Respiratory tract

Common Clinical Problems From Respiratory Tract Disease

Global estimates suggest that in the early 21st century respiratory diseases account for around 16% of all deaths worldwide. Acute respiratory infections account for around 4 million of which around 1.3 million are in children under 5 years (18% of childhood mortality). In 2011 there were 8.7 million new cases of tuberculosis (TB) and 1.6 million deaths. Up to 13% of TB cases were associated with HIV infection. Smoking-related conditions also account for many deaths. Lung cancer has an annual mortality of around 1.4 million (around 18% of all cancer deaths) and 2.5 million deaths occur from chronic obstructive pulmonary disease (COPD). There is also considerable morbidity due to respiratory disease: it is estimated that, in the UK, about 40% of absence from work is the result of respiratory disease, approximately 85% of which are transient infections of the upper respiratory tract ( Table 14.1 ).

Normal Structure and Function

The respiratory system extends from the nasal orifices to the periphery of the lung and includes the surrounding pleural cavity ( Fig. 14.1 ).

Nasal passages, sinuses and nasopharynx

These constitute the upper respiratory tract. The nasal passages and sinuses are in continuity and are lined by pseudostratified columnar epithelial cells with admixed goblet cells (respiratory mucosa). The hairs in the nose trap large particles of foreign material, thereby filtering the air. The air is also warmed and humidified as it passes through the nasal cavity. The middle ear, also lined with respiratory epithelium, connects with the nasal cavity via the Eustachian tube.

Larynx

The larynx connects the trachea to the pharynx. Consisting of a complicated system of cartilages and muscles, it allows air into the trachea, with the epiglottis preventing the passage of food into the lungs, and also produces sound for speaking. Part of the larynx, including the vocal cords and epiglottis, is covered with nonkeratinising squamous epithelium similar to that lining the oral cavity, pharynx and oesophagus.

Lungs

The lower respiratory tract consists of the trachea, bronchi, bronchioles, alveolar ducts and alveoli ( Fig. 14.2 ) that develop from an outpouching of the foregut at around the fifth week of development. The structure of the airway at each level differs ( Table 14.2 ).

Table 14.2

Structure of the respiratory tree

Part of respiratory tract	Structure
Trachea	Anterior C-shaped plates of cartilage with posterior smooth muscle. Mucous glands
Bronchi	Discontinuous foci of cartilage with smooth muscle. Mucous glands
Bronchioles	No cartilage or submucosal mucous glands. Clara cells secreting proteinaceous fluid. Ciliated epithelium
Alveolar duct	Flat epithelium. No glands. No cilia
Alveoli	Type I and II pneumocytes

The lungs are divided into lobes : the right lung has three lobes (upper, middle, lower); the left lung has only two lobes (upper and lower). Each lung is formed of anatomically defined bronchopulmonary segments, 10 on the right and 8 or 9 on the left. Each segment is supplied by segmental branches of the pulmonary artery and bronchus (the bronchovascular bundle). The veins draining adjacent segments often anastomose before they reach the hilum and run principally in the fibrous septae of the lungs.

The airways (trachea, bronchi and bronchioles) are lined by respiratory epithelium and branch until they form terminal bronchioles less than 2 mm in diameter. The respiratory system distal to the terminal bronchiole is called the acinus or terminal respiratory unit , and comprises respiratory bronchioles and alveoli where gas exchange occurs. A group of three to five acini is called a lobule.

The alveoli are lined by flattened type I pneumocytes with occasional type II pneumocytes; the latter are rounded cells with surface microvilli. Type II cells secrete surfactant, replicate quickly after injury to alveolar walls and are believed to be the stem cell population of the alveolus. Beneath the alveolar cells lies a basement membrane which is shared by the alveolar capillary endothelial cells, thus permitting rapid and efficient gas exchange by diffusion.

The lung is encased by the visceral pleura , which is a thin layer of fibroconnective tissue and elastin with overlying mesothelial cells. The lungs sit within the chest cavity surrounded by the parietal pleura, diaphragm, ribs and intercostal muscles, mediastinal structures, vertebral column and sternum.

Blood supply and lymphatic drainage

The lungs have a dual arterial blood supply . The trunk of the pulmonary artery arises from the right ventricle, splits into right and left main pulmonary arteries and then follows the airways, forming the bronchovascular bundles. The bronchial arteries arise from the descending thoracic aorta and supply oxygenated blood to lung parenchyma. Pulmonary veins run in the interlobular septae, taking all the blood from the lungs back to the left atrium.

Pulmonary lymphatic channels in the septae and pleura drain into the thoracic duct.

Acid-base balance

Normal acid-base balance in blood is dependent on efficient alveolar ventilation/perfusion, and adequate renal function. Metabolic and respiratory disease states can lead to disturbances in acid-base balance ( Fig. 14.3 ) with effects on respiration, for example, diabetic patients with ketoacidosis have a high [H] ⁺ (metabolic acidosis). This will result in an increased respiratory rate, reducing the blood concentrations of CO ₂ (compensatory respiratory alkalosis) buffering the acidosis. If the disease becomes chronic, compensatory mechanisms by both the lungs and kidneys operate in an attempt to restore blood pH.

Pulmonary Function Tests

In normal quiet respiration, only a relatively small proportion of the total lung capacity (TLC) is inhaled and exhaled; this is the tidal volume (TV). TLC is made up of the amount of air totally exhaled after maximum inspiration (the vital capacity or VC) and the residual volume (RV). TLC, RV, TV and VC are all easily measured in the laboratory using helium dilution techniques.

In addition to calculating volume parameters, some techniques also assess actual pulmonary function. Spirometry measures the amount of exhaled air per second. The maximum volume of air blown from the lungs within the first second after a previous maximum inspiration is called the forced expiratory volume (FEV ₁ ). This figure is a measure of small airway resistance and the predicted normal value is dependent on the patient's age, sex and size; for example, the small lungs of a child obviously cannot expel as much air as those of an adult. The ratio FEV ₁ :VC compensates to a degree for the variability of lung size. It is possible to inhale more rapidly than exhale because, during inspiration, forces on the airways tend to open them further; during expiration, opposite forces tend to close the airways and thus restrict airflow. For a given lung volume, the expiratory flow rate reaches a peak (PEFR), which is again a measure of airways resistance.

An assessment of the ability of the lungs to exchange gas efficiently can be made by measuring the transfer factor for carbon monoxide (T _CO ). Air containing a known concentration of carbon monoxide is inhaled; the breath is held for 15 seconds and then exhaled. The amount of carbon monoxide absorbed is a measure of pulmonary gas exchange. T _CO is dependent on the concentration of blood haemoglobin, which has a strong affinity for carbon monoxide. Diseases that diffusely affect the alveolar capillary membrane (such as diffuse pulmonary fibrosis or emphysema where there is loss of alveolar surface area) will result in a low T _CO .

Respiratory Failure

Respiratory failure can occur as a result of:

• impaired ventilation

  • —

    neural problems, for example, due to narcotics, encephalitis, a cerebral space-occupying lesion, poliomyelitis, motor neurone disease, and so on

  • —

    mechanical problems, for example, airway obstruction, trauma, kyphoscoliosis, muscle disease, pleural effusion, gross obesity (Pickwickian syndrome)

• impaired perfusion, if diffuse or extensive, for example, cardiac failure or multiple pulmonary emboli

• impaired gas exchange defects, if diffuse and severe, for example, emphysema or diffuse pulmonary fibrosis.

Type I respiratory failure is characterised by hypoxia and a low level of CO ₂ in the blood secondary to hyperventilation. In type II respiratory failure, the hypoxia is associated with hypoventilation resulting in impaired clearance of CO ₂ and hypercapnia. In acute type II respiratory failure, there is respiratory acidosis due to an increased [H] ⁺ . In chronic respiratory failure, this will be buffered by increased bicarbonate retention by the kidneys (compensatory metabolic alkalosis) (see Fig. 14.3 ).

Inflammatory Disorders

Rhinitis may be caused by many different viruses, especially rhinoviruses (the common cold virus), although respiratory syncytial virus (RSV), parainfluenza viruses, coronaviruses, Coxsackie viruses, echoviruses and bacteria, such as Haemophilus influenzae , may also be implicated. Rhinitis may also be caused by inhaled allergens as in ‘hay fever’ where the inflammatory reaction is mediated via type I and type III hypersensitivity reactions ( Chs. 8 and 9 ).

Nasal polyps most commonly arise due to chronic allergic inflammation. They consist of polypoid oedematous masses of mucosal tissue infiltrated with chronic inflammatory cells, especially plasma cells; eosinophils may be numerous.

Sinusitis is inflammation of the paranasal sinuses; it may be acute or chronic and can be infective or allergic. If the drainage orifice is blocked by inflamed swollen mucosa, an abscess may follow. Cranial osteomyelitis, meningitis or cerebral abscess may then result from sinusitis by direct extension.

Granulomatous angiitis (Wegener granulomatosis) , a granulomatous form of vasculitis (see Vascular Diseases , p. 299 ) may involve the nose and upper respiratory tract and present with septal perforation or collapse of the nasal cartilages.

Otitis media is infection of the middle ear, often viral, associated with generalised upper respiratory tract symptoms. The Eustachian tube may become swollen and blocked, leading to trapping of exudate in the middle ear. Eardrum perforation may ensue. In bacterial infections, more serious, but rare, complications include mastoiditis, meningitis and brain abscess.

Tumours

Tumours of the nasal passages and sinuses are uncommon. They may be:

• benign: squamous papilloma, juvenile angiofibroma

• malignant: squamous cell carcinoma (SqCC), adenocarcinoma (AC), melanoma, lymphoma.

Squamous papillomata are benign lesions some of which are related to human papillomavirus infection.

Juvenile angiofibromas are rare and occur exclusively in males, usually during adolescence. They are extremely vascular, and surgical removal can be difficult. These tumours contain androgen receptors, explaining the male preponderance.

SqCC may be well differentiated, producing keratin, or very poorly differentiated. In the nasopharynx ( nasopharyngeal carcinoma ), these may contain many lymphocytes and have been misnamed ‘lymphoepitheliomas’. Such tumours are most common in South-East Asia where the Epstein–Barr virus is involved in the aetiology, although this association is less commonly found in Caucasian populations.

AC of the nasal passages and sinuses are rare and may be more common in those with occupational exposure to wood dust for example, furniture makers. These tumours may present clinically up to 40 years after initial exposure.

Primary mucosal melanomas of the nose and sinuses are rare but have a very poor prognosis.

Primary extranodal lymphomas are almost always of non-Hodgkin type.

Inflammatory Disorders

Laryngitis may occur in association with viral or bacterial inflammation of trachea and bronchi; this is laryngotracheobronchitis. Diphtheria was once a common, and serious, bacterial cause of laryngitis, leading to the formation of a fibrinopurulent membrane that could cause airway obstruction. Chronic laryngitis may be irritative and due to cigarette smoke, chronic acid reflux or mechanical factors, for example, recent endotracheal intubation.

Epiglottitis is caused by capsulated forms of H. influenzae type B. The epiglottis becomes inflamed and greatly swollen, leading to airway obstruction ( Fig. 14.4 ). Treatment is by intubation, although, rarely, tracheostomy may be necessary; antibiotics are also given to treat the infection.

Laryngeal polyps often develop in singers and are thus sometimes referred to as ‘singer's nodes’. Even when only a few millimetres in diameter, they can alter the character of the voice.

Tumours

Laryngeal tumours may be:

• benign: squamous papilloma

• malignant: SqCC.

Papillomas may be caused by types of human papillomavirus. Papillomas consist of squamous epithelium covering fibrovascular cores of stroma. They may be multiple and recurrent, especially in children, but are usually single in adults. Such papillomas can extend into the trachea and bronchi.

SqCC of the larynx typically affects males over 40 years of age and are associated with cigarette smoking. Tumours are often preceded by a phase of dysplasia. The dysplasia, especially if low grade, may be reversible with smoking cessation.

Most laryngeal carcinomas arise on the vocal cords ( Fig. 14.5 ), although they may arise above, in the pyriform fossa, or below, as upper tracheal carcinomas. Symptoms are hoarseness of voice and, later, pain, haemoptysis and dysphagia. The lesions ulcerate, fungate, invade locally and metastasise to regional lymph nodes in the neck. Treatment is by chemoradiotherapy and/or resection. These patients often have widespread mucosal abnormalities throughout the upper aerodigestive and respiratory tracts and are at high risk of developing further cancers, especially if they continue to smoke.

Respiratory Infections

The lungs have an internal surface area of approximately 500 m ² which is exposed to the external environment and potentially subjected to inhaled microbes with every breath. It is therefore not surprising that respiratory infections are relatively common, with the World Health Organization projecting such infections to continue as one of the global leading causes of death and disability. Countering the threat of pathogens are the defence mechanisms, any abnormality of which may predispose to infection:

• loss or suppression of the cough reflex, for example, in coma, anaesthesia, neuromuscular disorders, or after surgery

• ciliary defects, for example, in immotile cilia syndromes, or loss of ciliated cells with squamous metaplasia

• mucus disorders, for example, excessive viscosity as in cystic fibrosis

• acquired or congenital hypogammaglobulinaemia, for example, with decreased immunoglobulin A in the mucus

• acquired or congenital immunosuppression, for example, thymic aplasia, neutropenia following chemotherapy, steroid therapy or HIV infection

• decreased macrophage function, for example, in people who smoke or are hypoxic

• the extremes of age and the presence of comorbid conditions.

Infections can be classified as primary , with no underlying predisposing condition in a healthy individual, or secondary , when local or systemic defences are weakened. The latter are by far the most common types of respiratory infection in developed countries.

Pneumonia

Pneumonia is usually due to infection affecting distal airways and alveoli, with the formation of an inflammatory exudate. It may be classified according to several criteria ( Table 14.4 ; Fig. 14.6 ).

Table 14.4

Classifications of pneumonia

Criterion	Type	Example/comment
Anatomical pattern	Bronchopneumonia Lobar pneumonia	Most widely used classification before identifying aetiological agent
Clinical circumstances	Primary	In an otherwise healthy person
	Secondary	With local or systemic defects in defence
Aetiological agent	Bacterial	Streptococcus pneumoniae , Staphylococcus aureus , Mycobacterium tuberculosis , etc.
	Viral	Influenza, measles, etc.
	Fungal	Cryptococcus , Candida , Aspergillus , etc.
	Other	Pneumocystis jiroveci , Mycoplasma , aspiration, lipid, eosinophilic
Host reaction	Fibrinous Suppurative	According to dominant component of exudate

Bronchopneumonia

• ➤

  Patchy consolidation — often several lobes or bilateral

• ➤

  Centred on bronchioles or bronchi

• ➤

  Usually in infancy or old age

• ➤

  Usually secondary to preexisting disease

Bronchopneumonia has a characteristic patchy distribution, centred on inflamed bronchioles and bronchi with subsequent spread to surrounding alveoli (see Fig. 14.6A ). It occurs most commonly in old age, in infancy and in patients with debilitating diseases, such as cancer, cardiac failure, chronic renal failure or cerebrovascular disease. Bronchopneumonia may also occur in patients with acute bronchitis, COPD or cystic fibrosis. Failure to clear respiratory secretions, such as is common in the postoperative period, also predisposes to the development of bronchopneumonia.

Typical organisms include staphylococci, streptococci and H. influenzae . Patients often become septicaemic and toxic, with fever and reduced consciousness.

Affected areas of the lung tend to be basal and bilateral, and appear focally grey or grey–red at postmortem with pus-filled bronchi ( Fig. 14.7 ). Histology shows typical acute inflammation with exudation in the bronchi and adjacent alveolar spaces. With antibiotics and physiotherapy, the inflammatory process may undergo resolution but healing by organisation or death may occur.

Lobar pneumonia

• ➤

  Affects anatomically delineated segment(s) or the entirety, of a lobe or lung

• ➤

  Relatively uncommon in infancy and old age

• ➤

  Affects males more than females

• ➤

  90% due to S. pneumoniae (pneumococcus)

• ➤

  Cough and fever with purulent or ‘rusty’ sputum

Pneumococcal pneumonia typically affects otherwise healthy adults between 20 and 50 years of age; however, lobar pneumonia caused by Klebsiella typically affects the elderly, diabetics or alcoholics. Symptoms include a cough, fever and production of sputum. The sputum appears purulent and may contain flecks of blood, so-called ‘rusty’ sputum. Fever can be very high (over 40°C), with rigors. Acute pleuritic chest pain on deep inspiration reflects inflammation of the pleura (pleurisy). As the lung becomes consolidated ( Fig. 14.8 ), the chest signs are dullness to percussion with bronchial breathing.

The pathology of lobar pneumonia is a classic example of acute inflammation, involving four stages.

• Congestion . This first stage lasts for about 24 hours and represents the outpouring of a protein-rich exudate into the alveolar spaces. The lung is heavy, oedematous and red.

• Red hepatisation . In this second stage, which lasts for a few days, there is massive accumulation in the alveolar spaces of polymorphs, together with some lymphocytes and macrophages. Many red cells are also extravasated from the distended capillaries. The overlying pleura bears a fibrinous exudate. The lung is red, solid and airless, with a consistency resembling fresh liver.

• Grey hepatisation . This third stage also lasts a few days and represents further accumulation of fibrin, with destruction of white cells and red cells. The lung is now grey–brown and solid.

• Resolution . This fourth stage occurs at about 8 to 10 days in untreated cases, and represents the resorption of exudate and enzymatic digestion of inflammatory debris, with preservation of the underlying alveolar wall architecture. Most cases of acute lobar pneumonia resolve in this way but infections with some more virulent bacterial organisms may lead to tissue damage and fibrosis or abscess formation (e.g. Staphylococcus aureus , Klebsiella pneumoniae ).