The Respiratory System at a Glance, 3rd Edition



The Respiratory System at a Glance





The Respiratory System at a Glance Jeremy P.T. Ward 3K' +HDG RI 'HSDUWPHQW RI 3K\VLRORJ\ DQG 3URIHVVRU RI 5HVSLUDWRU\ &HOO 3K\VLRORJ\ 'LYLVLRQ RI $VWKPD $OOHUJ\ DQG /XQJ %LRORJ\ .LQJ¶V &ROOHJH /RQGRQ /RQGRQ 8.

Jane Ward 0%&K% 3K' 6HQLRU /HFWXUHU 'HSDUWPHQW RI 3K\VLRORJ\ .LQJ¶V &ROOHJH /RQGRQ /RQGRQ 8.

Richard M. Leach 0' )5&3 &RQVXOWDQW 3K\VLFLDQ DQG +RQRUDU\ 6HQLRU /HFWXUHU *X\¶V DQG 6W 7KRPDV¶ +RVSLWDO 7UXVW DQG .LQJ¶V &ROOHJH /RQGRQ 6FKRRO RI 0HGLFLQH 6W 7KRPDV¶ +RVSLWDO /RQGRQ 8.

With contributions from

Charles M. Wiener 0' 3URIHVVRU RI 0HGLFLQH DQG 3K\VLRORJ\ 'HSDUWPHQW RI 0HGLFLQH -RKQV +RSNLQV 6FKRRO RI 0HGLFLQH %DOWLPRUH 0' 86$

Third edition

A John Wiley & Sons, Ltd., Publication



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Units and symbols

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List of abbreviations A–a gradient AAT AHI AIDS AIP ALI ANA ANCA AP ARDS ATPS ATS BAL BALT BCG BiPAP BP BTPS BTS CA cAMP CAP CCF CF CFA CFTR CL CMV CMV CNS COAD COLD COPD COX CPAP CREST CSA CSF CT CTPA CWP CXR DIP D L CO DLg D L O2 DRG 8

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List of abbreviations

DVT EBV ECG ECMO ECP EEG EGF ELISA EMG EOG ERV ESR FDG FDG PET FEF25−75 FER FEV1 FEV1 /FVC FGF FRC FVC GBM GM-CSF GU HAART HAP HCAP HIV HR HRCT ICU IFN-γ Ig IL ILD INPV IPF IPPV IRV IVC JVP K CO KS LA LDH LG LIP LMWH LT LV MBP

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List of abbreviations

9

r

1

Structure of the respiratory system: lungs, airways and dead space

(a) Lung lobes

RU

(b) The airways

LU RM

Nasal cavity

LL

RL Right lateral aspect

Pharynx

Left lateral aspect

Epiglottis Larynx Cricoid

C6

C7 T1

Sternal angle (angle of Louis)

RU LU

T2

Sternum

LL

Anterior aspect

Carina

T4

RM RL

Trachea (generation 0)

T3

Manubrium

T5 T6

Body

T7

R and L main bronchi (generation 1) Bronchi (generations 2–11) Bronchioles (generations 12–16)

T8 T9

LU

LL

RU

RL

RU RM RL LU LL

= Right upper = Right middle = Right lower = Left upper = Left lower

Respiratory bronchioles (generations 17–19)

Xiphoid process Diaphragm

T10

Alveolar ducts and sacs

T11

(generations 20–23)

T12

Posterior aspect

Anatomical dead space, Volume = VD

(c) Bohr equation for measuring dead space

Anatomical dead space, Volume = VD

End-tidal = alveolar gas

∴ Quantity of CO2 in mixed expired air = quantity of CO2 from alveolar region

Mixed expired gas: Volume = VT ; Mixed expired CO2 fraction = FECO2

Respiratory zone: Alveolar CO2 fraction = FACO2

End of inspiration

10

CO2-free gas

CO2-containing gas

In an expired breath none of the CO2 expired came from the dead space region

VT x FECO2 = (VT –VD) x FACO2 ∴ VD = VT (FACO2– FECO2)/ FACO2 End of expiration

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Structure of the respiratory system: lungs, airways and dead space

Structure and function

11

r

2

The thoracic cage and respiratory muscles

(a) The sternum and ribs and their relationship to the lungs and pleural cavities

(b) Inferior aspect of a rib Head

T1

Neck

Tubercle

Clavicle 1

Manubrium 2

Horizontal fissure

Body

Sternum

Articular facets of the head

Angle

Xiphoid process

3

Articular facet of the tubercle

4

Costal groove

Cardiac notch Oblique fissure

5

Oblique fissure

6

Shaft

7 8 9

Costodiaphragmatic recess

10

Lung lobes Pleural

Costal cartilage joins here

(d) Inferior aspect of the diaphragm

(c) An intercostal space

Xiphisternum

Intercostal: Vein Artery Nerve Innermost intercostal muscle Internal intercostal muscle External intercostal muscle

Costal part

Sternal part

Inferior vena cava

Left phrenic nerve Central tendon of diaphragm

Right phrenic nerve

Oesophagus Median arcuate ligament

Vagi Costal part

Aorta

L1

Medial arcuate ligament Lateral arcuate ligament

L2 12th rib To avoid the neurovascular bundle, needles being passed through the intercostal space (for example to drain a pleural effusion) should pass close to the top of the rib

12

L3

Right crus L4

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Quadratus lumborum Left crus Psoas major

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The thoracic cage and respiratory muscles

Structure and function

13

r

3

Pressures and volumes during normal breathing

(a) Functional residual capacity

‘Negative’ intrapleural pressure

Outward recoil of chest wall

(c) Pressure gradient distending the lung (transmural = alveolar – intrapleural)

Inward recoil of lungs

Pressure gradient driving air along airways (mouth – alveolar)

Mouth

(i) Intrapleural

Open thorax: Air

Air

Alveolar pressure ‘Zero’ pressure

Lungs collapse

Chest wall expands

(d) 0.5

(ii) Volume above FRC (L)

(b)

0 Intrapleural – 0.5 pressure relative to atmospheric (kPa) – 0.75 Intrapleural pressure, – 0.5 kPa

Oesophageal pressure, – 0.5 kPa

Alveolar pressure, 0 kPa

0.1

Alveolar pressure (kPa)

0 – 0.1 0.5

Airflow (L/sec)

Heart

0 – 0.5 Inspiration Expiration Inspiration Expiration

(e) IRV

TLC

IC

VC VT

FRC

ERV RV

(ii) Table 1 (i)

14

Tidal volume (VT) (at rest) Vital capacity (VC) Inspiratory reserve volume (IRV) Expiratory reserve volume (ERV)

500 mL 5 500 mL 3 300 mL 1 700 mL

Inspiratory capacity (IC) Total lung capacity (TLC) Functional residual capacity (FRC) Residual volume (RV)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

0

3800 mL 7300 mL 3500 mL 1 800 mL

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Pressures and volumes during normal breathing

Structure and function

15

r

4

Gas laws Barometric pressure with increasing altitude

(a) Altitude, barometric pressure, O2 fraction and PO2

PB = 250 mmHg (33.3 kPa) 1⁄3 sea level value FO2 dry air = 0.209 (20.9% O2) ∴ PO2 dry air = 0.209 x 250 = 52 mmHg (7 kPa)

Sea level (0m, 0ft)

700

Barometric pressure (PB, mmHG)

Mt Everest summit 8850 m (29 035 ft)

PB = 250 mmHg 33.3 kPa

800

600

Mexico City (2240 m, 7349 ft)

5486 m (18 000 ft) 1⁄

PB = 380 mmHg (50.6 kPa) 2 sea level value FO2 dry air = 0.209 (20.9% O2) PO2 dry air = 0.209 x 380 = 79 mmHg (10.6 kPa)

PB = 380 mmHg 50.6 kPa

500

Lhasa, Tibet (3600 m, 11810 ft) La Rinconda, Peru* (5100 m, 16 732 ft)

400

300

Mt Everest summit (8850 m, 29 035 ft)

200

Cruising altitude typical passenger jet (11 278 m, 37 000 ft)

Sea level 0 m (0 ft) PB = 760 mmHg (101.3 kPa) FO2 dry air = 0.209 (20.9% O2) PO2 dry air = 0.209 x 760 = 159 mmHg (21 kPa)

PB = 760 mmHg 101.3 kPa

100 0 0

10000

20000

30000

40 000

50 000

60 000

Altitude (feet) 0

2000

4000

6000

8000 10 000 12 000 13 000 14 000 16000 18000

Altitude (metres) *Highest permanently inhabited town PB = barometric pressure; FO2 = O2 fraction

(b) Correction factors for gas volumes Volume (BTPS) = volume (ATPS) Volume (STPD) = volume (ATPS)

273 + 37

PB – PH2O

273 + tOC

PB – 6.3*

273

PB – PH2O

273 + tOC

101*

*47 if PB and PH2O are in mmHg *760 if PB and PH2O are in mmHg

(c) Partial pressure of a gas in a liquid Liquid X containing dissolved gas, g, is exposed to a gas phase Gas phase (Pg)

P1

P2

P3

containing g at three different partial pressures, P1, P2, P3. Only when the Pg = P2 does the number of gas molecules leaving the

Liquid phase liquid X (P Xg)

liquid per minute ( ) equal the number entering the liquid ( ) – i.e. the liquid and gas phases are in equilibrium. ∴ Partial pressure of gas, g, in liquid X (P Xg) = P2 Liquid Y also contains gas, g, and is also in equilibrium with the

Gas phase (Pg) Liquid phase liquid Y (P Yg)

16

gas phase when Pg = P2 P1

P2

P3

∴ Partial pressure of gas, g, in liquid Y (P Yg) = P2 However, the solubility of gas, g, in liquid Y is less than in liquid X, so at the same partial pressure, liquid Y contains a lower concentration of g. Note: In the bottom left flask, gas moves against its concentration gradient.

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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5

Diffusion

(b) Transfer of gases across alveolar–capillary membrane

(a) The alveolar–capillary membrane

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Capillary partial pressure

Alveolus

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mmHg kPa 200 25 20

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The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Diffusion

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6

Lung mechanics: elastic forces

(b) Dynamic pressure–volume loop

(a) Static pressure–volume loop

If intrapleural pressure and volume are recorded continuously (lower panel), a pressure–volume loop (upper panel) can be constructed from pairs of simultaneous measurements of volume, e.g. (b) with pressure (b'). Alternatively the pressure and volume signals can be fed into an X-Y plotter. ΔV

50 FRC

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0 0

20 cmH2O 2 kPa

1

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(c) Surface tension Laplace’s equation R

Volume above FRC (litres)

Volume % TLC

100

e,e' f,f'

0.4

d,d' g,g'

0.3

0.2

c,c'

h,h' 0.1

i,i'

0 –0.5

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–0.7

–0.8

–0.9

–1.0

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P= 2T R T= Surface tension

Inspiration Expiration Inspiration Expiration (d) Effect of surface area

Pressure above ambient = P

R2 P1

P2

P1 > P 2

20

R1 Water molecule Surfactant molecule ∴ When tap is opened the small bubble empties into the large

R2 < R1 but T2 < T1 because surface concentration of surfactant is higher when the alveolus is small The fall in R is more than offset by the fall in T, ∴ since P = 2T , P does not rise, but falls as the alveolus shrinks R

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Lung mechanics: elastic forces

Structure and function

21

r

7

Lung mechanics: airway resistance (c) The effect of effort on inspiratory and expiratory airflow Effort dependent 6 A 600 Effort 5 independent

(a) Laminar and turbulent flow

4

Laminar flow

3

Airway smooth muscle

β-Adrenergic agonists (e.g. adrenaline and saltbutamol)

NANC nerves (inhibitory)

CO2

β2-Receptor

NO and VIP

Bronchodilation

(b) Main factors influencing bronchomotor tone

Expiration

Turbulent flow

0

1

1 2 3 4 5 6

300

TLC 600

Synapse

NANC nerves (excitatory)

Pulmonary stretch receptors (inhibit)

Airway irritant receptors (activate)

600

NO = Nitric oxide VIP = Vasoactive intestinal peptide SP = Substance P

ACh = Acetylcholine M3 = Muscarinic type 3 receptor

(d) Dynamic compression of airways

Expiration

Mast cells, eosinophil (Chapter 23)

= Nerve ending

(e) Maximum flow–volume loops

300

Vagal afferents = Receptor

RV

0

Inspiration

Brainstem (Chapter 12)

Histamine, Prostagladins Leukotrienes etc

Volume (L)

= Flow–volume curve for maximum effort from partly filled lungs A = Peak expiratory flow rate with lungs filled to total lung capacity B = Peak expiratory flow rate for partly filled lungs filled (RV + 3 L) TLC = Total lung capacity, RV = Residual volume

Airflow (L/min)

Vagal efferents

SP and neurokinins

Bronchoconstriction

ACh via M3 receptors

B 2

Inspiration

Airflow (L/min)

300

300

Intrathoracic airway Beginning of inspiration

Alveolus

6

0

0

0

Intrapleural space

During forced expiration

8.7

8 6

–0.5

4

0

+8.0 Numbers are pressures in kPa (1 kPa = 7.5 mmHg)

22

600

4 2 Lung volume (L)

0

Normal curve Obstructive airway disease of smaller airways. Note: • concave appearance of forced expiratory curve • forced inspiratory flow affected less than forced expiratory flow Upper airway obstruction (e.g. tracheal stenosis). Note: • flat topped flow–volume curve • forced inspiratory flow affected as much as expiratory flow Restrictive lung disease. Low peak flow rates are related to low volume. (Note: this figure is drawn to show the relationship between these traces by using absolute lung volume which cannot actually be obtained from a flow–volume loop alone).

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Lung mechanics: airway resistance

Structure and function

23

r

8

Carriage of oxygen

(a) Haemoglobin structure β

O2

O2

Haemoglobin is composed of four subunits, each containing a protein chain (globin) and a haem group. Normal adult haemoglobin, HbA, contains two identical α-chains composed of 141 amino acids and two β-chains composed of 146 amino acids. The haem group ( ) is attached to each chain at a histidine residue, and each has an iron atom in the ferrous form, which binds to an oxygen molecule. The haem groups lie in crevices in the crumpled ball of globin chains. The exact 3D (or quaternary) structure of haemoglobin can change and alter the accessibility of the oxygen-binding site. Each molecule of haemoglobin can bind up to four molecules of oxygen in a series of reactions which can be summarized as: Hb4 + 4O2 Hb4(O2)4

α O2

O2

75

150

50

25

a

pH, PCO2, temperature 2,3-DPG

200

Oxygen content (mL/L)

Oxygen saturation (%)

(b) The oxygen–haemoglobin 100 dissociation curve, haemoglobin concentration (150 g/L)

pH, PCO2, temperature 2,3-DPG

v

a = Normal arterial blood PO2 = 13.3 kPa (100 mmHg) O2 content = 200 mL/L O2 saturation = 97%

100

v = Resting mixed venous PO2 = 5.3 kPa (40 mmHg) O2 content = 150 mL/L O2 saturation = 75%

50 Dissolved oxygen

0

0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 kPa PO2 0

(c) Anaemia and carbon monoxide poisoning

50

100

150 mmHg Note: For simplicity the Bohr shift is ignored

200

Oxygen content (mL/L)

Tissues remove 50 m L/L 150

100 Tissues remove 50 m L/L 50

0

0 0

24

Hb = 150 g/L Hb = 75 g/L Hb = 150 g/L COHb = 50%

C 2 20

B 4

A 6 40

8 PO2 60

10 80

12

14 100

16 kPa 120 mmHg

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Carriage of oxygen

Structure and function

25

r

9

Carriage of carbon dioxide

550 Normal mixed venous V

Arterial

98% O2 X saturation

Haldane effect

500

480 mL CO2/L

CO2 content (mL/L)

(c) How CO2 is carried in arterial and venous blood

75% O2 saturation

A Normal arterial

Mixed venous

5%

Carbamino

30%

87%

HCO3–

60%

8%

Dissolved

10%

450 5.5

6.0

6.6

55 (mmHg)

50

45

40

(kPa)

7.0

The red line (A-X) shows what the relationship between blood PCO2 and CO2 content would be if Hb remained 98% saturated. However, as mixed venous blood HB is only 75% saturated, more CO2 can be carried for any given PCO2, as shown by the dashed line A-V (the Haldane effect, see box and text).

(b) CO2 uptake and O2 delivery in the tissues – role of red cells Cl– HCO3–

Red cell Cl– CO2

CO2 + H2O

CA

H2CO3

The basis of the Haldane effect

Chloride shift

HCO3– + H+

When haemoglobin is fully oxygenated, each of the four Hb subunits is bound to one O2: Hb4(O2)4 As O2 is released, i.e. Hb4(O2)4

CO2 + H•Hb Hb4(O2)4

Hb4(O2)3

O2 CA = carbonic anhydrase Hb = haemoglobin subunit H•Hb = reduced haemoglobin

26

H 2O

H2O

Hb•COOH

Carbamino formation

Hb4(O2)3

Hb4(O2)2

Hb4(O2)

the ability of each reduced (deoxygenated) Hb subunit (H•Hb) to buffer H+ and form Hb•COOH (carbaminohaemoglobin) is greatly increased This enhances carriage of CO2 by blood by: (a) buffering red cell acidity and therefore facilitating formation of HCO3– (b) formation of Hb•COOH When blood is reoxygenated in the lungs, the reverse occurs, facilitating removal of CO2 in the breath

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

520 mL CO2/L

(a) CO2 dissociation curve

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Carriage of carbon dioxide

Structure and function

27

r

10

Control of acid–base balance

K=

HCO3 + H+

H2CO3 [H+]

[HCO3] x [H2CO3]

log K = log [H+] + log

–log

[H+]

Polycythaemia ( red cells)

K = dissociation constant; KA = corrected for [CO2] instead of [H2CO3]

[HCO3] [H2CO3]

[HCO3] = –log K + log [H2CO3]

Solubility (s) = 0.23 mmol / L / kPa 0.03 mmol / L / mmHg

[HCO3] pH = pK + log [H2CO3]

30

A 20

C Whole blood buffer line

[HCO3] PCO2 x s

10 7.1

(c) Compensation and base excess PCO2 60 mmHg (7.8 kPa)

100

i os

s

20

o ab et

li

G R comespirat pens ory atio n

10 7.1

7.2

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7.4 pH

7.5

F PCO2 20 mmHg (2.6 kPa)

Res p alkairatory losis

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60

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Acute respiratory acidosis

7.4 pH

l na Re

7.5

e

Normal range

7.3 C

E

7.7

Metabolic acidosis

7.0

80

40

mp co

7.6

6.9

ic

Resp B acidiratory osis A

M

28

alk M alo et sis abo l

co R mp en en al sa tio n

Base excess

Plasma [HCO3 ] (mmol/L)

D

cid ca

7.3

[H+] (nmol/L) pH 120

24

7.2

(d) Flenley acid–base nomogram PCO2 40 mmHg (5.3 kPa)

40

30

PCO2 20 mmHg (2.6 kPa)

Plasma buffer line

B

But: [H2CO3] [CO2] (pKA = 6.1) and: [CO2] = PCO2 x s (solubility) pH = 6.1 + log

PCO2 40 mmHg (5.3 kPa)

40

(from law of mass action)

Plasma [HCO3 ] (mmol/L)

CO2 + H2O

PCO2 60 mmHg (7.8 kPa)

(b) Davenport diagram

(a) Relationship between PCO2, HCO3 and pH, and the Henderson–Hasselbalch equation

io n at ns

20

7.4 Respirator y alkalosis

7.5 7.6

Metabolic alkalosis 0

7.6

7.7

Chronic respiratory acidosis

0

10

20

2

30

4

40 50 PaCO2 (mmHg) 6 PaCO2 (kPa)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

60

8

70

80

10

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Control of acid–base balance

Structure and function

29

r

11

Control of breathing I: chemical mechanisms

Effect of CO2 , pH and O2 on ventilation: Normal pH

(a)

60

50

40 30 20

Metabolic alkalosis

10

Low PO2 ~5 kPa

40 30 20

High PO2 ~60 kPa

10

4

5 6 7 8 Alveolar PCO2 (kPa)

(d) Central chemoreceptors

9

40 High PCO2 6 kPa

30 20 10 0

0

0

Normal PCO2 5 kPa

50 Ventilation (L/min)

Metabolic acidosis Ventilation (L/min)

Ventilation (L/min)

(c)

60

60 50

Normal PO2 ~13 kPa

(b)

4

5 6 7 8 Alveolar PCO2 (kPa)

Central chemoreceptors

4

9

8 12 PO2 (kPa)

(e)

Glial cells CSF

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Cranial nerves V VII VIII

Capillary Neurone Blood–brain barrier

CSF

IX Medulla oblongata

16

Chemoreceptor

H+, HCO3

HCO3

X XI

CO2

H+

O2 Carbonic anhydrase

CO2 + H2O

H2CO3

Blood

H+ + HCO3–

[H+] at chemoreceptor PCO2 / [HCO3– ] PCO2 from blood, and [HCO3– ] from CSF

(f) Peripheral chemoreceptors Vagus nerve

Aortic bodies

Carotid sinus nerve Bifurcation

Aorta

Carotid sinus

Heart

30

Groups of cells surrounded by fenestrated sinusoidal capillaries

(g)

Common carotid artery

Glossopharyngeal nerve

Sheath (type II) cells

Glomus (type I) cells

Carotid body (not part of sinus)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Dense granules containing neurotransmitters Carotid sinus nerve fibres

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Control of breathing I: chemical mechanisms

Structure and function

31

r

12

Control of breathing II: neural mechanisms

Cortex

(g) Voluntary control of breathing via pyramidal tracts

Hypothalamus Emotion Temperature

Pons

Cut here No effect on breathing but loss of higher control

(a) Pneumotaxic centre Nucleus parabrachialis Kölliker-Fuse nucleus

Cut here Gasping (b) Dorsal respiratory group Nucleus tractus solitarius

Medulla

(f) Input from central and peripheral chemoreeceptors

(c) Ventral respiratory group Bötzinger complex Nucleus ambiguus and retro ambiguus

Cut here Abolition of breathing – apnoea

Respiratory muscles

Damage, inhaled irritants

(d) Descending respiratory motor neurones to diaphragm, intercostals and ancilliary respiratory muscles

Lung volume and muscle load

Spinal cord

(e) Lung receptors Stretch Proprioceptors Irritant Juxtapulmonary

32

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Control of breathing II: neural mechanisms

Structure and function

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Pulmonary circulation and anatomical right-to-left shunts

(b) The initial effects of a 20% right-to-left shunt on arterial O2 and C02 contents and partial pressures

(a) Pulmonary and systemic circulation and normal anatomical right-to-left shunts

Bronchial artery Pulmonary capillary pressure: Arterial end Venous end 14 mmHg 8 mmHg

O2 content = 200mL/L CO2 content = 480mL/L

80%

Alveoli *O2 content = 150 mL/L *CO2 content = 520 mL/L

Pulmonary artery pressure: 24/9, mean 15 mmHg LA

RA

Arterial O2 content = Arterial CO2 content =

Aorta RV

80 20 x 200 + x 15 = 190mL/L 100 100 80 20 x 480 + x 520 = 488m L/L 100 100

LV VCM

Systemic capillary pressure: Venous end Arterial end 10 mmHg 30 mmHg

Aortic pressure: 120/70, mean 90 mmHg

*Note: The mixed venous contents used are normal values. In fact, the abnormal arterial contents would lead to abnormal mixed venous contents so this simple analysis underestimates the effects on arterial contents.

The PO2 and PCO2 that result from these O2 and CO2 contents can be found from the O2 and CO2 dissociation curves:

Tissue 700

O2 and CO2 dissociation curves

VCM = venae cordis minimae (thebesian veins)

Normal O2 and CO2 pressures and contents O2 and CO2 pressures and contents following mixing 20% mixed venous blood with 80% blood undergoing normal gas exchange

O2 and CO2 content (mL/L)

600 CO2 500 400 300 O2

200 100 0 –1

34

1

3

5

7 9 PO2/PCO2 (kPa)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

11

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Pulmonary circulation and anatomical right-to-left shunts

Structure and function

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Ventilation–perfusion mismatching

(a) Different types of VA/Q r egions

Q = Normal VA/Q = Normal (close to 1)

Dead space

Dead-space effect

Shunt effect

True/anatomical shunt

VA = Normal

VA = Low

VA = 0

VA = Normal Q=0

Q = Low

VA/Q = ∞

VA/Q = High

Q = Normal

Q = Normal

VA/Q = Low

VA/Q = 0

Ventilation, VA , perfusion, Q (arbitrary units per unit lung volume) and ventilation–perfusion ratio, VA/Q

Normal VA = Normal

(b) Variation of ventilation, VA , perfusion, Q and ventilation–perfusion ratio, VA/Q with vertical height in the upright lung 3

Q

2

VA

1 VA/Q 0

Base

Apex

PO2 and O2 contents of blood from these regions breathing air and oxygen 02 content (mL/L) 200

200 0

0

0

10 20 PO2 kPa

02 content (mL/L) 02 content (mL/L) 02 content (mL/L) 200 200

0

10 20 PO2 kPa

O2 content of blood draining the region breathing air ( Normal Unchanged

No blood draining this region

0

0

10 20 PO2 kPa

VA = 4 Q=1

VA = 5 VA/Q = 0.3 Q = 15

36

0

10 20 PO2 kPa

) and breathing O2-enriched air (

Normal Unchanged

Low Increased

(c) The effect of a mixture of high and low VA/Q regions on arterial blood gases

VA/Q = 4

0

):

Low Unchanged

Alveoli at start and end of breath

Blood vessels at different heights

(d) Alveolar air equation This predicts the PO2 in the functioning or ‘ideal’ alveoli

Small flow with: High PO2 Normal O2 content Low PCO2 Low CO2 content

Peripheral and central chemoreceptors PA O2 =~ PΙO2 – PaCO2 R

Combined to give: Low O2 content High CO2 content Low PO2 Slightly high PCO2

Ventilation R = The respiratory gas exchange ratio = CO2 production O2 consumption

Large flow with: Low PO2 Low O2 content High PCO2 High CO2 content

Final picture: Low O2 content Normal or low CO2 content Low PO2 Normal or low PCO2

(R is usually about 0.8)

PΙO2 = Inspired O2 partial pressure PaCO2 = Arterial CO2 partial pressure (≈ alveolar)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Ventilation–perfusion mismatching

Structure and function

37

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15

Exercise, altitude and diving

(b) Typical alveolar ventilation, PCO2 and PO2 , at altitudes between sea level (0 m) and 6000 m for subjects exposed acutely (red solid line) and chronically (blue solid line) following acclimatization. The dashed line shows the values that would have occurred if alveolar ventilation remained at its sea level value.

Table 1 Typical values in a healthy but sedentary 20-year-old man at rest and in max. exercise Maximal exercise

Heart rate (bpm)

70

200

Stroke volume (mL)

75

90

Cardiac output (mL/min)

5 250

18 000

Arterial–mixed venous O2 content* (mL/mL)

0.048

0.167

O2 consumption (mL/min)

250

3 000

Ventilation (mL/min)

7 500

140 000

Respiratory frequency (breaths/min)

15

56

Tidal volume (mL)

500

2 500

Alveolar ventilation 14 Alveolar ventilation (L/min)

Rest

12 B

10

A

8 6 4 2 0

(*= O2 extraction)

0

1000 2000 3000 4000 5000 6000 Altitude (m)

kPa 6

20 15

kPa mmHg

Rest

140

. V

100

PO2/PCO2

160 140

Anaerobic threshold

120

120 100

PaO2

80

80

10

PvCO2

60

PaCO2

0 pHa

2

0

PvO2

Alveolar PCO2

35

A

30 25

B

20 15 10 5 0 0

1000 2000 3000 4000 5000 6000 Altitude (m)

40

0

kPa 16

pHa

mmHg 120

Alveolar PO2

100

7.2 1 2 3 25 50 75 Oxygen consumption

4 L/min 100 VO2

. (a) Typical changes in ventilation V, arterial PO2 (PaO2), arterial PCO2 (PaCO2), arterial pH (pHa), mixed venous PO2 (PvO2) and mixed venous PCO2 (PvCO2) in a fit young man as oxygen consumption is increased from its resting value of 0.25 L/min to his maximum oxygen consumption of 4 L/min.

Alveolar PCO2

12 0 0

38

3

1

Ventilation (L/min)

20

20 0 7.4

4

60

40

5

Alveolar PCO2

5

mmHg 45 40

80 8

60

B

40

A

4 20 0

0 0

1000 2000 3000 4000 5000 6000

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Altitude (m)

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Structure and function

39

r

16

Development of the respiratory system and birth Week 4

(b)

(a) Branching morphogenesis

Week 5

Week 6

Week 8

4th pharyngeal pouch Mesoderm

Epithelium

– +

+

+

+ –

Signalling factors

Trachea

Laryngotracheal tube

Bronchial buds

Factors released by mesoderm cells cause the epithelium to grow inwards towards them as a bud; inhibitory factors prevent budding either side

Embryonic Secondary oesophagus bronchi Mesoderm

Endoderm/ epithelium Segmental bronchi

4 Ductus arteriosus

(c) Fetal circulation 6

Pulmonary artery

Superior vena cava Ascending aorta

LA 3

Foramen ovale

RA 5

Inferior vena cava Fetal liver

Before birth:

Aorta

LV RV

2

Pulmonary vascular resistance > Systemic vascular resistance Ductus arteriosus OPEN Foramen ovale OPEN Ductus venosus OPEN O2 saturation in aorta ~67% ~4 kPa, 30 mmHg PO2 in aorta After birth:

Ductus venosus Systemic vascular resistance > Pulmonary vascular resistance Ductus arteriosus CLOSED Foramen ovale CLOSED Ductus venosus CLOSED O2 saturation in aorta ~97% PO2 in aorta ~13 kPa, 100 mmHg

Portal vein Umbilical vein 7 1

Umbilical arteries 8

Placenta

40

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Development of the respiratory system and birth

Structure and function

41

r

17

Complications of development and congenital disease

(b) Congenital diaphragmatic hernia

(a) Relationship between prematurity and development of NRDS

% Neonates developing NRDS

80 60 40

Heart

20

Diaphragm

0 Gestational age: Birth weight:

Hypoplastic compressed lung Intestine in thorax

Liver <30 <1250

30–34 <1500

34–37 weeks <1700 g

Stomach

Other factors such as socioeconomic status, maternal health, race and sex also affect incidence of NRDS (c) Trachea

Trachea Atresia

Fistula Fistula

Oesophagus

Oesophagus

Bronchi

Bronchi

Oesophageal atresia and tracheo-oesophageal fistula (85%)

Tracheo-oesophageal fistula (5%)

(d) Some genetic diseases in which the lung is a primary site of injury Disease

Inheritance

Lung pathology

Pathogenesis

Alpha1-antitrypsin deficiency

AD

Protease–antiprotease imbalance

Emphysema

Ciliary dyskinesia

AR

Impaired mucociliary clearance

Airway infection, bronchiectasis

Cystic fibrosis

AR

Abnormal chloride transport

Airway infection, bronchiectasis

Familial idiopathic fibrosis

AR

Unknown

Diffuse fibrosis

Lipoid proteinosis (Urbach–Wiethe syndrome)

AR

Lipoglycoprotein deposition in upper respiratory tract causing mucosal thickening and airway obstruction

Hyalinized or granular deposits in the tracheo-bronchial submucosa

Tracheobroncho-megaly (Mounier–Kuhn syndrome)

AR

Saccular bulges between cartilage rings resulting from atrophy of elastic and smooth muscle tissue and causing impaired mucociliary clearance

Recurrent airway infections

Deficiency of subsegmental bronchial cartilage with airway collapse

Recurrent airway infections, bronchiectasis

Congenital cartilage deficiency (Williams–Campbell syndrome)

?

AD = Autosomal dominant, AR = Autosomal recessive

42

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Complications of development and congenital disease

Structure and function

43

r

Lung defence mechanisms and immunology

(a) Physical and physiological defences

(b) Ciliated columnar epithelium Invading bacteria

Nasopharynx

Macrophage

IgA

Lumen

• Warms/humidifies air • Traps particles >10μm

Cilia

• Irritant receptors initiate sneezing

Gel phase Sol phase

Larynx, trachea and bronchi

Mucus

Epithelial cell

• Traps particles >5μm in mucus

Basement membrane

• Mucociliary clearance to mouth

Epithelium

18

Goblet cell

• Irritant receptors initiate coughing

Secretory component

Alveolar ducts and alveoli Submucosal gland

• Squamous epithelium (no cilia) (c) Immune response

• Alveolar macrophages • Surfactant protein A from type II pneumocytes

Complement

IgG

B-lymphocyte IgM

Phagocyte

tiation Differen ion t fe li pro ra

Plasma cells

IL-4,

IL-3,

IFN-

γ IL-2

Antigen

44

Dentritic cell

TH lymphocyte

TC lymphocyte

Infected cell

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Lamina propria

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Lung defence mechanisms and immunology

Structure and function

45

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History and examination

Sputum pot Look inside bedside sputum pot

Face Conjunctiva for anaemia Lips + tongue for central cyanosis Features of systemic disease

O2

Chest inspection Measure respiratory rate (normal 8–14/min) Look for: • use of accessory muscles - intercostal recession - paradoxical abdominal movement • chest wall shape + hyperinflation • scars (radiotherapy, surgery) • engorged veins (e.g. SVC obstruction) • chest wall movement - symmetrical, reduced

CHECK SaO 2 GIVE OXYGEN to prevent hypoxaemia

Neck JVP Cervical lymph nodes Tracheal position

Chest palpation Examine • position of trachea + apex beat • symmetry of movement of two sides • amount of chest wall movement • axillary lymph nodes • vocal fremitus

Pulse

Chest percussion Compare the percussion note over comparable areas on both sides of the chest (including apices). Note dullness or hyper-resonance

Hands Normal

Clubbing Loss of angle Increased curvature

Check charts for: Nicotine staining

Peripheral cyanosis

Chest auscultation Examine for: • nature and intensity of breath sounds - i.e. diminished or absent - i.e. vesicular or bronchial • added sounds (crackles, wheeze, rubs) • character + intensity of vocal resonance

- Temperature - Peak expiratory flow rate - Saturation (SaO2 )

Coarse flap of CO2 retention

Table 2. Typical physical signs associated with specific respiratory disorders Disorder Table 1. Causes of Clubbing Common: Bronchial carcinoma Suppurative lung infection - bronchiectasis - lung abscess - empyema Interstitial fibrosis Uncommon Bacterial endocarditis Cyanotic heart disease Inflammatory bowel disease Malabsorption Atrial myxoma Cirrhosis Familial Idiopathic Pleural mesothelioma

Consolidation Collapse

Chest Wall Movement On affected side On affected side

Percussion Note

Breath Sounds

Added Sounds

Dull

Bronchial

Coarse crackles

Dull

Absent or bronchial

None

Diminished*

None (±rub)

Pleural effusion

On affected side

Interstitial fibrosis

On both sides

Normal or ±

Vesicular or diminished

Fine inspiratory crackles

Pneumothorax

On affected side

Normal or hyper-resonant

Diminished**

None

Asthma/COPD

On both sides

Normal

Vesicular with prolonged expiration

Expiratory wheeze

Stony dull

* Bronchial breathing may occur above the effusion; ** an audible click (in time with cardiac systole) may occur on the left side.

46

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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History and examination

History, examination and investigation

47

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Pulmonary function tests

(a) Volume–time spirograms during forced expiration from total lung capacity 7

Normal forced expiratory trace

6

6

5

5

4 3

Middle 50% FVC FEF25–75 = v/t

v 2

FEV1 t

1 0

FVC

Volume BTPS (L)

Volume BTPS (L)

7

0

Traces from three subjects of same age, sex and height A

4

B

3

C

2 1

1

2

3 4 Time (second)

5

0

6

FEV1 = Forced expiratory volume in 1 second FVC = Forced vital capacity FEF25–75 = Mean forced expiratory flow from 25–75% of FVC

0

1

2

3 4 Time (second)

5

6

A = Normal respiratory system B = Obstructive airway disease C = Restrictive lung disease (c) The body plethysmograph for measuring lung volumes

(b) Helium dilution for measuring functional residual capacity* Pmouth Spirometer filled with volume, V1 , and helium concentration, [He], C1

Volume = V1+ FRC [He] = C2 Shutter V1, P1, Pbox

Volume = FRC [He] = 0%

V1 + ΔV, P2

Calibrating syringe

Starting at the end of a normal expiration (lung volume = FRC), the subject breathes in and out from the spirometer until equilibrium is reached. Since helium is poorly soluble in blood: V1 x C1 = (V1+ FRC) x C2

∴ FRC = V1 x

C1 – C2 C2

*Note: To measure TLC or RV, the subject is asked to breathe in fully or breathe out fully before breathing the helium gas mixture.

The subject inhales against a closed shutter Lung volume expands from V1 to V1 + ΔV ΔV can be deduced from the rise in box pressure, Pbox (calibrated with known volumes) Mouth (= alveolar) pressure falls from P1 to P2 From Boyle’s law: V1 x P1 = P2(V1 + ΔV) Hence the original volume in the lungs, V1 , can be found

48

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Pulmonary function tests

History, examination and investigation

49

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21

Chest imaging and bronchoscopy

Evaluation of the CXR includes all the following: 1 Date:

(a)

Chest radiograph interpretation

Normal chest X-ray

2 Name: 4

3 AP/PA: Is it AP (anteroposterior) or PA (posteroanterior)? (Heart size cannot be measured if AP)

15 16

4 Is it well positioned? The trachea should be midway between clavicles

11

16 12

10

5 Penetration: The disc spaces should be just visible through the cardiac shadows (underpenetrated = plethoric lungs overpenetrated = dark lungs)

10 5

9

6

6 Soft tissues and breast shadows (mastectomy in a female)

13

14

14

8

7

7 Right diaphragm 2 cm higher than left (raised when paralysed, flat in asthma/COPD)

7

Heart size less than 50% of chest width

8 Check ribs for fractures, metastases 9 Right heart border = right atrium

12 Aortic arch

15 Trachea and main bronchi

10 Hilium = bronchi, arteries and veins

13 Left heart border = left ventricle

16 Lung fields

11 Superior vena cava

14 Pulmonary vessels (b)

Chest radiograph interpretation

Normal lateral X-ray

1 Thoracic vertebral bodies 2 Scapula

5

3 Pulmonary trunk and hilium

6

4 Descending aorta

2

7 9

5 Head of clavicle 6 Trachea

8

3

11

7 Arch of aorta 1

8 Ascending aorta 10

9 Anterior space (thymus)

4

10 Heart 11 Sternum

12

12 Diaphragm 1 Oesophagus

(c)

2 Right lung 6

3 Right main bronchus

7

5

9

4 Right pulmonary artery and branches 8

5 Superior vena cava 6 Ascending aorta

4

7 Pulmonary trunk 8 Mediastinum and heart 9 Left pulmonary artery and branches

10

3 2

11

10 Left main bronchus 11 Left lung

1

12

12 Descending aorta

50

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Chest imaging and bronchoscopy

History, examination and investigation

51

r

22

Public health and smoking

(a) All UK deaths in 2004

(b) Progressive decline in lung function in smokers and non-smokers and the effect of stopping smoking at 45 and 65 years old

All UK deaths in 2004 Ischaemic heart disease Non-respiratory cancer All deaths from respiratory disease

587 808 106 081 122 512 117 456

Respiratory disease

Cases

%

• Pneumonia and TB • Lung cancer • Progressive non-malignant causes COPD + asthma Pulmonary circulatory disease Pneumoconiosis Cystic fibrosis Sarcoidosis • Others (congenital etc.)

35 814 34 721 35 979 28 859 3926 3024 139 31 10 527

30.5 29.6 30.6 24.6 3.3 2.6 0.1 0.03 9

100

% FEV1 at 25 years old

Never smoked not susceptibile

Stopped at 45 50

Smoked regularly and susceptible

(c) Total UK emergency medical admissions by diagnosis (2004) COPD Angina CCF Pneumonia Gastroenteritis Diabetes + complications

111 000 79 000 62 000 57 000 54 000 18 000

Stopped at 65

Disability

Death 0 25

50

75 Age (years)

Adapted from: Fletcher and Peto (1977) BMJ 1:1645

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Public health and smoking

Diseases and treatment

53

r

23

Respiratory failure (b) Mechanisms of arterial hypoxia (low PaO2)

(a) Causes of respiratory failure

Airway obstruction Foreign body or tumour Asthma COPD

Central drive CNS-depressant drugs (e.g. barbiturates) Head injury Cerebrovascular accident Primary alveolar hypoventilation Spinal cord Transection (apnoea if above C3) Poliomyelitis

Chest wall Crush injury — flail chest Kyphoscoliosis Lung parenchyma Fibrosis Emphysema Pneumonia Lung resection Pneumothorax Atelectasis NRDS/ARDS

Normal Normal alveolarcapillary membrane

Normal PΙO2 Normal alveolar ventilation

>98% cardiac output passing through gasexchanging alveoli

Normal PaO2

Matching of v entilation and perfusion throughout the lungs 1. Low inspired PO2 – e.g. altitude (low PB) or low inspired O2 concentration low alveolar PO2

2. Hypoventilation – Inadequate alveolar ventilation low alveolar PO2 Respiratory muscles Muscular dystrophies

Other Cyanotic congenital heart disease Pulmonary emboli Pulmonary oedema

Peripheral nerves Guillain–Barré Neuromuscular junction Myasthenia gravis Muscle relaxants

Air or alveolar gas with normal PO2 Air or alveolar gas with reduced PO2

3. Diffusion impairment – Pulmonary capillary blood fails to reach equilibrium with alveolar gas low pulmonary end-capillary PO2

4. Ventilation–perfusion mismatching – Blood from areas with high VA/Q mixes with blood from low VA/Q areas low pulmonary venous PO2

Deoxygenated blood (‘mixed venous’ or right-sided) Normal, fully oxygenated Incompletely oxygenated blood

5. Right-to-left shunt – Shunted blood fails to undergo gas exchanges, mixes with pulmonary capillary blood low pulmonary venous/left ventricular PO2

(c) Effects of hypoxia and hypercapnia

54

Acute

Chronic—compensation and complications

Low PaO2 (hypoxaemia/ hypoxia)

Impaired CNS function: irritability, confusion, drowsiness, convulsions, coma, death Central cyanosis (not very sensitive; may be absent in anaemia) Cardiac arrhythmias Hypoxic vasoconstriction* of pulmonary vessels

Erythropoietin from hypoxic kidney polycythaemia oxygen carriage despite low PaO2 but if excessive (haematocrit >55%) the viscosity impairs tissue blood flow Polycythaemia florid complexion; increased cyanosis Pulmonary hypertension* right ventricular hypertrophy Fluid retention/right heart failure (cor pulmonale*) peripheral oedema/ascites/ jugular venous pressure/enlarged liver

High PaCO2 (hypercapnia)

Low arterial pH (respiratory acidosis) Peripheral vasodilatation warm flushed skin, bounding pulse Cerebral vasodilatation intracranial pressure headache, worse on waking if nocturnal ventilation Impaired CNS/muscle function: irritability, confusion, somnolence, coma, tremor, myolonic jerks, hand flap Cardiac arrhythmias

Renal compensation (compensatory metabolic alkalosis) arterial [HCO3– ] arterial pH returned to near normal Cerebrospinal fluid (CSF) compensation CSF [HCO3– ] CSF pH returned to near normal respiratory drive less at any given PaCO2 than in acute hypercapnia *Hypercapnia accentuates the effects of hypoxia on pulmonary blood vessels and therefore contributes to the development of cor pulmonale (see above)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Asthma: pathophysiology (b) Hyperrresponsiveness Epithelium

65%

40% Healthy

Bronchoconstriction hyperresponsiveness, remodelling

20%

Patients often allergic to more than one allergen

Dose of stimulus (e.g. inhaled histamine)

(d) Typical response of an atopic asthmatic to inhaled antigen Allergen challenge

Late-phase response

Recurrent attacks

FEV1

Immediate response

5 Minutes 15 Bronchoconstriction Goblet cell

(e) Cellular mechanisms

4

6

8

Hours

10

2

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Inflammation, mucosal oedema, mucus, epithelial damage Hyperresponsiveness, bronchoconstriction and airway remodelling Sub-mucosal gland Mucus

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kin es

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Mucosal oedema

Epithelial damage

(c) Main causes of asthma

House dust mite

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Airway resistance to airflow

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The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Asthma: pathophysiology

Diseases and treatment

57

r

25

Asthma: treatment

(a) Step-wise approach to asthma therapy (adult)

v ut re

west

he lo

ec prov

o im

t e up Mov

ont te c equa

d

ot wn t

st

Mild and intermittent asthma

Regular preventer therapy

ADD: Inhaled longacting β2-agonist If improvement but still poor control, increase inhaled steroid (to 800 μg/day) If no improvement, increase steroid and trial leukotriene receptor antagonist or SR theophyline Initial add-on therapy

Step 1

Step 2

Step 3

o

ed Mov

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plian

Based on British Thoracic Society guidelines, 2009, update brit-thoracic.org.uk/

ADD: Inhaled low-dose steroid Inhaled short-acting β2agonist as required

Control of asthma is defined as: • No daytime symptoms • No need for rescue medication

Consider trials of: Increased inhaled steroid to high dose 2000 mg/day Addition of 4th drug: leukotriene receptor antagonist SR theophyline oral β2-agonist

ADD: Oral steroid, lowest dose possible Maintain high-dose inhaled steroid Consider other treatments to minimize use of oral steroids Refer to specialist

Persistent poor control

Frequent oral steroid

Step 4

Step 5

• No limitations on activity • No night-time awakening due to asthma

• No exacerbations • Normal lung function

(b) Most common drug classes used in asthma Type

Route and example

Effect

Adverse effects

β2–agonist (adrenoreceptor agonists)

Inhaled, oral, intravenous (IV) Short-acting: salbutamol (albuterol) Long-acting: salmeterol, formoterol

Bronchodilators May stabilize mast cells (increase cAMP)

Muscle tremor (most common) Tachycardia, palpitations (high dose)

Corticosteroids

Inhaled: Beclometasone proprionate Prednisolene Oral: Hydrocortisone IV:

Anti-inflammatory (Suppress activation of inflammatory genes)

Inhaled: oral candidiasis, cough, hoarseness Oral/high dose: Retarded growth, water retention, osteoporosis, hypertension, weight gain, eye problems, diabetes, psychosis

Xanthines

Oral, IV: Theophylline, aminophylline Slow release (SR) formulations

Bronchodilators Some anti-inflammatory action (increase cAMP)

Headache, nausea, diuresis, cardiac arrhythmias, vomiting, epilepsy; many drug interactions affect xanthine plasma levels

Muscarinic receptor antagonists

Inhaled: Ipratropium bromide

Bronchodilators Reduce mucus secretion (block cholinergic effects)

Rare, bitter taste

Antileukotrienes Receptor antagonist Lipoxygenase inhibitor

Oral: Montelukast, zafirlukast Zileuton (not licensed in UK)

Bronchodilators May reduce mucosal oedema (block action of LTC4, LTD4)

None-significant described

(c) Pressurized metered dose inhaler

58

• Remove the cap and shake the inhaler • Tilt the head back slightly and exhale • Position the inhaler in the mouth (or preferably just in front of the open mouth) • During a slow inspiration, press down the inhaler to release the medication • Continue inhalation to full inspiration • Hold breath for 10 seconds • Actuate only one puff per inhalation

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Severe uncontrolled asthma 5HTXLUHV LPPHGLDWH WUHDWPHQW DQG KRVSLWDOL]DWLRQ Indications: LQDELO LW\ WR FRPSOHWH VHQWHQFHV µWHOHJUDSK VSHDNLQJ¶  KLJK UHVSLUDWRU\ UDWH WDFK\FDUGLD 3()5 OHVV WKDQ  SUHGLFWHG %HFRPHV life-threatening ZLWK RQH RU PRUH RI 3()5 OHVV WKDQ  SUHGLFWHG K\SR[DHPLD K\ SHUFDSQLD VLOHQW FKHVW H[KDXVWLRQ Treatment: LPPHGLDWH QHEXOL]HG β DJRQLVWV +− LSUDWURSLXP GHOLYHUHG LQ R[\JHQ DQG LQWUDYHQRXV VWHURLGV ZLWK VXEVHTXHQW RUDO VWHURLGV ,Q XQUHVROYLQJ FDVHV LQWUD YHQRXV β DJRQLVWV RU [DQWKLQHV DQG YHQWLODWLRQ PD\ EH UHTXLUHG Asthma: treatment

Diseases and treatment

59

r

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Chronic obstructive pulmonary disease

(a) Risk factors for COPD

(b) Pathophysiology of chronic bronchitis and emphysema

Smoking Age >50 years old; prevalence ~5–10% Male gender Childhood chest infections Airways hyperreactivity • asthma/atopy Low socioeconomic status α 1-Antitrypsin deficiency Heavy metal exposure • cadmium Atmospheric pollution

Chronic bronchitis Pressure collapsing airway in expiration balanced by lung's elastic recoil and airway held open

Mucosal inflammation and mucous secretion cause narrowing (± obstruction) of some airways

Normal lung parenchyma provides lung's elastic recoil

Poor ventilation and collapse of some alveoli (e.g. mucous plugs) cause V/Q mismatch + hypoxaemia

(c) Spirometry. FEV1/FVC ratio decreases in COPD FVC FEV1 Volume

FVC

FEV1

1 second

4 seconds

Pressure collapsing Elastic recoil Increased upper airway pressure (purse-lip breathing, CPAP) will tend to hold airways open and allows increased alveolar emptying

Emphysema Pressure collapsing airway in expiration is greater than lung's elastic recoil causing distal airways collapse

Collapse of distal airways in expiration causes gas trapping and alveolar hyperinflation

Normal FEV1/FVC = >0.8 COPD FEV1/FVC = <0.8 COPD Irreversible with bronchodilators <15% increase in FEV1

Loss of alveolar septa and capillaries reduces the lung's elastic recoil. Large air spaces (bullae) develop

(d) Typical signs and symptoms of COPD Emphysema

Chronic bronchitis Chronic cough, producing sputum Hypoventilation, little respiratory effort Cyanosis, hypoxaemia with secondary polycythaemia CO2 retention/chronic hypercapnia – leading to peripheral vasodilatation and bounding pulse Oedema Cor pulmonale Normal lung volumes, DLCO, lung compliance

Chronic breathlessness (dyspnoea) Cyanosis unusual; normoxic at rest, hypoxic on exercise Barrel chest (hyperinflation), underweight Rarely exhibit oedema or cor pulmonale Increased TLC, RV, lung compliance Reduced DLCO

Note: Most patients may present with both chronic bronchitis and emphysema

60

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Chronic obstructive pulmonary disease

Diseases and treatment

61

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Pulmonary hypertension

(a) Causes of pulmonary hypertension (Venice/WHO 2003) 1. Pulmonary arterial hypertension (PAH): 1.1 Idiopathic (IPAH) 1.2 Familial (FPAH) (e.g. mutation in bone morphogentic protein receptor (BMPR) 1.3 Associated with (APAH) connective tissue diseases, congenital systemicpulmonary shunts, portal hypertension (cirrhosis), HIV infection, drugs and toxins + disorders (e.g. thyroid) 1.4 Associated venous or capillary involvement: pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis 1.5 Persistent PH in the newborn (PPHN) 2. PH associated with left heart disease including left-sided valvular heart disease 3. PH associated with lung diseases and/or hypoxia including COPD, interstitial lung disease, sleep-disordered breathing, hypoventilation, high altitude exposure + developmental abnormalities 4. PH due to chronic thrombotic and/or embolic disease including thromboembolic obstruction of pulmonary artery and non-thrombotic pulmonary embolism (e.g. tumour, parasites)

Secondary to respiratory disease: Alveolar hypoxia COPD (Chapter 26) Interstitial lung disease (Chapter 30) ARDS (Chapter 41) Sleep-disordered breathing (Chapter 44)

Secondary to thrombotic disease: Chronic thromboembolic disease Embolic obliterative disease

Disorders directly affecting the vasculature: Interstitial lung disease (Chapter 30) Vasculitis (Chapter 29) Emphysema (Chapter 26) Schistosomiasis

Pulmonary venous hypertension: Left ventricular heart failure Mitral stenosis/insufficiency Fibrosing mediastinitis Left atrial myxoma Veno-occlusive disease

(b) Evaluation of suspected pulmonary hypertension

Other studies: • Autoantibodies • HIV • Liver function • Sleep study

LV RV

Dyspnoea, Loud P2

Echocardiogram

Congenital heart disease LV dysfunction Valvular disease

Chest X-ray/ CT scan

Parenchymal lung disease

Ventilation/ perfusion scan

Chronic thromboembolic disease

Right heart catheterization

62

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Pulmonary hypertension 3+ LV GHILQH DV D PHDQ SXOPRQDU\ DUWHU\ 3$ SUHVVXUH RI PRUH WKDQ 25 mmHg DW UHVW RU PRUH WKDQ 30 mmHg GXULQJ H[HUFLVH QRUPDO YDOXH ∼ PP+J PHDQ  $ ULVH LQ 3$ SUHV VXUH FDQ EH GXH WR LQFUHDVHG pulmonary vascular resistance HJ K\SR[LD DQG HPEROLVP  SXOPRQDU\ EORRG IO Z DQG back-pressure SXOPRQDU\ YHQRXV SUHVVXUH HJ OHIW KHDUW IDLOXUH  3+ LV PRVW FRP PRQO\ FDXVHG E\ DQRWKHU GLVRUGHU secondary PH  0RUH UDUHO\ LW LV GXH WR D GLVRUGHU RI WKH SXOPRQDU\ FLUFXODWLRQ LWVHOI ZKHQ LW LV WHUPHG pulmonary arterial hypertension 3$+  ,GLRSDWKLF 3$+ ,3$+ KDV QR DSSDUHQW FDXVH 7KH 9HQLFH :+2 FODVVLILFDWLR RI 3+ LV VKRZQ LQ )LJ D

Types of pulmonary hypertension Secondary to respiratory disease: PRVW FRPPRQ GXH WR K\SR[ DHPLD ZKLFK FDXVHV VPDOO SXOPRQDU\ DUWHULHV WR FRQVWULFW hypoxic pulmonary vasoconstriction  3+ LV RIWHQ DVVRFLDWHG ZLWK &23' &KDSWHU   $Q\ FRQGLWLRQ OHDGLQJ WR K\SR[LD FDQ FDXVH 3+ LQFOXG LQJ VOHHSGLVRUGHUHG EUHDWKLQJ &KDSWHU  DQG H[SRVXUH WR DOWLWXGH &KDSWHU   Pulmonary venous hypertension: LQFUHDVHG OHIW DWULDO /$ SUHV VXUH PRVW FRPPRQO\ GXH WR OHIW YHQWULFXODU G\VIXQFWLRQ DV LQ congestive heart failure OHDGV WR HOHYDWLRQ RI 3$ SUHVVXUH E\ LQFUHDV LQJ EDFNSUHVVXUH WKURXJK WKH OXQJV Mitral insufficiency RU stenosis PD\ DOVR LQFUHDVH 3$ SUHVVXUH HQRXJK WR FDXVH K\SHUWHQVLRQ ,Q WKHVH FDVHV SDWLHQWV ZLOO RIWHQ KDYH VLJQV RI SXOPRQDU\ FDSLOODU\ K\SHU WHQVLRQ VXFK DV FUDFNOHV (FKRFDUGLRJUDSK\ VKRXOG GHPRQVWUDWH /$ HQODUJHPHQW Secondary to thrombotic disease: DFXWH DQG FKURQLF YHQRXV thromboembolism FDXVHV 3+ E\ PHFKDQLFDO REVWUXFWLRQ RI WKH SUR[ LPDO RU GLVWDO SXOPRQDU\ DUWHULHV ,Q DFXWH WKURPERHPEROLVP D FRP SRQHQW RI YDVRVSDVP LV DOVR SUHVHQW DV WKH SODWHOHWULFK WKURPERHP EROXV UHOHDVHV YDVRDFWLYH PHGLDWRUV VXFK DV WKURPER[DQH VHURWRQLQ RU SODWHOHWDFWLYDWLQJ IDFWRU 7KLV IRUP LV DOVR DVVRFLDWHG ZLWK VLFNOH FHOO GLVHDVH Disorders directly affecting the vasculature: LQFUHDVHV LQ SXO PRQDU\ YDVFXODU UHVLVWDQFH PD\ RFFXU LQ WKH YHLQV FDSLOODULHV RU DUWHU LHV ,QFUHDVHV LQ capillary resistance DUH FRPPRQ DQG PD\ RFFXU LQ DQ\ OXQJ GLVHDVH WKDW FDXVHV FDSLOODU\ GLVWRUWLRQ RU UHGXFWLRQ LQ VXUIDFH DUHD Interstitial lung diseases &KDSWHUV   VXFK DV SXOPRQDU\ fibrosis scleroderma RU sarcoidosis FDXVH FDSLOODU\ GLVWRUWLRQ DV OXQJ SDUHQFK\PD LV DIIHFWHG 'HVWUXFWLRQ RI FDSLOODULHV RFFXUV LQ emphysema &KDSWHU  RU SQHXPRQHFWRP\ ,Q VFKLVWRVRPLDVLV ELOKDU]LD WKH SDUDVLWLF ZRUPV FDQ EORFN SXOPRQDU\ FDSLOODULHV Pulmonary arterial hypertension LQFOXGHV ,3$+ 3+ DVVRFLDWHG ZLWK FRQGLWLRQV VXFK DV FROODJHQ YDVFXODU GLVHDVH +,9 DQG SRUWDO K\ SHUWHQVLRQ EXW ZKHUH QR FDXVDO UHODWLRQVKLS FDQ EH GHWHUPLQHG DQG SHU VLVWHQW SXOPRQDU\ K\SHUWHQVLRQ RI WKH QHZERUQ 33+1  ,3$+ LV UDUH ± SHU PLOOLRQ SRSXODWLRQ DQG LWV SDWKRJHQHVLV LV XQFOHDU *HQHWLF DEQRUPDOLWLHV LQ SDUWLFXODU UHODWHG WR ERQH PRUSKRJHQLF SURWHLQ DQG VHURWRQLQ WUDQVSRUWHUV PD\ SUHGLVSRVH SDWLHQWV WR ,3$+ EXW DOWKRXJK VRPH FDVHV DUH FOHDUO\ familial ZLWK DXWRVRPDO GRPLQDQW LQKHULWDQFH RWKHU DUH sporadic ZLWK QR IDPLO\ KLVWRU\ ,3$+ LV PRUH FRPPRQ LQ ZRPHQ WKDQ PHQ UDWLR  DQG PRVW SUHYDOHQW EHWZHHQ  DQG  \HDUV RI DJH &HUWDLQ DSSHWLWHVXSSUHVVDQW GUXJV DIIHFWLQJ VHURWRQLQ HJ IHQIOXUDPLQH DUH DVVRFLDWHG ZLWK D IROG LQFUHDVH LQ ULVN DI WHU  PRQWKV 5HPRGHOOLQJ RI SXOPRQDU\ DUWHULROHV LV FKDUDFWHULVWLF RI ,3$+ DOWKRXJK LQ VRPH SDWLHQWV D FRPSRQHQW RI DUWHULDO YDVRVSDVP LV VXJJHVWHG E\ WKH HIIHFW RI YDVRGLODWRUV

Clinical features 'HYHORSPHQW RI 3+ FDQ VXEVWDQWLDOO\ LQFUHDVH PRUELGLW\ DQG PRUWDO LW\ 7KH SURJQRVLV IRU &23' SDWLHQWV ZLWK 3+ LV PXFK ZRUVH ZLWK D \HDU VXUYLYDO IRU RI OHVV WKDQ  LI 3$ SUHVVXUH LV PRUH WKDQ  PP+J FRPSDUHG ZLWK PRUH WKDQ  ZLWK 3$ SUHVVXUH OHVV WKDQ  PP+J 0HDQ VXUYLYDO ZLWKRXW WUHDWPHQW LQ ,3$+ LV  \HDUV 3DWLHQWV XVXDOO\ GLH IURP progressive right-sided heart failure &KURQLF 3+ FDQ OHDG WR SXOPRQDU\ YDVFXODU remodelling DQG WKLFNHQLQJ RI WKH SXOPRQDU\ YDVFXODWXUH UHGXFLQJ WKH HIILFD \ RI YDVRGLODWRUV 3+ LV JHQHUDOO\ VORZ WR GHYHORS DQG SUHVHQWV ZLWK QRQVSHFLIL V\PSWRPV LQFOXGLQJ G\VSQRHD RQ H[HUWLRQ VKRUWQHVV RI EUHDWK SDOSLWDWLRQV FKHVW SDLQ OLJKWKHDGHGQHVV DQG V\QFRSH 6LJQV DUH GLIILFXO WR HOLFLW HDUO\ DQG PD\ RQO\ LQFOXGH DQ LQFUHDVHG SXOPRQLF FRPSRQHQW RI WKH VHFRQG KHDUW VRXQG :LWK PRUH VHYHUH K\SHUWHQVLRQ right ventricular dysfunction ZLOO EH DSSDUHQW LQFOXGLQJ MXJXODU YHQRXV GLVWHQVLRQ ULJKW YHQWULFXODU KHDYH SHGDO RHGHPD DQG KHSDWLF HQODUJHPHQW 'HWHFWLRQ RI 3+ UHTXLUHV D KLJK LQGH[ RI VXVSLFLRQ EHFDXVH VLJQV DQG V\PS WRPV DUH QRQVSHFLIL DQG WKH GLDJQRVLV UHTXLUHV IXUWKHU WHVWLQJ WKHUH LV VLJQLILFDQ XQGHUGLDJQRVLV

Diagnosis (YDOXDWLRQ RI SDWLHQWV ZLWK VXVSHFWHG 3+ )LJ E EHJLQV ZLWK echocardiography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ight heart catheterization LV WKH GHILQLW YH WHVW IRU WKH DVVHVVPHQW RI 3+ DV 3$ SUHVVXUH FDQ EH PHDVXUHG GL UHFWO\ DQG /$ SUHVVXUH HVWLPDWHG IURP WKH SXOPRQDU\ FDSLOODU\ ZHGJH SUHVVXUH 3DWLHQWV ZLWK 3+ ZLWKRXW DQ HOHYDWHG /$ SUHVVXUH DQG QR DS SDUHQW SXOPRQDU\ YHQRXV OXQJ SDUHQFK\PDO FKURQLF WKURPERHPEROL RU FRQJHQLWDO KHDUW GLVHDVH DUH DVVXPHG WR KDYH ,3$+

Treatment 7KHUDS\ LQ PRVW SDWLHQWV LV GLUHFWHG DW WKH XQGHUO\LQJ DEQRUPDOLW\ WR UHOLHYH ULJKW YHQWULFXODU VWUDLQ DQG SUHYHQW ULJKWVLGHG KHDUW IDLOXUH +\SR[DHPLF SDWLHQWV ZLWK &23' EHQHIL IURP 2 WKHUDS\ WR GLPLQ LVK K\SR[LF YDVRFRQVWULFWLRQ 3DWLHQWV ZLWK thromboembolic disease &KDSWHU  VKRXOG UHFHLYH DQWLFRDJXODWLRQ DQG HYDOXDWLRQ IRU VXU JLFDO WKURPERHPEROHFWRP\ 3DWLHQWV ZLWK ,3$+ VKRXOG DOVR UHFHLYH anticoagulation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prostacyclin DQDORJXHV LPSURYHV VXUYLYDO SDUWLDOO\ WKURXJK YDVRGLODWDWLRQ WKRXJK HIIHFWV RQ SXOPRQDU\ YDVFXODU UHPRGHOOLQJ RU HQGRWKHOLDO IXQFWLRQ PD\ H[SODLQ LWV SRVLWLYH ORQJWHUP HIIHFW /XQJ WUDQVSODQWDWLRQ LV UHVHUYHG IRU IDLOHG PHGLFDO WKHUDS\ Pulmonary hypertension

Diseases and treatment

63

r

28

Venous thromboembolism and pulmonary embolism

(a) Pulmonary angiograms (A, D) and V/Q scans (B, E = ventilation scans, C, F = perfusion scans) in a healthy patient and a patient with a massive rightsided pulmonary embolism. The angiogram (D) shows complete occlusion of the right pulmonary artery. On the V/Q scan there is loss of right lung perfusion (F) but normal ventilation (E) Normal A

(b) Contrast CT scan showing contrast in the heart and pulmonary arteries (PA). Both the right and left PA show irregular defects, consistent with pulmonary emboli

Pulmonary embolism D

Normal PA

Occluded right PA

Heart and pulmonary trunk Left pulmonary artery

B

C

E

Right pulmonary artery

F Pulmonary embolus

Pulmonary embolus Ventilation scan

Perfusion scan

Normal right lung ventilation

(c) Risk factors for DVT and PE

Aorta

(d) DVT prophylaxis

Surgery

Hip, knee, gynaecological procedures

Risk of DVT

Patient

Regime

Trauma

Spinal trauma

Low

<40 years old, minor surgery (<1 h)

Early ambulation

(<1%)

Minimal immobility

Compression stockings

Moderate

>40 years old, surgery (>1 h), cardiac,

Low-dose heparin

(5–10%)

medical problems, CVA, hypercoagulability

(UFH or LMWH)

High

Complicated surgery, hip or knee

Full-dose LMWH or

(>15%)

surgery, hip fracture, trauma

warfarin

General factors

Underlying disease

Cardiovascular disease

Inherited disorders (less common)

64

No right lung perfusion

Age, obesity, smoking, oral contraceptive pill (OCP) Malignancy, sepsis, stroke, autoimmune disease Low flow states (e.g. cardiac failure and immobility) Vascular injury (e.g. atherosclerosis and catheters)

LMWH = low-molecular-weight heparin UFH = unfractionated heparin CVA = cerebrovascular accident

Deficiencies (e.g. antithrombin III, protein C and protein S) Clotting disorders (e.g. factor V leiden, antiphospholipid syndrome and dysfibrinogenaemias)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Deep venous thrombosis 1HDUO\ DOO FOLQLFDOO\ VLJQLILFDQ FDVHV RI 3( ∼ DULVH IURP '97 LQ WKH ORZHU H[WUHPLWLHV ZLWK WKURPEL W\SLFDOO\ RULJLQDWLQJ LQ WKH FDOYHV DQG SURSDJDWLQJ DERYH WKH NQHH $SSUR[LPDWHO\ ± ZLOO SURSD JDWH LQWR WKH IHPRUDO DQG LOLDF YHLQV DQG KDYH D  ULVN RI HPEROL]LQJ WR WKH OXQJ 7KURPEL PD\ GHYHORS LQ WKH D[LOODU\ DQG VXEFODYLDQ YHLQV XVXDOO\ GXH WR VXUJHU\ RU LQWUDYHQRXV FDWKHWHUV EXW HPEROL DUH XVXDOO\ VPDOOHU ZLWK OHVV ULVN RI FDWDVWURSKLF FRQVHTXHQFHV 6RRQ DIWHU WKURP EXV IRUPDWLRQ WKH LQWULQVLF ILEULQRO\WL FDVFDGH EHJLQV WR RUJDQL]H WKH WKURPEXV 7KH ULVN RI D WKURPEXV HPEROL]LQJ LV JUHDWHVW HDUO\ GXULQJ RQJRLQJ SUROLIHUDWLRQ DQG GHFUHDVHV RQFH LW LV RUJDQL]HG

Pulmonary embolism :KHQ D WKURPEXV HPEROL]HV WR WKH OXQJ UHVSLUDWRU\ RU FLUFXODWRU\ DE QRUPDOLWLHV RFFXU GXH WR VXGGHQ RFFOXVLRQ RI D SXOPRQDU\ DUWHU\ RU DUWHULROH 2FFOXVLRQ RI UHJLRQDO SHUIXVLRQ FDXVHV DQ LQFUHDVH LQ GHDG VSDFH QHFHVVLWDWLQJ DQ increase in minute ventilation WR PDLQWDLQ QRU PDO PD co  6XUIDFWDQW SURGXFWLRQ GLVWDO WR WKH HPEROXV PD\ EH UHGXFHG DIWHU  KRXUV UHVXOWLQJ LQ atelectasis Hypoxaemia LV FRPPRQ DQG PRVWO\ GXH WR V$ /Q mismatch &KDSWHU   Pulmonary infarction RFFXUV LQ OHVV WKDQ  RI FDVHV RI 3( &LUFXODWRU\ FRPSOLFDWLRQV DULVH IURP REOLWHUDWLRQ RI WKH SXOPRQDU\ YDVFXODU EHG DQG D UHGXFWLRQ RI FDUGLDF RXWSXW 6HYHULW\ LV UHODWHG WR WKH DPRXQW RI OXQJ HPEROL]HG DQG WKH SUHH[LVWLQJ VWDWH RI WKH SXOPRQDU\ YDVFXODWXUH DQG ULJKW YHQWULFOH 59  $ VLQJOH ODUJH HPEROXV FDQ EH FDWDVWURSKLF ZKHUHDV PXOWLSOH VPDOO HPEROL FDQ FDXVH µSUXQLQJ¶ RI VPDOOHU DUWHULHV &LUFXODWRU\ FRO ODSVH PD\ RFFXU ZLWK PRUH WKDQ  REVWUXFWLRQ RI WKH SXOPRQDU\ YDVFXODU EHG /HVV VHYHUH HPEROL PD\ EH IDWDO WR SDWLHQWV ZLWK SUH H[LVWLQJ OXQJ RU KHDUW GLVHDVH

Clinical features &OLQLFDO IHDWXUHV RI '97 DUH QRQVSHFLILF ZLWK ORZHU H[WUHPLW\ SDLQ VZHOOLQJ DQG HU\WKHPD +RPDQ¶V VLJQ SDLQ LQ WKH FDOI RQ GRUVLIO [LRQ RI WKH IRRW RFFXUV LQ D PLQRULW\ RI SDWLHQWV )LIW\ SHU FHQW RI '97V DUH XQGHWHFWHG 0RVW SDWLHQWV ZLWK 3( KDYH dyspnoea pleuritic chest pain haemoptysis apprehension DQG tachypnoea :LWK VHYHUH 3( VLJQV UHODWHG WR RV failure HJ K\SRWHQVLRQ DQG MXJXODU YHQRXV GLVWHQVLRQ PD\ RFFXU 0RVW SDWLHQWV ZLWK 3( KDYH QRQVSHFLIL DEQRUPDOLWLHV RQ FKHVW ;UD\ LQFOXGLQJ DWHOHFWDVLV 7KH HOHFWURFDUGLRJUDP (&* PD\ VKRZ QRQVSHFLIL 67 VHJPHQW FKDQJHV DQG UDUHO\ ZLWK VLJQLILFDQ 59

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Treatment 7KH FRUQHUVWRQH RI WKHUDS\ IRU '973( LV anticoagulation ZKLFK VWRSV SURSDJDWLRQ RI H[LVWLQJ WKURPEXV DQG DOORZV RUJDQL]DWLRQ ,PPH GLDWH WKHUDS\ LQ SDWLHQWV ZLWK D KLJK VXVSLFLRQ RI 3( PD\ SUHYHQW IXUWKHU OLIHWKUHDWHQLQJ HPEROL]DWLRQ 6WDQGDUG WKHUDS\ LV WR JLYH unfractionated heparin (UFH) RU low-molecular-weight heparin (LMWH) IRU ± GD\V IROORZHG E\ warfarin IRU ± PRQWKV 8)+ DQG ZDUIDULQ PXVW EH PRQLWRUHG DV VXEWKHUDSHXWLF OHYHOV LQFUHDVH WKH ULVN RI UHFXUUHQW WKURPERHPEROLVP /0:+ LV PRUH ELRDYDLODEOH DQG GRHV QRW UHTXLUH PRQLWRULQJ 3DWLHQWV ZLWK LQKHULWHG RU DFTXLUHG K\SHUFRDJXODELOLW\ PD\ UHTXLUH OLIHORQJ WKHUDS\ ,Q SDWLHQWV ZLWK FRQWUDLQGLFDWLRQV WR DQWLFRDJXODWLRQ UHFHQW VXUJHU\ KDHPRUUKDJLF VWURNH FHQWUDO QHUYRXV V\VWHP PHWDVWDVHV DFWLYH EOHHG LQJ RU UHFXUUHQW 3( ZKLOH RQ WKHUDSHXWLF DQWLFRDJXODWLRQ DQ inferior vena cava (IVC) filter PD\ SUHYHQW IDWDO 3( $OWKRXJK DFWLYDWLRQ RI fibrinolysis ZLWK thrombolytics KDVWHQV UHV ROXWLRQ RI SHUIXVLRQ GHIHFWV DQG 59 G\VIXQFWLRQ FRQYLQFLQJ EHQHIL LV ODFNLQJ $V WKURPERO\WLFV FDXVH LQFUHDVHG EOHHGLQJ FRPSOLFDWLRQV LQFOXGLQJ D ± ULVN RI LQWUDFHUHEUDO KDHPRUUKDJH WKH\ DUH RQO\ UHFRPPHQGHG IRU OLIHWKUHDWHQLQJ 3( ZLWK FRPSURPLVHG KDHPRG\ QDPLFV

Venous thromboembolism and pulmonary embolism

Diseases and treatment

65

r

29

Pulmonary vasculitis

(a) CT scan of patient with Wegener’s granulomatosis, showing large cavitating masses

(b) Histological section showing necrobiotic regions with multinucleate giant cells (arrows)

Table 1 Disease

Feature

Diagnostic antibodies

Comment

Collagen vascular disease Rheumatoid arthritis Scleroderma SLE

Arteries Fibrosis in arterioles Capillaritis

Uncommon CREST syndrome Alveolar haemorrhage

Vasculitides Wegener’s granulomatosis

Churg–Strauss syndrome

Microscopic polyangiitis Goodpasture’s syndrome

Lymphomatoid granulomatosis

66

Granulomatous inflammation Arteriolar/venular vasculitis Capillaritis, fibrinoid necrosis Necrotizing vasculitis in small arteries, arterioles and venules Granulomas, eosinophils Fibrinoid necrosis Arteriole/venule vasculitis Capillaritis, fibrinoid necrosis Intra-alveolar haemorrhage Linear IgG in basement membrane Minimal inflammation Angiodestructive lymphocytes Plasma cells, atypical lymphocytes

PR3-ANCA >> MPO-ANCA

Alveolar haemorrhage

MPO-ANCA >> PR3-ANCA

Asthma, eosinophilia

MPO-ANCA > PRS-ANCA

Related to Wegener’s Hepatitis B, C Alveolar haemorrhage Smoking, recent infection

Anti-GBM antibodies Occassionally PR3-ANCA

Epstein–Barr virus Lymphoproliferative

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Diseases and treatment

67

r

30

Diffuse parenchymal (interstitial) lung diseases

(a) Classification

Usual insterstitial pneumonitis (UIP/IPF)

(b) Drug induced DPLD

and diagnostic process in DPLD

1. Idiopathic interstitial pneumonitis (IIP) Non-usual interstitial pneumonitis (non-UIP, e.g. NSIP, DIP)

2. DPLD due to specific causes

3. Granulomatous DPLD

4. Rare causes of DPLD

• Drug-induced • Hypersensitivity pneumonitis • Connective tissue disease • Occupational lung disease

Sarcoidosis and other granulomatous diseases

• Infiltrative (e.g. amyloidosis) • Malignant (e.g. lymphangitis carcinomatosis) • Post-inflammatory (ARDS) • Post-infective (e.g. HIV) • Bone marrow transplants • Langehams cell histiocytosis

History, examination, CXR and lung function tests Possible IIP

HRCT scan Characteristic clinical and CT features of UIP

Not IIP (e.g. drug-related, occupational, CTD, sarcoidosis and ARDS)

Atypical clinical or CT features for UIP

TBBx, BAL diagnostic in sarcoidosis in 60–90%

or suspected other DPLD or non-UIP IIP (e.g. NSIP and DIP)

TBBx, BAL or other relevant test

Features diagnostic of another DPLD e.g. sarcoidosis, LCH

Surgical biopsy not required

Surgical lung biopsy

If nondiagnostic

Non-UIP IIP UIP

NSIP

DIP

RB-ILD

COP

LIP

AIP

Not IIP

Antibiotics (e.g. nitrofurantoin) Antiarrythmias (e.g. Amiodarone and tocainide) Anti-inflammatory (e.g. gold and penacillamine) Anticonvulsants (e.g. dilantin) Antihypertensives (e.g. hydralazine) Chemotherapeutic agents (e.g. bleomycin, mitomycin C, methotrexate and busulphan) Oxygen toxicity Paraquat Narcotics (inhaled or intravenous) Therapeutic radiation

(c) Collagen vascular disease involvement in DPLD Rheumatoid arthritis (5% but commonest cause in view of disease frequency) Scleroderma (>70%) Polymyositis/dermatomyostis (20–50%) Systemic lupus erythematosus (5%) Sjogrens syndrome (25%) Ankylosing spondylitis (2%)

IPF = idiopathic pulmonary fibrosis; TBBx = transbronchial biopsy; BAL = bronchoalveolar lavage; UIP = usual interstitial pneumonia; NSIP = non-specific interstitial pneumonia; DIP = desquamative interstitial pneumonia; RB = respiratory bronchiolitis; AIP = acute interstitial pneumonia; COP = organising pneumonia; LIP = lymphoctic interstitial pneumonia; DPLD = diffuse parenchymal lung disease; CTD = connective tissue disease

(d) HRCT scan showing subpleural honeycomb fibrosis in UIP

Subpleural honeycomb fibrosis

(e) HRCT scan showing subpleural sparing, coarse reticular shadowing and traction bronchiectasis in NSIP

(f) HRCT scan showing ground glass opacification (GGO) and mosaic pattern typical of alveolitis in DIP

Traction bronchodilation

Coarse reticular opacities

GGO and mosaic patterning

Normal lung

Subpleural sparing

(g) Clinical features, age at onset, histologic pattern and radiographic features of idiopathic interstitial pneumonias Clinical name

Age, sex

CT distribution

Clinical features, relation to smoking and response to treatment

Typical CT findings Reticular abnormality + volume loss, honeycombing, traction bronchiectasis, focal GGO

Peripheral, basal + subpleural (Fig. d)

UIP/IPF

50–80 yrs M>>F

Gradual onset. Acute exacerbations. Worse in smokers. BAL shows neutrophils (±eosinophils). Poor response to steroids and immunosuppressive agents. Median survival 2–3 years from diagnosis

NSIP

40–50 yrs M=F

Gradual onset 6–30 months or subacute. Not related to smoking. BAL lymphocytosis. Prognosis better than UIP, especially in cellular (inflammatory) disease. Most patients improve or recover with steroid (±immunosuppressive) therapy

GGO, consolidation, reticular opacities

Peripheral, subpleural, basal (Fig. e)

COP

~55 yrs M=F

Subacute, related to CTD or lower respiratory tract infections and more common in smokers. Most patients recover with steroids but may be slow (>6 months)

Patchy consolidation and/or nodules

Subpleural, peribronchial

RB-ILD

40–50 yrs M:F 2:1

Usually occurs in heavy smokers (>30 packs a year). Characterized by pigmented intraluminal macrophages in bronchioles. Many patients improve with smoking cessation but steroid therapy may be required

Bronchial wall thickening, patchy GGO, centrilobular nodules

Diffuse

DIP

40–50 yrs M>>F

A form of severe RB-ILD. Characterized by BAL pigment-laden alveolar macrophages which fill alveolar spaces. Nearly always due to smoking. Prognosis >10 years following smoking cessation and/or steroid therapy in 70%. Progression to fibrosis in <20%.

GGO++, reticular lines

Lower zone, mainly peripheral (Fig. f)

AIP

Any age M=F

Rapidly progressive disease, indistinguishable from ARDS. Often presents after a viral URTI. No effective therapy and mortality is >50% and occurs within 4–8 weeks of onset. Recurrence or progressive fibrosis may occur in survivors.

Consolidation, GGO (lobular sparing), late traction bronchiectasis

Diffuse

LIP

Any age F>M

Often due to an underlying systemic condition (e.g. rheumatoid arthritis, systemic lupus erythematosus and myasthenia gravis). BAL lymphocytosis. Most respond to steroids but ~30% progress to diffuse fibrosis.

Centilobular nodules, GGO bronchovascular +septal thickening

Diffuse

IPF = idiopathic pulmonary fibrosis; UIP = usual interstitial pneumonia; NSIP = non-specific interstitial pneumonia; DIP = desquamative interstitial pneumonia; RB = respiratory bronchiolitis; RB-ILD = respiratory bronchiolitis-interstitial lung disease; AIP = acute interstitial pneumonia; DAD = diffuse alveolar damage; COP = cryptogenic organizing pneumonia; LIP = lymphocytic interstitial pneumonia; GGO = ground glass opacification; BAL = bronchoalveolar lavage; CTD = connective tissue disease, SLE = systemic lupus erythematosus

68

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Diffuse parenchymal (interstitial) lung diseases

Diseases and treatment

69

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31

Sarcoidosis

(a) Causes of lung granuloma

(b) Causes of bihilar lymphadenopathy on CXR

Idiopathic: Sarcoidosis Infective: Tuberculosis, leprosy, brucellosis, fungal, schistosomiasis, cat-scratch fever, syphilis Malignancy: Lymphoma Gastrointestinal: Crohn’s disease, primary biliary cirrhosis Allergic: Extrinsic allergic alveolitis Occupational: Berylliosis, silicosis Vasculitic: Wegener's granulomatosis, giant cell arteritis, polyarteritis nodosa, Takyasu’s arteritis Others: Thyroiditis, Langerhans’ cell histiocytosis, hypogammaglobulinaemia, orchitis

Sarcoidosis Tuberculosis Lymphoma, leukaemia Fungal infections (e.g. histoplasmosis) Berylliosis Hypogammaglobulinaenia (+recurrent infection)

(c) Characteristic CXR features in pulmonary sarcoidosis

RPTA ULF

BHL

(i) Bihilar lymphadenopathy (BHL) and right paratracheal adenopathy (RPTA)

Perihilar infiltrates

(ii) Upper lobe fibrosis (ULF)

(d) Initial evaluation of sarcoidosis

(f) CT scan of pulmonary sarcoidosis showing hilar adenopathy and peribronchovascular nodules. Inset shows fissural nodules/‘beading’ on HRCT

History (+occupational/environmental exposure) Examination including fundoscopy Full blood count including lymphocyte count Biochemistry, calcium, liver function, LDH, SACE, ECG, CXR, urine analysis (±calcium excretion) Spirometry and gas transfer (DLCO) Mantoux test (to exclude tuberculosis)

Fissural ‘beading’ on HRCT

LDH = lacate dehydrogenase; SACE = serum angiotensin-converting enzyme; ECG = electrocardiogram; CXR = chest X-ray

(e) Radiographic staging in sarcoidosis and likelihood of spontaneous resolution

Stage 0 I II III IV

70

Finding Normal chest radiograph Bilateral hilar lymphadenopathy (BHL) BHL plus pulmonary infiltrates Pulmonary infiltrates (without BHL) Pulmonary fibrosis (± bullae)

(iii) Perihilar infiltrates

Likehood of spontaneous resolution >90% 60–90% 40–60% 10–20% <20%

Peribronchovascular nodularity Hilar adenopathy Parenchymal nodules

(g) Criteria for steroid therapy in sarcoidosis Progressive symptomatic pulmonary disease Asymptomatic pulmonary disease with ongoing loss of lung function Cardiac disease Neurological disease Eye disease not responding to topical therapy Symptomatic hypercalcaemia Other symptomatic/progressive extrapulmonary disease

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Sarcoidosis

Diseases and treatment

71

r

32

Pleural diseases

(a) Causes of pleural effusions Exudative

Transudative

(protein ratio pleural/serum >0.5 or LDH ratio pleural/serum >0.6 or pleural LDH >0.66 of top normal serum value)

(meets none of the criteria for exudative)

Infectious Para-pneumonic • aerobic bacterial pneumonia • anaerobic bacterial pneumonia Empyema Tuberculosis Parasitic • amoeba • echinococcus • paragonimus Viral Autoimmune/collagen vascular Systemic lupus erythematosus Rheumatoid arthritis

Abdominal Pancreatitis/pseudocyst Oesophageal rupture Liver abscess Splenic abscess

Congestive heart failure Cirrhosis Hepatic hydrothorax Myxoedema

Miscellaneous Pulmonary embolism Drug reactions Asbestos exposure Haemothorax Chylothorax Post-cardiac surgery Post-myocardial infarction Meig’s syndrome

Nephrotic disease Peritoneal dialysis

Neoplastic Lung cancer Metastatic disease Mesothelioma

(b) CXR showing large pleural effusion in left lung (contrast with pneumothorax CXR in Chapter 35)

72

(c) CT scan demonstrating irregular (lumpy) pleural thickening of mesothelioma over lateral right chest wall (see arrows)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Pleural diseases

Diseases and treatment

73

r

33

Occupational and environmental-related lung disease

(a) Common examples of irritant gases and other agents causing lung-specific responses Agent

Source

Response

Ammonia

Industrial refrigeration leaks, fertilizers

Chlorine gas

Industrial leakage, water purification including swimming pools, household bleach (liquid/powder) interactions

Hydrogen sulphide

Sewers and manure pits, fossil fuel extraction

Nitrogen dioxide Nitrogen oxides

Vehicle exhausts, welding, power stations, oil refineries, gas and oil burning equipment, organic decomposition, structural or polymer fires

Ozone

Vehicle exhausts, welding, copiers, ozone generators, bleaching, water treatment, plasma welding

Low exposure Exacerbations of asthma and COPD Enhanced response to allergen Moderate exposure Mild mucosal irritation Airway inflammation and bronchiolitis Severe exposure Epithelial damage leading to diffuse alveolar damage Pulmonary oedema and ARDS In some cases – late response (2–8 weeks) Bronchiolitis obliterans after initial recovery

Sulphur dioxide

Combustion of fossil fuels, power stations, oil refineries, smelters, oil burning heaters, mining, ore refining, cement manufacturing, refrigeration plants

Also: direct bronchoconstriction, especially in asthmatics

Acrolein, aldehydes

Structural or wildland fires, other combustion

Also: strongly pro-inflammatory (esp. acrolein)

Diesel particulates (<10 μm)

Diesel engines

Airway/alveolar inflammation Increased deaths in elderly

Welding, brazing, metal cutting, metal reclamation Heavy metals (cadmium, mercury)

Acute pneumonitis 12–24 hours after exposure

Paraquat

Ingestion of herbicides

Accelerated, chemically induced pulmonary fibrosis

Polycyclic hydrocarbons Hydrocarbons

Diesel exhaust, tobacco smoke Ingestion of hydrocarbons (children)

Cancer Aspiration hydrocarbon pneumonitis

(b) Typical causes of allergic alveolitis Disease/occupation

74

Material

Causative agent

Farmer’s lung

Mouldy hay or other vegetable matter

Thermophilic actinomycetes bacteria (Saccharopolyspora rectivirgula, Thermoactinomyces species)

Bagassosis

Sugarcane

Mushroom workers

Compost

Humidifier fever

Contaminated water

– Also Klebsiella oxytoca, amoebae

Pigeon fancier’s (breeder’s) lung

Feathers and excreta

Avian proteins

Farmers, sawmill, tobacco, esparto grass and brewery workers

Fungal contamination of materials

Primarily Aspergillus species

Cheese, laboratory, cork workers

Fungal contamination of materials

Primarily Penicillium species

Household

Fungal infestations of damp walls and woodwork

Multiple fungal species

– other bacterial causes

Contamination of water , wood shavings, etc.

Bacillus subtilis, Klebsiella, Epicoccum nigrum, non-tubercular mycobacteria

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Occupational and environmental-related lung disease

Diseases and treatment

75

r

34

Cystic fibrosis and bronchiectasis

(a) Mean survival of CF patients

(c) Other conditions associated with CF

% Survival

100

Condition

% of CF patents

Delayed development, puberty

100%

Male infertility (absent/obstructed vas deferens and epididymis)

98%

Female infertility

20%

Pancreatic insufficiency

85%

50

Nasal polyps 0 0

25 Age (years)

50 Symptomatic sinusitis

Rectal prolapse (b) Development of respiratory problems in CF Treatment CFTR gene mutation (e.g. ΔF508)

15–20%, most in 2nd decade

Gene therapy (potential)

Bone demineralization (vitamin D deficiency) Hypertrophic osteoarthropathy Dysfunctional gallbladder or gallstones

Defective CFTR

Biliary cirrhosis Defective epithelial ion transport

Amiloride, nucleotide triphosphates

Mucus viscosity and stasis

Postural drainage, inhaled DNase, aerosolized saline

Chronic infections

Antibiotics, immunization

Inflammation and bronchiectasis

Steroids

Impaired lung function Progressive respiratory failure

Bronchodilators

10% children 25% adults 20% children Rare in adults Common

15% adults 10–30%

5% adults

(d) Some conditions associated with bronchiectasis

Cell damage, DNA

76

Allergic bronchopulmonary aspergillosis (Chapter 33) α 1-Antitrypsin deficiency (Chapters 18, 26) Bronchial obstruction (foreign bodies, mucus, tumour) Congenital cartilage deficiency (Williams–Campbell syndrome) Cystic fibrosis Fibrotic disease and alveolitis (Chapters 30 and 33) HIV and immunodeficiency (Chapter 39) Infection (e.g. measles and pertussis), pneumonia (Chapters 36 and 37) Lung transplant Primary ciliary dyskinesia (Kartagener’s syndrome, Chapter 18) Rheumatoid arthritis Tuberculosis (Chapter 38) Tracheobronchomegaly (Mounier–Kuhn syndrome)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Cystic fibrosis and bronchiectasis

Diseases and treatment

77

r

35

Pneumothorax

(a) Pneumothorax

Small pneumothorax

Moderate pneumothorax

<30%

>30%

Complete pneumothorax

Tension pneumothorax Deviated trachea

Compressed lung

Arrows depict edge of collapsed lung

Mediastinal shift

Lung

Degree of collapse Type of pneumothorax

Complete

Moderate

Small

Primary

Aspirate/ chest drain

Aspirate

Observe

Secondary

Chest drain

Chest drain

Chest drain

Traumatic/ latrogenic

Chest drain

Chest drain

Observe/ chest drain

(c) Aspiration

nPeumothorax

(d) 'Blunt dissection' technique for chest drain insertion Edge of pectoralis muscle

(b) Pneumothorax management

Local anaesthetic above rib edge (avoid neurovascular bundle) Nipple line Safe triangle for chest drain insertion

Blunt dissect tract into pleural space with forceps

Local anaesthetic Finger into pleural space to enlarge tract

Plastic cannula Aspirate using three-way tap

Position in apex of chest cavity

Discharge aspirated air through underwater seal

78

Pneumotho rax

50 mL

Intercostal drain gently inserted with forceps NOT TROCAR Lung

Tie drain in place

Connect to underwater seal

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Ultrasound guidance is always preferred

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Pneumothorax

Diseases and treatment

79

r

36

Community-acquired pneumonia

(a) Pneumonia affecting the right lower lobe

Table 2. Risk factors for pneumonia

(b) Pneumonia affecting lingula lobe

Age: >65, <5 years old Chronic disease (e.g. renal and lung) Diabetes mellitus Immunosuppression (e.g. drugs and HIV) Alcohol dependency Aspiration (e.g. epilepsy) Recent viral illness (e.g. influenza) Malnutrition Mechanical ventilation Postoperative (e.g. obesity and smoking) Environmental (e.g. psittacosis) Occupational (e.g. Q fever) Travel abroad (e.g. paragonimiasis) Air conditioning (e.g. Legionella) Consolidation lingula lobe

Consolidation right lower lobe

Table 1. Microorganisms and pathological insults that cause pneumonia Bacterial infections

Atypical infections

Fungal infection

Streptococcus pneumoniae Haemophilus influenzae Klebsiella pneumoniae Pseudomonas aeruginosa Gram-negative (E. coli)

Mycoplasma pneumoniae Legionella pneumophila Coxiella burnetii Chlamydia psittaci

Aspergillus Histoplasmosis Candida Nocardia

Viral infections

Protozoal infections

Other causes

Influenza Coxsackie Adenovirus Respiratory syncytial Cytomegalovirus

Pneumocystis carinii Toxoplasmosis Amoebiasis Paragonimiasis

Aspiration Lipoid pneumonia Bronchiectasis Cystic fibrosis Radiation

(e) Complications and infection specific features of pneumonia Cold agglutinins, e.g. Mycoplasma ** often present with cerebral symptoms Sinus infection* Respiratory failure Haemoptysis*, e.g. Klebsiella Pneumatocoeles**, e.g. Staph. aureus Pleural effusions or empyema (often occur with S. pneumoniae + S. aureus) Cholestatic jaundice** e.g. Legionella

* = Rare ** = Very rare Meningitis ** e.g. Streptococcus pneumoniae Lung abscess (often with S. aureus or aspergillus) Pericardial infection** Myocarditis** Hypotension Bacteraemia Septicaemia arthritis Haemolysis** (e.g. Mycoplasma)

3QHXPRQLD LV DQ acute lower respiratory tract (LRT) illness XVXDOO\ GXH WR infection DVVRFLDWHG ZLWK fever focal chest symptoms (±signs) DQG new shadowing on chest X-ray (CXR) )LJ D  7DEOH  OLVWV PLFURRUJDQLVPV DQG SDWKRORJLFDO LQVXOWV WKDW FDXVH SQHXPRQLD

80

(c) Non-hospital (i.e. community) management of CAP using the recently validated CRB-65 score Score 1 point for each of: • Confusion (mental test score <8 or new disorientation) • Respiratory rate >30/min • Blood pressure (SBP<90 mmHg or DBP <60 mmHg) • Age >65 years CRB-65 score (Associated mortality)

0 (1.2%)

1 or 2 (5–12%)

3 or 4 (33–48%)

Likely suitable for home treatment

Consider hospital referral

Urgent hospital admission

(d) Management of CAP in patients admitted to hospital using the recently validated CURB-65 score Score 1 point for each of: • Confusion (mental test score <8 or new disorientation) • Urea >7 mmol/L (i.e. includes use of laboratory tests) • Respiratory rate >30/min • Blood pressure (SBP<90 mmHg or DBP <60 mmHg) • Age >65 years CURB-65 score (Associated mortality) Likely suitable for home treatment

0 or 1 (1–3%)

2 (13%)

Consider hospitalsupervized treatment Options include: a) Short stay inpatient b) Hospital-supervized outpatient

3 or more (17–57%)

Manage in hospital as severe pneumonia Assess for ICU admission especially if CURB-65 is >4

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The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Diseases and treatment

81

r

37

Hospital-acquired (nosocomial) pneumonia

(a) (i) CXR; (ii) CT scan from a patient with hospital-acquired pneumonia (HAP) showing consolidation, cavitation and abscess formation (i)

Table 1. Risk factors and modifiable risk factors for HAP and VAP Unmodifiable risk factors

Modifiable risk factors

1. Host related • Malnutrition • Age: >65, <5 years old • Chronic disease (e.g. renal) • Diabetes • Immunosuppression (e.g. SLE) • Alcohol dependency • Aspiration (e.g. epilepsy) • Recent viral illness • Obesity • Smoking

1. Host related • Nutrition (e.g. enteral feeding) • Pain control, physiotherapy • Limit immunosuppressive therapy • Posture, kinetic beds • Preoperative smoking cessation

2. Therapy related • Mechanical ventilation • Postoperative Consolidation (ii)

3. Epidemiological factors • Environmental (e.g. psittacosis) • Occupational (e.g. Q fever) • Travel abroad (e.g. paragonomiasis) • Air conditioning (e.g. Legionella)

Cavitation Fluid-filled abscess

2. Therapy related • Semi-recumbent position (30˚ head up) • Early removal of iv lines, ET and NG tubes • minimize sedative use • Avoid gastric overdistention • Avoid intubation + re-intubation • Maintain ET cuff pressure >20 cm H2O* • Subglottic aspiration during intubation • Change + drain ventilator circuits • Sucrulfate for stress ulcer prophylaxis 3. Infection control • Hand washing, sterile technique • Patient isolation • Microbiological surveillance

(b) Pathogenesis of hospital aquired pneumonia Hospitalization + antibiotic therapy Colonization of the nasopharynx by Gram-negative bacilli

Table 2. Risk factors for multidrug-resistant pathogens causing hospital-acquired pneumonia • Antimicrobial therapy in the previous 90 days • Current hospitalization of >5 days • High frequency of local antibiotic resistance • Presence of risk factors for HCAP Hospitalization for >2 days in the previous 90 days Residence in a nursing home Home wound care or intravenous therapy Chronic dialysis within 30 days Family member with MDR pathogen • Immunosuppressive disease and/or therapy

Supine positioning Impaired consciousness (e.g. drugs) Swallowing difficulty + vomiting Immobility + debility Instrumentation (e.g. NG tube) Gastro-oesophageal aspiration

Aspiration of nasopharyngeal secretions

Cough reflex (e.g. drugs and pain)

Infected ventilators/circuits Direct access to LRT (ET/tracheostomy tubes)

Mucociliary clearance

Blood spread from distant focus (iv lines, infected emboli, abdominal sepsis)

Immunity Local lung defences

(c) Likely pathogens and empirical antibiotic treatment of hospital-acquiredt pneumonias

HAP or VAP or HCAP

82

ONSET + MDR PATHOGEN RISK

LIKELY PATHOGENS

TREATMENT

Early-onset (<4 days in hospital) + no risk factors for MDR pathogens

Streptococcus pneumoniae Haemophilus influenza S. aureus (methicillin-sensitive) Antibiotic-sensitive Gram-negative bacilli, e.g. E. coli, Proteus spp. Klebsiella pneumoniae, Serratia

Narrow-spectrum (single-agent) antibiotic therapy e.g. ceftriaxone or fluoroquinolones (e.g. ciprofloxacin) or co-amoxiclav or ertapenem

Late-onset (>4 days in hospital) + risk factors for MDR pathogens

All the early-onset HAP pathogens + MDR pathogens e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp., MRSA, Legionella pneumophilia

Broad-spectrum (multiagent) antibiotic therapy Antipseudomonal cephalosporin (e.g. ceftazidine) or Antipseudomonal carbapenem (e.g. imipenem) or β-lactam/ β-lactamase inhibitor (e.g. piperacillin-tazobactam) + Antipseudomonal fluoroquinolones (e.g. levofloxacin) or Aminoglycoside (e.g. amikacin, gentamicin) + Vancomycin or linezolid (if risk factors for MRSA)

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Hospital-acquired (nosocomial) pneumonia

Diseases and treatment

83

r

38

Pulmonary tuberculosis

(a)

Giant cells (multinucleate) Central caseation (‘cheesy pus’)

Ghon focus and hilar lymphadenopathy = ‘Primary complex’

Lymphocytes Acid-fast bacilli

(b) CXR of patients with TB

Upper lobe shadowing and cavitation

Abscess

Tuberculosis

(c) Pulmonary complications Mycetoma Apical cavities Pneumothorax Collapsed lung

Pleural fluid

Miliary TB • Malaise • Weight loss • Low-grade fever

84

General • Malaise • Fever and weight loss • Night sweats

Neurological TB • Meningitis • Cerebral abscess • Nerve lesions

Lymph node TB • Painless lymph node enlargement

Cardiac TB • Pericardial TB • Calcification and tamponade

Respiratory TB • Dyspnoea • Cough/sputum • Haemoptysis • Crackles Renal TB • Haematuria • Sterile pyuria • Chronic renal failure

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Spinal TB • Vertebral collapse • Paralysis

Skin TB • Lupus vulgaris

Large joint TB

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Pulmonary tuberculosis

Diseases and treatment

85

r

39

The immunocompromised host

(a) Causes of new pulmonary infiltrates Infectious • Bacterial pneumonia • Fungal pneumonia (e.g. aspergillosis) • Opportunistic pneumonia (e.g. PCP) • Viral pneumonoia Non-infectious • Pulmonary oedema, ARDS • Radiation pneumonitis • Drug-induced, e.g. amiodarone, busulphan • Malignant infiltration • Pulmonary haemorrhage • Non-specific interstitial pneumonitis

(b) Infectious causes of respiratory disease in immunocompromised patients Immunological defect

Clinical conditions

Types of infection

Neutropaenia

Chemotherapy, leukaemia, aplastic anaemia

Bacterial (e.g. E. coli, staph aureus) Fungal (e.g. aspergillus)

Impaired T-cell function

Transplantation, steroids, lymphoma, HIV infection, chemotherapy

Bacteria (e.g. mycobacteria), fungi (e.g. PCP), viruses (e.g. CMV)

Impaired B-cell function

Lymphoma, leukaemia, myeloma, hypogammaglobulinaemia

Streptococcus pneumoniae, Haemophilus influenza

Impaired compliment

Mannose lectin deficiency, complement deficiency

Streptococcus pneumonia

(c) Clinical features of AIDS Causes of respiratory disease and CXR infiltrates in HIV-infected patients Clinical features and diseases that are indicators of AIDS Cerebral HIV encephalopathy, dementia Cerebral toxoplasmosis Cryptococcus neoformans Primary brain lymphoma Respiratory Pneumocystis pneumonia Mycobacterium avium complex Mycobacterium tuberculosis Pneumonia (e.g. S. pneumoniae) General Weight loss, fatigue Lymphadenopathy CMV retinitis Gastrointestinal Diarrhoea Cytomegalovirus colitis Oral + oesophageal candida Small bowel lymphoma Skin Herpes simplex Kaposi’s sarcoma Dermatitis Malignancy Non-Hodgkins lymphoma Burkitts lymphoma Blood Lymphopaenia Bacteraemia

Causes of chest disease + CXR infiltrates in HIVinfected patients (*commonest) Infection* • Bacterial (e.g. S. Pneumoniae) • Pneumocystis pneumonia • Fungal (e.g. cryptococcus) • Mycobacterial infection (e.g. MTB, MAC) • Viral (e.g CMV) Malignancy Non-Hodgkin lymphoma Kaposi’s sarcoma Burkitt’s lymphoma Lung cancer (e) Cerebral toxoplasmosis with ring enhancement on a post-contrast CT brain scan Drug toxicity e.g. amiodarone, busulphan Interstitial pneumonitis e.g. Non-specific interstitial pneumonitis Lymphocytic interstital pneumonitis General causes Heart failure, pulmonary oedema Sepsis-induced acute respiratory distress syndrome (ARDS) Radiation pneumonitis Pulmonary haemorrhage

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(d) Pneumocystis Jirovecii pneumonia (PCP) showing bilateral diffuse infiltrates

Mass lesion with ring enhancement

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The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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The immunocompromised host

Diseases and treatment

87

r

40

Lung cancer

(a) Mass on CT: a >3 cm spiculated mass is seen in upper lobe of the right lung

(d) Staging system for non-small cell lung cancers N M T Stage (tumour) (node) (metastasis) IA IB IIA IIB

IIIA (b) Fibreoptic bronchoscopy showing tumour invading bronchus

IIIB

T1 T2 T1 T2 T3

N0 NO N1 N1 N0

T1, 2, 3 N2 T3 N1 T1, 2, 3, 4 N3 T4 N1, 2

T1–4

IV

N0–3

Key

M0 M0 M0 M0 M0

T1: ≤3cm without division T2: >3cm, or invasion of main bronchus >2cm from main carina, or invades visceral pleura, or bronchus causing obstruction T3: Invades chest wall or pleura, or main bronchus <2cm from main carina T4: Invades adjacent structure, malignant effusion, satellite nodules

M0 M0 M0 M0

N0: No lymph node metastasis N1: Ipsilateral hilar lymph nodes N2: Ipsilateral mediastinal or subcarinal lymph nodes N3: Contralateral, scalene or supraclavicular lymph nodes

M1

M0: No distant metastasis M1: Any distant metastasis

(e) Survival for non-small cell cancer 100

Stage IA

(c) CXR showing squamous cell tumour in hilar region % Survival

IB 50

Postresection pathological diagnosis

IIA IIB IIIA

IIIA IIIB IV

0 0

88

Years

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

5

Inoperable clinical diagnosis

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Lung cancer

Diseases and treatment

89

r

41

Acute respiratory distress syndrome

(a) Acute respiratory distress syndrome Pathophysiology Systemic inflammatory response (sepsis/trauma)

xin oto Fα End -6, TN , IL IL-1

Loss of surfactant and increased permeability

White cell adhesion and migration

Direct alveolar damage (aspiration/pneumonia)

CXR of aspiration-induced ARDS

Whit activ e cell ation

IL-1, IL-8 Increased permeability and consolidation

Decreased surfactant with alveolar collapse H2O

Widespread alveolar and dependent consolidation Alveolar flooding CT scan of ARDS

Endothelial and alveolar cell damage (b) Ventilator-induced lung damage 3. Normal alveoli As normal alveoli are easiest to inflate, they are damaged by overinflation = 'volutrauma'. This causes increased membrane permeability and flooding

1. Loss of surfactant Repeated alveolar collapse and re-expansion cause damage. Aim to prevent alveolar collapse and encourage alveolar recruitment

2. Damaged/fibrosed/ consolidated alveoli: difficult to inflate (reduced compliance) This is achieved with PEEP and increased mean airways pressure (i.e. reverse I:E ratio) to hold open alveoli

High peak inspiratory pressures (PIP) cause alveolar damage, 'barotrauma' and pneumothorax in normal lung tissue Use low PIP (<30 cmH2O)

(d) V/Q matching 1. PEEP: recruits collapsed alveoli 2. Nitric oxide

NO increases blood flow past ventilated alveoli

NO

NO Reduces shunt

(c) Common causes of ARDS

90

Dependent consolidation with air bronchograms

Use low tidal volumes (6 mL/kg)

Direct pulmonary

Indirect

Infective (pneumonia, tuberculosis) Pulmonary trauma Near-drowning Toxic gas inhalation Smoke NO2, NH3, Cl2 Phosgene Oxygen toxicity (FiO2 >0.8) Inhalation of gastric contents (pH <2)

Sepsis Non-thoracic trauma Burns Haemorrhage, multiple transfusion Post arrest Bowel infarction Anaphylactic Pancreatitis Uraemia, toxins, eclampsia Drugs (salicylates, barbiturates)

Consolidated alveoli

3. Prone position Back

Consolidated lung Normal lung

Front

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Blood flow greatest in dependent lung

V/Q matching improved

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Acute respiratory distress syndrome

Diseases and treatment

91

r

42

Mechanical ventilation

(a) Indications for mechanical ventilation or support in adults Surgery General anaesthesia with neuromuscular blockade Postoperative management following major surgery

Cervical cord damage above C4 Neck fractures Neuromuscular disorders– when VC <20–30mL/kg Guillain–Barré Myasthenia gravis Poliomyelitis Polyneuritis

Respiratory centre depression Usually when PaCO2 >7–8 kPa (50–60 mmHg) Head injury Drug overdose, e.g. opiates, barbiturates Raised intracranial pressure: cerebral haemorrhage/ tumours/meningitis/encephalitis Status epilepticus

Chest wall disorders Kyphoscoliosis Trauma: especially flail segment (multiple rib fractures section of chest wall unattached)

Lung disease Pneumonia Acute respiratory distress syndrome (ARDS) Severe asthma attack Acute exacerbation of chronic obstructive pulmonary disease (COPD), cystic fibrosis Trauma–lung contusion Pulmonary oedema

Other Cardiac arrest Severe circulatory shock Resistant hypoxia in type 1 respiratory failure (reduces oxygen consumption)

(c) Airway pressure profiles in different types of ventilation SV INPV

(b) Nasal mask and NIPPV

cm H2O

20

CPAP

BiPAP

IPPV IPPV + PEEP (CMV) (5cmH2O) Synchronized breath Spontaneous breath

SIMV Timing

Unsynchronized mandatory breath

0

SV = spontaneous ventilation, INPV = intermittent negative pressure ventilation, CPAP = continuous positive airway pressure, BiPAP = biphasic continuous airway pressure (trace shown is fixed time period BiPAP), IPPV = intermittent positive pressure ventilation (= CMV), CMV = controlled mechanical ventilation, PEEP = positive end-expiratory pressure, SIMV = synchronized intermittent mandatory ventilation. If a spontaneous breath occurs in the timing window it triggers a synchronized ventilator breath and if not a mandatory breath is given soon after the timing window. (d) Complications of mechanical ventilation Risks during endotracheal intubation or tracheostomy Myocardial depression from anaesthetic Aspiration of gastric contents Fall in PaO2 during apnoea Reflex bronchoconstriction and laryngospasm

Risks associated with sedation and paralysis Cardiac depression Depression of respiratory drive (delays weaning) Increases danger of disconnection/ventilator failure

Risks of endotracheal intubation and tracheostomy Intubation of the oesophagus Intubation of a bronchus Blockage/accidental extubation Laryngeal/tracheal damage or stenosis Infection

Risks associated with mechanical ventilation High airway pressure barotrauma Alveolar overdistension volutrauma: • Pneumothorax, pneumomediastinum • Subcutaneous emphysema (= air in skin) • Structural damage to lung, airways and capillaries • Bronchopulmonary dysplasia (see Chapter 17)

Risks associated with high inspired oxygen (see Chapter 43)

92

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Mechanical ventilation

Diseases and treatment

93

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43

Oxygenation and oxygen therapy

(a) Indications for acute oxygen therapy 1. Cardiac and respiratory arrest 2. Hypoxaemia (PaO2 <8kPa, SaO2 <90%) 3. Hypotension (systolic BP <100 mmHg) 4. Low cardiac output 5. Metabolic acidosis (bicarbonate <18 mmol/L) 6. Respiratory distress (respiratory rate >24/min)

(d) Oxygen delivery devices 1. Variable performance devices Air is entrained during breathing whilst oxygen is delivered from a reservoir (i.e. mask, reservoir bag, nasopharynx) The FiO2 delivered to the lungs depends on the oxygen flow rate, the patient’s inspiratory flow, respiratory rate and the amount of air entrained e.g. Figure (i) ‘Low-flow face masks’, O2 flows at ~2–10 L/min into the mask and is supplemented by air drawn into the mask. The FiO2 achieved depends on ventilation Ventilation = 5 L/min O2 flow = 2 L/min; air (21% O2) flow = 3 L/min FiO2 = (2+0.21 x 3)/5 x 100 = 53%

(c) Risks associated with high-dose oxygen therapy 1. Carbon dioxide retention: ~10% of breathless patients, mainly COPD, have type 2 respiratory failure (RF). ~40–50% of COPD patients are at risk of type 2 RF 2. Rebound hypoxaemia: occurs if oxygen is suddenly withdrawn in type 2 RF 3. Absorption collapse O2 in poorly ventilated alveoli is rapidly absorbed whereas N2 absorption is slow, so high FO2 can cause collapse 4. Pulmonary oxygen toxicity FiO2>60% may damage alveolar membranes causing ARDS if inhaled for >24–48 hrs (Chapter 41). Hyperoxia can cause coronary and cerebral vasospasm 5. Fire Deaths and burns occur in smokers during O2 therapy 6. Paul–Bert effect Hyperbaric O2 can cause cerebral vasoconstriction and epileptic fits (i) ‘Low-flow’ facemask

(ii) Nasal cannulae O2 flow rates up to 4 L/min. Higher rates dry mucosa

3 L/min air drawn into mask 2L/min oxygen into mask 2 L/min oxygen

5L/min inspired

FiO2 can be 60% at 15 L/min O2

O2 flows at ~2–15 L/min into the mask and is supplemented by air drawn into the mask. Flow rate must be > 5 L/min to prevent CO2 rebreathing

Ventilation = 25 L/min O2 flow = 2 L/min; air (21% O2) flow = 23 L/min FiO2 = (2+0.21 x 23)/25 x 100 = 27%

(iii) Non-rebreathing and anaesthetic masks

These devices cannot be used if accurate control of FiO2 is desirable, e.g. COPD with hypercapnia

One-way valve stops exhaled air entering reservoir bag

Examples of variable performance devices are ‘low-flow’ facemasks (see i), nasal cannulae (see ii) and nonrebreathing face masks with reservoir bags (see iii)

FiO2 is 60–100% at O2 flow rates of 10–15 L/min

Reservoir bag O2 flow 10–15 L/min

2. Fixed performance devices

This system delivers more gas than is inspired (i.e. >30 L/min). Consequently, FiO2 is less affected by the breathing pattern. The resulting masks are high flow, low concentration and fixed performance Used in patients with COPD and respiratory failure to avoid CO2 retention

94

The O2 flow is constant so FiO2 varies with ventilatory volume. More comfortable and not removed during eating or coughing. O2 inhaled even when mouth breathing

High (10–15 L/min) flow rates of O2 provide high FiO2 > 60% and up to 100% Non-rebreathing masks have a reservoir bag which should be filled before use. They increase FiO2 by preventing O2 loss during expiration

(iv) ‘High-flow’ (Venturi), low concentration face mask

Are independent of the patient’s pattern of breathing and inspiratory volume Figure (iv) illustrates that a fixed O2 flow through a Venturi valve entrains the correct proportion of air to achieve the required O2 concentration

FiO2 is between 24 and 35%

30 L/min total gas flow at fixed O2 concentration Venturi Valve

2 L/min jet of oxygen

Venturi valves are colour coded and deliver 24, 28, 31, 35, 40 or 60% FiO2 for a fixed flow rate

25 L/min escapes from mask

28 L/min entrained 30 L/min into air mask at FiO2 24%

5 L/min inspired

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

Continuous positive airways pressure (CPAP) masks Use a tight fitting mask and a flow generator to deliver a fixed FiO2 with a positive pressure (5–10 cm/H2O) throughout the respiratory cycle

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Oxygenation and oxygen therapy

Diseases and treatment

95

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44

Sleep apnoea

Polysomnogram (simplified)

(a) Normal

(b) Obstructive sleep apnoea

(c) Central sleep apnoea

EOG (eye movement) Arousal

Arousal EEG Desaturation SaO2 (blood O2 saturation)

Desaturation No airflow

No airflow

Airflow Thoracic movement

No effort

Continued effort

(e) Cheyne-Stokes respiration

Tongue Uvula Blocked airway Pharynx

Normal airflow

96

Obstructed airflow

O2 saturation

Ventilation

(d) Obstructive sleep apnoea

Time Cheyne-Stokes respiration occurs in heart failure and at altitude, and is characterized by slowly increasing and decreasing depth of each breath

The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd.

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Case studies: questions Case 1

Questions

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1 Is this peak flow normal? Apart from the nomogram values, can you think of any other peak flow reading with which it would be useful to compare today’s clinic reading? 2 If you measured the following: r FEV1 /FVC r Airway resistance r Functional residual capacity (FRC) r Lung compliance r Arterial 3o2 and arterial 3co2 – how would they compare with the normal for a boy of his age and size? On a school trip to a countryside park, Tom becomes breathless running across a field. His teacher is alarmed by his noisy breathing and asks you, a passing medical student, to assess whether they need to get him to hospital. 3 What simple observations can you make that will help you decide how severe this attack is? In his backpack he has a salbutamol inhaler, a salmeterol inhaler, a sodium cromoglycate inhaler and a beclometasone inhaler. Which should he use? 4 If you had been able to measure the following during his episode of breathlessness: r FEV1 /FVC r Peak flow rate r Airway resistance r Functional residual capacity r Lung compliance r Arterial 3o2 and arterial 3co2 – how do you think they would compare with the normal for a boy of his age and size? 5 If you had had your stethoscope with you, what would you have heard on examining his chest? At 18 years of age, Tom goes to college in London. He stops taking regular medication, as he feels he has ‘grown out’ of his asthma. He keeps a salbutamol inhaler in his room ‘just in case’. During the first term he is well, apart from a couple of wheezy episodes while playing football. In the second term, he develops a heavy cold, and over 24 hours he becomes progressively more breathless despite frequent puffs of salbutamol. His friends call out his GP, who finds the following: Tom is fully alert, but talking in broken sentences because he is very breathless. He is not cyanosed. He is using his accessory muscles of respiration. On auscultation, there are widespread expiratory rhonchi (wheezes). BP is 115/80 mmHg, HR 110 beats/min, respiratory rate 30 breaths/min, peak flow 200 L/min. 6 Which observations suggest that this is a fairly severe attack? 7 If the GP had measured airway resistance, FRC, lung compliance, arterial 3o2 and 3co2 , how would they compare to the predicted values? His GP decides that this attack warrants hospital admission, and he calls an ambulance. Unfortunately, owing to heavy traffic it is 40 minutes before he arrives at the local Accident and Emergency department. By this time, Tom is confused, too breathless to talk and unable to produce a peak flow reading. The Accident and Emergency

Questions 1 You are worried whether either or both could have a pulmonary embolus (PE). From the history and findings so far, is this likely in either or both of these patients? If these patients had not had surgery recently but had presented with the same symptoms and signs in Accident and Emergency, would your answer be different? 2 Which of these oxygen saturations is ‘typical’ of a pulmonary embolus? 3 Pulmonary emboli produce an area of lung that is ventilated but not perfused; that is, they produce alveolar dead space and therefore increase physiological dead space. Does increased physiological dead space inevitably lead to a reduced arterial 3o2 ? 4 What other aspects of the history might be relevant? 5 d-dimer tests are a useful addition to the diagnostic armoury but false-positives are common. False-negatives also occur. Which sort of PE is most likely to be associated with a false-negative PE? How long do D-dimers remain elevated? 6 What is the role of chest X-ray (CXR) and electrocardiogram (ECG)? How will they be affected in the presence of a pulmonary embolus? 7 What other investigations are appropriate? 8 What are the treatment options for Elizabeth and Alice?

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officer notices he is now cyanosed, although the widespread rhonchi noted in the GP’s letter have now disappeared. Arterial blood gases show arterial 3o2 = 7 kPa and arterial 3co2 = 5.5 kPa while breathing 60% oxygen. 8 Discuss the features that suggest this asthma attack is lifethreatening. Do the reduced rhonchi on auscultation contradict the other findings? 9 What is the cause of the low arterial 3o2 ? Was the inhaled oxygen helpful, and if so was the correct concentration used? Is this 3co2 normal, and how does it affect your assessment of the severity of this attack?

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Questions 1 What patterns of abnormalities do these patients exhibit? 2 Based on the lung function results, what is the most likely pathophysiology explaining each patient’s symptoms? 3 What is the likely explanation for the differences in FRC and RV between the two patients? 4 What is the differential diagnosis for Patient A? 5 What is the differential diagnosis for Patient B? 6 Both patients have hypoxaemia. Which patient is more likely to have hypercapnia?

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Questions 1 What would you expect the patient’s FRC and residual volume (RV) to be? 2 Why is the cardiac point of maximal impulse (PMI) shifted to the midline? 3 Why is the FVC low? 4 Why is the 'L co low? 5 What will happen to the patient’s oxygenation with exercise? Why? 6 Why is the patient’s jugular venous pressure elevated? 7 What are the most likely diagnosis and pathophysiology of his disease?

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Questions 1 What are the most common causes of haemoptysis, and from which circulation does bleeding occur? 2 Is haemoptysis life-threatening, and how is the severity of bleeding classified? 3 What are the clinical features that may help establish the diagnosis? What is the most likely cause in this case? 4 What investigations would you perform to establish the diagnosis in this case? 5 What is bronchiectasis, and what causes it? 6 How should a large haemoptysis be managed?

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Questions 1 Why is each patient hypoxaemic and what will happen when the FiO2 is raised to 1.0 (i.e. 100% oxygen therapy)? Precise answers cannot be calculated but assume reasonable values for unknown data. 2 How will you ensure improved oxygenation in each patient?

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Questions:

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Cases and self assessment

Case studies: questions

What brings you to suspect PSP? How do you confirm your diagnosis? What causes PSP, and is it likely to happen to James again? What treatment would you prescribe? You advise him neither to play another game for at least some months nor to climb Mount Kilimanjaro, which he had intended to do for charity. Why?

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Case studies: answers

Cases and self assessment

101

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Cases and self assessment

Case studies: answers

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Chapter 5: Diffusion 5.1 Diffusion through the alveolar–capillary membrane D LV VORZHU IRU FDUERQ GLR[LGH WKDQ IRU R[\JHQ EHFDXVH LWV PROHF XODU ZHLJKW LV KLJKHU E RFFXUV DW D UDWH ZKLFK LV SURSRUWLRQDO WR WKH GLIIHUHQFH LQ FRQ FHQWUDWLRQ P/ JDV SHU P/ IOXLG RQ HLWKHU VLGH RI WKH PHPEUDQH F LV XQDIIHFWHG E\ RHGHPD I XLG LQ WKH DOYHROXV EHFDXVH LW LV RQO\ FHOOV WKDW DFW DV D EDUULHU WR GLIIXVLRQ G LV VORZHU IRU JDVHV ZLWK ORZ VROXELOLW\ LQ WKH PHPEUDQH 5.2 Diffusion-limited uptake of a gas through the alveolar– capillary membrane D RFFXUV ZKHQ WKH JDV LQ WKH DOYHROXV UHDFKHV HTXLOLEULXP ZLWK JDV LQ WKH SXOPRQDU\ FDSLOODU\ EORRG HDUO\ LQ WKH MRXUQH\ WKURXJK WKH SXOPRQDU\ FDSLOODU\ E DSSOLHV WR WKH XSWDNH RI QLWURXV R[LGH 1 2 F ZRXOG PHDQ WKDW WKH UDWH RI XSWDNH RI WKH JDV ZRXOG EH LP SURYHG LI WKH DUHD RI WKH DOYHRODU±FDSLOODU\ PHPEUDQH LQFUHDVHG G DSSOLHV WR R[\JHQ XSWDNH LQ D KHDOWK\ SHUVRQ DW VHD OHYHO 5.3 Carbon monoxide (CO) diffusing capacity (transfer factor) D FDQQRW EH PHDVXUHG LQ SDWLHQWV ZLWK UHVSLUDWRU\ GLVHDVH EHFDXVH FDUERQ PRQR[LGH LV WRR WR[LF E HTXDOV WKH &2 XSWDNH IURP WKH OXQJV GLYLGHG E\ WKH DOYHRODU SDUWLDO SUHVVXUH RI &2 IROORZLQJ LQKDODWLRQ RI D &2FRQWDLQLQJ JDV PL[WXUH F LV PHDVXUDEOH EHFDXVH P&2 ULVHV UDSLGO\ LQ WKH SXOPRQDU\ FDSLOODU\ WR TXLFNO\ HTXDO DOYHRODU P&2 G LV RQO\ DIIHFWHG E\ WKH WKLFNQHVV RI WKH DOYHRODU FDSLOODU\ PHP EUDQH 5.4 One condition that does NOT reduce the carbon monoxide diffusing capacity (transfer factor) is D DQDHPLD E K\SRYHQWLODWLRQ F OXQJ ILEURVL G HPSK\VHPD

Chapter 6: Lung mechanics: elastic forces 6.1 When producing a pressure–volume loop for the measurement of static lung compliance 108

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Chapter 7: Lung mechanics: airway resistance 7.1 Airway resistance in the human lung is D JUHDWHVW LQ WKH JHQHUDWLRQ RI GLVWDO EURQFKLROHV LQ KHDOWK\ SHRSOH EHFDXVH WKHVH DLUZD\V KDYH WKH VPDOOHVW UDGLL E QRW LQFUHDVHG GXULQJ D IRUFHG H[SLUDWLRQ LQ D KHDOWK\ VXEMHFW F LQYHUVHO\ SURSRUWLRQDO WR WKH UDGLXV LQ D JLYHQ DLUZD\ G GHFUHDVHG ZKHQ EUHDWKLQJ WKURXJK WKH PRXWK 7.2 Airway smooth muscle constriction is D UHGXFHG E\ UHIO [ VWLPXODWLRQ RI V\PSDWKHWLF QHUYHV WR DLUZD\ VPRRWK PXVFOH E LV LQKLELWHG ZKHQ SXOPRQDU\ VWUHWFK UHFHSWRU UHIO [HV DUH DFWL YDWHG F LQFUHDVHV ZKHQ LUULWDQW UHFHSWRUV UHOHDVH KLVWDPLQH G LQFUHDVHG E\ VWUHVV YLD WKH DFWLRQ RQ HSLQHSKULQH DGUHQDOLQH RQ DLUZD\ VPRRWK PXVFOH 7.3 During a forced expiration D SHDN H[SLUDWRU\ IO Z LV QRW PXFK DIIHFWHG E\ WKH HIIRUW WKH VXEMHFW XVHV E I RZ WRZDUGV WKH HQG RI D EUHDWK IURP WRWDO OXQJ FDSDFLW\ WR UHVLGXDO YROXPH LV QRW PXFK DIIHFWHG E\ WKH HIIRUW WKH VXEMHFW XVHV F G\QDPLF FRPSUHVVLRQ RI DLUZD\V LV PRVWO\ D SUREOHP GXULQJ IRUFHG LQVSLUDWLRQ

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Chapter 8: Carriage of oxygen 8.1 Haemoglobin D LV FRPSRVHG RI IRXU LGHQWLFDO VXEXQLWV E KDV LURQ DW WKH FHQWUH RI KDHP JURXSV ZKLFK PXVW EH LQ WKH IHUURXV IRUP WR ELQG 2 F ELQGLQJ RI R[\JHQ LV UHGXFHG LQ WKH SUHVHQFH RI KLJK Pco EHFDXVH &2 DQG 2 FRPSHWH IRU WKH VDPH ELQGLQJ VLWHV RQ KDHPRJORELQ G YDULDQWV VXFK DV IHWDO KDHPRJORELQ RIWHQ GLIIHU IURP QRUPDO DGXOW KDHPRJORELQ LQ WKH SUHFLVH VWUXFWXUH RI WKH KDHP JURXS 8.2 In an anaemic patient D DUWHULDO P2 LV UHGXFHG E DUWHULDO R[\JHQ VDWXUDWLRQ LV UHGXFHG F UHVWLQJ R[\JHQ H[WUDFWLRQ LV LQFUHDVHG G UHVWLQJ PL[HG YHQRXV P2 LV UHGXFHG 8.3 A low P50 D PHDQV WKDW WKH DII QLW\ RI KDHPRJORELQ IRU R[\JHQ LV UHGXFHG E PD\ RFFXU LQ D SDWLHQW ZLWK D IHYHU F QRUPDOO\ RFFXUV DV EORRG SDVVHV WKURXJK WLVVXH FDSLOODULHV G RFFXUV LQ WKH SUHVHQFH RI IHWDO KDHPRJORELQ 8.4 Replacing inspired air with a gas mixture contains 60% oxygen D FDXVHV D ODUJH LQFUHDVH LQ DUWHULDO P2 DQG D VPDOO LQFUHDVH LQ R[\JHQ FRQWHQW LQ D KHDOWK\ SHUVRQ DW VHD OHYHO E FDXVHV D ODUJH LQFUHDVH LQ R[\JHQ FRQWHQW ZLWK OLWWOH LQFUHDVH LQ R[\JHQ VDWXUDWLRQ LQ D KHDOWK\ SHUVRQ DW KLJK DOWLWXGH F ZRXOG JUHDWO\ UHGXFH WKH H[HUFLVH LQWROHUDQFH RI D SDWLHQW ZLWK VHYHUH DQDHPLD G ZRXOG JUHDWO\ UHGXFH WKH R[\JHQ GHOLYHU\ SUREOHPV RI D SDWLHQW LQ FLUFXODWRU\ VKRFN

Chapter 9: Carriage of carbon dioxide 9.1 CO2 is transported in mixed venous blood as approximately D  ELFDUERQDWH  FDUEDPLQR FRPSRXQGV < GLVVROYHG E  ELFDUERQDWH  FDUEDPLQR FRPSRXQGV  GLVVROYHG F  ELFDUERQDWH  FDUEDPLQR FRPSRXQGV  GLVVROYHG G  ELFDUERQDWH  FDUEDPLQR FRPSRXQGV  GLVVROYHG 9.2 Decreased pH within the red blood cell D SURPRWHV 2 ELQGLQJ WR KDHPRJORELQ E FDXVHV IRUPDWLRQ RI FDUEDPLQR FRPSRXQGV F LPSDLUV 2 GHOLYHU\ WR WLVVXHV G LV OLPLWHG E\ KDHPRJORELQ 9.3 The Haldane effect states that D DQ LQFUHDVH LQ Pco VKLIWV WKH 2 GLVVRFLDWLRQ FXUYH WR WKH OHIW E IRU DQ\ JLYHQ Pco PRUH &2 LV FDUULHG E\ R[\JHQDWHG EORRG F IRU DQ\ JLYHQ Pco OHVV &2 LV FDUULHG E\ R[\JHQDWHG EORRG G DQ LQFUHDVH LQ Pco UHGXFHV WKH DPRXQW RI KDHPRJORELQ LQ WKH UHG FHOO 9.4 Hyperventilation D RFFXUV GXULQJ H[HUFLVH

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Chapter 10: Control of acid–base balance 10.1 The Henderson–Hasselbalch equation D FDQ RQO\ EH DSSOLHG WR EORRG VDPSOHV WDNHQ IURP WKH VXEMHFW EXW QRW LQ YLYR E DVVXPHV WKDW WKH FRQFHQWUDWLRQ RI FDUERQLF DFLG LV HTXDO WR WKH Pco F HPSOR\V WKH VDPH YDOXH IRU S. IRU DOO ZHDN DFLGV G UHODWHV S+ WR WKH S. DQG FRQFHQWUDWLRQV RI ZHDN DFLG DQG FRQMXJDWH EDVH 10.2 Which of the following statements about buffers is true? D 7KH PD[LPDO EXIIHULQJ FDSDFLW\ RFFXUV ZKHQ S+ = S. E 7KH S+ RI D EXIIHUHG VROXWLRQ UHPDLQV FRQVWDQW QR PDWWHU KRZ PXFK DFLG RU EDVH LV DGGHG WR WKH VROXWLRQ F :HDN DFLGV DQG EDVHV DUH QRW XVHIXO DV EXIIHUV G 3URWHLQV FRQWULEXWH YHU\ OLWWOH WR WKH EXIIHULQJ FDSDFLW\ RI EORRG 10.3 Why do CO2 and bicarbonate provide a good buffer system for the blood? D 7KH\ GR QRW KDHPRJORELQ LV WKH SULPDU\ EXIIHU E 7KH S. RI ELFDUERQDWHFDUERQLF DFLG LV HTXDO WR WKH S+ RI EORRG F %ORRG ELFDUERQDWH LV DW D KLJK FRQFHQWUDWLRQ FRPSDUHG WR WKDW RI &2  G 7KH\ DUH DFWLYHO\ UHJXODWHG E\ WKH OXQJV DQG NLGQH\V UHVSHF WLYHO\ 10.4 An arterial blood sample from a patient has a pH of 7.25, Pco2 of 6.6 kPa, and a base excess of −3. What is the mostly likely acid–base status of the patient? (hint: look at Chapter 10, panel c) D PHWDEROLF DFLGRVLV E XQFRPSHQVDWHG UHVSLUDWRU\ DFLGRVLV F UHVSLUDWRU\ DFLGRVLV FRPELQHG ZLWK PHWDEROLF DFLGRVLV G FRPSHQVDWHG UHVSLUDWRU\ DFLGRVLV

Chapter 11: Control of breathing I: chemical mechanisms 11.1 Ventilation is NOT increased by D LQFUHDVHG PD co E GHFUHDVHG DUWHULDO S+ F GHFUHDVHG P2 DW WKH FHQWUDO FKHPRUHFHSWRU G GHFUHDVHG &6) S+ 11.2 The peripheral chemoreceptors D DUH ORFDWHG LQ WKH FDURWLG VLQXV DQG DRUWLF DUFK E DUH UHVSRQVLEOH IRU  RI WKH YHQWLODWRU UHVSRQVH WR LQFUHDVHG Pco F UHVSRQG WR FKDQJHV LQ DUWHULDO S+ G FRQWDLQ W\SH ,, FHOOV ZKLFK GHWHFW K\SR[LD 11.3 The central chemoreceptor D UHVSRQVH LV GHSHQGHQW RQ WKH >+&2 − @ RI WKH &6) E LV ORFDWHG RQ WKH YHQWURODWHUDO VXUIDFH RI WKH SRQV F UHVSRQGV WR FKDQJHV LQ DUWHULDO S+ G GLUHFWO\ UHVSRQGV WR &2 11.4 The ventilatory response to increased Pco2 D LV GHFUHDVHG E\ PHWDEROLF DFLGRVLV E LV XQDIIHFWHG E\ WKH P2 XQWLO WKH P2 IDOOV EHORZ  N3D Self-assessment questions

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109

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Chapter 12: Control of breathing II: neural mechanisms 12.1 The receptors located on the bronchial walls close to the capillaries are D SXOPRQDU\ VWUHWFK UHFHSWRUV E MX[WDSXOPRQDU\ UHFHSWRUV F LUULWDQW UHFHSWRUV G SURSULRFHSWRUV 12.2 Ascending input from the lung receptors D LV FDUULHG E\ WKH ,; FUDQLDO QHUYH E DOZD\V GHSUHVVHV EUHDWKLQJ F LV I UVW UHFHLYHG E\ WKH QXFOHXV WUDFWXV VROLWDULL G LV I UVW UHFHLYHG E\ WKH SQHXPRWD[LF FHQWUH 12.3 Stretch receptors in the lung D DUH PRVWO\ UDSLGO\ DGDSWLQJ E DUH UHVSRQVLEOH IRU WKH +HULQJ±%UHXHU LQVSLUDWRU\ UHIO [ F GHWHFW IOXL DFFXPXODWLRQ LQ WKH OXQJ LQWHUVWLWLXP G DUH RI OLPLWHG LPSRUWDQFH LQ KXPDQV 12.4 Which of the following has NOT been implicated in the generation of basic respiratory rhythm? D SUH%ŽRW]LQJHU FRPSOH[ E D VZLWFKLQJ FLUFXLW EHWZHHQ SRQV DQG PHGXOOD F GRUVDO UHVSLUDWRU\ JURXS G WKH S\UDPLGDO WUDFWV

Chapter 13: Pulmonary circulation and anatomical right-to-left shunts 13.1 Compared to the systemic circulation, the pulmonary circulation D KDV OHVV SXOVDWLOH IO Z LQ WKH FDSLOODULHV E KDV WRWDO UHVLVWDQFH ZKLFK LV DERXW RQHWKLUG WKDW RI WKH V\V WHPLF FLUFXODWLRQ F ODFNV DXWRUHJXODWLRQ RI EORRG IO Z G LV VWURQJO\ FRQWUROOHG E\ DXWRQRPLF QHUYHV 13.2 The forces affecting fluid movement across the pulmonary capillaries D UHVXOW LQ QHW DEVRUSWLRQ LQ QRUPDO SXOPRQDU\ FDSLOODULHV E DUH UHGXFHG O\LQJ GRZQ F IDYRXU LQFUHDVHG ILOWUDWLR LQ D SDWLHQW ZLWK VHYHUH PLWUDO VWHQR VLV G IDYRXU LQFUHDVHG I OWUDWLRQ LQ D SDWLHQW ZLWK VHYHUH SXOPRQDU\ VWHQRVLV 13.3 All of the following are examples of conditions that usually give a pure right-to-left shunt EXCEPT: D DWULDO VHSWDO GHIHFW E OREDU SQHXPRQLD F WHWUDORJ\ RI )DOORW G DWHOHFWDVLV 13.4 Some right-to-left shunting occurs in healthy people D EHFDXVH WKHUH LV XVXDOO\ VRPH DUHDV RI XQYHQWLODWHG DOYHROL E EHFDXVH DOO RI WKH YHQRXV EORRG IURP WKH EURQFKLDO FLUFXODWLRQ GUDLQV LQWR WKH SXOPRQDU\ YHLQV F EHFDXVH DOO RI WKH YHQRXV EORRG IURP WKH YHQWULFXODU P\ RFDUGLXP GUDLQV LQWR WKH SXOPRQDU\ YHLQV G DQG LV WKH PDLQ UHDVRQ ZK\ DUWHULDO P2 LV DOZD\V OHVV WKDQ SXOPRQDU\ FDSLOODU\ P2 110

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Chapter 14: Ventilation–perfusion mismatching 14.1 In a person with ventilation–perfusion mismatching D UHJLRQV ZLWK YHQWLODWLRQ±SHUIXVLRQ UDWLRV RI  DUH GHDG VSDFH HIIHFW UHJLRQV E UHJLRQV ZLWK KLJK YHQWLODWLRQ±SHUIXVLRQ UDWLRV KDYH HTXDO DQG RSSRVLWH HIIHFWV RQ DUWHULDO Pco DQG Po DV UHJLRQV ZLWK ORZ YHQWLODWLRQ±SHUIXVLRQ UDWLRV F UHJLRQV ZLWK ORZ YHQWLODWLRQ±SHUIXVLRQ UDWLRV DUH WKH PDLQ FDXVH RI F\DQRVLV LQ D SDWLHQW ZLWK D VHYHUH DVWKPD DWWDFN G WKH HIIHFWV RQ DUWHULDO Po DQG Pco DUH XVXDOO\ TXLWH GLIIHUHQW IURP WKRVH RI D SXUH ULJKWWROHIW VKXQW 14.2 Oxygen-enriched inspired air D FDQ VLJQLILFDQWO LPSURYH R[\JHQ VDWXUDWLRQ RI WKH EORRG HPHUJLQJ IURP UHJLRQV ZLWK VRPH YHQWLODWLRQ EXW D ORZ YHQWLODWLRQ±SHUIXVLRQ UDWLR E LV PRUH OLNHO\ WR UHYHUVH WKH F\DQRVLV RI D SDWLHQW ZLWK WHWUDO RJ\ RI )DOORW WKDQ WKDW RI DQ DVWKPDWLF SDWLHQW ZLWK VHYHUH YHQWLODWLRQ±SHUIXVLRQ PLVPDWFKLQJ F ZLOO FDXVH SXOPRQDU\ EORRG YHVVHOV WR GLODWH G FDQ VLJQLILFDQWO LPSURYH R[\JHQ VDWXUDWLRQ RI EORRG HPHUJ LQJ IURP UHJLRQV ZLWK KLJK YHQWLODWLRQ±SHUIXVLRQ UDWLR 14.3 In a young asthmatic patient with arterial hypoxia during a severe attack D WKH DUWHULDO Pco ZRXOG EH H[SHFWHG WR EH KLJK E D ORZ DUWHULDO Pco ZRXOG EH H[SHFWHG EXW LI KLJK ZRXOG QRW EH DQ LPSRUWDQW SUREOHP F D ORZ DUWHULDO Pco ZRXOG EH H[SHFWHG DQG LI QRUPDO  N3D  PP+J RU KLJK ZRXOG EH FDXVH IRU FRQFHUQ G  R[\JHQ LV WKH DSSURSULDWH LQVSLUHG JDV 14.4 The A–a PO2 gradient D LV WKH GLIIHUHQFH EHWZHHQ WKH P2 LQ WKH DOYHRODU JDV DQG LQ WKH EORRG DW WKH HQG RI WKH SXOPRQDU\ FDSLOODU\ E LV QRUPDOO\ DERXW  N3D  PP+J LQ D \RXQJ SHUVRQ F LV LQFUHDVHG E\ K\SRYHQWLODWLRQ G LV XVXDOO\ LQFUHDVHG E\ HLWKHU ULJKWWROHIW VKXQWV RU YHQWLODWLRQ±SHUIXVLRQ PLVPDWFKLQJ

Chapter 15: Exercise, altitude and diving 15.1 In exercise, as the work load increases progressively D WKH R[\JHQ H[WUDFWLRQ LQFUHDVHV SURJUHVVLYHO\ XQWLO DW PD[ LPXP H[HUFLVH DOO WKH R[\JHQ KDV EHHQ UHPRYHG IURP WKH YHQRXV EORRG E DUWHULDO Pco LV OLWWOH FKDQJHG LQ PLOG WR PRGHUDWH H[HUFLVH EXW IDOOV LQ KHDY\ H[HUFLVH F DOYHRODU YHQWLODWLRQ DSSUR[LPDWHO\ GRXEOHV ZKHQ WKH FDUERQ GLR[LGH SURGXFWLRQ KDV ULVHQ IRXUIROG G WKH PDLQ GHWHUPLQDQW RI WKH PD[LPXP R[\JHQ XSWDNH WKDW D SHUVRQ FDQ DFKLHYH LV KLVKHU PD[LPXP YHQWLODWLRQ 15.2 On acute ascent to high altitude D YHQWLODWLRQ ULVHV WR DERXW IRXU WLPHV WKH VHD OHYHO YDOXH DW  P   IW E KLJK DOWLWXGH SXOPRQDU\ RHGHPD RQO\ RFFXUV LQ SDWLHQWV ZLWK KHDUW IDLOXUH F D ULVH LQ KDHPRJORELQ FRQFHQWUDWLRQ RFFXUV DQG LPSURYHV WLV VXH R[\JHQDWLRQ G K\SR[LF SXOPRQDU\ YDVRFRQVWULFWLRQ RFFXUV EXW LV RI OLWWOH EHQHIL DW DOWLWXGH

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Chapter 16: Development of the respiratory system and birth 16.1 Airway smooth muscle D RULJLQDWHV IURP WKH SULPLWLYH HQGRGHUP RI IRUHJXW E RULJLQDWHV IURP VSODQFKQLF PHVRGHUP F LV PRVWO\ IRUPHG GXULQJ WKH SVHXGRJODQGXODU SHULRG G GRHV QRW DSSHDU LQ WHUPLQDO EURQFKLROHV XQWLO DIWHU ELUWK 16.2 The lung increases in size over the first 3 years after birth D DV D UHVXOW RI EUDQFKLQJ PRUSKRJHQHVLV E XQWLO WKHUH DUH DERXW  JHQHUDWLRQV RI DLUZD\V F ODUJHO\ GXH WR LQFUHDVHG QXPEHU RI DOYHROL DQG UHVSLUDWRU\ EURQFKLROHV G GXH WR JURZWK RI DLUZD\ VPRRWK PXVFOH DQG FDUWLODJH 16.3 The Pa O2 of fetal blood D PDLQWDLQV WKH SDWHQF\ RI WKH GXFWXV DUWHULRVXV E LV LQGHSHQGHQW RI WKH PDWHUQDO PD 2 F LV PDLQWDLQHG E\ D VSHFLDO IHWDO IRUP RI KDHPRJORELQ G LV DERXW  N3D 16.4 At birth D WKH UDSLG ULVH LQ PD 2 LQLWLDWHV FORVXUH RI WKH GXFWXV YHQRVXV E WKH IRUDPHQ RYDOH RQO\ FORVHV VRPH GD\V DIWHU ELUWK F I XLG LQ WKH OXQJV LV H[SHOOHG E\ UK\WKPLF FRQWUDFWLRQ RI DLUZD\ VPRRWK PXVFOH G VXUIDFWDQW LV HVVHQWLDO IRU H[SDQVLRQ RI WKH DOYHROL

Chapter 17: Complications of development and congenital disease 17.1 Neonatal respiratory distress syndrome (NRDS) D RFFXUV LQ ∼ RI SUHPDWXUH ELUWKV ZLWK D ZHLJKW RI < J E DOZD\V IROORZLQJ SUHPDWXUH ELUWKV EHIRUH ZHHN JHVWDWLRQ F LV FRPPRQO\ WUHDWHG E\ JLYLQJ WKH QHRQDWH FRUWLFRVWHURLGV G RFFXUV LQ  LQ  RI DOO ELUWKV 17.2 Which of the following congenital diseases affecting the lung is most common? D ODFN RI SXOPRQDU\ VXUIDFWDQW SURWHLQ % E WUDFKHRRHVRSKDJHDO ILVWXO F FRQJHQLWDO GLDSKUDJPDWLF KHUQLD G 0DUIDQ¶V GLVHDVH 17.3 Which option is NOT correct concerning oesophageal atresia? D ,W OHDGV WR GLVWHQVLRQ RI WKH JXW ZLWK DLU

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Chapter 18: Lung defence mechanisms and immunology 18.1 Physical defences in the upper airways D LQFOXGH FLOLD LQ WKH QDVRSKDU\Q[ WKDW FDWFK ODUJH SDUWLFOHV E SUHYHQW SDUWLFOHV JUHDWHU WKDQ  μP HQWHULQJ WKH EURQFKL F LQFOXGH KXPLGLILFDWLR RI DLU WR SUHYHQW WKH HSLWKHOLXP IURP GU\LQJ RXW G DUH LQGHSHQGHQW RI PXFXV 18.2 Mucus D FRQWDLQV LPPXQRJOREXOLQV RI ZKLFK ,J0 LV WKH PRVW SUHYDOHQW E FRQVLVWV ODUJHO\ RI JO\FRSURWHLQV F LV VHFUHWHG E\ VTXDPRXV HSLWKHOLDO FHOOV LQ WKH ORZHU DLUZD\V G DFWV DV D SXUHO\ SDVVLYH EDUULHU DQG WUDQVSRUW PHFKDQLVP 18.3 Removal of invading materials/organisms from the alveoli D UHTXLUHV PXFRFLOLDU\ WUDQVSRUW E LV GHSHQGHQW RQ SKDJRF\WRVLV E\ PDFURSKDJHV F LV HQKDQFHG E\ FRXJKLQJ G UHTXLUHV LQILOWUDWLR RI SODVPD FHOOV 18.4 Which form of immunoglobulin is secreted across the epithelium? D ,J( E ,J* F ,J$ G ,J0

Chapter 19: History and examination 19.1 What is the most common cause of haemoptysis? D OXQJ LQIDUFWLRQ E EURQFKLDO FDUFLQRPD F SXOPRQDU\ YDVFXOLWLV G LQIHFWLRQV 19.2 On examination of the hands of a patient with type 2 respiratory failure, which of the following would be most common? D I QJHU FOXEELQJ E I QH WUHPRU F FODPP\ VNLQ G FRDUVH WUHPRU 19.3 On auscultation of the patient’s chest you hear fine inspiratory crackles; with which condition is this most often associated? D DVWKPD E OXQJ FRQVROLGDWLRQ F LQWHUVWLWLDO I EURVLV G HPSK\VHPD 19.4 The sound on percussion of a patient’s chest is hyperresonant; which condition might this reflect? D DVWKPD RU &23' E SQHXPRWKRUD[ Self-assessment questions

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Chapter 20: Pulmonary function tests 20.1 When trying to determine whether a breathless patient has obstructive or restrictive pulmonary disease D LW LV QHFHVVDU\ WR PDNH PHDVXUHPHQWV RI DLUZD\ UHVLVWDQFH DQG OXQJ FRPSOLDQFH E D SHDN H[SLUDWRU\ IO Z UDWH DERYH WKH SUHGLFWHG YDOXH LQGLFDWHV UHVWULFWLYH GLVHDVH F WKH PRVW XVHIXO WHVW LV WKH IRUFHG H[SLUDWRU\ VSLURJUDP H[ KDOHG YROXPH YV WLPH G LQVSLUDWRU\ ZKHH]LQJ ZRXOG EH H[SHFWHG LQ REVWUXFWLYH SXO PRQDU\ GLVHDVH 20.2 Forced expiratory volume in 1 second (FEV1 ) D LQFUHDVHV ZLWK DJH XQWLO D SHUVRQ VWRSV JURZLQJ ZKHQ KHVKH LV DERXW  \HDUV ROG E UHPDLQV DW WKH VDPH OHYHO RQFH LW KDV UHDFKHG LWV SHDN YDOXH SURYLGHG WKDW WKH SHUVRQ GRHV QRW VPRNH RU GHYHORS D UHVSL UDWRU\ GLVHDVH F LI LWV YDOXH LQ OLWUHV LV UHGXFHG EXW LW LV QRUPDO DV D SHUFHQWDJH RI WKH VXEMHFW¶V IRUFHG YLWDO FDSDFLW\ > )9&  LW LQGLFDWHV UHVWULFWLYH OXQJ GLVHDVH G LV QRW JUHDWO\ DIIHFWHG E\ WKH VXEMHFW¶V HIIRUW DQG WHFKQLTXH 20.3 The best single measurement indicating a respiratory problem and which is reproducible and best correlates with function and prognosis is D IRUFHG H[SLUDWRU\ YROXPH LQ  VHFRQG )(9 E IRUFHG YLWDO FDSDFLW\ )9& F SHDN H[SLUDWRU\ IO Z UDWH 3()5 G PD[LPDO YROXQWDU\ YHQWLODWLRQ 099 20.4 In patients with restrictive ventilatory defects D D KLJK WUDQVGLDSKUDJPDWLF SUHVVXUH ZRXOG VXJJHVW UHVSLUDWRU\ PXVFOH ZHDNQHVV E D QRUPDO Kco = D/ co9$ VXJJHVWV D FDXVH RXWVLGH WKH OXQJV VXFK DV UHVSLUDWRU\ PXVFOH ZHDNQHVV F UHVWLQJ K\SR[LD FDQ EH H[SHFWHG ZKHQ D/ co LV  SUHGLFWHG G IXQFWLRQDO UHVLGXDO FDSDFLW\ LV YHU\ ORZ LQ SDWLHQWV ZLWK UHV SLUDWRU\ PXVFOH ZHDNQHVV

Chapter 21: Chest imaging and bronchoscopy 21.1 A routine screening chest X-ray (CXR) D DOZD\V LQFOXGHV D ODWHUDO &;5 E LV SHUIRUPHG DW IXOO H[SLUDWLRQ F DOORZV YLVXDOL]DWLRQ RI WKH PHGLDVWLQXP G ZLWK DQWHULRU±SRVWHULRU $3 ILOP DOORZ D GHWDLOHG YLHZ RI OXQJ SDUHQFK\PD 21.2 Which of the following is NOT normally an indication for computed tomography? D SOHXUDO GLVHDVH E SXOPRQDU\ YDVFXOLWLV F SXOPRQDU\ HPEROL G SDUHQFK\PDO GLVHDVH 21.3 What is the gold standard for diagnosing pulmonary emboli? D YHQWLODWLRQ±SHUIXVLRQ VFDQV E +LJKUHVROXWLRQ FRPSXWHG WRPRJUDSK\ F SRVLWURQ HPLVVLRQ WRPRJUDSK\ G SXOPRQDU\ DQJLRJUDSK\ 112

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Chapter 22: Public health and smoking 22.1 Respiratory disease D DFFRXQWV IRU  RI DOO GHDWKV LQ WKH 8. E DFFRXQWV IRU  RI HPHUJHQF\ KRVSLWDO DGPLVVLRQV F GXH WR HPSK\VHPD FDXVHV UHGXFHG H[HUFLVH WROHUDQFH LQ  PLOOLRQ SHRSOH LQ WKH 86$ G DFFRXQWV IRU ∼  KRVSLWDO DGPLVVLRQV SHU \HDU LQ WKH 8. 22.2 Smoking-related disease D DFFRXQWV IRU ∼ RI DOO GHDWKV LQ WKH 8. E LV WKH VHFRQG JUHDWHVW FDXVH RI SUHYHQWDEOH LOOQHVV DQG PRU WDOLW\ ZRUOGZLGH F LV ODUJHO\ UHVWULFWHG WR UHVSLUDWRU\ SUREOHPV G LV GHFUHDVLQJ ZRUOGZLGH 22.3 Progressive decline in lung function (FEV1 ) D FHDVHV RQ VWRSSLQJ VPRNLQJ E GRHV QRW RFFXU LQ KHDOWK\ QRQVPRNHUV F FDXVHV GLVDELOLW\ ZKHQ WKH )(9 IDOOV WR DERXW  RI WKDW DW  \HDUV ROG G LV VWURQJO\ DFFHOHUDWHG LQ DOO VPRNHUV 22.4 Smoking cessation D UHGXFHV WKH ULVN RI OXQJ FDQFHU WR WKDW LQ QRQVPRNHUV E FDXVHV DQ LQFUHDVH LQ EUDLQ GRSDPLQH F UDWHV DUH LPSURYHG PRVW E\ WUHDWPHQW ZLWK EXSURSLRQ G UDWHV DUH LPSURYHG E\ GHFUHDVLQJ WKH UHZDUG HIIHFWV ZLWK SDU WLDO DJRQLVWV RI QLFRWLQLF DFHW\OFKROLQH UHFHSWRUV

Chapter 23: Respiratory failure 23.1 Hypercapnia is in inevitable when the cause of hypoxia is D YHQWLODWLRQ±SHUIXVLRQ PLVPDWFKLQJ E GLIIXVLRQ LPSDLUPHQW F K\SRYHQWLODWLRQ G ORZ LQVSLUHG P2 23.2 Respiratory failure D LV SUHVHQW DQG NQRZQ DV µW\SH ¶ LQ D SDWLHQW ZLWK DQ DUWHULDO P2 RI  N3D  PP+J DQG D Pco RI  N3D  PP+J E LV SUHVHQW LQ D SDWLHQW GLVDEOHG E\ EUHDWKOHVVQHVV DW UHVW ZLWK DQ DUWHULDO P2 RI  N3D F LV FODVVHG DV W\SH  LI PD co LV KLJK EXW P2 LV QRUPDO G QHDUO\ DOZD\V UHTXLUHV VRPH NLQG RI PHFKDQLFDO YHQWLODWRU\ VXSSRUW 23.3 Typical symptoms and signs caused by a high Pa co2 include D FROG SDOH VNLQ E ZHDN SXOVH F KHDGDFKH ZKLFK LV RIWHQ ZRUVH IROORZLQJ VOHHS G FHQWUDO F\DQRVLV 23.4 Chronic arterial hypoxia combined with chronic arterial hypercapnia D LV RIWHQ DVVRFLDWHG ZLWK DQDHPLD E FRXOG H[SODLQ DQ DUWHULDO S+ RI  EHFDXVH RI WKH KLJK DUWHULDO Pco

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Chapter 24: Asthma: pathophysiology 24.1 Which of the following is NOT a characteristic of asthma? D LQFUHDVH LQ ,J* LPPXQRJOREXOLQV E DLUZD\ K\SHUUHVSRQVLYHQHVV F LQILOWUDWLR RI HRVLQRSKLOV LQWR WKH DLUZD\V G LQFUHDVHG PXFXV SURGXFWLRQ 24.2 The most common allergens associated with asthma in the UK are (in order of importance) D SROOHQV KRXVH GXVW PLWH IXQJDO VSRUHV E KRXVH GXVW PLWH SROOHQV DQLPDO GDQGHU F KRXVH GXVW PLWH SROOHQV IXQJDO VSRUHV G KRXVH GXVW PLWH DQLPDO GDQGHU SROOHQV 24.3 The immediate response of asthma involves D PDVW FHOO GHJUDQXODWLRQ E ELQGLQJ RI DQWLJHQ WR ,J( RQ PDFURSKDJHV F UHOHDVH RI F\WRNLQHV VXFK DV ,/ G DFWLYDWLRQ RI FKROLQHUJLF QHUYHV 24.4 Chronic asthma is associated with: D DFWLYDWLRQ RI HRVLQRSKLOV E DFWLYDWLRQ RI 7+ O\PSKRF\WHV F UHGXFHG IXQFWLRQ RI JREOHW FHOOV G GHFUHDVHG SHUPHDELOLW\ RI VXEPXFRVDO FDSLOODULHV

Chapter 25: Asthma: treatment 25.1 Which test is NOT used during diagnosis or monitoring of asthma? D GLIIXVLQJ FDSDFLW\ E SHDN H[SLUDWRU\ IO Z UDWH F EURQFKLDO FKDOOHQJH WHVW G VNLQ SULFN WHVW 25.2 Which drug is the most commonly prescribed preventer therapy in asthma? D β DGUHQRUHFHSWRU DJRQLVWV E [DQWKLQHV VXFK DV WKHRSK\OOLQH F PXVFDULQLF UHFHSWRU DQWDJRQLVWV G LQKDOHG VWHURLGV 25.3 Long-acting β2 -adrenoreptor agonists D ZRUN E\ LQFUHDVLQJ F*03 LQ DLUZD\ VPRRWK PXVFOH E PD\ EHFRPH OHVV HIILFDFLRX GXH WR WROHUDQFH DIWHU ORQJWHUP XVH F FDQ EH XVHG DV WKH VROH WKHUDS\ LQ DVWKPD G DUH WKH I UVW FKRLFH IRU D UHOLHYHU WKHUDS\ 25.4 Which of the following is NOT a common adverse effect of low-dose inhaled steroids? D FRXJK E ZHLJKW JDLQ F RUDO FDQGLGLDVLV G KRDUVHQHVV

Chapter 26: Chronic obstructive pulmonary disease 26.1 Which of the following is NOT normally associated with chronic bronchitis? D LQFUHDVHG WRWDO OXQJ FDSDFLW\ E &R UHWHQWLRQ

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Chapter 27: Pulmonary hypertension 27.1 Pulmonary hypertension is defined as D D PHDQ SXOPRQDU\ DUWHU\ SUHVVXUH 3$3 > PP+J GXULQJ H[HUFLVH E D PHDQ 3$3 ∼ PP+J DW UHVW WKDW LQFUHDVHV WR > PP+J GXULQJ H[HUFLVH F D PHDQ 3$3 > PP+J DW UHVW RU > PP+J GXULQJ H[HUFLVH G D PHDQ 3$3 >  PP+J DW UHVW RU >  PP+J GXULQJ H[HUFLVH 27.2 The most common cause of pulmonary hypertension is D K\SR[DHPLD VHFRQGDU\ WR UHVSLUDWRU\ GLVHDVHV E OHIW KHDUW IDLOXUH F SXOPRQDU\ HPEROLVP G JHQHWLF GHIHFWV 27.3 Idiopathic pulmonary arterial hypertension D FRPPRQO\ FDXVHV SXOPRQDU\ RHGHPD E LV PRVW SUHYDOHQW LQ ZRPHQ DJHG  \HDUV RU PRUH F KDV D PHDQ VXUYLYDO ZLWKRXW WUHDWPHQW RI  \HDUV G RFFXUV LQ  SHU   SRSXODWLRQ 27.4 Which of the following drugs is NOT used for treatment of pulmonary hypertension? D VLOGHQDIL W\SH  SKRVSKRGLHVWHUDVH LQKLELWRU E ERVHQWDQ HQGRWKHOLQ UHFHSWRU DQWDJRQLVW F SURVWDF\FOLQ DQDORJXHV LQFUHDVHV F$03 G IHQIOXUDPLQ PRGXODWHV VHURWRQLQ XSWDNH DQG UHOHDVH

Chapter 28: Venous thromboembolism and pulmonary embolism 28.1 Deep vein thrombosis D SURSDJDWLQJ LQWR WKH IHPRUDO DQG LOLDF YHLQV KDV D  FKDQFH RI FDXVLQJ SXOPRQDU\ HPEROLVP E RFFXUV LQ  RI SDWLHQWV XQGHUJRLQJ KLS RU NQHH UHSODFHPHQW VXUJHU\ LQ WKH DEVHQFH RI SURSK\ODFWLF WKHUDS\ Self-assessment questions

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Chapter 29: Pulmonary vasculitis 29.1 Pulmonary vasculitis D UDUHO\ LQYROYHV RWKHU YDVFXODU EHGV E LV SULPDULO\ DVVRFLDWHG ZLWK LQIODPPDWLR DQG QHFURVLV RI WKH EORRG YHVVHOV F LV WKH PRVW FRPPRQ PDQLIHVWDWLRQ RI UKHXPDWRLG DUWKULWLV LQ WKH OXQJ G LV PRVWO\ FDXVHG E\ LQIHFWLRQ 29.2 Which of the following is NOT a primary vasculitides? D &KXUJ±6WUDXVV V\QGURPH E :HJHQHU¶V JUDQXORPDWRVLV F *RRGSDVWXUH¶V V\QGURPH G V\VWHPLF OXSXV HU\WKHPDWRVXV 29.3 Which of the following is NOT normally associated with vasculitides? D ,QFUHDVHG DQWLQHXWURSKLO F\WRSODVPLF DQWLERGLHV $1&$ E FDSLOODU\ UXSWXUH DQG DOYHRODU KDHPRUUKDJH F K\SR[DHPLD G LQILOWUDWLR RI HRVLQRSKLOV 29.4 What is the most common therapy for pulmonary vasculitis? D LQKDOHG ORZGRVH FRUWLFRVWHURLGV E FKHPRWKHUDS\ F RUDO FRUWLFRVWHURLGV G SODVPDSKHUHVLV

Chapters 30 and 31: Diffuse parenchymal (interstitial) lung diseases/Sarcoidosis 30.1 The most common form of DPLD is D RFFXSDWLRQDO OXQJ GLVHDVH E VDUFRLGRVLV F LGLRSDWKLF LQWHUVWLWLDO SQHXPRQLWLV G GUXJ LQGXFHG 30.2 DPLD is commonly associated with D LQFUHDVHG OXQJ FRPSOLDQFH E DQ REVWUXFWLYH GHIHFW F GHFUHDVHG D/ co G LQFUHDVHG UHVLGXDO YROXPH 30.3 The most frequent form of non-usual interstitial pneumonitis is D QRQVSHFLIL LQWHUVWLWLDO SQHXPRQLWLV 16,3 E FU\SWRJHQLF RUJDQL]LQJ SQHXPRQLD &23 114

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F K\SHUVHQVLWLYLW\ SQHXPRQLWLV G O\PSKRLG LQWHUVWLWLDO SQHXPRQLWLV /,3 30.4 Which of the following is least likely to respond to treatment with steroids? D QRQVSHFLIL LQWHUVWLWLDO SQHXPRQLWLV 16,3 E GHVTXDPDWLYH LQWHUVWLWLDO SQHXPRQLWLV ',3 F VDUFRLGRVLV G XVXDO LQWHUVWLWLDO SQHXPRQLD 8,3

Chapter 32: Pleural diseases 32.1 Pleurisy D LV D FRPPRQ WHUP XVHG IRU DOO GLVHDVHV RI WKH SOHXUD E LV GXH WR LQIODPPDWLR RI WKH SOHXUD F LV PDGH ZRUVH E\ GHHS LQVSLUDWLRQ G LV QRW SUHVHQW LQ SQHXPRWKRUD[ 32.2 The fluid between the parietal and visceral pleurae D LV QRUPDOO\ SURWHLQULFK E LV SULPDULO\ GUDLQHG E\ WKH YLVFHUDO O\PSKDWLFV F LV IRUPHG E\ QHW ILOWUDWLR RI D WUDQVXGDWLYH IOXL G KDV D YROXPH RI > P/ 32.3 Exudative pleural effusions D DUH SURWHLQSRRU E DUH DOZD\V DVVRFLDWHG ZLWK LQIHFWLRQ F DUH PRVWO\ FRPPRQO\ FDXVHG E\ FRQJHVWLYH KHDUW IDLOXUH G RIWHQ KDYH UDLVHG ODFWDWH GHK\GURJHQDVH 32.4 Mesothelioma D KDV D PHGLDQ VXUYLYDO RI > \HDUV E PRVW FRPPRQO\ RFFXUV ± \HDUV DIWHU DVEHVWRV H[SRVXUH F LV LQYDULDEO\ IDWDO G FDQ EH WUHDWHG ZLWK VWHURLGV

Chapter 33: Occupational and environmental-related lung disease 33.1 The most common form of occupational and environmental lung disease D LV GXH WR DWPRVSKHULF SROOXWLRQ DQG VHFRQGDU\ VPRNLQJ E FDXVHV OXQJ ILEURVL F LV WULJJHUHG DV D UHVXOW RI ZRUNSODFH VXEVWDQFHV LQ   SHRSOH LQ WKH 8. SHU \HDU G LV DVWKPD 33.2 Which of the following statements about inhaled irritants is UNTRUE? D +LJKO\ VROXEOH DJHQWV HJ DPPRQLD IDYRXU GDPDJH WR WKH DOYHRODU HSLWKHOLXP E ([WHQVLYH H[SRVXUH FDQ OHDG WR EURQFKLROLWLV REOLWHUDQV DIWHU ± ZHHNV F $FWLYDWLRQ RI LUULWDQW UHFHSWRUV OHDGV WR G\VSQRHD G 'LHVHO SDUWLFXODWHV LQFUHDVH PRUWDOLW\ SDUWLFXODUO\ LQ WKH HO GHUO\ 33.3 Pneumoconiosis D LV FDXVHG E\ LQKDODWLRQ RI RUJDQLF PDWHULDOV E FDQ LQ VRPH FDVHV GHYHORS LQWR SURJUHVVLYH PDVVLYH ILEURVL F WHQGV WR UHVXOW LQ UHYHUVLEOH DLUZD\V REVWUXFWLRQ G GRHV QRW LQFOXGH DVEHVWRVLV 33.4 Which of the following statements about Farmer’s lung is UNTRUE? D ,W LV WKH PRVW FRPPRQ H[DPSOH RI H[WULQVLF DOOHUJLF DOYHROLWLV E ,W LV GXH WR FRQWDPLQDWLRQ ZLWK WKHUPRSKLOLF DFWLQRP\FHWHV EDFWHULD

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Chapter 34: Cystic fibrosis and bronchiectasis 34.1 Cystic fibrosis is D DQ DXWRVRPDO GRPLQDQW WUDLW E GXH WR WKH ) PXWDWLRQ LQ < RI FDVHV F DVVRFLDWHG ZLWK LQIHUWLOLW\ LQ PDOHV PRUH FRPPRQO\ WKDQ LQ IHPDOHV G FKDUDFWHUL]HG E\ LQFUHDVHG PXFXV SURGXFWLRQ 34.2 The cystic fibrosis transmembrane conductance regulator (CFTR) D LV DFWLYDWHG E\ F\FOLF JXDQLQH PRQRSKRVSKDWH E LV DQ HSLWKHOLDO VRGLXP FKDQQHO F FRQWUROV PXFXV K\GUDWLRQ DQG YLVFRVLW\ G LV RQO\ SUHVHQW LQ WKH HSLWKHOLXP RI WKH ORZHU DLUZD\V 34.3 The most important treatment for cystic fibrosis is D WR LPSURYH QXWULWLRQ E WR FRQWURO LQIHFWLRQ F WR SURPRWH PXFXV FOHDUDQFH G WR UHGXFH LQIODPPDWLR 34.4 Which statement is NOT true concerning bronchiectasis? D ,W LV FDXVHG E\ SHUVLVWHQW LQIHFWLRQ DQG LQIODPPDWLR LQ SUR[ LPDO EURQFKL E )LQJHU FOXEELQJ LV RIWHQ VHHQ LQ SDWLHQWV ZLWK EURQFKLHFWDVLV F 0RVW FDVHV LQ WKH 8. DUH DVVRFLDWHG ZLWK F\VWLF ILEURVLV G ,W FDQ UDUHO\ EH GHWHFWHG E\ UDGLRJUDSKLF LPDJLQJ

Chapter 35: Pneumothorax 35.1 A pneumothorax that causes mediastinal shift and compression of the functioning lung is called D SULPDU\ SQHXPRWKRUD[ E VHFRQGDU\ SQHXPRWKRUD[ F WUDXPDWLF SQHXPRWKRUD[ G WHQVLRQ SQHXPRWKRUD[ 35.2 Primary pneumothorax D RFFXUV LQ  SHU  \RXQJ PHQ RYHU  P LQ KHLJKW LQ D \HDU E LV WKH PRVW FRPPRQ IRUP RI SQHXPRWKRUD[ F XVXDOO\ RFFXUV ZKHQ WKHUH LV DQ XQGHUO\LQJ OXQJ GLVHDVH G LV FDXVHG E\ DLU OHDNLQJ DFURVV WKH SDULHWDO SOHXUD 35.3 A pneumothorax of <30% D ZLOO DOZD\V EH DVSLUDWHG ZKDWHYHU WKH W\SH E LV JHQHUDOO\ DV\PSWRPDWLF F XVXDOO\ UHTXLUHV KRVSLWDO DGPLVVLRQ LI LW LV VHFRQGDU\ WR UHV SLUDWRU\ GLVHDVH G LV WUHDWHG ZLWK SOHXURGHVLV 35.4 Secondary pneumothorax is a particular risk for D PHFKDQLFDO YHQWLODWLRQ IRU OXQJ GLVHDVH E WXEHUFXORVLV F SQHXPRQLD G DVWKPD

Chapters 36 and 37: Community-acquired pneumonia/Hospital-acquired (nosocomial) pneumonia 36.1 Concerning community acquired pneumonia D WKH LQFLGHQFH LV ± FDVHV SHU   SRSXODWLRQ

E WKH PRVW IUHTXHQWO\ LGHQWLILH RUJDQLVPV DUH *UDPQHJDWLYH EDFWHULD F ULVN IDFWRUV LQFOXGH DJH < > \HDUV G V\PSWRPV DOZD\V LQFOXGH SOHXULV\ DQG KDHPRSW\VLV 36.2 Concerning hospital acquired pneumonia D LQFLGHQFH LV ± RI DOO KRVSLWDO SDWLHQWV E WKH PRVW IUHTXHQWO\ LGHQWLILH RUJDQLVP LV Streptococcus pneumonia F ULVN LV GRXEOHG E\ PHFKDQLFDO YHQWLODWLRQ G WUHDWPHQW LV WKH VDPH DV IRU FRPPXQLW\ DFTXLUHG SQHXPRQLD 36.3 Which of the following statements in NOT true concerning the management of pneumonia? D &;5 LV XVHG WR FRQILU GLDJQRVLV E $QWLELRWLFV WKHUDS\ VKRXOG RQO\ VWDUW RQFH WKH LQIHFWLQJ RU JDQLVP LV LGHQWLILHG F 7\SLFDO DQG DW\SLFDO SQHXPRQLDV DUH GLIILFXO WR GLIIHUHQWLDWH G 2 WKHUDS\ LV FRPPRQO\ XVHG WR PDLQWDLQ SD o > 36.4 Which of the following does NOT suggest increased risk of mortality in patients admitted to hospital for pneumonia? D UHVSLUDWRU\ UDWH >PLQ E DJH > \HDUV F PHDQ EORRG SUHVVXUH > PP+J G XUHD > PPRO/

Chapter 38: Pulmonary tuberculosis 38.1 Which statement is INCORRECT concerning TB? D ,QIHFWLRQ ZLWK 7% LV YLD LQKDODWLRQ E 6XVFHSWLELOLW\ WR 7% LV JUHDWHU LQ WKH HOGHUO\ F ,QIHFWLRQ UHVXOWV LQ IRUPDWLRQ RI D JUDQXORPD G 7KH *KRQ IRFXV LV NQRZQ DV WKH SULPDU\ FRPSOH[ 38.2 Investigations of TB D WKH 0DQWRX[ WHVW LV RIWHQ QHJDWLYH LQ 0LOLDU\ 7% E WKH +HDI WHVW LV WKH PRVW FRPPRQO\ XVHG WHVW F 0LOLDU\ 7% LV HDVLO\ GHWHFWHG E\ XSSHU OREH VKDGRZLQJ LQ &;5 G Mycobacterium tuberculosis EDFLOOL DUH DFLGIDVW DQG JURZ UDSLGO\ 38.3 Which of the following is NOT a common feature of TB? D HU\WKHPD QRGRVXP E SOHXUDO HIIXVLRQV F SXOPRQDU\ RHGHPD G EURQFKLHFWDVLV 38.4 Treatment of TB D FRUWLFRVWHURLGV DUH SUHVFULEHG WR DOO SDWLHQWV E DQ LPSRUWDQW IDFWRU LV SDWLHQW FRPSOLDQFH ZLWK WKHUDS\ F GUXJ WUHDWPHQW LV PDLQWDLQHG IRU  PRQWKV LQ XQFRPSOLFDWHG FDVHV G 3\ULGR[LQH LV JLYHQ ZLWK LVRQLD]LG WR OLPLW OLYHU G\VIXQFWLRQ

Chapter 39: The immunocompromised host 39.1 Which of the following is NOT normally associated with immunosuppression? D GLDEHWHV E WUHDWPHQW ZLWK VWHURLGV F VPRNLQJ G PDOQXWULWLRQ Self-assessment questions

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39.2 Which of the following is NOT a consequence of chemotherapy? D QHXWURSDHQLD E LPSDLUHG 7FHOO IXQFWLRQ F FRPSOHPHQW GHILFLHQ \ G LQFUHDVHG VXVFHSWLELOLW\ WR IXQJDO LQIHFWLRQV 39.3 The HIV-positive patient D +,9 FDXVHV GHSOHWLRQ RI &' 7O\PSKRF\WHV E WKH FRPPRQHVW FKHVW LQIHFWLRQ LV 3&3 Pneumocystis jirovecii pneumonia F LQ WKH 8.  RI FDVHV ZLWK P\FREDFWHULXP WXEHUFXORVLV DUH FRLQIHFWHG ZLWK +,9 G Cytomegalovirus &09 LQIHFWLRQ LV UDUH LQ +,9 39.4 Which statement is NOT true concerning identification of respiratory infections in the Immunocompromised host? D &KHVW FRPSXWHG WRPRJUDSK\ FDQ EH GLDJQRVWLF IRU DVSHUJLOOR VLV E (DUO\ EURQFKRDOYHRODU ODYDJH FDQ DLG GLDJQRVLV LQ ∼ RI FDVHV F 3OHXUDO IOXL LV UDUHO\ LQYHVWLJDWHG LQ VXFK SDWLHQWV G &;5 PD\ VKRZ GLIIXVH LQILOWUDWH EXW EH RWKHUZLVH QRQ VSHFLILF

Chapter 40: Lung cancer 40.1 Lung cancer D KDV DQ RYHUDOO \HDU VXUYLYDO RI < E KDV DQ LQFUHDVHG ULVN RI  GXH WR SDVVLYH VPRNLQJ F LV OLNHO\ WR GHFUHDVH LQ ZRPHQ RYHU WKH QH[W  \HDUV G LV PRVW FRPPRQO\ FDXVHG LQ UXUDO DUHDV E\ QDWXUDO UDGRQ JDV 40.2 The least common type of lung cancer is: D VPDOO FHOO E VTXDPRXV FHOO F ODUJH FHOO G DGHQRFDUFLQRPD 40.3 In the context of lung cancer, which of the following is NOT a paraneoplastic syndrome? D /DPEHUW±(DWRQ V\QGURPH E LGLRSDWKLF RUWKRVWDWLF K\SRWHQVLRQ F H[WUDWKRUDFLF PHWDVWDVLV G &XVKLQJ¶V V\QGURPH 40.4 Staging for small cell cancer D DV limited disease SUHGLFWV PHGLDQ VXUYLYDO RI  \HDUV E DV extensive disease GHVFULEHV PHWDVWDWLF VSUHDG EH\RQG WKH KHPLWKRUD[ F LV VLPLODU WR WKDW IRU QRQVPDOO FHOO FDQFHU G GHSHQGV RQ WKH WXPRXU QRGH DQG PHWDVWDVLV FODVVLILFDWLR

Chapter 41: Acute respiratory distress syndrome 41.1 Which of the following is NOT part of the criteria for diagnosis of ARDS? D VHYHUH K\SR[DHPLD E K\SHUFDSQLD F ELODWHUDO GLIIXVH SXOPRQDU\ LQILOWUDWH RQ FKHVW ;UD\ G QHDU QRUPDO OHIW DWULDO SUHVVXUH 41.2 Which of the following statements about ARDS is true? D 7KH LQFLGHQFH RI $5'6 LV RQO\ VOLJKWO\ OHVV WKDQ WKDW RI DFXWH OXQJ LQMXU\ E $5'6 SUHFLSLWDWHG E\ VHSVLV KDV WKH JUHDWHVW PRUWDOLW\ F 0RVW SDWLHQWV GLH IURP K\SR[DHPLD DORQH 116

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G 7KH SULPDU\ GHIHFW LV LQFUHDVHG SHUPHDELOLW\ RI WKH DOYHRODU±FDSLOODU\ PHPEUDQH 41.3 Clinical features of ARDS D WKH DFXWH LQIODPPDWRU SKDVH ODVWV  KRXUV E WKH ODWH ILEURSUROLIHUDW YH SKDVH LV DVVRFLDWHG ZLWK PXOWLRUJDQ IDLOXUH F SQHXPRWKRUD[ LV FRPPRQ LQ WKH ODWH I EURSUROLIHUDWLYH SKDVH G WKH FRPELQDWLRQ RI F\DQRVLV G\VSQRHD FRQIXVLRQ DQG OXQJ FUHSLWDWLRQV LV GLDJQRVWLF 41.4 Which of the following is NOT generally beneficial in early ARDS? D DYRLGDQFH RI H[FHVVLYH IOXL ORDGLQJ E WUHDWPHQW ZLWK VWHURLGV DQG RWKHU DQWLLQIODPPDWRU DJHQWV F SK\VLRWKHUDS\ G 1RQLQYDVLYH RU IXOO PHFKDQLFDO YHQWLODWLRQ

Chapter 42: Mechanical ventilation 42.1 Mechanical ventilation D LV XVHG PRUH RIWHQ IRU W\SH  WKDQ W\SH  UHVSLUDWRU\ IDLOXUH E ZLOO DOZD\V EH QHHGHG IRU D SDWLHQW ZLWK D FHUYLFDO FRUG WUDQ VHFWLRQ DW & F LQ QRQVXUJLFDO SDWLHQWV LV LQFUHDVLQJO\ EHLQJ FDUULHG RXW XVLQJ QRQLQYDVLYH WHFKQLTXHV G LV UHODWLYHO\ IUHH IURP FRPSOLFDWLRQV 42.2 In a paralysed patient on intermittent positive pressure ventilation (IPPV) D LQVSLUDWLRQ LV EURXJKW DERXW E\ D IDOO LQ LQWUDSOHXUDO DQG DOYH RODU SUHVVXUH E LI K\SR[LD RFFXUV WKH WLGDO YROXPH DQG UHVSLUDWRU\ IUHTXHQF\ RI WKH YHQWLODWRU VKRXOG EH LQFUHDVHG F WKH XVXDO VHWWLQJV LQFOXGH DQ LQVSLUDWRU\ WLPH ZKLFK LV ORQJHU WKDQ WKH H[SLUDWRU\ WLPH G PLQXWH YHQWLODWLRQ LV XVXDOO\ DGMXVWHG WR PDLQWDLQ D PD co DW D QHDU QRUPDO OHYHO ∼ N3D  PP+J 42.3 Which statement is INCORRECT concerning continuous positive airway pressure (CPAP)? D ,W FDQ EH XVHG WR WDNH RYHU WKH ZRUN RI EUHDWKLQJ E ,W LV DSSOLHG XVLQJ D QDVDO RU IDFH PDVN F ,W FDQ EH XVHG WR SUHYHQW XSSHU DLUZD\V FROODSVH LQ VOHHS DSQRHD G ,W FDQ EH XVHG LQ LQWHUVWLWLDO GLVHDVHV WR UHGXFH 9$ 4 PLVPDWFK 42.4 Non-invasive intermittent positive pressure ventilation, NIPPV, D SURGXFHV D VLPLODU DLUZD\ SUHVVXUH SURILO WR WKH SURGXFHG E\ D WDQN YHQWLODWRU µLURQ OXQJ¶ E KHOSV UHGXFH WKH ZRUN RI EUHDWKLQJ DQG LV YHU\ XVHIXO IRU H[KDXVWHG SDWLHQWV ZLWK UHVSLUDWRU\ IDLOXUH F LV QRW D VXLWDEOH WHFKQLTXH IRU H[DFHUEDWLRQV RI VHYHUH FKURQLF REVWUXFWLYH SXOPRQDU\ GLVHDVH &23' G LV XVXDOO\ DSSOLHG WKURXJK DQ HQGRWUDFKHDO WXEH

Chapter 43: Oxygenation and oxygen therapy 43.1 Tissue hypoxia D RFFXUV ZLWKLQ  PLQXWHV RI IDLOXUH RI YHQWLODWLRQ E LV XQOLNHO\ LQ SDWLHQWV ZLWK SRO\F\WKDHPLD F FDQ EH FDXVHG E\ &2 SRLVRQLQJ G RQO\ RFFXUV ZKHQ SD o LV ORZ 43.2 In O2 therapy the initial target Sa o2 D VKRXOG DOZD\V EH OHVV WKDQ  WR SUHYHQW K\SHUFDSQLD

E VKRXOG EH ± LQ SDWLHQWV DW ULVN RI W\SH  UHVSLUDWRU\ IDLOXUH F VKRXOG DOZD\V EH DV KLJK DV SRVVLEOH G VKRXOG EH ± LQ SDWLHQWV ZLWK KLJK Pco DQG ELFDUERQDWH EXW QRUPDO S+ 43.3 Preferred method for O2 delivery in patients at the risk of type 2 respiratory failure D I [HG SHUIRUPDQFH 9HQWXUL PDVN ZLWK ± 2 E QDVDO FDQQXODH ZLWK ± 2 F QDVDO FDQQXODH ZLWK ± 2 G QRQUHEUHDWKLQJ UHVHUYRLU PDVN ZLWK ± 2 43.4 Which is NOT a recognized risk for high-dose O2 therapy? D FROODSVH RI SRRUO\ YHQWLODWHG DLUZD\V E DGXOW UHVSLUDWRU\ GLVWUHVV V\QGURPH $5'6 F SXOPRQDU\ K\SHUWHQVLRQ GXH WR SXOPRQDU\ DUWHU\ FRQVWULFWLRQ G FHUHEUDO YDVRVSDVP RU YDVRFRQVWULFWLRQ

Chapter 44: Sleep apnoea 44.1 Which of the following is NOT commonly associated with sleep apnoea? D GD\WLPH K\SHUVRPQROHQFH

E LQFUHDVHG ULVN RI K\SHUWHQVLRQ F LQFUHDVHG KDHPRJORELQ G QRFWXULD 44.2 Which statement is NOT true concerning obstructive sleep apnoea (OSA)? D  RI SDWLHQWV ZLWK VOHHS DSQRHD KDYH 26$ E 26$ LV DVVRFLDWHG ZLWK LQFUHDVHG QHFN FLUFXPIHUHQFH F 26$ LV HTXDOO\ FRPPRQ LQ PHQ DQG ZRPHQ G 26$ LV DVVRFLDWHG ZLWK 5(0 VOHHS 44.3 Which is generally the most long-term therapy for OSA? D PRGHUDWH ZHLJKW ORVV E QRFWXUQDO 2 WKHUDS\ F QDVDO FRQWLQXRXV SRVLWLYH DLUZD\ SUHVVXUH &3$3 G VXUJHU\ 44.4 Central sleep apnoea D LV DOZD\V GXH WR D GHIHFW LQ WKH UHVSLUDWRU\ FHQWUDO SDWWHUQ JHQHUDWRU E LV DOZD\V DVVRFLDWHG ZLWK GD\WLPH K\SHUFDSQLD F FDQ RFFXU GXULQJ 5(0 VOHHS LQ VRPH SDWLHQWV ZLWK &23' G FDQ EH HIIHFWLYHO\ WUHDWHG ZLWK &3$3

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120

Index

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Index

121

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122

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