Respiratory Flashcards
1
Q
What is COPD?
A
Disease state which is characterised by persistent airflow limitation that is not fully reversible. Associated response in the airways and the lungs to noxious particles or gases.
NICE: “COPD is characterised by airflow obstruction… usually progressive, not fully reversible and does not change markedly over several months. The disease is predominantly caused by smoking.”
2
Q
What is a COPD exacerbation?
A
An acute event characterised by a worsening of the respiratory system that is beyond normal day-to-day variations and leads to a change in medication.
3
Q
What is emphysema?
A
Abnormal and permanent enlargement of air spaces distal to terminal bronchiole, accompanied by destruction of alveolar walls.
4
Q
What is the FEV1 in COPD?
A
<80% predicted.
5
Q
What is the FEV1/FVC in COPD?
A
<0.7.
6
Q
What is the most common cause of COPD?
A
Smokers account for 90% but only 10-20% of smokers develop.
7
Q
What is COPD associated with the development of?
A
Emphysema and chronic bronchitis.
8
Q
What is chronic bronchitis?
A
Cough with sputum for 3 months per year for 2 or more consecutive years.
9
Q
What are the types of emphysema?
A
- Centri-acinar emphysema: distension and damage more concentrated around the respiratory bronchioles whereas the more distal alveolar ducts and alveoli tend to be well preserved, most common
- Pan-acinar emphysema: associated with alpha1-antitrypsin deficiency. Distension and destruction affect the whole acinus so severe airflow limitation and mismatch
- Irregular emphysema: scarring and damage which affects the lung parenchyma patchily, independent of acinar structure.
10
Q
What are the causes of COPD?
A
Cigarette smoking.
Chronic exposure to: pollutants at work, air pollution.
Alpha-1-antitrypsin deficiency: alpha-1-antitrypsin is a proteinase inhibitor produced in the liver which inhibits proteolytic enzymes which are capable of destroying alveolar wall connective tissue.
Respiratory infections are often the precipitating cause of acute exacerbations.
11
Q
What is the pathophysiology of COPD?
A
Vascular changes: poor V/Q (ventilation/perfusion) match, low PaO2, poor ventilation may give high pCO2, obliteration and vasoconstriction causes pulmonary hypertension.
Mechanisms underlying airflow limitation in COPD:
• Small airways disease: airway inflammation with predominance of neutrophils, CD8 lymphocytes and macrophages which results in scarring and airway fibrosis and luminal plugs and increased airway resistance
• Parenchymal destruction: loss of alveolar attachments and decrease of elastic recoil.
Cigarette smoke causes mucosal gland hypertrophy in larger airways and leads to an increase in neutrophils, macrophages and lymphocytes in airways and walls of bronchi and bronchioles. These cells release inflammatory mediators that attract inflammatory cells (amplify the process), induce structural changes and break down connective tissue in lung (emphysema). This also inactivates alpha-1 antitrypsin.
12
Q
What is the pathophysiology of chronic bronchitis?
A
- Airway narrowing (bronchoconstriction) and so airflow limitation as a result of hypertrophy and hyperplasia of mucous secreting glands (goblet cells) of bronchial tree, bronchial wall inflammation and mucosal oedema
- Epithelial layer may become ulcerated and eventually squamous epithelium replaces the columnar cells by squamous metaplasia whilst the ulcer heals
- Inflammation is followed by scarring and thickening of walls which narrows small airways
- The capillary bed remains intact and the body responds to increased obstruction by decreasing ventilation and increasing cardiac output
- Causes a poor ventilation to perfusion mismatch which causes hypoxia
- Obstruction causes increasing residual lung volume (bloating).
So overall, compensatory increase in cardiac output leads to hypoxia.
Acute bronchitis likely to have a viral cause and then a bacterial infection with Strep. Pneumoniae or H. influenzae.
13
Q
What is the pathophysiology of emphysema?
A
- Destruction of lung tissue distal to terminal bronchioles
- Results in loss of elastic recoil (normally keeps airways open during expiration)
- Leads to expiratory airflow limitation and air trapping
- This causes premature airway closure which limits expiratory flow while loss of alveoli decreases capacity for gas transfer
- Also causes damage to capillary bed so inability to oxygenate and hyperventilation (puffing).
So overall, compensatory hyperventilation prevents hypoxia.
14
Q
What is the MRC dyspnoea scoring?
A
1: SOB on marked exertion
2: SOB on hills
3: slow down or stop on flat
4: exercise tolerance
5: housebound/SOB on minor tasks.
15
Q
What are the symptoms of COPD?
A
Shortness of breath.
Chest tightness.
Systemic effects: hypertension, osteoporosis, depression, weight loss, reduced muscle mass with general weakness and right heart failure.
16
Q
What are the signs of COPD?
A
- Tachypnoea with prolonged expiration
- Poor chest expansion
- Pursed lips on expiration and intercostal indrawing on inspiration
- Hyper-expansion of lungs: gives barrel shaped chest
- Cyanosis if become insensitive to CO2
- Weight loss
- Cor pulmonale: HF, raised JVP, cardiac output maintained.
17
Q
What is the phenotype for emphysema?
A
• Pink puffer: increased alveolar ventilation, weight loss, breathless, emphysematous, maintained paO2, normal or low paCO2, may progress to type 1 respiratory failure.
18
Q
What is the phenotype for chronic bronchitis?
A
Blue bloated: cough, phlegm, cor pulmonale, type 2 respiratory failure, decreased alveolar ventilation, low paO2, high paCO2, respiratory centres relatively insensitive to CO2.
19
Q
What are the FEV1% stages in COPD?
A
Stage 1: >=80% (mild)
Stage 2: 50-79% (moderate)
Stage 3: 30-49% (severe)
Stage 4: <30% (very severe).
20
Q
What is the FEV1/FVC for airways obstruction?
A
<0.7.
21
Q
What are the investigations for COPD?
A
• COPD Assessment Score
• Spirometry
• Lung function test: shows progressive airflow limitation with increasing severity and breathlessness. Check it pre and post bronchodilator inhalation.
FEV1% and FEV1/FVC.
Multiple peak flow measurements to exclude asthma.
• Chest X-ray: may be normal or show evidence of hyperinflated lungs (>6 ribs visible) indicated by low, flattened diaphragms and a long narrow heart shadow. There may be reduced peripheral lung marking and bullae (complete destruction of lung tissue producing an airspace > 1cm). Blood vessels may be ‘pruned’ with large proximal vessels. Will show barrel chest in emphysema, flat diaphragm.
• Pulse oximetry
• ABG: may be normal or show hypoxia +/- hypercapnia
• High resolution CT: show emphysematous bullae, particularly useful when X-ray is normal, bronchial wall thickening
• Carbon dioxide gas transfer factor is low when significant emphysema is present
• Haemoglobin level and packed cell volume: can be elevated as a result of persistent hypoxaemia (secondary polycythaemia)
• Sputum examination: may reveal Step.pneumoniae or H.influenzae and Moraxella catarrhalis which can cause infective exacerbations
• ECG: often normal, but may show tall P wave if the patient has pulmonary hypertension secondary to COPD and there might be a RBBB and evidence of right ventricle hypertrophy
• FBC: raised packed cell volume.
22
Q
What is bronchiectasis?
A
Airways become abnormally widened resulting in build-up of excess mucus making lungs more susceptible to infection.
23
Q
What is the difference between asthma and COPD?
A
Asthma: • Lots of inflammation • Smooth muscle hypertrophy • Basement membrane thickening • Little fibrosis and little alveolar disruption • Cells: mast cells, eosinophils, CD4 T cells, macrophages, • Affects all airways • Responds to steroids • Spirometry may be normal. COPD : • Lots of inflammation • Lots of fibrosis • Lots of alveolar disruption • Little smooth muscle hypertrophy and basement membrane thickening • Cells: neutrophils, CD8 T cells, macrophages • Affects peripheral airways • Does not respond to steroids • Spirometry always abnormal.
24
Q
What is the management for COPD?
A
- SABA (short acting beta-2-agonist)/SAMA (short acting anti-cholinergics)
- LABA (long-acting beta-2-agonist)
- LAMA (long-acting anti-cholinergic)
- LAMA + inhaled corticosteroids.
- Smoking cessation: most useful, may slow rate of deterioration/ Pharmacotherapy and nicotine replacement increase long term abstinence rates. Encourage patients to exercise regularly.
- Beta-agonists: short acting beta-2-agonists e.g. salbutamol and terbutaline, long acting beta-2-agonists e.g. formoterol and salmeterol
- Anti-cholinergics/muscarinic: short acting: e.g. ipratropium, long acting cholinergics e.g. tiotropium bromide
- Combinations of short/long acting beta-2 agonists + anticholinergic in an inhaler
- Inhaled corticosteroids e.g. beclomethasone
- Phosphodiesterase-4-inhibitors e.g. Roflumilast which has anti-inflammatory properties (used in addition to bronchodilators in patients with FEV1 <50% and chronic bronchitis)
- Oral corticosteroids in acute exacerbations
- Antibiotics shortens exacerbations and azithromycin can improve quality of life long term
- Mucolytic agents reduce sputum viscosity and reduce the number of acute exacerbations
- Influenza and pneumococcal vaccines offered
- Alpha1-antitrypsin replacement given weekly or monthly.
25
What are the bronchodilators used in COPD?
* Beta-2 agonists
* Anticholinergics
* Theophylline
* Combination therapy.
26
What is the combined therapy in COPD?
Inhaled corticosteroid combined with long-acting beta-2-agonists are more effective in improving lung function, health status and reducing exacerbations in moderate to severe COPD.
27
What are the inhaled corticosteroids used in COPD?
e.g. beclomethasone. Regular treatments with inhaled corticosteroids improve symptoms, lung function, quality of life and reduces frequency of exacerbations and FEV1< 50% predicted. Associated with an increased risk of pneumonia and can lead to exacerbation in some patients. Avoid chronic treatment with systemic corticosteroids due to unfavourable benefit-to-risk ratio. More likely to be beneficial if eosinophilia.
28
How are COPD exacerbations treated?
ABC: airways, breathing, circulation
Oxygen: titrate to improve hypoxaemia. Target PaO2 saturation in COPD with a risk of hypercapnia is 88-92% and target saturation for normal patients is 94-98%.
Monitor ABG.
Bronchodilators: SABA (+/- SAMA) are preferred.
Systemic corticosteroids and antibiotics:
Antibiotics should be given to patients who have 3 cardinal symptoms: increased dyspnoea, increased sputum volume and increased sputum purulence, and also to those that require mechanical ventilation.
Non-invasive ventilation: CI in asthma, facial burns, vomiting.
Patients should be encouraged to cough up secretions and physiotherapy can help with chest clearance.
29
When might somebody need oxygen on flights?
FEV1<50%.
30
What score is used to monitor COPD?
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BODE:
B odd mass index.
D egree of airflow obstruction.
D yspnoea.
E exercise capacity.
A patient with a bode index of 0-2 has a 4 year mortality rate of 10% compared with 80% in someone with a BODE index of 7-10.
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31
What are the indications for specialist referral in COPD?
* Onset of cor pulmonale
* Bullous lung disease
* <10 pack years smoking or <35
* Frequent infections: to exclude bronchiectasis.
32
What are the complications of COPD exacerbations?
* Accelerated lung function decline
* Polycythaemia
* Respiratory failure
* Cor pulmonale: oedema, raised jugular venous pressure
* Pneumothorax: ruptured bullae
* Lung carcinoma.
33
What is asthma?
Reversive obstruction of the airways. Airway hyper-responsiveness to a wide range of stimuli with histamine and methacoline. Bronchial inflammation with T lymphocytes, mast cells, eosinophils with associated plasma exudation, oedema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage.
34
What is atopy?
Tendency to develop IgE (produced by B cells) mediated reactions to common allergens.
35
What are the 2 types of asthma?
Eosinophilic (extrinsic):
• Atopic: associated with allergy (occupation, pets exposures, fungal allergy)
• Non-allergic variant: typically later onset
• T cells involved in allergy (Th2 cells) recruited to lung which trigger eosinophils that damage the epithelium and so excess production of mucous and narrowing/damage of the airways.
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Non-eosinophilic (intrinsic):
• Pathology poorly understood
• Smoking
• Obesity-related
• Sensitisation to occupational agents
• Intolerance to NSAIDs
• Prescription of B adrenoceptor blocking agents that block the protective effect of endogenous catecholamines.
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36
What are the environmental causes of asthma?
* Early childhood exposure and childhood infections
* Maternal smoking
* ‘Hygiene hypothesis’: growing up in a relatively clean environment
* Fungal spores in aspergillus fumigatus.
37
What triggers asthma?
NSAIDs, particularly aspirin and ibuprofen trigger asthma.
38
What type of hypersensitivity reaction is asthma?
Type 1.
Triggers cause an inflammatory cascade in the bronchial tree. Mast cells, eosinophils, T lymphocytes and dendritic cells increased in bronchial wall, membranes and secretions. Lymphocytes produce interleukins to start the cascade and so IgE is produced. There is increased contraction of smooth muscle in the bronchial wall and remodelling causes more muscle mass in wall and an increased number of goblet cells.
39
What are the 3 factors contributing to airway narrowing in asthma?
* Bronchial muscle contraction triggered by a variety of stimuli
* Mucosal swelling/inflammation caused by mast cell and basophil degranulation resulting in release of inflammatory mediators
* Increased mucus production.
40
Why does the diameter of the lumen narrow in asthma?
* Increased number of and hypertrophy of smooth muscle
* Constriction of smooth muscle cells (bronchoconstriction)
* Increased mucous production
* Swelling and inflammation of mucosa
* Thickened basement membrane
* Airway hyperactivity, cellular infiltration.
41
What are the precipitating factors for asthma,a?
* Occupational asthma: wood dust, bleaches and dyes, isocyanates (industrial coating and spray painting), latex
* Cold air and cold water
* Exercise
* Atmospheric pollution and irritant dust e.g. exhaust fumes and tobacco smoke
* Emotion: high risk asthma attacks in those who are anxious
* Drugs: such as NSAIDs and particularly asthma.
42
What are the symptoms of asthma?
* Dyspnoea
* Wheeze, exercise induced is driven by release of histamines, prostaglandins, leukotrienes from mast cells, as well as stimulation of neural reflexes
* Cough (often nocturnal)
* Sputum production
* Breathlessness
* Tight chest
* Associated symptoms: eczema and hayfever (rhinitis), nasal disease (Samter’s triad), other food and drug allergies, reflux disease.
43
What makes a diagnosis of asthma less likely?
* Dizziness/tingling
* No wheeze
* Change in voice
* Normal PEF when symptomatic
* Cardiac disease
* Significant smoking history
* Symptoms with colds only.
44
What are the signs of asthmma?
* Episodic wheeze: polyphonic, expiratory and widespread
* Tachypnoea
* Tripoding
* Hyperinflated chest
* Hyper-resonant percussion
* Diurnal variation: often worse in morning (nocturnal waking), good days and bad days
* 40-60% have acid reflux
* Provoking factors: allergens, infections, menstrual cycle, exercise, cold air, laughter/emotion, drugs
* Brittle disease: type 1 (severe) is all the time, type 2 (sudden dips where sometimes you’re fine and others you’re not.
45
What are the investigations in asthma?
Lung function tests: airway obstruction may be present so reduced FEV1 and reduced FEV1/FVC ratio <0.7.
Peak flow test:
• Peak expiratory flow rate reduction from percent predicted variability
• Increased responsiveness to challenge agents e.g. mannitol, methacholine
• Can often be lower in morning and then have a normal one the rest of the time.
Reversibility testing so give treatment (beclomethasone) and see if they get better or not. Increase in lung capacity with bronchodilators or anti-inflammatory treatment. Increase of greater than 15% in FEV1 or PEFR together with increase of 200ml in volume is positive, >=400ml increase makes asthma highly likely. 20% variability in PEFR also suggests asthma.
Bloods for eosinophils:
• Measure FeNO (fraction exhaled nitric oxide)
• Good to test whether there is eosinophilic inflammation in lung
• Marker of eosinophilic inflammation
• Sputum eosinophilia is a more specific diagnostic test.
Tests for atopy and allergy:
• Skin prick tests, IgE
• RAST.
Chest X-ray: to exclude pneumothorax, lung cancer, COPD, infection etc. Shows hyperinflation in chronic or an acute episode. May be useful in detecting the pulmonary infiltrates associated with allergic bronchopulmonary aspergillosis.
Oxygen saturations.
ABG: normal or slightly low PaO2 but low PaCO2 (hyperventilation). If PaCO2 is normal or high, refer to ITU for ventilation because this is a sign of failing respiratory effort.
Carbon monoxide transfer test.
Histamine or methacholine provocation test: suspected patients given increasingly higher doses of histamine or methacholine which induces transient airflow limitation in susceptible individuals. The severity of airway hyper-responsiveness can be graded according to the dose or concentration of the agonist that produces a 20% fall in FEV. Can also be assess by exercise testing or inhalation of cold, dry air, mannitol or hypertonic saline.
Exhaled nitric oxide is a measure of airway inflammation and an index of corticosteroid response. It is used to measure the efficacy of corticosteroids.
Allergen provocation tests is useful in patients with suspected occupational asthma but not ordinary asthma.
46
What is the management of asthma?
Occasional symptoms: SABA (salbutamol), if using more than once daily or night-time symptoms, go to step 2.
Mild: SABA (salbutamol) + ICS (beclomethasone)
Moderate: SABA (salbutamol) + LABA (salmeterol) + ICS (beclomethasone)
Severe: SABA (salbutamol) + LABA (salmeterol) + ICS (beclomethasone) + 4th drug e.g. omalizumab anti-IgE monoclonal antibody, oral leukotriene.
Very severe: add oral prednisolone. 30mg given daily for 2 weeks with lung function measure before and immediately after. Improvement of >15% in FEV1 confirms the presence of a reversible element.
Rescue courses of prednisolone can be used at any time.
47
Why are drugs inhaled in asthma?
To avoid first pass metabolism in the liver so lower doses are needed and fewer side effects.
48
What are the treatments for asthma?
Bronchodilators (SABA, LABA, SAMA, LAMA) treat symptoms not disease. Others include:
• Leukotriene receptor antagonists e.g. Motelukast
• Methylxanthines: theophylline and aminophylline
New biologics, monoclonal antibodies (for eosinophilic, not non-eosinophilic):
• Omalizumab: anti-IgE for atopic disease, chelates free IgE and downregulates the number and activity of mast cells and basophils.
• Mepolizumab, reslizumab, benralizumab: anti-IL-5
• Against Th2 cytokine targets such as thymic stromal lymphopoietin.
Anti-inflammatory drugs like sodium cromoglicate and nedocromil sodium prevent activation of many inflammatory cells, particularly mast cells, eosinophils and epithelial cells (but not lymphocytes) by blocking a specific chloride channel, which in turn prevents calcium influx.
Bronchial thermoplasty for non-eosinophilic asthma heat up bronchial wall from inside using a bronchoscope and kill smooth muscle (rarely used), decreasing bronchoconstriction.
Do not give beta blockers as they innervate PSNS which causes bronchoconstriction.
Mixed evidence for use of macrolide antibiotic azithromycin in long term treatment which has both anti-inflammatory and antibacterial actions.
49
What is the treatment for acute asthma attacks?
• High flow oxygen
• Emergency beta agonists and steroids: nebuliser salbutamol 5mg (+ipratropium nebuliser if life threatening), repeated IV infusion. Prednisolone orally 30-60mg +/- hydrocortisone 200mg IV. Consider magnesium sulphate or aminophylline IV (bolus/load) if not improved
• Monitor response to treatment: PEFR check within 15-30 minutes/regularly. Oximetry to maintain SaO2>92%. Repeated ABG within 2 hours of severe attack or patient is deteriorating. Watch K+ and glucose. Consider rehydration.
Discharge when patient is ready: need to be off nebuliser and on stable treatment for at least 24 hours. Give steroids for a minimum 7-14 days. Early clinical review (48 hours after at GP surgery).
50
What are the features of an acute severe asthma attack?
* An inability to complete a sentence in one breath
* A respiratory rate of >=25 breaths per minute
* A tachycardia of >=110 bpm
* A PEFR of 33-50%.
51
How do you recognise a life-threatening asthma attack?
* A silent chest, cyanosis or feeble respiratory effort
* Exhaustion or altered level of consciousness
* Bradycardia, hypotension or arrhythmia
* PEFR of <33% of predicted normal or best (approximately 150ml in adults) or SpO2 <92%.
* ABG: gases of acute severe or low saturations (<92% on air, or needing oxygen)
* Chest X ray if suspect pneumothorax, consolidation, life-threatening asthma, failure to respond
* Pulse oximetry is useful in monitoring oxygen saturation
* A high PaCO2 >6
* Severe hypoxaemia: PaO2<8 despite treatment with oxygen
* A low or falling arterial pH.
52
How are asthma attacks classified?
* Uncontrolled/moderate: PEFR >50%, respiratory rate <25, pulse <110, normal speech
* Severe: PEFR 33-50% predicted, respiratory rate >=25, heart rate >=110, inability to complete sentences.
* Life-threatening: PEFR: <33%, SaO2<92% or PaO2<8kPa, normal PaCO2 4.6-6 kPa, altered conscious level, exhaustion, arrhythmia, hypotension, silent chest, poor effort, cyanosis
* Near fatal: raised PaCO2 and/or requiring ventilation with raised airway pressures.
53
What is a pulmonary embolus?
Blood clot in the lungs. Thromboembolus blocks right ventricular outflow, pulmonary arteries and branches.
54
What causes a pulmonary embolus?
Blood clots breaking off and passing through veins into inferior vena cava then into right side of the heart before lodging in pulmonary circulation. Emboli usually arise from thrombi in the iliofemoral veins (DVT).
55
What are the risk factors for PE?
* Change in blood flow: immobility e.g. post-op or paralysis, obesity, pregnancy
* Change in blood vessels: smoking, hypertension
* Change in blood constituents: dehydration, malignancy, high oestrogen combined contraceptive pill, polycythaemia, nephrotic syndrome
* Recent surgery: especially abdominal/pelvic or hip/knee replacement, always suspect PE in sudden collapse 1-2 weeks after surgery
* Family history or past history of thromboembolism.
56
What is a risk for thrombosis in PE?
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Thrombosis risk:
• Active cancer or cancer treatment
• >=60 years
• Dehydration
• Known thrombophilias
• Obesity
• Medical comorbidities
• Use of HRT
• Oestrogen containing contraceptive pill
• Varicose veins with phlebitis
• Pregnancy or <6 weeks postpartum.
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57
What are the 3 main factors which predispose you to clots?
* Circulatory stasis
* Endothelial injury
* Hypercoagulable state.
58
What is the pathophysiology of a PE?
Blood clots (usually in pelvis or legs) break off and pass through veins, into IVC then through the right side of the heart into pulmonary circulation where it becomes lodged, most likely in the small capillaries suppling the alveoli.
A large embolus obstructs the right ventricle outflow tract and suddenly increases pulmonary vascular resistance which causes right heart failure.
A small embolus impacts in a terminal, peripheral pulmonary vessel and may be clinically silent until it causes pulmonary infarction.
Lung tissue is ventilated but not perfused so there is impaired gas exchange.
After some hours, non-perfused lung no longer produces surfactant and so alveolar collapse which exaggerates hypoxaemia.
Primary haemodynamic consequence of PE is a reduction in cross-sectional area of pulmonary atrial bed which causes an elevation of pulmonary atrial pressure due to the increased resistance and a reduction in cardiac output.
Right ventricle ischaemia can be detected by elevations of troponin and creatinine kinase.
59
What are heritable thrombophilias?
* Factor V Leiden: mutation in clotting factor V that causes activated clotting factor V to be resistant to inactivation by activated protein C and so leads to an increase in thrombin formation. Thrombin converts soluble circulating plasma fibrinogen into insoluble fibrin
* Mutation in the 3’ untranslated region of the prothrombin gene: causes levels of prothrombin to rise
* Antithrombin: a serine protease inhibitor (serpin) that inhibits predominantly thrombin and factor Xa reactions that are catalysed by heparin. Reduced antithrombin means more thrombin (can also be low in liver disease or acute illness). Because antithrombin is required for the action of heparin, those with antithrombin deficiency may be relatively resistant to heparin
* Protein C and protein S deficiency: vitamin K dependent, naturally occurring anticoagulants. Together they inhibit the activated forms of the clotting system co-factors Va. Deficiency leads to an increase in thrombin generation. Can be deficient with vitamin K deficiency, liver disease, warfarin of in the case of protein S, in pregnancy or oestrogen therapy.
60
What is the extrinsic system?
Inactive circulating clotting factors become locally activated and the binding of circulating factor VII to tissue factor (a receptor expressed on subendothelial and adventitial cells) and leads to the generation of activated factor X. This is the extrinsic system. This in turn results in initial thrombin generation and subsequent amplification of the process through the intrinsic system, leading to further factor X and thrombin generation.
61
What are the symptoms of PE?
* Sudden onset dyspnoea
* Pleuritic chest pain
* Haemoptysis.
62
What are the signs of a PE?
* Pyrexia
* Hypotension
* Tachypnoea
* Pleural rub
* Exudative pleural effusion
* Tachycardia
* Raised JVP (if massive)
* RV heave (if massive)
* Second heart sound and gallop (if massive).
63
What is the definitive investigation for a PE?
CT pulmonary angiograph, or if not available a transthoracic echocardiogram.
64
What are the investigations of a PE?
Definitive: CT pulmonary angiograph, or if not available a transthoracic echocardiogram.
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Chest X-ray:
• Often normal
• Decreased vascular marking
• Blunting of costophrenic angle
• Wedge-shape areas of infarction
• Pulmonary oligaemia (local reduction in blood perfusion) in massive embolism
• Raised hemi diaphragm.
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Bloods: raised troponin.
Ventilation-perfusion isotope lung scanning:
• Perfusion phase: technetium labelled aluminium aggregates are injected intravenously and blood flow to the lungs is assessed
• Ventilation phase: patients inhale radiolabelled xenon or technetium to assess air delivery to the lungs.
Diagnosis is made if perfusion is abnormal but ventilation is normal.
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ECG:
• May be normal
• May show sinus tachycardia
• Right atrial dilation with tall peaked P waves in lead II
• Right bundle branch block
• RV strain: inverted T wave in V1-V4
• May exclude differentials e.g. MI.
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ABG:
• May be normal
• With significant PE, there will be arterial hypoxaemia i.e. low PaO2 and low PaCO2 (type 1 respiratory failure).
Plasma D-dimer: subset of fibrinogen degradation products released into circulation when clots begin to dissolve. Not diagnostic as it can be raised in other conditions e.g. cancer, pregnancy, post-op. Negative D-dimer excludes chance that it could be a PE.
Ultrasound: look at leg and pelvis for clots.
Echocardiography: diagnostic and can be performed at bedside, good for massive.
65
What is raised in a PE?
Troponin and plasma D-dimer.
66
What is the treatment for a PE?
* High flow oxygen
* LMWH e.g. enoxaparin or dalteparin initially then warfarin when PE is confirmed (warfarin not given originally as it needs at least 5 days to provide therapeutic anticoagulation. When INR is 2 or more on 2 consecutive days can stop heparin)
* DOACs or warfarin
* IV fluids and inotropic agents to improve pumping of right ventricle
* Thrombolysis for massive PE (severe hypotension): actually dissolve the blood clots, alteplase
* Analgesia
* Surgical embolectomy: when thrombolysis is CI
* If high risk of recurrence or CI to anticoagulation e.g. active bleeding, do vena cava filter. Prevents blood clot from the deep veins in the leg from entering the lungs.
67
What treatment in PE is CI in pregnancy?
Warfarin and DOACs cross the placenta and so should not be used in pregnancy. Warfarin causes embryopathy between the 6th and 12th weeks., later in the pregnancy it causes bleeding in the foetus. Women on warfarin at the time of becoming pregnant are safe until 6 weeks.
LMWH is safe in pregnancy.
Both warfarin and LMWH safe in breast-feeding but DOACs should be avoided. LMWH more effective than warfarin in patients with active cancer.
68
What are the monitoring scores for a PE?
Revised Geneva score to predict probability of PE.
| Two level-Wells score for prediction.
69
What are the complications of a PE?
Acute right heart failure, syncope and death follow a massive PE rapidly.
Mortality rate by 1 month is around 5% (half are due to associated comorbidities). Most common cause of hospital-related death.
70
Where does the upper respiratory tract go from?
Upper respiratory tract goes from nose to larynx above vocal cords.
71
What are types of upper respiratory tract infections?
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Viral illnesses:
• Rhinoviruses (45-50%)
• Influenza A virus (25-30%)
• Coronaviruses (10-15%)
• Parainfluenza viruses (5%)
• Respiratory syncytial viruses (5%).
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Emergency respiratory infections:
• Severe acute respiratory syndrome (SARS): associated with coronavirus, outbreak from China, severe respiratory illness with respiratory failure
• Middle East Respiratory Syndrome novel Coronavirus (MERS-nCV): from middle east, similar to SARS but low person-to-person spread (camels, bats etc)
• Avian flu: novel form of influenza A virus, occasional human cases with severe illness, seen in SE Asia, associated with poultry exposure, low person-to-person spread.
72
What are complications of upper respiratory tract infections?
Sinusitis, pharyngitis, otitis media, bronchitis. Influenza A in particular causes systemic symptoms.
73
What are the defences in upper respiratory tract infections?
Defences:
Mucosal defences:
• Cough reflex
• Mucus barrier and respiratory cilia (mucocilliary escalator which clears gunk)
• Swallowing
• Commensal flora: colonisation resistance.
Innate immune defences:
• Alveolar macrophages: orchestrate immune response, phagocytic
• Soluble factors: IgA, defensins, collectins, lysozyme
• Neutrophils: first cells recruited, phagocytic.
Adaptive immune defences:
• B cells: antibody formation
• T cells: cell mediated CD8 cytotoxicity, CD4 helper cell function, regulatory function.
74
What are the types of influenza?
Member of the Orthomyxoviridae family with three separate genera: serotype A, (worldwide pandemics) B (localised outbreaks) and C (akin to common cold). Further divided into 2 key surface antigens:
• Haemagglutinin (15 subtypes): virus binding and entry to cells e.g. “grappling hook” for getting in so facilitates entry into host respiratory cell
• Neuraminidase (9 subtypes): “bolt cutter” for getting out, cuts newly formed virus loose from infected cells and prevents it clumping together so facilitates release of virions from infected cells. Immunity to subtype reduces amount of virus released from cells resulting in a less severe disease.
75
How is influenza transmitted?
Mainly via aerosols generated by coughs and sneezes. Also possible via hand-to-hand contact, other personal contact or fomites.
It is seasonal.
76
What is the incubation period for influenza?
1-3 days.
77
What are the symptoms of influenza?
* Abrupt fever
* Aching in limbs
* Sore throat
* Dry cough
* Headache
* Myalgia and weakness
* Diarrhoea in H5N1 ‘bird flu’.
78
How is a diagnosis of influenza made?
Definitive diagnosis can be established by demonstrating a four-fold increase in complement-fixing antibody or haemagglutinin antibody measure at onset and after 1-2 weeks or taking nasopharyngeal swabs.
Viral PCR, rapid antigen testing, viral culture of clinical samples (swabs).
79
What medical treatment is given in influenza?
Antivirals e.g. Tamiflu (neuraminidase inhibitor):
• Reduce risk of transmission to others
• Reduce severity and duration of symptoms
• Only give if at increased risk.
Bed rest and paracetamol, with antibiotics to prevent secondary infection in those with chronic bronchitis or cardiac renal disease.
80
What precautions are taken in a patient with influenza?
Inpatients should be cared for in a side room.
81
What is a complicated influenza?
Includes lower respiratory tract infection, exacerbation of any underlying medical condition, all needing hospital admission.
82
What drugs are given in complicated influenza?
* Oseltamivir, first line
| * Zanamivir e.g. in type AH1N1.
83
In how many people are the influenza vaccines effective?
About 70%.
84
Who is routine flu vaccine suggested for?
for >65 years or if younger and have chronic heart, lung (including asthma), kidney disease, diabetes mellitus or in the immunosuppressed. Should be careful in those with egg protein allergy.
85
What are the complications of influenza?
Bacterial pneumonia, staphylococcus aureus can be life-threatening. Particularly streptococcus pneumoniae and H influenzae.
* Post infectious encephalomyelitis
* Exacerbation of chronic lung disease
* Otitis media
* Diarrhoea and vomiting.
86
Who is the mortality risk in influenza high in?
* Chronic cardiac, pulmonary and liver diseases
* Old age
* Chronic metabolic diseases
* Chronic renal diseases
* Immunosuppressed
* Diabetes mellitus
* Pregnancy
* BMI
* >65 years
* BMI> 40.
87
What is pharyngitis/tonsillitis?
Infections in the throat that cause inflammation. If tonsils primarily affected, tonsillitis. If throat primarily affected, pharyngitis.
88
What are the causes of pharyngitis/tonsillitis?
```
Viral (70-80%):
• Adenovirus (most common)
• Rhinovirus
• EBV
• Acute HIV.
```
```
Bacterial:
• Lancefield Group A Beta-haemolytic strep e.g. S.pyogenes
• Mycoplasma pneumoniae
• Neisseria gonorrhoea
• Fusobacterium necrophorum.
```
89
What are the symptoms of pharyngitis/tonsillitis?
* Sore throat for >24 hours
| * Fever.
90
What can glandular fever present with?
Tonsillitis.
91
What are the signs of pharyngitis/tonsillitis?
* Tender glands in neck
* Red oropharynx and soft palate
* Inflamed and swollen tonsils
* Stable vitals
* Tender anterior cervical lymph nodes.
92
What is persistent/severe tonsillitis treated with?
Phenoxymethylpenicillin or cefaclor.
93
What is sinusitis?
Infection of the paranasal sinuses. Bacterial or occasionally fungal.
94
What are the causes of sinusitis?
* Virus is most common
* Bacterial: strep. Pneumoniae (40%), H. influenza (30-35%)
* Most commonly associated with upper respiratory tract infection and occasionally asthma and allergic rhinitis.
95
What are the symptoms of sinusitis?
* Frontal headache
* Facial pain
* Fever.
96
What are the signs of sinusitis?
* Purulent nasal discharge
| * Tenderness.
97
What is the management of sinusitis?
* Nasal decongestants e.g. xylometazoline
| * Broad spectrum antibiotics e.g. co-amoxiclav (H.influenzae can be resistant).
98
What is acute epiglottitis?
Inflammation of the epiglottis (flap of cartilage behind the root of the tongue which is depressed during swallowing to cover opening of the windpipe).
99
Why is acute epiglottitis now rare?
H. influenzae B vaccine.
100
What are the causes of acute epiglottitis?
* H. influenzae type B (Hib)
* Causes of pharyngitis and other bacterial infections of airway
* Caused by additional pathogens in immunocompromised e.g. AIDs.
101
What are the symptoms of acute epiglottitis?
* Sore throat and pain on swallowing (odynophagia)
* High pitched wheeze (inspiratory stridor)
* Diarrhoea
* Fatigue
* Weight loss
* High fever.
102
What are the signs of acute epiglottitis?
* Severe airflow obstruction
* Meningitis
* Septic arthritis
* Osteomyelitis.
103
What is the management for acute epiglottitis?
* Endotracheal intubation
| * IV antibiotics: amoxicillin, co-amoxiclav, erythromycin, doxycycline.
104
Who does whooping cough affect?
Children <5.
105
What are the causes of whooping cough?
* Bordatella pertussis: gram negative coccobacillus (rod)
| * Brodatella parapertussis and bordatella bronchiseptica produce milder infections.
106
What are the symptoms of whooping cough?
* Chronic cough
* Vomiting
* Malaise
* Anorexia
* Rhinorrhoea.
107
What are the signs of whooping cough?
* Classic inspiratory whoop: only seen in younger individuals in whom the lumen of the respiratory tract is compromised by mucous secretion and mucosal oedema
* May be associated with complications: pneumonia, encephalopathy, sub-conjunctival haemorrhage.
108
How is a diagnosis of whooping cough made?
* Chronic cough and one clinical feature indicated pertussis
* Culture of nasopharyngeal swab
* PCR
* ELISA for IgG against PT.
109
What is the management for whooping cough?
* Antimicrobials: eliminate carriage of bacteria e.g. clarithromycin
* Vaccination.
110
What is croup/acute laryngotracheobronchitis a complication of?
Acute laryngitis is an occasional complication of URT infections, particularly those caused by parainfluenza and measles.
111
When is croup/acute laryngotracheobronchitis most severe?
In children under 3.
112
What causes croup/acute laryngotracheobronchitis?
Parainfluenza viruses.
113
What is the pathophysiology of croup/acute laryngotracheobronchitis?
Inflammatory oedema extends to vocal cords and epiglottic, causing narrowing of airway (may be associated with tracheobronchitis). Progressive airway obstruction may occur, with recession of soft tissue of neck and abdomen during inspiration and in severe cases central cyanosis.
114
What is the main symptom of croup/acute laryngotracheobronchitis?
Prominent barking cough (croup).
115
What are the signs of croup/acute laryngotracheobronchitis?
* Febrile
* Respiratory rate of 40
* Cyanosis
* Inspiratory stridor
* Hoarse throat.
116
What is the management for croup/acute laryngotracheobronchitis?
* Nebulised adrenaline: short term relief
| * Oral or IM corticosteroids e.g. dexamethasone + oxygen and fluids.
117
What is pneumonia?
Pneumonia is the general term attached to inflammation of the lung parenchyma.
118
What are the most common causes of pneumonia?
Usually due to infection that affects distal airways and alveoli with formation of an inflammatory exudate. Usually bacterial but can be viral or fungal. With intense infiltration of neutrophils in and around alveoli and terminal bronchioles.
119
How are the types of pneumonia categorised?
The setting which person has contracted the infection in.
120
What are types of pneumonia?
* Community-acquired pneumonia
* Hospital-acquired pneumonia: acquired at least 48 hours after hospital admission, usually most resistant. In the elderly, ventilator-associated, post-op, immunocompromised, aspiration pneumonia (inhaling something that shouldn’t be allowed e.g. food which isn’t sterile)
* Aspiration pneumonia: associated with the aspiration of food material or stomach contents into the lungs and caused by impaired swallowing. Most likely to end up in the right middle lobe or the right upper lobe.
* Pneumonia in immunocompromised patient: acquired through either a genetic defect, immunosuppressive medication or acquired immunodeficiency, as in HIV
* Ventilator-acquired pneumonia: acquired through mechanical ventilation on a critical care e.g. Acinetobacter baumanii).
121
What is the common cause of immunocompromised pneumonia?
Pneumocystis jirovecii.
Radiographic appearance is diffuse bilateral alveolar and interstitial shadowing, localised infiltration and first line treatment co-trimoxale.
122
What is the most common cause of community acquired pneumonia?
Strep pneumoniae.
123
What type of bacteria is strep pneumonia?
Gram positive cocci. Alpha haemolytic.
124
What are the causes of community acquired pneumonia?
```
Strep pneumoniae (40%).
Chlamydophila pneumoniae (13%).
Mycoplasma pneumoniae (11%).
H. influenzae B (5%).
Legionella pneumophilia (5%).
Klebsiella pneumoniae (rare).
S. aureus.
No diagnosis (31%).
```
125
What type of bacteria is H. influenzae?
Gram negative coccobacilli.
126
What is atypical pneumonia?
Immunosuppressed, pre-existing lung disease and don’t respond to amoxicillin.
127
What do atypical pneumonia not respond to?
Amoxiciilin.
128
What are the causes of atypical pneumonia?
* Legionella pneumophilia
* Mycoplasma pneumoniae
* Chlamydophilia pneumoniae (often older adults, sometimes closed outbreaks, longer duration of symptoms)
* Chlamydophila psittaci: contact with sick birds (parrots) and poultry workers
* Coxiella brunetti: exposure to partuent animals e.g. sheep.
129
What are the most common causes of pneumonia which present to ITU?
* Strep pneumoniae
* S. aureus
* Legionella sp.
* Viruses.
130
What are the causes of hospital acquired pneumonia?
* Early onset <=5 days of hospital: organisms similar to CAP and also anaerobes.
* Late onset >5 days: Staphy. Aureus including methicillin resistant MRSA, pseudomonas aeruguinosa, acinetobacter baumanii or klebsiella pneumoniae.
131
What is the pathophysiology of pneumonia?
Bacteria “translocate” to normally sterile distal airway. Bacteria from URT that has either came in quickly or colonised for a while are micro-aspirated into lower lung. Resident host cells become overwhelmed. Develop an inflammatory response where neutrophils and inflammatory exudate fill alveolar space.
132
What is the resolution phase in pneumonia?
There is a resolution phase when the bacteria is cleared. Inflammatory cells are removed by apoptosis. The resolution phase leads to complete recovery.
133
What are the symptoms of pneumonia?
Infection:
• Fever
• Sweats
• Rigors.
Chest:
• Dyspnoea
• Dry or productive cough, sometimes with haemoptysis
• Sputum production: classically rusty sputum suggests S.pneumoniae. May be no sputum, particularly with atypical pathogens such as mycoplasma, Chlamydophila and legionella
• Pleuritic chest pain: pain worse on deep breathing (sandpaper on sandpaper). Parenchyma doesn’t have somatic neurons so any sensation from inside lungs will feel like irritation or need to cough. Lining of lungs does have somatic neurones so can localise pain to edge of lungs.
Systemic:
• Weakness
• Malaise (particularly common on Legionella and Mycoplasma).
134
What are the symptoms of community acquired pneumonia?
Confusion in the elderly.
135
What are the symptoms of hospital acquired pneumonia?
* New fever
* Purulent secretions
* New radiological infiltrates
* New leucocytosis/CRP increases
* + increasing O2 requirements.
136
What are the signs of pneumonia?
```
Signs of lung consolidation on percussion and auscultation:
• Crackles +/- wheeze
• Pleural rub
• Bronchial breath sounds
• Increased vocal resonance
• Dull to percussion
• Consolidation
• Decreased air entry
• +/- hypoxia and signs on respiratory failure especially if chronic lung disease or severe pneumonia.
```
```
Abnormal vitals: more present, the greater severity
• Raised HR
• Raised RR
• Low BP
• Fever
• Dehydration.
```
137
What are the indicators of severity in pneumonia?
```
Significant infection yields a systemic inflammatory response and all of these lead to sepsis:
• Pro-inflammatory cytokines
• Vasodilation
• Impaired cardiac contractility
• Reduced BP
• Impaired organ perfusion
• Tissue hypoxaemia.
```
These will lead to sepsis so patient will develop:
• Delirium, confusion
• Renal impairment, urea rise
• Increased oxygen demand so high RR, lactic acid production
• Systolic and diastolic BP drop.
138
What are the investigations in pneumonia?
* Chest X-ray: shows distribution, extent of infiltrate +/- cavitations. Can initially be normal in CAP so should be repeated after 2-3 days.
* Sputum microscopy, culture and sensitivities +/- gram stain.
* Blood cultures
* Bloods: FBC, serum creatinine, electrolytes, C-reactive protein, WBC count aids diagnosis and is a marker of severity (high in strep. Pneumoniae, normal in mycoplasma, reduced lymphocytes in legionella)
* Low albumin levels
* Legionella urinary antigen: doesn’t respond well to antibiotics
* Biochemistry: U&E and LFTs (renal function required to assess severity, other tests for complications)
* C-reactive protein: helps with diagnosis, assessment of severity and recovery
* Pulse oximetry: assess severity and if required ABG define respiratory failure
* Microbiological tests
* Serology
* Viral throat swab
* HIV test as pneumonia is very common in HIV
* PCR: only in outbreaks or specific patients
* ABG if sats <94%.
139
What is used to assess the severity of community acquired pneumonia?
```
CURB65:
C onfusion
U rea >= 7mmol
R espiratory rate >= 30/min
B P: low systolic <90mmHg or diastolic <=60mmHg
65 Age >=65.
```
One point for each. Predicts mortality (0=0.7%, 1=2.1%, 3=9.2%, 4-5=15-40%). 0-1 is mild, only admit if social circumstance or single worrying feature. 2 is moderate, admit to hospital. 3-5 is severe, admit and monitor closely. 4-5 consider admission to critical care unit.
Can’t be used in community as no urea available so CRB65: 0 is mild, 1-2 is moderate and 3-4 is severe.
140
What is the management for community acquired pneumonia?
Antibiotics:
• Mild severity, CURB65 0-1 (5 days): amoxicillin and if allergic give clarithromycin or doxycycline
• Moderate severity, CURB65 2 (5 days): amoxicillin + clarithromycin
• Severe CURB65 3-5 (>5 days, 14-21 if S.Aureus): IV co-amoxiclav + clarithromycin. Alternatives are cefuroxime + clarithromycin.
Once pathogen is known:
• S. Pneumoniae: use amoxicillin, cefuroxime or cefotaxime. Alternatives are clarithromycin or ciprofloxacin (only use if needed)
• H. Influenzae: doxycycline or, amoxicillin + clavulanic acid
• S. Aureus: flucloxacillin, cefuroxime or MRSA (vancomycin or linezolid)
• Klebsiella pneumoniae : cephalosporins or co-amoxiclav
• Atypical: not susceptible to B-lactams/penicillin. Macrolides e.g. erythromycin or clarithromycin, fluroquinolones e.g. ciproflaxin or tetracyclines e.g. doxycline.
IV saline in hypotensive patients.
Oxygen for sats 94-98%.
Analgesia e.g. paracetamol or NSAIDs.
Thromboprophylaxis if >12 hours.
141
What is the treatment for hospital acquired pneumonia?
* Piperacillin-tazobactam or meropenem or ceftazidime
* May need linezolid or vancomycin for MRSA
* IV colistin for multi-drug resistant gram-negatives.
142
What is the prevention of pneumonia?
* Polysaccharide pneumococcal vaccine protects against 23 serotypes
* Influenza vaccination to those >65, immunocompromised or with medical comorbities
* Smoking cessation.
143
What are the complications of pneumonia?
* Parapneumonic effusion: cause of failure to settle and source of complications. Light’s criteria to determine if the effusion is transudative or exudative
* Empyema: purulent fluid in the pleural space. Failure of fever or markers on inflammation (CRP/ESR) to settle on antibiotics, pain on deep inspiration and signs of pleural collection (stony dull to percussion, reduced air entry).
* Parapneumonic effusion requires thoracocentesis: to identify markers that suggest effusion will fail to resolve. Markers suggesting drainage pH<7.2, glucose<3.3, LDH>1000, positive gram stain or culture, pus or thick fluid
* Sepsis
* Respiratory failure
* Lung abscess.
144
What is the top infectious killer in the world?
TB.
1/3 of the world's population is infected.
Cause of death for most people with HIV.
145
What is the cause of TB?
Mycobacteria “Acid Fast Bacilli”.
146
What is "Acid Fast Bacilli"?
* Slightly curved, beaded bacilli. Aerobic, intracellular pathogen
* High lipid content with mycolic acids in cell wall makes mycobacteria resistant to gram stain
* Stain acid fast bacilli with Ziehl-Neelsen stain instead (stain red/pink). Carbol fuchsin, acid alcohol (AFB resistant to de-staining), methylene blue
* Resistant to phagolysosomal killing by macrophages
* Flurochrome stains e.g. auramine phenol aid screening at lower power objective.
147
What stain is used in TB?
Stain acid fast bacilli with Ziehl-Neelsen stain instead (stain red/pink).
148
What are the four main mycobacterial species?
* Mycobacterial tuberculosis (most common)
* Mycobacterium bovis (where milk is unpasteurised, extrapulmonary more frequently involved)
* Mycobacterium africanum
* Mycobacterium microti.
149
What are the risk factors for TB?
* Born in high prevalence area
* Intravenous drug users
* Homeless
* Alcoholic
* Prisons
* HIV
* Immunosuppression.
150
What is the pathophysiology of pulmonary TB?
* 2-5% develop clinically evident primary pulmonary disease
* Bacilli and macrophages coalesce to form a granuloma called the Primary (Ghon) focus
* Granuloma slowly enlarges, centre becomes necrotic and produces pus
* Mediastinal lymph nodes which enlarge
* Primary focus + mediastinal lymph nodes = primary (Ghon) complex
* As granuloma grows, it develops into a cavity
* More likely in the apex of lung as there is more air and less blood supply/immune cells
* Cavity is full of TB bacilli, which are expelled when patient coughs.
151
How is TB transmitted?
In aerosol from infected individual’s lung to another or via spitting/sneezing on plates, hands etc. Bovine TB from drinking unpasteurised milk.
152
What happens in primary TB?
‘Primary TB’ describes the first infection with TB. When the bacteria reaches the alveolar macrophages, they are ingested and the subsequent inflammatory reaction results in tissue necrosis and formation of a granuloma. These granulomatous lesions consist of a central area of necrotic material called caesation, surrounded by epitheloid cells and Langhans giant cells. Subsequently, the ceasated areas heal completely and many become calcified. Some of these contain bacteria which are contained by the immune system (cell mediated immunity) and can lie dormant for many years (latent TB). This is known as the primary focus or Ghon focus. On initial contact, less that 5% develop active disease and this increases to 10% within the first year of exposure.
153
What is the main reason for the majority of TB cases?
Reactivation tuberculosis.
154
What type of immunity response is TB?
Catabolic.
155
What are the symptoms of TB?
Immune response is catabolic.
```
Systemic:
• Weight loss
• Night sweats
• Low grade fever
• Anorexia
• Malaise.
```
```
Pulmonary:
• Cough > 3 weeks (dry then productive, most other causes resolve by then)
• Chest pain
• Breathlessness
• Pleural effusion.
```
156
What are the signs of TB?
* Consolidation in lung with or without cavitation
* Lung collapse
* Pleural effusion: if cavity is near lining of lung instead of large airway, infection can spill into pleural cavity. For effusion secondary to TB, desired treatment is anti-TB medication
* Pericardial effusion depending on site of granuloma/lymph node and subsequent rupture
* Thickening or widening of the mediastinum.
157
What are the extrapulmonary manifestations of TB?
Miliary TB: bacteria that weren’t contained in the lung have managed to spread everywhere in the body. This causes tiny granulomata to form wherever they are so chest X-ray will show lots of little dots in chest.
Lymph node TB: swelling +/- discharge. Enlargement of a cervical or supraclavicular node which is firm to touch.
Bone or spinal TB: pain or swelling of joints, Potts disease with spinal cord lesion.
Abdominal TB: ascites, abdominal lymph nodes, ileal malabsorption.
Genito-urinary TB: epididymitis, frequency, dysuria and haematuria. Granuloma may cause fibrosis, strictures, infertility and genital ulceration.
CNS TB: meningitis + CN palsy, foci can enlarge to form tuberculoma.
Skin TB: Lupus vulgaris: persistent, progressive, cutaneous TB.
Gastrointestinal TB: most disease is iliocaecal. Causes colicky abdominal pain and vomiting, sometimes bowel obstruction.
Cardiac TB: pericarditis, pericardial effusion, constrictive pericarditis.
158
How is TB bacteria identified?
Once samples have been taken, the rapid identification of the presence of mycobacterium by stains is essential and should be done within 24 hours:
• Auramine-rhodamine: highlights bacilli as yellow-orange on a green background, more sensitive but less specific than Ziehl-Neelson. This is diagnostic
• Ziehl-Neelson: appear red/pink.
Majority of the developed world uses liquid/broth culture of mycobacteria in addition to solid media (Lowenstein-Jensen slopes or Middlebrook agar). Takes 1-3 weeks.
Histopathology would show caseating granulomata.
159
What do chest X-rays show in TB?
Chest X-ray shows patchy or nodular shadows in upper zones with loss of volume and fibrosis + cavitation. May show consolidation. Normal X-ray with primary.
160
What do the bloods show in TB?
* Normochromic normocytic anaemia
* Thrombocytosis
* Raised ESR/CRP
* Hypoalbuminaemia
* Hypergammaglobulinaemia
* Hypercalcaemia
* Sterile pyuria (white cells in renal tract).
161
What are the definitive investigations in TB?
* Urine
* CSF
* Pleural fluid
* Biopsy specimen of any lymph nodes (cervical, axillary, inguinal, mediastinal, abdominal)
* PCR (nucleic acid amplification testing works by using PCR to replicate and then identify mycobacterium DNA.
162
How is latent TB diagnosed?
Diagnosing Latent TB:
It isn’t possible to find “dormant” bacteria. So instead, an indirect measure is used to detect an immune memory response to the organism. This can only answer whether the patient has ever been exposed to TB. If yes, the patient is clearly not suffering active TB, we assume this means they still harbour dormant bacteria with the potential to reactivate in the future,
Tuberculin skin test “Mantoux”:
• Protein tuberculin derived from organism
• Inject intradermally
• Stimulated type 4 delayed hypersensitivity reaction 48-72 hours later
• Not sensitive, immunosuppressed or military TB won’t react (false negatives)
• Only moderately specific (false positives)
• Won’t easily distinguish infection from disease
• Drawback of tuberculin skin test is that if the patient has had BCG vaccine, there will be a reaction and cannot tell if patient has latent TB.
Interferon gamma release assays (IGRAs):
• Use antigens specific to M. tuberculosis
• Detect T-cell secretion of IFN-gamma following exposure to M. tuberculosis
• Distinguished between BCG, environmental mycobacteria and TB exposure
• Does not distinguish between active and latent infection.
163
What are the tests required in TB?
Routine blood tests, a viral hepatitis screen and HIV test.
164
How long is treatment required for in TB?
Require at least 4 drugs for 6 months of treatment or 12 months if TB in CNS.
165
What is the first line treatment in TB?
Isoniazid, rifampicin, pyrazinamide, ethambutol.
166
What are the side effects of quadruple TB therapy?
Nausea, vomiting, rash and itching.
167
What is the management in CNS and pericardial TB?
Corticosteroids are used as an adjunct at treatment initiation to reduce long-term complications.
168
Do you refer TB to public health?
Yes.
169
Why is chemoprophylaxis offered in TB?
To reduce the risk of active infection in:
• Household and close workplace contacts of patients with pulmonary and laryngeal TB
• Health workers
• Recent new migrant entrants from high-risk countries
• Patients who are immunocompromised e.g. HIV
• Those about to commence treatment with biologic agents e.g. infliximab
• Those who have stem cell or solid organ transplants.
This is either isoniazid (with pyridoxine) and rifampicin for 3 months or isoniazid (with pyridoxine) monotherapy for 6 months.
170
Is there a vaccine for TB?
BCG vaccine derived from M. bovis. Limited use.
171
What is the prevention for TB?
* Active case finding to reduce infectivity
* Detection and treatment of latent TB: Community TB nursing team using Mantoux skin test
* Vaccination: neonatal BCG, limited efficacy but does protect vs disseminated TB, false positive Mantoux tests, previously routine in UK teenagers, now just for neonates from high risk groups, no other vaccine available
* Latent TB: identify and treat to reduce risk of post-primary TB (recent infection (contact-tracing), new entrants, HCWs, immunocompromised)
* Diagnosis by Mantoux test or IGRA
* Treatment: 6 months isoniazid, 3 months rifampicin + isoniazid
* Reduces risk of developing active TB by 2/3.
172
What is the staging of TB?
Primary tumour:
• TX: malignant cells in bronchial secretions, no other evidence of tumour
• TIS: carcinoma in situ
• T0 : none evident
• T1 : <= 3cm in lobar or more distal airway
• T2 : >3cm and >2cm distal to carina or any size if pleural involvement or obstructive pneumonitis extending to hilum, but not all lung
• T3 : involves the chest wall, diaphragm, mediastinal pleura, pericardium, or <2cm from but not at carina. T>7cm in diameter and nodules in the same lobe
• T4 : involves mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina, malignant effusion, or nodules in another lobe.
Regional nodes:
• N0: none involved (after mediastinoscopy)
• N1: peribronchial and/or ipsilateral hilum
• N2: ipsilateral mediastinum or subcarinal
• N3: contralateral mediastinum or hilum, scalene or supraclavicular.
Distant metastases:
• M0: none
• M1: a) nodule in other lung, pleural lesions or malignant effusion
b) distant metastases present.
```
Stages:
• I: TIS/T1/T2 N0 M0
• II: T1/T2 N1 M0 or T3 N0 M0
• IIIa : T3 N1 M0 or T1-3 N2 M0
• IIIb : T1-4 N3 M0 or T4 N0-2 M0
• IV : T1-4 N0-3 M1.
```
173
What is the most common type of lung cancer?
Bronchial carcinoma.
174
What are the types of primary lung cancer?
Small cell lung carcinoma:
• High grade epithelial neoplasm with strong cigarette smoking association
• Has usually spread by time of presentation
• Chemotherapy is primary treatment.
Non-small cell lung carcinoma (large cell):
• Squamous, large cell or adenocarcinoma (most common lung cancer in non-smokers, asbestos exposure)
• Variable grade/type epithelial neoplasm with cigarette smoking association
• May have metastasised by presentation
• Chemotherapy may be offered but surgery and radiotherapy mainstay of treatment
• New drugs: EGFR, ALK1, ROS1, PDL1.
Primary:
35% adenocarcinoma (most common):
• Commonly associated with asbestos exposure
• May be central or peripheral (usually)
• Originate from mucus-secreting glandular cells
• Most common cell type in non-smokers
• Metastases common: pleura, lymph nodes, brain, bone, adrenal glands.
25% squamous cell carcinoma :
• Most strongly associated with cigarette smoke
• Most present as obstructive lesion leading to infection
• Usually central in location and frequently cavitate with central necrosis
• Arise from epithelial cells, associated with keratin production.
20% small cell lung carcinoma (most aggressive):
• Strong association with cigarette smoke
• Often rises in central bronchus
• Grows rapidly and is highly malignant, almost always inoperable at presentation
• Arises from Kulchitsky cells (endocrine cells which manufacture polypeptides and amines which act as hormones or neurotransmitters) and secretes polypeptide hormone resulting in paraneoplastic syndromes:
ACTH: Cushing’s syndrome
ADH: dilutional hyponatraemia (SIADH)
PTH-like substance: hypercalcaemia
HCG or related hormones: gynecomastia (enlargement of male breast tissue).
10% large (non-small) cell undifferentiated carcinoma:
• Associated with cigarette smoke
• Often treated best by surgical oblation with lymph node sampling
• More susceptible to a new therapy e.g. tyrosine kinase therapy.
5% carcinoid tumour:
• Usually associated with presentation at an earlier age (middle age)
• Have characteristic neuroendocrine secreting cells
• Relatively low rates of invasion and growth.
5% others:
• Lymphomas: main lung lymphoma is BALTOMA (bronchus associated tissue lymphoma) which is a B cell lymphoma which responds to standard chemotherapy regimes
• Benign: hamartomas is most common. Irregular proliferations of benign/normal tissues and most common in lung is chondroid hamartoma which involves cartilage, glandular tissue, fat, fibrous tissue and blood vessels
• Fibroma
• Lipoma
• Leiomyoma.
175
How are lung cancers classified?
How big it is:
• T1: <3cm
• T2: >3cm
• T3: invades chest wall, diaphragm and pericardium
• T4: invades mediastinum, heart, great vessels, trachea, oesophagus, vertebra, carina.
Nodes (how many and where they are):
• N0: none
• N1: Hilar nodes
• N2: same side mediastinal nodes or subcarinal
• N3: contralateral mediastinum or supraclavicular.
```
Metastases:
• 0: none
• 1a: tumour on same side
• 1b: tumour elsewhere
• X: unknown.
```
176
What are the causes of lung cancer?
Remember SHOE:
S moking (including passive smoking) is most common, 90% of lung cancer
H ost factors: pre-existing lung disease e.g. pulmonary fibrosis, HIV infection, genetic factors
O ccupation e.g. asbestos, arsenic, coal, nickel
E nvironmental e.g. radon or ionising radiation.
177
Is primary or secondary lung cancer more common?
Secondary.
178
Where does secondary cancer to the lungs most commonly come from?
* Kidney cancer: renal cell carcinoma (most commonly spreads to lung)
* Breast cancer
* Bowel cancer
* Bladder cancer.
179
Where are the sites of metastatic spread from lung cancer?
* Liver: anorexia, nausea, weight loss, and right upper quadrant pain radiating across abdomen
* Bone: bony pain and pathological features
* Adrenal glands: usually asymptomatic
* Brain: space-occupying lesion with signs of raised ICP.
180
What are the symptoms of lung cancer?
* Dry cough
* Dyspnoea
* Haemoptysis
* Chest pain
* Weight loss
* Pain in shoulder and arm due to spread to brachial plexus
* Pain and fractures due to involvement of pleura/ribs
* Horner’s syndrome when spread to sympathetic ganglion
* Hoarse voice when spread to sympathetic ganglion.
181
What are the signs of lung cancer?
• Recurring chest infections
• Cachexia (extreme muscle wasting, weight loss)
• Anaemia
• Clubbing
• Extra-pulmonary changes (directly/indirectly due to cancer):
Heart: pericarditis, pericardial tamponade
Oesophagus compression: dysphagia
Phrenic nerve: paralysed diaphragm
Recurrent laryngeal nerve: hoarseness
• Paraneoplastic changes (conditions which occur as a side effect of tumour, 10% of cases):
Secretion of PTH
Syndrome of inappropriate ADH secretion (SIADH)
Secretion of ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal glands
Hypertrophic pulmonary osteo-arthropathy
Finger clubbing
Non-infective endocarditis
Disseminated intravascular coagulation
Myasthenic syndrome (Eaton Lambert)
Migratory thrombophlebitis.
182
What does a chest X-ray show in lung cancer?
* Round fluffy/spiking shadow
* Hilar enlargement
* Consolidation (fluid)
* Pleural effusion
* Edge has fluffy spiked appearance
* Lung collapse.
183
What investigations are done in lung cancer?
Chest X-ray.
```
Cytology and histology via:
• Sputum
• Biopsy
• BAL
• Lobectomy, wedge, pneumonectomy.
```
PET scans.
CT thorax: to stage tumour.
Bronchoscopy to give histology and access.
Bloods: FBC.
Lung function tests to test suitability for lobectomy.
184
What is the management for lung cancer?
* Chemotherapy with monoclonal antibodies e.g. cetuximab
* Radiotherapy
* Surgery
* Pleural drainage
* Palliative care.
For non-small cell, surgery can be curative. Chemo can downstage tumours to render them operable. Large doses of radiotherapy can help localised squamous cancers (can cause fibrosis).
185
What are the complications of lung cancer?
* Recurrent laryngeal nerve palsy
* Horner’s syndrome (Pancoast tumour)
* Metastatic: in brain (confusion, fits, neuro deficit) and in bone (pain, hypercalcaemia) and in liver (hepatomegaly)
* Non-metastatic: Addison’s, Cushing’s, hyperthyroidism, skeletal clubbing.
186
What is bronchitis?
Self-limiting inflammation of epithelia of bronchi due to upper airway infection.
187
What are the causes of bronchitis?
* Mycoplasma pneumoniae
* Chlamydia pneumoniae
* Bordatella pertussis.
188
What are the symptoms of bronchitis?
* Cough ± phlegm
* SOB
* Wheeze
* Fever.
189
What are the investigations of bronchitis?
* CXR
* Viral and bacterial throat swabs
* Serology for mycoplasma and chlamydia.
190
What is the management for bronchitis?
Usually none especially if viral.
191
What is bronchiectasis?
Chronic infection of the bronchi and bronchioles leading to permanent dilatation of central and medium-sized airways due to inflammatory destruction of airway walls resulting in persistently infected mucous.
192
Who is bronchiectasis more common in?
More common in women than men.
193
What is the most common pathogen once bronchiectasis is established?
Pseudomonas aeruginosa.
194
What are the causes of bronchiectasis?
```
Distal pulmonary inflammation and scarring from infection, bronchial obstruction or lung fibrosis (e.g. following radiotherapy).
Obstruction:
• Foreign body e.g. peanut
• Post TB stenosis
• Tumour
• Thick mucus
Post-infection:
• Pseudomonas aeruginosa
• TB
• Measles
• Pneumonia
• Pertussis
Impaired defences, leads to interference of drainage, chronic infections and inflammation:
• Cystic fibrosis
• Immunodeficiency: AIDS and immunoglobulin deficiency
• Congenital: Kartagener’s syndrome, immotile cilia and chronic sinusitis
Radiotherapy.
```
195
Where does bronchiectasis usually affect?
Lower lobes.
196
What is the pathophysiology of bronchiectasis?
Bronchitis -> bronchiectasis -> fibrosis. Overtime, airways become dilated and clogged with mucus) due to pulmonary inflammation and scarring as fibrosis contracts).
Secondary inflammation changes lead to further destruction of airways.
Chronic inflammation causes damage to airways. There is elastin destruction (lung dilates) and collagen deposition which causes stiff, large airways that are plugged with mucous.
197
What are the symptoms of bronchiectasis?
* History of chronic productive cough and recurrent chest infections (pneumonia)
* Finger clubbing, especially with cystic fibrosis, due to long term hypoxia
* Crackles over affected areas, usually at base of lungs.
198
What are the investigations for bronchiectasis?
Lung function test: shows obstructive pattern, less lung capacity and less FEV1.
CXR:
• Dilated bronchi with thickened walls (tramline and ring shadows)
• Multiple cysts containing fluid showing up as cystic shadows.
High resolution CT
• Thickened, dilated bronchi with cysts at end of bronchioles
• Airways larger than associated blood vessels.
Sputum culture: to see colonisation status and exclude non-tuberculous mycobacterial disease
• Pseudomonas aeruginosa
• H. influenzae
• Strep. Pneumoniae
• S. Aureus.
199
What is the management for bronchiectasis?
* Smoking cessation
* Improved mucus clearance: postural drainage, chest physio, mucolytics
Antibiotics:
• Pseudomonas aeruginosa: oral ciprofloxacin
• H. influenzae: oral amoxicillin, co-amoxiclav or doxycycline. Some multi-resistant species needs IV cephalosporin
• S. Aureus: flucloxacillin.
Vaccination: influenza and pneumonia .
Bronchodilators: nebulised salbutamol useful for asthma or COPD sufferers.
Anti-inflammatory agents e.g. azithromycin to reduce exacerbation frequency.
Surgery to remove foreign bodies.
200
What are the complications of bronchiectasis?
* Haemoptysis
* Pneumonia
* Pneumothorax
* Fungal colonisation
* Metastatic abscesses e.g. brain and heart
* Amyloid formation
* Emphysema
* Septicaemia
* Meningitis
* Further necrosis and destruction of lung tissue leading to pulmonary fibrosis
* Cor pulmonale.
201
What inheritance is cystic fibrosis?
Autosomal recessive.
202
What do most people with cystic fibrosis have?
A pancreatic insufficiency.
203
What is the cause of cystic fibrosis?
Mutation in a single gene on long arm of chromosome 7 that codes for cystic fibrosis transmembrane conductance regulator (CFTR) protein.
Deranged transport of chloride and/or other CFTR-affected ions (such as sodium and bicarbonate) leads to an alteration in the viscosity and tenacity of mucous produced at these epithelial surfaces and to increased salt content in sweat glands secretions.
Thick mucus secretions from exocrine glands (lungs, pancreas, skin, gonads), blockage of secretory glands and impaired mucociliary clearance which causes severe lung disease, recurrent infections and pancreatic insufficiency.
Resultant inflammatory responses damage the airways and results in progressive bronchiectasis, airflow limitation and eventually respiratory failure.
204
What is the cystic fibrosis transmembrane regulator (CFTR) protein?
It is a chloride channel and regulatory protein found in epithelial cell membranes in the lungs, pancreas, GI and reproductive.
205
What are the symptoms of cystic fibrosis?
* Cough
* Thick mucus production
* Haemoptysis
* Wheeze
* Fever
* Pancreatic insufficiency: poor weight gain, ateatorrhea
* Neonates: meconium ileus (first stool gets stuck in intestines).
206
What are the signs of cystic fibrosis?
* Recurrent infections
* Salty sweat
* Pancreatic insufficiency: DM and steatorrhea (since enzymes not released to digest fat)
* Bronchiectasis and airflow limitation
* Male infertility due to atrophy of vas deferens and epididymis
* Nasal polyps
* Clubbing
* Sinusitis
* Spontaneous pneumothorax
* Reduced pancreatic enzymes as mucous blocks pancreatic duct.
207
What are the investigations for cystic fibrosis?
* Sweat test: diagnostic, will show high chlorine and sodium
* Genetic newborn screening for known CF mutations: measures immunoreactive trypsinogen (IRT) at time of neonatal heel prick test
* Faecal elastase test
* CXR: shows hyperinflation, increased pulmonary markings and bronchiectasis
* Lung function test: early on only small airways affected and later on it is characteristic of obstructive disease with airflow limitation, hyperinflation and decreased DLCO (the extent oxygen transfers from air sacs to blood)
* Blood DNA analysis of gene defect.
208
Is cystic fibrosis screened for?
Yes as a neonate in the heel prick test.
209
What is the diagnostic test for cystic fibrosis?
Sweat test. Will should high chlorine and sodium.
210
What is the management of cystic fibrosis?
* MDT
* Smoking cessation
* Regular chest physiotherapy: postural drainage, forced expiratory techniques.
Prophylactic antibiotics:
• S. Aureus: flucloxacillin
• H. influenzae: amoxicillin
• Pseudomonas aeruginosa: ciprofloxacin
```
Pulmonary:
• Lung function tests (FEV1)
• Regular sputum cultures
• B2 agonists (salbutamol) and inhaled corticosteroids (beclomethasone) for symptomatic relief
• Lung transplant.
```
211
What type of disease is sarcoidosis?
Type of interstitial lung disease (disease of alveolar/capillary interface).
Multi-system granulomatous disease with lung involvement in 90%. Characterised by non-caseating granulomas throughout body.
212
What is characteristic of sarcoidosis?
Non-caseating granulomas throughout body.
213
Who does sarcoidosis most commonly affect?
* More common in blacks and females
* Usually affects 20-40.
Environmental risk factor: prior infection with mycobacterium tuberculosis.
214
What does a typical sarcoid granuloma contain?
Focal accumulations of epithelioid cells, macrophages and lymphocytes, mainly T cells.
215
What are the symptoms of sarcoidosis?
Depends on region affected.
• Asymptomatic
• General symptoms: fever, weight loss and malaise
• Arthralgia
• If interstitial disease is present: dyspnoea, chest pain and non-productive cough (crackles rare).
216
What is the sign for sarcoidosis?
Bilateral hilar lymphadenopathy.
217
What are the extrapulmonary manifestations of sarcoidosis?
```
Common:
• Eye: anterior uveitis
• Skin: Erythema nodosa, skin papule
• Peripheral lymphadenopathy
• Hepatosplenomegaly
Less common:
• Bone
• Heart: arrhythmias
• CNS
• Kidney
Lofgren’s syndrome:
• Erythema nodosum
• Bilateral hilar lymphadenopathy
• Fever
• Arthralgias.
```
218
How is sarcoidosis staged?
Chest X-ray:
• Stage 0: no changes
• Stage I: bilateral hilar lymphadenopathy
• Stage II: bilateral hilar lymphadenopathy and diffuse interstitial disease
• Stage III: interstitial disease only (reticulonodular pattern)
• Stage IV: pulmonary fibrosis (honeycombing).
219
What are the investigations in sarcoidosis?
```
Chest X-ray.
CT chest.
Bloods:
• Hypercalcaemia: excess Vit D produced by macrophages
• Elevated ACE
• FBC: low WBC count
• Raised ESR
• Hypergammaglobulinemia
• Raised LFTs.
Biopsy.
```
220
What is the diagnostic investigation in sarcoidosis?
Biopsy:
• Transbronchial or mediastinoscopic biopsy of lymph node for non-caseating granulomas
• In around 75% of cases, transbronchial biopsy shows granulomas in parenchyma even if CXR is normal.
221
What is the management for sarcoidosis?
* 85% of stage 1 resolve spontaneously
* 50% of stage 2 resolve spontaneously
* Steroids (prednisolone) for persistent pulmonary infiltrates, lung function abnormalities, hypercalcaemia or involvement of eye, CNS, kidney or heart
* Transplant in severe cases.
222
What value is pulmonary hypertension defined as?
mPAP above 25mmHg.
223
What are the causes of pulmonary hypertension?
```
Pulmonary vascular disorders:
• PE
• Primary pulmonary hypertension
• Veno-occlusive disease
Disease of lung and parenchyma:
• COPD
• Chronic lung disorders
CV:
• Mitral stenosis
• LV HF
• Congenital heart disease.
```
224
What are the symptoms of pulmonary hypertension?
* Exertional dyspnoea
* Fatigue
* Ankle swelling
* Chest pain
* Syncope.
225
What are the signs of pulmonary hypertension?
* Right parasternal heave due to RV hypertrophy
* Loud pulmonary second sound
* Elevated JVP
* Ascites.
226
What are the investigations in pulmonary hypertension?
```
CXR:
• Enlarged pulmonary vessels
• Lucent lung fields
• Enlarged RA
• Elevated cardiac apex due to RV hypertrophy.
ECG: RV hypertrophy and P pulmonale.
Echo.
```
227
What is the management for pulmonary hypertension?
* Treat underlying cause
* Oxygen
* Warfarin
* Diuretics for oedema
* Phosphodiesterase-5 inhibitors
* CCB e.g. amlodipine as pulmonary vasodilators
* Endothelial receptor antagonists e.g. bosenten.
228
What is a pleural effusion?
Excessive accumulation of fluid in the pleural space (can be detected clinically when there is 500ml present or by CXR when there is 300ml present).
229
What do recurrent pleural effusions suggest?
Malignant mesothelioma.
230
What are the 2 types of pleural effusion?
Transudate and exudate.
231
What are the causes of transudate pleural effusions?
Balance of hydrostatic forces in chest favour accumulation of pleural fluid:
• Increased hydrostatic pressure (pushing pressure): Congestive HF (both RHF and LHF), fluid overload, constrictive pericarditis
• Decreased plasma oncotic pressure: nephrotic syndrome, cirrhosis and hepatic failure amd other causes of hypoalbuminaemia (protein losing enteropathy)
232
What are the causes of exudate pleural effusions?
Damaged or altered pleura (resulting in loss of tissue fluid and protein) or impaired lymphatic drainage (typically due to inflammation of pulmonary capillaries)
• Trauma
• Neoplastic: lung carcinoma, lymphoma, metastases (breast, ovary, kidney), mesothelioma
• Inflammatory: non-infectious (collagen vascular disease e.g. RA, SLE), sub-diaphragmatic irritation (pancreatitis), PE and infarction and chronic CHF) and infectious (pneumonia: parapneumonic effusion), empyema (pus in pleural space) and lung abscess and subphrenic abscess).
233
What are the causes of lymphatic pleural effusion (chylothorax)?
Lymphatic fluid accumulates in pleural space:
• Damage during surgery
• Malignancy.
234
What are the risk factors for pleural effusion?
Previous lung infection.
| Asbestos exposure.
235
What is the pathophysiology of a transudate pleural effusion?
Transparent i.e. less protein:
• Pleural fluid protein is less than 30g/L since vessels are normal so fluid can leak out but not protein
• Occurs when the balance of hydrostatic forces in chest favour accumulation of pleural fluid i.e. increased pressure due to the backing up of blood in left-sided congestive HF
236
What is the pathophysiology of an exudate pleural effusion?
Exudes proteins:
• 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
• Occurs due to increased permeability and therefore leakiness of pleural space and/or capillaries, usually as a result of inflammation, infection or malignancy.
237
What are the symptoms of a pleural effusion?
* Cough
* Pleuritic chest pain: sore when inhaling
* SOB: may be worse when lying down.
238
What are the investigations in pleural effusion?
```
CXR:
• Transudates usually bilateral (TB)
• Exudates usually unilateral (EU)
• Blunting of costophrenic angle.
Thoracentesis/Pleural tap (drainage and analysis of fluid):
• Transudate: clear
• Exudate: cloudy
• Lymphatic: looks like milk
Pleural biopsy for TB or malignancy.
Ultrasound: detects small effusions and can guide thoracentesis.
```
239
What is the management of pleural effusion?
* Treatment of underlying cause ± drainage if symptomatic: exudates usually drained if symptomatic and transudates managed by treating underlying cause.
* Pleurodesis: injection that causes adhesion of visceral and parietal pleura to help prevent reaccumulation of effusion e.g. tetracycline.
* Surgery: pleurectomy.
240
What is a pneumothorax?
Air in pleural space leads to partial or complete collapse of lung.
241
Who are spontaneous pneumothorax most common in?
Young males.
242
What is the cause of a pneumothorax?
Caused by rupture of a pleural bleb/sub-pleural bulla (serous filled blister), usually apical (top) and thought to be due to congenital defects in connective tissue of alveolar walls.
Primary (simple):
• Spontaneous rupture of pleural bleb of lung at apex into pleural space
• Predominantly healthy young tall males or those with Marfan’s.
Secondary (complicated):
• Trauma especially iatrogenic e.g. CVP lines, post thoracentesis, mechanical ventilation
• Alveolar rupture due to increased alveolar pressure
• Rupture of subpleural bleb e.g. COPD
• Necrosis of lung tissue adjacent to pleural surface e.g. pneumonia, abscess, lung carcinoma.
Catamenial pneumothorax during menstruation
Tension: 1-way valve of air entering.
243
What are the risk factors for a pneumothorax?
* Male
* Tall and thin
* Smoking
* Age
* Mechanical ventilation.
244
What is the pathophysiology of a pneumothorax?
Normally, pressure in pleural space is negative but this is lost once there is communication with atmospheric pressure i.e. breach in pleura. The elastic recoil of the lung then causes it to deflate partially. Once the communication between the lung and pleural space is closed, air will be reabsorbed slowly.
245
How many people get a recurrence of a pneumothorax?
1/3.
246
What are the symptoms of a pneumothorax?
• Can be asymptomatic
• Pleuritic chest pain
• Dyspnoea
As pneumothorax enlarges, patient becomes more breathless and may develop pallor and tachycardia.
247
What are the signs of a pneumothorax?
* Diminished breath sounds on affected side
* Reduced chest expansion
* Hyper-resonant percussion notes on affected side
* Trachea deviates away
* Decreased tactile/vocal fremitus.
248
What are the investigations in a pneumothorax?
```
CXR:
• Loss of lung markings
• Visible visceral pleural edge
• Radiolucent space
• Do not request in tension pneumothorax as it wastes time.
ABG.
```
249
What is the management of a pneumothorax?
* Observation: small pneumothoraxes resolve spontaneously
* Needle aspiration: at 2nd intercostal space in midclavicular line above rib
* Chest tube connected to underwater seal ± suction: large ones or those complicating underlying disease
* Pleurodesis with sclerosing agent for repeated episodes
* Bleb resection.
250
What is a tension pneumothorax?
Considered to be present when a pneumothorax leads to significant impairment of respiration and/or blood circulation.
251
What are the causes of a pneumothorax?
Tends to occur in ventilation, resuscitation, trauma or in patients with lung disease.
252
What are the symptoms of a tension pneumothorax?
* Dyspnoea
* Pleuritic chest pain
* Trachea deviated away from affected side
* Mediastinal shift
* Tachycardia
* Tachypnoea
* Low O2
* Low BP.
253
What is the management of a pneumothorax?
ABCDE, 100% O2 non-rebreather mask, needle aspiration and chest drain.
254
What is a pulmonary fibrosis?
Fibrosis of the lung interstitium causing restrictive defect.
255
Who is usually affected by pulmonary fibrosis?
Usually male >60.
256
What is the pathophysiology of pulmonary fibrosis?
Patchy fibrosis of interstitium, minimal or absent inflammation, acute fibroblastic proliferation and collagen deposition.
257
What are the symptoms of pulmonary fibrosis?
```
• Breathlessness
• Non-productive cough
• Finger clubbing (2/3)
• Inspiratory basal crackles.
Eventually leading to: respiratory failure, pulmonary hypertension, cor pulmonale.
```
258
What are the investigations in pulmonary fibrosis?
* Chest X-ray: ground glass appearance (honeycomb lung)
* CT is the most sensitive
* ABG: hypoxia normal CO2
* Spirometry: ANA and RF antibody in 1/3.
259
What is the management of pulmonary fibrosis?
High dose prednisolone (30mg).
| Lung transplant.
260
What is Goodpasture's syndrome?
Co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage and presence of circulating antibodies against an intrinsic agent to basement membrane of both lung and kidney.
261
What is the cause of Goodpasture's syndrome?
Autoimmune. Anti-GBM antibodies.
Specific autoimmune disease caused by a type II antigen-antibody reaction leading to diffuse pulmonary haemorrhage, glomerulonephritis (and often AKI and CKD). These are circulating anti-glomerular basement membrane (anti-GBM) antibodies.
262
What are the symptoms of Goodpasture's syndrome?
* Typically starts with upper respiratory tract infection e.g. sneezing, nasal discharge, nasal congestion, runny nose
* Fever
* Cough
* Tiredness.
263
What are the signs of Goodpasture's syndrome?
* Intermittent haemoptysis
* Anaemia: may result from persistent intrapulmonary bleeding
* Acute glomerulonephritis.
264
What are the investigations in Goodpasture's syndrome?
* Anti-GBM antibodies in blood
* CXR: transient patchy shadows/pulmonary infiltrates due to pulmonary haemorrhage often in lower zones
* Kidney biopsy: crescentic glomerulonephritis.
265
What is the management in Goodpasture's syndrome?
* Corticosteroids: prednisolone
* Plasmapheresis: remove blood and clean to remove anti-GBM antibodies before inserting it back
* Bilateral nephrectomy in severe/unresponsive cases.
266
What is Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
Type of Anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitis.
Multisystem disorder of unknown origin characterised by necrotising granulomatous inflammation and vasculitis (patchy inflammation of walls of blood vessels that leads to damage and thrombosis) of small and medium vessels.
267
What is the pathophysiology of Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
* Inflammation of blood vessels with granulomas
* As neutrophil rolls along blood vessels before it migrates into tissues, autoantibodies bind to it and activate neutrophils inappropriately (before they have entered tissues where there are no pathogens)
* Results in recruitment of more neutrophils and more activated neutrophils when there is no infection
* Results in production of ROS and neutrophil degranulation
* Leading to the generation of micro-abscesses, recruitment of monocytes, macrophages and lymphocytes to make granulomas
* Results in devastating inflammation affecting many organs including lung and kidney.
268
What are the symptoms for Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
* Fever
* Anorexia
* Weight loss
* Cough
* Pleuritic chest pain.
269
What are the signs of Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
Triad of:
• Necrotising granulomatous lesions of upper and lower respiratory tract
• Focal necrotising lesions of arteries and veins
• Focal glomerulonephritis.
* Saddle-nose deformity: nasal mucosal ulceration
* Haemoptysis.
270
What are the investigations for Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
CXR: solitary or multiple lesions (1-10cm) with marked tendency to cavitate.
Bloods:
• C-ANCA positive
• Elevated PR3 antibodies
• Raised ESR and CRP.
CT: diffuse alveolar haemorrhage.
Biopsy: lung and/or kidney.
271
What is the major differential diagnosis for Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
Churg-Strauss syndrome (also affects small arteries):
• Presents as late onset asthma
• Symptoms: malaise, fever, weight loss
• Signs:
Rhinitis (inflammation inside of nose)
Asthma
Eosinophilia
Systemic vasculitis involving lungs, pericardium, heart, kidneys, skin and PNS
High eosinophil count
ANCA positive.
• Treatment: corticosteroids and cyclophosphamide.
272
What is the management for Wegener’s Granulomatosis (Granulomatosis with Polyangiitis [GPA])?
* Corticosteroids e.g. prednisolone and cyclophosphamide or rituximab to induce remission
* Azathioprine and methotrexate used as maintenance.
273
What cells is methothelioma a tumour of?
Mesothelial cells of the pleura. Other sites include mesothelial cells of the peritoneum, pericardium and testes.
274
What are the main pulmonary tumours that affect the pleura?
• Malignant mesothelioma
• Pleural fibroma.
And metastatic disease.
275
How long is the latent period in mesothelioma?
Latent period between exposure and development of tumour may be up to 45 years.
276
What is the risk factor for mesothelioma?
Asbestos exposure.
277
What is the pathophysiology of mesothelioma?
High grade malignancy of the pleura (80%) that spreads around pleural surfaces but can also start in pericardial space, peritoneal space and paratesticular space. Tumour begins as nodules in pleura which extend as a confluence sheet to surround the lung and extend into fissures. There is pentration of the visceral pleura which leads to transport of the fibre to the pleural surface. Chest wall often invaded, with infiltration of intercostal nerves, giving severe intractable pain. Lymphatics may be invaded, giving hilar node metastases.
278
How likely is mesothelioma to metastasise?
Rarely.
279
What are the symptoms of mesothelioma?
* Persistent chest pain, dull diffuse
* Dyspnoea
* Cough
* Weight loss.
280
What are the signs of mesothelioma?
* Clubbing (finger)
* Recurrent bloody pleural perfusion
* Signs of metastases: lymphadenopathy, hepatomegaly, bone pain and abdominal pain/obstruction.
281
What are the investigations in mesothelioma?
* Gold standard is pleural biopsy
* Thoracoscopy
* Chest X-ray and CT showing unilateral pleural effusion and pleural thickening
* Pleural aspiration: straw coloured or blood stained.
282
What is the gold standard investigation for mesothelioma?
Pleural biopsy.
283
What is the management of mesothelioma?
* Pemetrexed + Cisplatin chemotherapy
* Rarely successful (average year of survival < 1 year)
* Surgery: resection (pleurectomy and decortication may relieve all pain and effusions)
* Radiotherapy mostly for pain control
* Pleurodesis and indwelling intra-pleural drain may help.
284
What is a lung abscess?
Localised cavity with pus resulting from tissue necrosis, with surrounding pneumonitis.
285
What are the causes of lung abscesses?
* Aspiration of upper airway anaerobic organisms
* Inadequately treated pneumonia especially S. Aureus and klebsiella pneumoniae
* Bronchi obstruction: tumour, foreign body
* Pulmonary infarction
* Septic emboli.
286
What are the symptoms of lung abscesses?
• Acute or insidious with early symptoms similar to pneumonia
• Purulent sputum, may be blood streaked ( putrid odour so anaerobes)
Chronic abscess:
• Weight loss
• Anaemia
• Clubbing
• Physical signs of consolidation.
287
What are the investigations in a lung abscess?
* CXR: thick-walled cavity with fluid level
* CT
* Sputum culture and gram stain
* Transtracheal/thoracic aspiration
* Bronchoscopy with culture.
288
What is the management in a lung abscess?
* Antibiotics depending on culture and sensitivity
* Postural drainage
* Surgical drainage and resection is rarely necessary.
289
What can exposure to dusts, gases, vapours and fumes at work lead to?
* Occupational asthma is the most common industrial lung disease in developed world
* Acute bronchitis and pulmonary oedema from irritants such as sulphur dioxide, chlorine, ammonia, oxides or nitrogen
* Pulmonary fibrosis from inhalation of inorganic dust e.g. coal, silica, asbestos, iron and tin
* Hypersensitivity pneumonitis
* Bronchial carcinoma due to asbestos, polycyclic hydrocarbons and radon in mines.
290
What are the causes of occupational lung disorders?
* Fumes
* Dust
* Gas
* Vapour
* Mists.
291
What are the key points relating to occupational asthma?
* Latent period
* Deteriorating symptoms, worse as week goes on
* Gradual improvement, on days off
* Most jobs but in exams: wood, flour, metal working fluids, isocyanate spray paint
* Depression
* Destroys lives.
292
What are the risk factors for occupational asthma?
* Woodcutting
* Working in a bakery
* Isocyanate spray paint
* Metal working
* Chlorine based cleaning solutions
* Biomass.
293
What is hypersensitivity pneumonitis (previously known as extrinsic allergic alveolitis)?
Type of interstitial lung disease with distinct cell infiltrates and ECM deposition in lung distal to the terminal bronchiole i.e. disease of the alveolar/capillary interface.
294
What type of hypersensitivity is hypersensitivity pneumonitis?
Combined type III/IV.
295
What are the causes of hypersensitivity pneumonitis?
* Usually from mould
* Farmer’s lung: mouldy hay (micropolyspora faeni)
* Bird fancier’s lung: handling pigeons, cleaning lofts or bird cages
* Malt worker’s lung: turning germinating barley (aspergillus clavatus)
* Humidifier fever: contaminated humidifying systems in air conditioners or humidifiers
* Mushroom workers: turning mushroom compost (thermophilic actinomycetes)
* Cheese washer’s lung: mould cheese (penicillium casei and/or aspergillus clavatus)
* Wine maker’s lung: mould on grapes (botrytis).
296
What is the most common type of hypersensitivity pneumonitis?
Farmer's lung from mouldy hay.
297
What is the pathophysiology of farmer's lung?
* Fungus in mouldy hay 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 granuloma
* The inflammatory process may resolve on withdrawal of the antigen but if there is chronic exposure then pulmonary fibrosis will develop.
298
What is always present in hypersensitivity pneumonitis?
Granulomas always present.
299
What are the symptoms of hypersensitivity pneumonitis?
```
Acute: 4-6 hours after exposure
• Fever
• Dry cough
• Dyspnoea
• Malaise
• Rigors
• Inspiratory squeaks due to bronchiolitis
• Crackles (no wheeze)
• Tight chest
• CXR: diffuse infiltrates
• Lung function tests: modestly and transiently restrictive
• Type 3 (immune complex) reaction
```
Subacute:
• History of repeated acute attacks
• Signs same as acute, symptoms less severe and more gradual
• Can present as recurrent pneumonia
• Improvement is seen in weeks to months following removal from exposure
Chronic:
• Usually no history of preceding acute symptoms
• If the source of antigen is removed only partial improvement of symptoms
• Cyanosis and clubbing may develop
• Weight loss
• Increased dyspnoea
• Type 1 Respiratory failure (low PaO2, normal/low PaCO2)
• CXR: predominantly upper lobe, nodular/reticulonodular pattern
• Lung function test: progressively restrictive
• Type 4 (cell mediated, delayed hypersensitivity) reaction.
300
What are the investigations for hypersensitivity pneumonitis?
* CXR
* Lung function test
* FBC: raised WBC count and ESR
* High-resolution CT
* Bronchoalveolar lavage: shows increased T-lymphocytes and granulocytes
* Video Assisted Thoracoscopic Surgical (VATS) biopsy.
301
What is the management for hypersensitivity pneumonitis?
```
Prevention.
Acute:
• Remove allergen
• Give O2 (35-60%)
• Oral prednisolone followed by reducing dose
Chronic:
• Avoid exposure to allergen
• Prednisolone.
```
302
What is pneumoconiosis?
Lung disease caused by inhalation of mineral dust.
• Asbestosis. Can cause: pleural disease, pulmonary fibrosis, cancer
• Coal worker’s pneumoconiosis: inhaling coal particles
• Silicosis: inhaled silica particles
• Other unspecified pneumoconiosis.
303
What is asbestosis?
* Interstitial lung fibrosis
* Long latency (decades)
* History of heavy exposure
* No effective treatment
* May progress slowly (without further exposure)
* Progressive breathlessness
* CXR: fibrosis (linear streaking, especially at base), asbestos exposure can also cause pleural thickening (± calcification) or pleural effusion
* Microscopic examination characteristically reveals ferruginous bodies: yellow-brown rod-shaped structures which represent asbestos fibres coated in macrophages
* Increases risk of bronchogenic carcinoma and malignant mesothelioma.
304
What is silicosis?
* Workers at risk: sandblasters, rock miners, quarry workers, stone cutters
* Need around 20 years of exposure
* CXR: upper lobe reticulonodular disease. When nodules become larger and coalescent, disease has changed from simple silicosis to complicated silicosis (progressive massive fibrosis)
* Possible hilar lymph node enlargement (frequent calcification)
* Risk factor for mycobacterial infection i.e. TB.
305
What drugs cause pneumoconiosis?
* Chemotherapeutics: bleomycin, mitomycin, busulfan, cyclophosphamide, MTX
* Amiodarone
* Gold
* Nitrofurantoin.
306
What is FEV1?
Volume of air that can be forcefully expired in 1 second.
307
What is FVC?
Total volume of air that can be forcibly exhaled after maximum inhalation.
308
What is the FEV1/FVC ratio in restrictive?
>0.8.
| E.g. in pulmonary fibrosis.
309
What is reduced in restrictive?
FVC.
310
What is type 1 respiratory failure?
Low PO2 and low/normal pCO2.
311
What is type 2 respiratory failure?
Low PO2 and high pCO2 (hypoventilation).
312
What is the thin serious layer that covers the lungs?
Visceral pleura.
313
Where is the parietal pleura?
On the chest wall and pericardium.
314
What are the functions of the pleura?
* Allows movement of lung against chest wall
* Coupling system between lungs and chest
* Clearing fluid from pulmonary interstitium.
315
What is the normal amount of fluid in the pleural space?
Around 25ml.
316
What is the pleural space?
Between the parietal and visceral pleura. Lubricates movement between them.
