LUNG DEFENCE AND HISTOLOGY

The lung is exposed to 6 litres of potentially infected and irritant-laden air every minute. There are, therefore, numerous defence mechanisms to ensure survival. The nose humidifies, warms and filters the air and contains lymphocytes of the B series which secrete immunoglobulin A. The epiglottis protects the larynx from inhalation of material from the gastrointestinal tract.

The cough reflex is both a protective and a clearing mechanism. Cough receptors are found in the pharynx, larynx and larger airways. A cough starts with a deep inspiration followed by expiration against a closed glottis. Glottal opening then allows a forceful jet of air to be expelled.

The main clearance mechanism is the remarkable mucociliary escalator. Bronchial secretions from bronchial glands and goblet cells, together with secretions from deeper in the lungs, form a sheet of fluid which is propelled upwards continuously by the beat of the cilia lining the bronchial epithelium (Figs 5.13, 5.14). This cilial action can fail either from the rare immotile cilia syndromes or commonly from cigarette smoke.

Fig. 5.13 (a) Low-power photomicrograph of a bronchus. (b) High-power photomicrograph of normal bronchial wall.

Fig. 5.14 Electron micrograph of bronchial cilia and the mucus sheet.

The chief defence of the alveoli is the alveolar macrophage (Fig. 5.15), which, in conjunction with complement and immunoglobulin, ingests foreign material that is then transported either up the airways or into the pulmonary lymphatics. T and B lymphocytes are present throughout the lung substance and most of the immunoglobulin in the lung is made locally. The blood supplies neutrophils that pass into the lung structure in inflammation.

Fig. 5.15 Normal lung. Occasional pigment-containing macrophages are present within the alveolar spaces. Haematoxylin and eosin stain (× 25).

LUNG FUNCTION

The function of the lung is to oxygenate the blood and to remove carbon dioxide. To achieve this, ventilation of the lungs is performed by the respiratory muscles under the control of the respiratory centre in the brain. The rhythm of breathing depends on various inhibitory and excitatory mechanisms within the brainstem. These can be influenced voluntarily from higher centres and from the effect of chemoreceptors. The medullary or central chemoreceptors in the brainstem respond to changes in partial pressure of carbon dioxide in the blood (PCO₂). Chemoreceptors in the aortic and carotid body respond to low partial pressure of oxygen (PO₂) but only when this falls below 8  kPa. Thus, alteration in PCO₂ is the most important factor in respiratory control in health.

The sensitivity of the medullary chemoreceptor to PCO₂ can be reset either upwards in prolonged ventilatory failure or downwards, as when a patient is placed on a mechanical ventilator. The first situation is most commonly seen in chronic airflow limitation (chronic obstructive pulmonary disease) when patients may become dependent on hypoxic drive to maintain respiration. The injudicious administration of oxygen can then lead to ventilatory failure and death. In the second situation, ‘weaning’ a patient away from a ventilator is difficult because the medullary centre demands a low PCO₂ that cannot be maintained by the patient unaided.

Ventilation is largely performed by nerve impulses in the phrenic nerve acting to contract the diaphragm and expand the volume of the chest. Scalene and intercostal muscles act mainly by stabilising the chest wall. The result is to decrease the pressure in the pleura (already less than atmospheric). As the air inside the airways is at atmospheric pressure, the lungs must follow the chest wall through pleural apposition and expand, sucking in air. Expiration is largely a passive process: when the muscles relax the lung recoils under the influence of its own elasticity. Ventilation is, therefore, much more than just forcing air through tubes. Higher brain centres, the brainstem, spinal cord, peripheral nerves, intercostal muscles, spine, ribs and diaphragm are all involved. Moreover, the lung tissue itself must overcome its own inertia and stiffness. Malfunction of any of these can lead to respiratory failure.

Diaphragm function is in two parts: contraction leads to descent of the diaphragm and the costal parts elevate the lower ribs. A common consequence of chronic airflow limitation and hyperinflation is a low flat diaphragm which may pull the ribs inwards rather than out.

ASSESSING RESPIRATORY FUNCTION

As the function of the lungs is to add oxygen to the blood and to remove carbon dioxide, it might be thought that measurement of the PO₂ and PCO₂ in the blood would be an adequate assessment of its efficiency. However, the lung has such an enormous reserve capacity that it can sustain considerable damage before blood gases are affected. There are, nonetheless, a number of other tests of lung function that are briefly described here. These are tests of static lung volumes, ventilation or dynamic lung volumes and gas exchange across the alveolar–capillary membrane.

Although some tests of pulmonary function are quite complex, most problems only need the simpler tests to diagnose. Spirometry and peak flow measurements can be made available in many primary care centres.

Static lung volumes

When attempting to take as deep an inspiration as possible we are eventually stopped partly by the resistance of the chest wall to further deformation and partly by the inability to stretch the lung tissues any further (Fig. 5.16). Total lung capacity (TLC) at one end is, therefore, largely influenced by this ‘stretchability’ or elasticity of the lung. The stiffer the lung, as in fibrosis or scarring, the less distensible it will be. Conversely, damage to the elastic tissue of the lung (e.g. emphysema) with destruction of the alveolar walls will make it more distensible, leading to an increase in TLC. TLC is also high is some patients with asthma and chronic obstructive bronchitis, probably because the lungs are overexpanded in an attempt to widen the airways.

Fig. 5.16 Subdivisions of lung volume.

As already indicated, breathing out from TLC is largely passive by progressive retraction of the lung; this process will end at functional residual capacity (FRC) when the tendency of the lung to contract is balanced by the thorax resisting further deformation. This point is also the end of normal expiration. Further expiration is an active process involving expiratory muscles. By using these muscles, more air can be forced out until, at least in older individuals, the limiting factor is closure of the small airways which have been getting smaller along with the alveoli. Beyond this the lungs can only become smaller by direct compression of gas (Boyle’s law) by the expiratory muscles. At this point, the amount of air left in the lung is designated residual volume (RV).

In chronic bronchitis, the small airways are narrowed and inflamed; in emphysema, the elastic tissue supporting the small airways is lost and they collapse in expiration. Both mechanisms lead to an increase in RV. Conversely, if the lungs are stiffer (fibrosis), the increased tension in the lung tissue holds the airways open with closure occurring later in expiration, thus reducing the RV.

In summary, stiff lungs from fibrosis cause a low TLC and low RV, emphysema causes a high TLC and a high RV and chronic bronchitis causes a high RV. Vital capacity (VC) depends on the relative changes in RV and TLC but usually the overall effect in lung disease is a reduction.

Dynamic lung volumes

Assessment of airflow involves measuring the volume exhaled in unit time by use of a spirometric trace (Fig. 5.17). This is produced by a forced exhalation from TLC to RV. The conventional parameters derived from this trace are the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV₁). FVC is the amount exhaled forcefully from a single deep inspiration, FEV₁ is the fraction of that volume exhaled in the first second. These are then expressed as a ratio of the FEV₁ over the FVC (FEV₁%). This is normally approximately 75%, which indicates that a normal person can exhale forcibly three-quarters of their VC in 1 second. VC and FVC, one in slow expiration and the other in fast expiration, give similar results in normal individuals, although FVC is reduced in many disease states because of premature airway closure.

Fig. 5.17 Normal expiratory spirogram.

In diseases causing airways obstruction, the proportion of the VC that can be exhaled in 1 second is reduced and the FEV₁% falls. Conversely, in restrictive lung disease the airways are held open by the stiff lungs and the FEV₁% is normal, even increased. Nevertheless, the FVC will be reduced because the TLC is reduced. In restrictive lung disease, FEV₁ is reduced in proportion to FVC; in airways obstruction, it is reduced disproportionately.

Peak flow

The peak expiratory flow rate (PEFR) is the flow generated in the first 0.1 seconds of a forced expiration; the resulting figure is extrapolated over 1 minute. It can be measured easily by a variety of portable devices (Fig. 5.18) and serial recordings can be very useful in the diagnosis and monitoring of asthma (Fig. 5.19).

Fig. 5.18 The Mini-Wright Flow Meter in use.

Fig. 5.19 Peak flow chart in a child with asthma whose main symptom was cough. The dips coincide with the symptoms.

LUNG VOLUMES IN DISEASE

In summary, it is possible to distinguish two main patterns of abnormal lung function. An ‘obstructive pattern’ is seen in asthma, chronic obstructive bronchitis and emphysema. FVC, FEV₁ and FEV₁% are all reduced and RV increased; TLC is often reduced but high in emphysema. TF is low in emphysema but otherwise normal. A ‘restrictive pattern’ is seen in lung fibrosis, such as occurs in cryptogenic fibrosing alveolitis. TLC, VC, FEV₁, RV and TF are all reduced but FEV₁% is normal or high.

When other results do not give a clear pattern, RV can be very helpful, being high in airways obstruction and low in fibrosis.

DISTRIBUTION OF VENTILATION AND PERFUSION

Distribution of air within the lung is best assessed for clinical purposes by radioactive isotopes. The usual tracer gas is radioactive xenon. The measurement of radioactivity over the lung gives a measure of the distribution and also the rate at which gas enters and leaves various parts of the lung. Thus, it can be used to detect ‘air trapping’ or absence of ventilation. Perfusion of blood can be measured in a similar way, usually by microaggregates of albumin labelled with technetium-99m, and injected into a peripheral vein. These microaggregates form small emboli within the lung and the radioactivity they give off is a measure of blood distribution. These tests are most useful in the diagnosis of pulmonary embolism when perfusion to an area of lung is reduced but ventilation is maintained (Fig. 5.20). If both ventilation and perfusion are reduced, then the defect probably lies within the airways and is a failure of ventilation with secondary changes in the blood supply.

Fig. 5.20 Perfusion (upper) and ventilation (lower) scans in pulmonary emboli. Note the multiple perfusion defects but the normal ventilation pattern.

BLOOD GASES

Blood gases can be measured directly by electrodes in blood obtained by arterial puncture. The results are expressed as partial pressure of gas in the plasma (PO₂ and PCO₂). It is important to realise that this is not the same as the amount of gas carried by the blood. If all the red cells were removed, the PO₂ would be unchanged, yet the patient would be in a perilous state. The haemoglobin in the red cell packages and transports oxygen and carbon dioxide just as a subway train packages and transports passengers.

The relationship between PO₂ and saturation of the haemoglobin by oxygen (and hence the volume of oxygen carried) is given by the oxygen dissociation curve (Fig. 5.21). It will be seen that the PO₂ can drop significantly before there is a drop in the saturation, clearly a good thing in the early stages of lung disease. Nevertheless, it means that overventilation of the lung’s good parts cannot fully compensate for underventilation of bad parts because the good parts on the flat part of the curve cannot increase the carriage of oxygen in the blood supplied to them beyond a certain maximum. Thus, when there is a shunt of blood from the right to the left heart, either directly through the heart or through unventilated lung, the total amount of oxygen carried is bound to be reduced and cannot be restored to normal either by increasing ventilation or administering oxygen.

Fig. 5.21 Oxygen dissociation curve relating the partial pressure of oxygen in the blood to saturation of haemoglobin and amount of oxygen carried (assuming haemoglobin is normal).

The steep part of the curve indicates that a small increase in inspired oxygen gives a large increase in the amount of oxygen carried – clearly useful for oxygen therapy in sick patients. It also indicates how readily hypoxic tissues can remove large amounts of oxygen from the blood.

The dissociation curve for carbon dioxide is very different to that for oxygen; lowering the PCO₂ continuously lowers the saturation and hence the volume of gas carried (Fig. 5.22). This means that overventilation in one part of the lung can compensate for underventilation elsewhere. Arterial PCO₂ is a good measure of overall alveolar ventilation, being increased in alveolar hypoventilation (e.g. severe chronic airflow limitation) and decreased in alveolar hyperventilation (e.g. anxiety states, heart failure, pulmonary embolus, asthma), in which hypoxia and other factors stimulate an increase in ventilation.

Fig. 5.22 Carbon dioxide dissociation curve relating partial pressure of gas in the blood to amount carried.

The lungs help to regulate the acid–base balance by their ability to excrete or to retain carbon dioxide. In cases of metabolic acidosis (e.g. diabetic ketoacidosis, renal failure), the lungs can ‘blow off’ carbon dioxide to restore the pH towards normal. In cases of metabolic alkalosis (e.g. prolonged vomiting with loss of acid from the stomach), the retention of carbon dioxide again restores the pH towards normal. Retention or secretion of carbon dioxide as a result of lung disease (respiratory acidosis and alkalosis) alters pH, which is then secondarily restored by excretion or retention of bicarbonate by the kidney. Thus, changes in arterial PCO₂ (whether primary or secondary) can be regarded as functions of the lung, and changes in bicarbonate (again, either primary or secondary) can be regarded as functions of the kidney.

DYSPNOEA

Most lung diseases will cause dyspnoea or difficulty in breathing. Patients will express this in different ways as ‘shortness of breath’, ‘shortwindedness’, ‘can’t get my breath’ or in terms of functional disability (‘can’t do the housework’).

Some patients will talk about ‘tightness’. It may not be immediately clear whether they are describing breathlessness or pain. If the complaint is really a pain then this may well be angina, which is in itself sometimes associated with breathlessness. If asked directly, patients can usually tell you whether their tightness means pain or breathlessness. Some patients with pleuritic pain complain of breathlessness, but what they really mean is that they are unable to take a deep breath because of pain. It is of interest to consider why patients complain of breathlessness. Most normal people do not regard themselves as ill when they are short of breath, say when running for a bus. It seems probable that the sensations reported by patients are the same as the rest of us but they recognise that the work the lungs are being asked to do is disproportionate to the task the body is performing, that is, it feels inappropriate.

COUGH

Cough arises from the cough receptors in the pharynx, larynx and bronchi; it, therefore, results from irritation of these receptors from infection, inflammation, tumour or foreign body. Cough may be the only symptom in asthma, particularly childhood asthma. Cough in children occurring regularly after exercise or at night is virtually diagnostic of asthma. Many smokers regard cough as normal: ‘only a smoker’s cough’ or may deny it completely despite having just coughed in front of the examiner. In these patients, a change in the character of the cough can be highly significant.

Patients can often localise cough to above the larynx (‘a tickle in the throat’) or below. Postnasal drip from rhinitis can cause the former and may be accompanied by sneezing and nasal blockage.

Laryngitis will cause both cough and a hoarse voice. Recurrent laryngeal nerve palsy causes a hoarse voice and an ineffective cough because the cord is immobile. The usual cause is involvement of the left recurrent laryngeal nerve by tumour in its course in the chest. Cough from tracheitis is usually dry and painful. Cough from further down the airways is often associated with sputum production (bronchitis, bronchiectasis or pneumonia). In the latter, associated pleurisy makes coughing very distressing and reduces its effectiveness. Other possibilities are carcinoma, lung fibrosis and increased bronchial responsiveness (this is an inflammatory condition of the airways, thought to be part of the mechanism underlying asthma and often made worse by the factors listed in the ‘symptoms and signs’ box on allergic and nonallergic factors in asthma). A cause of cough, which is often overlooked, is aspiration into the lungs from gastro-oesophageal reflux or a pharyngeal pouch. Cough will then follow meals or lying down. Prolonged coughing bouts can cause both unconsciousness from reduction of venous return from the brain (cough syncope) and also vomiting. Sometimes the history of cough is omitted, making diagnosis difficult!

SPUTUM

Patients may understand the term ‘phlegm’ better than sputum. It is the result of excessive bronchial secretion; itself a manifestation of inflammation and infection. Like cough, smokers may not acknowledge its existence. Children usually swallow their sputum. It is essential to be certain that the complaint relates to the chest, because some patients have difficulty in distinguishing sputum production from gastrointestinal reflux, postnasal drip or saliva. Sometimes asking the patient to ‘show me what you have to do to get phlegm up’ can be helpful. If the patient denies sputum, a cough producing a rattle (a ‘loose cough’) suggests that it is present.

Sputum caused by chronic irritation is usually white or grey, particularly in smokers; if infected, it becomes yellow from the presence of leucocytes and this may turn to green by the action of the enzyme verdoperoxidase. Yellow or green sputum in asthma can be caused by the presence of eosinophils rather than infection. Questions on frequency are most useful in the diagnosis of chronic bronchitis, an epidemiological definition of this is ‘sputum production on most days for three consecutive months for two successive years’. Sputum production is common in asthmatics and is occasionally the main complaint. The diagnosis of bronchiectasis is made on a story of daily sputum production stretching back to childhood.

Patients can often give an estimate of the amount of sputum they bring up each day, usually in terms of a cup or teaspoon and so on. Large amounts occur in bronchiectasis and lung abscess and in the rare bronchioloalveolar cell carcinoma.

Sticky ‘rusty’ sputum is characteristic of lobar pneumonia, and frothy sputum with streaks of blood is seen in pulmonary oedema.

Highly viscous sputum, sometimes with plugs, is characteristic of asthma and in some patients with chronic bronchitis. Small bronchial casts, like twigs, may be described by a patient with the condition of bronchopulmonary aspergillosis associated with asthma.