Respiratory

The airways are also prone to being affected by hypersensitivity reactions – these are abnormal immune responses to normal stimuli. These are categorised into 4 different types.   Type 1 This is a rapid allergic reaction due to pre-formed IgE antibody to an exposed antigen. – It eventually leads to a large increase in histamine which can lead to anaphylactic shock.   Histamine is stored in mast cells and is released by calcium-dependent exocytosis: – IgE binds IgE receptor –> increases intracellular IP3 –> increases Calcium – Intracellular cAMP is an antagonist and works to block release of histamine Histamine

At the lungs, alveolar ventilation is matched with pulmonary blood flow to create a concentration gradient to exchange O2 and CO2 – Oxygen binds to haemoglobin and is transported in the blood. – The dissociation curve is sigmoidal, due to the cooperative binding of oxygen molecules. – This means that it is at first difficult to load the first oxygen molecule onto haemoglobin – However, once the first one binds, this causes a conformational shift which increases haemoglobin’s affinity for oxygen   It is then easier to bind the next oxygen molecules. This causes the steep rise in the oxygen dissociation

We can use spirometry to measure some key volumes of the lungs: Tidal volume = volume of air breathed in and out of the lungs during quiet breathing (500ml)   Inspiratory reserve volume = the maximal volume that can be inhaled from the end-inspiratory level   Expiratory reserve volume = describes the maximal volume of air that can be further exhaled subsequent to the volume achieved at the end of the exhalation phase of quiet breathing   Residual volume (RV) = the volume of air left in the lungs following expiration of the expiratory reserve volume i.e. the maximal exhalation capacity   Inspiratory capacity =

The breathing system relies on creating a pressure gradient between the inside and external environment, which needs an intimate relationship between the lungs and chest wall. – Lungs are lined by visceral and parietal pleura, which are separated by a thin layer of fluid.   The volume of thoracic cavity is determined by the outward recoil of chest wall + inward elastic recoil of lungs – These opposing forces are balanced by small negative pleural pressure. Breathing relies on increasing thoracic cage volume which then decreases intrapleural pressure i) At the end of expiration, alveolar pressure (PA) = 0 and

The thorax is divided by a transverse plane at the angle of Louis (T4/5) into the superior and inferior mediastinum. The latter can be subdivided into the anterior, middle and posterior compartments.   Ribs There are a total of 12 ribs: – Ribs 1 to 7 attached to sternum by costal cartilage – “true ribs” – Ribs 8 to 10 attached to the rib above by costal cartilage – “false ribs” – Ribs 11 and 12 are so-called “floating ribs,” as do not articulate with the sternum anteriorly   Airways The airway starts with the trachea which begins, beneath the

Obstructive Sleep Apnoea This is a condition where the walls of the airway briefly collapse during sleep. This obstructs the airway causing cessation of breathing during sleep (apnoea) followed by partial arousal to regain breath. The patient then falls asleep again and the cycle repeats itself. It can lead to pulmonary hypertension and type II respiratory failure. It is classically seen in middle-aged obese men who complain of loud snoring.   Risk factors Obesity Large tonsils Large tongue (macroglossia) Symptoms Loud snoring Lethargy with daytime napping Morning headache Decreased libido Hypertension Compensated respiratory acidosis   Key tests Epworth sleepiness scale

Acute Respiratory Distress Syndrome (ARDS) This refers to widespread inflammation at the alveolar-capillary interface, increasing the permeability of the alveolar capillaries. Fluid moves out of the permeable capillaries, resulting in non-cardiogenic pulmonary oedema that impairs ventilation. ARDS can progress to organ failure and carries a high morbidity and mortality risk. Causes Direct – this is due to direct lung injury (such as smoke inhalation) Indirect – due to conditions which cause inflammation (such as sepsis, shock and acute pancreatitis)   Symptoms Acute onset tachypnoea, dyspnoea Bilateral inspiratory crackles Low oxygen saturations and cyanosis with respiratory distress   Key tests ABG

This is a broad term which is most common cancer in the UK, which typically occurs in people of 60 years. It can be broken down into several types of specific types of cancers, which have different histology. Metastases are more common, typically arising from breast, prostate, colon, kidney and uterus. NICE Referral Guidelines   Carcinoma of the bronchus This type of carcinoma is generally divided into 2 main categories:   Small Cell Carcinoma This is a tumour which arises from neuro-endocrine cells in the lungs. It is named “small cell” because the cancerous cells look small when viewed under

These conditions are characterised by a restrictive pattern of spirometry. They occur due to inflammation which leads to fibrosis (irreversible scarring) of the lungs, meaning they cannot expand fully, reducing the vital capacity. Both the FVC and FEV1 are reduced in restrictive conditions. However, the FEV1/FVC ratio stays constant as both FEV1 and FVC decrease proportionally. Different conditions cause fibrosis predominantly in the upper or lower zones.   Upper Zone Fibrosis (BREASTS) Lower Zone Fibrosis (BRAINS) Berylliosis Bronchiectasis Radiation Rheumatoid Arthritis Extrinsic Allergic Alveolitis Asbestosis Ankylosing spondylitis Idiopathic Pulmonary Fibrosis Silicosis Nitrofurantoin (+ amiodarone, bleomycin, methotrexate) TB Scleroderma Sarcoidosis     Interstitial

Asthma Asthma is a disease that is characterised by reversible bronchoconstriction, bronchial hyper-responsiveness, and airway inflammation. Allergens induce a Th2 response which stimulates production of IgE and attracts eosinophils to the airways, leading to airway inflammation. This leads to the release of chemical mediators (such as histamine and leukotrienes) which leads to bronchoconstriction increasing airway resistance.   Risk factors Personal or family history of atopic conditions (allergic rhinitis, eczema) Air pollution Precipitants – cold air, allergens (ask about pets, carpet etc.) Drugs – e.g., aspirin intolerant asthma (usually features nasal polyps) Occupational (baking, factory work) – this classically causes reduced peak

Pneumonia This used to describe a lower respiratory tract infection which often occurs when normal defences are impaired It is a blanket term which can be subdivided into a number of types, with different causes and features:   Lobar pneumonia This is characterised by continuous consolidation of a lobe of the lung. It is most frequently due to a bacterial agent, e.g., Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.   Bronchopneumonia This is characterised by discontinuous areas of consolidation, often bilaterally in the basal lobes, with predominance around the bronchioles. It is usually caused by bacterial agents: Staph

Acute epiglottitis This refers to acute inflammation of the epiglottis, which is often caused by the bacteria Haemophilus influenzae type B. It needs to be recognised and treated quickly as it can lead to airway obstruction. It usually presents in children. However, due to the Haemophilus influenzae type B vaccination, its prevalence has decreased.   Symptoms Rapid onset high fever and malaise Drooling of saliva Muffled voice – due to very sore throat Inspiratory stridor (is a high-pitched sound due to turbulent air flow in the upper airway)   Key tests Usually clinical diagnosis, but fibre-optic laryngoscopy may be performed

Nasal polyp This is a benign, inflammatory proliferation of the lining of the nose, which usually occurs after recurrent colds (infective sinusitis).   Associations Eosinophilic granulomatosis with polyangiitis Conditions causing poor cilia motility, e.g., cystic fibrosis and primary ciliary dyskinesia (previously known as Kartagener’s syndrome) Samter’s triad – nasal polyps and asthma in conjunction with aspirin sensitivity Symptoms Nasal congestion Rhinorrhoea Changes to taste (ageusia) and smell (anosmia)   Management Steroid spray to reduce size of polyp If remains persistent, refer to ENT for examination and removal   Nasopharyngeal Carcinoma This is a malignant squamous cell tumour of the nasopharynx.

Ventilation Ventilation is the movement of air between the lungs and the surrounding environment. Ventilation is key to maintaining adequate arterial oxygenation and for the removal of CO2. Under normal circumstances, breathing is a passive process controlled by centres in the brainstem. These respiratory centres are specialised groups of neurones. The complex interaction of these neuronal collections are responsible for ventilation. Three such groups have been identified: the pons respiratory centre, the medullary respiratory centre and the pre-Bötzinger complex. Respiratory centres Pons respiratory centre The pons (primary) respiratory centre is composed of two centres. Pneumotaxic centres: can interact with the dorsal respiratory group (see below) to suppress inspiration.

Introduction Tuberculosis (TB), caused by bacteria of the mycobacterium tuberculosis complex, is one of the world’s most common and deadly infective diseases. TB is an infectious disease responsible for significant morbidity and mortality worldwide. There is a great deal of variety in the clinical presentation and the disease can manifest in a number of organs. It most commonly affects the lungs in what is called pulmonary TB. The disease may exist in a number of phases: Latent TB: This refers to individuals infected with TB, who suppressed the initial infection, have no active disease and are not infectious. It is thought that around

Introduction A pneumothorax is a collection of air within the pleural space. The pleural space (or cavity) refers to the space between the parietal (lines the inner wall of the lung) and visceral pleura (lines the surface of the lung). When air enters this space it is referred to as a pneumothorax. There are two major types of pneumothorax: Spontaneous: occurring without prior trauma, normally in older patients with underlying lung disease or younger patients with apical blebs. Traumatic: occurring in the setting of trauma, may be open (direct communication between the outside air and pleural space) or closed. Aetiology Spontaneous pneumothoraces may be either primary or secondary First

Overview Sarcoidosis is a rare multisystem granulomatous disorder of unknown aetiology. Sarcoidosis is considered a multi-system disorder that most commonly affects the lungs. The aetiology, though poorly understood, is thought to involve immune dysfunction and T-cell overactivity. Sarcoidosis can have a wide range of clinical manifestations and is able to affect most organ systems within the body. Nonetheless, sarcoidosis most frequently affects the lungs causing a form of interstitial lung disease. Epidemiology Sarcoidosis affects approximately 10-20 people per 100,000 in the UK. There is a great deal of geographic variation in the prevalence and clinical manifestations of sarcoidosis. In Finland the prevalence is approximately

Introduction Respiratory failure occurs when there is inadequate gaseous exchange in the lungs. Respiratory failure is defined by the partial pressure of oxygen and carbon dioxide in the arterial blood. Arterial samples, termed an arterial blood gas (ABG), are typically obtained with an arterial sample drawn from the radial artery (other arteries may be used) or a sample taken from an arterial line. Two types of respiratory failure are defined based upon the partial pressure of oxygen and carbon dioxide: Type 1 respiratory failure (T1RF): is characterised by hypoxaemia (PaO2 < 8 kPa) and a normal or low CO2. Type 2 respiratory failure (T2RF):

Overview Pulmonary embolism can be a life-threatening condition caused by occlusion within the pulmonary arteries. Venous thromboembolism Venous thromboembolism (VTE) is a term that encompasses two conditions: Pulmonary embolism (PE): acute/chronic occlusion of pulmonary arteries. Clot breaks off and travels to the lungs (emboli). Deep vein thrombosis (DVT): acute/chronic occlusion of deep vein(s). Commonly affects the lower limbs through the formation of a clot (thrombus). VTE is commonly asymptomatic, but 1-2 per 1000 people every year have symptomatic VTE. DVT accounts for two-thirds of these cases and is commonly seen with PE. It is estimated that 80% of cases of PE are associated with

Definition & classification Pneumonia is the inflammation of the parenchyma of the lung. Pneumonia is a common type of infection affecting the lung tissue (i.e. parenchyma). In pneumonia, the air sacs (i.e. alveoli) become filled with microorganisms and inflammatory cells leading to poor lung function with features of cough, fever, and shortness of breath. Pneumonia can be life-threatening, particularly in frail, elderly patients or those who are immunosuppressed. Pneumonia is one of several types of respiratory infections, which include: Upper respiratory tract infection (URTI): inflammation of the mucosa of the nostrils, nasal cavity, mouth, throat (i.e. pharynx), and larynx. Colloquially known as

Overview A pleural effusion refers to an abnormal collection of fluid within the pleural space. A pleural effusion is the most common manifestation of pleural disease and it may occur from a wide range of aetiologies. It refers to an abnormal collection of fluid within the pleural space. Pleural effusions are most commonly detected on chest x-ray. They are seen as blunting of the costophrenic angle (where the diaphragm meets the ribs). This may progress to form a dense white area with a meniscus (curve formed by the upper layer of fluid). Large right-sided pleural effusion Pleural effusion is a broad

Mechanics of respiration The basics of ventilation are simple. To inspire, the intrathoracic pressure must be below that of atmospheric pressure. The reverse must be true in order to expire. There are two mechanisms by which we may change the intrathoracic volume (and therefore pressure): Movement of the diaphragm: the diaphragm is the main muscle of respiration. When it contracts its domes descend expanding the thoracic cavity. Movement of the ribcage: The action of various muscles can either move the ribcage up and outward or down and inward. The muscles of the neck, thorax and abdomen all contribute by causing changes

Introduction Lung function tests aid the diagnosis of numerous respiratory conditions. Ventilation is the process by which air (or other gases) is moved in and out of the lungs to facilitate gas exchange. Lung function tests allow us to measure the volume and flow of inhaled gases. An understanding of these tests and what they show, both in health and disease, aids clinicians in the diagnosis of respiratory (and related) disease. Volumes The volume of air during inspiration and expiration, at different levels of exertion, can be categorised into lung volumes. These volumes are highly dependent on height, weight, gender, age

Introduction Lung cancer is a common malignant tumour, with around 48,500 cases diagnosed in the UK each year. It is the third most common malignancy in the UK and is the leading cause of cancer-related death. Smoking is the most important aetiological factor, implicated in upwards of 80% of cases. It is categorised by the underlying cell type: Small-cell lung cancer (SCLC) Non-small cell lung cancer (NSCLC): Adenocarcinoma Squamous cell carcinoma Large cell Management depends on the subtype, stage at diagnosis and patient co-morbidities. Broadly the options include chemotherapy, radiotherapy and surgical resection. Figures from Cancer Research UK (last accessed Nov 2021). Aetiology Smoking is by far

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic condition characterised by progressive fibrosis of unknown aetiology with typical imaging and histological findings. Interstitial lung disease Interstitial lung disease (ILD) refers to a family of conditions with shared characteristics of interstitial inflammation, fibrosis and/or cellular changes in the absence of infection or malignancy. In most cases interstitial fibrosis is found and commonly related to sarcoidosis, chronic hypersensitivity pneumonitis, autoimmune disease or in cases with an unknown aetiology, idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis IPF is the most common form of idiopathic interstitial pneumonia. It occurs more commonly with advancing age and is rare

Overview Cystic fibrosis (CF) is an autosomal recessive multi-system disease predominantly characterised by respiratory features. It is caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene found on chromosome 7. This encodes a chloride channel and abnormalities have wide-ranging effects. Since the introduction of newborn screening for CF in 2007, the vast majority of patients are diagnosed in the first two months of life. Others are diagnosed following characteristic presentations (e.g. failure to thrive, recurrent chest infections, steatorrhea) As treatment improves, we are seeing significant improvements in life-expectancy, based on data from the 2019 CF Registry Report the median predicted survival

Introduction Bronchiectasis describes the irreversible and abnormal dilatation of the airways. It normally results from the inflammatory destruction of the elastic and muscular components of the airways. This leads to abnormally dilated airways, persistent sputum production with ineffectual clearance and recurrent chest infections. Bronchiectasis commonly occurs secondary to cystic fibrosis though this is often considered and covered separately. Epidemiology In 2012 it was estimated that 210,000 people in the UK had bronchiectasis. The figures for prevalence and incidence vary widely by source as the condition often goes unrecognised or undiagnosed. Data from the British Lung Foundation indicates females are affected more than males. In 2012 they

Introduction Asthma is a common chronic inflammatory disorder of the airways. Approximately, 12% of the UK population have a diagnosis of asthma and 5.4 million are receiving treatment for the condition. Clinically it presents with classical features including cough, wheeze, chest tightness, and shortness of breath. It can present acutely as an ‘exacerbation of asthma’, which may be life-threatening. It is characterised by: Reversible airflow limitation Airway hyperresponsiveness Inflammation of the bronchi Over the last decade, the approach to the diagnosis and management of asthma has been changing rapidly. There are currently two broad guidelines for the management of asthma (NICE