Respiratory disease

Chapter 15 Respiratory disease

Structure of the respiratory system

The trachea, bronchi and bronchioles

The trachea is 10–12 cm 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 sterni and the second right costal cartilage. The right main bronchus is more vertical than the left and, hence, inhaled material is more likely to end up in the right lung.

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 subsegmental bronchi. There are about 25 divisions in all between the trachea and the alveoli.

The first seven divisions are bronchi that have:

The next 16–18 divisions are bronchioles that have:

The ciliated epithelium is a key defence mechanism. Each cell bears approximately 200 cilia beating at 1000 beats per minute in organized waves of contraction. Each cilium consists of nine peripheral parts and two inner longitudinal fibrils in a cytoplasmic matrix (Fig. 15.1). 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 (see also p. 22). Absence of dynein 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 cm/min (the ‘mucociliary escalator’, see below).

The bronchioles finally divide within the acinus into smaller respiratory bronchioles that have alveoli arising from the surface (Fig. 15.2). Each respiratory bronchiole supplies approximately 200 alveoli via alveolar ducts. The term ‘small airways’ refers to bronchioles of <2 mm; the average lung contains about 30 000 of these.

Physiology of the respiratory system


Lung ventilation can be considered in two parts:

Mechanical process

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: 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. 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. The volume of air remaining in the lung after a quiet expiration is called the functional residual capacity (FRC).

Inspiration from FRC is an active process: a negative intrapleural pressure is created by descent of the diaphragm and movement of the ribs upwards and outwards through contraction of the intercostal muscles. During tidal breathing in healthy individuals, inspiration is almost entirely due to contraction of the diaphragm. More vigorous inspiration requires the use of accessory muscles of ventilation (sternomastoid and scalene muscles). Respiratory muscles are similar to other skeletal muscles but are less prone to fatigue. However, inspiratory muscle fatigue contributes to respiratory failure in patients with severe chronic airflow limitation and in those with primary neurological and muscle disorders.

At rest or during low-level exercise, expiration is passive and results from the natural tendency of the lung to collapse.

Forced expiration involves activation of accessory muscles, chiefly those of the abdominal wall, which help to push up the diaphragm.

The control of respiration

Coordinated respiratory movements result from rhythmical discharges arising in an anatomically ill-defined group of interconnected neurones in the reticular substance of the brainstem, known as the respiratory centre. Motor discharges from the respiratory centre travel via the phrenic and intercostal nerves to the respiratory musculature.

In healthy individuals, the main driver for respiration is the arterial pH, which is closely related to the partial pressure of carbon dioxide in arterial blood. Oxygen levels in arterial blood are usually above the level which triggers respiratory drive. In a typical normal adult at rest:

Ventilation is controlled by a combination of neurogenic and chemical factors (Fig. 15.5).

Breathlessness on physical exertion is normal and not considered a symptom unless the level of exertion is very light, such as when walking slowly. Surveys of healthy western populations reveal that over 20% of the general population report themselves as breathless on relatively minor exertion. 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:

The airways of the lungs

From the trachea to the periphery, the airways decrease in size but increase in number. Overall, the cross-sectional area available for airflow increases as the total number of airways increases. The airflow rate is greatest in the trachea and slows progressively towards the periphery (since the velocity of airflow depends on the cross-sectional area). In the terminal airways, gas flow occurs solely by diffusion. The resistance to airflow is very low (0.1–0.2 kPa/L in a normal tracheobronchial tree), steadily increasing from the small to the large airways.

Airways expand as the lung volume increases. At full inspiration (total lung capacity, TLC) they are 30–40% larger in calibre than at full expiration (residual volume, RV). In chronic obstructive pulmonary disease (COPD), the small airways are narrowed but this can be partially compensated by breathing closer to TLC.


Movement of air through the airways results from a difference between atmospheric pressure and the pressure in the alveoli; alveolar pressure is negative in inspiration and positive in expiration. During quiet breathing, the pleural pressure is negative throughout the breathing cycle. With vigorous expiratory efforts (e.g. cough), the pleural pressure becomes positive (up to 10 kPa). This compresses the central airways, but the smaller airways do not close off because the driving pressure for expiratory flow (alveolar pressure) is also increased.

Alveolar pressure (PALV) is equal to the pleural pressure (PPL) plus the elastic recoil pressure (Pel) of the lung.

When there is no airflow (i.e. during 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 drop of pressure owing to flow resistance (Fig. 15.6a).

In forced expiration, as mentioned above, the driving pressure raises both the alveolar pressure and the intrapleural pressure. Between the alveolus and the mouth, there is a point (C in Fig. 15.6b) where the airway pressure equals the intrapleural pressure, and the airway collapses. However, this collapse 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 collapse’.

As lung volume decreases during expiration, the elastic recoil pressure of the lungs decreases and the ‘collapse point’ moves upstream (i.e. towards the smaller airways – see Fig. 15.6c). Where there is pathological loss of recoil pressure (as in chronic obstructive pulmonary disease, COPD), the ‘collapse point’ is located even further upstream and causes expiratory flow limitation. The measurement of the forced expiratory volume in 1 second (FEV1) is a useful clinical index of this phenomenon. To compensate, patients with COPD often ‘purse their lips’ in order to increase airway pressure so that their peripheral airways do not collapse. During inspiration, the intrapleural pressure is always less than the intraluminal pressure within the intrathoracic airways, so increasing effort does not limit airflow. Inspiratory flow is limited only by the power of the inspiratory muscles.

Flow-volume loops

The relationship between maximal flow rates and lung volume is demonstrated by the maximal flow-volume (MFV) loop (Fig. 15.7a).

In subjects with healthy lungs, maximal flow rates are rarely achieved even during vigorous exercise. However, in patients with severe COPD, limitation of expiratory flow occurs even during tidal breathing at rest (Fig. 15.7b). To increase ventilation these patients have to breathe at higher lung volumes and allow more time for expiration, both of which reduce the tendency for airway collapse. To compensate they increase flow rates during inspiration, where there is relatively less flow limitation.

The volume that can be forced in from the residual volume in 1 second (FIV1) will always be greater than that which can be forced out from TLC in 1 second (FEV1). Thus, the ratio of FEV1 to FIV1 is below 1. The only exception to this occurs when there is significant obstruction to the airways outside the thorax, such as tracheal tumour or retrosternal goitre. Expiratory airway narrowing is prevented by tracheal resistance 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 FEV1 to FIV1 exceeds 1. This phenomenon, and the characteristic flow-volume loop, is diagnostic of extrathoracic airways obstruction (Fig. 15.7c).

Ventilation and perfusion relationships

For optimum gas exchange there must be a match between ventilation of the alveoli (image) and their perfusion (image). However, in reality there is variation in the (image) ratio in both normal and diseased lungs (Fig. 15.8). In the normal lung both ventilation and perfusion are greater at the bases than at the apices, but the gradient for perfusion is steeper, so the net effect is that ventilation exceeds perfusion towards the apices, while perfusion exceeds ventilation at the bases. Other causes of (image) mismatch include direct shunting of deoxygenated blood through the lung without passing through alveoli (e.g. the bronchial circulation) and areas of lung that receive no blood (e.g. anatomical deadspace, bullae and areas of underperfusion during acceleration and deceleration, e.g. in aircraft and high performance cars).

An increased physiological shunt results in arterial hypoxaemia since it is not possible to compensate for some of the blood being underoxygenated by increasing ventilation of the well-perfused areas. An increased physiological deadspace just increases the work of breathing and has less impact on blood gases since the normally perfused alveoli are well ventilated. In more advanced disease this compensation cannot occur, leading to increased alveolar and arterial PCO2 (PaCO2), together with hypoxaemia which cannot be compensated by increasing ventilation.

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 cells, with a non-linear relationship between the volume carried and the partial pressure (Fig. 15.5, p. 341). Alveolar hyperventilation reduces the alveolar PCO2 (PACO2) and diffusion leads to a proportional fall in the carbon dioxide content of the blood (PaCO2). However, as the haemoglobin is already saturated with oxygen, there is no significant increase in the blood oxygen content as a result of increasing the alveolar PO2 through hyperventilation. The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation.

In individuals who have mild degrees of image mismatch, the PaO2 and PaCO2 will still be normal at rest. Increasing the requirements for gas exchange by exercise will widen the image mismatch and the PaO2 will fall. image mismatch is by far the most common cause of arterial hypoxaemia.

Alveolar stability

Pulmonary alveoli 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, an insoluble lipoprotein largely consisting of dipalmitoyl lecithin, which forms a thin monomolecular layer at the air-fluid interface. Surfactant is secreted by type II pneumocytes within the alveolus and reduces surface tension so that alveoli remain stable.

Fluid surfaces covered with surfactant exhibit a phenomenon known as hysteresis; that is, the surface-tension-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 this mechanism, e.g. 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). Lack of surfactant plays a central role in the respiratory distress syndrome of the newborn. Severe reduction in perfusion of the lung impairs surfactant activity and this may explain the characteristic areas of collapse associated with pulmonary embolism.

Defence mechanisms of the respiratory tract

Pulmonary disease often results from a failure of the normal host defence mechanisms of the healthy lung (Fig. 15.9). These can be divided into physical, physiological, humoral and cellular mechanisms.

Physical and physiological mechanisms

Respiratory tract secretions (Fig. 15.9)

The mucus of the respiratory tract is a gelatinous substance consisting of water and highly glycosylated proteins (mucins). The mucus forms a thick gel that is relatively impermeable to water and floats on a liquid or sol layer found 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. In addition to the mucins, the gel contains various antimicrobial molecules (lysozyme, defensins), specific antibodies (IgA) and cytokines, which are secreted by cells in airways and get incorporated into the mucus gel. Bacteria, viruses and other particles get trapped in the mucus and are either inactivated or simply expelled before they can do any damage. Under normal conditions the tips of the cilia engage with the undersurface of the gel phase and by coordinated movement they push the mucus blanket upwards and outwards to the pharynx where it is either swallowed or coughed up. While it only takes 30–60 minutes for mucus to be cleared from the large bronchi, it can be several days before mucus is cleared 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 prolongs contact with carcinogenic material. Air pollutants, local and general anaesthetics and products of bacterial and viral infection also reduce mucociliary clearance.

Congenital defects in mucociliary transport lead to recurrent infections and eventually to bronchiectasis. For example, in the ‘immotile cilia’ syndrome there is an absence of the dynein arms in the cilia themselves, while in cystic fibrosis there is ciliary dyskinesia and abnormally thick mucus.

Humoral and cellular mechanisms



Approximately 100 mL of mucus is produced daily in a healthy, non-smoking individual. This flows gradually up the airways, through the larynx, and is then swallowed. Excess mucus is expectorated as sputum. Cigarette smoking is the commonest cause of excess mucus production.

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.

Haemoptysis (blood-stained sputum) varies from small streaks of blood to massive bleeding.

Haemoptysis should always be investigated. Although a diagnosis can often be made from a chest X-ray, a normal chest X-ray does not exclude disease. However, if the chest X-ray is normal, CT scanning and bronchoscopy are only diagnostic in about 5% of patients with haemoptysis.

Firm plugs of sputum may be coughed up by patients suffering from an exacerbation of allergic bronchopulmonary aspergillosis. Sometimes such sputum looks like casts of inflamed bronchi.

Examination of the respiratory system

The chest

Examination of the chest


Assess mental alertness, cyanosis, breathlessness at rest, use of accessory muscles, any deformity or scars on the chest and movement on both sides. CO2 intoxication causes coarse tremor or flap of the outstretched hands. Prominent veins on the chest may imply obstruction of the superior vena cava.

Cyanosis (see p. 676) is a dusky colour of the skin and mucous membranes, due to the presence of more than 50 g/L of desaturated haemoglobin. When due to central causes, cyanosis is visible on the tongue (especially the underside) and lips. Patients with central cyanosis will also be cyanosed peripherally. Peripheral cyanosis without central cyanosis is caused by a reduced peripheral circulation and is noted on the fingernails and skin of the extremities with associated coolness of the skin.

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 in Table 15.1. Clubbing is not a feature of uncomplicated COPD.

Table 15.1 Some causes of finger clubbing

Added sounds

Wheeze. Wheeze results from vibrations in the collapsible part of the airways when apposition occurs as a result of the flow-limiting mechanisms. Wheeze is usually heard during expiration and is commonly but not invariably present in asthma and in chronic obstructive pulmonary disease. In acute severe asthma wheeze may not be heard, as airflow may be insufficient to generate the sound. Wheezes may be monophonic (single large airway obstruction) or polyphonic (narrowing of many small airways). An end-inspiratory wheeze or ‘squeak’ may be heard in obliterative bronchiolitis.

Crackles. These brief crackling sounds are probably produced by opening of previously closed bronchioles – early inspiratory crackles are associated with diffuse airflow limitation, while late inspiratory crackles are characteristically heard in pulmonary oedema, lung fibrosis and bronchiectasis.

Pleural rub. A creaking or groaning sound that is usually well localized. It indicates inflammation and roughening of the pleural surfaces, which normally glide silently over one another.

Vocal resonance. Healthy lung attenuates high-frequency notes, as compared to the lower-pitched components of speech. Consolidated lung has the reverse effect, transmitting high frequencies well; the spoken word then takes on a bleating quality. Whispered (and therefore high-pitched) speech can be clearly heard over consolidated areas, as compared to healthy lung. Low-frequency 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. Tactile vocal fremitus is the palpation of this vibration, usually by placing the edge of the hand on the chest wall. For all practical purposes this duplicates the assessment of vocal resonance and is not routinely performed as part of the chest examination.

Cardiovascular system examination (p. 676) gives additional information about the lungs.

Investigation of respiratory disease


Radiology is essential in investigating most chest symptoms. Some diseases such as tuberculosis or lung cancer may be undetectable on clinical examination but are obvious on the chest X-ray. Conversely, asthma or chronic bronchitis may be associated with a normal chest X-ray. Always try to get previous films for comparison.

X-ray abnormalities

Computed tomography

CT provides excellent images of the lungs and mediastinal structures (Fig. 15.11). Narrow slice, high-resolution CT scans show the lung parenchyma well, while thicker slice staging CT scans are used for diagnosis of malignant disease. Mediastinal structures are shown more clearly after injecting intravenous contrast medium.

CT is essential in staging bronchial carcinoma by demonstrating tumour size, nodal involvement, metastases and invasion of mediastinum, pleura or chest wall. CT-guided needle biopsy allows samples to be obtained from peripheral masses. Staging scans should assess liver and adrenals, which are common sites for metastatic disease.

High-resolution CT (HRCT) scanning samples lung parenchyma with 1–2 mm thickness scans at 10–20 mm intervals and are used to assess diffuse inflammatory and infective parenchymal processes. It is valuable in:

Multi-slice CT scanners can produce detailed images in two or three dimensions in any plane. This detail is particularly useful for the detection of pulmonary emboli. Pulmonary nodules and airway disease are more easily defined and the technique makes HRCT less necessary.

Mar 31, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Respiratory disease
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