Diseases of the respiratory system

Department of Respiratory Medicine The First Affiliated Hospital of Xinjiang Medical University

HE Yuanbing

General description

The lungs, with their combined surface area of greater than 500m 2, are directly open to the external environment. Thus structural, functional or microbiological changes within the lungs can be closely related to epidemiological, environmental, occupational, personal and social factors. Primary respiratory diseases are responsible for a major burden of morbidity and untimely deaths, and the lungs are often affected in multisystem diseases.

Respiratory symptoms are the most common cause of presentation to the family practitioner. Asthma occurs in more than 10% of British children; bronchial carcinoma is the most common fatal malignancy in the developed world; the lung is the major site of opportunistic infection in those immunocompromised patients; and the spectre of tuberculosis, particularly the emergence of multiple drug-resistant strains, is back with us.

A number of important research advances have occurred in recent years. The discovery of genetic mechanism of cystic fibrosis provides a novel opportunity to develop gene therapy strategies to replace the defective gene. Finally, recent advances in our understanding of the cellular and molecular mechanisms underlying diseases such as asthma and the ARDS are likely to lead to rational, mechanism-based therapy within the foreseeable future.

APPLIED ANATOMY AND PHYSIOLOG The upper respiratory tract includes the nose, nasopharynx and larynx. It is lined by vascular mucous membranes with ciliated epithelium on their surfaces. The lower respiratory tract includes the trachea and bronchi. These form an interconnecting tree of conducting airways eventually joining, via around 64 000 terminal bronchioles, with the alveoli to form the acini.

The acinus is the gas exchange unit of the lung and comprises branching respiratory bronchioles leading to clusters of alveoli.

The alveoli are lined mostly with flattened epithelial cells (type I pneumocytes), but there are some, more cuboidal, type II pneumocytes. The latter produce surfactant, a mixture of phospholipids, which acts to reduce surface tension and counteract the tendency of alveoli to collapse. Type II pneumocytes also display a remarkable capacity to divide and reconstitute the type I pneumocytes after lung injury.

The right ventricle pumps blood against the relatively low pulmonary vascular resistance. Blood flows through a remarkably rich capillary network, intimately adjacent to alveoli , facilitating gas exchange. Increased pulmonary vascular resistance, due for example to thromboembolism or to destructive changes caused by COPD, results in right ventricular hypertrophy, and eventually right heart failure (cor pulmonale) ensues.

GAS EXCHANGE, VENTILATION, BLOOD FLOW AND DIFFUSION Gas exchange in the lungs is suboptimal unless there is sufficient ventilation, distributed uniformly to different parts of the lungs and matched by uniform distribution of blood flow. Furthermore, abnormal diffusion of oxygen or carbon dioxide across the alveolar-capillary membrane impairs gas exchange.

In clinical practice the important consequences of impaired gas exchange are hypoxaemia and hypercapnia. Hypercapnia (PaCO2 > 6 kPa (45 mmHg)) is generally caused by conditions resulting in alveolar hypoventilation or ventilation-perfusion mismatch . Hypoventilation may be caused by depression of the respiratory centre in the medulla; in contrast, stimulation of the respiratory centre causes hypocapnia and respiratory alkalosis.

Some influences on the respiratory centre

Mechanism Example

Stimulant
Voluntary Upper brain-stem lesions Input from receptors Increased PaCO2 Increased arterial hydrogen ion concentration Decreased PaO2 (<8kPa at rest) Pyrexia Depressant Overbreathing Central neurogenic hyperventilation Pain; muscles and joints; pulmonary afferents Via central and peripheral chemoreceptors Via peripheral chemoreceptors Via peripheral chemoreceptors

Voluntary
Brain-stem lesions Sedative drugs Hypothermia

Breath-holding
Opiates,benzodiazepines

Common causes of hypercapnia (raised PaCO2) Central Chest wall Brain-stem lesion Kyphoscoliosis Central sleep aponea Ankylosing spondylitis Trauma Neuromuscular Pulmonary Peripheral neuropathy COPD(and emphysema) Myasthenia gravis Myopathies

Common cause of hypoxaemia Venous admixture effect (poorly ventilated lung) Alveolar underventilation (Raised PaCO2) Impairment of diffusion (less important at rest) Right to left shunts (circulatory channels bypassing lungs) Reduced oxygen content (PaO2 may be normal) (anaemia; inactivated haemoglobin)

Causes of hypoxaemia are shown in the information box. Blood flow wasted on perfusing poorly ventilated lung is probably the most important of these and contributes to the hypoxaemia found, for example, in bronchial obstruction (due to secretions, mucosal oedema, bronchoconstriction or tumours), destruction of elastic tissue (e.g. emphysema), pulmonary collapse, consolidation, fibrosis or oedema, and chest wall deformities.

Hypoxaemia due to ventilation-perfusion mismatch, hypoventilation or diffusion impairment is reversed by giving oxygen. In right to left shunts--as, for example, in congenital heart diseases and pulmonary vascular abnomalies blood does not pass through alveolar capillaries and therefore oxygen does not fully correct the hypoxaemia.

Hypoxaemia also occurs if the oxygen-carrying capacity of the blood is reduced as, for example, in anaemia or carbon monoxide poisoning. The normal arterial PaO2 is over 12 kPa (90 mmHg) at the age of 20 and falls to around 11 kPa (82 mmHg) at 60: Above this age a further fall in PaO2 of up to 1.3 kPa (10 mmHg) may occur on lying down because of closure of small airways in the dependent regions of the lungs.

Under physiological conditions hypoxaemia and hypercapnia both stimulate ventilation. In some patients with COPD, tolerance of chronic hypercapnia ensures, and in such patients administration of high concentrations of oxygen removes the remaining hypoxaemic stimulus for ventilation, resulting in worsening hypercapnia. Patients with COPD who have chronic hypercapnia should therefore receive, if required, low concentrations of oxygen (e.g. 24---28%), adjusted according to arterial blood gas analysis.

INVESTIGATION OF RESPIRATORY DISEASE It is essential to take a detailed history from the patient, and much can be learned from a careful physical examination . A number of special investigations are often required in the diagnosis and monitoring of lung disease.

IMAGING The 'plain' chest radiograph Many diseases, including bronchial carcinoma and pulmonary tuberculosis, cannot be detected at an early stage without a radiograph of the chest. A lateral film provides additional information about the likely nature and situation of a pulmonary, pleural or mediastinal abnormality.

Comparison with previous radiographs may help to distinguish between a new or progressive change which is thus potentially serious , and old or static abnormalities which may be of no importance.

Computed tomography (CT) CT is more sensitive and accurate.

CT is now widely used in the pre-operative assessment of patients with lung cancer, particularly for assessing mediastinal spread, the presence of metastases in the liver or adrenals. High-resolution CT is particularly useful in diagnosing interstitial fibrosis, and in identifying bronchiectasis.

Ventilation-perfusion imaging

The main value of this technique is in the detection of pulmonary thromboemboli, 133Xe gas is inhaled (the ventilation scan) and 99mTclabelled macroaggregates of albumin, or albumin microspheres, are injected intravenously, the particles becoming transiently trapped in pulmonary microvessels and providing the

'perfusion' scan.

Ventilation-perfusion scanning may also be useful in pre-operative assessment of the functional effects of

lung cancer and bullae.

Pulmonary angiography

This is the definitive method of diagnosing pulmonary emboli, particularly in the acutely ill and shocked patient or when ventilationperfusion scans are equivocal.

Digital subtraction angiography (DSA) is a technique whereby images obtained before contrast injection are digitised and subtracted from post-contrast images . This technique is more sensitive and requires much less contrast to obtain high-quality images

ENDOSCOPIC EXAMINATION

Bronchoscopy

The trachea and larger bronchi are inspected by a bronchoscope of either flexible fibreoptic or rigid type. Structural changes, such as distortion or obstruction, can be seen. Abnormal tissue in the bronchial lumen or wall can be biopsied, and bronchial brushings, washings or aspirates can be taken for cytological or bacteriological examination.

Pleural aspiration and biopsy

Pleural aspiration and biopsy using an Abram's needle is a 'blind' procedure but often provides histological evidence of the cause of pleural effusion. Transthoracic needle biopsy (often with radiological guidance) may be useful in obtaining a cytological diagnosis from a peripheral lung lesion.

SKIN TESTS

The tuberculin test may be of value in the diagnosis of tuberculosis. Skin hypersensitivity tests are useful in the investigation of allergic disease.

MICROBIOLOGICAL INVESTIGATIONS

Sputum, pleural fluid, blood and bronchial washings and aspirates can be examined for bacteria, fungi and viruses. In some cases, as when M. tuberculosis is isolated, the information is diagnostically conclusive.

HISTOPATHOLOGICAL AND CYTOLOGICAL EXAMINATION

Histopathological examination of biopsy material (obtained from pleura, lymph node or lung) often allows a 'tissue diagnosis' to be made. This is of particular importance in suspected malignancy or in elucidating the pathological changes in interstitial lung disease .

Small cell carcinoma

LUNG FUNCTION TESTING

Most pulmonary function tests detect impairment and assess the effects of treatment or progress of the disease .

Measurements of ventilatory capacity

The forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and vital capacity (VC) are obtained from maximal forced and relaxed expirations into a recording spirometer and compared with predicted values based on age, sex, height and ethnic group. Typical patterns of abnormality known as obstructive and restrictive ventilatory defects are
shown in Table 4.4.

Patterns of abnormal ventilatory capacity Test Obstructive Restrictive FEV1 VC or normal FEV1/VC Normal or RV/TLC Normal

If an obstructive ventilatory defect is found, the response to bronchodilators in standard doses (salbutamol 200ug from pressurised aerosol) can be measured. Reversibility of airflow obstruction is found in asthma and in some patients with COPD.

Measurements of lung volumes

Normal landmarks and patterns of abnormality of lung volumes in obstructive and restrictive ventilatory defects are shown in Figure 4.9 on page 312. The values are obtained either by diluting helium (a non-toxic, non-absorbed gas) into the gas in the lungs, or in a whole body plethysmograph.

Arterial blood gas analysis

Modern automatic analysers give a rapid direct readout of PaO2, PaCO2 and pH hydrogen ion concentration in arterial blood, often supplemented by derived variables (such as SaO2 oxygen saturation and AB BE bicarbonate concentration) which may be of value in assessment of hypoxaemia or acid-base balance . Such measurements are of particular value in the management of respiratory failure , asthma and acute respiratory distress syndrome (ARDS) .

Ear or pulse oximeters allow continuous noninvasive measurement of arterial oxygen saturation, of value in assessing hypoxaemia and the effects of oxygen therapy.

MAJOR MANIFESTATION OF LUNG DISEASE COUGH EXPECTATION DYSPNOEA

Breathlessness or dyspnoea can be defined as an unpleasant subjective awareness of the sensation of breathing. It is a common symptom of cardiac and respiratory disease, but it may occur as a result of disorders of other systems, e.g. diabetic ketoacidosis or severe anaemia.

It follows that diseases presenting with dyspnoea often have a multifactorial aetiology, e.g. acute respiratory infections may stimulate the respiratory rate as a consequence of fever, hypoxaemia and, in severe cases, by acidaemia or hypercapnia.

Some causes of dyspnoea

System Acute dyspnoea Chronic exertional dyspnoea Chronic cardiac failure Cardiovascular Acute pulmonary oedema

system
Respiratory system

Pulmonary embolus
Major neonatal congenital heart disease

Chronic pulmonary throboembolism

Congenital heart disease COPD Chronic asthma Bronchial carcinoma

Acute severe asthma Acute exacerbation of COPD Pneumothorax

Pneumonia
ARDS Inhaled foreign body Lobar collapse Laryngeal oedema Others Metabolic acidosis(e.g diabetic

Interstitial lung disease

extrinsic allergic alveolitis Lymphatic carcinomatosis Large pleural effusion Severe anaemia

ketoacidosis ,Uraemia) hysterical hyperventilation

COPD: Chronic cough productive of sputum, usually most troublesome in the mornings, is the rule and there is often a history of recurrent acute exacerbations. In late disease orthopnoea, nocturnal breathlessness and ankle swelling may supervene as a result of the development of cor pulmonale.

Central cyanosis at rest or after minimal exertion, wheeze and pursing of the lips during expiration, and intercostal indrawing during inspiration, are common examination findings. The anteroposterior diameter of the chest may be increased (barrel chest) and there may be a reduced cricosternal distance with a 'tracheal tug' on inspiration.

CHEST PAIN HAEMOPTYSIS

Coughing up blood, irrespective of the amount, is an alarming symptom and nearly always brings the patient to the doctor. A clear history should be taken to establish that it is true haemoptysis, and not haematemesis or epistaxis (nosebleed). Haemoptysis must always be assumed to have a serious cause until appropriate investigations have excluded bronchial carcinoma, thromboembolic disease, tuberculosis etc.

CAUSES OF HAEMOPTYSIS Bronchial disease Carcinoma Bronchiectasis Lung vascular disease Pulmonary infarction Polyarteritis nodosa

Acute bronchitis Goodpastures syndrome Bronchial adenoma Idiopathic pulmonary haemosiderosis Foreign body Parenchymal disease Cadiovascular disease Tuberculosis Acute left ventricular failure Suppurative pneumonia Mitral stenosis Lung abscess Aortic aneurysm Parasites(e.g. hydatid disease, flukes) Blood disorders Trauma Leukaemia Actinomycosis Haemophilia Aspergilloma Anticoagulants

Many episodes of haemoptysis are unexplained, even after full investigation, and are likely to be caused by simple bronchial infection. A history of repeated small haemoptyses, or blood-streaking of sputum, is highly suggestive of bronchial carcinoma. Chronic fever and weight loss may suggest tuberculosis. Pneumococcal pneumonia is often the cause of 'rusty'-coloured sputum but can cause frank haemoptysis, as can all the pneumonic infections which lead to suppuration or abscess formation

Bronchiectasis can cause catastrophic bronchial haemorrhage and in these patients there may be a history of previous tuberculosis or whooping cough in early life. In hospital practice pulmonary thromboembolism is the most common cause of haemoptysis. Major risk factors include immobilisation, malignant disease of any organ, cardiac failure and pregnancy.

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