, the nervous and endocrine systems, uses the products of all of them and directs them. A failure anywhere spreads: kidney failure poisons the brain, lung failure starves the heart, heart failure floods the lungs, and starvation weakens all.

Informational links. Every system tells the others what it needs and what it is doing. The stomach tells the hypothalamus it is empty; the duodenum tells the pancreas that acid has arrived; the muscles tell the medulla that they are working and producing carbon dioxide; the concentrated blood tells the hypothalamus to make us drink; the stretched bladder tells the spinal cord and the cortex; the warm blood tells the hypothalamus to sweat. The messages travel as nerve impulses when speed is needed and as hormones when the change must be sustained, and most of them work by negative feedback, so that each quantity, glucose, water, carbon dioxide, temperature, pressure, is held near a set value. This maintenance of a steady internal environment, homeostasis, is the purpose of the whole coordination, and the hypothalamus, small as it is, sits at the centre of it, controlling hunger, thirst, temperature, water balance, the pituitary and the autonomic nerves.

Behavioural links. Finally, the body coordinates its processes through what the whole animal does. Hunger sends it to food, thirst to water, cold to shelter and heat to shade; breathlessness makes it stop, pain makes it withdraw, a full bladder makes it seek a place. These sensations are produced by the brain from internal signals and are the way in which the life processes reach out into the environment to get what the body cannot make for itself. In humans the cortex can override them for a time, to fast, to hold the breath, to work in heat, but only for a time; the deeper systems always win in the end, and a person who ignores thirst in the sun or the urge to breathe under water discovers how firmly the life processes are in charge.

For the student, the practical lesson is that any question about one life process can be answered more fully by asking what the others contribute: how the food is carried, where the energy comes from, what is excreted, which nerve or hormone gave the order. That habit of mind, seeing the organism as a coordinated whole, is what this chapter has tried to teach, and it is the foundation of medicine, in which every symptom is read as a message from one system about the state of the others.