LO01 - Acute dyspnoea and haemoptysis

Question 1

What is dyspnoea?

Answer 1

The sensation of breathlessness

Question 2

Outline the three mechanisms that trigger the sensation of dyspnoea, and the physiological basis for each.

Answer 2

1. Increased central respiratory drive: chemoreceptors detect hypercapnia, hypoxaemia and acidosis. Central chemoreceptors in the medulla respond to changes in CSF pH. Peripheral chemoreceptors in the aortic and carotid bodies respond to changes in arterial pO2, pCO2 and pH. 2. Increased respiratory load: due to increased airway resistance, decreased lung compliance, or decreased environmental pO2. 3. Lung irritation: detected by a shit ton of receptors.

Question 3

Outline important DDxs for dyspnoea (do it systematically).

Answer 3

(Don’t have to have aaaall of these, but make sure you remembered all these categories)

Resp:

• Parenchyma: COPD, tumour, infection, sarcoidosis, interstitial lung disease
• Airways: asthma, infection, foreign body
• Vasculature: PE, pulmonary HTN
• Pleura: pneumothorax, pleural effusion

CV: MI, CCF, aortic dissection, pericarditis, arrhythmia, VHD, CM

MSK: kyphoscoliosis, pectus excavatum Haem: anaemia, CO poisoning

GI: GORD, ascites Neuro: stroke, tetanus, GBS, ALS, MG

Endocrine: thyroid disease, Cushing’s, phaeochromocytoma

Psych: anxiety, panic attacks

Physiological: ageing, deconditioning, obesity

Other: shock, anaphylaxis

Question 4

Outline factors predisposing to VTE

Answer 4

Hypercoagulability: cancer, coagulopathy, inflammation, antiphospholipid syndrome, pregnancy, OCP/HRT, surgery? Stasis/turbulence: recent surgery esp ortho/abdo, COPD, CCF, varicose veins, stroke/spinal cord injury, prolonged travel Endothelial dysfunction (usually more relevant to arterial thromboembolism but hypercholesterolaemia, DM etc)

Question 5

Signs/symptoms of PE

Answer 5

Dyspnoea, pleuritic chest pain, haemoptysis, Sx of DVT, tachypnoea, tachycardia, circulatory collapse (SBP

Question 6

Sequence of PE investigations

Answer 6

Wells score to stratify risk If low risk: D-dimers - negative result excludes PE If high risk or positive D-dimer: CTPA (gold standard) or VQ scan (Plus other investigations for other differentials, obviously)

Question 7

Outline the mechanisms of action, use and other pertinent issues relating to common anticoagulant and fibrinolytic meds.

Answer 7

Antiplatelet (acute ischaemic events and long-term prophylaxis): - aspirin (COX inhibitor): no antidote, GI side effects. - dipyridamole (PDE inhibitor): has an antidote - clopidogrel (ADP receptor antagonist): no antidote - abciximab (integrin a11b beta2 blocker): no antidote, biological agent side effects Anticoagulant: Long-term prophylaxis - dabigatran (direct thrombin inhibitor): : NO ANTIDOTE - apixaban (factor Xa inhibitor): NO ANTIDOTE - warfarin (vit K antagonist): SO MANY INTERACTIONS, antidote: vitamin K plus coagulation factors (eg through FFP) - heparin, LMW heparin (antithrombin activator): antidote: protamine Thrombolytic (acute thrombolysis): tPA/streptokinase (activate plasminogen to plasmin): antidote: tranexamic acid

Question 8

Outline the causes of heart failure (systematically, thinking about the different parts of the cardiac cycle)

Answer 8

Ventricular inflow obstruction: Mitral stenosis, tricuspid stenosis Diastolic dysfunction: Constrictive pericarditis, cardiac tamponade, restrictive cardiomyopathy, left ventricular hypertrophy and fibrosis Arrhythmia: Atrial fibrillation, complete heart block Reduced ventricular contractility: MI, myocarditis/cardiomyopathy Ventricular outflow obstruction: (L): Hypertension, aortic stenosis (R): Pulmonary hypertension, pulmonary valve stenosis

Question 9

Outline the compensatory responses of the body to heart failure

Answer 9

• Sympathetic nervous activation: causes vasoconstriction and increases renin secretion • Renin-angiotensin system activation: angiotensin II causes vasoconstriction, sodium and water retention and aldosterone release. Aldosterone also acts to increase sodium and water retention • ADH activation: causes vasoconstriction and sodium and water retention • Endothelin activation: highly potent vasoconstrictor These work to increase afterload (by inducing arterial vasoconstriction) and preload (through sodium and water retention, venous vasoconstriction and thirst).

Question 10

Explain the signs and symptoms of left and right sided heart failure

Answer 10

LHF: Pulmonary oedema (with acute heart failure, or advanced chronic heart failure - initially with chronic heart failure you get reflex pulmonary vasoconstriction and pulmonary hypertension) -> cardiomegaly, Kerley B lines on CXR RHF: peripheral oedema, ascites, elevated JVP, pleural effusion

Question 11

Outline the pharm management of CCF, the mech of action and the important considerations for each

Answer 11

Firstline: - ACE inhibitors (inhibit angiotensin converting enzyme): can worse renal function and cause hyperkalaemia - Beta blockers (antagonise beta-AR in the heart) Secondline: - Aldosterone receptor blockers: can worsen renal function and cause hyperkalaemia - AngII receptor blockers (not sure about effect on renal function) Thirdline: - Digoxin (increases ventricular contractility): improving quality of life Symptomatic: - Frusemide (inhibits Na+/Cl- reabsorption in the thick aLH): may cause hyperkalaemia

Question 12

Outline the pathology of ARDS

Answer 12

ARDS occurs when the alveolar-capillary membrane is damaged. Neutrophils are significantly implicated in this process. This leads to increased vascular permeability, which causes alveolar flooding. There is also damage to type II pneumocytes, leading to a loss of surfactant and contributing to alveolar collapse. This causes a reduction in lung compliance. Hence, the morphological hallmarks of ARDS are 1. Collections of neutrophils in capillaries 2. Necrosis of alveolar epithelial cells 3. Capillary congestion 4. Interstitial and intra-alveolar haemorrhage and pulmonary oedema with hyaline membrane formation If the underlying cause is not treated and resolved, this can progress to pulmonary fibrosis. Type II pneumocytes proliferate to try and regenerate the alveolar lining. The fibrinous exudate present from the acute inflammation is organised, leading to intra-alveolar fibrosis. Interstitial cells proliferate and collagen is deposited causing thickening of the alveolar septa.

Question 13

Outline the management of ARDS

Answer 13

1. Prevention of complications: oxygen saturation should be above 88%, which will usually require mechanical ventilation. You may need to sedate the patient. Fluid balance should be maintained as slightly negative or neutral (as long as the patient isn’t in shock) to create a driving force for re-absorption of pulmonary oedema. 2. Supportive care: this includes things like DVT prophylaxis, blood glucose control, maintaining blood pressure and Hb, and prophylaxis against stress-induced GI bleeding 3. Treat underlying cause if infective: use an appropriate antibiotic

Question 14

Explain how ABG results can help with investigating acute dyspnoea

Answer 14

Hypoxaemia indicates respiratory impairment or failure. The presence of hypercapnia enables differentiation between Type 1 and Type 2 respiratory failure: • Type 1: hypoxaemic BUT NOT hypercapnic. This is due to a failure of gas exchange – able to breathe off CO2 fine, but not enough oxygen is getting across into the blood. This is due to VQ mismatch. • Type 2: hypoxaemia AND hypercapnic. This is due to alveolar hypoventilation – the respiratory muscles can’t work hard enough to clear the carbon dioxide.

Question 15

Haemoptysis DDx (eg using VITAMIN D)

Answer 15

• Vascular: o PE: the embolus causes infarction of the lung tissue, blood collects in the infarcted zone o Pulmonary venous hypertension: high blood pressures damage venous walls, causing blood excursion into the lung and eventually haemoptysis. • Inflammatory/infective: o Bronchitis, pneumonia, tuberculosis: inflammation damages the vasculature, can be exacerbated by a repetitive cough. • Traumatic: o Airway trauma, foreign body: the trauma damages the vasculature • Autoimmune • Metabolic • Idiopathic/iatrogenic: who knows • Neoplastic: o Cancer: the cancer invades through the superficial mucosa and into blood vessels, causing bleeding into the lung. A highly vascular tumour with fragile vessel walls can itself bleed and cause the haemoptysis. • Degenerative

Question 16

Describe the four types of lung carcinoma

Answer 16

• Squamous cell carcinomas: closely correlated with smoking history. Arise centrally in major bronchi, eventually spread to local hilar nodes, disseminate outside the thorax later than other types. Preceded by squamous dysplasia and carcinoma in situ, which can last for several years before stromal invasion. • Adenocarcinoma: Usually located peripherally, grow slowly, metastasise widely at an early stage. Preceded by atypical adenomatous hyperplasia and adenocarcinoma in situ. • Large cell carcinomas: undifferentiated malignant epithelial tumours without cytological features of SCLC or glandular/squamous differentiation. Probably represent squamous or adenocarcinomas with complete loss of differentiation. • Small cell carcinomas: Centrally located with early involvement of hilar and mediastinal nodes.

Question 17

Explain how the biological behaviour of small cell vs non-small cell lung carcinoma affects management

Answer 17

Small cell lung carcinomas have usually metastasised by the time of diagnosis, whereas non-small cell carcinomas may have not. Thus, surgical resection and radiotherapy are suitable treatment modalities for NSCLC (which responds poorly to traditional chemotherapy), whereas SCLC is usually treated with chemotherapy +/- radiotherapy. SCLC is very sensitive to chemotherapy, but usually recurs. Median survival with treatment is 1 year.

Question 18

What are the common modes of spread of lung cancer?

Answer 18

Haematogenous and lymphatic

Question 19

Describe the symptoms you might expect at each stage of lung cancer and the basis for these symptoms

Answer 19

Preneoplastic lesions: usually asymptomatic Neoplastic lesions: usually initially asymptomatic. Later in the course can cause cough (due to irritation of the lung mucosa), weight loss (due to release of cytokines such as IL-1 and TNF-alpha which induce anorexia and catabolism), chest pain (due to irritation of pulmonary nerves) and dyspnoea (due to airway obstruction). Obstruction of an airway can also lead to pneumonia, abscess or lobar collapse. Lesions which have invaded into local structures: can cause symptoms based on the site of spread – pleural effusion (pleura), hoarseness (recurrent laryngeal nerve), dysphagia (oesophagus), diaphragm paralysis (phrenic nerve), rib destruction (chest wall), SVC syndrome (SVC compression), Horner’s syndrome (sympathetic ganglia), pericarditis or tamponade (pericardium) Metastatic lesions: can be the first sign of malignant disease. Likely metastatic sites for lung carcinoma are adrenal glands (>50%), liver (30-50%), brain (20%) and bone (20%). This can result in pain, or alteration of function eg altered mental status from brain mets.

Question 20

Describe the common causes of bronchiectasis

Answer 20

Congenital causes • Cystic fibrosis • Ciliary dysfunction syndromes eg primary ciliary dyskinesia, Kartagener’s syndrome • Primary hypogammaglobulinaemia (=immune dysfunction) Acquired infectious causes • Suppurative pneumonia • Pulmonary TB • Allergic aspergillosis complicating asthma Acquired obstructive causes (where the bronchiectasis is localised to the obstructed lung segment) • Inhaled foreign body • Bronchial tumours

Question 21

Describe the morphology of bronchiectasis

Answer 21

Bronchiectasis usually affects the lower lobes bilaterally. Given the definition of bronchiectasis, you would expect airway dilatation and signs of inflammation: acute and chronic inflammatory exudates within the walls of the bronchi and bronchioles, ulceration of the lining epithelium, peribronchiolar fibrosis (in chronic cases).

Question 22

Describe the clinical manifestations of bronchiectasis

Answer 22

Bronchiectasis manifests with signs and symptoms of infection: • Chronic productive purulent cough: usually worse in mornings • Haemoptysis: can be slight or massive • Fever, malaise • Weight loss, anorexia, lassitude

Question 23

Explain how a lung abscess may produce haemoptysis.

Answer 23

Aetiology: microbial infection of the lung -> necrosis of the pulmonary parenchyma -> localised collection of pus. The necrotising infection can erode into the vasculature, causing minor or massive haemoptysis.

Question 24

List some pathogens that can cause a lung abscess

Answer 24

A variety of microbial pathogens can cause a lung abscess: • In a previously healthy host: Staph aureus, Klebsiella pneumonia, Strep pyogenes, others • In an aspiration prone host: Anaerobic bacteria, others • In an immunocompromised host: Mycobacterium tuberculosis, others

Question 25

Describe how you would investigate haemoptysis

Answer 25

Bedside • ECG: in case of cardiac cause of pulmonary hypertension Imaging • CXR: firstline • CT chest: if nothing comes up on CXR • Bronchoscopy: if suspicion of cancer • Echo: if suspicion of cardiac cause Laboratory investigations • FBC: looking for signs of infection, chronic blood loss or a haematological disorder • Coags: could find a coagulopathy • ABG: if concerned about respiratory failure • UEC: uraemia affects platelet aggregation • Sputum: cytology to identify malignant cells, microscopy for acid-fast bacilli, culture to identify infectious agent

Question 26

What would you be looking for on history and exam if the patient presents with haemoptysis

Answer 26

History • Quantify and qualify the nature of the haemoptysis • Risk factors for the differentials Examination • Clubbing: non-small-cell bronchogenic carcinoma, bronchiectasis, chronic lung abscess • Unilateral wheeze: cancer blocking the laminar flow of air • Heart sounds: sounds suggesting mitral stenosis (low-pitched rumbling diastolic murmur, opening snap, loud S1, loud P2) • Purpura: coagulopathy • Rheum signs: rheum disease

Question 27

Outline the investigations appropriate to the diagnosis of TB

Answer 27

First of all you need a high clinical index of suspicion, based on likely symptoms (fever, malaise, pleuritic chest pain, cough longer than 2-3 weeks, night sweats, weight loss, haemoptysis) and risk factors (recent travel or infectious contacts). Laboratory investigations include: • Sputum (3 specimens): microscopy (for AFB) culture and sensitivity. Sputum culture is the gold standard test for TB • Molecular assay: faster than culture, more sensitive than acid-fast microscopy • FBC Imaging includes: • CXR: air space consolidation, cavitation, fibrous contraction

Question 28

Outline the management of TB

Answer 28

TB is a notifiable disease, and a public health issue. A smear positive pulmonary TB diagnosis results in treatment, government notification, patient isolation (until at minimal risk of transmitting infection) and contact tracing. Antibiotic agents form the mainstay of TB treatment. Isoniazid resistance is prevalent enough in Australia to warrant a four-drug regime. MDR-TB is uncommon, but should be tested for. Directly observed therapy (DOT) is recommended to prevent the development of further resistance. The standard short course is used if there is no resistance to these agents and no evidence of miliary or CNS TB. It involves: 1. 2 months of RIPE: rifampicin, isoniazid, pyrazinamide and ethambutol 2. 4 more months of RI: rifampicin and isoniazid These can be taken daily or three times a week. If there’s resistance, seek expert advice, I think.

Question 29

Describe the pathological changes you would expect to see at the different stages of TB infection

Answer 29

1. Initial infection: bacillary proliferation within alveolar macrophages and air spaces, leading to bacteraemia and seeding of multiple sites. 2. Cell-mediated immunity develops (~3 weeks): Th1 cells stimulate macrophages to kill the bacilli, with accompanying tissue destruction o Bacilli in distal air spaces of upper part of lower lobe or lower part of upper lobe o Granulomatous inflammatory reaction causing caseating and non-caseating granulomas: these contain epithelioid histiocytes and multinucleate giant cells o Ghon focus: 1-1.5cm area of gray-white inflammatory consolidation with central caseous necrosis, which undergoes progressive fibrosis and then calcification o Regional lymph node also have caseous necrosis 3. Reinfection/reactivation of latent bacilli o Grey-white foci of consolidation with central caseation and peripheral fibrosis. Again, if it’s healing well, it will become fibrosed then calcified. Progressive TB o The caseating necrosis expands. When the lesion erodes into bronchi, the necrotic debris falls into the bronchi (?is evacuated) leaving behind a irregular cavity lined by caseous material. o When the lesion erodes into blood vessels, haemoptysis occurs. o Healing by fibrosis Miliary TB o Lots of tiny foci of consolidation throughout the lung parenchyma. TB can also be found in lymph nodes, bronchi, trachea, larynx, systemically (systemic miliary TB) or any isolated organ.

Question 30

Outline the pathological process of TB and how it relates to the hosts’ immune function

Answer 30

Basically this diagram: