A. 33
B. 12
C. 56
D. 89
E. 8
12. Which one of the following is associated with narcolepsy?
A. Increased daytime sleep latency
B. Reduced levels of cerebrospinal fluid (CSF) hypocretin
C. Improvement in symptoms with clonazepam
D. Temporal lobe abnormalities
E. HLA-B29
13. A 65-year-old woman with severe kyphoscoliosis undergoes a preoperative pulmonary function test. Which one of the following components of the lung function test is likely to be maximally impacted by the above disorder?
A. Increased total lung capacity (TLC)
B. Increased functional residual capacity (FRC)
C. Increased maximal inspiratory pressure (MIP)
D. Decreased vital capacity (VC)
E. Reduced forced expiratory volume in 1 s (FEV1)-to-forced vital capacity (FVC) ratio
14. Omalizumab is the first monoclonal antibody used in the treatment of asthma. The mechanism of action of omalizumab is best explained by:
A. Binding to immunoglobulin E (IgE) with reductions in serum IgE and reduced IgE binding to the IgE receptor on basophils and mast cells
B. Blockage of the binding of leukotrienes to type 1 cysteinyl leukotriene receptor
C. Binding to tumour necrosis factor (TNF)
D. Inhibition of IgE synthesis
E. Inhibition of degranulation of mast cells
Theme: Arterial blood gases (for Questions 15–17)
For each patient described below, select the most likely arterial blood gas findings.
15. A 20-year-old woman was brought in after ingesting a hundred 300 mg aspirin tablets. She is semi-conscious but responding to painful stimuli. Her blood pressure is 125/80 mmHg, pulse rate of 100 beats/min and respiratory rate of 36 breaths/min.
16. A 63-year-old man has long-term chronic obstructive pulmonary disease (reformed smoker) and is currently on domiciliary oxygen. He has previously been admitted to hospital with acute exacerbation of his respiratory symptoms and required non-invasive ventilation.
17. A 19-year-old pregnant woman with type 1 diabetes presents with a 2-day history of polyuria, dysuria and general unwellness. There is a history of poor compliance with medical therapy. On examination, she is afebrile and her blood pressure is 110/60 mmHg. Chest examination is normal. The results of investigations are given below.
| Value | Reference range | |
|---|---|---|
| Sodium (mmol/L) | 135 | 137–145 |
| Potassium (mmol/L) | 4.8 | 3.2–4.3 |
| Chloride (mmol/L) | 101 | 100–109 |
| Bicarbonate (mmol/L) | 10 | 22–32 |
| Urea (mmol/L) | 8.1 | 2.7–8.0 |
| Creatinine (μmol/L) | 90 | 50–110 |
| Glucose (mmol/L) | 24.0 | 3.2–5.5 |
Urinalysis results: +++ ketones, ++++ glucose.
Clinical
18. Which one of the following features excludes a diagnosis of chronic obstructive pulmonary disease (COPD)?
A. FEV1/FVC <0.70 post bronchodilator
B. FEV1/FVC >0.70 post bronchodilator
C. Non-smoker
D. Weight loss
E. Improvement with pulmonary rehabilitation programmes
19. Which one of the following treatment modalities for cystic fibrosis is described correctly?
A. Bronchodilator therapy is helpful in the majority of patients
B. Nebulised dornase alpha can improve the viscosity of the mucus
C. Oral azithromycin is used to eradicate Staphylococcus aureus
D. Regular use of oral corticosteroids reduces the frequency of infective exacerbations
E. A course of a single intravenous antibiotic is adequate in the treatment of a severe exacerbation
20. A 58-year-old woman develops a moderate pleural effusion following a right lower lobe pneumonia. Thoracocentesis reveals straw-coloured fluid with Gram-positive diplococci on Gram stain, pH 6.9, glucose 2.2 mmol/L and lactate dehydrogenase 1400 U/L. Which one of the following is the best next step?
A. Continue current antibiotics for pneumonia
B. Intravenous ceftriaxone for 5 days
C. Tube thoracostomy to drain the effusion
D. Administer streptokinase intrapleurally
E. Repeat chest X-ray in 2 weeks to evaluate the size of the effusion
21. Which one of the following does not preclude an attempt at curative lobectomy for bronchogenic non-small cell lung carcinoma?
A. Pulmonary osteoarthropathy
B. Hoarseness of voice
C. Superior vena cava obstruction
D. Blood-stained pleural effusion
E. Preoperative forced expiratory volume in 1 s (FEV1)of 1.0 L
22. Which one of the following is correct in patients with malignant mesothelioma?
A. A median survival from diagnosis of 30 months
B. Positron emission tomography (PET) scanning is not helpful in diagnosis
C. Mesothelioma does not affect the peritoneum
D. It is associated with prior exposure to amphibole asbestos fibres
E. Imatinib therapy significantly improves survival
23. Which one of the following findings indicates a high risk of adverse outcomes in a patient with newly diagnosed acute pulmonary embolism?
A. Normal troponin
B. Hypertension
C. Normal C-reactive protein
D. Westermark’s sign on chest X-ray
E. Right ventricular dysfunction on echocardiography
24. A 58-year-old man has worked as a miner for 20 years. He presents with a 3-month history of cough and breathlessness. Chest X-ray shows diffuse interstitial shadowing. A sputum sample is positive for acid-fast bacilli. Which one of the following dusts is most likely to have predisposed the patient to tuberculosis?
A. Beryllium
B. Cadmium
C. Coal dust
D. Copper dust
E. Silica
25. Which one of the following antibiotics has been found to have potential immunomodulatory benefits in the treatment of non-cystic fibrosis bronchiectasis?
A. Azithromycin
B. Tobramycin
C. Amoxycillin with clavulanic acid
D. Vancomycin
E. Metronidazole
26. Which one of the following is commonly associated with secondary pneumothorax?
A. Bronchiectasis
B. Cystic fibrosis
C. Wegener granulomatosis
D. Osteogenesis imperfecta
E. Pneumocystis jirovecii pneumonia in patients with human immunodeficiency virus (HIV) infection
27. A 56-year-old woman with a history of depression and chronic back pain is admitted to an Acute Medical Unit after her daughter found her unresponsive on the floor with shallow breathing. She was well 2 h before her daughter left to go shopping. Her arterial blood gas on room air is shown below. What is the most likely explanation for her presentation?
| Value | Reference range | |
|---|---|---|
| pH | 7.23 | 7.35–7.45 |
| PaCO2 (mmHg) | 68 | 35–45 |
| PaO2 (mmHg) | 60 | 80–110 |
| Bicarbonate (mmol/L) | 26 | 22–32 |
| Anion gap (mmol/L) | 12 | 8–14 |
A. Lactic acidosis
B. Opioid overdose
C. Distal renal tubular acidosis
D. Proximal renal tubular acidosis
E. Ethylene glycol poisoning
28. A 38-year-old Aboriginal man presents with a 4-week history of low-grade fever, weight loss and cough. As the treating medical practitioner, you are considering the possibility of active pulmonary tuberculosis. Which one of the following is the most sensitive test to confirm the diagnosis?
A. Tuberculin skin test
B. Sputum smear
C. Rapid polymerase chain reaction (PCR) test
D. Sputum mycobacterial culture
E. Interferon-gamma release assay
29. A 72-year-old woman with a known history of sarcoidosis presents with hypercalcaemia (total calcium 3.10 mmol/L; reference range: 2.10–2.55 mmol/L) and renal impairment (creatinine 219 μmol/L; reference range: 50–100 μmol/L). Which one of the following best explains the mechanism of hypercalcaemia in sarcoidosis?
A. Chronic renal failure with secondary hyperparathyroidism
B. Increased formation of 1, 25-alpha hydroxy vitamin D
C. Milk alkali syndrome
D. Immobility
E. Ectopic calcitonin formation
30. A 65-year-old Caucasian man with a 60-pack year smoking history and previous asbestos exposure presents with dyspnoea. He has a past medical history of congestive cardiac failure with a recent echocardiogram showing impairment of LV function with an ejection fraction of 28%. Chest X-ray shows a large right-sided pleural effusion. A pleural tap reveals fluid with an LDH of 150 U/L (with a serum LDH of 300 U/L) and a pleural fluid protein of 12 g/L (with a concurrent serum protein of 40 g/L). These results are most consistent with which one of the following as the cause of the effusion?
A. Congestive cardiac failure
B. Mesothelioma
C. Pulmonary embolism
D. Carcinoma of the bronchus
E. Tuberculosis
31. Which one of the following has been found to reduce lung function decline and mortality rates in patients with chronic obstructive pulmonary disease (COPD)?
A. Budesonide
B. Salbutamol
C. Cessation of cigarette smoking
D. Long-term antibiotics
E. Ipratropium
32. A 25-year-old pregnant woman was found to have pulmonary embolism on investigation for dyspnoea during her third trimester (week 39). Which one of the following treatment options is the most appropriate in this setting?
A. Warfarin
B. Low molecular weight heparin
C. Aspirin
D. Intravenous unfractionated heparin
E. Graduated compression stockings
33. A 70-year-old man presents with a history of progressive dyspnoea for the past several years. He has chronic obstructive pulmonary disease (COPD) resulting from a 45-pack year smoking history but quit about 4 years before his current presentation. He is currently on combination budesonide 160 μg and formoterol 4.5 μg per dose, two inhalations twice a day; and salbutamol 100 μg per dose, two inhalations every 4–6 h as required. The results of his investigations are shown below. Which one of the following treatments is the most likely to improve his long-term survival?
| Value | Reference range | |
|---|---|---|
| Arterial blood gas on air at rest: | ||
| pH | 7.40 | 7.35–7.45 |
| PaCO2 (mmHg) | 40 | 35–45 |
| PaO2 (mmHg) | 53 | 80–110 |
| Spirometry: | ||
| FEV1/FVC (%) | 43 | |
| FEV1 (% of predicted value) | 30 |
A. Pulmonary rehabilitation
B. Ambulatory oxygen therapy for 18 h/day
C. Lung volume reduction surgery
D. Lung transplantation
E. Theophylline sustained-release 200 mg once a day
34. Which one of the following is a major risk factor for chronic allograft dysfunction due to bronchiolitis obliterans after lung transplantation?
A. Silent aspiration
B. Acute cellular rejection
C. Use of azithromycin
D. Cyclosporine
E. Nissen fundoplication
35. A 55-year-old woman has had six admissions in the past 12 months for infective exacerbations of her bronchiectasis. A trial of long-term oral macrolides is being considered. Prior to commencing the macrolide, which one of the following investigations must be undertaken?
A. Sputum specimen to exclude non-tuberculous mycobacterial infection
B. Chest X-ray to exclude a pleural effusion
C. High-resolution computed tomography of the chest to evaluate the extent of disease
D. Spirometry to assess the forced expiratory volume in 1 s (FEV1)
E. Transthoracic echocardiography to estimate pulmonary arterial pressure
Theme: Chronic infiltrative lung disease (for Questions 36–39)
A. Bronchiolitis obliterans organising pneumonia (BOOP)
B. Desquamative interstitial pneumonitis (DIP)
C. Idiopathic pulmonary fibrosis (IPF)
D. Acute interstitial fibrosis (Hamman–Rich syndrome)
E. Allergic bronchopulmonary aspergillosis
F. Alveolar proteinosis
G. Löffler syndrome
H. Lymphangioleiomyomatosis
For each of the following scenarios, select the most likely diagnosis.
36. A 43-year-old woman who has had asthma for 15 years presents with progressive dyspnoea, chills and productive cough. Physical examination reveals a thin woman in moderate respiratory distress. She is afebrile but has mild tachypnoea and tachycardia. Lung examination reveals moderate air movement, diffuse wheezes and egophony in the left upper lung zone without change in tactile fremitus. The chest X-ray is shown below. Which of the following diagnoses best explains the constellation of clinical findings and radiological changes?
37. A 64-year-old Caucasian man presents with a 1-year history of worsening dyspnoea on exertion and mild non-productive cough. He reports previous asbestos exposure when he was working in a shipyard. The patient has never smoked. He has been treated with several inhaled beta-agonists, without any improvement. The physical examination is significant for dry inspiratory crackles and clubbing of his digits. A chest X-ray shows a diffuse infiltrative process, without lymphadenopathy or effusions. The patient undergoes an open lung biopsy, which shows minimal inflammatory round cell infiltrate, widening of alveolar septa and fibrosis with fibroblastic foci. What is the most likely diagnosis for this patient?
38. A 34-year-old man presents with a cough of abrupt onset, fever and chest pain. He has no significant medical history. He is admitted to the intensive care unit, where his respiratory distress worsens to the point that he requires intubation. The patient’s chest radiograph shows diffuse, patchy ground-glass opacities and intralobular septal thickening. Bronchoscopy with bronchoalveolar lavage (BAL) show copious amounts of grossly turbid exudates in the airways with material that tests positive with periodic acid–Schiff (PAS) reagent on pathological examination. What is the most likely diagnosis for this patient?
39. A 32-year-old woman presents with dyspnoea, non-productive cough and a previous history of left-sided spontaneous pneumothorax. Bronchoscopic biopsy revealed proliferation of atypical pulmonary interstitial smooth muscle cells. What is the diagnosis for this patient?
Answers
Basic Science
1. Answer B
The majority of the carbon dioxide in blood is carried as bicarbonate ions. The solubility of carbon dioxide in blood is about 20 times greater than that of oxygen. It diffuses into the red blood cell and is rapidly hydrated to carbonic acid (H2CO3) by intracellular carbonic anhydrase. The carbonic acid then dissociates into the hydrogen ion and bicarbonate that enters the plasma.
Some of the carbon dioxide in the red blood cell reacts with haemoglobin to form carbamino compounds. This binding stabilises the deoxy form of haemoglobin, leading to a decrease in its affinity for oxygen and a shift of the oxygen dissociation curve to the right.
Seventy to 80% of carbon dioxide in the blood is carried as bicarbonate ion, while 5–10% is carried as carbamino compounds bound to haemoglobin. Another 5–10% of the carbon dioxide circulates dissolved in the plasma.
The majority of the carbon dioxide in blood is carried as bicarbonate ions. The solubility of carbon dioxide in blood is about 20 times greater than that of oxygen. It diffuses into the red blood cell and is rapidly hydrated to carbonic acid (H2CO3) by intracellular carbonic anhydrase. The carbonic acid then dissociates into the hydrogen ion and bicarbonate that enters the plasma.
Some of the carbon dioxide in the red blood cell reacts with haemoglobin to form carbamino compounds. This binding stabilises the deoxy form of haemoglobin, leading to a decrease in its affinity for oxygen and a shift of the oxygen dissociation curve to the right.
Seventy to 80% of carbon dioxide in the blood is carried as bicarbonate ion, while 5–10% is carried as carbamino compounds bound to haemoglobin. Another 5–10% of the carbon dioxide circulates dissolved in the plasma.
2. Answer C
The diaphragm is innervated by the phrenic nerves that arise from the nerve roots at C3–C5. Normal diaphragmatic contraction leads to an outward motion of the abdomen, but in diaphragmatic paralysis there is a paradoxical inward motion of the abdomen during inspiration (abdominal paradox). The accessory inspiratory muscles contract, lifting the rib cage and lowering the intrathoracic pressure and causing the flaccid diaphragm to move in a cephalad direction and the anterior abdominal wall to move inward. Damage to the phrenic nerve may occur in up to 2% of patients undergoing cardiothoracic surgery and is one of the commonest causes of diaphragmatic paralysis (McCool and Tzelepis, 2012).
Diaphragmatic dysfunction is an underdiagnosed cause of breathlessness and should be considered in the differential diagnosis of unexplained dyspnoea. In bilateral diaphragmatic paralysis, there is usually moderate-to-severe restriction in total lung capacity. In both unilateral and bilateral diaphragmatic paralysis, the restrictive dysfunction becomes more severe when the patient is lying down. A decrease in vital capacity of 30–50% when the patient is supine supports the diagnosis of bilateral diaphragmatic paralysis.
Sleep-disordered breathing is common among patients with diaphragmatic dysfunction, since reduced activity of accessory inspiratory muscles during rapid eye movement (REM) sleep can lead to hypoventilation. Non-invasive positive-pressure ventilation can improve symptoms.
The diaphragm is innervated by the phrenic nerves that arise from the nerve roots at C3–C5. Normal diaphragmatic contraction leads to an outward motion of the abdomen, but in diaphragmatic paralysis there is a paradoxical inward motion of the abdomen during inspiration (abdominal paradox). The accessory inspiratory muscles contract, lifting the rib cage and lowering the intrathoracic pressure and causing the flaccid diaphragm to move in a cephalad direction and the anterior abdominal wall to move inward. Damage to the phrenic nerve may occur in up to 2% of patients undergoing cardiothoracic surgery and is one of the commonest causes of diaphragmatic paralysis (McCool and Tzelepis, 2012).
Diaphragmatic dysfunction is an underdiagnosed cause of breathlessness and should be considered in the differential diagnosis of unexplained dyspnoea. In bilateral diaphragmatic paralysis, there is usually moderate-to-severe restriction in total lung capacity. In both unilateral and bilateral diaphragmatic paralysis, the restrictive dysfunction becomes more severe when the patient is lying down. A decrease in vital capacity of 30–50% when the patient is supine supports the diagnosis of bilateral diaphragmatic paralysis.
Sleep-disordered breathing is common among patients with diaphragmatic dysfunction, since reduced activity of accessory inspiratory muscles during rapid eye movement (REM) sleep can lead to hypoventilation. Non-invasive positive-pressure ventilation can improve symptoms.
McCool, F.D. and Tzelepis, G.E. (2012). Dysfunction of the diaphragm. N Engl J Med 366, 932–942.
3. Answer B
Carbon dioxide, acidosis and 2, 3-bisphosphoglycerate(2, 3-BPG) decrease the oxygen affinity of haemoglobin, which manifests as the oxygen dissociation curve shifting to the right.
Haemoglobin consists of four globin chains, each of which is linked to a haem molecule. Haem is a complex of protoporphyrin IX and the ferrous iron which binds oxygen. While binding of the first oxygen molecule to the first haem is difficult, subsequent binding to the remaining haems in the haemoglobin becomes progressively easier. The net effect is that the affinity of haemoglobin for the fourth oxygen to be bound is approximately 300 times greater than its affinity for the first oxygen to be bound. This positive cooperative binding leads to the sigmoidal shape of the oxygen-binding curve of haemoglobin.
The oxygen dissociation curve is a graph that shows the percentage saturation of haemoglobin (y axis) at various partial pressures of oxygen (x axis). In the lungs with higher partial pressures of oxygen, haemoglobin binds to oxygen to form oxyhaemoglobin. As the red blood cells travel to tissues with reduced oxygen tension, oxyhaemoglobin releases oxygen to form deoxyhaemoglobin.
Carbon dioxide and acidosis stabilise the deoxyhaemoglobin form preferentially and consequently haemoglobin releases its oxygen, a desired effect in the peripheral tissues. This effect is known as the Bohr effect.
2, 3-BPG, which is an intermediate in the glycolytic pathway, also stabilises the deoxyhaemoglobin form and thus shifts the oxygen dissociation curve to the right. The concentration of 2, 3-BPG is raised in the red blood cells in response to chronic hypoxia, such as is seen in COPD or at high altitude.
The adult haemoglobin consists of two α- and two β-globin chains. 2, 3-BPG binds to a pocket in the centre of the deoxyhaemoglobin tetramer, formed by the two β-chains.
Carbon monoxide (CO) binds to haemoglobin with an avidity that is 220 times greater than oxygen. Binding of CO to one or more of the four binding sites of haem causes the remaining haem sites to bind oxygen with increased affinity. This leads to oxygen being effectively trapped within the haemoglobin and hence the oxygen dissociation curve shifts to the left.
Carbon dioxide, acidosis and 2, 3-bisphosphoglycerate(2, 3-BPG) decrease the oxygen affinity of haemoglobin, which manifests as the oxygen dissociation curve shifting to the right.
Haemoglobin consists of four globin chains, each of which is linked to a haem molecule. Haem is a complex of protoporphyrin IX and the ferrous iron which binds oxygen. While binding of the first oxygen molecule to the first haem is difficult, subsequent binding to the remaining haems in the haemoglobin becomes progressively easier. The net effect is that the affinity of haemoglobin for the fourth oxygen to be bound is approximately 300 times greater than its affinity for the first oxygen to be bound. This positive cooperative binding leads to the sigmoidal shape of the oxygen-binding curve of haemoglobin.
The oxygen dissociation curve is a graph that shows the percentage saturation of haemoglobin (y axis) at various partial pressures of oxygen (x axis). In the lungs with higher partial pressures of oxygen, haemoglobin binds to oxygen to form oxyhaemoglobin. As the red blood cells travel to tissues with reduced oxygen tension, oxyhaemoglobin releases oxygen to form deoxyhaemoglobin.
Carbon dioxide and acidosis stabilise the deoxyhaemoglobin form preferentially and consequently haemoglobin releases its oxygen, a desired effect in the peripheral tissues. This effect is known as the Bohr effect.
2, 3-BPG, which is an intermediate in the glycolytic pathway, also stabilises the deoxyhaemoglobin form and thus shifts the oxygen dissociation curve to the right. The concentration of 2, 3-BPG is raised in the red blood cells in response to chronic hypoxia, such as is seen in COPD or at high altitude.
The adult haemoglobin consists of two α- and two β-globin chains. 2, 3-BPG binds to a pocket in the centre of the deoxyhaemoglobin tetramer, formed by the two β-chains.
Carbon monoxide (CO) binds to haemoglobin with an avidity that is 220 times greater than oxygen. Binding of CO to one or more of the four binding sites of haem causes the remaining haem sites to bind oxygen with increased affinity. This leads to oxygen being effectively trapped within the haemoglobin and hence the oxygen dissociation curve shifts to the left.
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