Category Archives: Respiratory disease

Examination of the respiratory system

The nose

The anterior part of the nose can be examined using a nasal speculum and light source. In allergic rhinitis the mucosa lining the nasal septum and inferior turbinate appears swollen and a dark red or plum colour. Nasal polyps can also be identified, as can a frequent site of nasal haemorrhage (Little’s area).

The chest

Radiology has become an essential part of examination of the chest. Diseases such as tuberculosis or lung cancer may not be detectable on clinical examination but are obvious on the chest X-ray. Conversely, the abnormal physical signs in asthma or chronic bronchitis may be associated with a normal chest X-ray.


The patient should be observed carefully, paying particular attention to mental alertness, cyanosis, breathlessness at rest, use of accessory muscles and any deformity or scars on the chest. A coarse tremor or flap of the outstretched hands indicates CO2 intoxication. Prominent veins on the chest may imply obstruction of the superior vena cava. The jugular venous pressure should be assessed.
Central cyanosis is assessed on the colour of the tongue and lips, and indicates a Pa02 below 6 kPa. Peripheral cyanosis is noted on the fingernails and skin of the extremities and in the absence of central cyanosis is due to a reduced peripheral circulation. Finger clubbing is present when the normal angle between the base of the nail and the nail fold is lost. The base of the nail is fluctuant owing to increased vascularity, and there is an increased curvature of the nail in all directions, with expansion of the end of the digit. Some causes  of clubbing are given. Clubbing is not seen in chronic bronchitis.


The position of the mediastinum should be ascertained by checking whether the trachea is central and whether the cardiac apex is in the fifth intercostal space. The supraclavicular fossa is examined for enlarged lymph nodes. The distance between the sternal notch and the cricoid cartilage (three to four finger breadths in full expiration) is reduced in patients with severe airflow limitation. Movement of the upper and lower parts of the chest should be assessed. Compression of the chest laterally and anteroposteriorly may produce a localized pain suggestive of a rib fracture.


This should be performed symmetrically on both sides for comparison. Liver dullness is usually detected anteriorly at the level of the sixth rib. Liver and cardiac dullness are lost with over-inflated lungs. The percussion note is dull over consolidation and stony dull over a pleural effusion.


The diaphragm of the stethoscope should be used. The patient is asked to take deep breaths through the mouth.

Physical signs of respiratory disease.

Physical signs of respiratory disease.

Some causes of finger clubbing.

Some causes of finger clubbing.

Inspiration sounds more prolonged than expiration. Healthy lungs filter off most of the high-frequency component, mainly due to turbulent flow in the larynx. Normal breath sounds are harsher anteriorly over the upper lobes (particularly on the right) and described as vesicular. Vesicular sounds may be loud in a thin healthy subject or soft in patients with emphysema. Breath sounds are reduced or absent in a pneumothorax, over a pleural effusion or when the bronchus to a lobe is obstructed by a carcinoma.
BRONCHIAL BREATHING. These abnormal breath sounds are heard best over consolidated or collapsed lung and sometimes over areas of localized fibrosis or bronchiectasis. Such areas conduct the high-frequency hissing component of breath sounds well. Characteristically, the noise heard during inspiration and expiration is equally long but separated by a short silent phase. Bronchial breathing can be imitated by listening over the larynx, particularly if the subject breathes with the vocal cords in a position to sound a whispered ‘eee’.

Whispering pectoriloquy (whispered, and therefore higher-pitched, sounds heard distinctly) invariably accompanies bronchial breathing.
ADDED SOUNDS. The terms rhonchi, rales and crepitations are best discarded and replaced with the simple terms wheezes and crackles.

WHEEZE is usually heard during expiration and results from vibrations in the collapsible part of the airways when apposition occurs as a result of the flow-limiting mechanisms. Wheezes are heard in asthma and in chronic bronchitis and emphysema, but are not invariably present. In the most severe cases of asthma a wheeze may not be heard, as the airflow may be insufficient to generate the sound. Wheezes may be monophonic (single large airway obstruction) or polyphonic (narrowing of many small airways).
CRACKLES. These brief crackling sounds are probably produced by opening of previously closed bronchioles, and their timing during breathing is of significanceearly inspiratory crackles are associated with diffuse airflow limitation, whereas late inspiratory crackles are characteristically heard in pulmonary oedema, fibrosis of the lung and bronchiectasis. They may be described as fine or coarse but this is of no significance.
PLEURAL RUB. This is a creaking or groaning sound that is usually well localized. It is indicative of inflammation and roughening of the pleural surfaces, which normally glide silently over one another.
VOCAL RESONANCE AND FREMITUS. Healthy lung attenuates high-frequency notes, leaving the booming low-pitched components of speech. Consolidated lung has the reverse effect, transmitting the high frequencies; the spoken word then takes on a bleating quality. Whispered speech can barely be heard over healthy lung, whereas consolidation allows its clear transmission. Sonorous sounds such as ‘ninety-nine’ are well transmitted across healthy lung to produce vibration that can be felt over the chest wall. Consolidated lung transmits these low-frequency noises less well, and pleural fluid severely dampens or obliterates the vibrations altogether.

Additional bedside tests

Since so m ny patients with respiratory disease have airflow limitation, airflow should be routinely measured at the bedside using a peak flow meter. This will provide a much more accurate assessment than any physical sign.

Respiratory symptoms

Runny, blocked nose and sneezing

Nasal symptoms are extremely common. The differentiation between the common cold or allergic rhinitis as a cause of ‘runny nose’ (rhinorrhoea), nasal blockage and attacks of sneezing is difficult. In allergic rhinitis, symptoms may be seasonal, following contact with grass pollen, or perennial, when the house-dust mite is the important allergen. Colds are frequent during the winter but, if more than three occur, the patient is probably suffering from perennial rhinitis rather than from infection due to a virus. Patients may be able to identify the cause of their symptoms if, for example, they sneeze whilst walking in the park in summer or after making beds.
Nasal secretions are usually thin and runny in rhinitis but thicker and yellow-green in the common cold. Nose bleeds and blood-stained nasal discharge are common occurrences and are not as serious as haemoptysis. Nevertheless, a blood-stained nasal discharge associated with nasal obstruction and pain may be the presenting feature of a nasal tumour. Total nasal blockage with loss of smell is often a feature of nasal polyps.


Cough is the commonest manifestation of lower respiratory tract disease. Smokers often have a morning cough with little sputum. Cough is the cardinal feature of chronic bronchitis, while sputum production and coughing, particularly at night, can be symptoms of asthma. Cough also occurs in asthmatics after mild exertion or following a forced expiration. A cough can also occur for psychological reasons.
A worsening cough is the commonest presenting symptom of a bronchial carcinoma. The explosive character of a normal cough is lost when laryngeal paralysis is present- a bovine cough-usually resulting from carcinoma of the bronchus infiltrating the left recurrent laryngeal nerve. Cough may be accompanied by stridor in whooping cough and in the presence of laryngeal or tracheal obstruction.
Despite the popularity of cough mixtures, the correct treatment of this symptom is to identify and treat the underlying cause. Cough may persist in some individuals for many weeks following a respiratory tract infection, perhaps as the result of persisting bronchial inflammation and increased airway responsiveness, a process that may settle with inhaled corticosteroid treatment.


Approximately 100 rnl of mucus is produced daily in a healthy, non-smoking individual. This flows at a regular pace up the airways, through the larynx, and is swallowed Excess mucus is expectorated as sputum. The most common cause of excess mucus production is cigarette smoking.
Mucoid sputum is clear and white but can contain black specks resulting from the inhalation of carbon. Yellow or green sputum is due to the presence of cellular material, including bronchial epithelial cells, or neutrophil or eosinophil granulocytes. Yellow sputum is not necessarily due to infection, as eosinophils in the sputum, as seen in asthma, can give the same appearance. The production of large quantities of yellow or green sputum is characteristic of bronchiectasis. Blood-stained sputum (haemoptysis) varies from small streaks of blood to massive bleeding. It requires thorough investigation. The following should be borne in mind.
• The commonest cause of haemoptysis is acute infection, particularly in exacerbations of chronic bronchitis and emphysema, but it should not be attributed to this without investigation.
• Other common causes are pulmonary infarction, bronchial carcinoma and tuberculosis.
• In lobar pneumonia, the sputum is rusty in appearance when blood is present.
• Pink, frothy sputum is seen in pulmonary oedema.
• In bronchiectasis, the blood is often mixed with purulent sputum.
• Massive haemoptyses (>200 rnl of blood in 24 hours) are usually due to bronchiectasis or tuberculosis.
• Uncommon causes of haemoptyses are idiopathic pulmonary haemosiderosis, Goodpasture’s syndrome, microscopic polyarteritis, trauma, blood disorders and benign tumours.
Haemoptysis should always be investigated. Often, the diagnosis can be made from a chest X-ray. Firm plugs of sputum may be coughed up by patients suffering from an exacerbation of allergic bronchopulmonary aspergillosis; sometimes such sputum may appear as firm threads representing casts from inflamed bronchi.

Breath lessness

Breathlessness should be assessed in relation to the patient’s life-style. For example, a moderate degree of breathlessness may be totally disabling if the patient has to climb many flights of stairs to reach home. A grading for breathlessness is given The term dyspnoea should be used to describe a sense of awareness of increased respiratory effort that is unpleasant and that is recognized by the patient as being inappropriate. It is highly unlikely that this term will be used by the patient. Patients may complain of tightness in the chest; this must be differentiated from angina. Orthopnoea is breathlessness on lying down and is partly due to the weight of the abdominal contents pushing the diaphragm further into the thorax. Such patients are also made uncomfortable by bending over. The terms tachypnoea and hyperpnoea refer, respectively, to an increased rate of breathing and an increased level of ventilation, which may be appropriate to the situation (e.g. during exercise). Hyperventilation is overbreathing and results in a lowering of the alveolar and arterial Pco2.

Paroxysmal nocturnal dyspnoea is described

Respiratory diseases can cause breathlessness within minutes or hours or else more slowly over days, weeks or months. The typical causes of breathlessness over differing time periods are:
1 Sudden
(a) Inhaled foreign body
(b) Pneumothorax
(c) Pulmonary embolism
2 Over a few hours
(a) Asthma
(b) Pneumonia
(c) Pulmonary oedema
(d) Extrinsic allergic alveoli tis
3 Intermittent
(a) Asthma
(b) Pulmonary oedema
4 Over days
(a) Pleural effusions
(b) Carcinoma of the bronchus/trachea
5 Over months or years
(a) Chronic bronchitis and emphysema
(b) Cryptogenic fibrosing alveoli tis
(c) Occupational fibrotic lung disease
(d) Non-respiratory causes-anaemia, hyperthyroidism


Wheezing is a common complaint and is the result of airflow limitation due to any cause. The symptom of wheezing is not diagnostic of asthma; it may be absent in the early stages of this disease, and may also occur in patients with chronic bronchitis and emphysema.

Chest pain

The commonest type of chest pain encountered in respiratory disease is a localized sharp pain, often referred to as pleuritic. It is made worse by deep breathing or coughing and can be precisely localized by the patient. Localized anterior chest pain may be accompanied by tenderness of a costochondrial junction due to costochondritis. Pain in  the shoulder tips suggests irritation of the diaphragmatic pleura, whereas central chest pain radiating to the neck and arms is typically of cardiac origin. Retrosternal soreness may occur in patients with tracheitis, and a constant, severe, dull pain may be the result of invasion of the thoracic  wall by carcinoma.

Defence mechanisms of the respiratory tract

Pulmonary disease often results from a failure of the many defence mechanisms that usually protect the lung in a healthy individual. These can be divided into physical and physiological mechanisms and humoral and cellular mechanisms.

Physical and physiological mechanisms 

HUMIDIFICATION-prevents dehydration of the epithelium. PARTICLE REMOVAL-over 90% of particles greater than 10 J.Lm in diameter are removed in the nostril or nasopharynx. Of the remainder, 5-10 J.Lm particles become impacted in the carina and 1-2 J.Lm particles are deposited in the distal lungs. Most pollen grain (>20 J.Lm) particles are deposited in the nose and conjunctiva.
PARTICLE EXPULSION-by coughing, sneezing or gagging.
The mucus of the respiratory tract is a gelatinous substance consisting chiefly of acid and neutral polysaccharides. The mucus consists of a 5 J.Lm thick gel that is relatively impermeable to water. This floats on a liquid or sol layer that is present around the cilia of the epithelial cells. The gel layer is secreted from goblet cells and mucous glands as distinct globules that coalesce increasingly in the central airways to form a more or less continuous mucus blanket. Under normal conditions the tips of the cilia are in contact with the undersurface of the gel phase and coordinate their movement to push the mucus blanket upwards. Whilst it may only take 30-60 min for mucus to be cleared from the large bronchi, there may be a delay of several days before clearance is achieved from respiratory bronchioles. One of the major long-term effects of cigarette smoking is a reduction in mucociliary transport. This contributes to recurrent infection and in the larger airways it prolongs contact with carcinogens. Congenital defects in mucociliary transport occur. In the ‘immotile cilia’ syndrome there is an absence of the dynein arms in the cilia themselves, and in cystic fibrosis an abnormal mucus is associated with ciliary dyskinesia. Both diseases are characterized by recurrent infections and eventually with the development of bronchiectasis.

Defence mechanisms present at the epithelial surface.

Defence mechanisms present at the epithelil surface.

Humoral and cellular mechanisms

Non-specific soluble factors

ai-ANTITRYPSIN is present in lung secretions. It inhibits chymotrypsin and trypsin and neutralizes proteases and elastase.
LYSOZYME is an enzyme found in granulocytes that has bacteriocidal properties.
LACTOFERRIN is synthesized from epithelial cells and neutrophil granulocytes and has bacteriocidal properties.
INTERFERON (see p. 139) is produced by most cells in response to viral infection. It is a potent suppressor of lymphocyte function and lowers the threshold for mast cell histamine release. It renders other cells resistant to infection by any other virus.
COMPLEMENT is present in secretions. In association with antibodies, it plays an important cytotoxic role. Pulmonary alveolar macrophages
These are derived from precursors in the bone marrow and migrate to the lungs via the bloodstream. They phagocytose particles, including bacteria, and are removed by the mucociliary escalator, lymphatics and bloodstream. They are the dominant cell in the airways and at the level of the alveoli and comprise 90% of all cells obtained by bronchoalveolar lavage. Macrophages (see p. 133) process antigens and playa part in both cellular and humoral immunity.

Lymphoid tissue

The bronchus-associated lymphoid tissue (BALT) consistsof lymphocytes present either in aggregates (tonsils and adenoids) or scattered. It forms an important immunological defence mechanism. Lymphocytes become sensitized to antigens, resulting in local production of secretory IgA. IgG and IgE are also present in secretions derived from B lymphocytes in the lamina propria.

Ventilation and perfusion relationships

For efficient gas exchange it is important that there is a match between ventilation of the alveoli (VA) and their perfusion (Q). There is a wide variation in the VA/Q ratio throughout both normal and diseased lung. In the normal lung the extreme relationships between alveolar ventilation and perfusion are:
• Ventilation but no perfusion (physiological dead space)
• Perfusion but no ventilation (physiological shunting)
These and the ‘ideal’ match are illustrated. In normal lungs there is a tendency for ventilation not to be matched by perfusion towards the apices, with the reverse occurring at the bases.
An increased physiological shunt results in arterial hypoxaemia. The effects of an increased physiological dead space can usually be overcome by a compensatory increase in the ventilation of normally perfused alveoli. In advanced disease this compensation cannot occur, leading to increased alveolar and arterial Pc02, together with hypoxaemia.
Hypoxaemia occurs more readily than hypercapnia because of the different ways in which oxygen and carbon dioxide are carried in the blood. Carbon dioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cell, and the relationship between the volume carried and the partial pressure is not linear. Alveolar hyperventilation resulting in a low alveolar Pc02 and a high alveolar PO, will therefore lead to a marked reduction in the carbon dioxide content of the resulting blood but no increase in the oxygen content.
The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation. The Pa02 and PaCOZ of some individuals who have mild disease of the lung causing slight VA/Q mismatch may still be normal. Increasing the requirements for gas exchange by exercise will widen the VIQ mismatch and the PaOZ will fall. VIQ mismatch is by far the commonest cause of arterial hypoxaemia.

Relationships between

Relationships between

Hypoxaemia occurs more readily than hypercapnia because of the different ways in which oxygen and carbon dioxide are carried in the blood. Carbon dioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cell, and the relationship between the volume carried and the partial pressure is not linear . Alveolar hyperventilation resulting in a low alveolar Pc02 and a high alveolar PO, will therefore lead to a marked reduction in the carbon dioxide content of the resulting blood but no increase in the oxygen content.
The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation. The Pa02 and PaCOZ of some individuals who have mild disease of the lung causing slight VA/Q mismatch may still be normal. Increasing the requirements for gas exchange by exercise will widen the VIQ mismatch and the PaOZ will fall. VIQ mismatch is by far the commonest cause of arterial hypoxaemia.

Alveolar stability

The alveoli of the lung are essentially hollow spheres. Surface tension acting at the curved internal surface tends to cause the sphere to decrease in size. The surface tension within the alveoli would make the lungs extremely difficult to distend were it not for the presence of surfactant. The type II cells within the alveolus secrete an insoluble lipoprotein largely consisting of dipalmitoyl lecithin, which forms a thin monomolecular layer at the air-fluid interface. Surfactant reduces surface tension so that alveoli remain stable.
Fluid surfaces covered with surfactant exhibit a phenomenon known as hysteresis, i.e. the surfacetension- lowering effect of the surfactant can be improved by a transient increase in the size of the surface area of the alveoli. During quiet breathing, small areas of the lung undergo collapse, but it is possible to re-expand these rapidly by a deep breath, hence the importance of sighs or deep breaths as a feature of normal breathing. Failure of such a mechanism, which can occur, for example, in patients with fractured ribs, gives rise to patchy basal lung collapse. Surfactant levels may be reduced in a number of diseases that cause damage to the lung (e.g. pneumonia), and may playa central role in the respiratory distress syndrome of the newborn. Severe reduction in perfusion of the lung causes impairment of surfactant activity and may well account for the characteristic areas of collapse associated with pulmonary embolism.

Physiology of the respiratory system

The nose

The major functions of nasal breathing are:
• To heat and moisten the air
• To remove particulate matter
About 10 000 litres of particle-laden air are inhaled daily. Deposited particles are removed from the nasal mucosa within 15 min, compared with 60-120 days from the alveolus. The relatively low flow rates and turbulence of inspired air are ideal for particle deposition, and few particles greater than 10 /-lm pass through the nose. For this reason nasal secretion contains many protective proteins in the form of antibodies, lysozymes and interferon. In addition, the cilia of the nasal epithelium move the mucous gel layer rapidly back to the oropharynx where it is swallowed. Bacteria have little chance of settling in the nose. Mucociliary protection against viral infections is more difficult because viruses bind to receptors on epithelial cells. The majority of rhinoviruses bind to an adhesion molecule, intracellular adhesion molecule 1 (lCAM-l), a receptor shared by neutrophils and eosinophils. Many noxious gases, for example S02′ are almost completely removed by nasal breathing .


Lung ventilation can be considered in two parts:
• The mechanical process of inspiration and expiration
• The control of respiration to a level appropriate for the metabolic needs


Inspiration is an active process and results from the descent of the diaphragm and movement of the ribs upwards and outwards under the influence of the intercostal muscles. In resting healthy individuals, contraction of the diaphragm is responsible for most of inspiration. Respiratory muscles are similar to other skeletal muscles but are less prone to fatigue. However weakness may play a part in respiratory failure resulting from neurological and muscle disorders and possibly with severe chronic airflow limitation.
Expiration follows passively as a result of gradual lessening of contraction of the intercostal muscles, allowing the lungs to collapse under the influence of their own elastic forces.
Inspiration against increased resistance may require the use of the accessory muscles of ventilation, such as the sternomastoid and scalene muscles. Forced expiration is also accomplished with the aid of accessory muscles, chiefly those of the abdominal wall, which help to push up the diaphragm.
The lungs have an inherent elastic property that causes them to tend to collapse away from the thoracic wall, generating a negative pressure within the pleural space. The strength of this retractive force relates to the volume of the lung; for example, at higher lung volumes the lung is stretched more, and a greater negative intrapleural pressure is generated.
Lung compliance is a measure of the relationship between this retractive force and lung volume. It is defined as the change in lung volume brought about by unit change in transpulmonary (intrapleural) pressure and is measured in litres per kilopascal (litres kPa -I). At the end of a quiet expiration, the retractive force exerted by the lungs is balanced by the tendency of the thoracic wall to spring outwards. At this point respiratory muscles are resting and the volume of the lung is known as the functional residual capacity (FRC). Diseases that can affect the movement of the thoracic cage and diaphragm can have a profound effect on ventilation.  These include diseases of the thoracic spine such as ankylosing spondylitis and kyphoscoliosis, neuropathies (e.g. the Guillain-Barre syndrome), injury to the phrenic nerves, and myasthenia gravis.


Coordinated respiratory movements result from rhythmical discharges arising in an anatomically ill-defined group of interconnected neurones in the reticular substance of the brain stem known as the respiratory centre. Motor discharges from the respiratory centre travel via the phrenic and intercostal nerves to the respiratory musculature.
The pressures of oxygen and carbon dioxide in arterial blood are closely controlled. In a typical normal adult at rest:
• The pulmonary blood flow of 5 litres min -I carries 11 mmol min-I (250 ml min-I) of oxygen from the lungs to the tissues.
• Ventilation at about 6 litres min-I carries 9 mmol min-I (200 ml min-I) of carbon dioxide out of the body.
• The normal pressure of oxygen in arterial blood (Pa02) is between 11 and l3 kPa (83 and 98 mmHg).
• The normal pressure of carbon dioxide in arterial blood (PaC02) is 4.8-6.0 kPa (36-45 mmHg). Neurogenic and chemical factors are involved in the control of ventilation.

Neurogenic factors

Neural stimuli include:
• Consciously induced changes in rate and depth of breathing
• Impulses from limb receptors, as in exercise, which cause respiratory stimulation
• Impulses arising from pulmonary receptors sensitive to stretch and bronchial irritation
• Juxtapulmonary capillary receptors (J receptors) stimulated by pulmonary congestion
• Impulses arising from receptors in muscles and joints of the chest wall
Abnormal stimuli include:
• Lesions in the pons and midbrain, which give rise to central neurogenic hyperventilation or hypoventilation
• Medullary compression, which leads to respiratory depression

Chemical stimuli

These cause an increase in ventilation when they stimulate central or peripheral chemoreceptors.
1 Central
(a) Carbon dioxide. The strongest respiratory stimulant to breathing is a rise in Paco2 Sensitivity to this may be lost in chronic bronchitis, so that in these patients hypoxaemia is the chief stimulus to respiratory drive; treatment with oxygen may therefore reduce respiratory drive and produce a further rise in Paco2
(b) Hydrogen ion concentration of arterial blood. An increase in [H+] due to metabolic acidosis will increase ventilation with a fall in Pac02. In respiratory disease, [H+] and Pac02 rise together.
2 Peripheral. A reduced Pa02 stimulates peripheral chemoreceptors in the carotid and aortic bodies. This stimulus is not strong unless the Pa02 is below 8 kPa. These chemoreceptors also respond to increases in [H+] and Pac02
The respiratory centre is depressed by severe hypoxaemia and sedatives (e.g. opiates) and stimulated by large doses of aspirin or by pyrexia. In certain common conditions such as mild asthma, pulmonary embolism and pneumonia there is an increase in ventilation, leading to a reduction in the Pac02  These conditions probably cause this effect through stimulation of irritant receptors in the bronchioles and J receptors stimulated deep in the parenchyma of the lung. Anxiety or hysteria cause hyperventilation, and increased ventilation is also a prominent feature of metabolic acidosis.
Breathlessness on physical exertion is normal and not considered a symptom unless the level of exertion is very light, e.g. walking slowly. Although breathlessness is a very common symptom the sensory and neural mechanisms underlying it remain obscure. The sensation of breathlessness is derived from at least three sources:
1 Changes in lung volume are sensed by receptors in thoracic wall muscles signalling changes in their length.
2 The tension developed by contracting muscles can be sensed by Golgi tendon organs. The tension developed in normal muscle can be differentiated from that developed in muscles weakened by fatigue or disease.
3 Central perception of the sense of effort.

The airways of the lungs

From the trachea to the periphery, the airways become smaller in size (although greater in number). The crosssectional area available for airflow increases as the total number of airways increases. The flow of air is maximum in the trachea and slows progressively towards the periphery (as the velocity of airflow depends on the ratio of flow to cross-sectional area). In the terminal airways, gas flow occurs solely by diffusion. The resistance to airflow is very low-0.l-O.2 kPa litre-I in a normal tracheobronchial tree.
Airways expand as lung volume is increased and at full inspiration (total lung capacity, TLC) they are 30-40% larger in calibre than at full expiration (residual volume, RV). In chronic bronchitis and emphysema, which principally affect the smaller airways, the airway narrowing is partially overcome by breathing at a larger lung volume.

Control of airway tone

This is under the autonomic nervous system. Bronchomotor tone is maintained by vagal efferent nerves and, even in a normal subject, is reduced by atropine or {3- adrenoreceptor agonists. The many adrenoreceptors on the surface of bronchial muscles respond to circulating catecholamines, although sympathetic nerves do not directly innervate them. Airway tone shows a circadian rhythm, which is greatest at 04.00 and lowest in the midafternoon. Tone can be increased briefly by inhaled stimuli acting on epithelial receptors, which trigger reflex bronchoconstriction via the vagus.
These stimuli include cigarette smoke, inert dust, cold air; airway responsiveness to these increases following respiratory tract infections even in healthy subjects. In asthma, the characteristic increased airway responsiveness is an exaggeration of this normal response and, as the circadian rhythm remains the same, asthmatic symptoms are worst in the early morning.

Air flow

Movement of air through the airways results from a difference between the pressure in the alveoli and the atmospheric pressure; a positive alveolar pressure occurs in expiration and a negative pressure occurs in inspiration. During quiet breathing the subatmospheric pleural pressure throughout the breathing cycle slightly distends the airways. With vigorous expiratory efforts (e.g. cough), although the central airways are compressed by positive pleural pressures exceeding 10 kPa, the airways do not close completely because the driving pressure for expiratory flow (alveolar pressure) is also increased. Alveolar pressure PALV is equal to the elastic recoil pressure of the lung plus the pleural pressure PEL’ When there is no airflow (i.e. a pause in breathing) the tendency of the lungs to collapse (the positive recoil pressure) is exactly balanced by an equivalent negative pleural pressure. As air flows from the alveoli towards the mouth there is a gradual loss of pressure owing to flow resistance. In forced expiration, as mentioned above, the driving  pressure raises both the alveolar pressure and the intrapleural pressure. Between the alveolus and the mouth, a point will occur  where the airway pressure will equal the intrapleural pressure, and airway compression will occur. However, this compression of the airway is temporary, as the transient occlusion of the airway results in an increase in pressure behind it (i.e. upstream) and this raises the intra-airway pressure so that the airways open and flow is restored. The airways thus tend to vibrate at this point of ‘dynamic compression’. The elastic recoil pressure of the lungs decreases with  decreasing lung volume and the ‘collapse point’ moves upstream (i.e. towards the smaller airways). Where there is pathological loss of recoil pressure (as in chronic bronchitis and emphysema), the ‘collapse point’ starts even further upstream and these patients are often seen to ‘purse their lips’ in order to increase airway pressure so that their peripheral airways do not collapse. The expiratory airflow limitation is the disordered physiology that underlies chronic airflow limitation. The measurement of the forced expiratory volume in 1 s (FEV,) is a useful clinical index of this phenomenon. On inspiration the intrapleural pressure is always less  than the intraluminal pressure within the intrathoracic airways, so there is no limitation to airflow with increasing  effort. Inspiratory flow is limited only by the power of the inspiratory muscles.

Diagrams showing the ventilatory forces during

Diagrams showing the ventilatory forces during

Flow-volume loops

The relationship between maximal flow rates on expiration and inspiration is demonstrated by the maximal flow-volume (MFV) loops. Figure 12.8a shows this in a normal subject.
In subjects with healthy lungs the clinical importance of flow limitation will not be apparent, since maximal flow rates are rarely achieved even during vigorous exercise. However, in patients with severe chronic bronchitis and emphysema, limitation of expiratory flow occurs even during tidal breathing at rest. To increase ventilation these patients have to breathe at higher lung volumes and also allow more time for expiration by increasing flow rates during inspiration, where there is proportionately much less flow limitation. This explains the clinical phenomenon of a prolonged expiratory time in patients with severe airflow limitation. The measurement of the volume that can be forced in from RV in 1 s (FIV,) will always be greater than that which can be forced out from TLC in 1 s (FEV,). Thus, the ratio of FEV, to FIV, is below 1. The only exception to this occurs when there is significant obstruction to the airways outside the thorax, e.g. a tumour mass in the upper part of the trachea. Under these circumstances expiratory airway narrowing is prevented by the tracheal resistance (a situation similar to pursing the lips) and expiratory airflow becomes more effort-dependent. During forced inspiration this same resistance causes such negative intraluminal pressure that the trachea is compressed by the surrounding atmospheric pressure. Inspiratory flow thus becomes less effort-dependent, and the ratio of FEV, to FlV, becomes greater than 1. This phenomenon, and the characteristic flow volume loop, is  used to diagnose extra thoracic airways obstruction.
When obstruction occurs in large airways within the thorax (lower end of trachea and main bronchi), expiratory flow is impaired more than inspiratory flow but a characteristic plateau to expiratory

and b) Maximal flowvolume loops, showing the relationship

and b) Maximal flowvolume
loops, showing the relationship

The pleura

The pleura is a layer of connective tissue covered by a simple squamous epithelium. The visceral pleura covers the surface of the lung, lines the interlobar fissures, and is continuous at the hilum with the parietal pleura, which lines the inside of the hemithorax. At the hilum the visceral pleura continues alongside the branching bronchial tree for some distance before reflecting back to join the parietal pleura. The pleurae are in apposition apart from a small quantity of lubricating fluid, so the pleural cavity is only a potential space.

Chest X-rays.

Chest X-rays.

The diaphragm

The diaphragm is lined by parietal pleura and peritoneum. Its muscle fibres arise from the lower ribs and insert into the central tendon. Motor and sensory nerve fibres go separately to each half of the diaphragm via the phrenic nerves. Fifty per cent of the muscle fibres are of the slow-twitch type with a low glycolytic capacity that are relatively resistant to fatigue.
• Pulmonary vasculature and lymphatics
The pulmonary artery divides to accompany the bronchi. The arterioles accompanying the respiratory bronchioles are thin-walled and contain little smooth muscle. The pulmonary venules drain laterally to the periphery of the lobules, pass centrally in the interlobular and intersegmental  septa, and eventually join to form the four main pulmonary veins.
In addition, a further bronchial circulation arises from the descending aorta. These bronchial arteries supply tissues down to the level of the respiratory bronchiole. The  bronchial veins drain into the pulmonary vein, forming part of the physiological shunt observed in normal individuals. Lymphatic channels lie in the potential interstitial space between the alveolar cells and the capillary endothelium of the pulmonary arterioles.

Nerve supply to the lung

The innervation of the lung remains incompletely understood. The parasympathetic supply is from the vagus and the sympathetic from the adjacent sympathetic chain. The nerve supplies entwine in a plexus at the nerve root and branches accompany the pulmonary arteries and the airways. Airway smooth muscle is innervated by vagal afferents, postganglionic cholinergic vagal efferents and vagally derived non-adrenergic non-cholinergic (NAN C) fibres. The parietal pleura is innervated from intercostal and phrenic nerves whilst the visceral pleura has no innervation.

Respiratory disease

Structure of the respiratory system

The nose

The anterior one-third of the nasal cavity is divided into right and left halves by the nasal septum. The nasal vestibule leads to the internal ostium (a) which is the narrowest part of the nasal cavity. This causes a 50% increased resistance to airflow when breathing through the nose rather than through the mouth. The respiratory region (b) is divided by three folds arising from the lateral wall, termed the superior, middle and inferior turbinates. Behind these turbinates are situated the openings of the nasolacrimal duct and the frontal, ethmoidal and maxillary sinuses. The olfactory region for smell is found above the superior turbinate. The nasal cavities communicate with the nasopharynx via the posterior nasal apertures (the choanae (c)), and the eustachian tube opens into this area just above the soft palate.

The pharynx and larynx

The pharynx is divided by the soft palate into an upper nasopharyngeal and lower oropharyngeal region. There are numerous collections of lymphoid tissue arranged in a circular fashion around the nasopharynx; these include the adenoids. The tonsils lie between the anterior and posterior fauces, separating the mouth from the oropharynx.

The anatomy of the nose in longitudinal section.

The anatomy of the nose in longitudinal section.

The larynx consists of a number of articulated cartilages, vocal cords, muscles and ligaments, all of which serve to keep the airway open during breathing and occlude it during swallowing. The main motor nerve to the larynx is the recurrent laryngeal nerve. The left recurrent laryngeal nerve leaves the vagus at the level of the aortic arch, hooking round it to run upwards through the mediastinum between the  trachea and the oesophagus; it can be affected by disease in these areas. The principal tensor of the vocal cords is the external branch of the superior laryngeal nerve, which can be injured during thyroidectomy. The trachea, bronchi and bronchioles
The trachea is 10-12 em in length. It lies slightly to the right of the midline and divides at the carina into right and left main bronchi. The carina lies under the junction of the manubrium sternum and the second right costal cartilage. The right main bronchus is more vertical than the left and, hence, inhaled material is more likely to pass into it.
The right main bronchus divides into the upper lobe bronchus and the intermediate bronchus, which further subdivides into the middle and lower lobe bronchi. On the left the main bronchus divides into upper and lower lobe bronchi only. Each lobar bronchus further divides into segmental and sub segmental bronchi. There are about 25 divisions in all between the trachea and the alveoli. Of the first seven divisions the bronchi have:
• Walls consisting of cartilage and smooth muscle
• Epithelial lining with cilia and goblet cells
• Submucosal mucus-secreting glands
• Endocrine cells-Kulchitsky or APUD (amine precursor and uptake decarboxylation) containing 5- hydroxytryptamine

In the next 16-18 divisions the bronchioles have:
• No cartilage and a muscular layer that progressively becomes thinner
• A single layer of ciliated cells but very few goblet cells
• Granulated Clara cells that produce a surfactant-like substance
The ciliated epithelium is an important defence mechanism. Each cell contains approximately 200 cilia beating at 1000 min-I in organized waves of contraction. Each cilium consists of nine peripheral parts and two inner longitudinal fibrils in a cytoplasmic matrix. Nexin links join the peripheral pairs. Dynein arms consisting of ATPase protein project towards the adjacent pairs. Bending of the cilia results from a sliding movement between adjacent fibrils powered by an ATP-dependent shearing force developed by the dynein arms. Absence of dyne in arms leads to immotile cilia. Mucus, which contains macrophages, cell debris, inhaled particles and bacteria, is moved by the cilia towards the larynx at about 1.5 em min-I-the ‘mucociliary escalator’ (see below). The bronchioles finally divide within the acinus into smaller respiratory bronchioles that have alveoli arising from the surface. Each respiratory bronchiole supplies approximately 200 alveoli via alveolar ducts. The term ‘small airways’ refers to bronchioles of less than 2 mm; there are 30000 of these in the average lung.

 The alveoli

There are approximately 300 million alveoli in each lung. Their total surface area is 40-80 m”, The epithelial lining consists largely of type I pneumocytes. These cells have an extremely attenuated cytoplasm, and thus provide only a thin barrier to gas exchange. They are derived from type IIpneumocytes. Type I cells are connected to each other by tight junctions that limit the fluid movements in and out of the alveoli.

Cross-section of a cilium.

Cross-section of a cilium.

Branches of a terminal bronchiole ending in the alveolar sacs.

Branches of a terminal bronchiole ending in the
alveolar sacs.

The structure of alveoli, showing the pneumocytes and capillaries.

The structure of alveoli, showing the pneumocytes
and capillaries.

Type IIpneumocytes are slightly more numerous than type Icells but cover less of the epithelial lining. They are found generally in the borders of the alveolus and contain distinctive lamellar vacuoles, thought to be a source of surfactant. Macrophag~s are also present in the alveoli and are involved in the defence mechanisms of the lung. The pores of Kohn are holes in the alveolar wall allowing communication between alveoli of adjoining lobules.

The lungs

The lungs are separated into lobes by invaginations of the pleura, which are often incomplete. The right lung has three lobes, whereas the left lung has two. The position of the oblique fissures and the right horizontal fissure are shown. The upper lobe lies mainly in front of the lower lobe and therefore signs on the right side in the front of the chest found on physical examination are due to lesions mainly of the upper lobe or part of the middle lobe.
Each lobe is further subdivided into bronchopulmonary segments by fibrous septa that extend inwards from the pleural surface. Each segment receives its own segmental bronchus.
The bronchopulmonary segment is further divided into individual lobules approximately 1 cm in diameter and generally pyramidal in shape, the apex lying towards the bronchioles supplying them. Within each lobule a terminal bronchus supplies an acinus and within this structure further divisions of the bronchioles eventually give rise to the alveoli.
A chest X-ray illustrates the above features.

Surface anatomy of the chest

Surface anatomy of the chest