CRL Quiz 2 2004

1

Which one or more of the following statements regarding pneumonia is / are correct?


  The work of breathing is increased because pneumonia is an inflammatory disorder causing obstruction of the large airways.

  Gas exchange is abnormal because of ventilation / perfusion mismatch and sometimes shunt.

  The common causes of pneumonia in previously well adults include bacteria, viruses, fungi and worms.

  Severe pneumonia can result in an acidosis due to respiratory and metabolic factors. Answer 1 if only A, B and C are correct


A Incorrect. Pneumonia involves the terminal lung units (ie small airways, alveolar spaces +/- interstitial spaces)
B Correct. There may also be diffusion impairment, but this is less of a problem at rest.
C Incorrect. Strepococcus pneumoniae and (in younger adults) Mycoplasma pneumoniae and Chlamydia pneumoniae are the common causes of community ñ acquired pneumonia in previously well adults (Legionella can be important in outbreaks). Viral pneumonia is rare (except in influenza or SARS epidemics). Fungal, protozoal and worm lung infections are very rare in the immunocompetent.
D Correct. Poor tissue oxygenation due to a very low PaO2 can cause a metabolic acidosis and an elevated PaCO2 due to severe pneumonia will cause a respiratory acidosis.

2

Which of the following statements is/are correct?


  Mucus protects the underlying epithelium from inhaled oxidants.

  Alveolar macrophages scavenge inhaled particles of small size that evade protective mechanisms in the upper respiratory tract.

  Surfactant has a role in protecting the alveolar unit from fluid accumulation.

  Mucus is primarily removed from the airways by cough. Answer 1 if only A, B and C are correct


A Correct. Mucoproteins and glutathione present in the mucus detoxify inhaled oxidants, but such defenses may become depleted upon inhalation of high concentrations of oxidants.
B Correct. The upper respiratory tract functions to trap larger inhaled particles (>20 µm), whereas smaller particles settle by diffusion in the alveolar region where they may be cleared by macrophage phagocytosis.
C Correct. Surfactant lowers the surface tension of the airway. In its absence there is a tendency for fluid to be drawn into the alveolus due to the attractive forces between water molecules that are normally reduced by the presence of surfactant.
D Incorrect. Although cough may be used to clear mucus and its impairment may lead to mucus accumulation, the normal means of mucus clearance is via the action of the mucociliary escalator which rapidly beats mucus towards the glottis where it is either swallowed or expectorated.

3

Activation of the transcription factors c-maf, STA-6 and GATA-3 would most likely directly result in the transcription of which one or more of the following factors?


  Interleukin 8 (IL-8)

  Interferon g (IFNg)

  Interleukin 18 (IL-18)

  Interleukin 4 (IL-4) Answer 1 if only A, B and C are correct


These transcription factors control TH2 "allergic" cytokine genes, especially IL-4. IL-8 is a chemokine whereas IL-18 and IFNg are TH1 cytokines controlled by transcription factors such as T-bet.

4

In the pathogenesis of allergic asthma interleukin 12 (IL-12) /interleukin 18 (IL-18) and interferon g (IFNg) are thought to cause which one or more of the following actions?


  Suppression of dendritic cell micropinocytosis.

  Augmentation of mucus via IL-13 production.

  Promotion of plasma extravasation.

  Inhibition of TH2 immune responses. Answer 1 if only A, B and C are correct


IL-12/IL18 and IFN g act in concert to oppose TH2 immunity and induce TH1 biased responses. They would suppress IL-13 production, tend to activate macrophages and have little direct effect on microvessels.

5

Salbutamol, a β2-adrenoceptor agonist, causes relaxation of bronchial smooth muscle. In comparison to normal conditions, in the presence of marked bronchoconstriction, the response to salbutamol would demonstrate which one or more of the following effects?


  Increased potency, with decreased efficacy of salbutamol.

  Enhanced cAMP production in response to salbutamol.

  A greater decrease in intracellular calcium concentrations.

  Reduced potency and reduced efficacy of salbutamol. Answer 1 if only A, B and C are correct


High airway smooth muscle tone induces suppression of relaxation of β-adrenoceptor agonists resulting in loss of potency and efficacy.

6

Which of the following statements regarding the valves of the heart is/are correct?


  The purpose of the valves is to ensure unidirectional flow.

  The edges of the atroventricular valve cusps are attached directly to the papillary muscles which prevent eversion during ventricular systole.

  The aortic and pulmonary valves are composed of 3 semilunar cusps attached at their bases to the vessel wall.

  The mitral (bicuspid) valve is closed during ventricular systole preventing regurgitation of blood from the right ventricle to the right atrium. Answer 1 if only A, B and C are correct


Answers A and C are correct.
B The edges of the valve cusps are attached to chordae tendinae which in turn are attached to the papillary muscles.
D The mitral valve guards the passage of blood between the left ventricle and the left atrium.

7

Which one of the following statements regarding respiratory function is not correct?


  Ventilation is greatest in the dependent part of the lungs.

  At functional residual capacity (FRC), outward chest recoil is balanced by inward lung elastic recoil.

  Airway closure at low lung volumes is a determinant of residual volume (RV).

  Closing volume is normally higher than FRC.

  Chest wall stiffness is a determinant of both residual volume (RV) and total lung capacity (TLC).


The closing volume is the volume of the lung at which dependent airways begin to close. In young, normal subjects, the closing volume is about 10% of the vital capacity. It increases steadily with age and becomes equal to FRC at about 65 years of age.

8

Which of the following statements is true about airflow obstruction due to smoking?


  Emphysema is characterised by inflammation of alveolar walls.

  Cigarette smoke has been shown to suppress pulmonary proteases.

  Only smokers with a1 antitrypsin deficiency develop emphysema.

  Airflow obstruction in emphysema results from increased collapsibility of the airways. Answer 1 if only A, B and C are correct


Response A is incorrect as the characteristic feature of emphysema, and in fact its definition, is destruction of alveolar walls. This destruction is due to increased activity of proteases, so response B is incorrect. Smokers with alpha 1 antitrypsin deficiency are more prone to developing emphysema, but the vast majority of smokers with emphysema do not have alpha 1 antitrypsin deficiency, so response C is incorrect.

9

When treating respiratory failure, which of the following is correct?


  The primary aim is to maintain the PaCO2 in the normal range.

  High concentrations of oxygen should not be given to patients with acute asthma attacks as hypercapnia may be made more severe.

  During a severe acute asthma attack, a normal PaCO2 value gives the treating doctor confidence that the treatment is successful.

  In an acute exacerbation of severe COAD with worsening hypercapnia, non-invasive positive pressure ventilation is often a useful treatment option.

  In a patient with pulmonary embolism, a low PaCO2 indicates that the patient is hyperventilating and requires the administration of a respiratory depressant.


When treating respiratory failure, one important variable is the PO2 (or oxygen saturation)which should be kept above 60 mmHg (SpO2 > 90 %) on the flat portion of the oxygen dissociation curve, so that any minor changes in alveolar PO2 do not have major effects on the oxygen content of the blood. The pH is the other important factor, and is more important than the PCO2, because patients with chronic hypercapnia may have a high HCO3 to compensate for the chronic respiratory acidosis. In this situation, if the PCO2 is brought into the normal range, the patient will be left with a metabolic alkalosis, as the HCO3 levels do not change quickly. Thus the goal should be to get the pH normal, so response 1 is incorrect.

Response 2 is incorrect, as the principal of not giving high doses of oxygen immediately during an exacerbation applies to patients with COPD who may have chronic hypercapnia. In this situation, the oxygen may overcome hypoxic pulmonary vasoconstriction in some parts of the lung, leading to a worsening of V/Q mismatch, making the patient more hypoxaemic and hypercapnic. There is also another explanation, that the high flow oxygen will suppress hypoxic drive, and that these patients may not have hypercapnic drive, and so there will be worsening hypoventilation. In acute asthma, these factors do not have a role. It is the hypoxia that kills in acute asthma, so patients must receive adequate oxygen. This is even more important if the patient is getting large doses of beta agonists, as these can cause more pulmonary vasodilatation than bronchial dilatation, worsening V/Q mismatch, and so making the hypoxaemia worse.

Response 3 is not correct. Initially PCO2 falls during an acute asthma attack, and it will rise back into the normal range if the attack is being relieved. But if the attack is not being relieved, and the asthma is getting worse, the patient may develop ventilatory failure and the PCO2 will start to rise, back into the normal range, and then higher into hypercapnia. In a patient with an acute asthma attack, which is not getting better, a rising PCO2, even from low to normal, is an ominous sign that requires urgent intervention.

Response 4 is correct as this treatment approach has been shown to be of benefit in several well conducted clinical studies. It is now standard treatment in this situation.

A patient with acute pulmonary embolism may have increased ventilation due to hypoxaemia. This can lower PCO2 as CO2 moves across the alveolar-capillary membrane more easily than O2. However, the treatment is to give supplemental oxygen to reverse the hypoxaemia. A respiratory depressant will worsen the hypoxaemia and may kill the patient. Response 5 is thus incorrect.

10

Which of the following statements concerning pulmonary hypertension is / are correct?


  Causative mechanisms include pulmonary arteriolar constriction, obliteration or obstruction of the pulmonary capillary bed and increased flow through the pulmonary circulation because of large left to right shunts.

  Pulmonary hypertension can cause dilatation or hypertrophy of the right ventricle.

  Swelling of the ankles can occur with pulmonary hypertension because of increased hydrostatic pressure transmitted to the systemic veins.

  Domicillary, low flow oxygen is prescribed to people with a chronically low PaO2 (< 55-60 mmHg) due to lung disease in order to delay or prevent death from right heart failure. Answer 1 if only A, B and C are correct

11

Which of the following statements regarding the cardiac action potential of a ventricular myocyte is/are correct?


  The rapid upstroke is the result of calcium movement into the cell.

  Repolarisation is the result of potassium movement into the cell.

  The plateau phase is the result of sodium movement into the cell.

  The absolute refractory period is associated with closed sodium channels. Answer 1 if only A, B and C are correct


A Incorrect. The rapid upstroke is due to the opening of Na channels. This allows Na influx and depolarizes the membrane.
B Incorrect. Repolarisation is the result of the opening of slow K channels that allow K efflux, not influx.
C Incorrect. The plateau phase results from the opening of Ca channels which allows Ca influx.
D Correct. Closed Na channels prevent depolarization during the refractory period and, therefore, prevent tetany.

12

Which of the following statements regarding cardiac myocyte contraction is/are correct?


  Contraction is activated by a rise in cell calcium.

  Calcium is stored in the sarcoplasmic reticulum for release during contraction.

  Increased calcium permits the interaction between myosin and actin.

  Drugs such as digoxin will result in a reduction of intracellular calcium. Answer 1 if only A, B and C are correct


A Correct. Contraction is activated by a rise in cell calcium that allows the interaction of actin and myosin.
B Correct. Calcium is stored in the sarcoplasmic reticulum for release during contraction.
C Correct. Increased calcium permits the interaction between myosin and actin
D Incorrect. Digoxin inhibits the NaK-ATPase pump and causes an increase in intracellular [Na], which is exchanged for extra extracellular Ca through the Na-Ca exchanger, resulting in increased intracellular [Ca] and increased contractility.

13

Which one or more of the following statements regarding the regulation of heart rate is/are correct?


  b-adrenoceptor antagonists prevent the effects of activation of cardiac parasympathetic nerves.

  Stimulation of cardiac parasympathetic nerves increases heart rate.

  In a healthy human at rest there is no influence of sympathetic nerves on heart rate.

  Muscarinic receptor antagonists increase resting heart rate. Answer 1 if only A, B and C are correct


A Incorrect. Stimulation of cardiac parasympathetic nerves decreases heart rate due to the release of acetylcholine which activates muscarinic receptors.
B Incorrect. Acetylcholine released from parasympathetic nerves acts on muscarinic receptors to decrease heart rate.
C Incorrect. At rest there is low level of tonic activity of the cardiac sympathetic nerves to increase heart rate.
D Correct. At rest there is significant tonic activity of the cardiac parasympathetic nerves to keep heart rate low. Muscarinic receptor antagonists will prevent that effect and allow heart rate to increase.

14

The prothrombin time (or INR) is typically normal in which one or more of the following patients?


  A patient suffering from von Willebrand disease.

  A patient being treated with Warfarin therapy.

  A patient with Haemophilia A.

  A patient with a deficiency in Vitamin K. Answer 1 if only A, B and C are correct


A Correct. von Willebrand disease is associated with low F VIII that may prolong APTT, but INR or prothrombin time is unaffected.
B Incorrect. Warfarin therapy is reliably monitored by prothrombin time or INR.
C Correct. Again, Haemophilia A is associated with decreased F VIII levels and increased APTT, but normal Prothrombin time or INR.
D Incorrect. Vitamin K is necessary for the appropriate function of factors II, VII, IX, X, and reduced activity of these factors is reflected in increased prothrombin time or INR.

15

Which one or more of the following statements regarding drugs affecting haemostasis is/are correct?


  Warfarin, an oral anticoagulant, inhibits the synthesis of vitamin K dependent clotting factors.

  Aspirin, by inhibiting thromboxane synthesis, inhibits platelet aggregation.

  Heparin binds to, and enhances the activity of, antithrombin III.

  Activation of plasminogen by alteplase will result in the degradation of fibrin. Answer 1 if only A, B and C are correct


A Correct. Warfarin prevents the synthesis of the vitamin K dependent clotting factors and therefore inhibits fibrin formation.
B Correct. Aspirin is a cyclooxygenase inhibitor, which prevents thromboxane synthesis by platelets and therefore inhibits platelet aggregation. It is useful in the treatment and prevention of arterial thrombosis.
C Correct. Heparin by enhancing the activity of antithrombin III results in the breakdown of active clotting factors.
D Correct. Alteplase by promoting fibrin degradation is used to breakdown thrombi and emboli for example in the treatment of coronary thrombosis (acute myocardial infarction) and pulmonary embolism.