Respiratory Medicine Flashcards

Question

What investigations would you request for asthma and in what order?

Answer 1

**Investigations:** N.B. Cant diagnose a child under 5. LUNG FUNCTION TESTS: **1.Spirometry**: * It is a test which measures the amount (volume) and speed (flow) of air during exhalation and inhalation. * It is helpful in categorising respiratory disorders as either obstructive (conditions where there is obstruction to airflow, for example due to bronchoconstriction in asthma) or restrictive (where there is restriction to the lungs, for example lung fibrosis). * Key metrics include: * **FEV1**: forced expiratory volume - volume that has been exhaled at the end of the first second of forced expiration * **FVC**: forced vital capacity - volume that has been exhaled after a maximal expiration following a full inspiration * Typical results in asthma: * FEV1 - significantly reduced * FVC - normal * FEV1% (FEV1/FVC) \< 70% **2.Peak expiratory flow rate (PEFR):** * This is the most useful test in asthma. * Patients should take two readings per day, to show the variability of the disease. * In patients with suspected asthma, you should get them to take two weeks worth of measurements whilst at work, and 2 weeks whilst at home, to prove the cause of the disease. * It can also show variation between exercise/rest, night/day, before/after bronchodilator **3.Carbon monoxide transfer test**- normal in asthma Airway inflammation measures: **Fractional exhaled nitric oxide (FeNO):** * nitric oxide is produced by 3 types of nitric oxide synthases (NOS). * one of the types is inducible (iNOS) and levels tend to rise in inflammatory cells, particularly eosinophils * levels of NO therefore typically correlate with levels of inflammation. Airway hyperreactivity measures (only in adults, rarely done as its dangerous, don’t know with brittle asthma): **Direct bronchial challenge test with histamine or methacholine** Other investigations to consider: * chest x-ray: particular in older patients or those with a history of smoking, good at excuding pneumothorax (which is also a complication of asthma) * **skin prick tests –** you should perform these on all newly diagnosed asthmatics to help **find a cause** * **Blood and sputum tests –** you can test these for high number of eosinophils; and this may help form your diagnosis, but is not diagnostic on its own * **Trial of corticosteroids –** this can be very useful in children at first presentation. * Exercise test – often used in children, a negative result does not exclude asthma

Answer 2

**Management**: * Optimal control should include assessment of a combination of the patient’s symptoms and their PFTs. * The goal for optimal control is to have the patient asymptomatic with normal PFTs * **Controlling extrinsic factors-** You may want to try and reduce the risk of a person coming into contact with a provoking factor. Dust mite faeces is a major cause, and so changing bedding regularly is a good way to manage this risk. * Patients should also avoid taking **β- blockers in any form**. This is an **absolute contra-indication.** * **50% of those with occupational asthma will have no problems if they are kept away from the cause.** The other 50% may still continue to have symptoms, and will have bad exacerbations if they back into contact with the causing agent. **STEPWISE TREATMENT:** For adults ( ages 17+): 1. short-acting beta₂ agonist (SABA) regas reliever therapy 2. SABA+ low dose ICS – first line maintenance therapy 3. SABA+ low dose ICS+ LTRA (Montelukast)- review treatment response in 4-8 weeks 4. SABA+ low dose ICS +LABA +/- LTRA 5. MART\* regimen (that has low dose ICS in it) +/- LTRA 6. MART\* regimen (that has moderate ICS in it) +/- LTRA **OR** fixed dose regimen of moderate dose ICS, LABA and SABA +/- LTRA 7. Any options from: 1. Increasing the ICS to a high maintenance dose (this should **only** be offered as part of a fixed-dose regimen, with a SABA used as a reliever therapy) 2. a trial of an additional drug (for example, a long-acting muscarinic receptor antagonist or theophylline) 3. seeking advice from a healthcare professional with expertise in asthma. Maintenance and reliever therapy (MART)\* * a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required * MART is only available for ICS and LABA combinations in which the LABA has a fast-acting component (for example, formoterol)

Answer 3

**Beta2-agonists:** * Are beta-2 selective i.e. work only in lungs (B1 is heart & B3 is adipose tissue) - however is high doses the B2-agonists are not selective and will act on other receptors * When B2 agonist binds to B2 receptor coupled with Gs protein this results in adenyl cyclase converting ATP to cyclic AMP and increases in cyclic AMP leads to bronchodilation * Beta-agonists also inhibit mast cell activity thereby reducing inflammatory response * Short acting Beta agonist (SABA) (4 hours): * SALBUTAMOL (partial agonist) * TERBUTALINE * Prescribed as two puffs as required * Long acting Beta agonist (LABA) (12 hours): * SALMETEROL * FORMOTEROL (full agonist) * Longer acting since are more lipophilic so remain in tissue for longer * At high concentrations e.g. in badly controlled asthmatics a tolerance may develop due to B2-receptor desensitisation

Answer 4

**Muscarinic antagonists:** * Short-acting e.g. IPRATROPIUM * Long acting e.g. TIOTROPIUM - has high affinity and disassociates slowly from muscarinic receptors * Act on **airway M3 receptors** * Normally ACh (parasympathetic) binds to M3 receptor bound to Gq protein resulting in phospholipase C converting phosphate to DAG resulting in protein kinase C production that results in smooth muscle contraction * Muscarinic antagonists prevent ACh from binding since they bind to the M3 receptor thereby blocking ACh action

Answer 5

**Methylxanthines:** * These are phosphodiesterase (PDE) inhibitors they prevent the conversion of cyclic-AMP to 5’-AMP resulting in a build up of cyclic-AMP and thus increased smooth muscle relaxation * Long-acting; THEOPHYLLINE (non-selective so has wide range of side effects e.g. CVS, CNS & GI tract) & AMINOPHYLLINE

Answer 6

**Inhaled corticosteroids (ICS):** * All patients who have regular persistent symptoms need regular treatment with inhaled corticosteroids * There are two types of corticosteroids; mineralocorticoids (aldosterone - involved in Na+ retention) and glucocorticoids (hydrocortisone - ensures glucose levels are correct, anti- inflammatory properties) * Hydrocortisone has anti-inflammatory properties but also has significant mineralocorticoid action so is not suitable as a treatment * Examples: BECLOMETASONE, BUDESONIDE * Glucocorticoids interfere with gene transcription * Glucocorticoid receptor is found on promoter region of DNA has zinc fingers that anchor receptor to DNA and recognise discrete sequences * There is either a + Glucocorticoid response element (GRE) - increases transcription or - GRE - decreases transcription on the glucocorticoid receptor * -GRE results in the suppression of cytokines e.g. TNF, IL-5 and IL-3 thereby reducing inflammation and thus reducing symptoms * +GRE results in increased lipocortin which inhibits PLA2 meaning there is a decrease in arachidonic acid and thus a decrease in prostaglandins and leukotrienes resulting in reduced inflammation and thus reducing symptoms * Side effects * Susceptibility to infection due to cytokine suppression * Metabolic such as osteoporosis and muscle wasting

Answer 7

**Other agents with bronchodilator activity:** * Leukotriene receptor antagonist e.g. MONTELUKAST * Oral corticosteroid needed for those not controlled on inhaled * corticosteroids e.g. PREDNISOLONE **Steroid-sparing agents:** * METHOTREXATE * CICLOSPORIN * iv immunoglobulin * anti-IgE monoclonal antibody - OMALIZUMAB

Answer 8

* In addition, a normal pCO₂ in an acute asthma attack indicates exhaustion and should, therefore, be classified as life-threatening. **Pulsus paradoxis –** on inspiration, the diastolic pressure

Answer 9

**Pulsus paradoxus –** on inspiration, the diastolic pressure decreases by 10mmHg. This is present in about 45% of cases of asthma.

Answer 10

**Hospital management – ideally you should start treatment before doing investigations!** 1. **Do an** [ABG](https://almostadoctor.co.uk/encyclopedia/abg-arterial-blood-gas-interpreting-results) **–** it may be life-threatening if: 1. CO2 \> 5kPa (high) 2. O2 \<8kPa (low) 3. Low pH 2. **Start on 100% O2** (non-rebreathing mask) **with the patient sat upright in bed-** aim for 94-98% ( do not delay this even in the absence of pulse oximetry) 3. **Give 5mg salbutamol via nebulizer on 100% O2** 4. **Give hydrocortisone 100mg IV or 50mg prednisolone orally.** Give both if very unwell 5. **Give 0.5mg ipratropium bromide via nebulizer** 6. **Do CXR to exclude pneumothorax if failed to respond to treatment** **If life-threatening signs are present:** 1. Inform ITU and seniors 2. Give **magnesium sulphate 1.2-2g IV over 20 minutes** 3. **Change the nebulized salbutamol every 15 minutes,** or give 10mg continuously per hour. Only give more ipratropium every 4-6 hours 4. Repeat PEF every 15-30 minutes to assess the situation. If improving then gradually reduce O2 and nebs. If not, try and find senior, keep giving nebs, and consider aminophyline. 1. Check pulse oximetry – aiming for sats \>92% 2. Check blood gases every 2 hours, **and definitely within 2 hours of admission** 3. **Record PEF’s and β-agonists** when given / carried out 4. A maximum of 60mg/day of prednisolone can be given (orally) 5. **You can give 200mg hydrocortisone every 4 hours for a max of 24 hours** 6. Give oral prednisolone for 5 days after they are starting to recover 7. Ventilation is an option – you would have to call an anaesthetist 8. Patients have to have \>75% predicted PEF for discharge * After recovery from a severe asthma attack, oral corticosteroids should be continued until there are no residual symptoms, especially at night, and the peak expiratory flow rate is at least 80% of the person’s previous best. * High doses of these drugs can be stopped abruptly if used for 3 weeks or less, or tapered off if they have been used for a longer period. **Brittle asthma –** ‘catastrophic sudden severe asthma’ These patients are at risk from sudden death, even if their asthma is well controlled between attacks. An attack can come on very quickly within minutes.

Answer 11

**CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)** * COPD is an umbrella term encompassing the older terms chronic bronchitis and emphysema. * A disease state characterised by airflow limitation that is not fully reversible * The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to certain particles * Patients typically have recurrent exacerbations – some are mild while some need hospitlization * CHRONIC BRONCHITIS: Cough with sputum for 3 months for 2 or more years * EMPHYSEMA: Histologically its enlarged airspaces distal to terminal bronchioles, with destruction of alveolar walls * In COPD the FEV₁:FVC ratio is \<70%. COPD can also be diagnosed in patients with FEV₁:FVC ratio is \>70% on the basis of clinical signs and symptoms – such as shortness of breath, or cough. * **The three main pathological effects in COPD:** * Loss of elasticity of the alveoli * Inflammation and scarring – reducing the size of the lumen, as well as reducing elasticity * Mucus hypersecretion – reducing the size of the lumen and increasing the distance gasses have to diffuse

Answer 12

* Smoking (10-20% of all smokers will develop COPD)- MOST COMMON CAUSE * Alpha-1 antitrypsin deficiency\*\* - causes early onset COPD * cadmium (used in smelting) * coal mining * cotton * cement * grain \*\*Mutations in the alpha-1 antitrypsin gene on chromosome 14 lead to reduced hepatic production of alpha-1 antitrypsin which normally inhibits the proteolytic enzyme - neutrophil elastase. Therefore it causes early-onset COPD due to proteolytic lung damage. (Also causes cirrhosis so more on this disease in hebas GI notes)

Answer 13

**Pathophysiology:** _Chronic bronchitis:_ * There is **airway narrowing** and hence **airflow limitation** as a result of **hypertrophy and hyperplasia of mucus secreting glands of the bronchial tree**, **bronchial wall** **inflammation** and **mucosal oedema** * Microscopically there is infiltration of the walls of the bronchi and bronchioles with acute and chronic inflammatory cells * The epithelial layer may become ulcerated and, with time, squamous epithelium replaces the columnar cells (squamous metaplasia) when the ulcer heals * The inflammation is followed by scarring and thickening of the walls, which narrows the small airways * The small airways are particularly affected early in the disease, initially without the development of any significant breathlessness * The initial inflammation is *reversible* and accounts for the improvement in airway function if smoking is stopped early * In the later stages, the inflammation continues, even if smoking is stopped * Patients chronic bronchitis are referred to as blue bloaters _Emphysema_ * Defined as dilatation and destruction of the lung tissue *distal* to the terminal bronchioles * Results in loss of elastic recoil, which normally keeps the airways open during expiration * Leads to expiratory airflow limitation and air trapping Premature closure of airways limits expiratory flow while the loss of * alveoli decreases capacity for gas transfer * Patients with emphysema are referred to as the pink puffers * Classification: * Centri-acinar emphysema: * Distension and damage of lung tissue is concentrated around the respiratory bronchioles, whilst the more distal alveolar ducts and alveoli tend to be well preserved * Extremely common * Pan-acinar emphysema: * Less common * Distension and destruction affect the whole acinus and in * severe cases the lung is just a collection of bullae * Associated with alpha-1 antitrypsin deficiency * Irregular emphysema: * Scarring and damage that affects the lung parenchyma patchily, independent of acinar structure _COPD_ * Most have both emphysema and chronic bronchitis * The combination of emphysema (loss of elastic recoil of the lung with collapse of small airways during expiration) and chronic bronchitis (airway narrowing) results in severe airflow limitation * V/Q (ventilation perfusion) mismatch is partly due to damage and mucus plugging of smaller airways from the chronic inflammation and partly due to rapid closure of smaller airways in expiration owing to the loss of elastic support - this mismatch leads to a fall in PaO2 and increased work or respiration * CO2 excretion is less affected by V/Q mismatch and many patients have low- normal PaCO2 values due to increasing alveolar ventilation in an attempt to correct their hypoxia (pink puffers) * Other patients fail to maintain their respiratory effort and then their PaCO2 levels increase * In the short term, this rise in CO2 leads to stimulation of respiration, but in the longer term, these patients often become insensitive to CO2 and come to depend on the hypoxaemia to drive ventilation * Such patients appear less breathless and because of renal hypoxia, they start to retain fluid and increase erythrocyte production (leading eventually to **polycthaemia**) - they become **bloated** and **cyanosed** (blue) and have a typical **blue bloater** appearance _Cigarette smoke:_ * Causes mucus gland hypertrophy in the larger airways and leads to an increase in neutrophils, macrophages and lymphocytes in the airways and walls of the bronchi and bronchioles * These cells release inflammatory mediators (elastases, proteases, IL-1,-8 & TNF-alpha) that attracts inflammatory cells (further amplify the process), induce structural changes and break down connective tissue (protease-antiprotease imbalance) in the lung resulting in emphysema * Inactivates the major protease inhibitor alpha-1 antitrypsin

Answer 14

_Pink Puffers and Blue Bloaters:_ * **Pink Puffers –** have a near normal PaO2, and a normal or low PaCO2 (due to hyperventilation). They ‘puff’ to increase their alveolar ventilation – and by doing so they are able to keep their blood gas values normal. These patients generally have *emphysema* or at least a higher degree of emphysema than bronchitis. These are likely to enter _type I respiratory failure._ * **Blue Bloaters –** these have decreased alveolar ventilation. They have a low PaO2 and a high PaCO2. They are cyanosed but not breathless (because their respiratory centre has become sensitised). They rely on **hypoxic drive** to maintain adequate ventilation. They often go on to develop **cor pulmonale.** These patients are more likely to be type II respiratory failure. ‘Bloater’ – due to cor pulmonale.

Answer 15

Often a wheeze is **polyphonic-** this means it is made up of many different notes, and thus this shows it is caused by many abnormal airways. Wheeze is normally caused by **abnormal small airways.** A **monophonic wheeze** is caused by a single airway obstruction, and is more likely to be cancer.

Answer 16

**Clinical features: Symptoms:** * cough: often productive (white or clear sputum) * dyspnoea * wheeze * frequent exacerbations * symptoms made worse by cold/damp weather or pollution **Signs:** * Tachypnoea * Use of accessory muscles of respiration * Hyperinflation of lungs (barrel chest) * Reduced chest expansion * Resonant chest sounds – suggestive of hyperinflation * Reduced cricosternal angle \<3cm- this is reduced due to hyperinflation * Quiet breath sounds – over areas of emphysematous bullae * Wheeze * Pursed lip breathing\*\*- helps to prevent alveolar and airway collapse * Prolonged expiration - because their FEV1 is low, they have to have a prolonged expiratory phase to allow for adequate respiration Later signs: * Cyanosis * Cor pulmonale - This is right sided heart failure, as a result of pulmonary hypertension * **peripheral oedema** (this happens in severe cases)

Answer 17

**Differential diagnosis:** * Asthma * CHF * Bronchiectasis * Pneumoconiosis / asbestosis * Allergic fibrosing alveolitis

Answer 18

**Diagnosis:** * NICE recommend considering a diagnosis of COPD in patients over 35 years of age who are smokers or ex-smokers and have symptoms such as exertional breathlessness, chronic cough or regular sputum production. * The following investigations are recommended in patients with suspected COPD: * post-bronchodilator spirometry to demonstrate airflow obstruction: FEV1/FVC ratio less than 70% * chest x-ray: * hyperinflation * bullae: if large, may sometimes mimic a pneumothorax * flat hemidiaphragm * **Decreased peripheral vascular markings** * Long narrw heart shadow/ cylindrical heart * also important to exclude lung cancer * full blood count: exclude secondary polycythaemia * body mass index (BMI) calculation * High resolution CT scans are used particularly to show emphysematous bullae * In advances cases ABGs may show hypoxia +/- hypercapnia * Alpha-1 antitrypsin levels and genotypes are worth measuring in premature disease or lifelong non-smokers

Answer 19

**General management** * \>smoking cessation advice: including offering nicotine replacement therapy, varenicline or bupropion * annual influenza vaccination * one-off pneumococcal vaccination * pulmonary rehabilitation to all people who view themselves as functionally disabled by COPD (usually Medical Research Council [MRC] grade 3 and above) _Bronchodilator therapy_ * a short-acting beta2-agonist (SABA) or short-acting muscarinic antagonist (SAMA) is first-line treatment * for patients who remain breathless or have exacerbations despite using short-acting bronchodilators the next step is determined by whether the patient has *'asthmatic features/features suggesting steroid responsiveness'* There are a number of criteria NICE suggest to determine whether a patient has asthmatic/steroid responsive features: * any previous, secure diagnosis of asthma or of atopy * a higher blood eosinophil count - note that NICE recommend a full blood count for all patients as part of the work-up * substantial variation in FEV1 over time (at least 400 ml) * substantial diurnal variation in peak expiratory flow (at least 20%) note: NICE do not recommend formal reversibility testing as one of the criteria. If No asthmatic features/features suggesting steroid responsiveness: * add a long-acting beta2-agonist (LABA) + long-acting muscarinic antagonist (LAMA) * if already taking a SAMA, discontinue and switch to a SABA Asthmatic features/features suggesting steroid responsiveness * LABA + inhaled corticosteroid (ICS) * if patients remain breathless or have exacerbations offer triple therapy i.e. LAMA + LABA + ICS * if already taking a SAMA, discontinue and switch to a SABA * NICE recommend the use of combined inhalers where possible Oral theophylline * NICE only recommends theophylline after trials of short and long-acting bronchodilators or to people who cannot used inhaled therapy * the dose should be reduced if macrolide or fluoroquinolone antibiotics are co-prescribed _Oral prophylactic antibiotic therapy_ * azithromycin prophylaxis is recommended in select patients * patients should not smoke, have optimised standard treatments and continue to have exacerbations * other prerequisites include a CT thorax (to exclude bronchiectasis) and sputum culture (to exclude atypical infections and tuberculosis) * LFTs and an ECG to exclude QT prolongation should also be done as azithromycin can prolong the QT interval _Mucolytics:_ should be 'considered' in patients with a chronic productive cough and continued if symptoms improve _Cor pulmonale_ * features include peripheral oedema, raised jugular venous pressure, systolic parasternal * heave, loud P2 * use a loop diuretic for oedema, consider long-term oxygen therapy * ACE-inhibitors, calcium channel blockers and alpha blockers are not recommended by NICE _Surgery_ * Some patients who have a large **emphysematous bullae** may benefit form a **bullectomy.** This enables adjacent areas of collapsed lung to re-expand into the space, and function again. This **improves VQ mismatch.** * Another option – you can put a valve in on bronchoscopy – this will allow air out of an emphysematous bullae, but not allow air in, and this eventually allows the bullae to collapse. * Another option is **lung volume reduction surgery.** This aims to increase the elastic recoil of the lung. Patients have to be carefully selected, and have an FEV1 \<1L. it improves symptoms, but does not improve mortality. * **Lung transplant** can be performed on certain patients with **end stage emphysema.** It has a 3-year survival of 75%, and again, the treatment improves symptoms, but does not really affect quality of life. Factors which may improve survival in patients with stable COPD: * smoking cessation - the single most important intervention in patients who are still smoking * long term oxygen therapy in patients who fit criteria * lung volume reduction surgery in selected patients **C****OPD: long-term oxygen therapy** * NICE guidelines on COPD clearly define which patients should be assessed for and offered long-term oxygen therapy (LTOT). * Patients who receive LTOT should breathe supplementary oxygen for at least 15 hours a day. * Oxygen concentrators are used to provide a fixed supply for LTOT. * Assess patients if any of the following: * very severe airflow obstruction (FEV1 \< 30% predicted). Assessment should be 'considered' for patients with severe airflow obstruction (FEV1 30-49% predicted) * cyanosis * polycythaemia * peripheral oedema * raised jugular venous pressure * oxygen saturations less than or equal to 92% on room air * Assessment is done by measuring arterial blood gases on 2 occasions at least 3 weeks apart in patients with stable COPD on optimal management. * Offer LTOT to patients with a pO2 of \< 7.3 kPa or to those with a pO2 of 7.3 - 8 kPa and one of the following: * secondary polycythaemia * peripheral oedema * pulmonary hypertension * In terms of smoking, NICE advise the following: * do not offer LTOT to people who continue to smoke despite being offered smoking cessation advice and treatment, and referral to specialist stop smoking services. * NICE suggest that a structured risk assessment is carried out before offering LTOT, including: * the risks of falls from tripping over the equipment * the risks of burns and fires, and the increased risk of these for people who live in homes where someone smokes (including e‑cigarettes)

Answer 20

Acute exacerbations of COPD are one of the most common reasons why people present to hospital in developed countries. Features: * increase in dyspnoea, cough, wheeze * there may be an increase in sputum suggestive of an infective cause * patients may be hypoxic and in some cases have acute confusion

Answer 21

The most common bacterial organisms that cause infective exacerbations of COPD are: * Haemophilus influenzae (most common cause)- this is a Gram-negative coccobascillus. * Streptococcus pneumoniae- Gram-positive diplococcus. * Moraxella catarrhalis Respiratory viruses account for around 30% of exacerbations, with the human rhinovirus being the most important pathogen.

Answer 22

Management: * Give controlled oxygen to mainan sats at 88-92%: * **Perform repeat ABGs** (e.g. every 20 minutes) **to assess for a rise in PaCO₂** * If PaCO₂ has risen \> 1.5kPa consider use of CPAP or other assisted ventilation * **PaCO₂** is dependent on VENTILATION – i.e. the volume of air inhaled and exhaled * **PaO₂** is dependent on alveolar gas transfer (“OXYGENATION”) and the percentage of oxygen inhaled * VENTILATION and OXYGENATION are not the same! * In COPD, the normal respiratory drive, (usually driven by PaCO₂) is not longer effective – the feedback mechanism between respiratory rate and PaCO₂ has been lost. So, a patient may be adequately ***oxygenating*** due to the quality of O2 inhaled, but may not be adequately ***ventilating*** to “blow off” CO2 * Rising PaCO2 can lead to reduced level of consciousness and is a poor prognostic factor L * Give nebulised salbutamol (2.5-5mg in solution), and ipratropium (0.5mg) * give prednisolone 30 mg daily for 5 days * it is common practice for all patients with an exacerbation of COPD to receive antibiotics. NICE do not support this approach. They recommend giving oral antibiotics 'if sputum is purulent or there are clinical signs of pneumonia' * the BNF recommends one of the following oral antibiotics first-line: amoxicillin or clarithromycin or doxycycline.

Answer 23

Fibrosis predominately affecting the upper zones use acronym ‘CHARTS’ * coal worker's pneumoconiosis/progressive massive fibrosis * hypersensitivity pneumonitis (also known as extrinsic allergic alveolitis) * histiocytosis * ankylosing spondylitis (rare) * Radiation * Tuberculosis * silicosis * sarcoidosis

Answer 24

Fibrosis predominately affecting the lower zones * idiopathic pulmonary fibrosis * most connective tissue disorders (except ankylosing spondylitis) e.g. SLE * drug-induced: amiodarone, bleomycin, methotrexate * asbestosis

Answer 25

* Dry cough * Dyspnoea (progressive) * Digital clubbing * Diffuse inspiratory crackles

Answer 26

**EXTRINSIC ALLERGIC ALVEOLITIS (**also known as hypersensitivity pneumonitis) * It is a condition caused by hypersensitivity induced lung damage due to a variety of inhaled organic particles. * It is thought to be largely caused by immune-complex mediated tissue damage (type III hypersensitivity) although delayed hypersensitivity (type IV) is also thought to play a role in EAA, especially in the chronic phase. * There is diffuse granulomatous inflammation of the lung parenchyma * It is a type of interstitial lung disease * There are acute, subacute and chronic forms. * Acute and subacute forms cause a pneumonitis which can be recurrent. * Chronic disease can cause fibrosis, emphysema and permanent lung damage * It is usually a disease of adults but bird fancier's lung can occasionally present in children * Examples: * bird fanciers' lung: avian proteins * farmers lung: spores of *Saccharopolyspora rectivirgula* (formerly *Micropolyspora faeni*) – one of the most common * Cheese-worker's lung - exposure to cheese mould, *Penicillium casei*. * malt workers' lung: *Aspergillus clavatus* * mushroom workers' lung: thermophilic actinomycetes\* **Risk factors:** - Pre-existing lung disease - Specific occupations including *farmers, cattle workers, ventilation system workers, vets and those jobs that involve working with chemicals* - Bird keeping - Regular use of hot tubs

Answer 27

**Pathophysiology:** * The allergic response to the inhaled antigen involves both cellular immunity and the deposition of immune complexes (TYPE 3 HYPERSENSITIVITY REACTION) resulting in inflammation through the activation of complement via the classical pathway * Some of the inhaled antigen may lead to inflammation by directly activating the alternate complement pathway * These mechanisms attract and activate alveolar and interstitial macrophages so that continued antigenic exposure results in the progressive development of pulmonary fibrosis * In the acute phase; the alveoli are infiltrated with acute inflammatory cells * With chronic exposure, granuloma formation and obliterative bronchiolitis occur * Farmers lung: * Fungus in mouldy hay is inhaled * If individual is already sensitised to the organism, a type III immune complex hypersensitivity reaction follows * Clinically there is acute dyspnoea (difficulty breathing) and cough a few hours after inhalation of the antigen * One of the earliest features is bronchiolitis * Later, chronic inflammatory cells are seen in the interstitium together * with non-caveating granulomas * The inflammatory process may resolve on WITHDRAWAL of the antigen but if there is chronic exposure then pulmonary fibrosis (build up of scar tissue, makes lungs stiff) will develop

Answer 28

**Presentation:** Acute- occurs 4-8 hrs after exposure: * SOB * dry cough * flu-like illness with fever * malaise * chills * generalised aches and pains * Symptoms are directly related to level of exposure, * signs: fever, tachypnoea and bibasal fine inspiratory crackles. Wheeze is rare . * In very severe cases, patients may develop life-threatening respiratory failure with cyanosis * Resolution occurs 24-48hrs following removal of the antigen Subacute: * Syx less severe and more gradual onset * Productive cough * Dyspnoea * Fatigue * Anorexia * Weight loss * Signs same as acute * It can present as recurrent pneumonia. * After the exposure is removed it can take weeks or months for symptoms to resolve Chronic: * often no systemic symptoms except weight loss and gradual diminution of exercise tolerance due to dyspnoea. * Cyanosis * Clubbing * Other signs: tachypnoea, type 1 respiratory failure, inspiratory crackles over lower lung fields, eventually, chronic hypoxemia, pulmonary hypertension with right heart failure * If the source of antigen is removed only partial improvement of symptoms * There may also be acute exacerbations in those with chronic disease

Answer 29

**Differential diagnosis:** * Infection (bacterial, fungal, viral including tuberculosis). * Connective tissue disorders causing interstitial lung disease. * Pulmonary fibrosis (including idiopathic). * Asthma. * Sarcoidosis. * Histoplasmosis. * Drug-induced interstitial lung disease **Investigations:** * Blood tests: * inflammatory markers e.g. raised WCC, ESR but-these are nonspecific. * There may be serum antibodies detectable – non specific . * No eosinophilia * **CXR:** * acute form this may be normal in some or show diffuse micronodular interstitial shadowing. * In the subacute form, there may be micronodular or reticular opacities in the **mid/upper** lung fields. * In the chronic form, there may be features of fibrosis with loss of lung volume * **Bronchoalveolar lavage**: shows lymphocytosis and the CD4/CD8 ratio is reduced to less than 1 * CT scanning: high-resolution CT is a good way to evaluate the stage of disease and usually shows typical changes * Lung function testing: * can be normal * Spirometry shows a restrictive defect in acute and subacute forms but there may be a mixed restrictive/obstructive picture in the chronic form. * Reduced gas transfer during attacks * Transbronchial or open lung biopsy: this may show characteristic histopathological features. **Management:** Acute: * Remove allergen * In severe acute cases where there is cyanosis or resp distress- admit and give oxygen Severe acute and subacute: * Avoid allergen * Oral prednisolone (corticosteroid) followed by reducing dose Chronic: * Avoid exposure to allergen * Long term Corticosteroids e.g. prednisolone * Resistant cases give azathioprine **Complications:** Pulmonary fibrosis, Cor pulmonale, Type 1 resp failure, spontaneous pneumothorax

Answer 30

**INTERSITIAL LUNG DISEASES** * Interstitial lung diseases (ILDs) affect the lung interstitium, i.e. the space between the alveolar epithelium and the capillary endothelium, causing inflammation and fibrosis. * The two main types of interstitial lung disease are **pulmonary fibrosis and** [**sarcoidosis**](https://almostadoctor.co.uk/encyclopedia/sarcoidosis)**.** Other types include: * occupational lung diseases ([pneumoconiosis](https://almostadoctor.co.uk/encyclopedia/pneumoconiosis)), * Drug induced ILD (e.g. amiodarone, methotrexate) * Hypersensitivity ILD (extrinsic allergic alveolitis) * Secondary to connective tissue disorders * Sarcoidosis tends to occur in younger adults, and can also affect any other organ system in the body, although in 90% of cases the lungs are involved * Sarcoidosis has a more benign prognosis and in many cases, resolves by itself * Pulmonary fibrosis tends to occur in older adults, and causes significant morbidity and mortality

Answer 31

**IDIOPATIC PULMONARY FIBROSIS** * This is a relatively rare, progressive, chronic pulmonary fibrosis of unknown aetiology. * Commonest cause of interstitial lung disease * There is patchy fibrosis of the interstitium and minimal or absent inflammation, acute fibroblastic proliferation and collagen deposition * INVOLVES THE LOWER LOBES - The alveolar walls are affected predominantly in the subpleural regions of the lower lobes. * Also known as cryptogenic organising pneumonia * Pulmonary fibrosis has a very poor prognosis – the median age of survival is only 3-4 years. **Risk factors:** * Factors implicated in triggering the aberrant wound healing include: * Cigarette smoking * Infectious agents (CMV, Hep C, EBV) * Occupational dust exposure (metals, woods) * Drugs - methotrexate, imipramine (anti-depressant) * Chronic gastro-oesophageal reflux disease (GORD) * Genetic predisposition

Answer 32

**Pathophysiology:** * The pathogenesis of IPF is unknown * It is thought that repetitive injury to the alveolar epithelium, caused by currently unidentified environmental stimuli leads to the activation of several pathways responsible for repair of the damaged tissue * However in IPF, the wound healing mechanisms become uncontrolled, leading to the over-production of fibroblasts and deposition of increased extracellular matrix in the interstitium (fibrosis) with little inflammation * The structural integrity of the lung parenchyma (functional tissue of organ) is therefore disrupted; there is loss of elasticity and the ability to perform gas exchange is impaired, leading to progressive respiratory failure

Answer 33

**Clinical presentation:** Symptoms: * progressive breathlessness * dry cough * considerable weight loss * fatigue/malaise. Signs O/E include: * Reduced chest expansion * Final bi-basal end inspiratory crackles * Finger Clubbing (2/3 patients) * Cyanosis * Over time this disease progresses to cause pulmonary [hypertension](https://almostadoctor.co.uk/encyclopedia/diagnosis-pathology-and-management-of-hypertension), [cor pulmonale](https://almostadoctor.co.uk/encyclopedia/heart-failure) and type 1 respiratory failure. * Important: his histological pattern is called **“Usual Interstitial Pneumonitis” (UIP) –** it’s the most common pattern of lung disease that IPF shows. * Other patterns of the disease can include DIP (Desquamative Interstitial Pneumonitis) and [Bronchiolitis](https://almostadoctor.co.uk/encyclopedia/bronchiolitis) Obliterans

Answer 34

**Differential diagnosis:** * COPD * Asthma * Bronchiectasis * congestive heart failure, * lung cancer * hypersensitivity pneumonitis

Answer 35

**Investigations:** Aims of investigation in IPF are to confirm the presence of pulmonary fibrosis and exclude identifiable (a potentially reversible) causes * Blood * FBC (raised ESR), Rh factor (+ve 50% patients), ANA (30% +ve) * CXR * Irregular, reticulo-nodular shadows, often in lower zones, sometimes called the ***reticulonodular pattern*** * CXR is often normal * High resolution CT * Needed for diagnosis as it confirms it * Ground-glass opacification * “Honeycombing” i.e. basal layers of small, cystic airspaces with irregularly thickened walls composed of fibrous tissue * Traction bronchiectasis - the fibrotic process distorts the normal lung architecture, pulling the airways open and causing bronchiectasis * Subpleural reticulation * “Mosaicism” * Basal distribution i.e. abnormalities are more pronounced at the bases * Lung Function Tests (spirometry) * Restrictive Pattern FEV1/FVC ratio greater than 70% but FVC * low i.e less than 80% predictive value) * [ABG](https://almostadoctor.co.uk/encyclopedia/abg-arterial-blood-gas-interpreting-results) * Hypoxaemia * Transbronchial or open lung biopsy to confirm histological diagnosis * Assists in defining the type of ILD that is present most commonly its **usual interstitial pneumonia (UIP)**

Answer 36

**Management:** * Serial lung function testing is used to monitor disease progression * Pulmonary rehabilitation * Best supportive care: * Oxygen e.g ambulatory (portable) oxygen if they need it * Palliative care i.e. opiates * Smoking cessation advice * Pirfenidone - an antifibrotic agent that can slow the rate of FVC decline (need to check eligibility) * Treat GORD since it contributes to repetitive alveolar epithelial damage – give PPIs * Lung transplant * DO NOT GIVE STEROIDS

Answer 37

**SARCOIDOSIS** * Sarcoidosis is a ***multisystem granulomatous disorder*** of unknown aetiology. * It is characterised by non-caseating granulomas * It most commonly affects the lungs (\>90% of cases) and lymphatic system, but can affect any organ. * When it affects the lungs, we refer to it as an ***interstitial lung disease.*** * Many cases are asymptomatic, although some patients can have very severe disease. * Sometimes they give the appearance of [TB](https://almostadoctor.co.uk/encyclopedia/tb-tuberculosis) on chest x-ray.

Answer 38

**Epidemiology:** * Usually affects young people (ages 20-40 years) * More common in women * African-Caribbeans are affected more frequently and more severely than Caucasians - particularly by extra-thoracic disease * First degree relatives have an increased risk of developing sarcoidosis * (particularly in Caucasians) * Lungs are most commonly affected, followed by eyes and skin. * The liver is also often affected, but this is rarely clinically significant * Rarely it an affect the heart and nervous system * Between 10-30% of patients will have a chronic or progressive disease course. The rest will typically resolve spontaneously, although this can take several year

Answer 39

**Pathology:** * A granuloma is a collection of WBC’s (mononuclear cells and macrophages) , surrounded by lymphocytes, plasma cells, mast cells, fibroblasts, and *collagen.* They can occur in any organ, but in sarcoidosis most commonly occur in the lung and lymphatics. * *In the lung they tend to be distributed along the line of lymph nodes –* Hence the association of sarcoidosis and hilar [CXR](https://almostadoctor.co.uk/encyclopedia/chest-x-ray) changes **Clinical presentation:** * Many patients are asymptomatic -Up to 50%! * Acute sarcoidosis: erythema nodosum (red lumps form on the shins and less commonly thighs and forearm), bilateral hilar lymphadenopathy, swinging fever, polyarthralgia * Insidious symptoms: * Dry cough * Dyspnoea (usually progressive) * Malaise * Weight loss * Chest pain

Answer 40

Signs: * A restrictive pattern may be seen on spirometry * Bilateral hilar Lymphadenopathy * Crackles on auscultation * Erythema nodsoum * Sarcoidosis is often a differential for a patient with lots of non-specific signs! Other Features: * Hepatomegaly * Splenomegaly * Bell’s palsy * Eyes: uveitis, conjunctivitis and cataracts. * skin: lupus pernio - blueish-red/purple nodules and plaques over nose, cheek and ears * hypercalcaemia: macrophages inside the granulomas cause an increased conversion of vitamin D to its active form (1,25-dihydroxycholecalciferol) * Enlargement of lacrimal & parotid glands

Answer 41

**Syndromes associated with sarcoidosis** * Lofgren's syndrome is an acute form of the disease characterised by bilateral hilar lymphadenopathy (BHL), erythema nodosum, fever and polyarthralgia. It usually carries an excellent prognosis * In Mikulicz syndrome\* there is enlargement of the parotid and lacrimal glands due to sarcoidosis, tuberculosis or lymphoma * Heerfordt's syndrome (uveoparotid fever) there is parotid enlargement, fever and uveitis secondary to sarcoidosis

Answer 42

[![]()](https://d32xxyeh8kfs8k.cloudfront.net/images_Passmedicine/xrb119b.jpg)**Investigations:** * There is no one diagnostic test for sarcoidosis and hence diagnosis is still largely clinical. * Bloods: * FBC – may cause anaemia or raised WCC * ESR – often raised * U+E * Ca2+- raised in 10% of patients * LFTs – may be deranged * Raised immunoglobulins * Serum ACE (angiotensin converting enzyme) * Elevated in 60% of cases * Falls with treatment * Not routinely used for diagnosis or monitoring of treatment (lung function and CXR are better indicators) * CXR: * Often discovered incidentally on CXR. * The classical finding is ***hilar lymphadenopathy,*** * Other changes may include fibrosis and lung infiltrates * CXR is used to stage the disease * 90% of patients with sarcoidosis will show CXR change **STAGING** * stage 0 = normal * stage 1 = bilateral hilar lymphadenopathy (BHL) * stage 2 = BHL + interstitial infiltrates * stage 3 = diffuse interstitial infiltrates only without BHL * stage 4 = Progressive pulmonary fibrosis ± bulla (honeycombing on CXR) * Other investigations\* * spirometry: may show a restrictive defect * tissue biopsy: non-caseating granulomas (Suitable biopsy sites include lung and liver tissue, lymph nodes and lacrimal glands) * Broncheoaleolar lavage – can show increased lymphocytes and neutrophils CT/MRI – useful in some cases to assess the extent of pulmonary involvement * ECG - may show arrhythmias or bundle branch block * Hand X-ray – *sometimes shows* punched out *lesions in the peripheral phalanges*

Answer 43

**Management:** * Stage 0 and 1 – *usually resolve spontaneously* * Stage 2+ and acute disease – *may improve with NSAIDs and bed rest* * Patients with asymptomatic and stable stage 2 or 3 disease who have only mildly abnormal lung function **do not require treatment** * *prednisolone 40mg for 4-6 wks, then gradually decline dose over 1yr depending on symptoms.* * Indications for steroids * patients with chest x-ray stage 2 or 3 disease who are symptomatic. * hypercalcaemia * eye involvement – uveitis * cardiac involvement * neuro involvement * in severe illness give IV methylprednisolone * If steroid-resistant then: Methotrexate or Infliximab * Patients should also have regular ophthalmology assessment for eye manifestations of the disease as Sarcoidosis can cause optic neuritis which can cause blindness if untreated. **Prognosis:** * \<5% of patients with sarcoidosis will die as a result of complications of their disease * 20% of patients will have chronic or progressive disease – the rest will either resolve spontaneously or respond well to treatment * Those that do die of their complications typically develop severe pulmonary fibrosis, and may also develop pulmonary hypertension

Answer 44

**OCCUPATIONAL LUNG DISORDERS:** • Response to inhaling something at work • Can be; fumes, dust, gas or vapour causing: * Acute bronchitis and even oedema from irritants such as sulphur dioxide, chlorine, ammonia or the oxides of nitrogen * Pulmonary fibrosis from inhalation of inorganic dust e.g. coal, silica, asbestos, iron and tin * Occupational asthma - this is the commonest industrial lung disease in the developed world * Hypersensitivity pneumonitis * Bronchial carcinoma due to asbestos, polycyclic hydrocarbons and radon in mines * Pneumoconiosis - term used to describes a range of interstitial lung diseases caused by inhalation of mineral dusts, resulting in interstitial fibrosis * They are usually occupational diseases (but not always) * Examples include coal workers pneumoconiosis, silicosis, asbestosis * Where the process of pneumoconiosis occurs alongside rheumatoid arthritis, it is called ***CAPLAN’S SYNDROME.*** * Differentials: COPD, heart failure, cardiomyopathy * There is no treatment or cure.

Answer 45

* It is sometimes referred to as ‘black lung disease’, is an occupational lung disease caused by long term exposure to coal dust particles. * Pneumoconiosis = accumulation of dust in the lungs and the response of the bodily tissue to its presence, most commonly used in relation to coal worker’s pneumoconiosis. * It is most commonly experienced by those who have been involved in the coal mining industry and severity is linked to the extent of exposure. * Often there is a long lead time between the first exposure and the development of the disease. * Coal dust particles are ingested by alveolar macrophages in the small airways and alveoli which then die, releasing enzymes and causing fibrosis

Answer 46

Diagnosis is usually 15-20 years after initial exposure to the coal dust.

Answer 47

**Pathophysiology:** * Coal dust (2-5 μm in size) is inhaled and enters the lungs. * The dust reaches the terminal bronchioles and there it is engulfed by alveolar and interstitial macrophages. * The dust particles are then moved by the macrophages via the mucociliary elevator and removed from the body as mucus. * In coal miners who are exposed over many years, the system is overwhelmed and the macrophages begin to accumulate in the alveoli, which starts an immune response, causing damage to the lung tissue.

Answer 48

**Presentation:** Exposure to coal dust can lead to one of two presentations: _1.Simple pneumoconiosis:_ * Is the commonest type of pneumoconiosis. * Patients are often asymptomatic. * Produces fine micro nodular shadowing in the chest x-ray * Its presence increases the risk of lung diseases such as COPD. * Simple pneumoconiosis may lead to Progressive Massive Fibrosis (PMF), occurring in around 30% of those with stage 3 grading. Staging  * The disease is graded on the appearance of the chest X-ray using categories outlined by the International Labour Office: * Category 1: some opacities but normal lung markings visible * Category 2: large number of opacities but normal lung markings visible * Category 3: large number of opacities with normal lung not visible _2.Progressive Massive Fibrosis_ * Dust exposure causes patients to develop round fibrotic masses which can be several centimetres in diameter, with necrotic central cavities * These are most commonly in the upper lobes. * The exact pathogenesis is not known. * Patients are often symptomatic and have both breathlessness on exertion and cough, some may have black sputum. * Lung function testing shows a mixed obstructive/restrictive picture. * Rheumatoid factor and anti-nuclear antibodies are both often present in the serum of patients with PMF and also in those suffering from asbestosis or silicosis * There is apical destruction and disruption of the lung resulting in emphysema and airway damage

Answer 49

**Investigations:** * Chest x-ray: upper zone fibrosis * Spirometry: restrictive lung function tests - a normal or slightly reduced FEV1 and a reduced FVC **Management:** * Avoid exposure to coal dust and other respiratory irritants (e.g. Smoking). * Manage symptoms of chronic bronchitis * Patients may be eligible for compensation via the Industrial Injuries Act.

Answer 50

**SILICOSIS:** * Uncommon but seen in stonemasons, sand-blasters, pottery and * ceramic workers and foundry workers involved in fettling * Caused by the inhalation of silica particles (silica dioxide) which is very * fibrogenic * Silica is particularly toxic to alveolar macrophages and readily initiates fibrogenesis * CXR appearance show diffuse nodular pattern in upper and mid-zone and thin streaks of calcification (egg-shell calcification) of the hilar nodes * Spirometry shows a restrictive ventilatory defect * Patients have progressive dyspnoea and an increased incidence of TB * Manage by avoiding exposure to silica and claim compensation

Answer 51

* Type of Interstitial Lung Disease - distinct cellular infiltrates and extracellular matrix deposition in lung distal to the terminal bronchiole i.e. diseases of the alveolar/capillary interface * Fibrosis of the lungs caused by asbestos dust, which may or may not be associated with fibrosis of the parietal or visceral layers of the pleura * LOWER LOBE FIBROSIS * Progressive disease characterised by breathlessness and progressive dyspnoea and accompanied by finger clubbing and bilateral basal end-inspiratory crackles * Also causes pleural plaques and increases risk of mesothelioma and bronchial adenocarcinoma * The severity of asbestosis is related to the length of exposure. This is in contrast to mesothelioma where even very limited exposure can cause disease. * Only symptomatic management is known e.g. corticosteroids

Answer 52

* Malignant mesothelioma is STRONGLY ASSOCIATED with ASBESTOS EXPOSURE * Tumour of the mesothelial cells of the pleura * Other sites include the mesothelial cells of the peritoneum, pericardium and testes * Metastases to contralateral lung and peritoneum * Right lung affected more often than left **Epidemiology:** * Malignant mesothelioma is more common in men than women * Most often presents between 40-70 years * Exposure to asbestos is a well-established cause - but relationship is complex; only 20% of patients have pulmonary asbestosis * There is a latent period between exposure and development of the tumour may be up to 45 years

Answer 53

**Pathophysiology:** * It is a high grade malignancy of the pleura, that spreads around the pleura surfaces, but can also start in the pericardial space, peritoneal space and in the paratesticular space * Tumour begonia as nodules in the pleura which extend as a confluent sheet to surround the lung and extend into fissures * The chest wall is often invaded, with infiltration of intercostal nerves, giving severe intractable pain * Lymphatics may be invaded, giving hilar node metastases

Answer 54

**Clinical presentation:** * Dyspnoea, weight loss, chest wall pain * Clubbing * 30% present as painless pleural effusion * Only 20% have pre-existing asbestosis * History of asbestos exposure in 85-90%, latent period of 30-40 years * *Signs of metastases;* **Lymphadenopathy, hepatomegaly, bone pain/ tenderness, abdominal pain/obstruction**

Answer 55

**Investigations:** * suspicion is normally raised by a chest x-ray showing either **a pleural effusion** (unilateral) or **pleural thickening** * the next step is normally a **pleural CT** * if a pleural effusion is present fluid should be sent for MC&S, biochemistry and cytology (but cytology is only helpful in 20-30% of cases) – plueral fluid is usually bloody or straw coloured. * local anaesthetic thoracoscopy is increasingly used to investigate cytology negative exudative effusions as it has a high diagnostic yield (around 95%) * if an area of pleural nodularity is seen on CT then **an image-guided pleural biopsy** may be used **Management** * Symptomatic relief * Industrial compensation * Palliative Chemotherapy * Surgery if operable and extremely localised * Prognosis poor, median survival 8-12 months

Answer 56

The vast majority of these are primary, and related to smoking, however, you can also get lung secondaries from cancer of the: * Breast * Kidney * Uterus * Ovary * Testes * thyroid

Answer 57

**BRONCHIAL CARCINOMA** * **80% of tumours are in the lobar bronchi –** the rest are in larger bronchi. * It is initially classified histologically as being either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) * SCLC accounts for around 15% of cases and generally carries a worse prognosis. * NSCLC can be broken down into (more common to less common) * squamous * adenocarcinoma * large cell * alveolar cell carcinoma: not related to smoking, ++sputum * bronchial adenoma: mostly carcinoid

Answer 58

**Epidemiology:** * This is ***the most common cancer*** worldwide * 3x increase since 1950 * Increasing in women, particularly in northern Europe. **It now causes more deaths in women than any other malignant tumour** * the male to female ratio is 3:1 * It is the **third most common cause of death in the UK.** The first two are heart disease and CVD

Answer 59

**Aetiology/RF:** * **SMOKING! –** this is a huge risk factor – causes 90% of cases * Living in an urban, as opposed to a rural area * **Passive smoking** increases the risk 1.5x * Asbestos * Arsenic (in batteries and paints and fertilizer) * Iron oxide * Chromium * Petroleum products * Oil * Coal mining * Radiation * Radon * Scarring – e.g. post [TB](https://almostadoctor.co.uk/encyclopedia/tb-tuberculosis) * Pre-existing lung disease like pulmonary fibrosis * **Tumours associated with occupational factors tend to be adenocarcinomas.** Sites of metastatic spread from lung cancer: * Lymph nodes- supraclavical and mediastinal LNs affected * Liver - *anorexia, nausea, weight loss & right upper quadrant pain radiating across the abdomen* * Bone - *bony pain & pathological fractures occur as a result of tumour spread. Spinal cord compression can occur too (emergency!)* * Adrenal glands - *usually asymptomatic* Brain - *present as space-occupying lesions with signs of raised intercranial pressure, change in personality, epilepsy.*

Answer 60

_Squamous cell cancer_ * Tumours are typically central and **frequently cavitate** with **central necrosis** * Arise form epithelial cells, associated with production of keratin * Usually present as obstructive lesions of the bronchus leading to infection. * Occasionally cavitates (10% at presentation): * this will occur when the central part of the tumour undergoes necrosis. * On x-ray this may have the appearances of an abscess, or a TB cavity. * On CT, you will clearly be able to see the jagged edge of the cavity, * associated with parathyroid hormone-related protein (PTHrP) secretion → hypercalcaemia * strongly associated with finger clubbing * hypertrophic pulmonary osteoarthropathy (HPOA) * VERY STRONGLY ASSOCAITED WITH CIGARETTE SMOKING * Metastasize relatively late * Local spread is common

Answer 61

_Adenocarcinoma-_ MOST COMMON OVERALL * tumour is typically peripheral * Originate from mucus-secreting glandular cells in the bronchial epithelium * Does not usually cavitate * most common type of lung cancer in non-smokers, although the majority of patients who develop lung adenocarcinoma are smokers * Metastases common especially to; pleura, mediastinal lymph nodes, brain, bones, adrenal glands * Most likely to cause pleural effusion

Answer 62

_Large cell lung carcinoma_ * typically peripheral * they are essentially squamous cell or adenocarcinomas have a longer time to develop before presentation, they will present as large cell carcinomas. * anaplastic, poorly differentiated tumours with a poor prognosis * may secrete β-hCG * they metastasize early

Answer 63

* It is a variation of adenocarcinoma * they account for 1-2% of all lung carcinoma * they will present as a single nodule, or many small nodular lesions * occasionally they cause production of huge amounts of mucous (which will be coughed up as sputum) * may appear like consolidation on the CXR * Causes ‘bronchorrhoea’ – diarrhoea of the bronchus – produces huge amounts of white sputum!

Answer 64

Carcinoid tumours: * Usually associated with presentation at an earlier age (middle age) and have characteristic neuroendocrine secreting cells and relatively low rates of invasion and growth * However they are still malignant

Answer 65

Lymphomas: - Involve the lung primarily but are usually a component of disseminated disease - The main lung lymphoma is known as BALTOMA (Bronchus Associated Tissue Lymphoma) - it is a B cell lymphoma, and responds to standard chemotherapy regimes

Answer 66

SCC Adenocarcinoma LCLC Bronchoalveolar cell carcinoma Carcinoid tumours Lyphoma Benign tumour-Hamartomas:

Answer 67

Benign tumour: - Hamartomas: * Irregular proliferations of benign/normal tissues that are not normally found in this pattern within lung tissue * The commonest in the lung is that of the chondroid hamartoma which incorporates cartilage, glandular tissue, fat, fibrous tissue and blood vessels

Answer 68

Features: * usually central * arise from Arise from endocrine cells (**Kulchitsky cells**). These are APUD\* cells * associated with ectopic ADH, ACTH secretion * ADH → hyponatraemia (Addisonianism) * ACTH → Cushing's syndrome * ACTH secretion can cause bilateral adrenal hyperplasia, the high levels of cortisol can lead to hypokalaemic alkalosis * Lambert-Eaton syndrome: antibodies to voltage gated calcium channels causing myasthenic like syndrome * **Small cell carcinoma spreads very early and is almost always inoperable at presentation.** * These tumours do respond to **chemotherapy,** but the prognosis is generally poor. * You can also get primary small cell carcinoma in the oesophagus, stomach and cervix. \*an acronym for * Amine - high amine content * Precursor Uptake - high uptake of amine precursors Decarboxylase - high content of the enzyme decarboxylas

Answer 69

**Symptoms:** * persistent cough * haemoptysis * dyspnoea * chest pain * weight loss and anorexia * hoarseness * seen with Pancoast tumours pressing on the recurrent laryngeal nerve * superior vena cava syndrome- causing **early morning headache oedema of the upper limbs, facial congestion and distension of the jugular vein and veins on the chest** * recurrent chest infections e.g. pneumonia Signs: * a fixed, monophonic wheeze may be noted * supraclavicular lymphadenopathy or persistent cervical lymphadenopathy * clubbing * stridor - **tends to be present when there is an obstruction above the main carina.** * hoarseness of the voice * chest auscultation is usually normal unless tumour has spread ot large nronchial obstruction- also check axillary LN during examination looking for mets.

Answer 70

Pancoast tumour: It is a apical tumour which can affect the lower part of the brachial plexus – **C8, T1 and T2 –** and this will cause severe pain in the **shoulder and down the inner surface of the arm. (known as Pancoast syndrome)**

Answer 71

**Investigations:** * Chest x-ray: * this is often the first investigation done in patients with suspected lung cancer * Symptomatic tumours will usually be visible on x-ray * Asymptomatic tumours can be seen on x-ray if they are **greater than 1cm in diameter.** * **70% of lung cancers present with a mass:** * Virtually all small cell carcinomas and squamous cells will present as a visible mass * Adenocarcinomas, tend to occur more around the periphery of the lung than other tumours. * Look for: * Round shadow with jagged edge * Peripheral circular opacities * Hilar enlargement * Lung collapse * Consolidation * Pleural effusion * Bony secondaries * CT: * is the investigation of choice to investigate suspected lung cancer * Must do one with contrast and one without * Needed for staging too * Bronchoscopy * this allows a biopsy to be taken to obtain a histological diagnosis sometimes aided by endobronchial ultrasound * **Percutaneous aspiration and biopsy – CT guided biopsy** * This is useful for peripheral lesions that cannot be seen by bronchoscopy. * Chance of pneumothaox very high * PET scanning * is typically done in non-small cell lung cancer to establish eligibility for curative treatment * uses 18-fluorodeoxygenase which is preferentially taken up by neoplastic tissue * no need to do it if you don’t plan to operate * more accurate than CT for finding mets. So useful for staging * has been shown to improve diagnostic sensitivity of both local and distant metastasis spread in non-small cell lung cancer * Bloods: * FBC: raised platelets may be seen, look for anaemia * LFTS- check for liver involvement * U+Es- high Ca2+, low Na+ * Cytology: * Sputum and pleural fluid

Answer 72

**Staging:** * Non-small cell carcinoma is staged using the TNM system (see below). * Small cell is generally very [aggressive](https://almostadoctor.co.uk/encyclopedia/aggressive-behaviour), and is staged as either ***limited*** *or **extensive.*** * *TNM staging is used for non-small cell carcinoma****à**

Answer 73

**Non-small cell lung cancer:** * only 20% suitable for surgery * surgical excision for peripheral tumours with no mets * mediastinoscopy performed prior to surgery as CT does not always show mediastinal lymph node involvement * curative or palliative radiotherapy * poor response to chemotherapy Surgery contraindications * assess general health * stage IIIb or IV (i.e. metastases present) * FEV1 \< 1.5 litres is considered a general cut-off point\* * malignant pleural effusion * tumour near hilum * vocal cord paralysis * SVC obstruction \* However if FEV1 \< 1.5 for lobectomy or \< 2.0 for pneumonectomy then some authorities advocate further lung function tests as operations may still go ahead based on the results

Answer 74

**Small cell lung cancer:** * usually metastatic disease by time of diagnosis * patients with very early stage disease (T1-2a, N0, M0) are now considered for surgery. most patients with limited disease receive a combination of chemotherapy and radiotherapy * patients with more extensive disease are offered palliative chemotherapy à for superior vena cava obstruction Mx: * general: dexamethasone, balloon venoplasty, stenting * small cell: chemotherapy + radiotherapy * non-small cell: radiotherapy

Answer 75

**lung cancer referral:** * Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) for lung cancer if they: * have chest x-ray findings that suggest lung cancer * are aged 40 and over with unexplained haemoptysis * Offer an urgent chest x-ray (to be performed within 2 weeks) to assess for lung cancer in people aged 40 and over if they have 2 or more of the following unexplained symptoms, or if they have ever smoked and have 1 or more of the following unexplained symptoms: * cough * fatigue * shortness of breath * chest pain * weight loss * appetite loss * Consider an urgent chest x-ray (to be performed within 2 weeks) to assess for lung cancer in people aged 40 and over with any of the following: * persistent or recurrent chest infection * finger clubbing * supraclavicular lymphadenopathy or persistent cervical lymphadenopathy * chest signs consistent with lung cancer * thrombocytosis

Answer 76

**BRONCHIECTASIS** * Bronchiectasis describes a permanent dilatation of the bronchi and bronchioles secondary to chronic infection or inflammation. * Bronchial walls become inflamed, thickened and irreversibly damaged * The mucociliary transport mechanism is impaired and frequent bacterial infection ensue * It is an **obstructive lung disease.**

Answer 77

**Aetiology** * post-infective: **tuberculosis** (most common cause worldwide), **measles, pertussis**, pneumonia * **cystic fibrosis-** most common cause in developed countries * bronchial obstruction e.g. **lung cancer/foreign body** * immune deficiency: selective IgA, **hypogammaglobulinaemia** * **allergic bronchopulmonary aspergillosis (ABPA)-**immunological overresponse * ciliary dyskinetic syndromes: **Kartagener's syndrome** (primary ciliary dyskinesia), Young's syndrome * yellow nail syndrome * **Rheumatoid arthritis** * **Ulcerative colitis** * HIV

Answer 78

**Pathophysiology:** * There will be **destruction of the alveolar walls** (and the elastin contained in them), **with fibrosing of the remaining parenchyma.** * The [airway](https://almostadoctor.co.uk/encyclopedia/airway-management) will then dilate as the fibrosis surrounding scar tissue contracts. * This can in itself cause **secondary inflammatory changes** which leads to further destruction of the airways. * Usually the **lower lobes** are most greatly affected. * This can lead to **pooling of bronchial secretions,** which increases the risk of further infections in this area. There will often also be collections of pus. * **The mucociliary transport system is also damaged.** * Failure of mucociliary clearance and impaired immune function contribute to continued insult to bronchial wall, through the recruitment of inflammatory cells and uncontrolled neutrophilic inflammation**; *bronchitis* → *bronchiectasis* → *fibrosis***

Answer 79

**Presentation:** * Chronic cough * Production of large amounts of foul smelling sputum, which may also contain flecks of blood * The cough is usually worse in the mornings, and may be brought on by changes in posture * Finger clubbing may be present * **Recurrent RTI’s,** as the patient is unable to clear the pooled secretions that collect * **Fever and malaise –** as a result of recurrent (and perhaps ever-present) infection. * **Haemoptysis –** may just be flecks of the sputum, but in ‘dry bronchiectasis’ it may be the only symptom. * **Wheeze** * **In advanced disease, there is a general decline in health;** probably include; weight loss, [anorexia](https://almostadoctor.co.uk/encyclopedia/eating-disorders), low-grade fever, and failure to thrive (children). It is in these patients that clubbing is common – i.e. clubbing is late to show itself. **Signs:** May be unilateral or bilateral. * Usually affects lower lobes * Coarse crackles (numerous) over areas containing large amounts of sputum * Possible collapse (no breath sounds) * Reduced or absent breath sounds at areas distal to places of obstruction

Answer 80

**Differential diagnosis:** - COPD, asthma, TB, chronic sinusitis, cough due to acid reflux, pneumonia, pulmonary fibrosis, cancer, inhalation of foreign body

Answer 81

**Investigations:** * **Sputum culture! –** you may find **pseudomonas aeruginosa, H influenzae, staph aureus, aspergillus fumigates, fungi** (e.g. Aspergillus) and various **mycobacteria** * [CXR](https://almostadoctor.co.uk/encyclopedia/chest-x-ray) **–** In most cases, this will be normal, unless the bronchiectasis is widespread. In advanced disease you may be able to see areas of **dilated bronchi with thickened walls, cystic spaces/shadows, and consolidation or collapse.** * **High resolution CT –** much more sensitive than CXR, and shows thickened and dilated bronchi with cysts at the end of the bronchioles, and the classic signet ring appearance * **Spirometry- s**hows obstructive pattern * **Genotyping –** if the cause is a genetic disorder (CF) you may want to genotype(also if you don’t know the cause you could do this if you suspect CF) **– however this is a very poor predictor of prognosis.** For example, twins with the same genotype, may have a very different phenotype * **Sweat electrolyte testing –**if you suspect CF * **Bronchoscopy** to **locate site** of **haemoptysis, exclude obstruction** and **obtain culture samples** * **Immunology;** e.g. **t**otal IgE to exclude bronchopulmonary aspergillosis * **Sinus X-rays: 30%** of patients with **bronchiectasis** also have **rhino sinusitis** * **Measure mucociliary clearance –**you put a 1mm cube of **saccharin** on the inferior nasal concha and measure the time taken to taste it. This should be less than 30 minutes in a normal individual. If longer it could be a result of excess mucous production (CF)

Answer 82

**Management:** There is no cure L After assessing for treatable causes (e.g. immune deficiency) management is as follows: * physical training (e.g. inspiratory muscle training) - has a good evidence base for patients with non-cystic fibrosis bronchiectasis * postural drainage- Where **physio** tips patients so the **affected lobes** can **drain mucus**- done **3 times a day** for **10-20mins** * antibiotics for exacerbations + long-term rotating antibiotics in severe cases * Treatment of **exacerbations** usually lasts **2 weeks** * Initially, try a broad spectrum, such as **cefaclor** or **ciprofloxacin.** * If **pseudomonas aeruginosa** then **high dose** **oral ciprofloxacin or IV cephalosporin e.g. ceftazidime** * **Haemophilus influenzae** is **common** and responds to **oral amoxicillin, co-amoxiclav** or **doxycycline** - *some **multi-resistant species*** need **IV cephalosporin e.g. ceftazidime** * If **staphylococcus aureus** then give **flucloxacillin** * Bronchodilators e.g. salbutamol in selected cases * Immunisations * Anti-inflammatory agents e.g. long term azithromycin can reduce exacerbation frequency * surgery in selected cases (e.g. Localised disease or to control severe haemoptysis)

Answer 83

**Complications:** * Pneumonia * Abscess * **Empyema** * Pulmonary fibrosis * [**Cor pulmonale**](https://almostadoctor.co.uk/encyclopedia/heart-failure) * Metastatic abscesses e.g. in the brain– due to the continued presence of infection * Amyloid formation * Amyloid plaques are insoluble fibrous protein aggregates. Their accumulation can lead to **amyloidosis.** A protein as described as being amyloid if it has a slightly altered structure, making it insoluble. * Amyloidosis can occur in many organs, and the symptoms vary greatly from organ to organ * Massive haemoptysis – this can result from the high pressure found in arteries in the condition. Treatment for this would probably only consist of bed rest and antibiotics until the bleeding stops. Blood transfusion is given if required

Answer 84

**PLEURAL EFFUSION** * This is the **accumulation of fluid within the pleural space.** * *empyema* (collection of pus within the pleural cavity), *haemothorax* (collection of blood within the pleural cavity), *chylothorax* (lymph fluid caused by leakage of lymph from the thoracic duct as a result of trauma or infiltration by carcinoma) are different conditions. * Lungs are covered by a thin serous layer known as the visceral pleura * This is reflected on the chest wall and pericardium as the parietal pleura * The lung hila connect the visceral and parietal pleura * Functions of pleura: * Allows movement of the lung against the chest wall * Coupling system between lungs and chest wall * Clearing fluid from the pulmonary interstitium * There is normally a small amount of fluid in the pleural space, between the parietal and visceral pleura, which lubricates movement between them * The pleural fluid contains: - Proteins - mainly albumin, globulin & fibrinogen - Many mesothelial cells, monocytes & lymphocytes * Pleural fluid is produced and reabsorbed by the parietal pleura (via lymphatic stoma) * Reabsorption occurs mainly at the dependent areas of parietal pleura i.e. posteriorly and inferiorly - in these areas more lymphatic stoma are found * Drainage of fluid is achieved by the lymphatic pump - contractions of smooth muscles of lymphatic walls * N.B Parietal pleura is highly sensitive to pain

Answer 85

Transudate Exudate **In transudates, proteins have moved down their concentration gradient. In exudates, proteins have been moved against their concentration gradient.**

Answer 86

* Pleural effusions may be classified as being either a transudate or exudate according to the protein concentration. Transudate (\< 30g/L protein): * Pleural fluid protein is less than 30g/L since vessels are normal so only fluid is able to leak out and not protein * The fluid typically only contains mononuclear cells (such as macrophages and lymphocytes). * Occurs when the balance of hydrostatic forces in the chest favour the accumulation of pleural fluid – disturbance in oncotic pressure not inflammation * Due to high venous pressure: * heart failure (most common transudate cause) * Congestive pericarditis * Hypoproteinaemia: * Hypalbuminaemia * liver disease(cirrhosis) * nephrotic syndrome * hypothyroidism * Meigs' syndrome * Peritoneal dialysis

Answer 87

Exudate (\> 30g/L protein) * Pleural fluid protein is more than 30g/L since endothelial cells of vessels are more apart meaning fluid and protein is able to leak out * It will nearly always have water and dissolved solutes, and may also have white and red blood cells, as well as platelets. * Occurs due to the increased permeability and thus leakiness of pleural space and or capillaries usually as a result of inflammation, infection or malignancy * pneumonia (most common exudate cause), TB, subphrenic abscess * connective tissue disease: RA, SLE * neoplasia: lung cancer, mesothelioma, metastases * pancreatitis * pulmonary embolism * Dressler's syndrome * yellow nail syndrome

Answer 88

**Clinical features:** * Can be asymptomatic * Dyspnoea especially on exertion * Pleuritic chest pain * Cough * Loss of weight (malignancy) Signs: * Chest expansion reduced on side of effusion * In large effusion the trachea may be deviated away from effusion * If there is associated lung collapse the trachea will deviate towards the lesion * Stony dull percussion note on affected side * Diminished or absent breath sounds on affected side * Decreased tactile vocal fremitus (vibration of chest wall when speaking) * Loss of vocal resonance * There will be no additional unusual sound * These will generally only be present when the effusion is greater than 500ml

Answer 89

**Investigations:** * posterioranterior (PA) **X-ray (done in all patients):** * An effusion of less than 500ml is unlikely to cause anything other than blunting of the costophrenic recess. \>500ml will cause a clear fluid level * **An effusion of less than 300ml may not be seen on x-ray** * Remember to look for the meniscus – it is likely to be a very long curve, perhaps rising all the way to the axilla. * **If the fluid level appear perfectly horizontal, it is likely to due co-existing** [pneumothorax](https://almostadoctor.co.uk/encyclopedia/pneumothorax) * If the effusion is large enough, the whole of one lung field may appear opaque, and the mediastinum may be shifted to the opposite side * Fluid below the lung can **simulate a raised hemidiaphragm.** * **Ultrasound** is recommened- for guiding the aspiration, as well as for diagnosis. It sensitive for detecting pleural fluid septations. * **Diagnostic aspiration (aka pleural tap/ thoracentesis):** * as above, ultrasound is recommended to reduce the complication rate * a 21G needle and 50ml syringe should be used * fluid should be sent for pH, protein, lactate dehydrogenase (LDH), cytology and microbiology * Purulent in empyema (pus effusion) Turbid (cloudy/opaque) in infected effusion * Milky in chylothorax (lymph fluid effusion) * if aspiration inconclusive then consider parietal pleural biopsy

Answer 90

**Light's criteria** was developed in 1972 to help distinguish between a transudate and an exudate. The BTS recommend using the criteria for borderline cases: * exudates have a protein level of \>30 g/L, transudates have a protein level of \<30 g/L * if the protein level is between 25-35 g/L, Light's criteria should be applied. An exudate is likely if at least one of the following criteria are met: * pleural fluid protein divided by serum protein \>0.5 pleural fluid LDH divided by serum LDH \>0.6 * * pleural fluid LDH more than two-thirds the upper limits of normal serum LDH

Answer 91

**Pleural infection** * All patients with a pleural effusion in association with sepsis or a pneumonic illness require diagnostic pleural fluid sampling * if the fluid is purulent or turbid/cloudy a chest tube should be placed to allow drainage * if the fluid is clear but the **pH is less than 7.2 in patients with suspected pleural infection a chest tube should be placed**

Answer 92

**Management of recurrent pleural effusion** Options for managing patients with recurrent pleural effusions include: * Treat underlying cause * recurrent aspiration/drainage via chest drain or aspiration needle, either work * NOTE: BTS guidelines advises to avoid draining transudates!!! pleurodesis - An injection that causes the adhesion of the visceral and parietal pleura to help prevent reaccumulation of the effusion e.g. tetracycline or ta * lc * indwelling pleural catheter * drug management to alleviate symptoms e.g. opioids to relieve dyspnoea * *In Malignancy –* most cases will reccurr within a month, and so *pleurodesis talc* or *long-term in-dwelling chest drains* may be considered. *Pleurectomy* may be used in certain instances.

Answer 93

A pneumothorax is an abnormal collection of air ***in the pleural space –*** between the lung and the chest wall. It leads to partial or comThey can be: * **Primary –** no underlying lung disease. * **Secondary –** to underlying lung disease – such as [COPD](https://almostadoctor.co.uk/encyclopedia/copd) * They can also separately be classified as **spontaneous** or **traumatic.** * The majority of cases of spontaneous pneumothorax are minor and will self resolve. * In a small number of cases, a one way valve can form, allowing more and more air into the pleural space. – this is **tension pneumothorax**

Answer 94

* Generally a pneumothorax is MUCH MORE COMMON in MALES * Often patients are tall and thin * Both lungs are affected with equal frequency i.e. can occur in any lung right or left equally * In patients over 40 years of age the usual cause is underlying COPD

Answer 95

**Risk factors:** * pre-existing lung disease: COPD, asthma, cystic fibrosis, lung cancer, Pneumocystis pneumonia * connective tissue disease: Marfan's syndrome, rheumatoid arthritis * ventilation, including non-invasive ventilation * catamenial pneumothorax is the cause of 3-6% of spontaneous pneumothoraces occurring in menstruating women. It is thought to be caused by endometriosis within the thorax

Answer 96

**Primary Spontaneous Pneumothorax (PSP):** * Usually the result of rupture of a pleural bleb or subpleural bullae – the bleb is often from congenital defect in the tissue of the alveolar wall. * These blebs are more common in tall young men * Rare – incidence from 4 – 40 per 100,000 per year * More common in men – M:F is around 2.5:1 * Recurrence rate of 25-50% – usually recur within the first year * Patients typically in their 20’s – rare after age of 40 * Risk factors include * Smoking (including smoking cannabis) – ***about 90% of cases occur in smokers –*** smoking probably increases the risk by causing airway inflammation. The risk is proportional to the amount smoked * Family history – 25% of cases have an associated FHx * [Marfan Syndrome](https://almostadoctor.co.uk/encyclopedia/marfan-syndrome) * Homocystinurea * A tension pneumothorax occurs in about 1-2% of cases

Answer 97

**Secondary Pneumothorax** Causes include * COPD * Cystic fibrosis * Lung malignancy * Pneumonia * TB **Pathophysiology:** * Normally, the pressure in the pleural space is negative but this is lost once there is communication with atmospheric pressure i.e. a breach in pleura, the elastic recoil of the lung then causes it to deflate partially * If the communication between the airways and the pleural space remains open then a bronchopleural fistula results * Once the communication between the lung and the pleural space is closed, air will be reabsorbed slowly for example a 50% collapse of the lung will take around 40 days to reabsorb completely once the air leak is closed

Answer 98

**Presentation:** Symptoms tend to come on suddenly and develop at rest Symptoms often proportional to the size of the pneumothorax * Dyspnoea – typically on the side of the pneumothorax * chest pain: often pleuritic - typically on the side of the pneumothorax * sweating Signs: * Reduced breath sounds on affected size * Hyperresonance to percussion on affected side * Reduced expansion on affected side * tachypnoea * tachycardia * hypoxia (hypercapnia usually not present)

Answer 99

**Investigations:** * Often a clinical diagnosis. * if you suspect a tension pneumothorax DO NOT DO XRAY TREAT FIRST THERE IS NO TIME FOR XRAY!) * **CXR** (visible on both inspiratory and expiratory films): * Small pneumothraces: ppear as a ‘rim’ of air around the lung, no vascular lung markings. * Large pneumothoraces- clearly collapsed lung, and a large proportion of the hemithorax with no vascular margins. * If there is a mediastinal shift= TENSION PNEUMOTHORAX * **CT** indications: * Evidence of underlying lung disease on CXR * Uncertain diagnosis – e.g. a large bleb/emphysetmoutous bullae may mimic pneumothorax * Not routinely indicated * **Beside USS:** * not routine but may be used I acute settings like A+E. * shows absence of ‘lung sliding’ (at the interface of the lung and the pleura). * **Arterial Blood Gases (ABG):** * Hypoxia * Usually normal carbon dioxide – the lung function is still good and often the remaining normal lung can provide sufficient alveolar ventilation – but can be low * Respiratory alkalosis – can occur if there is sufficient hyperventilation to cause low carbon diaxoide. This hyperventilation can be due to a combination of hypoxia, anxiety and pain.

Answer 100

**Differential diagnosis:** * PE (may produce haemoptysis and a few rales over the affected area. It more commonly affects the lower rather than the upper lungs) * Pleural effusion (tends to be slower in onset and there is dullness on percussion) * Chest pain e.g. pleurodynia, Bornholm disease

Answer 101

**Complications:** Compression of the mediastinum = Decrease Cardiac Output (compressed heart), increase Heart Rate, jugular vein distension, ***cardiac arrest***

Answer 102

**Primary pneumothorax** * if the rim of air is \< 2cm and the patient is not short of breath then *consider observation for 4-6 hours and repeat CXR to ensure it is not progressing*. *Then; discharge on advice – dont do strenuous exercise – and return if breathless.* * *If rim of air \>2cm +SOB:* * Give supplemental oxygen for hypoxia * If acutely unwell (i.e. haemdynamically unstable), or tension pneumothorax: * Attempt aspiration – 2^ND INTERCOSTAL SPACE, MIDCLAVICULAR LINE! * If unsuccessful, repeat * If unsuccessful, consider [chest drain](https://almostadoctor.co.uk/encyclopedia/inserting-a-chest-drain) * Once successfully decompressed, will need a chest drain to allow continuing decompression

Answer 103

**Secondary pneumothorax** * if the patient is \> 50 years old and the rim of air is \> 2cm and/or the patient is short of breath then a chest drain should be inserted. * otherwise aspiration should be attempted if the rim of air is between 1-2cm. If aspiration fails (i.e. pneumothorax is still greater then 1cm) a chest drain should be inserted. All patients should be admitted for at least 24 hours * if the pneumothorax is less the 1cm give high flow oxygen and admit for 24 hours

Answer 104

**Iatrogenic pneumothorax** * less likelihood of recurrence than spontaneous pneumothorax * majority will resolve with observation, if treatment is required then aspiration should be used * ventilated patients need chest drains, as may some patients with COPD

Answer 105

**To prevent recurrence:** * pleurodesis- If there has been recurrence or the risk is considered high then prevention of further pneumothorax by obliterating the pleural space by pleurodesis should be considered * Surgery- Open thoracotomy and pleurectomy remains the procedure with the lowest recurrence rate

Answer 106

**Prognosis:** * While death from spontaneous pneumothorax is rare, rates of recurrence are high: 15.8% at one year for PSP and 31.2% at one year for SSP. * pneumothorax recurrence is more common in pregnancy and poses risks to the mother and fetus. * SSP is associated with a higher morbidity and mortality than PSP * Risk factors for the recurrence of PSP include **age, height and smoking** * Risk factors for recurrence of SSP include **age, pulmonary fibrosis and emphysema** * *It is recommended that patient avoid air travel for at least 2 weeks after resolution.* * regarding scuba diving, 'Diving should be permanently avoided unless the patient has undergone bilateral surgical pleurectomy and has normal lung function and chest CT scan postoperatively.'

Answer 107

* May occur following thoracic trauma when a lung parenchymal flap is created. * This acts as a one way valve and allows allowing air into the pleural space on inspiration, but not out again on expiration. * This causes a rapid increase in intra-thoracic pressure * Clinical features: * Pleuritic chest pain * Breathlessness * Tracheal deviation * Reduced breath sounds in the affected area and hyper-resonant on percussion

Answer 108

* CXR shows *the trachea may be **deviated _away_ from the side of the pneumothorax.*** Lung collapse likely to be more obvious. (AGAIN DO NOT DO CXR AS IT WASTES TIME- TREAT BEFORE IF YOU SUSPECT) Differentiating a simple pneumothorax from a tension pneumothorax A tension pneumothorax will have: * Worsening clinical signs and symptoms (simple will be stable) * Tracheal deviation * Haemodynamically ***un***stable * Hypotensive * Tachycardic * Elevated respiratory rate

Answer 109

* clinical situations where tension pneumothorax arises include: * Ventilated patients. * Trauma patients. * Resuscitation patients (CPR). * Lung disease, especially acute presentations of asthma and COPD. * Blocked, clamped or displaced chest drains. * Patients receiving non-invasive ventilation. * Patients undergoing hyperbaric oxygen treatment. Treatment: needle decompression (needle thoracostomy) at the **2nd intercostal space at the**

Answer 110

* Pulmonary hypertension (PH) is an increase in mean pulmonary arterial pressure (PAP);it is defined as an increase in mean PAP ≥25 mm Hg at rest as assessed by right heart catheterisation. * The lung circulation offers a low resistance to flow compared to the systemic circulation (about 90mmHg) * Normal mean pulmonary artery pressure (mPAP) is 14 +/- 3 mmHg with an upper limit of normal of 20mmHg

Answer 111

**Aetiology:** * Idiopathic * Drug or toxin induced * Associated with HIV infection, portal hypertension, Congenital heart disease, CREST syndrome, chronic haemolytic anaemia * Occurs due to an increase in pulmonary vascular resistance or an increase in pulmonary blood flow: * Pulmonary vascular disorders: * Pulmonary embolism * Primary pulmonary hypertension * Veno-occlusive disease * Diseases of lung and parenchyma: * COPD * Interstitial lung disease * MSK: * Kyphoscoliosis (abnormal curvature of spine) * Poliomyelitis * Myasthenia gravis (causes muscle weakness) * Disturbance of resp drive: * Obstructive sleep apnoea (where walls of throat relax during normal sleep resulting in normal breathing interruption) * Morbid obesity * Cerebrovascular disease * Cardiac: * Mitral stenosis (narrowing of mitral valve of heart) - Left ventricle failure * Left atrial myxoma (heart tumour) * Congenital heart disease

Answer 112

**Pathophysiology:** * Hypoxic vasoconstriction, inflammation, cell proliferation resulting in narrower vessels and increased right ventricular pressure caused pulmonary hypertension * Leads to the damage of the pulmonary endothelium resulting in the release of vasoconstrictors such as endothelin which in turn increases pulmonary vascular resistance (PVR) meaning the right ventricle must pump harder causing right ventricular hypertrophy * Increased platelet and leukocyte adhesion, elevated serotonin as well as other factor cause further vasoconstriction and remodelling further increasing PVR * Patients with progressive pulmonary hypertension develop right ventricular hypertrophy, dilatation and eventually failure resulting in death

Answer 113

**Clinical presentation:** * Exertional dyspnoea, lethargy and fatigue are the initial features due to an inability to increase cardiac output with exercise * Ankle swelling * Chest pain * Syncope (temporary loss of consciousness caused by a sudden drop in blood pressure) * As right ventricular failure develops there will be oedema & abdominal pain from hepatic congestion * Loud pulmonary second sound * Right parasternal heave caused by right ventricular hypertrophy * In advanced disease there are features of right heart failure (cor pulmonale): * Elevated jugular venous pressure * Prominent V wave if tricuspid regurgitation present • Hepatomegaly * Pulsatile liver * Peripheral oedema * Ascites * Pleural effusion **Differential diagnosis:** * Cor pulmonale – causing secondary PH * Cardiomyopathy * CHF * Portal hypertension * Pulmonary emboli

Answer 114

**Investigations:** * Right heart catheterisation is needed to confirm the diagnosis by directly measuring pulmonary pressure. * CXR: to exclude other lung diseases but this is not useful for diagnosing PH. May show *Enlarged heart, enlarged procimal pulmonary arteries which taper distally.* * ECG – can show *right ventricular hypertrophy and P pulmonale (tall and peaked P wave)* and strain patterns but may be normal. * Echocardiography: to assess right ventricular function and estimate pulmonary arterial pressures. *Will show RV dilatation and or hypertrophy.* * Bloods: LFTs (portal hypertension), TFTs and autoimmune screening - particularly antinuclear antibody to detect possible SLE/scleroderma-like syndrome. Other tests: * High-resolution CT of the thorax to investigate other possible causes of PH. * MRI: to assess cardiac structure and function, prognosis and response to treatment. * Pulmonary function tests. * Lung biopsy may be needed to exclude interstitial lung disease. * Polysomnography may be used to exclude obstructive sleep apnoea.

Answer 115

**Management:** * Treat underlying cause * Supplemental oxygen to help symptomatically * Diuretics (for peripheral oedema) and digoxin for Right sided heart failure * Oral calcium channel blockers for idiopathic PH * Oral endothelin receptor antagonist e.g. bosenten * Phosphodiesterase-5 inhibitors * Prostacyclin (mediators of vasoconstriction) analogues e.g. inhaled iloprost * Warfarin - due to intrapulmonary thrombosis * Pulmonary thrombo-arterectomy is sometimes considered for those with chronic thrombo-emboli. * Consider heart-lung transplant in young patients

Answer 116

**Complications:** * Right sided heart failure * Gross peripheral oedema * Hepatic congestion * Pleural effusion * Sudden cardiac death

Answer 117

**SINUSITIS:** * Infection of the mucous membranes of the paranasal sinuses that is bacterial or occasionally fungal * Aetiology: * Bacterial: * Streptococcus pneumoniae (40%) * Haemophilus influenzae (30-35%) * Rhinovirus * Most commonly associated with upper respiratory tract infection and occasionally asthma * Predisposing factors include: * nasal obstruction e.g. septal deviation or nasal polyps * recent local infection e.g. rhinitis or dental extraction * swimming/diving * smoking

Answer 118

* Clinical presentation: * facial pain: typically frontal pressure pain which is worse on bending forward * nasal discharge: usually thick and purulent * nasal obstruction * Diagnosis: * Bacterial sinusitis presents with unilateral pain and purulent discharge with or without fever for more than 10 days * Treatment: * Analgesia * Nasal decongestants such as xylometazoline or nasal saline – limited evidence though * NICE- intranasal corticosteroids may be considered if the symptoms have been present for more than 10 days * Antibiotics are generally not recommended unless severe - phenoxymethylpenicillin is first-line * If 'systemically very unwell, signs and symptoms of a more serious illness, or at high-risk of complications'- give co-amoxiclav * 'double-sickening' may sometimes be seen, where an initial viral sinusitis worsens due to secondary bacterial infection * Complications include; brain abscess, sinus vein thrombosis and orbital cellulitis

Answer 119

**Chronic rhinosinusitis** * Chronic rhinosinusitis affects up to 1 in 10 people. * It is generally defined as an inflammatory disorder of the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer. * Predisposing factors include: * atopy: hay fever, asthma * nasal obstruction e.g. Septal deviation or nasal polyps * recent local infection e.g. Rhinitis or dental extraction * swimming/diving * smoking * Features * facial pain: typically frontal pressure pain which is worse on bending forward * nasal discharge: usually clear if allergic or vasomotor. Thicker, purulent discharge suggests secondary infection * nasal obstruction: e.g. 'mouth breathing' * post-nasal drip: may produce chronic cough * Management of recurrent or chronic sinusitis * avoid allergen * intranasal corticosteroids * nasal irrigation with saline solution * Red flags symptoms * unilateral symptoms * persistent symptoms despite compliance with 3 months of treatment * epistaxis

Answer 120

Centor criteria Fever Pain score

Answer 121

**Tonsillectomy:** NICE recommend that surgery should be considered only if the person meets all of the following criteria * sore throats are due to tonsillitis (i.e. not recurrent upper respiratory tract infections) * the person has five or more episodes of sore throat per year * symptoms have been occurring for at least a year * the episodes of sore throat are disabling and prevent normal functioning Other established indications for a tonsillectomy include * recurrent febrile convulsions secondary to episodes of tonsillitis * obstructive sleep apnoea, stridor or dysphagia secondary to enlarged tonsils * peritonsillar abscess (quinsy) if unresponsive to standard treatment Complications of tonsillectomy * primary (\< 24 hours): haemorrhage in 2-3% (most commonly due to inadequate haemostasis), pain * secondary (24 hours to 10 days): haemorrhage (most commonly due to infection), pain * A peritonsillar abscess typically develops as a complication of bacterial tonsillitis. Features include: * severe throat pain, which lateralises to one side * deviation of the uvula to the unaffected side * trismus (difficulty opening the mouth) * reduced neck mobility Management * Patients need urgent review by an ENT specialist. * needle aspiration or incision & drainage + intravenous antibiotics * tonsillectomy should be considered to prevent recurrence

Answer 122

* Defined as inflammation of the lung tissue An acute lower respiratory tract infection Usually caused by bacteria but can also be caused by viruses and fungi * Usually due to infection affecting distal airways and alveoli with the formation of an inflammatory exudate * *Pneumonia is the most fatal hospital acquired infection*

Answer 123

**Risk factors/precipitating factors:** * Hospitalisation! – hospital acquired infection is often with Gram-negative organisms * **Cigarette smoking –** this is the most important risk factor for pneumococcal disease * Old age (over 65) * [Alcohol](https://almostadoctor.co.uk/encyclopedia/alcohol-and-alcohol-abuse) excess * Co-morbidities: * Bronchiectasis (e.g. in [CF](https://almostadoctor.co.uk/encyclopedia/cystic-fibrosis-cf)) * Bronchial obstruction (e.g. carcinoma) * COPD * HIV infection * Diabetes mellitus * Immunosuppression * IV drug use * [Dysphagia](https://almostadoctor.co.uk/encyclopedia/dysphagia) (both oesophageal and co-ordination disorders – leading to aspiration)

Answer 124

Classification: * by anatomical location: * if one particular lobe is affected, then it is localised/lobar pneumonia * it can be a more diffuse pneumonia, affecting the lobules and bronchioles; in which case it is called **bronchopneumonia.** * according to their aetiology: * pneumococcal * atypical (e.g. caused by [Chlamydia](https://almostadoctor.co.uk/encyclopedia/chlamydia), legionella, coxiella burnetti). * 75% of cases are pneumococcal in cause, and 20% atypical. * The remaining 5% may be caused by aspiration of vomit, radiotherapy and [allergic](https://almostadoctor.co.uk/encyclopedia/allergy) mechanisms. * ***the most useful distinction is between community acquired and hospital acquired pneumonias.*** The difference between the two is in the causatory organism.

Answer 125

**Aspiration pneumonia:** * It is a pneumonia that develops as a result of foreign materials gaining entry to the bronchial tree, usually oral or gastric contents such as food and saliva. * Acute aspiration of gastric contents into the lungs can produce an extremely severe and sometimes fatal illness owing to the intense destructiveness of gastric acid * Seen in those with stroke, MS, myasthenia gravis, bulbar palsies and lack of consciousness/intoxication. * Can also be iatrogenic i.e. intubation * Risk factors for development of aspiration pneumonia: * Poor dental hygiene * Swallowing difficulties * Prolonged hospitalization or surgical procedures * Impaired consciousness * Impaired mucociliary clearance

Answer 126

* The right middle and lower lung lobes are the most common sites affected, due to the larger calibre and more vertical orientation of the right main bronchus. * The bacteria often implicated in aspiration pneumonia are **aerobic,** and often include: * *Streptococcus pneumoniae* * *Staphylococcus aureus* * *Haemophilus influenzae* * *Pseudomonas aeruginosa* * It can complicate anaesthesia, particularly during pregnancy (Mendelson syndrome)

Answer 127

Features of Klebsiella pneumonia: * more common in alcoholic and diabetics * may occur following aspiration * 'red-currant jelly' sputum * often affects upper lobes * commonly causes lung abscess formation and empyema

Answer 128

**Presentation:** Symptoms * Cough * Can be dry or productive * Usually dry in atypical causes * sputum * dyspnoea * chest pain: * may be pleuritic. * **Pleuritic chest pain –** a sharp shooting or stabbing pain, usually in the side, that is most painful on inspiration, but can also be felt on expiration, or even whilst talking. * may on occasion radiate to the shoulder (if diaphragm is involved) or the anterior abdominal wall * fever * Rigors * Vomiting * Loss of appetite * Headache * Very occasionally – haemoptysis Signs * signs of systemic inflammatory response: fever, tachycardia * tachypnoea * reduced oxygen saturations * auscultation (shows signs of consolidation): reduced breath sounds, bronchial breathing, decreased air entry, dull to percussion * in strep pneumonia; pleural rub, rapid shallow breathing * confusion (may be the only sign in elderly patients)

Answer 129

**Differentials:** * Pulmonary embolism (PE) – patient is not usually systemically unwell. Shortness of breath is more likely to be sudden onset. * Pulmonary / pleural TB * Pulmonary oedema * Lung cancer

Answer 130

Primary care -CRB65 Secondary care- CURB65

Answer 131

**Investigations:** **Pulse oximetry** chest x-ray: * *Evidence of infiltrate in the form of consolidation* on the x-ray *– can also show the spread of any infection by distribution of the infiltrate* * *Changes may not appear on x-ray for up to 48 hours after symptoms, however, after effective treatmnet, consolidation may still be seen on x-ray for up to 6 weeks* * Radiological abnormalities can lag behind clinical signs * ‘air bronchogram’ in consolidated area * Multi-lobar is suggestive of S.pneumoniae, S.aureus & Legionella spp. * Multiple abscesses is suggestive of S.aureus * Upper lobe cavity is then Klebsiella pneumoniae but MUST EXCLUDE TB FIRST! * *Persistent x-ray changes may suggest underlying carcinoma with secondary pneumonia* * *X-ray should be repeated at least weekly as an inpatient, and then at 6 weeks follow-up. Any signs still present indicate the need for a further x-ray.* *Blood tests ( FBC, U+E, LFT, ESR, CRP):* * Results may show: * ↑WCC * ↑ESR (\>100mm/h) and ↑CRP * Possible [anaemia](https://almostadoctor.co.uk/encyclopedia/summary-of-anaemias) (sign of abscess) * CRP monitoring is recommend for admitted patients to help determine response to treatment * Poor renal function = severe infection Blood and sputum cultures * Only in intermediate or high-risk patients pneumococcal and legionella urinary antigen tests * only in intermediate or high-risk patients

Answer 132

**Management:** * Maintain O2 sats between 94-98% (provided the patient is not at risk of CO2 retention, due to loss of hypoxic drive in COPD) * In patients with COPD saturations should be maintained between 88-92% * Analgesia such as paracetamol or NSAID can help with pleuritic pain low-severity community acquired pneumonia ( CURB-65 0-1) * PO amoxicillin is first-line * if penicillin allergic then use a PO doxycycline or erythromycin (in pregnancy) * Abx for 5 days moderate and high-severity community acquired pneumonia (CURB-65 2) * dual antibiotic therapy is recommended with PO amoxicillin and PO clarithromycin or erythromycin * if penicillin allergy – PO Doxycycline or Clarithromycin * a 7-10 day course is recommended High-severity community acquired pneumonia * IV co-amoxiclav and PO clarithromycin or erythromycin (in pregnancy) * If penicillin allergy- PO/IV levofloxacin **If legionella pneumophila** * 1st line: PO/IV Levofloxacin or Clarithromycin * 2nd line: PO Azithromycin If MRSA: First line: IV vancomycin If PVL- staph aureus: * IV linezolid or IV rifampicin If pseudomonas aeruginosa: * IV ceftazidime

Answer 133

**Discharge criteria and advice post-discharge** NICE recommend that patients are not routinely discharged if in the past 24 hours they have had 2 or more of the following findings: * temperature higher than 37.5°C * respiratory rate 24 breaths per minute or more * heart rate over 100 beats per minute * systolic blood pressure 90 mmHg or less * oxygen saturation under 90% on room air * abnormal mental status * inability to eat without assistance. They also recommend delaying discharge if the temperature is higher than 37.5°C. NICE recommend that the following information is given to patients with pneumonia in terms of how quickly their symptoms should symptoms should resolve:

Answer 134

**Prevention:** * Polysaccharide Pneumococcal Vaccine (protects against 23 serotypes) * Influenza vaccine to those who are older than 65 years, * immunocompromised or with medical co-morbidities * Smoking cessation

Answer 135

**Complications:** Immediate: * Respiratory failure (Type 1) * Treat with high flow O2 (be careful in those with COPD though) * Hypotension- as a result of dehydration, and vasodilation due to [sepsis](https://almostadoctor.co.uk/encyclopedia/sepsis-and-sirs). Medium term (days): * Pleural effusion * Empyema * Features: * Ongoing fever * Pain on deep inspiration * Failure of fever and markers of inflammation to settle on abx * Signs of pleural effusion may be present (***decreased chest expansion, dullness, reduced breath sounds, pleural rub –*** *all on affected side.* * Do fluid aspiration – the fluid is usually yellow, with a pH \<7.2, and low levels of glucose. * CXR indicates pleural effusion * treatment is with the insertion of a [chest drain](https://almostadoctor.co.uk/encyclopedia/inserting-a-chest-drain) with radiological guidance and Abx (IV cefuroxime and co-amoxilac for 5 days. Then 3-5 weeks of metronidozle * Pneumothorax – esp. with Staph aureus * Pulmonary embolism Late complications (days to weeks): * **Lung abscess** * Is a serious complication- it is a *cavitating lesion* containing pus, within the lung. * Commonly results from aspiration, bronchial obstruction, e.g. – *bronchial carcinoma or the* pneumonia was not adequately treated. * S*taph aureus* and *klebsiella pneumoniae* are more likely to cause this. * In some instances, *septic emboli,* particularly in the case of staphylococci, can result in multiple lung abscesses. * Presentation: * pneumonia that worsens despite treatment, with the production of purulent sputum, as a result of the growth of smelly anaerobic organisms. * Fever*, malaise, anaemia and weight loss.* * Clubbing can occur if the abscess has been present for long enough. * Investigations * X-ray – *a walled cavity is visible, usually with a fluid level.* * Bloods – FBC for anaemia and neutrophilia * ESR + CRP – will be raised * Sputum sample – microscopy to identify organism * Bronchoscopy – sometimes performed to get samples * Treatment * Treat the infection as per antibiotic sensitivities for 4-6 weeks * Consider postural drainage to remove excess sputum * In serious cases, antibiotic instillation / aspiration, and sometimes even surgical excision may be required * ARDS * Sepsis with multiorgan failure * Hepatitis, Pericarditis, Myocarditis and meningitis are seen most commonly in mycoplasma pneumoniae infection, which is most prevalent in young adults.

Answer 136

* It is a cause of atypical pneumonia which often affects younger patients. * It is associated with a number of characteristic complications such as erythema multiforme and cold autoimmune haemolytic anaemia. * Epidemics of Mycoplasma pneumoniae classically occur every 4 years. * It is important to recognise atypical pneumonia as it may not respond to penicillins or cephalosporins due to it lacking a peptidoglycan cell wall. * Features * the disease typically has a prolonged and gradual onset * flu-like symptoms classically precede a dry cough * bilateral consolidation on x-ray * Complications * cold agglutins (IgM): may cause an haemolytic anaemia, thrombocytopenia * erythema multiforme, erythema nodosum * meningoencephalitis, Guillain-Barre syndrome and other immune-mediated neurological diseases * bullous myringitis: painful vesicles on the tympanic membrane * pericarditis/myocarditis * gastrointestinal: hepatitis, pancreatitis * renal: acute glomerulonephritis * Investigations * diagnosis is generally by Mycoplasma serology * positive cold agglutination test * Management * doxycycline or a macrolide (e.g. erythromycin/clarithromycin)

Answer 137

*Pneumocystis jiroveci* pneumonia (HIV related) * Whilst the organism *Pneumocystis carinii* is now referred to as *Pneumocystis jiroveci*, the term *Pneumocystis carinii* pneumonia (PCP) is still in common use (lol diff places say diff things so here ya go the reason ) * *Pneumocystis jiroveci* is an unicellular eukaryote, generally classified as a fungus but some authorities consider it a protozoa * PCP is the most common opportunistic infection in AIDS * all patients with a CD4 count \< 200/mm³ should receive PCP prophylaxis * Features * dyspnoea * dry cough * fever * very few chest signs * Pneumothorax is a common complication of PCP. * Extrapulmonary manifestations are rare (1-2% of cases), may cause * hepatosplenomegaly * lymphadenopathy * choroid lesions * Investigation * CXR: typically shows bilateral interstitial pulmonary infiltrates but can present with other x-ray findings e.g. lobar consolidation. May be normal * exercise-induced desaturation * sputum often fails to show PCP, bronchoalveolar lavage (BAL) often needed to demonstrate PCP (silver stain shows characteristic cysts) * Management * PO/IV co-trimoxazole * IV pentamidine in severe cases * aerosolized pentamidine is an alternative treatment for *Pneumocystis jiroveci* pneumonia but is less effective with a risk of pneumothorax * steroids if hypoxic (if pO2 \< 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)

Answer 138

**TUBERCULOSIS –** NOTIFIBALE DISEASE * Tuberculosis (TB) is a chronic infectious disease, caused by *Mycobacterium tuberculosis (MTB)* of which there are three types that infect humans: * *M. tuberculosis –* by far the most common type * *M. bovis* (bovine TB)- where milk is unpasteurised * *M.* *africanum* * Infectious patients cough up large quantities of mycobacterium which can remain in the environment for a long period of time. * MTB is: * Aerobic, non-motile, non-sporing, slightly curved rods/bacilli with a * thick waxy capsule * Acid-fast bacilli (resist decolorisation) - go red/pink with Ziehl-neelsen stain * Only stained weakly with Gram stain due to high lipid content in their cell wall * Slow growing - generation time is 15-20 hours * Resistant to phagolysosomal killing by macrophage, hence granulomata * Able to remain dormant

Answer 139

* Tuberculosis is present in about 30% of the global population, but in developed countries it is rare since the advent of TB inoculation. * Majority of cases are seen in Africa and Asia (India and China) * Leading cause of death due to a curable [infectious disease](https://almostadoctor.co.uk/browse/infectious-diseases) * Significant number cases occur in those co-infected with [HIV](https://almostadoctor.co.uk/encyclopedia/hiv-and-hiv-counselling) * TB is though to be responsible for the deaths of 20% of patients with HIV * Around 10% of cases are drug resistant

Answer 140

**Transmission** * Via droplet spread – *only the pulmonary form is infectious* Usually needs sustained close contact with an infectious case. * Patients with active TB will infect on average 10-15 people per year * It is thought that most cases of active TB occurs many years after the initial infection was contracted * **NOT ALL INFECTED** actually **develop ACTIVE DISEASE**

Answer 141

**Risk factors:** * HIV (13% cases also have HIV) * Overcrowding/close contact with active case (1/3 chance of contracting from household member) * Ethnic minority groups/ origination from a high incidence country e.g. sub saharan Africa * Malnutrition * IV drug use * Homelessness * Chronic lung disease * Immunosuppression

Answer 142

**Pathophysiology:** **Primary tuberculosis** * A non-immune host who is first exposed to M. tuberculosis may develop primary infection of the lungs. * Once **inhaled** into the **lung**, **alveolar macrophages ingest** the **bacteria** * The **bacilli/rods** then **proliferate inside** the macrophages and cause the **release** of **neutrophil chemoattractants** and **cytokines**, resulting in an **inflammatory cell infiltrate** reaching the lung and **draining hilar lymph nodes** * **Macrophages present** the **antigen** to the **T lymphocytes** with the **development** of a **cellular immune response** * A **delayed hypersensitivity-type reaction (TYPE 4 reaction) occurs**, resulting in **tissue necrosis** and formation of a **granuloma** * **Granulomatous lesions** consist of a **central area** of **necrotic material** caused **caseation**, surround by **epithelioid cells** and **Langhans giant cells** with **multiple nuclei** - **both cells** being **derived** from the **macrophage** * **Lymphocytes** are present and there is a varying degree of **fibrosis** * The **initial granuloma** that forms is called the **Primary Ghon Focus** composed of tubercle-laden macrophages. * The **Ghon focus** is seen on **CXR (picture)**as a **small calcified nodule** often in the **upper parts** of the **lower lobes** or the **lower parts** of the **upper lobes** in the midzone - happens where **bacilli settle** * Primary lesion can **also** occur in the **GI tract**, particularly in the **ileocaecal region** * **Bacilli** can be taken to the **lymph nodes (mediastinal** and **hilar**, **paratracheal** and **subclavicular)** and **secondary lesions** can **develop here** * The **primary Ghon focus** and **caseous lesions** in the **lymph nodes** are called the **Ghon Complex** * In immunocpmpetent people, the **caveated areas heal completely** and may become **calcified** * Some of these **calcified nodules** contain **bacteria**, which are **contained** by the **immune system** and the **hypoxic acidic environment** created **within** the **granuloma** - these **bacteria** are capable of **lying DORMANT** for **many years** * If the **bacteria cannot** be **contained** and there is **dissemination** of the **primary infection** this can lead to **miliary tuberculosis** whereby **TB spreads to other organs** * Upon **initial contact** with infection, **less than 5%** of patients develop **active disease** * This percentage **increases** to **10%** within the **first year** of **exposure** * Those who are immunocompromised may develop disseminated disease (miliary tuberculosis).

Answer 143

**Presentation:** * *90% of cases exhibit pulmonary features only* * *10% exhibit extrapulmonary features* General Symptoms: * Weight loss * Low grade fever * Anorexia * Night sweats * Malaise Pulmonary TB: * Productive cough * Occasional haemoptysis * Chest pain: may be pleuritic if pleural involvement * Dyspnoea * Hoarse voice (if laryngeal involvement)

Answer 144

**Secondary (post-primary) tuberculosis –** Majority of cases are this. * If the host becomes immunocompromised the initial infection may become reactivated. * Reactivation generally occurs in the apex of the lungs and may spread locally or to more distant sites. * Possible causes of immunocomprise or depression of immune system include: * immunosuppressive drugs including steroids * HIV * Malnutrition * Severe infection * The lungs remain the most common site for secondary tuberculosis. Extra-pulmonary infection may occur in the following areas: * central nervous system (tuberculous meningitis - the most serious complication) * vertebral bodies (Pott's disease) * cervical lymph nodes (scrofuloderma) * renal * gastrointestinal tract (GI TB) * Miliary TB – widespread systemic TB * Note extrapulmonary infection is much more common in post-primary TB than primary TB

Answer 145

**Latent tuberculosis:** This is when the immune system contains the infection and the patient develops cell-mediated immunity memory to the bacteria

Answer 146

Extrapulmonary TB: * GU TB (most common site outside the lungs) - sterile pyuria m * LN TB – Lymphadenopathy +/- discharging sinuses * Bone TB – Pain, swelling of joint, arthritis, abscess formation * GI TB – Ascites (due to peritonela spread), ileocaecal lesions (abdominal pain, bloating, obstruction and simulating appendicitis) * Skin TB- erythema nodosum, skin sinus formation ('scrofuloderma'), erythema induratum. * CNS TB – tuberculous meningitis and tuberculomas ( eadache, vomiting, altered behaviour) followed by diminished consciousness ± focal neurological signs. * Pericardial TB - signs of pericardial effusion (pulsus paradoxus, elevated JVP) or constrictive pericarditis.

Answer 147

* Lung cancer * Pneumonia * Lymphoma * Fibrotic lung diseases (e.g. sarcoidosis, pneumoconiosis) * Its important to consider TB in any chronic illness with weight loss and fever

Answer 148

**Complications:** Multi-drug resistant TB (MDR-TB)- can develop of TB is not properly treated.

Answer 149

**Screening for latent tuberculosis** * The Mantoux test (tuberculin skin test) is the main technique used to screen for latent tuberculosis: * purified protein derivative (PPD) injected intradermally * result read 2-3 days later * Stimulates type 4 hypersensitivity reaction * If positive then indicates immunity and thus contact with TB * Won’t easily distinguish infection from disease * the interferon-gamma assay/blood test is used in a number of specific situations such as: * the Mantoux test is positive or equivocal * people where a tuberculin test may be falsely negative which maybe due to: * miliary TB * sarcoidosis * HIV * lymphoma * very young age (e.g. \< 6 months) * IGRAs use antigens specific to M. tuberculosis to distinguish between this and BCG vaccine or environmental mycobacteria * IGRAs demonstrate exposure to M.tuberculosis but NOT ACTIVE INFECTION

Answer 150

**Diagnosis of active tuberculosis:** Chest x-ray * upper lobe cavitation is the classical finding of reactivated TB * bilateral hilar lymphadenopathy * consolidation * Patchy nodal shadows in the upper zones * Milliary TB – multiple 1-10mm nodules throughout the lungs * It may be difficult to distinguish active from latent TB on CXR alone Sputum smear * 3 specimens are needed * rapid and inexpensive test * stained for the presence of acid-fast bacilli (Ziehl-Neelsen stain) * all mycobacteria will stain red meaning positive (i.e. nontuberculous mycobacteria) * the sensitivity is between 50-80% * this is decreased in individuals with HIV to around 20-30% * _use_ _broncoscopy and lavage or gastric washings if no sputum avialble_ Sputum culture * the gold standard investigation * culture on Lowenstein-Jensen slopes or Middlebrook agar * more sensitive than a sputum smear and nucleic acid amplification tests * can assess drug sensitivities * can take 1-3 weeks (if using liquid media, longer if solid media) Nucleic acid amplification tests (NAAT) * allows rapid diagnosis (within 24-48 hours) * more sensitive than smear but less sensitive than culture * Useful in differentiating between tuberculosis mycobacteria and non- * tuberculosis mycobacteria On histology: * Hallmark is the presence of caseating granulomata Lumbar puncture & CSF examination: * In all cases of Miiary TB, due to high rate of spread to meninges

Answer 151

* Contact tracing- Offer latent TB testing to household contacts to close work and school contacts to patients who have been diagnosed with active TB * Patients with TB require 6 MONTHS of treatment - First 2 months all 4 drugs, and last 4 months just rifampicin and isoniazid * The treatment for **latent tuberculosis** is 3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine) * Patients with **meningeal tuberculosis** are treated for a prolonged period (at least 12 months) with the addition of steroids * MDR-TB should be treated with at least four effective antibiotics for 18 to 24 months is recommended. * Compliance is critical to reduce relapse and resistance * To aid compliance there are special clinics called **DOT (Direct Observed Therapy)** where they give medication under supervision 3 times a week. * DOT usually given to: * homeless people with active tuberculosis * patients who are likely to have poor concordance * all prisoners with active or latent tuberculosis

Answer 152

Prevention: Active case finding to reduce infectivity i.e. TB testing of patients contacts BCG vaccine: - In the UK it is given to high-risk infants. - The vaccine contains live attenuated Mycobacterium bovis. It also offers limited protection against leprosy. - Until 2005 it was also routinely given to children at the age of 13 years. - the vaccine is administered to the following groups (greenbook summary): § all infants (aged 0 to 12 months) living in areas of the UK where the annual incidence of TB is 40/100,000 or greater § all infants (aged 0 to 12 months) with a parent or grandparent who was born in a country where the annual incidence of TB is 40/100,000 or greater. The same applies to older children but if they are 6 years old or older they require a tuberculin skin test first § previously unvaccinated tuberculin-negative contacts of cases of respiratory TB § previously unvaccinated, tuberculin-negative new entrants under 16 years of age who were born in or who have lived for a prolonged period (at least three months) in a country with an annual TB incidence of 40/100,000 or greater § healthcare workers § prison staff § staff of care home for the elderly § those who work with homeless people - any person being considered for the BCG vaccine must first be given a tuberculin skin test. The only exceptions are children \< 6 years old who have had no contact with tuberculosis - given intradermally, normally to the lateral aspect of the left upper arm - BCG can be given at the same time as other live vaccines, but if not administered simultaneously there should be a 4 week interval - The BCG vaccine is not given to anyone over the age of 35, as there is no evidence that it works for people of this age group. - Contraindications: o previous BCG vaccination o a past history of tuberculosis o HIV o pregnancy o positive tuberculin test (Heaf or Mantoux)

Answer 153

**ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)** * is essentially acute lung inflammation as a result of [sepsis](https://almostadoctor.co.uk/encyclopedia/sepsis-and-sirs), pneumonia, (these two causes account for 60% of cases), trauma or aspiration. * It is caused by the increased permeability of alveolar capillaries leading to fluid accumulation in the alveoli, i.e. non-cardiogenic pulmonary oedema. It is a serious condition that has a mortality of around 40% and is associated with significant morbidity in those who survive

Answer 154

Indirect: * infection: sepsis, pneumonia * massive blood transfusion * systemic trauma * acute pancreatitis * shock * stroke * drug overdose (aspirin, heroin) * smoke inhalation

Answer 155

Direct: * trauma * aspiration pneumonia * fat embolism * alveolar haemorrhage * cardio-pulmonary bypass

Answer 156

**Pathophysiology:** * Results from local or systematic inflammatory processes. Cytokines and other inflammatory mediators recruit macrophages and neutrophils to the area * These WC’s then release other inflammatory agents, and there is disruption of the boundary between lung tissue and normal capillaries, leading to ‘leaking’ of blood products (blood / protein etc) into the air spaces. * This process generally occurs throughout the lung tissue * There is reduced lung compliance, and disruption of surfactant leading to collapse of airways

Answer 157

**Clinical features** are typically of an acute onset and severe: * Dyspnoea * Tachycardia * Tachypnoea * bilateral basal lung crackles * low oxygen saturations * chest pain * peripheral vasodilation * *can be difficult to differentiate from acute* [*heart failure*](https://almostadoctor.co.uk/encyclopedia/heart-failure)

Answer 158

**Investigations:** * A chest x-ray and arterial blood gases are the key investigations. * CXR- Bilateral, widespread infiltrates. May take several hours to appear on CXR after the onset of symptoms * ABG shows low O2, pH can be low initially (due to respiratory acidosis), or may be high in the presence of sepsis, * Bloods – amylase, FBC, U+E, CRP * **Pulmonary catheter –** to measure pulmonary capillary wedge pressure. *This is to rule out heart failure. Pressure of \<19mmHg is required to consider ARDS as a diagnosis*

Answer 159

**Diagnostic Criteria** (American-European Consensus Conference): * acute onset (within 1 week of a known risk factor) * pulmonary oedema: bilateral infiltrates on chest x-ray ('not fully explained by effusions, lobar/lung collapse or nodules) * non-cardiogenic (pulmonary artery wedge pressure needed if doubt) * pO2/FiO2 \< 40kPa (200 mmHg)

Answer 160

**Management:** * due to the severity of the condition patients are generally managed in ITU * oxygenation/ventilation to treat the hypoxaemia * If early try 40-60% O2 on CPAP * If ABG O2 remains low (\<8.2kPa) then give mechanical ventilation(intubate)- be careful though because this can lead to pneumothorax so keep tidal volume and pressures a slow as possible to avoid this * general organ support e.g. vasopressors as needed like inhaled nitric oxide * circulatory support – give fluids, consider ionotrope (increase cardiac output without affecting rate), such as dobutamine * treatment of the underlying cause e.g. antibiotics for sepsis * certain strategies such as prone positioning and muscle relaxation have been shown to improve outcome in ARDS

Answer 161

**Prognosis:** * mortality is about 50-70&

Answer 162

* A chest drain is a tube inserted into the pleural cavity which creates a one-way valve, allowing movement of air or liquid out of the cavity. Chest drain insertion is indicated in cases of: * Pleural effusion * Pneumothorax not suitable for conservative management or aspiration * Empyema * Haemothorax * Haemopneumothorax * Chylothorax * In some cases of penetrating chest wall injury in ventilated patients

Answer 163

Insertion of a chest drain is relatively contraindicated in patients with any of the following: * INR \> 1.3 * Platelet count \< 75 * Pulmonary bullae * Pleural adhesions

Answer 164

Indications for a chest drain for pneumothorax include: * In any ventilated patient. * Tension pneumothorax after initial needle relief. * Persistent or recurrent pneumothorax after simple aspiration. Large SSP in patients aged over 50 years

Answer 165

Complications that may occur and which the patient should be advised of in the process of obtaining consent: * Failure of insertion - the drain may be abutting the apical pleura, in which case it should be pulled back, or may be subcutaneous or in rare cases could enter the abdominal cavity. In both latter cases, the drain should be removed and re-sited. * Bleeding - around the site of the drain or into the pleural space * Infection * Penetration of the lung * Re-expansion pulmonary oedema