Week 8 - Respiratory Flashcards

Question

How can lung volumes be measured?

Answer 1

* Unable to measure residual volume by spirometry * 2 methods of measuring: * Helium dilution (inspire known quantity of inert gas) * Body plethysmography (respiratory manoeuvres in a sealed box lead to changes in air pressure - can derive lung volumes)

Answer 2

* Parathyroid hormone produced by parathyroid gland in response to low serum calcium * Stimulates osteoclast activity in bones * Serum calcium raised, negative feedback to parathyroid gland to stop excessive PTH production * When PTHrP secreted by tumour there is no negative feedback on tumour so secretion is constant * Hypercalcaemia

Answer 3

FEV1 \<80% - worsening airflow limitation and shortness of breath typically developing on exertion FEV1 \<50% - increased breathlessness and repeated exacerbations impact patient quality of life (increasing number and severity of exacerbation will likely lead to increasing hospitalisation FEV1 \<30% - severe breathlessness and respiratory failure, marked by hypoxaemia. Pulmonary hypertension usually develops following severe hypoxaemia. Systemic, extrapulmonary effects may include systemic inflammation and skeletal muscle dysfunction.

Answer 4

* Able to force air through small spaces quickly - average man breathes out 4-5L of air in 6 seconds (woman 4L) * Flexible tubes for high speed flow * Significant vulnerability - few tubes for large volume of air * Large surface area for gas exchange

Answer 5

* Respiratory failure = low pO2 (paO2 \<8kPa on room air - 21% inspired oxygen) * Type 1 - low pO2, low/normal CO2 (e.g. PE, pneumonia) * Type 2 - low pO2, CO2 high (acidotic) e.g. COPD * Respiration driven by levels of CO2 in blood * In COPD airways tight so don't breathe out CO2 as effectively so CO2 levels constantly high * Brain relies less on CO2 as drive to breathe - uses low O2 level as indicator to increase respiratory drive * Low pO2, in hospital given oxygen * When relying on being hypoxic to breathe lose respiratory drive, respiratory rate drops, get much more ill --\> comatose

Answer 6

Lots of lipid due to retention of secretions including surfactant = yellowish colour

Answer 7

* Spectrum of increasing symptoms/breathlessness, number of exacerbations in past year and severity of airflow limitation * Severe airflow limitation = more exacerbations * A = few symptoms, mild airflow limitation * B = very symptomatic, mild airflow limitation * C = severe airflow limitation, few symptoms * D = severe airflow limitation, very symptomatic * High risk of exacerbations - severe airflow limitation * C, D * Low risk of exacerbations - mild airflow limitation * A, B

Answer 8

* Evaluation of the breathless patient * Screening for COPD (e.g. in symptomatic smokers) or occupational lung disease * Lung cancer - fitness for treatment * Pre-operative assessment (anaesthetic risk) * Disease progression and treatment response * Monitoring of drug treatment toxic to the lungs * Pulmonary complications of systemic disease

Answer 9

* Inappropriate ACTH secretion by tumour * Adrenal hyperplasia, raised blood cortisol --\> Cushing's syndrome * Inappropriate ADH secretion by tumour * Retention of water by kidneys, dilutional hyponatraemia (SIADH - syndrome of inappropriate antidiuretic hormone secretion) * Parathyroid hormone related peptide secretion * Osteoclastic activity --\> hypercalcaemia * Other non-metastatic effects: * Encephalopathy * Cerebellar degeneration * Neuropathy * Myopathy * Eaton Lambert myasthenia-like syndrome * Cancer associated retinopathy - antibodies to photoreceptor cells produced

Answer 10

Tolerance - not a medical state (expected) Intolerance * Inability to cope with something normally acceptable * Not same as poison - everyone reacts the same

Answer 11

* Time to steady state 2-3 days - plasma theophylline levels at 5 days/3 days after dose adjustment * Narrow therapeutic window: 10-20mg/L * Drug monitoring 4-6 hours post-dose * Toxicity - severe vomiting, hypokalaemia/hypocalcaemia, seizures, arrhythmias, hypotension * Weight based dosing for IV infusions * Metabolised in the liver - caution in liver disease and with concomitant use of some antibiotics including rifampicin, clarithromycin, ciprofloxacin * Rifampicin reduces levels, clarithromycin/ciprofloxacin increases * Smoking increases theophylline clearance - dose may need adjusted following smoking cessation

Answer 12

* Imaging * Bloods * Sampling * As few interventions as possible * Never drain an undiagnosed effusion - easier to get samples to aid diagnosis if not drained fully * Local anaesthetic thoracoscopy

Answer 13

Up to 50% of pneumonias will have an associated effusion

Answer 14

* FEV1 of 85% predicted may be considered 'normal' in some patients * FEV1 of 100% predicted may represent significant decline if values supra-normal at the start * Corrected for age, gender, race, height and atmospheric values

Answer 15

PTE, musculoskeletal pain, pleurisy/pneumonia

Answer 16

Brainstem related - brain not giving signal to maintain respiration e.g. due to opioids

Answer 17

* Upper/extra-thoracic airways * Not susceptible to intra-thoracic pressure - thick walled, tubes held open so linear airflow * Narrowing causes stridor - whistling on inspiration * E.g. laryngeal oedema - thyroid, scarring, epiglottis * Stridor * Flow-volume loops * CXR not helpful * Aspiration to right middle/lower lobe * Bronchial disease * Susceptible to intra-thoracic pressure * Thin-walled airways, susceptible to changes in resistance * Easily collapsible e.g. due to allergy

Answer 18

* Direct visual examination of the pleura with a thoracoscope * Indicated in undiagnosed cytology negative pleural effusion * Performed under local anaesthesia and mild sedation * Direct visualisation of the pleural surface * Biopsy of areas which appear abnormal * Definitive effusion management * Diagnostic rate approx. 90% for malignant pleural disease * E.g. nodular plaques = asbestos exposure, loculations = infection

Answer 19

PAO2 = FiO2 – (1.25 x PaCO2) PAO2 = Alveolar oxygen partial pressure, kPa FiO2 = Inspired oxygen concentration, kPa

Answer 20

* Occupational and environmental - silicosis, asbestosis, hypersensitivity pneumonitis (EAA) * Drug induced - amiodarone, nitrofurantoin, methotrexate, cocaine * Connective tissue diseases - lupus, RA, scleroderma * Primary diseases - sarcoidosis, LAM * Idiopathic (25%)- IPF, NSIP * Genetics \>200 causes

Answer 21

Non-small cell carcinoma generally has the better prognosis

Answer 22

Cough Haemoptysis Shortness of breath Chest pain Weight loss/anorexia General malaise

Answer 23

* Hyperinflated - air spaces destroyed w big balls of air, lose recoil of lung * Count no. of ribs above diaphragm - more than 6 anterior or 10 posterior = hyperinflation * Dark lungs due to loss of BVs (white) * Heart thin * Flattened hemidiaphragms * Ribs flattened

Answer 24

* ADH secreted by posterior pituitary in response to low sensed volume/low BP/low osmolality * Acts on kidneys to retain water - negative feedback to stop over secretion of ADH * When secreted by tumour there is no negative feedback on the tumour so secretion of ADH is constant * Kidneys always stimulated to retain water

Answer 25

Acute PE 1. Risk stratify * High risk - thrombolysis * Intermediate risk - ?thrombolysis * Low risk - ?early discharge 2. LMWH * LMWH * 3-6/12 warfarin * 3-6/12 novel agent 3. Risk stratify * Long term anticoagulation? * CTEPH screening * Cancer screening?

Answer 26

Treatment of asthma Treatment of COPD

Answer 27

* Amphotericin B has to be infused intravenously * Quite toxic - high concentration locally when injected, interacts w/ cholesterol at high concentration, destroys cells * New formulation * Amphotericin B integrated into part of liposomes - infused into bloodstream, diffuses slowly to where fungal infection is * Much more safe

Answer 28

* Fungi that cause common infections of skin, nails and hair * Do not colonise 'live' tissues, instead keratinised areas such as nails and outer skin * Specialised niche, use keratinases, elastase and other proteinases from digestion of skin/hair/nails as virulence factors * Slow growing/slow response to treatment - slowly digest tissues to release virulence factors to feed themselves and grow * Also known as 'ringworm' or 'tinea' * Spreads radially outwards from principal contact point

Answer 29

* Blue Bloater - chronic bronchitis * Low respiratory drive * Type 2 respiratory failure * Low pO2, high pCO2 * Signs * Cyanosis * Warm peripheries * Bounding pulse * Flapping tremor * Confusion, drowsiness * Right heart failure * Oedema, raised JVP * Pink Puffer - emphysema * High respiratory drive * Type 1 respiratory failure * Low pO2, low pCO2 * Signs * Desaturates on exercise * Pursed lip breathing - automatic response to prevent airways collapsing * Use accessory muscles * Wheeze * Indrawing of intercostals * Tachypnoea

Answer 30

Treatment of asthma Treatment of COPD

Answer 31

* History - esp. from partner v important * Clinical examination * Weight * BMI * BP * Neck circumference (\>40cm) * Craniofacial appearance (Retrognathia, Micrognathia) * Tonsils * Nasal patency * Mallampati score - relates tongue size to pharyngeal size, visualise size of airway * Risk criteria/scores for excessive daytime sleepiness * The Epworth sleepiness score - how likely would you be to fall asleep in different situations? * The STOP-BANG questionnaire - risk criteria for how likely to have OSA * The Berlin questionnaire

Answer 32

* Very high mortality and short life expectancy following diagnosis * UIP mortality 50% by 2 years

Answer 33

If CXR shows bilateral hilar lymphadenopathy and all other causes have been excluded 99% are sarcoidosis, don’t really need biopsy

Answer 34

High, intermediate-high and intermediate-low risk patients should be hospitalised Low risk patients do not need hospitalisation - early discharge and home treatment

Answer 35

* Relates oxygen saturation to partial pressure of oxygen in the blood (pO2) - determined by haemaglobin affinity for oxygen * As the partial pressure of oxygen increases the affinity of haemoglobin for oxygen increases and so the oxygen saturation increases * Plateaus as saturation reaches close to 100% * Normal partial pressure = 12kPa * Increase beyond normal makes very little difference to oxygen saturation - oxygen carrying capacity not improved (giving oxygen if normal sats is useless) * If saturation is low, increasing pO2 by a small amount increases saturation significantly (can give a small amount of O2 to correct low sats)

Answer 36

Thickened smooth muscle of airways is 'twitchy' - saw-toothing of peak flow morning to night and reduces as week goes on Consequence of hyperactivity of smooth muscle in airway

Answer 37

Polycythaemia - raised Hb and PCV

Answer 38

* Flu-like illness * Cough * High fever, chills * Dyspnoea, chest tightness * Malaise, myalgia * 4-8 hours after exposure * Chronic disease - dyspnoea in strain, sputum production, fatigue, anorexia, weight loss

Answer 39

* Hypoventilation (e.g. drugs, neuromuscular disease) * Ventilation/perfusion mismatch (e.g. COPD, pneumonia - perfusing parts of lung which aren't ventilated) * Shunt e.g. congenital heart disease * Low inspired oxygen (altitude, flight) * Assessment for fitness to fly can be done

Answer 40

* Smoking induces inflammatory infiltrate around airways * Infiltration with neutrophils and CD8+ lymphocytes * Neutrophils not very responsive to steroids (unlike asthma) * Inflammation = squamous metaplasia * Increased epithelial mucous cells + mucous gland hyperplasia --\> more mucous, clogs airways (further inflammation) * Free oxygen radicals - loss of interstitial support

Answer 41

1. Is the tumour central or peripheral in the lung? 2. Has the cancer spread locally or distantly? 3. Non-metastatic effects of the tumour

Answer 42

* Metastatic spread * Lung most common * Breast, ovarian * Also bowel, renal, lymphoma etc.

Answer 43

* Forced expiration manoeuvre from total lung capacity followed by full inspiration * Take a big breath in as far as you can and blow out as hard as you can for as long as possible - then take a big breath all the way in * Best of 3 acceptable attempts (within 5%)

Answer 44

* Appropriate symptoms with signs * Wheeze, cough, yellow/clear sputum * Breathlessness, exercise intolerance * Episodic, triggered, variable - paroxysmal * Exercise * Allergy e.g. cats * Chemical/physical (salicylate/aspirin) - hyper-reactivity * 15% asthmatics can't tolerate aspirin - side effects exaggerated due to hyper-reactivity * Diurnal - nocturnal awakening * Respond to asthma therapies

Answer 45

Clinical signs * Decreased breath sounds, stony dull to percussion, decreased tactile or vocal fremitus CXR Appearance: * Need \>300ml of fluid to be present to be seen on CXR * Uniformly white appearance * Blunting of the costophrenic and cardiophrenic angles * A meniscus at the upper edge

Answer 46

Appropriate clinical story Supportive physiological tests: * Serial peak flow measurement * Bronchial challenge test * Reversibility of airflow obstruction * Skin prick test * Plethysmography

Answer 47

* Loss of elasticity and alveolar attachments due to emphysema - airways collapse on expiration * Causes air-trapping and hyperinflation --\> increased work of breathing --\> breathlessness * Goblet cell metaplasia with mucous plugging of lumen * Inflammation of the airway wall * Thickening of the bronchiolar wall * Smooth muscle hypertrophy and peri-bronchial fibrosis

Answer 48

* Probably a multi-step process * Chronic irritation/stimulation of cells by carcinogens * Increased cell turnover * Metaplasia - from normal pseudostratified columnar ciliated with goblet cells to squamous * Progressive accumulation of genetic abnormalities in molecules involved in cell cycle, signalling and angiogenesis pathways * Little known about rate of progression/regression * Phenotypic changes potentially reversible (but genotypic alterations persist)

Answer 49

Problematic patients, severe retrognathia/micrognathia

Answer 50

NOACs/DOACs: * Fixed dose * No monitoring * Few drug-drug or drug-food interactions * Lots of studies show efficacy in VTE * Just as good as warfarin at preventing further clots, with lower bleeding risk (safer)

Answer 51

* Limited polysomnography * Full polysomnography * Transcutaneous oxygen saturations and carbon dioxide assessment (TOSCA)

Answer 52

* Cilia are damaged/destroyed by smoking, cilial motility reduced - don't clear secretions as effectively leading to increased susceptibility to infection and damage to the lungs * Airway inflammation * Hypertrophy of goblet cells and mucous cells, higher mucous production - cough more * Increased protease activity (released from inflammatory cells), anti-proteases inhibited * Digestion of lung, not enough anti-protease activity to inhibit * Oxidative stress - free radicals * Squamous metaplasia --\> higher risk of lung cancer * Carcinogens absorbed and circulate - higher risk of other cancers

Answer 53

* Pulmonary hypertension causes pressure overload of RV * RV does not cope well with overload, dilatation and reduced stroke volume * Increase pressure from normal mean pulmonary artery pressure of 14mmHg --\> \>25, stroke volume of RV drops massively * Small clots can have big impact on function of heart

Answer 54

* Multiple - not very specific agents * Diabetes, osteoporosis, hypertension, muscle wasting, peptic ulceration, cataracts, Cushing's syndrome, adrenal suppression, acute pancreatitis, hyperlipidaemia, increased appetite, salt and water retention, immune suppression

Answer 55

* Lung function tests - need full PFTs if considering surgery * ECG * PET-CT for staging, to check if surgically treatable

Answer 56

Can be normal Common features - sinus tachycardia, S1Q3T3 appearance (pathopneumonic of acute PE but only in 20% cases)

Answer 57

* Rapidly absorbed orally, can cause phlebitis intravenously so avoid if possible * Undergoes hepatic metabolism therefore caution in liver failure and reduce dose in significant renal impairment * Inhibits CYP450 - risk of adverse drug interactions * Withhold simvastatin * Cardiac cautions: QT prolongation, giving risk of arrhythmia

Answer 58

Low BMI (\<21) associated with poorer prognosis

Answer 59

* Treat the symptomatic - OSAS (daytime sleepiness) * AIM = improve daytime somnolence and quality of life * Explain OSAS * Weight loss * Avoid triggering factors e.g. alcohol * Treat underlying conditions - tonsils, hypothyroidism, nasal obstruction * Come off sedating medications overnight * Continuous positive airway pressure (CPAP) * Mandibular advancement device (MAD) * Maxillary-mandibular surgery * Sleep position trainers

Answer 60

Immunologically mediated inflammatory reaction in the alveoli and in the respiratory bronchioles It is NOT atopy, it is a T-cell mediated response

Answer 61

Interstitial lung disease (stiff lungs) Kyphoscoliosis - chest wall abnormality Previous pneumonectomy Neuromuscular disease - Guillain-Barre, MND Obesity Poor effort/technique

Answer 62

* Mask over nose gently directs air into the throat to keep the airway open * Splints airway open * Stops snoring * Stops sleep fragmentation * Improves daytime sleepiness and quality of life * Need compliance \>4 hours for \>70% days * Fixed vs autoset CPAP * Fixed = same pressure throughout * Auto = varying pressure calculated by machine throughout sleep, generally tolerated better * Nasal vs full face mask * Follow up - annually by physiology once CPAP established * 2 way remote monitored CPAP - can remotely monitor compliance and oxygen/CO2 levels etc.

Answer 63

* Larger airways \>4mm in diameter * Inflammation leads to scarring and thickening of airways * Breathing inefficient - trapped air, can't breath out efficiently * Exercise - respiratory rate increases, not enough time to breathe out properly so become hyperinflated (causes discomfort) * Small airways disease: * 'Bronchiolitis' in airways of 2-3mm * May be an early feature of COPD * Narrowing of the bronchioles due to mucous plugging, inflammation and fibrosis

Answer 64

Adjunct to inhaled therapy in asthma/intravenous infusion in severe exacerbations of asthma Not very effective in COPD

Answer 65

* CTPA - most common, time contrast to maximise in main pulmonary artery to see vasculature * VQ - ventilation perfusion scanning, inhale radioactive gas and inject radioactive albumin, sits in pulmonary vasculature, look at two and see if they match up (if ventilation but no perfusion suggests PE) * VQ spect - used in pregnant women, lower radioactive dose * Pulmonary angiography - inject dye * CT - look at pulmonary artery and RV function

Answer 66

* Outcome - Median survival 3 -5 years from time of diagnosis * Rate of progression varies - generally have a steady, progressive decline but may also have sudden steps of decline after exacerbations/infections * Most patients (around 75%) will die of respiratory illness. Approximately 1in 10 patients will develop lung cancer.

Answer 67

* How well can they tolerate breathing in histamine, methacholine or mannitol (which causes histamine release by making mast cells in the lung burst) * Everyone would eventually react but asthmatics show bronchial hypersensitivity * FEV1 dips faster than normal in asthmatics * Positive = fall by \>20% FEV1 by \<8mg/ml methacholine/histamine/mannitol * Not an allergy to histamine, just hypersensitivity compared to normal

Answer 68

* Drainage (12-16F) * Larger drains more painful and no more effective * IV antibiotics * Fibrinolytics - enzymes to break down * Surgery * Ongoing clinical trials

Answer 69

* Damaged epithelial cells * Activated to release growth factors - TGFβ1 one of most important * Fibroblasts/myofibroblasts * Myofibroblasts secrete excessive amounts of extracellular matrix proteins, mainly collagens * Type 1 pneumocytes are reduced * Injured cells produce TGFβ1 which promotes the transformation of fibroblasts to myofibroblasts * Fail to develop from type 2 pneumocytes add to the deveopment of dysfunctional alveolar epithelium * Reduced levels of calveolin 1, an anti-fibrotic molecule produced by these cells * Eosinophils, mast cells, macrophages and lymphocytes * Release cytokines such as IL-4, IL-1, TNFα and IFNγ

Answer 70

If not improving after 15-30 minutes (or if life-threatening features are present): * Discuss with senior clinician and ICU tam * Consider giving infusion of IV magnesium sulphate 1.2-2g infusion over 20 minutes and then either IV aminophylline or IV salbutamol (or terbutaline) * Consider transfer to ITU for mechanical ventilation if no improvement

Answer 71

* Serial peak expiratory flow measurements - look for diurnal variation * Spirometry - have airflow obstruction, \>400ml improvement in FEV1 following bronchidilator * Metacholine or histamine bronchial provocation test- look for a drop of 20% in FEV1 from baseline * Exhaled nitric oxide - a marker of airway inflammation (raised level \>25 ppb) * CXR - usually normal, pneumothorax in acute asthma or infiltrates in ABPA * Skin prick tests or specific IgE levels - should be done, common allergens * Blood and sputum tests - may have raised blood eosinophils, often have raised sputum eosinophils but not routinely done

Answer 72

Patients can experience headache, blurred vision, epilepsy, can be silent depending on location

Answer 73

Numerous poorly defined small (\<5mm) opacities throughout both lungs Sometimes with sparing of the apices and bases Airspace disease - usually seen as ground glass opacities Fine reticulation may also occur Zonal distribution

Answer 74

* Allergy is immune system mediated intolerance * Requires exposure to a trigger * Memory * Characteristic clinical features * Dependent on which arm of the immune system * Clinical reaction * Acute - sudden or slow - progressive * Chronic allergy leads to tissue remodelling * Acute inflammation - repair 1. Trigger (which most people are tolerant of) 2. Immune system recognises as foreign (external, not part of own body) * Antigen-presenting cell, T cell * IL-4, IL-33 or IL-12, IFN 3. Memory 4. Response * IL-4, IL-33 --\> IgE, mast cell - immediate response (anaphylaxis, asthma etc.) * IL-12, IFN --\> reactive T cells - delayed response

Answer 75

* Acute illness due to type II reaction * Serum sickness or immune complex disease * Sub-acute days to weeks * Type IV T-cell mediated reaction (like chronic dermatitis of lung) * Chronic disease - fibrosis and emphysema * Final pathway of all chronic inflammatory conditions

Answer 76

From a practical point of view division into - * Small cell and non-small cell lung cancer is the most important decision for treatment * Small cell - usually advanced at diagnosis and responds to chemotherapy * Non-small cell - may be localised at diagnosis and can be treated by surgery or radiotherapy * With advancement in therapies subdivision of non-small cell cancers is increasingly important

Answer 77

Supine OSA Vibration when on back Weeks to change sleeping position Appropriate in few patients with supine OSA

Answer 78

Arterial pO2 (PaO2) can be directly measured- ABG The difference between the calculated alveolar pO2 and the arterial pO2 is the alveolar arterial (A-a) oxygen gradient Difference between alveolar and arterial oxygen partial pressures should be \<2-4 kPa- more than this suggests V/Q mismatch

Answer 79

* Oedema of face and arms * Raised JVP * Dilated veins on chest wall * Plethoric face * Headache worse on stooping

Answer 80

* Straightforward * Many over the counter products * Sprays, creams, tablets, powders, liquids * Topical administration usually * Oral medication * Severe infections, nail infections * Topical medication has not worked * Adults only * Active ingredients * Terbinafine (Lamisil) * Itraconazole * Ketoconazole * Miconazole

Answer 81

* Chest X-ray * CT * Ultrasound

Answer 82

* A specific form of chronic fibrosing interstitial pneumonia of unknown aetiology * Limited to the lung * Histopathological appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy * Known causes of ILD such as drugs, environmental exposure and connective tissue disease have been excluded * Abnormal lung function tests with evidence of restriction and/or impaired gas exchange * Characteristic abnormalities on CXR or HRCT chest (bibasal reticular abnormalities with minimal or no ground glass opacities on HRCT)

Answer 83

* Routine bloods - FBC, U&Es, LFTs, serum calcium, CRP * CT chest and upper abdomen - look for lymph nodes, evidence of liver or adrenal metastases * Bronchoscopy - will detect more central lesions * Percutaneous needle biopsy - peripheral lesions * CT/CT-PET - combined imaging to look for metastases * Endobronchial ultrasound - to visualise and guide needle biopsy of mediastinal lymph nodes * Ultra-sound guided aspiration of supraclavicular lymph nodes * VATS (video-assisted thoracoscopic surgery) - to diagnose and treat pleural effusion

Answer 84

* 3rd most common cancer in the UK * In men second commonest after prostate * In women second commonest after breast * Accounts for 13% of all new cancer cases * \>44% in over 75s, highest in 85-89 y/o

Answer 85

* For asthma maintenance - not for treatment of acute attacks * Taken orally * High affinity antagonist of cysteinyl leukotriene receptor (CysLT1) inhibiting the action of LT-D4 in smooth muscle cells of the airway and airway macrophages --\> reduces airway oedema and smooth muscle contraction * Useful for prophylaxis of exercise-induced asthma, allergic rhinitis * Short half-life - often take at night (when symptoms are worse)

Answer 86

* Always look at the pO2 first - normal approx. 13 * Is the patient in respiratory failure (\<8) requiring additional oxygen (\<6)? * Then look at the PCO2 (type 1 vs type 2 respiratory failure) * pCO2 \>6 - type 2 respiratory failure * pCO2 \<6 - type 1 respiratory failure * Then consider acid base balance * Acute (decompensated) respiratory acidosis- elevated pCO2, normal bicarbonate, acidosis (H+ \> 44) * Compensated respiratory acidosis- elevated pCO2, elevated bicarbonate (renal compensation), not acidotic (H+ normal) * Acute on chronic respiratory acidosis - elevated pCO2, elevated bicarbonate, acidotic * = mixed picture - chronic respiratory failure with acute respiratory event which prevents compensation

Answer 87

* Pathology - thickening of the septae, filling of the alveolus with fluid * Impact on passive diffusion of gases * Loss of O2 - hypoxaemia * Normal CO2 - soluble in water so can still transfer in fluid * Air space shadowing on CXR Chronic Exposure: * Fibrosis * Interstitial scarring from chronic tissue remodelling/repair pathways * More exposure = more fibrosis * Emphysema * Interstitial destruction from neutrophilic enzyme release Passive Diffusion Consequences: * Emphysema - reduced surface area, reduced amount of BV available to oxygen * Increased distance for O2 to travel to be absorbed * Pulmonary fibrosis * Thicker alveolar walls, reduced solubility of oxygen = Reduced oxygen transport into the bloodstream, measured by carbon monoxide gas transfer during full PFTs. Airspace shadowing on CXR

Answer 88

British Thoracic Society (BTS) Statement on Driving and OSA/OSAS * DVLA need to be informed if moderate/severe OSAS with excessive sleepiness or mild OSAS with excessive sleepiness which can't be controlled after 3 months * DVLA do not need to be informed without symptoms of excessive sleepiness * OSA without daytime somnolence, do not need to stop driving * OSAS (DTS) - likely impairment of driving, inform DVLA on diagnosis * OSAS can hold license if compliant with treatment and reduced DTS * CAT 2 license require ongoing monitoring by DVLA with regards to treatment compliance

Answer 89

Single breath of a very small concentration of carbon monoxide CO has very high affinity to Hb (100x O2) Measure concentration of CO2 in expired gas to derive uptake in the lungs

Answer 90

* Patient inside sealed box, breathing monitored * Could introduce potential trigger and measure response * Not done - could trigger potentially life-threatening asthma attack

Answer 91

Obstructive Sleep Apnoea: Recurrent episodes of partial or complete upper (pharyngeal) airway obstruction during sleep, intermittent hypoxia sleep fragmentation Obstructive Sleep Apnoea Syndrome: Manifests as excessive daytime sleepiness

Answer 92

\<25% operable, stage 1 operable, some stage II Gives best chance of cure

Answer 93

* Reversibility Testing: * Nebulised or inhaled salbutamol given * Spirometry before and 15 minutes after salbutamol * 15% and 400ml reversibility in FEV1 suggestive of asthma

Answer 94

* Sharply rises as most of forced vital capacity expired in first second, then plateaus * Can measure * Peak expiratory flow rate - first 0.1 seconds * Forced expiry volume in one second - should be most of functional lung capacity * Forced vital capacity * FEV1:FVC ratio

Answer 95

Mostly infected through airways, can spread through meninges to CNS Only causes infection in immunocompromised Treatment can be problematic

Answer 96

* Causes cryptococcosis of lungs, and meningitis * Often secondary infection with HIV

Answer 97

* Unilateral pleural effusion - more likely to be exudative * Bilateral pleural effusion - more likely to be transudative * D sign - doesnt follow gravity, suggests infection/empyema (more complex)

Answer 98

* Common multisystem inflammatory disease of unknown aetiology that predominantly affects the lungs and intrathoracic lymph nodes * Cause is unknown - efforts to identify a possible infectious aetiology unsuccessful * Characterised by 'non-necrotising granulomatous inflammation' * Inflammation in interstitium of organ (working tissue) * Diagnosis of exclusion

Answer 99

Frequent exacerbations Persistent breathlessness Chronic bronchitis Muscle wasting syndrome (emphysema)

Answer 100

* Medical emergency * Immediate management - insert Venflon 2nd intercostal space mid-clavicular line to relieve pressure

Answer 101

* Causes * Organic dusts (\<5um - have to be small enough to escape mucous and cilia of airways) * Moulds * Foreign proteins (animals) * Some chemicals * Often heavy, repeated exposure, most often at the work place * Farmer's lung - mouldy hay * Saw mill worker's lung - mouldy wood dust * Bird fancier's lung - proteins in bird dropping * Mushroom worker's lung - spores, moulds * Malt worker's lung - mouldy malt * Humidifier lung - contaminated humidifier water * Cheese washer's lung - penicillium casei * Suberosis - cork dust mould * Disocyanate lung - polyurethane hardeners * Hard metal worker's lung - hard metal dust, cobalt

Answer 102

* Oncogenes (ras, myc) * Growth factors receptors (epidermal growth factor, bombesin-like peptide) * Genetic predisposition (Li-Fraumeni syndrome, Hippel-Lindau) * Antioncogenes (P53, 3P, rb)

Answer 103

Cough, haemoptysis

Answer 104

KRAS EGFR ALK HER2

Answer 105

Due to invasion of cervical sympathetic chain Ptosis, exophthalmos, miosis, anhidrosis

Answer 106

* Moderate Exacerbation: * Increasing symptoms * PEF \>50-75% best or predicted * No features of acute severe asthma * Acute Severe: * Any one of * PEF 33-50% best or predicted * Respiratory rate \>25/min * Heart rate \>110/min * Inability to complete sentences in one breath * Life Threatening: * In a patient with severe asthma, any one of * PEF \<33% best or predicted * SpO2 \<92% * PaO2 \<8kPa * Normal PaCO2 (4.6-6kPa) * Silent chest * Cyanosis * Poor respiratory effort * Arrhythmia * Exhaustion, altered conscious level * Near Fatal: * Raised PaCO2 and/or requiring mechanical ventilation with raised inflation pressures.

Answer 107

* Calculated by adding the number of apnoea and hypopnoeas and dividing by the total sleep time (in hours) * AHI\>15 is diagnostic of OSA * AHI 5-15 with compatible symptoms * AHI \<5 normal * AHI 5-15 mild * AHI 16-30 moderate * AHI \>30 severe * Oxygen Desaturation Index (ODI) * The number of times per hour of sleep that the SpO2 falls \>4% from baseline

Answer 108

Inflammatory cells seen: * Activated T helper (Th2) lymphocytes produce IL-3, 4, 5 and 14 which maintain the allergic phenotype * IL-4 stimulates IgE production, IL-5 activates eosinophils, IL-13 stimulates mucous secretion and promotes IgE production * Eosinophils - in bronchial walls and secretions of asthmatics, attracted to airways by IL-3 and 5, GMCSF and chemokines (eotaxin, RANTES), release mediators such as LTC4 when activated * Mast cells - increased in mucous glands, smooth muscle and epithelium, produce histamine, PGD2, cysteinyl leukotrienes, tryptase * Dendritic cells - present allergens to T lymphocytes Mediators in the (late) acute asthma response * Leukotrienes (LT C4, D4, E4) - bronchoconstriction, increase vascular permeability, increase mucous secretion * Acetyl choline - released from intrapulmonary nerves, directly stimulates muscarinic receptors on airway smooth muscle * Histamine - bronchoconstriction * Prostaglandin PGD2 - bronchoconstriction and vasodilation * Others - platelet-activating factor, IL-1, TNF, IL-6, chemokines, neuropeptides (eotaxin), nitric oxide

Answer 109

* Target steps in ergosterol synthesis * Azoles inhibit 14-methylsterol alpha-demethylase * Terbinafine inhibits squalone 2,3-epoxidase * Amphotericin B binds to ergosterol and creates pores

Answer 110

Epithelium damaged due to inflammation, undergoing continuous repair (scarring/fibrosis) BM thickened Smooth muscle hypertrophy - target of asthma therapies

Answer 111

* Happens to a degree in normal lungs * Due to gravity apices are well ventilated, bases are less well ventilated * Areas of lungs that are perfused but not well ventilated e.g. pneumonic consolidation * Shunt an 'extreme' form of V/Q mismatch where blood bypasses the lungs entirely, does not correct with oxygen administration

Answer 112

* Therapeutic anticoagulation for \>3 months is recommended for all patients with PE * For patients with first PE/VTE secondary to a major transient/reversible risk factor, discontinuation of therapeutic oral anticoagulation is recommended after 3 months * Oral anticoagulant treatment of indefinite duration is recommended for patients presenting with recurrent VTE (at least one previous episode of PE/DVT) not related to a major transient or reversible risk factor * Oral anticoagulant treatment with a VKA for an indefinite period is recommened for patients with antiphospholipid antibody syndrome

Answer 113

4-6 hours after exposure Wheeze, cough, fever, chills, headache, myalgia, malaise, fatigue May last several days Serum sickness illness

Answer 114

Long-term oxygen therapy in COPD patients who have: * PaO2 \<7.3kPa when stable - his paO2 is too good at present * OR PaO2 7.3-8kPa * And any of * Secondary polycythaemia * Nocturnal hypoxaemia * Peripheral oedema * Pulmonary hypertension * And non-smoker for \>3 months

Answer 115

* Consider the diagnosis of COPD for people who are over 35, and smokers or ex-smokers, with any of: * Exertional breathlessness * Chronic cough * Regular sputum production * Frequent winter 'bronchitis' * Wheeze

Answer 116

* Recent rise in adenocarcinoma and small cell carcinoma with fall in squamous carcinoma * Due to changes in smoking habits or composition of cigarettes * Change in smoking demographics (more women now getting lung cancer) * Filter tips, lower tar and nicotine * Deeper inhalation exposes more peripheral airways to carcinogens

Answer 117

CXRs in patients with sarcoidosis have been classified into 4 stages: * Stage I - bilateral hilar lymphadenopathy without infiltration * Stage II - bilateral hilar lymphadenopathy with infiltration * Stage III - infiltration alone * Stage IV - fibrotic bands, bullae, hilar retraction, bronchiectasis, diaphragmatic tenting Represent radiographic patterns and do not indicate disease chronicity or correlate with changes in pulmonary function.

Answer 118

* Malignant mesothelioma - malignant tumour of the pleural caused by asbestos exposure * Encases lung and spreads in interlobar fissure * Compresses lung

Answer 119

Wheeze due to: * Reversible/variable airflow obstruction - physiological * Airways inflammation/allergy - pathological * Triggers, cold, exercise, cats, nocturnal/diurnal - clinical Variable clinical presentation - used to direct management 1. Physiological * Yellow mucous * Repair pathways * Non-elastic airways * Increased responsiveness/sensitivity 2. Pathological * Inflammation * Scabby epithelium * Thickened BM * Thickened smooth muscle * Mast cells in smooth muscle 3. Clinical * Cough * Wheeze * Hyper-reactivity * Hyper-sensitivity

Answer 120

* Pleural - haemorrhagic effusion * Hilar lymph nodes (--\> cervical) * Adjacent lung tissue - may involve large blood vessel leading to haemoptysis * Pericardium - pericardial effusion with subsequent involvement of pericardium * Mediastinum * Superior vena caval obstruction - raised JVC, visible veins on chest, swelling of face, headache * Recurrent laryngeal nerve compression as it hooks under arch of aorta and travels up side of larynx - hoarseness * Phrenic nerve - hemidiaphragm paralysis * Pancoast tumour * Involvement of brachial plexus giving sensory and motor symptoms * Horner's syndrome/oculosympathetic palsy (cervical sympathetic chain)

Answer 121

NSCLC - surgery, radiotherapy, chemotherapy, palliative care SCLC - radiotherapy, chemotherapy, palliative care

Answer 122

* Tend to arise centrally from major bronchi * Often within dysplastic epithelium following squamous metaplasia * Slow growing and metastasise late therefore may be good candidate for surgery * May undergo cavitation - outgrow blood supply, necrosis in centre * May block bronchi leading to retention pneumonia or collapse * Appearance * A malignant epithelial tumour showing keratinisation and/or intercellular bridges (desmosomes, same as stratum spinosum layer of skin) * In situ squamous cell carcinoma may be seen in the adjacent airway mucosa

Answer 123

* Lung volumes reduced in restrictive lung disease * Increased residual volume and residual volume/total lung capacity in obstructive lung disease

Answer 124

* Inhaled bronchodilators * Short-acting - salbutamol (beta 2 agonist - SABA) * Long-acting - salmeterol (beta 2 agonist) - LABA, tiotropium (muscarinic antagonist - LAMA) * Inhaled corticosteroids * Budesonide and fluticasone - combination inhalers * Oxygen therapy * Oral theophylline * Mucolytics - carbocysteine (symptomatic relief) * Nebulised therapy

Answer 125

Can give rise to 3 different conditions: * Allergic bronchopulmonary aspergillosis * Allergic reaction to fungal infection * Association with cystic fibrosis, asthma * Prednisone (anti-allergic agent) * Invasive pulmonary aspergillosis * Becomes systemic and spreads throughout the body * Common in immunocompromised * Treatment - voriconazole, amphotericin B * Aspergilloma * A fungal ball that develops in an area of past lung disease or lung scarring - encapsulated in lung tissue * E.g. tuberculosis or lung abscess * No treatment unless bleeding occurs - surgery (excision) * Irresponsive to drugs as encapsulated

Answer 126

1. Centri-acinar (acinus = area of lung supplied by one respiratory bronchiole) * Damage around respiratory bronchioles * More in upper lobes 2. Pan-acinar * Uniformly enlarged from the level of terminal bronchiole distally * Can get large bullae * Associated with alpha 1 anti-trypsin deficiency 3. Paraseptal * Peripheral alveolar damage around the septae of the lungs/pleura

Answer 127

* Spontaneous pneumothorax - if bilateral/haemodynamically unstable proceed to chest drain * Age \>50 and signifcant smoking history, evidence of underlying lung disease on exam or CXR? * No - primary pneumothorax * Yes - secondary pneumothorax * Primary * Size \>2cm and/or breathless - aspirate 16-18G cannula, aspirate \<2.5L * Success (\<2cm and breathing improved) - consider discharge review in OPD in 2-4 weeks * No success - chest drain, size 8-14 Fr, admit * Size \<2cm, not breathless - consider discharge review in OPD in 2-4 weeks * Secondary * \>2cm or breathless - chest drain, size 8-14Fr, admit * Size 1-2cm - aspirate 16-18G cannula, \<2.5L * Success (size now \<1cm) - admit, high flow oxygen (unless suspected oxygen sensitive), observe for 24 hours * No success - chest drain, size 8-14Fr, admit * Smaller than 1cm - admit, high flow oxygen (unless suspected oxygen sensitive), observe for 24 hours

Answer 128

Due to action on beta 1 receptors * Tremor, hypokalaemia, hyperglycaemia, hypomagnesaemia * Flushing, tachycardia, arrhythmias, headache, muscle cramps

Answer 129

* Tumours of mesenchymal tissues * Inflammatory myofibroblastic tumour * Salivary gland-type tumours * Adenoid cystic carcinoma * Tumours of ectopic origin * Germ cell tumours * Tumours of neuroendocrine cells * Carcinoid * Tumours of lymphatic system * Lymphoma

Answer 130

* A diagnosis of exclusion * Usually arises centrally * An undifferentiated malignant epithelial tumour that lacks the cytological features of SCLC and glandular or squamous differentiation

Answer 131

Predominantly renally excreted therefore reduce dose in severe renal impairment Can cause cholestatic jaundice, Stevens Johnson syndrome or toxic epidermal necrolysis

Answer 132

Short-acting - ipratropium bromide Long-acting - tiotropium, glycopyrronium, umeclidinium Renally excreted

Answer 133

* Grade 1 - dyspnoea on strenuous exercise * Grade 2 - short of breath when hurrying or walking up a slight hill * Grade 3 - walks slower than contemporaries on level ground because of breathlessness, or has to stop for breath when walking at own pase * Grade 4 - stops for breath after walking about 100m or after a few minutes on level ground * Grade 5 - too breathless to leave the house, or breathless when dressing and undressing

Answer 134

* Alpha 1 antitrypsin deficiency - genetic * Alpha 1 antitrypsin - anti-protease (serine protease inhibitor), prevents protease digestion of lung tissue * Present in 1-3% of COPD patients * M alleles normal variant * SS and ZZ homozygotes have clinical disease * Unable to 'counterbalance' destructive enzymes in lung * Non-smokers get emphysema in 30-40s, smokers get emphysema much earlier * Smokers have increased risk of COPD if it is in the family

Answer 135

Elevated domed hemidiaphragm on affected

Answer 136

* Inflammatory response from epithelium due to repeated damage * Epithelial lining regrows - GF, cytokines released by mast cells, macrophages, lymphocytes and epithelial cells * Cytokines - IL-5, TSLP, IL-13 * IL-5/13 important targets for treatment * Drives eosinophilic inflammation * Growth factors - TNF alpha, TGF beta, VEGF * Fibrosis, remodelling cytokines, responsible for growth of smooth muscle, angiogenesis, epithelial cell damage, airway remodelling Inflammation * Corticosteroid responsive disease * Routinely identified in airways of asthma * If stimulated will drive an asthma phenotype * Viral infections, late allergic reactions * Multiple candidate genes and non-hierarchical genes associated with asthma are inflammatory

Answer 137

Cause of pulmonary fibrosis NSIP = non-specific interstitial pneumonia, treat with immune modulating drugs

Answer 138

T – tumour size N – regional lymph node involvement M – presence or absence of distant metastases TNM used together to give stage of disease - helps decide treatment options TNM Staging Stage I: localized, no LN involvement Stage IA - \< 2 cm in size Stage IB – 2 - 3 cm in size Stage 2: 3 – 7 cm or involves main bronchus/visceral pleura/lobar collapse or hilar LN Stage 2A – 3 – 5cm in size Stage 2B – 5 -7 cm in size Stage 3: \> 7 cm in size or invades into adjacent structures or whole lung collapse Stage 3A- any size and spreads into mediastinal lymph nodes or local spread to chest wall, pleural or mediastinum Stage 3B – spread to contralateral or supraclavicular nodes, or spread to another major structure such as the oesophagus, heart, trachea or major vessel, or two or more tumours in the same lung, or pleural effusion Stage 4 – distant spread

Answer 139

Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Other

Answer 140

* How likely would you be to fall asleep in different situations? * Sitting and reading * Watching TV * Sitting, inactive in a public place (e.g. a theatre or a meeting) * As a passenger in a car for an hour without a break * Lying down to rest in the afternoon when circumstances permit * Sitting and talking to someone * Sitting quietly after lunch without alcohol * In a car, while stopped for a few minutes in the traffic

Answer 141

* PEFR testing * Look for diurnal variation and variation over time * Response to inhaled corticosteroid * Occupational asthma * Bronchial provocation * Spirometry before and after trial of inhaled/oral corticosteroid

Answer 142

* Pharyngeal narrowing * Negative thoracic pressure * Arousal * Sleep disruption - sleepiness, reduced quality of life, road traffic accidents * Blood pressure surge - heart attacks, strokes

Answer 143

Symptoms suspicious of lung cancer: * Cough - that doesn't go away or is long-standing and gets worse * Recurrent infections * Breathlessness - lobar/lung collapse (co-existing COPD) * Haemoptysis * Unexplained weight loss * Chest and/or shoulder pains * Hoarse voice Clinical signs which may be associated with lung cancer: * Finger clubbing * Signs of lobar collapse or a pleural effusion * From metastases - hepatomegaly, cervical lymphadenopathy, bone tenderness * Cachexia * Horner's syndrome (Pancoast tumour) * Evidence of superior vena cava obstruction (SVCO) or spinal cord compression (SCC) * Cushingoid

Answer 144

* Approximately 5% of cases are asymptomatic and incidentally detected by CXR * Presentation depends on the extent and severity of the organ involved * Systemic symptoms occur in 45% of cases such as * Fever * Anorexia * Fatigue * Night sweats * Weight loss * Macrophages produce systemic effect * Pulmonary - dyspnoea on exertion, cough, chest pain and haemoptysis (rare) occur in 50% of case

Answer 145

Smoking, male gender and height are risk factors Young, tall, slim males most at risk Underlying lung disease (secondary) Recurrence rate 40-50% after first episode

Answer 146

Strep pneumoniae, haemophilus influenzae

Answer 147

Like a virtual MDT Multi-professional Consult on the complex sub-massive/massive PTEs Rapid risk stratification

Answer 148

* Measure FEV1 before and after inhaled/nebulised salbutamol (or other bronchodilator) * In asthma - \>15% improvement in FEV1 after bronchodilator

Answer 149

Inhaled opportunistic pathogen Encapsulated yeast - fluffy surrounding capsule, easily airborne Contracted from environment e.g. pigeon droppings

Answer 150

* Immediate asthma (early reaction) * Starts within minutes, maximal at 15-20 minutes, subsides by 1 hour * Bronchoconstriction triggered by direct stimulation of subepithelial vagal receptors, increased mucous production, vasodilation and increased vascular permeability * Late-phase reactions * Follows immediate reaction, more sustained attack of airflow limitation that may respond less well to bronchodilators * Inflammation with recruitment of eosinophils, neutrophils and lymphocytes

Answer 151

* Assess severity: Symptoms, ABG, CXR * Controlled oxygen therapy: 24 -28 % oxygen, aim to maintain SpO2 88 – 92 %; repeat ABGs at 1 hour * Bronchodilators: nebulised salbutamol 2.5 – 5 mg and ipratropium bromide 0.5 mg qds (and PRN) * Consider IV aminophylline if not improving * Corticosteroids: prednisolone 30 – 40 mg od * Antibiotics: if signs of bacterial infection (purulent sputum, increased sputum volume, WCC, CRP * Non-invasive ventilation (NIV): for acidotic type II respiratory failure * Other: consider DVT prophylaxis (LMWH), monitor fluid balance and nutrition, manage co-morbidities

Answer 152

* Population targeting oncogenic drivers has transformed the care of patients with lung adenocarcinoma * Those with actionable genes do better than those without - can target therapy, much better outcomes * In NHS GGC * 13% have mutation in EGFR receptor and may respond to tyrosine kinase inhibitors * 2% of NSCLC patients have EML4-ALK gene fusions present in their tumours - may respond to ALK inhibitors * Approximately 1-2% of NSCLC patients have ROS-1 oncogenic fusion which may respond to targeted therapies * PD-L1 is overexpressed on some tumours in some patients with NSCLC - may be treated with PD-L1 inhibitors

Answer 153

* Allergy - avoid trigger (occupation) * Inflammation - corticosteroids * Neutrophils are modestly steroid responsive * Cytotoxics * Oxygen supplementations

Answer 154

* HRCT * Video-assisted thoracoscopic surgery (VATS) * Need 3 biopsies for diagnostically competent sample * Don’t take biopsy from lingula (damaged by heart) or points of lungs (damaged by infections)

Answer 155

Pink abnormal infiltrate - macrophages Surrounded by normal purple lymphocytes

Answer 156

Systemic examination - clubbing, ascites, lymphadenopathy Chest Cardiovascular

Answer 157

Diseases of airflow limitation - emphysema, chronic bronchitis and asthma, can have overlap between all Asthma-COPD overlap syndrome

Answer 158

Alveolar surface area Pulmonary capillary blood volume Haemoglobin concentration Ventilation perfusion mismatch

Answer 159

* Bibasilar crackles, clubbing * Peripheral interstitial pattern * Subpleural honeycombing (holes in lung tissue) Symptoms: * Breathlessness (worse with exercise) * Hacking dry cough * Fatigue and weakness * Appetite and weight loss

Answer 160

Tumour of the pulmonary apex which can involve the brachiocephalic vein, brachial plexus, subclavian vein/artery Causes severe pain in the shoulder/scapula, pain the in arm and weakness of the hand on the affected side and Horner's syndrome

Answer 161

Pleuritic chest pain - worse when breathing in Breathlessness, can be minimal if primary Respiratory distress (especially if secondary) Reduced air entry on affected side Hyper-resonance to percussion (?) Reduced vocal resonance Tracheal deviation if tension (+/- circulatory collapse) - late sign

Answer 162

COPD characterised by airflow obstruction Airflow obstruction usually progressive, not fully reversible and does not change markedly over several months

Answer 163

Irreversible airflow obstruction (Reversibility - if given a bronchodilator the airways open)

Answer 164

* Surgery - early stages (usually stage I or II) * Radiotherapy * Curative intent (radical radiotherapy) in some with early stages if not thought to be fit for surgery * Side effects - radiation pneumonitis in 10-15% (acute infiltrate \<3 months after treatment), radiation fibrosis around one year after * For symptom control (palliative radiotherapy) - good for bone and chest wall pain, haemoptysis, occluded bronchi, SVCO * Chemotherapy * Platinum based chemotherapy (cisplatin/carboplatin) in combination with paclitaxel or gemcitabine * Can be used to down-stage tumours for surgery or to palliate symptoms

Answer 165

* Adenocarcinoma - 40% * Squamous cell carcinoma - 30% * Small cell lung carcinoma - 15% * Large cell carcinoma - 10% * Other non-small cell lung carcinoma - 3%

Answer 166

* Pleural cavity usually a potential space * Negative intrapleural pressure * Opposing forces of chest wall (outwards) and lung (inwards - natural elastic recoil) * Any breach of the pleural space leads to collapse of the elastic lung

Answer 167

* Initiation of anticoagulation is recommended without delay in patients with high or intermediate clinical probability of PE, while diagnostic workup is in progress * If anticoagulation is initiated parenterally, LMWH or fondaparinux is recommended (over UFH) for most patients * When oral anticoagulation is started in a patient with PE who is eligible for a NAOC (apixaban, dabigatran, edoxaban or rivaroxaban), a NOAC is recommended in preference to a VKA * When patients are treated with a VKA, over-lapping with parenterally anticoagulation is recommended until an INR or 2.5 is reached * NOACs are not recommended in patients with severe renal impairment, during pregnancy and lactation, and in patients with antiphospholipid antibody syndrome

Answer 168

* Largest class of antifungal agents * Pharmacologically active part of molecule = azole * Many applications * Examples * Miconazole (Micatin or Daktarin) * Ketoconazole (Nizoral, Fungoral and Sebizole) * Clotrimazole (Lotrimin, Lotrimin AF and Canesten) * Econazole * Isoconazole * Fluconazole * Itraconazole * Abafungin

Answer 169

* CXR * CT chest * Routine blood tests * FBC * U+Es * LFTs * Calcium * ESR * CRP * Immunology * Rheumatoid factor * ANA screen * ANCA screen * Avian precipitans and aspergillus precipitans * Serum angiotensin converting enzyme level (sarcoid) * Serum immunoglobulins (sarcoid) As condition progresses or if felt to have evidence of respiratory failure or cor pulmonale at presentation: * Arterial blood gases - Type 1 Respiratory Failure * Caused by a combination of alveolar capillary block (loss of capillary volume) and V/Q mismatch * PaCO2 normal or low owing to hyperventilation * High in obstructive disease – not breathing out effectively * Six-minute walk test/ambulatory oxygen assessment - to assess if desaturation on exertion. * Echocardiogram - to look for the development of pulmonary hypertension

Answer 170

* Roflumilast * Selective inhibitor of phosphodiesterase-4 * Inhibits hydrolysis of cAMP in inflammatory cells --\> increased intracellular cAMP --\> reduces release of pro-inflammatory mediators and cytokines * Orally administered, metabolism by cytochrome P450 * Reduction in exacerbations of COPD - but many side effects * Azithromycin * Macrolide antibiotic with immunomodulatory and anti-inflammatory effects - inhibition of pro-inflammatory AP-1, NFkB and mucin release * Reduction in exacerbations of COPD * Carbocysteine * Mucolytic that increases concentrations of sialomucins and reduces concentrations of fucomucins, resulting in reduced sputum viscosity * Less viscose sputum means secretions are cleared more easily, reduction in retained secretions = reduction in infections/exacerbations

Answer 171

Persistent systemic inflammation Eosinophilic or Th2 high COPD Persistent pathogenic bacterial colonisation - long term antibtioics Alpha-1 antitrypsin deficiency

Answer 172

An exacerbation is a sustained worsening of the patient's symptoms from their usual stable state which is beyond normal day-to-day variations, and is acute in onset. Commonly reported symptoms are worsening breathlessness, cough, increased sputum production and change in sputum colour. The change in these symptoms often necessitates a change in medication.

Answer 173

* Secondary spread to lungs is very common - the commonest tumour in the lungs is metastatic * Multiple tumours in lungs suggests metastatic spread * Many primary tumours spread to lung

Answer 174

No genetic factors consistently associated with sporadic cases of IPF MUC5B gene polymorphisms is associated with familial cases of IPF

Answer 175

Snorer Witnessed apnoeas Disruptive sleep - nocturia, choking, dry mouth, sweating Unrefreshed sleep Daytime somnolence Fatigue/low mood/poor concentration

Answer 176

* Asbestos inhaled - macrophages try to digest, indigestible * Creates reactive oxygen species which cause iron deposits to be laid down

Answer 177

Occupation Past medical history Travel Environment Drugs Smoking

Answer 178

* 15% adult population have/had * If not currently symptomatic but diagnosed in childhood - well controlled or not currently presenting * Life long - expensive * 80% easy to manage, 20% severe asthma - difficult to manage * 2014 - 198 deaths

Answer 179

1. Parenteral therapy - short, quick acting, given in hospital * LMWH * Unfractionated heparin * Fondaparinux * Thrombolytic agents 2. Oral medication (anticoagulation) * Mainstay is vitamin K antagonists - warfarin * Used much less frequently now - monitoring is difficult, many interactions * Novel agents with less bleeding risk are becoming available * Not suitable in all cases for example cancer * Difficulties with warfarin include time TTR (time in therapeutic range) * Drug/food interactions * Pharmacogenomic approach

Answer 180

Send for analysis in acute exacerbations

Answer 181

'One way valve' leads to increased intrapleural pressure Air can move into the intrapleural space but not out Build up of air in the intrapleural space

Answer 182

Opiates to treat pain and breathlessness (important as lung cancer often diagnosed at an advanced stage in patients with other health problems e.g. COPD, IHD)

Answer 183

* Often initiated by partner or media coverage * GP * ENT * Pre-operative assessment for elective surgery * Post-operative presentation * Weight management clinics * Diabetes clinic * Neurology

Answer 184

* Non-selective inhibition of phosphodiesterases --\> increased intracellular cAMP --\> bronchial smooth muscle relaxation * Immunomodulatory action - improved mucociliary clearance and anti-inflammatory effect (inhibits synthesis of leukotrienes and TNF alpha)

Answer 185

* At home * Peak flow * Oximetry (patients often buy) * At the GP * Spirometry (quality varies) * Oximetry * In a specialist lab * Spirometry * Transfer factor * Lung volumes * Blood gases * Bronchial provocation testing * Respiratory muscle function * Exercise testing

Answer 186

* Common environmental fungus * No pathology in immunocompetent * Pneumonia * Fever * Cough * Shortness of breath, rapid breathing * Treatment and prophylaxis * Trimethoprim-sulfamethoxazole

Answer 187

* Radiology - changes predominantly at lung bases * CXR - ground glass changes→ irregular reticulonodular shadowing → honeycombing * High resolution CT Chest * Subpleural reticular abnormalities * Honeycombing - thick-walled cysts 0.5 - 2 cm in diameter in respiratory and terminal bronchioles * Traction bronchiectasis – scar tissue pulling bronchiole wider, thickened Ground glass changes - hazy areas of increased attenuation in the lung with preserved bronchial and vascular

Answer 188

* Aseptic technique * Local anaesthetic - can be painful (pleural highly innervated) * If pneumothorax should be lying back with hand above head, expose 'triangle of safety' * Use big introducer needle with syringe on end, head air escaping as enter the intrapleural space * Feed guide wire in, make incision to make hole bigger * Use dilator to make space bigger to insert drain into * Chest drain fed over guide wire, remove guide wire * Attach 3 way trap + underwater seal

Answer 189

Macroscopically * Pleural surfaces of the lung are "cobblestoned" * Fibrotic areas of lung - firm rubbery and white * Disease mainly basal and subpleural, with thickening of the interlobular septae Histology * Patchy interstitial fibrosis, varies in intensity and age (temporal heterogeneity) * Fibroblastic foci in early fibrosis - areas of fibroblastic/myofibrobalastic proliferation - become less cellular as disease progresses and collagen deposited

Answer 190

Cor pulmonale – pumping against high resistance due to fibrosis, pre-load in R heart increased, R heart hypertrophy then failure

Answer 191

* Can be traumatic, iatrogenic or spontaneous * Traumatic - stabbing, fractured rib * Iatrogenic - CT guided lung biopsy, TBLB (transbronchial lung biopsy), pleural aspiration * Spontaneous - * Primary - young patient, no underlying lung disease * Secondary - underlying lung disease (e.g. COPD, cystic fibrosis)

Answer 192

TB * Granulomatous - creamy, necrotic encapsulated mass * Necrosis * Multinucleated giant cells * Ziehl-Neelson staining

Answer 193

* Antibiotics - nitrofurantoin * Disease-modifying antirheumatic drugs - methotrexate, sulphasalazine, gold, pencillinamine, lefluonamide, etanercept * Cardiovascular agents - amiodarone, ACE-inhibitors, statins * Chemotherapeutic agents - bleomycin, cyclophosphamide * Ilicit drugs - heroin, methadone, talc * Miscellaneous - oxygen, radiation, aspirin, interferons

Answer 194

Depends on adequate perfusion (shock, cardiac failure) Does NOT measure carbon dioxide, so no measurement of ventilation False reassurance in patient on oxygen with normal saturations (acute asthma, COPD, hypoventilation)

Answer 195

* Chest X-ray * Pathology

Answer 196

GI upset, palpitations, tachycardia/arrhythmias, headache, insomnia, hypokalaemia

Answer 197

* Short acting - salbutamol, terbutaline (elimination half life 3-5 hours) * Long acting - salmeterol, formoterol, vilanterol, indacaterol * Salbutamol can be given via inhaled, nebulised, oral, intravenous routes * Inhalation route preferable/nebulised if severe

Answer 198

* Reperfusion treatment * Systemic/catheter directed thrombolysis * Haemodynamic support * Inotropic support e.g. ECMO

Answer 199

* To assess cardiac status if has clinical features of cor pulmonale * Enlargement of the right side of the heart due to disease of the lungs or pulmonary vessels

Answer 200

* Antagonist of cholinergic M1 and M3 (muscarinic) receptors in the lung, countering the parasympathetic direct broncho-constriction of muscarinic receptor activation, which is coupled to Gq G-proteins and hence to phospholipase P, IP3 production and intracellular Ca * On vasculature, M3 activation increases NO production, causing vasodilation

Answer 201

* Different causes in transudative vs exudative pleural effusion * Transudate = pressure effect, fluid pushed out * Exudate = something added which disrupts fluid drainage * Light's criteria * Fluid protein : serum protein \>0.5 * Fluid LDH : serum LDH \>0.6 * Fluid LDH \>2/3 maximum serum normal * Any 1 of 3 = exudate * Always send paired samples

Answer 202

Oxygen 40-60% (maintain spO2 94-98%) Salbutamol 5mg or terbutaline 10mg via an oxygen-driven nebuliser Ipratropium bromide 0.5mg via an oxygen-driven nebuliser Prednisolone tablets 40-50mg or IV hydrocortisone 100mg or both if very ill No sedatives of any kind Chest radiography only if pneumothorax or consolidation suspected

Answer 203

Squamous cell (40-60%) - closely linked to smoking history, keratinization and/or intercellular bridges on histology, central airways, high frequency of p53 mutations Adenocarcinoma (10 -20%) - glandular differentiation or mucin production, most common form in women and non-smokers, more peripherally located, TTF-1 positive, if EGFR mutations present may benefit from treatment with EGFR inhibitors Large cell (5-15%) - undifferentiated epithelial tumour

Answer 204

Target pathology with specific treatments: * Established therapies * Anti-IgE biological therapy - type 1 allergies driven by IgE, block pathways * Corticosteroids (inhaled - bad to swallow) * Anti-leukotriene receptor drugs * Bronchodilators - relax smooth muscle * New Therapies * Immunotherapy * Biological therapies - TNF, IL-5, IL-13 * Anti-TNF tried but doesn’t work - get a bit better then get cancer * IL-5/12 very effective - injectable monthly * Thermoplasty - heat airway * Gets rid of smooth muscle bulk - deinnervates

Answer 205

Smoking in 85% Passive smoking Occupation asbestos Silica and nickel exposure Pulmonary fibrosis

Answer 206

Air within the pleural cavity

Answer 207

* Asthma sensitising agent * Asthmatic airway inflammation - CD4+, T lymphocytes, eosinophils * Completely reversible * COPD noxious agent * COPD airway inflammation - CD8+, T lymphocytes, macrophages, neutrophils * Irreversible

Answer 208

Home or inpatient Shows periodic dips in oxygen and peaks in CO2 when not breathing properly

Answer 209

Most to least common clinical characteristics: * Dyspnoea * Pleuritic chest pain * Cough * Substernal chest pain * Fever * Haemoptysis * Syncope * Unilateral leg pain * Signs of DVT (unilateral extremity swelling)

Answer 210

* "Repeated cycles" of epithelial activation/injury by some unidentified agent * Abnormal activation of epithelial cells leads to a dysregulated repair process * Abnormal epithelial repair at site of injury/inflammation leads to the formation of the fibroblastic foci * Inflammatory pathways also promote fibrosis

Answer 211

Fluid fills the empty hemithorax - white

Answer 212

* Used to determine risk of mortality within 30 days post-PE * Early mortality risk high * Shock or hypotension * PESI class II-V or sPESI \> 1 (pulmonary embolism severity index) * Signs of RV dysfunction on imaging test * Cardiac laboratory biomarkers * Intermediate-high early mortality risk * No shock or hypotension * PESI class III-IV or sPESI \> 1 * Signs of RV dysfunction on imaging * Cardiac laboratory biomarkers * Intermediate-low early mortality risk * No shock or hypotension * PESI class III-IV or sPESI \> 1 * One (or none) of signs of RV dysfunction on imaging or cardiac laboratory biomarkers positive * Low early mortality risk * No shock or hypotension * Not PESI class III-IV or sPESI \>1 * Assessment of RV function/cardiac laboratory biomarkers optional, if assessed both negative

Answer 213

1. Chronic Bronchitis: * The production of sputum on most days for at least 3 months in 2 years (when other causes of chronic cough have been excluded) * Narrowing of airways due to inflammation, lack of support around airways 2. Emphysema: * Abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles

Answer 214

* Time/volume plot * FEV1 and FVC both reduced in proportion * FEV1/FVC ratio \>70% * Flow volume loop * Normal shape but smaller - reduced capacity of lungs

Answer 215

* Medium-small airways flaccid walls * Not supported by cartilage * Expiratory phase narrowing - wheeze * Muco-ciliary clearance impairment - sputum * Characteristic flow-volume loops * CXR - unhelpful (except for hyperinflation)

Answer 216

* Positive = expiration (initially effort dependent and rapid then passive effort independent) * Tails off due to airway resistance meaning the pressure of airflow decreases from alveoli --\> mouth * Negative = inspiration

Answer 217

* Haematogenous * Common due to invasion of pulmonary veins * Liver, bone, brain, adrenal * Lymphatic * Hilar lymph nodes --\> cervical lymph nodes

Answer 218

* Development of subpleural blebs/bullae at lung apex * Shape of lungs and chest cavity in tall thin people mean they are more prone to these defects * Possible additional diffuse, microscopic emphysema below the surface of the visceral pleura * Spontaneous rupture leads to tear in visceral pleura * Air flows from airways to pleural space (pressure gradient) * Elastic lung then collapses

Answer 219

Need appropriately trained technician Effort and technique dependent Patient frailty Pain, patient too unwell

Answer 220

Pirfenidone * Approved for use in IPF (patients with FVC 50 - 80 % predicted) * Antifibrotic and anti-inflammatory effects; slows lung function decline * Mechanism of action unclear but likely to suppress fibroblast proliferation, so reducing the production of fibrosis-associated proteins and cytokines * Reduces pO2 max capacity in lung Nintedanib * Intracellular inhibitor of multiple tyrosine kinases * Slows lung function decline in recent trial. Steroids and immunosuppressants are not routinely recommended for treatment of IPF * Steroids not effective in most cases * Azathioprine may worsen prognosis when used with prednisolone No longer advised to give the "triple therapy” of steroids + azathioprine + N-acetylcysteine Trial of steroids may be considered if there is felt to be a possibility of an inflammatory component in some cases e.g. younger women with a possible underlying connective tissue disease. N-acetyl cysteine * Does not improve survival or slow lung function decline * Is a mucolytic, so might be tried if a patient has cough or sputum, as has little toxicity For many patients, especially if over 80 years old therapy for IPF is essentially aimed at symptom control * Long term oxygen therapy – home oxygen eventually (stop smoking) * Diuretics for fluid retention if develop cor-pulmonale * Antibiotics to treat infection * Lung transplantation in younger patients (age \< 65)

Answer 221

* Size is less important than symptoms * Small pneumothorax very symptomatic if bad COPD * Can tolerate complete lung collapse very well if healthy * 2cm rim of air at axilla = 50% lung volume * \<2cm defined as small, \>2cm large * Options for management * Observation (serial CXR) if small or not very symptomatic - can be as outpatient * Aspiration (small bore catheter 2nd intercostal space midclavicular line - aspirate air with syringe/3 wat tap) - up to 2.5L * Intercostal drain with underwater seal * Good guideline developed by British Thoracic Society

Answer 222

* Antibodies from past exposure collect in lungs - complexes of proteins develop when antigen-antibody binding occurs * Infarction of capillaries in lungs * Inflammatory fluid fills lungs * Wall thickened with inflammation Immune complex disease = acute inflammation --\> neutrophils --\> consolidation

Answer 223

* 2 weeks of IV amphotericin B for meningitis * V unpleasant, toxic * Fluconazole or flucytosine (non-CNS) * Doesn’t penetrate CNS well enough for meningitis treatment on its own but less toxic * Can give combination therapy

Answer 224

Mild-moderate OSAS unable to tolerate CPAP Needs good dentition

Answer 225

* VATS - video assisted thoracic surgery * Considered if not resolved in 5 days * Can staple blebs * Talc pleurodesis - causes inflammatory reaction and pleural adhesion, highly effective * Pleural abrasion/stripping * Surgical pleurodesis considered if 2nd pneumothorax on same side, first contralateral event * Professional considerations e.g. airline pilots, scuba divers * After spontaneous pneumothorax should wait 7 days before flying, should not dive again

Answer 226

* Environmental exposure to allergen - house dust mite (dermatophagoides pteronyssinus), gross pollen, domestic pets * Occupation sensitisers * Non-IgE related - isocyanates, colophony fumes * IgE related - latex, animal allergens * Viral infections - rhinovirus, parainfluenza virus, RSV * Atmospheric pollution - sulphur dioxide, ozone, particulates * Drugs - NSAID, beta-blockers * Irritant drugs, vapours and fumes - perfume cigarette smoke * Exercise * Cold air * Emotion * Genetic factors - IL-4, IL-13 pathways, ADAM 33, others

Answer 227

* First look at FEV1:FVC ratio * If \<70% - obstruction * If obstructed, look at %predicted FEV1 (severity) and any reversibility (COPD vs asthma) * If FEV1/FEV ratio normal, look at % predicted FVC (if low, suggests restrictive abnormality) * Can also get mixed picture e.g. obesity and COPD - obstructive and restrictive

Answer 228

Mediastinum shifted to left, collapse of R lung

Answer 229

* Macrophages try to phagocytose something they can't digest and present so they become activated and can form giant cells (coalescence of cells with multiple nuclei) in the alveolar tissue (not in air spaces) * Giant cells can have some calcification, are multinucleated * Asteroid body - cytokeratin, specific structure in giant cells

Answer 230

* No evidence to suggest they cause COPD * Do have potential to induce inflammation and hypersensitivity pneumonitis, and have effects on blood pressure * UK advice - reasonable alternative to cigarette smoking, harm reduction but not harm free

Answer 231

* Abnormal volume of fluid in the pleural space * Normal is 15ml per hemithorax, anything more is abnormal * \>300ml before seen on X-ray

Answer 232

* COPD * Nearly all smoker/ex-smoker * Rarely symptoms under age 35 * Common to have chronic productive cough * Breathlessness persistent and progressive * Uncommon to have night time waking with breathlessness and/or wheeze * Uncommon to have significant diurnal or day-to-day variability of symptoms (progressively worsening) * Asthma * Possibly smoker/ex-smoker * Often symptoms under age 35 * Chronic productive cough uncommon * Variable breathlessness * Common night time waking with breathlessness and/or wheeze * Common significant diurnal or day-to-day variability of symptoms * If have \>400ml reversibility on spirometry, asthma more likely

Answer 233

* Scarring of lung tissue * Lots of possible causes (including sarcoidosis + EAA) * Idiopathic pulmonary fibrosis (IPF) is the clinical manifestation or equivalent of the pathological diagnosis of usual interstitial pneumonia (UIP) * It is a difficult diagnosis to make in some cases and the whole picture has to add up - radiology, pathology and clinical picture

Answer 234

* Directly measurable * Vital capacity * Inspiratory capacity * Inspiratory reserve volume (difference between tidal inspiration and full inspiration) * Tidal volume (volume in and out of lungs in quiet breathing) - 500ml normally * Expiratory reserve volume (difference between tidal expiration and full expiration) * Indirectly measureable * Residual volume - left over air in lung after full expiration, prevents collapse of lung * Total lung capacity * Functional residual capacity

Answer 235

Laser, stents to deal with tumour obstructing large airways

Answer 236

* Give controlled oxygen - smaller amounts more controlled * Aim for lower pO2 in COPD - 88-92% to stop patients developing hypercapnia * When oxygen is given, should expect PaO2 to be roughly 10-15 units below inspired O2 - i.e. for 28% O2 should expect levels of 13-18kPa

Answer 237

Central tumours arise in and around hilus of the lung and are usually squamous or small cell carcinomas Peripheral tumours are predominantly adenocarcinomas

Answer 238

* Chemoattractant substances in cigarette smoke attract inflammatory cells to the alveoli * Cell types * Macrophages, CD8 and CD4 T lymphocytes, neutrophils * Inflammatory mediators * TNF, IL8 and other chemokines * Neutrophil elastase, proteinase 3, cathepsin G (from activated neutrophils) * Elastase and MMPs (from macrophages) * Reactive oxygen species * Airway inflammation persists after smoking ceased

Answer 239

Healthy and immunocompromised people

Answer 240

Venous return impaired, cardiac output and blood pressure fall PEA (pulseless electrical activity) arrest without intervention

Answer 241

Controls muscles of larynx, long root Hoarseness - 80% of patients Usually L side affected

Answer 242

* pH \<7.2 * LDH \>1000 * Glucose \<2.2 * Loculated on ultrasound

Answer 243

* Confirm diagnosis * Assess precipitating factor * Duration of anticoagulation * Selected thrombophilia testing * Selected malignancy screening * CTEPH screening - 4% * Pulmonary hypertension persists * Clots don’t resolve, scar tissue * Counselling, for example family (e.g. COCP)

Answer 244

Consider diagnosis of COPD in those over 35 y/o, smokers or ex-smokers, with any of: * Exertional breathlessness * Regular sputum production * Wheeze * Chronic cough * Frequent winter 'bronchitis'

Answer 245

* Primary pleural tumour (also occurs in peritoneum, pericardium and tunica vaginalis testis) * Almost always due to asbestos exposure * High incidence in GGC due to Clyde shipbuilding industry * Very long lag period before disease develops * Tumour has either an epithelial or sarcomatoid appearance or a mixture of both (biphasic)

Answer 246

* Mesothelioma * Highest incidence worldwide, 200 cases per year in Scotland * Poor prognosis (1 year), treatment supportive

Answer 247

* Leads to irreversible airflow obstruction * Overall thickening of the airway wall * Epithelium - loss of ciliated columnar cells, increased number and activity of mucous secreting goblet cells * Epithelial basement membrane - sub-basement membrane fibrosis due to deposition of collagen and proteoglycans * Smooth muscle - hypertrophy and/or hyperplasia of smooth muscle layer * In the inflammation of chronic asthma - Th1 cells also activated, TNF alpha production

Answer 248

* Bird dander * Pigeon fancier's lung, budgie lung * Mushroom worker's lung * Farmer's lung (fungal spores) * Aspergillus lung * Cheese workers * Wheat weevil * Mollusc shell workers * Malt worker's lung * Humidifier lung Each with an antibody that can be measured in serum e.g. avian precipitatans

Answer 249

Post-bronchodilator FEV1 % predicted Stage 1 (mild) = 80 % Stage 2 (moderate) = 50 - 79 % Stage 3 (severe) = 30 - 49 % Stage 4 (very severe)\*\* = \< 30 Or FEV1 \<50% with respiratory failure FEV1% doesn't always correlate to loss function

Answer 250

Normal = \>70%

Answer 251

16.7/100,000 (men), 5.8/100,000 (women) Mortality rate very low (1/million/year) Recurrence rate 40-50% after first episode

Answer 252

* Associated symptoms * Red flag symptoms - weight loss, haemoptysis * Onset - fall, change in medications (e.g. Warfarin), travel? * Past medical history * Previous cancer * TB - travel * Smoking history * Occupation history

Answer 253

* Age, genetic factors, environmental factors, nature of injury --\> repetitive alveolar epithelial injury * + oxidative stress, profibrotic cytokines, chemokines, eicosnoid imbalance, impaired fibrinolysis, TIMPs-MMPs imbalance = altered alveolar microenvironment * Dysregulated repair, loss of epithelial cells, accumulation of mesenchymal cells * = fibrosis

Answer 254

* Management is symptom driven, patient centered * Chest drain +/- talc pleurodesis (80% success) * Indwelling pleural catheter * Patient choice unless talc failed/lung trapped

Answer 255

* Apnoea * The cessation, or near cessation of airflow * 4% oxygen desaturation, lasting \>10 seconds * Hypopnoea * Hypopnoea is a reduction of airflow to a degree insufficient to meet the criteria for an apnoea * Respiratory effort related arousals * Arousals associated with a change in airflow that does not meet the criteria for apnoea or hypopnoea

Answer 256

* The disease is commonly cause by smoking * Only 15-20% of smokers get COPD * Can also be caused by environmental pollution, burning of biomass fuels, occupational dusts, alpha 1 anti-trypsin deficiency (genetic)

Answer 257

* Low (\<3% per year) * Major transient or reversible factors associated with \>10 fold increased risk for the index VTE event (compared to those without risk factor) e.g. surgery with general anaesthesia for \>30 mins, confined to bed in hospital for \>7 day due to acute illness or acute exacerbation of chronic illness, trauma with fractures * Intermediated (3-8% per year) * Transient or reversible factors associated with \<10-fold increased risk for first VTE e.g. minor surgery (general anaesthesia for \<30 mins), admission to hospital for \<3 days with an acute illness, oestrogen therapy/contraception, pregnancy or post-partum, leg injury (without fracture) associated with reduced mobility for \>3 days, long haul flight * Non-malignant persistent risk factors - inflammatory bowel disease, active autoimmune disease, no identifiable risk factor * High (\>8% per year) - active cancer, one or more previous episodes of VTE in the absence of a major transient or reversible factor, antiphospholipid antibody syndrome

Answer 258

* Anti-IL5 monoclonal antibody * Reduces circulating eosinophils * Severe refractory eosinophilic asthma * Subcutaneous injection every 4 weeks * Headaches commonly reported

Answer 259

Staged as limited or extensive disease * Limited - confined to one hemithorax and the ipsilateral supraclavicular fossa (30%) * Extensive disease - all other patients (70%) * Without treatment - survival 2-3 months in limited disease, 4 weeks in extensive disease * With treatment - limited disease survival 15-20 months, 10-13% 5 year survival, extensive disease 8-13 months median survival, 1-2% survive 5 years

Answer 260

* Monoclonal anti-IgE antibody * Severe persistent allergic asthma * Subcutaneous injection every 4 weeks * Dose based on IgE and weight * Risk of severe hypersensitivity reaction

Answer 261

25,000,000 snorers in UK (40% population) 5% of UK adults thought to have undiagnosed OSA (2.5 million) 250,000 men have OSA in UK Men 2-3 \> premenopausal females Average age of presentation 40-50 y/o Incidence increasing with obesity epidemic

Answer 262

* Chronic inflammatory condition of the airways, causes recurrent episodes of wheezing, breathlessness, chest tightness and cough - particularly at night and/or early morning * Symptoms usually associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment * Airflow limitation usually reversible in early disease, but may have an irreversible component in longstanding disease Key Features: * Increased airways hyper-responsiveness to a variety of stimuli resulting in episodic bronchoconstriction * Inflammation of the bronchial walls * Increased mucous secretion

Answer 263

* Aspiration * Often need tissue for genetics

Answer 264

* In men lung cancer peaked in 1970s then decreased by around 45% reflecting reduction in smoking since 1940s * In women lung cancer rates have increased by 64% reflecting increased smoking rates in women between WW2 and the 1970s

Answer 265

* Leukotriene receptor antagonists (Montelukast and Zafirlukast) * Omalizumab * Mepolizumab

Answer 266

* In the UK incidence rates for lung cancer highest in Scotland * Scotland is the only UK nation where lung cancer remains the overall most common cancer * Lung cancer incidence is 1/3 higher in GGC compared with Scotland as a whole * Reflects the high smoking prevalence

Answer 267

Pleural fluid more grey = exudate (due to high protein content)

Answer 268

E.g. Rhinitis * Can occur due to hyperreactivity to a stimulus e.g. spicy food, cold air - most people will react if extreme but varying tolerance at low levels * Dose dependent - the more you are exposed the more likely you are to react * Can occur due to allergy to a stimulus e.g. cats - if not allergic will never react, if allergic will always react * Not dose dependent - if allergic to cats will react to one cat or 3 cats

Answer 269

Predominantly renally excreted - caution prescribing in renal impairment

Answer 270

If patient is improving continue * 40-60% oxygen * Prednisolone 40-50mg daily (should continue for at least 5 days or until recovery) * Nebulised B2 agonist and ipratropium 4-6 hourly

Answer 271

Can give replacement - not a wide-spread therapy, quitting smoking more effective

Answer 272

* Known * Occupational - asbestos, beryllium * Environmental - hypersensitivity pneumonitis (birds, mould etc) * Medication * Connective tissue disease - scleroderma, polymyositis, rheumatoid arthritis * Unknown * Idiopathic interstitial pneumonia - IPF, NSIP, other * Granulomatous - sarcoidosis * Other - vasculitis, eosinophilic

Answer 273

* Bind to activated glucocorticoid receptors to suppress multiple pro-inflammatory genes that are activated in asthmatic airways by reversing histone acetylation (promotes histone deacetylase 2) * Reduces number of inflammatory cells in airways and release of pro-inflammatory cytokines, reduces airway oedema and mucous secretion, allows beta 2 agonist to work better by freeing beta 2 receptors

Answer 274

* Central - bronchi and hila * Ulceration of bronchus - cough, haemoptysis * Bronchial obstruction - pneumonia, lung abscess, bronchiectasis, wheeze, shortness of breath * Build up of secretions - retention pneumonia, irritation (chronic cough) * Peripheral - out towards chest wall * May not have symptoms - have extra lung capacity * If involves chest wall may have chest wall pain * Pleural involvement - pain, effusion * Apical lung cancer * Compression of - sympathetic chain (Horner's syndrome), T1 and T2 roots to brachial plexus (wasting of hand muscle, pain down arm)

Answer 275

* Limited polysomnography (limited sleep study) * 5 channel home study * Oxygen saturations * Heart rate * Flow * Thoracic and abdominal effort * Position * Full polysomnography * EEG - sleep staging * Video * Audio * Thoracic and abdominal bands * Position * Flow * Oxygen saturations * Limb leads * Snore Advantages of Full PSG: * Correct patient * Accurate assessment of sleep efficiency * Sleep staging via EEG * Parasomnic activity - acting out dreams, sleep talking * Can diagnose other sleep disorders e.g. narcolepsy

Answer 276

During an asthma exacerbation there is air trapping and ventilation/perfusion mismatch, resulting in hypoxemia. Initially compensation occurs and hyperventilation causes the PCO2 to decrease. When further air trapping leads to decreased lung compliance and increased work of breathing, the PCO2 will begin to increase. Thus, a “normal” pCO2 in a wheezing patient is a sign of a severe/life-threatening attack.

Answer 277

* Not acidotic, pCO2 normal, bicarbonate normal * pO2 high - recieving too much oxygen * Patients with COPD develop hypercapnia (CO2 retention, hypoventilation) when pO2 too high

Answer 278

Spirometry: Obstructive pattern - FEV1:FVC ratio \<70% (both reduced)

Answer 279

* Step-wise approach to asthma management in Adults (BTS SIGN Guideline 2019) * Drug treatment is directed at relieving smooth muscle spasm and reducing underlying airway inflammation - use of the lowest effective doses of convenient medications to minimise short-term and long-term side effects. Short acting beta 2 agonist as required + 1. Regular preventer - low dose inhaled corticosteroid (ICS) 2. Initial add-on therapy - add inhaled LABA to low dose ICS (fixed fose or MMT) 3. Additional controlled therapies - consider increasing ICS to medium dose or adding LTRA (if no response to LABA consider stopping LABA) 4. Specialist therapies - refer patient for specialist case

Answer 280

* Generally asthma or COPD * FEV1:FVC ratio \<70% * Time/volume plot - much slower rising curve * Flow/volume loop * Loss of support holding airway open --\> airway obstruction * Typical 'church and steeple' pattern - scooped out appearance of expiratory loop * Passive exhalation of air not occurring as efficiently

Answer 281

* Shortness of breath * Weight loss * Cough * Haemoptysis * Chest pain/pressure * Lethargy * Fever

Answer 282

* Many resistance mechanisms documented - efflux via ABC-transporters, ribosome protection proteins (RPPs) preventing tetracycline binding * Well absorbed orally * Avoid/caution in patients with hepatic impairment * Chelates calcium (avoid in young children and pregnancy) * Brown discolouration of teeth, abnormal bone development

Answer 283

Adenocarcinomas now tested for genetic mutations, and if positive, specific treatments may be offered * EGFR mutations - erlotinib * ALK mutations - crizotinib * PD-L1 mutations - immunotherapy e.g. Nivolumab * ROS-1 mutations - crizotinib, increased senstivity to premetrexed

Answer 284

Aminophylline is a mixture of theophylline and ethylenediamine (ratio 2:1). This formulation improves solubility and is preferred for IV administration, also non-selective adenosine receptor antagonist.

Answer 285

Most common to least common complications following PTE: * Reduced functional status * Persistent thrombi * Measurable limitations in cardiopulmonary function * CTEPH * Post-PE syndrome

Answer 286

* Azoles are inhibitor of 14-methylsterol alpha-demethylase which produces ergosterol * Ergosterol is an essential component of the fungal plasma membrane * Sterols insert themselves into the lipid bilayer and are essential for its proper functioning and viscosity * Does not occur in animal or plant cells * Equivalent of cholesterol in yeast, fungi * Eradicate fungus without affecting human cells * Resistance to azoles emerging

Answer 287

1. Dermatophytes 2. Systemic fungal infections

Answer 288

When lungs working well airflow is linear - evenly straight down Airflow partially interrupted by divisions in airways, which causes turbulence Turbulence increased by narrowing of airways - air circulates round making high pitched noise --\> wheeze

Answer 289

For smokers who have already developed moderate obstruction, stopping smoking at the age of 45 can make the difference between a normal lifespan and premature death If continue to smoke - disability and death occur more quickly

Answer 290

* Higher specificity for pulmonary beta 2 receptors vs. cardiac beta 1 receptors * Stimulate adenyl cyclase to increase intracellular cAMP --\> relaxation of bronchial smooth muscle

Answer 291

* Tumour of neuroendocrine cells * Central or peripheral * Classified as typical or atypical * Can metastasise but much better prognosis than other conventional lung cancers (5 year survival for typical 85-90%, atypical 5 year survival 50-75%) * Appearance * Polypoid projections in airways * Yellowish brown colour

Answer 292

* Inherent weakness in lung tissue e.g. emphysema * Increased airway pressure e.g. asthma, ventilated patient (high positive pressure) * Increased lung elasticity e.g. pulmonary fibrosis * Patient is generally much more symptomatic * Poor underlying lung function * Management more complex, prognosis less good * More likely to require intervention

Answer 293

Pink Puffer * High respiratory drive, low PaO2, PaCO2, desaturates on exercise, type 1 respiratory failure * O/E - pursed lip breathing, use accessory muscles, wheeze, indrawing of intercostals, tachypnoea Blue Bloater - loss of central sensitivity to CO2 and reliance on hypoxic drive to stimulate breathing * Low respiratory drive, low PaO2, high PaO2 right heart failure (oedema), type 2 respiratory failure * O/E - confusion, drowsiness, cyanosis, wheeze, hypoventilation, warm peripheries and bounding pulse, flapping tremor, peripheral oedema

Answer 294

Bronchiolocentric pattern Foamy macrophages in alveolar spaces - lung produces surfactant, washed out by staining process so looks foamy Chronic interstitial inflammation Organising pneumonia

Answer 295

Asthma - mainstay of asthma therapy COPD with recurrent exacerbation Exacerbations of asthma/COPD

Answer 296

LABA/LAMA - usually once daily E.g. Anoro Ellipta (umeclinidium/vilanterol) LABA/ICS E.g. Relvar Ellipta (fluticasone/vilanterol), seretide accuhaler/evohaler (fluticasone/salmeterol) - increases risk of pneumonia

Answer 297

* Emotional disturbance * Enlarged sella turcica * Moon facies * Osteoporosis * Cardiac hypertrophy (hypertension) * Buffalo hump * Obesity * Adrenal tumour or hyperplasia * Thin, wrinkled skin * Abdominal striae * Amenorrhoea * Muscle weakness * Purpura * Skin ulcers (poor wound healing)

Answer 298

* Age of onset \>50 * Male\>female * Progressive breathlessness, productive cough, cyanosis * Respiratory failure, cor pulmonale, pulmonary hypertension * Fine bilateral end-inspiratory crackles * Finger clubbing (2/3) * Usually a history of cigarette smoking

Answer 299

* Fungal meningitis * Cryptococcus neoformans * Aspergillosis of the lungs * Aspergillus fumigatus * Pneumocystis pneumonia * Pneumocystis Jiroveci

Answer 300

Can cause cirrhosis - proteases in liver To avoid need to minimise alcohol intake/stop smoking

Answer 301

* Smoking is the main avoidable risk for lung cancer - 72% of cases * Predisposes to lung cancer of all major histological types but link strongest for squamous and small cell * Smoking risks * \<5% are life long non-smokers * 10-20 cig/day - 30x risk * 60cig/day - 60x risk * Stopping smoking reduces risk but depends on number of years of smoking and takes time