respiratory system at aglance

1.The Respiratory System at a Glance

2. The Respiratory System at a Glance Jeremy P.T. Ward Jane Ward Richard M. Leach With contributions from Charles M. Wiener Third edition A John Wiley & Sons, Ltd., Publication 3. Library of Congress Cataloging-in-Publication Data 4. Contents Structure and function History, examination and investigation Diseases and treatment Cases and self assessment Contents 5 5. Preface to third edition The Respiratory System at a Glance At a Glance 6 Preface to third edition 6. Units and symbols Units Pressure conversion: = = = = = = = = = = = = Contents = = = = Standard symbols Primary symbols = = = P = = = = Q = Secondary symbols Gas = Blood = = = = = = = = = = = Tertiary symbols Examples = = = PAco = = Typical values Po Po Po Po Po < < > Pco Pco Pco + Po Pco Units and symbols 7 7. List of abbreviations Aa gradient Po Po 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 DLCO DLg DLO2 DRG DVT EBV ECG ECMO ECP EEG EGF ELISA EMG EOG ERV ESR FDG FDG PET FEF2575 FER FEV1 FEV1/FVC FGF FRC FVC GBM GM-CSF GU HAART HAP HCAP HIV HR HRCT ICU IFN- Ig IL ILD INPV IPF IPPV IRV IVC JVP KCO D co KS LA LDH LG LIP LMWH LT LV MBP 8 List of abbreviations 8. MDR MI MIE MMV MOF MRSA Staphylococcus aureus MVV NANC NHL NIPPV NRDS NREM NSAID NSC NSIP OSA P50 PA PA PA PACO PaCO2 PACO2 PAF PAH PaO2 PCP Pneumocystis carinii PD20FEV1 PDGF PE PEEP PEFR PET Pg PH pHa pKA PMF PMI PPD PPHN PSP R RAD RANTES RAW RBBB RBC REM RV RV RVD SaO2 SC SCUBA SIADH SIMV SLE SO2 SP STPD SVC TB TGF TLC TLCO DL co UFH UIP VAP VA/Q VC VEGF VIP VO2max VRG VT WBC WCC WG List of abbreviations 9 9. r1 Structure of the respiratory system: lungs, airways and dead space (a) Lung lobes Right lateral aspect Anterior aspect Left lateral aspect RU RM RL LU LL = Right upper = Right middle = Right lower = Left upper = Left lower Posterior aspect (c) Bohr equation for measuring dead space Anatomical dead space, Volume = VD Respiratory zone: Alveolar CO2 fraction = FACO2 End of inspiration End of expiration End-tidal = alveolar gas Anatomical dead space, Volume = VD In an expired breath none of the CO2 expired came from the dead space region Quantity of CO2 in mixed expired air = quantity of CO2 from alveolar region VT x = (VT VD) x VD = VT ( )/ Mixed expired gas: Volume = VT ; Mixed expired CO2 fraction = CO2-free gas CO2-containing gas RU RM RL LU LL RU RM RL LU LL LU LL RL RU T1 T12 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 C7 C6 (b) The airways Sternal angle (angle of Louis) Sternum Xiphoid process Diaphragm Nasal cavity Pharynx Epiglottis Larynx Cricoid Trachea (generation 0) Carina R and L main bronchi (generation 1) Bronchi (generations 211) Bronchioles (generations 1216) Respiratory bronchioles (generations 1719) Alveolar ducts and sacs (generations 2023) Body Manubrium FECO2 FECO2 FECO2 FACO2 FACO2FACO2 10 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 10. Lungs lungs thoracic cage right lung transverse oblique ssures left lung oblique ssure hilum bronchopulmonary seg- ments pulmonary nerve plexus vagi ganglia sympathetic trunk visceral pleura parietal pleura costodi- aphragmatic recess intercostal nerves phrenic nerve pleurisy Lymph channels bronchopulmonary nodes tracheobronchial nodes posterior mediastinal nodes upper respiratory tract lower respiratory tract cricoid cartilage right left main bronchi sternal angle Airways generation trachea main bronchi segmental bronchi Bronchioles terminal bronchioles respiratory bronchioles alveolar ducts alveolar sacs alveoli bronchial arteries pulmonary circulation ciliated columnar epithelial cells Goblet cells submucosal glands mucus mucociliary clearance type I alveolar pneumocytes squamous epithelium alveolarcapillary membrane type II pneumocytes surfactant Dead space conducting airways anatomical dead space pulmonary embolus alveolar dead space physiological dead space tidal volume respiratory frequency minute ventilation = Alveolar ventilation = Bohr method Alveolar gas end-tidal gas Pco ideal alveoli Structure of the respiratory system: lungs, airways and dead space Structure and function 11 11. r2 The thoracic cage and respiratory muscles c 1 2 3 4 5 6 7 8 9 10 (a) The sternum and ribs and their relationship to the lungs and pleural cavities Pleural Horizontal fissure Oblique fissure Costodiaphragmati recess Cardiac notch Oblique fissure Xiphoid process Body Manubrium Clavicle (b) Inferior aspect of a rib Sternum Articular facets of the head Head Neck Tubercle Articular facet of the tubercle Angle Costal groove Shaft Costal cartilage joins here (c) An intercostal space Intercostal: Vein Artery Nerve Innermost intercostal muscle 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 (d) Inferior aspect of the diaphragm Sternal part Xiphisternum Costal part Right phrenic nerve Inferior vena cava 12th rib Right crus Left crus Psoas major Quadratus lumborum Lateral arcuate ligament Medial arcuate ligament Median arcuate ligament Aorta Oesophagus Vagi Left phrenic nerve Central tendon of diaphragm External intercostal muscle Internal intercostal muscle Costal part L1 L2 L3 L4 T1 Lung lobes 12 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 12. Thoracic cage thoracic cage sternum ribs intercostal spaces thoracic vertebral column diaphragm The sternum sternum manubrium body of the sternum manubriosternal joint sternal angle (angle of Louis) xiphoid process The ribs and intercostal space true vertebrosternal vertebrochondral oating vertebral ribs head facets tubercle angle of the rib external intercostal muscles internal intercostal muscles innermost intercostal layer intercostal nerves thoracic nerves Intercostal veins arteries nerves The diaphragm diaphragm central tendon right crus left crus median arcuate ligament medial lateral arcuate ligaments psoas major quadratus lumborum phrenic nerves (C3, 4, 5) Muscles of respiration diaphragm intercostal muscles scalene muscles pump action bucket-handle action paradoxical breathing abdominal breathing thoracic breathing accessory inspiratory muscles scalene muscles sternomastoids serratus anterior pectoralis major abdominal muscles (rectus abdominis external internal oblique) The thoracic cage and respiratory muscles Structure and function 13 13. r3 Pressures and volumes during normal breathing Total lung capacity (TLC) Functional residual capacity (FRC) Residual volume (RV) 7300 mL mL mL3500 1 800 mL Open thorax: Pressure gradient distending the lung (transmural = alveolar intrapleural) Pressure gradient driving air along airways (mouth alveolar) Intrapleural Alveolar pressure Mouth 0.5 0.5 0.1 0 0 0.1 0.75 0.5 0 0.5 Volume above FRC (L) Intrapleural pressure relative to atmospheric (kPa) Alveolar pressure (kPa) Airflow (L/sec) Inspiration Expiration Inspiration Expiration (b) (a) Functional residual capacity (c) (d) (e) Air Air Outward recoil of chest wall Inward recoil of lungs Negative intrapleural pressure Chest wall expands Zero pressure Lungs collapse Intrapleural pressure, 0.5 kPa Alveolar pressure, 0 kPa Heart Oesophageal pressure, 0.5 kPa Table 1 Tidal volume (VT) (at rest) Vital capacity (VC) Inspiratory reserve volume (IRV) Expiratory reserve volume (ERV) 500 mL 5500 mL 3300 mL 1700 mL Inspiratory capacity (IC) 3800 VT VC IRV IC ERV TLC FRC 0 RV (i) (ii) (i) (ii) 14 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 14. Functional residual capacity functional residual capacity (FRC) intrapleural space outward recoil inward recoil barrel chest Intrapleural pressure visceral pleura parietal pleura intrapleural pressure oesophageal pressure Pressures, ow and volume during a normal breathing cycle alveolar pressure + + Lung volumes simple water-lled spirometer tidal volume resting tidal volumes inspiratory reserve volume (IRV) expiratory reserve volume (ERV) vital capacity (VC = VT + IRV + ERV) residual volume total lung capacity helium dilution body plethysmography nomograms Pressures and volumes during normal breathing Structure and function 15 15. r4 Gas laws (a) Altitude, barometric pressure, O2 fraction and PO2 Mt Everest summit 8850 m (29035 ft) Sea level 0m (0ft) 5486 m (18 000 ft) PB = 250 mmHg (33.3 kPa) 13 sea level value FO2 dry air = 0.209 (20.9% O2) PO2 dry air = 0.209 x 250 = 52 mmHg (7 kPa) PB = 380 mmHg (50.6 kPa) 12 sea level value FO2 dry air = 0.209 (20.9% O2) PO2 dry air = 0.209 x 380 = 79 mmHg (10.6 kPa) 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) Barometric pressure with increasing altitude 800 700 600 500 400 300 200 100 0 0 10000 10 000 12000 13000 14 000 16000 18000 20000 30000 40000 50 000 60 000 20000 4000 6000 8000 Altitude (metres) Altitude (feet) Barometricpressure(PB ,mmHG) Sea level (0m, 0ft) Mexico City (2240 m, 7349 ft) Lhasa, Tibet (3600 m, 11810 ft) La Rinconda, Peru* (5100 m, 16 732 ft) Mt Everest summit (8850 m, 29 035 ft) Cruising altitude typical passenger jet (11 278 m, 37 000 ft) *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 + 37 273 + tO C PB PH2O PB 6.3* *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 Gas phase (Pg) Liquid phase liquid X (PXg) Gas phase (Pg) Liquid phase liquid Y (PYg) P1 Liquid X containing dissolved gas, g, is exposed to a gas phase containing g at three different partial pressures, P1, P2, P3. Only when the Pg = P2 does the number of gas molecules leaving the 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 (PXg) =P2 Liquid Y also contains gas, g, and is also in equilibrium with the gas phase when Pg = P2 Partial pressure of gas, g, in liquid Y (PYg) =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. 273 273 + tO C PB PH2O 101* 2 P3 P1 2 P3 Note: In the bottom left flask, gas moves against its concentration gradient. P P PB=760mmHg 101.3kPa PB=380mmHg 50.6kPa PB=250mmHg 33.3kPa 16 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 16. Fractional concentration and partial pressure of gases in a gas mixture Daltons law = = F P = F P = . = . altitude Water vapour pressure saturated water vapour pressure relative humidity Fo Fn Pb Pb partial pressure of moist inspired oxygen PIO2 = . P Pio = Po Pio Pio Pio The effect of pressure and temperature on gas volumes Boyles law = + Charles law ambient temperature and pressure saturated with water (ATPS) body temperature and pressure saturated with water (BTPS) standard temperature and pressure dry (STPD) Ph o = Gases dissolved in liquids Henrys law = partial pressure of a gas in a liquid gas tension Note on time derivative symbols Gas laws Structure and function 17 17. r5 Diffusion (a) The alveolarcapillary membrane (c) Diffusion through a sheet of tissue (d) The diffusion path through the alveolarcapillary membrane Alveolar epithelium O2 Alveolus Red blood cells Capillary (e) The oxygen cascade: oxygen tension from ambient air to mitochondria mmHg PO2 200 150 100 50 0 25 20 15 10 5 0 kPa Ambient,sea level Trachea (moistureadded) Alveolar(O 2takenup,CO 2added) Pulmonarycapillary(equilibrateswithalveolar) Arterial(R toLshunt,e.g.bronchialcirculation) M eantissuecapillary(veryvariable) M itochondria tissuecells(veryvariable) Restingmixed venousblood (venousvarieswithtissue) (b) Transfer of gases across alveolarcapillary membrane Alveolar Capillarypartial pressure 0 0 0 .25 0.5 0.75 Time along pulmonary capillary (second) CO O2 N2O Mixed venous blood T = thickness P1 A = area P2 Interstitial fluid Endothelium O2 O2 O2 O2 Red blood cells Pore of Kohn (gap between alveoli) Endothelium Alveolar epithelium Collagen and elastin fibres Alveolus AlveolusAlveolus Plasma pressure of N20, 02 or CO 18 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 18. bulk ow diffusion The alveolarcapillary membrane alveolar epithelium pulmonary capillaries elastin collagen bres alveolar epithelium capillary endothelium alveolarcapillary membrane < Type I pneumocytes type II pneumocytes Diffusion and perfusion limitation Pn o Pn o perfusion-limited Pco diffusion-limited Factors affecting diffusion across a membrane (Fick and Grahams laws) P P = P P diffusing capacity D , = D P PC , D o = o P o P o D o Po P o D o D co Pco D co = co P co D co Pco D co Kco D o D co T o T co Factors affecting DLco (TLco) D co D co Kco D co D co D co D co P co The oxygen cascade Po Po Po Po Po Diffusion Structure and function 19 19. r6 Lung mechanics: elastic forces (a) Static pressurevolume loop Volume%TLC 100 50 0 FRC RV P V CL = slope V/P 0 1 2 10 20 cmH2O kPa Transmural pressure (= intrapleural pressure since measurements taken at zero airflow) RV TLC = Residual volume = Total lung capacity FRC CL = Functional residual capacity = Lung compliance (c) Surface tension Laplaces equation T= Surface tension Pressure above ambient = P 1 P2 P1 > P2 When tap is opened the small bubble empties into the large (d) Effect of surface area R1 Water molecule Surfactant molecule R2 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 P= 2T R (b) Dynamic pressurevolume loop If intrapleural pressure and volume are recorded continuously (lower panel), a pressurevolume 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. Volume above FRC (litre) Intrapleural pressure relative to atmospheric 0.5 0 0.5 1.0 Inspiration Expiration Inspiration Expiration VolumeaboveFRC(litres) 0.5 0.4 0.3 0.2 0.1 0 0.5 0.6 0.7 0.8 0.9 1.0 Intrapleural pressure relative to atmospheric (kPa) a,a' b,b' c,c' d,d' e,e' f,f' g,g' h,h' i,i' j,j' a b c d e f g h i j a b c d e f g h i j R R P 20 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 20. airway resistance elastic resistance Assessing the stiffness of the lungs: lung compliance = static pressurevolume (PV) curve hysteresis Static lung compliance restrictive disease elastic recoil emphysema TLC FRC FEV FVC Dynamic pressurevolume loops and dynamic compliance dynamic pressurevolume loop dynamic compliance static compliance The airuid interface lining the alveoli surface tension = law of Laplace = 1 2 atelectasis surfactant Surfactant phospholipids type II pneumocytes alveolar lining uid hydrophilic hydrophobic alveolar interdependence neonatal respiratory distress syndrome (NRDS) Lung mechanics: elastic forces Structure and function 21 21. r7 Lung mechanics: airway resistance (a) Laminar and turbulent flow Laminar flow Turbulent flow (b) Main factors influencing bronchomotor tone (d) Dynamic compression of airways = Flowvolume 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 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 flowvolume 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 flowvolume loop alone). (c) The effect of effort on inspiratory and expiratory airflow Effort dependent 600 300 0 300 600 Airflow(L/min) ExpirationInspiration TLC RV Volume (L) Effort independent A B (e) Maximum flowvolume loops 6 4 2 0 Lung volume (L) 6 5 4 3 2 1 1 2 3 4 5 6 600 300 0 300 600 Airflow(L/min) ExpirationInspiration Beginning of inspiration Alveolus Intrathoracic airway Intrapleural space 0.5 0 8.7 8 6 4 0 +8.0 Numbers are pressures in kPa (1 kPa = 7.5 mmHg) 0 0 During forced expiration Airway smooth muscle Synapse Vagal efferents Pulmonary stretch receptors (inhibit) Vagal afferents Brainstem (Chapter 12) Airway irritant receptors (activate) NANC nerves (excitatory) Mast cells, eosinophil (Chapter 23) Histamine, Prostagladins Leukotrienes etc 2-Receptor -Adrenergic agonists (e.g. adrenaline and saltbutamol) NANC nerves (inhibitory) NO and VIP CO2 ACh via M3 receptors BronchodilationBronchoconstriction SP and neurokinins = Receptor = Nerve ending Nitric oxide Vasoactive intestinal peptide Substance P NO = VIP = SP = ACh = M3 = Acetylcholine Muscarinic type 3 receptor 22 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 22. = = = laminar ow l Poiseuilles equation = = = silent zone turbulent Factors affecting airway resistance Bronchial smooth muscle and epithelium parasympathetic bron- choconstrictor epinephrine Transmural (airwayintrapleural) pressure gradient = = effort-dependent effort-independent Peak expiratory ow rate dynamic compression of airways RAW in disease forced expiratory volume in 1 second forced vital capacity forced expiratory ratio = obstructive pulmonary disease air trap- ping Expiratory wheezes (rhonchi) Lung mechanics: airway resistance Structure and function 23 23. r8 Carriage of oxygen (a) Haemoglobin structure Haemoglobin is composed of four subunits, each containing a protein chain (globin) and a haem group. Normal adult haemoglobin, HbA, contains two identical -chains composed of 141 amino acids and two -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 (b) The oxygenhaemoglobin dissociation curve, haemoglobin concentration (150g/L) 100 75 50 25 0 200 150 100 50 0 10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 kPa PO2 50 100 150mmHg a v pH, PCO2, temperature 2,3-DPG pH, PCO2, temperature 2,3-DPG Dissolved oxygen O2 O2 O2 O2 0 Oxygencontent(mL/L) Oxygensaturation(%) a PO2 = Normal arterial blood = 13.3 kPa (100mmHg) v PO2 = Resting mixed venous = 5.3 kPa (40mmHg) = 150 mL/L = 75% (c) Anaemia and carbon monoxide poisoning 200 150 100 50 0 0 2 4 6 8 10 12 14 16 kPa PO2 0 20 40 60 80 100 mmHg120 Oxygencontent(mL/L) Tissues remove 50mL/L C B A Hb = 150g/L Hb = 75g/L Hb = 150g/L COHb = 50%Tissues remove 50mL/L = 200 mL/L = 97% O2 content O2 saturation Note: For simplicity the Bohr shift is ignored O2 content O2 saturation 24 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 24. Po Po solubility Po haemoglobin oxygen capacity Po oxygen saturation / / cooperative binding oxygenhaemoglobin dissociation curve Po Po Po < Po Po Pco Bohr effect Pco Po P = Pco = = P = P 2,3-di(or bi)phosphoglycerate P Anaemia and carbon monoxide poisoning anaemia Po = Po Po = = Po Po carboxyhaemoglobin cyanosis Other respiratory pigments Fetal haemoglobin, HbF adult haemoglobin, HbA double Bohr shift Pco Po Myoglobin Po Carriage of oxygen Structure and function 25 25. r9 Carriage of carbon dioxide (a) CO2 dissociation curve 550 500 450 CO2content(mL/L) 5.5 6.0 6.6 7.0 40 45 50 55 (mmHg) 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). (kPa) (c) How CO2 is carried in arterial and venous blood 480mLCO2/L 520mLCO2/L The basis of the Haldane effect 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. the ability of each reduced (deoxygenated) Hb subunit (HHb) to buffer H+ and form HbCOOH (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 HbCOOH When blood is reoxygenated in the lungs, the reverse occurs, facilitating removal of CO2 in the breath (b) CO2 uptake and O2 delivery in the tissues role of red cells CA = carbonic anhydrase Hb = haemoglobin subunit HHb = reduced haemoglobin O2 Red cell CA H2O H2O Chloride shift Carbamino formation Hb4(O2)4 Hb4(O2)3 Hb4(O2)2 Hb4(O2) Normal mixed venous Normal arterial 75% O2 saturation 98% O2 saturation Haldane effect Arterial Mixed venous 5% 87% 8% Dissolved 10% HCO3 Carbamino 30% 60%A V X CO2 + H2O H2CO3 HCO3 + H+ CO2 + HHb Hb4(O2)4 Hb4(O2)3 HbCOOH Cl Cl HCO3 CO2 26 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 26. CO dissociation curve Bicarbonate + + + carbonic anhydrase + + chloride shift + + haemoglobin acts as a buffer + + Haldane effect Pco + + + Carbamino compounds + CO2 in solution Hypoventilation and hyperventilation P co Vco V P co Vco V P co P co Pco P co P co Po difference Hypoventilation hyperventilation P co hypoventilating P co hyperventilating P co Po Hypoventilation hypercapnia P co hypoxia P o P co hypocapnia Respiratory gas exchange ratio Carriage of carbon dioxide Structure and function 27 27. r10 Control of acidbase balance CO2 + H2O H2CO3 HCO3 + H+ [HCO3] x [H+] [H2CO3] K = [HCO3] [H2CO3] log K = log [H+] + log [HCO3] [H2CO3] log [H+] = log K + log [HCO3] [H2CO3] pH = pK + log [HCO3] PCO2 x s pH = 6.1 + log But: [H2CO3] [CO2] (pKA = 6.1) and: [CO2] = PCO2 x s (solubility) K = dissociation constant; KA = corrected for [CO2] instead of [H2CO3] Solubility (s) = 0.23 mmol / L / kPa 0.03 mmol / L / mmHg Relationship between PCO2, HCO3 and pH, and the HendersonHasselbalch equation (from law of mass action) (a) Plasma[HCO3](mmol/L) 40 30 20 10 7.1 7.2 7.3 7.4 7.5 7.6 7.7 pH PCO2 60 mmHg (7.8 kPa) PCO2 40 mmHg (5.3 kPa) PCO2 20 mmHg (2.6 kPa) (b) Davenport diagram [H+ ] (nmol/L) pH 120 100 80 60 40 20 6.9 7.0 7.1 7.2 7.3 7.4 7.5 7.6 0 0 2 4 6 8 10 10 20 30 40 50 60 70 80 PaCO2 (mmHg) PaCO2 (kPa) (d) Flenley acidbase nomogram Metabolic acidosis Normal range Polycythaemia ( red cells) Plasma buffer line C B A Plasma[HCO3](mmol/L) 40 30 20 10 7.1 7.2 7.3 7.5 7.6 7.7 pH PCO2 60 mmHg (7.8 kPa) PCO2 20 mmHg (2.6 kPa) (c) Compensation and base excess C B A Base excess D F E G Renal compensation Metabolic alkalosis Respiratory compensation Respiratoryalkalosis Renal compensationMetabolic acidosi s Respiratoryacidosis Acute respiratory acidosis Chronic respiratory acidosisMetabolic alkalosis Respiratory alkalosis Whole blood buffer line PCO2 40 mmHg (5.3 kPa) 7.4 24 28 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 28. + = acidbase status Buffers + buffer curve bicarbonate haemoglobin + Pco HendersonHasselbalch equation Pco Pco P Pco Haemoglobin blood proteins Acidosis, alkalosis and compensation Pco Davenport diagram Pco buffer line Pco Pco Pco acute respiratory failure Pco respiratory acidosis respiratory alkalosis chronic respiratory failure compensated + Pco renal compensation metabolic acidosis alkalosis + metabolic acidosis Pco respiratory compensation metabolic alkalosis Base excess Pco Pco Po Base excess base decit calculated Pco Pco Pco Pco in vitro Flenley nomogram Pco Common causes of acidbase disorders Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis + Control of acidbase balance Structure and function 29 29. r11 Control of breathing I: chemical mechanisms (d) Central chemoreceptors Pons Medulla oblongata V VII VIII IX X XI Cranial nerves Central chemoreceptors (f) Peripheral chemoreceptors Vagus nerve Aorta Carotid sinus nerve Bifurcation Carotid sinus Common carotid artery Glosso- pharyngeal nerve Heart Groups of cells surrounded by fenestrated sinusoidal capillaries Sheath (type II) cells Glomus (type I) cells Dense granules containing neurotransmitters Carotid sinus nerve fibres Glial cells Capillary Neurone Bloodbrain barrier Chemoreceptor Blood HCO3 H+ CO2 O2 H+ , HCO3 CO2 + H2O H2CO3 H+ + HCO3 [H+ ] at chemoreceptor PCO2 / [HCO3 ] PCO2 from blood, and [HCO3 ] from CSF CSF CSF Carbonic anhydrase (a) (b) (c) (e) (g) Ventilation(L/min) 60 50 40 30 20 10 0 4 5 6 7 8 9 Alveolar PCO2 (kPa) Effect of CO2, pH and O2 on ventilation: Metabolic acidosis Metabolic alkalosis Normal pH Low PO2 ~5 kPa High PO2 ~60 kPa Normal PCO2 5 kPa High PCO2 6 kPa PO2 (kPa) Ventilation(L/min) 60 50 40 30 20 10 0 4 5 6 7 8 9 Alveolar PCO2 (kPa) Ventilation(L/min) 60 50 40 30 20 10 0 4 8 12 16 Normal PO2 ~13 kPa Carotid body (not part of sinus) Aortic bodies 30 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 30. Chemical control of ventilation central peripheral chemoreceptors Pco Po brainstem Pco Pco Po Ventilatory response to changes in PAco2 and PAo2 Pco P co P co P co P co P co metabolic acidosis + metabolic alkalosis + Pco respiratory acidosis P o P o P co P co P co P o P o P co synergistic P o P co The central chemoreceptor central chemoreceptor not Po bloodbrain barrier + Pco Pco Pco The peripheral chemoreceptors peripheral chemoreceptors carotid aortic bodies glomus sheath Pco + Po not Pco Po Pco Po + + Adaptation: chronic respiratory disease and altitude Pco Pco P co Po hypoxic drive Po P o Po hypocapnia Pco acclimatization to altitude Control of breathing I: chemical mechanisms Structure and function 31 31. r12 Control of breathing II: neural mechanisms (a) Pneumotaxic centre (b) Dorsal respiratory group Hypothalamus Emotion Temperature Cortex (g) Voluntary control of breathing via pyramidal tracts Spinal cord Respiratory muscles Lungvolumeandmuscleload Damage,inhaledirritants (c) Ventral respiratory group Medulla Pons (f) Input from central and peripheral chemoreeceptors (e) Lung receptors Stretch Proprioceptors Irritant Juxtapulmonary (d) Descending respiratory motor neurones to diaphragm, intercostals and ancilliary respiratory muscles Cut here Gasping Cut here No effect on breathing but loss of higher control Cut here Abolition of breathing apnoea Nucleus parabrachialis Klliker-Fuse nucleus Btzinger complex Nucleus ambiguus and retro ambiguus Nucleus tractus solitarius 32 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 32. central pattern generator sensors chemoreceptors mechanoreceptors Brainstem and central pattern generator central pattern generator pons medulla inspiratory expiratory Reciprocal inhibition The medulla dorsal respiratory group nucleus tractus solitarii nucleus ambiguus caudal rostral ventral respiratory groups pre-Botzinger Botzinger gasping pneumotaxic centre nucleus parabrachialis KollikerFuse nucleus pons apneusis apneustic centre pyramidal tracts Ondines curse origin of the respiratory rhythm switching concept Lung receptors and reexes Stretch receptors slowly adapting HeringBreuer inspiratory reex deation reex > Juxtapulmonary or J receptors apnoea Irritant receptors Proprioceptors (position/length sensors) Other receptors that may modulate respiration: Pain receptors trigeminal region larynx Arterial baroreceptors Control of breathing II: neural mechanisms Structure and function 33 33. r13 Pulmonary circulation and anatomical right-to-left shunts (a) Pulmonary and systemic circulation and normal anatomical right-to-left shunts Pulmonary capillary pressure: Arterial end 14 mmHg Venous end 8 mmHg Bronchial artery Pulmonary artery pressure: 24/9, mean 15 mmHg VCM Aortic pressure: 120/70, mean 90 mmHg VCM = venae cordis minimae (thebesian veins) Alveoli Venous end 10 mmHg Arterial end 30 mmHg Systemic capillary pressure: Aorta Tissue LARA RV LV The PO2 and PCO2 that result from these O2 and CO2 contents can be found from the O2 and CO2 dissociation curves: 700 600 500 400 300 200 100 0 1 31 75 119 13 15 PO2/PCO2 (kPa) O2 and CO2 dissociation curves O2 CO2 Normal O2 and CO2 pressures and contents (b) The initial effects of a 20% right-to-left shunt on arterial O2 and C02 contents and partial pressures Arterial O2 content = Arterial CO2 content = + x + x O2andCO2content(mL/L) 80 100 20 100 x 200 15 = 190mL/L 80 100 20 100 x 480 520 = 488mL/L O2 content CO2 content = 200mL/L = 480mL/L O2 and CO2 pressures and contents following mixing 20% mixed venous blood with 80% blood undergoing normal gas exchange *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. *O2 content *CO2 content = 150 mL/L = 520 mL/L 80% 34 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 34. Pulmonary circulation compared with the systemic circulation pulmonary circulation systemic circulation Pulmonary vascular resistance pulmonary artery pressure hypoxic pulmonary vasoconstriction Pco autoregulation Starling forces The Cardiovascular System at a Glance Capillary oncotic pressure interstitial oncotic pressure interstitial hydrostatic pressure Pulmonary oedema mitral stenosis left ventricular failure Inspira- tory crepitations Anatomical or true right-to-left shunts bronchial circulation venae cordis minimae (Thebe- sian veins) right-to-left shunts Po Po At- electasis consolidation pneumonia cyanotic congenital heart disease tetralogy of Fallot left-to-right shunts Effect of right-to-left shunts on arterial blood gases Po Pco P o P co P co Po P co P o P co Pulmonary circulation and anatomical right-to-left shunts Structure and function 35 35. r14 Ventilationperfusion mismatching VA/Q (a) Different types of VA/Q regions PO2 and O2 contents of blood from these regions breathing air and oxygen Normal Dead space Dead-space effect Shunt effect True/anatomical shunt VA Q VA/Q = Normal = Normal = Normal (close to 1) VA Q VA/Q = Normal = 0 = VA Q VA/Q = Normal = Low = High VA Q VA/Q = Low = Normal = Low VA Q VA/Q = 0 = Normal = 0 PO2 kPa (c) The effect of a mixture of high and low VA/Q regions on arterial blood gases VA/Q = 4 Q = 1 VA/Q = 0.3 Q = 15 Small flow with: High PO2 Normal O2 content Low PCO2 Low CO2 content Large flow with: Low PO2 Low O2 content High PCO2 High CO2 content Combined to give: Low O2 content High CO2 content Low PO2 Slightly high PCO2 Peripheral and central chemoreceptors Ventilation Final picture: Low O2 content Normal or low CO2 content Low PO2 Normal or low PCO2 3 2 1 0 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 PAO2 ~ PO2 PaCO2 R = 0 10 20 02 content (mL/L) 200 0 0 10 20 02 content (mL/L) 200 0 0 10 20 02 content (mL/L) 200 0 0 10 20 02 content (mL/L) 200 0 PO2 kPa PO2 kPa PO2 kPa O2 content of blood draining the region breathing air ( ) and breathing O2-enriched air ( ): Normal Unchanged No blood draining this region Low Increased Low Unchanged Normal Unchanged (b) Variation of ventilation, VA, perfusion, Q and ventilationperfusion ratio, VA/Q withvertical height in the upright lung VA Q R = The respiratory gas exchange ratio = (R is usually about 0.8) PO2 = Inspired O2 partial pressure PaCO2 = Arterial CO2 partial pressure ( alveolar) CO2 production O2 consumption VA = 4 VA = 5 Ventilation,VA,perfusion,Q(arbitraryunitsper unitlungvolume)andventilationperfusionratio,VA/Q Base Apex 36 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 36. = = dead-space effect Po Pco shunt effect venous admixture Po Pco Po Effect of the upright posture on perfusion, ventilation and VA/Q P o Ventilationperfusion matching in disease Hypoxic vasoconstriction Effect of ventilationperfusion mismatching on arterial blood gases Po Po < P o P o P co P co P o P o P co oxygen-enriched air Po Assessment of ventilationperfusion mismatching Po Po alveolar air equation Aa Po gradient = Po = Po < Ventilationperfusion mismatching Structure and function 37 37. r15 Exercise, altitude and diving PvCO2 Table 1 Typical values in a healthy but sedentary 20-year-old man at rest and in max. exercise Rest Maximal exercise Heart rate (bpm) 70 200 Stroke volume (mL) 75 90 Cardiac output (mL/min) 5 250 18 000 Arterialmixed 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 (*= O2 extraction) mmHg Rest Oxygen consumption Anaerobic threshold kPa pHa PO2/PCO2 20 7.2 7.4 0 0 1 2 3 4 L/min 0 25 50 75 100 VO2 20 40 60 80 100 120 140 0 20 40 60 80 100 120 140 160 Ventilation (L/min) V . 15 10 5 0 kPa 6 5 0 (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. 14 Alveolar ventilation 12 10 Alveolarventilation(L/min) 8 6 4 2 0 0 1000 2000 3000 Altitude (m) 4000 5000 6000 120 A Alveolar PO2 100 80 60 40 20 0 0 1000 2000 3000 Altitude (m) 4000 5000 6000 45 Alveolar PCO2 40 35 AlveolarPCO2 30 25 20 15 10 5 0 0 1000 2000 3000 Altitude (m) 4000 5000 6000 B A B A B (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. PaO2 pHa PaCO2 PvO2 4 3 2 1 mmHg kPa 16 12 0 AlveolarPCO2 8 4 mmHg . 38 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 38. Exercise Oxygen delivery Oxygen extraction oxygen consumption = Po Pco + maximum oxygen consumption (VO2 max) V Po Pco P o P co anaerobic threshold P co Altitude Po P P Po P o P co P co P co Acute mountain sickness high-altitude pulmonary oedema high-altitude cerebral oedema acclimatization P o P co Erythropoietin 2,3-diphosphoglycerate P co P co chronic mountain sickness (Monges disease) Diving diving response SCUBA diving Pn Pn nitrogen narcosis Decompression sickness the bends Exercise, altitude and diving Structure and function 39 39. r16 Development of the respiratory system and birth 2 (a) Branching morphogenesis Epithelium Mesoderm Signalling factors Factors released by mesoderm cells cause the epithelium to grow inwards towards them as a bud; inhibitory factors prevent budding either side (b) Week 4 Week 5 Week 6 Week 8 4th pharyngeal pouch Trachea Embryonic oesophagus Bronchial buds Laryngo- tracheal tube Secondary bronchi Mesoderm Endoderm/ epithelium Segmental bronchi + + + + RA RV LV LA 1 7 3 4 6 5 (c) Fetal circulation Foramen ovale Fetal liver Pulmonary artery Ascending aorta Portal vein Aorta Inferior vena cava Umbilical vein Umbilical arteries Superior vena cava Ductus arteriosus Ductus venosus Placenta 8 Before birth: Pulmonary vascular resistance > Systemic vascular resistance Ductus arteriosus OPEN Foramen ovale OPEN Ductus venosus OPEN O2 saturation in aorta ~67% PO2 in aorta ~4 kPa, 30 mmHg After birth: 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 40 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 40. embryological origins endoderm splanchnic mesoderm branching morphogenesis 1. Embryonic period laryngotracheal tube bronchial buds 2. Pseudoglandular period segmental bronchopulmonary segment 3. Canalicular period terminal sacs type I alveolar pneumocytes alveolocapillary membrane type II alveolar pneumocytes neonatal respiratory distress syndrome 4. Saccular (terminal sac) period 5. Alveolar period Fetal breathing oligohydram- nios Fetal circulation and birth placenta ductus venosus foramen ovale ductus arteriosus P o At birth surfactant Po Development of the respiratory system and birth Structure and function 41 41. r17 Complications of development and congenital disease (a) Relationship between prematurity and development of NRDS %Neonatesdeveloping NRDS 80 60 40 20 0 Birth weight: Gestational age: < 2 Environmental and social factors r Asthma 3 Working conditions Smoking cessation > Management a Behavioural Strategies r A r A r A r A r A b Pharmacotherapy r Nicotine replacement therapy (NRT) r Antidepressants Bupropion (Zyban) Nortryptiline r Varenicline Public health and smoking Diseases and treatment 53 53. r23 Respiratory failure (a) Causes of respiratory failure Central drive CNS-depressant drugs (e.g. barbiturates) Head injury Cerebrovascular accident Primary alveolar hypoventilation Airway obstruction Foreign body or tumour Asthma COPD 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 Respiratory muscles Muscular dystrophies Peripheral nerves GuillainBarr Neuromuscular junction Myasthenia gravis Muscle relaxants (b) Mechanisms of arterial hypoxia (low PaO2) Normal Normal alveolarcapillary membrane >98% cardiac output passing through gas- exchanging alveoli Normal PaO2 Normal alveolar ventilation Normal PO2 Matching of ventilation and perfusion throughout the lungs (c) Effects of hypoxia and hypercapnia Low PaO2 (hypoxaemia/ hypoxia) High PaCO2 (hypercapnia) Acute 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 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 Chroniccompensation and complications 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 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) Other Cyanotic congenital heart disease Pulmonary emboli Pulmonary oedema 2. Hypoventilation Inadequate alveolar ventilation low alveolar PO2 4. Ventilationperfusion mismatching Blood from areas with high VA/Q mixes with blood from low VA/Q areas low pulmonary venous PO2 5. Right-to-left shunt Shunted blood fails to undergo gas exchanges, mixes with pulmonary capillary blood low pulmonary Air or alveolar gas with normal PO2 Air or alveolar gas with reduced PO2 Deoxygenated blood (mixed venous or right-sided) Normal, fully oxygenated Incompletely oxygenated blood venous/left ventricular PO2 3. Diffusion impairment Pulmonary capillary blood fails to reach equilibrium with alveolar gas low pulmonary end-capillary PO2 1. Low inspired PO2 e.g. altitude (low PB) or low inspired O2 concentration low alveolar PO2 54 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 54. Po type 1 respiratory failure Pco type 2 or ventilatory failure Pco acute chronic acute on chronic dyspnoea Po tachypnoea Mechanisms leading to hypoxia and hypercapnia hypoventilation P co P Aa Po gradient right-to-left shunts ventilationperfusion mismatching diffusion impairment Effects of hypoxia and hypercapnia Cyanosis peripheral cyanosis central cyanosis Respiratory failure in asthma P co P co Respiratory failure in chronic obstructive pulmonary disease pink puffer blue bloater P o P co P co P co P co F o P o Management Respiratory failure Diseases and treatment 55 55. r24 Asthma: pathophysiology (a) Cartoon of airway wall EpitheliumMucusSmooth muscle (b) Hyperrresponsiveness (c) Main causes of asthma Bronchoconstriction hyperresponsiveness, remodelling Epithelial damage Mucus hypersecretion Mucosal oedema Inflammatory cell infiltration Airwayresistancetoairflow Severe asthma Mild asthma Healthy Dose of stimulus (e.g. inhaled histamine) Housedustmite Pollen Dander Spores 5 15 Minutes 4 86 10 2 4 Inflammation, mucosal oedema, mucus, epithelial damage Hyperresponsiveness, bronchoconstriction and airway remodelling Bronchoconstriction DaysHours (e) Cellular mechanisms Goblet cell Sub-mucosal gland Mucus Smooth muscle growth Vascular leak Mucosal oedema TH2 lymphocyte Antigen presenting cell Cytokines Cytokines Eosinophil Histamine, PgD2 LTC4, LTD4 Epithelium Antigen 65% 80% 40% 20% Patients often allergic to more than one allergen FEV1 Allergen challenge (d) Typical response of an atopic asthmatic to inhaled antigen Mucus Smooth muscle IgE Mast cell Cyto kines PAF,LTC4 , LTD 4 MBP,ECP Immediate response Late-phase response Recurrent attacks 56 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 56. 1 Narrowing of the airways 2 hyperresponsiveness 3 inammatory cells hypersecretion of mucus mucus plugs oedema epithelial shedding remodelling of the airway wall Prevalence antigens tobacco smoke exhaust fumes emo- tional stress exercised-induced asthma viral infections occupational asthma Classication extrinsic intrinsic IgE antibodies allergic atopic asthma IgE-independent Atopic asthma house dust mite Dermatophagoids pteronyssinus DerP pollen domestic pets fungal spores immediate response late-phase response iso- cyanates isolated late phase recurrent asthma attacks type I hypersensitivity mast cell degranulation histamine prostaglandin D leukotriene C D type IV cell-based hypersensitivity TH2 lymphocytes cytokines eosinophils neutrophils antigen presenting cells leukotrienes PAF major basic protein eosinophil cationic protein Drug-associated asthma Asthma: pathophysiology Diseases and treatment 57 57. r25 Asthma: treatment (a) Step-wise approach to asthma therapy (adult) Based on British Thoracic Society guidelines, 2009, update brit-thoracic.org.uk/ Move down to the lowest step for adequate control Move up to improve control (but review compliance) Inhaled short-acting 2- agonist as required Step 1 ADD: Inhaled low-dose steroid Step 2 ADD: Inhaled long- acting 2-agonist If improvement but still poor control, increase inhaled steroid (to 800 g/day) If no improvement, increase steroid and trial leukotriene receptor antagonist or SR theophyline Consider trials of: Increased inhaled steroid to high dose 2000 mg/day Addition of 4th drug: leukotriene receptor antagonist SR theophyline oral 2-agonist ADD: Oral steroid, lowest dose possible Consider other treatments to minimize use of oral steroids Step 3 Step 4 Step 5 Control of asthma is defined as: No daytime symptoms No need for rescue medication No limitations on activity No night-time awakening due to asthma No exacerbations Normal lung function 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 (c) Pressurized metered dose inhaler Maintain high-dose inhaled steroid Refer to specialist (b) Most common drug classes used in asthma Type Route and example Effect Adverse effects 2agonist (adrenoreceptor agonists) Inhaled, oral, intravenous (IV) Short-acting: salbutamol (albuterol) Long-acting: salmeterol, formoterol Muscle tremor (most common) Tachycardia, palpitations (high dose) Corticosteroids Xanthines Muscarinic receptor antagonists Antileukotrienes Receptor antagonist Lipoxygenase inhibitor Inhaled: Oral: IV: Beclometasone proprionate Prednisolene Hydrocortisone Oral, IV: Theophylline, aminophylline Slow release (SR) formulations Inhaled: Ipratropium bromide Oral: Montelukast, zafirlukast Zileuton (not licensed in UK) Anti-inflammatory (Suppress activation of inflammatory genes) Bronchodilators Some anti-inflammatory action (increase cAMP) Bronchodilators May stabilize mast cells (increase cAMP) Bronchodilators Reduce mucus secretion (block cholinergic effects) Bronchodilators May reduce mucosal oedema (block action of LTC4, LTD4) Inhaled: oral candidiasis, cough, hoarseness Oral/high dose: Retarded growth, water retention, osteoporosis, hypertension, weight gain, eye problems, diabetes, psychosis Headache, nausea, diuresis, cardiac arrhythmias, vomiting, epilepsy; many drug interactions affect xanthine plasma levels Rare, bitter taste None-significant described Mild and intermittent asthma Regular preventer therapy Initial add-on therapy Persistent poor control Frequent oral steroid 58 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 58. Management of asthma Assessment Lung function: morning dipping Bronchial provocation tests hyperresponsiveness Skin prick tests Therapy step-wise treatment regimens inhaled MDI relievers preventers Short acting -adrenoceptor agonists Long-acting -agonists tolerance Corticosteroids Inhaled steroids Oral corticosteroids Combination therapies Muscarinic receptor antagonists Xanthines Antileukotriene therapy Cromones Allergen-specic immunotherapy: Bronchial thermoplasty Poorly controlled Severe uncontrolled asthma Indications: life-threatening Treatment: + Asthma: treatment Diseases and treatment 59 59. r26 Chronic obstructive pulmonary disease (d) Typical signs and symptoms of COPD Chronic bronchitis Emphysema 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 Note: Most patients may present with both chronic bronchitis and emphysema 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 Risk factors for COPD Spirometry. FEV1/FVC ratio decreases in COPD Smoking Age >50 years old; prevalence ~510% Male gender Childhood chest infections Airways hyperreactivity asthma/atopy Low socioeconomic status 1-Antitrypsin deficiency Heavy metal exposure cadmium Atmospheric pollution Pathophysiology of chronic bronchitis and emphysema Volume 1 second 4 seconds Normal FEV1/FVC = >0.8 COPD Irreversible with bronchodilators MPO-ANCA MPO-ANCA >> PR3-ANCA MPO-ANCA > PRS-ANCA Anti-GBM antibodies Occassionally PR3-ANCA Alveolar haemorrhage Asthma, eosinophilia Related to Wegeners Hepatitis B, C Alveolar haemorrhage Smoking, recent infection EpsteinBarr virus Lymphoproliferative 66 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 66. vasculitides collagen vascular disease rheumatoid arthritis scleroderma systemic lupus erythematosus (SLE) primary vasculitides Wegeners granulomatosis, ChurgStrausssyndrome,microscopicpolyangiitis,lymphomatoid granulomatosis angiitis Goodpastures syndrome anti-neutrophil cytoplasmic antibodies ANCA Collagen vascular diseases Rheumatoid arthritis pulmonary hypertension Caplans syndrome Limited cutaneous scleroderma pulmonary capillaritis SLE pulmonary arterial hypertension Vasculitides Wegeners granulomatosis granulomas ChurgStrauss syndrome allergic granulomatosis angiitis Treatment: Microscopic polyangiitis Treatment Goodpastures syndrome anti-glomerular basement membrane D co Treatment: Lymphomatoid granulomatosis EpsteinBarr virus Treatment: Pulmonary vasculitis Diseases and treatment 67 67. r30 Diffuse parenchymal (interstitial) lung diseases (a) Classification and diagnostic process in DPLD 1. Idiopathic interstitial pneumonitis (IIP) 2. DPLD due to specific causes 3. Granulomatous DPLD 4. Rare causes of DPLD Usual insterstitial pneumonitis (UIP/IPF) Non-usual interstitial pneumonitis (non-UIP, e.g. NSIP, DIP) 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 TBBx, BAL diagnostic in sarcoidosis in 6090%Possible IIP HRCT scan Not IIP (e.g. drug-related, occupational, CTD, sarcoidosis and ARDS) Characteristic clinical and CT features of UIP Surgical biopsy not required Features diagnostic of another DPLD e.g. sarcoidosis, LCH Atypical clinical or CT features for UIP or suspected other DPLD or non-UIP IIP (e.g. NSIP and DIP) TBBx, BAL or other relevant test If non- diagnostic Surgical lung biopsy UIP Non-UIP IIP NSIP DIP RB-ILD COP LIP AIP Not IIP (b) Drug induced DPLD 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 (2050%) Systemic lupus erythematosus (5%) Sjogrens syndrome (25%) Ankylosing spondylitis (2%) (g) Clinical features, age at onset, histologic pattern and radiographic features of idiopathic interstitial pneumonias Clinical name Age, sex Clinical features, relation to smoking and response to treatment Typical CT findings CT distribution UIP/IPF 5080 yrs M>>F Gradual onset. Acute exacerbations. Worse in smokers. BAL shows neutrophils (eosinophils). Poor response to steroids and immunosuppressive agents. Median survival 23 years from diagnosis Reticular abnormality + volume loss, honeycombing, traction bronchiectasis, focal GGO Peripheral, basal + subpleural (Fig. d) NSIP 4050 yrs M=F Gradual onset 630 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 4050 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 4050 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 50% and occurs within 48 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 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 (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 Subpleural honeycomb fibrosis Coarse reticular opacities Traction bronchodilation Subpleural sparing GGO and mosaic patterning Normal lung 68 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 68. Clinical features: Pulmonary function tests D co Chest X-ray > Bron- choalveolar lavage HRCT scans (histology) Classication: 1 Idiopathic interstitial pneumonitis r Usual interstitial pneumonia Pathogenesis Incidence Clinical features HRCT scans Histology Treat- ment: Median survival < r Non-usual interstitial pneumonitis > 2 DPLD due to specic causes r Drug-induced DPLD r Hypersensitivity pneumonitis r Connective tissue disease (CTD) DPLD r Occupational lung disease 3 Granulomatous DPLD: 4 Rare causes of DPLD Diagnosis (Fig. 30a): HRCT scans Surgi- cal biopsy Management: Supportive therapy Pharmacological therapy N Diffuse parenchymal (interstitial) lung diseases Diseases and treatment 69 69. r31 Sarcoidosis (a) Causes of lung granuloma Idiopathic: Sarcoidosis Infective: Tuberculosis, leprosy, brucellosis, fungal, schistosomiasis, cat-scratch fever, syphilis Malignancy: Lymphoma Gastrointestinal: Crohns disease, primary biliary cirrhosis Allergic: Extrinsic allergic alveolitis Occupational: Berylliosis, silicosis Vasculitic: Wegener's granulomatosis, giant cell arteritis, polyarteritis nodosa, Takyasus arteritis Others: Thyroiditis, Langerhans cell histiocytosis, hypogammaglobulinaemia, orchitis (b) Causes of bihilar lymphadenopathy on CXR Sarcoidosis Tuberculosis Lymphoma, leukaemia Fungal infections (e.g. histoplasmosis) Berylliosis Hypogammaglobulinaenia (+recurrent infection) (e) Radiographic staging in sarcoidosis and likelihood of spontaneous resolution Stage Finding Likehood of spontaneous resolution 0 I II III IV Normal chest radiograph Bilateral hilar lymphadenopathy (BHL) BHL plus pulmonary infiltrates Pulmonary infiltrates (without BHL) Pulmonary fibrosis ( bullae) >90% 6090% 4060% 1020% Incidence Aetiology: Histopathology Clinical features: > 1 Pulmonary sarcoidosis (a) Acute sarcoidosis (b) Progressive, interstitial lung disease Diagnosis: Disease progression D co r SACE r CXR < r High-resolution CT scans r Histological conrmation r Pulmonary function tests D co Management: r Steroid therapy > r Immunosuppressive therapy r Lung transplant 2 Extrathoracic disease r Skin r Eye > r Cardiac disease r Neurosarcoid Prognosis: D co Sarcoidosis Diseases and treatment 71 71. r32 Pleural diseases (a) Causes of pleural effusions (b) CXR showing large pleural effusion in left lung (contrast with pneumothorax CXR in Chapter 35) (c) CT scan demonstrating irregular (lumpy) pleural thickening of mesothelioma over lateral right chest wall (see arrows) Exudative (protein ratio pleural/serum >0.5 or LDH ratio pleural/serum >0.6 or pleural LDH >0.66 of top normal serum value) Infectious Para-pneumonic aerobic bacterial pneumonia anaerobic bacterial pneumonia Empyema Tuberculosis Parasitic amoeba echinococcus paragonimus Viral Autoimmune/collagen vascular Systemic lupus erythematosus Rheumatoid arthritis Neoplastic Lung cancer Metastatic disease Mesothelioma Abdominal Pancreatitis/pseudocyst Oesophageal rupture Liver abscess Splenic abscess Miscellaneous Pulmonary embolism Drug reactions Asbestos exposure Haemothorax Chylothorax Post-cardiac surgery Post-myocardial infarction Meigs syndrome Transudative (meets none of the criteria for exudative) Congestive heart failure Cirrhosis Hepatic hydrothorax Myxoedema Nephrotic disease Peritoneal dialysis 72 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 72. The pleurae parietal visceral pleurae transudative Pneumothorax Chylothorax Empyema Pleurisy Pathophysiology pleural effusion inammatory pulmonary mechanics pleuritic chest pain dull aching pain fullness of the chest dyspnoea Compressive atelectasis transudative exudative Transudative effusions congestive heart failure Exudative effusions Treatment Specic conditions Pneumonia Streptococcus pneumoniae Staphylococcus aureus Tuberculosis pleurisy Primary lung malignancies metastases pleurodesis Mesothelioma Pleural diseases Diseases and treatment 73 73. r33 Occupational and environmental-related lung disease (a) Common examples of irritant gases and other agents causing lung-specific responses Agent Source Response Ammonia Chlorine gas Hydrogen sulphide Nitrogen dioxide Nitrogen oxides Ozone Sulphur dioxide Acrolein, aldehydes Diesel particulates ( mucociliary clearance persistent respiratory infections Man- agement Cystic brosis and bronchiectasis Diseases and treatment 77 77. r35 Pneumothorax (c) Aspiration Small pneumothorax 30% (a) Pneumothorax (b) Pneumothorax management Local anaesthetic Aspirate using three-way tap Plastic cannula 50mL Lung Pntrxm Dischar aspirated air through underwater seal euoo ge ha 78 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 78. Pneumothorax classication Primary spontaneous pneumothorax (PSP) > > Secondary pneumothorax Traumatic (iatrogenic) pneumothorax Tension pneumothorax tension pneumothorax Clinical assessment < Monitoring Blood gases CXR Computed tomography (CT) scan Management < > always bronchopleural stula Air leaks Pneumomediastinum subcutaneous emphysema (SE) pneumopericardium Pneumothorax Diseases and treatment 79 79. r36 Community-acquired pneumonia Age: >65, Severity scoring: c u r < < b 65 Management Supportive measures: P o S o < Ventilatory support: Physiotherapy and bronchoscopy: Initial antibiotic therapy: r Non-hospitalized patients: S. pneumoniae r Hospitalized patients: S. pneumoniae H. inuenzae Community-acquired pneumonia Diseases and treatment 81 81. r37 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 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 Table 2. Risk factors for multidrug-resistant pathogens causing hospital-acquired pneumonia (b) Pathogenesis of hospital aquired pneumonia (c) Likely pathogens and empirical antibiotic treatment of hospital-acquiredt pneumonias ONSET + MDR PATHOGEN RISK Early-onset (4 days in hospital) + risk factors for MDR pathogens LIKELY PATHOGENS Hospitalization + antibiotic therapy Gastro-oesophageal aspiration Cough reflex (e.g. drugs and pain) Colonization of the nasopharynx by Gram-negative bacilli Aspiration of nasopharyngeal secretions Infected ventilators/circuits Direct access to LRT (ET/tracheostomy tubes) Blood spread from distant focus (iv lines, infected emboli, abdominal sepsis) Streptococcus pneumoniae Haemophilus influenza S. aureus (methicillin-sensitive) Antibiotic-sensitive Gram-negative bacilli, e.g. E. coli, Proteus spp. Klebsiella pneumoniae, Serratia All the early-onset HAP pathogens + MDR pathogens e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp., MRSA, Legionella pneumophilia TREATMENT Narrow-spectrum (single-agent) antibiotic therapy e.g. ceftriaxone or fluoroquinolones (e.g. ciprofloxacin) or co-amoxiclav or ertapenem Broad-spectrum (multiagent) antibiotic therapy Antipseudomonal cephalosporin (e.g. ceftazidine) or Antipseudomonal carbapenem (e.g. imipenem) or -lactam/ -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) HAP or VAP or HCAP Supine positioning Impaired consciousness (e.g. drugs) Swallowing difficulty + vomiting Immobility + debility Instrumentation (e.g. NG tube) (ii) Consolidation Fluid-filled abscess Cavitation Unmodifiable risk factors Modifiable risk factors 1. Host related Malnutrition Age: >65, 20cmH2O* Subglottic aspiration during intubation Change + drain ventilator circuits Sucrulfate for stress ulcer prophylaxis 3. Infection control Hand washing, sterile technique Patient isolation Microbiological surveillance Mucociliary clearance Immunity Local lung defences 82 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 82. Hospital-acquired (nosocomial) pneumonia (HAP) ventilator-associated pneumonia (VAP) healthcare-associated pneumonia (HCAP) Denitions HAP: VAP: HCAP: Epidemiology Incidence: Risk factors: prevented Mortality: Early-onset HAP/VAP < late-onset HAP/VAP > Pathogenesis Aetiology Klebsiella pneumoniae Pseudomonas aeruginosa Escherichia coli Staphylococcus aureus Streptococ- cus pneumoniae Haemophilus inuenza S. aureus S. aureus Diagnosis clinical microbiological Clinical: > Diagnostic tests: complications Management Supportive therapy oxygen P o S o < intravenous uids (vasopressors/inotropes) ventilatory support Phys- iotherapy analgesia Semi-recumbent Antibiotic therapy r early-onset HAP/VAP monotherapy r late-onset HAP/VAP combination therapy P. aeruginosa S. aureus > Other pneumonias Aspiration/anaerobic pneumonia: Bacteroides Pneumonia during immunosuppression Aspergillus Pneumocystis carinii Hospital-acquired (nosocomial) pneumonia Diseases and treatment 83 83. r38 Pulmonary tuberculosis Giant cells (multinucleate) Central caseation (cheesy pus) Lymphocytes Acid-fast bacilli Ghon focus and hilar lymphadenopathy = Primary complex (a) (c) Pulmonary complications Apical cavitiesMycetoma Pneumothorax Collapsed lung Pleural fluid Miliary TB Malaise Weight loss Low-grade fever Tuberculosis (b) CXR of patients with TB General Malaise Fever and weight loss Night sweats Large joint TB Neurological TB Meningitis Cerebral abscess Nerve lesions Cardiac TB Pericardial TB Calcification and tamponade Spinal TB Vertebral collapse Paralysis Skin TB Lupus vulgaris Lymph node TB Painless lymph node enlargement Respiratory TB Dyspnoea Cough/sputum Haemoptysis Crackles Renal TB Haematuria Sterile pyuria Chronic renal failure Abscess Upper lobe shadowing and cavitation 84 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 84. Pathogenesis Primary pulmonary TB Mycobac- terium tuberculosis granuloma Ghon focus primary complex tuberculin Mantoux Heaf Post-primary pulmonary TB tuberculous pneumonia pleural effusions miliary TB Clinical features Primary pulmonary TB erythema nodosum bronchiectasis Post-primary TB Miliary TB Investigation Blood tests Mantoux test: > Heaf test Microbiology: Histopathology: Chest radiography Drug therapy compliance with drug therapy Complications Prevention and contact tracing BCG must be notied Pulmonary tuberculosis Diseases and treatment 85 85. r39 The immunocompromised host (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) 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 (a) Causes of new pulmonary infiltrates (c) Clinical features of AIDS Causes of respiratory disease and CXR infiltrates in HIV-infected patients Cerebral HIV encephalopathy, dementia Cerebral toxoplasmosis Cryptococcus neoformans Primary brain lymphoma General Weight loss, fatigue Lymphadenopathy CMV retinitis Respiratory Pneumocystis pneumonia Mycobacterium avium complex Mycobacterium tuberculosis Pneumonia (e.g. S. pneumoniae) Infection* Bacterial (e.g. S. Pneumoniae) Pneumocystis pneumonia Fungal (e.g. cryptococcus) Mycobacterial infection (e.g. MTB, MAC) Viral (e.g CMV) Drug toxicity e.g. amiodarone, busulphan Gastrointestinal Diarrhoea Cytomegalovirus colitis Oral + oesophageal candida Small bowel lymphoma Skin Herpes simplex Kaposis sarcoma Dermatitis Interstitial pneumonitis e.g. Non-specific interstitial pneumonitis Lymphocytic interstital pneumonitis Blood Lymphopaenia Bacteraemia Malignancy Non-Hodgkin lymphoma Kaposis sarcoma Burkitts lymphoma Lung cancer Malignancy Non-Hodgkins lymphoma Burkitts lymphoma Clinical features and diseases that are indicators of AIDS Causes of chest disease + CXR infiltrates in HIV- infected patients (*commonest) General causes Heart failure, pulmonary oedema Sepsis-induced acute respiratory distress syndrome (ARDS) Radiation pneumonitis Pulmonary haemorrhage (e) Cerebral toxoplasmosis with ring enhancement on a post-contrast CT brain scan (d) Pneumocystis Jirovecii pneumonia (PCP) showing bilateral diffuse infiltrates Mass lesion with ring enhancement Impaired T-cell function Impaired B-cell function Impaired compliment Mannose lectin deficiency, complement deficiency Lymphoma, leukaemia, myeloma, hypogammaglobulinaemia Transplantation, steroids, lymphoma, HIV infection, chemotherapy Streptococcus pneumonia Streptococcus pneumoniae, Haemophilus influenza Bacteria (e.g. mycobacteria), fungi (e.g. PCP), viruses (e.g. CMV) 86 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 86. Clinical presentation Investigations Aspergillus Pneumocystis jiroveci Cryptococcus Diagnosis r Infection r Non-infectious causes Treatment r Antibiotic r Steroid therapy r Supportive therapy Respiratory manifestations in the HIV-positive patient 1 Infectious causes r Bacterial pneumonia Streptococcus pneumoniae Staphy- lococcus aureus Nocardia Legionella r Pneumocystis jirovecii pneumonia < > r Mycobacteria Mycobacterium tuberculosis My- cobacterium avium r Viral Cytomegalovirus r Fungal . Aspergillus Cryptococcus neoformans histoplasmosis coccidioidomycosis 2 Non-infectious causes r Malignancie Kaposis sarcoma Non-Hodgkins lymphoma Lung cancer r Interstitial pneumonitis r Drug-induced heart failure The immunocompromised host Diseases and treatment 87 87. r40 Lung cancer (a) Mass on CT: a >3cm spiculated mass is seen in upper lobe of the right lung (c) CXR showing squamous cell tumour in hilar region (b) Fibreoptic bronchoscopy showing tumour invading bronchus (e) Survival for non-small cell cancer Stage T (tumour) N (node) M (metastasis) Key IA IB IIA IIB IIIA IIIB IV T1 T2 T1 T2 T3 T1, 2, 3 T3 T1, 2, 3, 4 T4 T14 N0 NO N1 N1 N0 N2 N1 N3 N1, 2 N03 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 (d) Staging system for non-small cell lung cancers T1: T2: T3: T4: 3cm without division >3cm, or invasion of main bronchus >2cm from main carina, or invades visceral pleura, or bronchus causing obstruction Invades chest wall or pleura, or main bronchus < Passive smoking Asbestos exposure Radon gas Classication small cell SC non-small cell NSC NSC squamous cells large cells adenocarci- noma Adenocarcinomas < > Squamous cell carcinomas Large cell carcinoma SC Presentation extrathoracic metastasis Paraneoplastic syndromes autoantibodies parenchymal nodules Evaluation malignancy staging suitability for therapy Computed tomography CT) scans Positron emission tomography (PET) scanning Staging SC cancer limited extensive Limited disease Extensive disease NSC cancer tumour node metastasis T3 T4 TNM categories stage I II > surgical resection stage IIIA stage IIIB IV chemotherapy radiation therapy Stage IV Platinum taxol-based Lung cancer Diseases and treatment 89 89. r41 Acute respiratory distress syndrome 3. Normal alveoli As normal alveoli are easiest to inflate, they are damaged by overinflation = 'volutrauma'. This causes increased membrane permeability and flooding Use low tidal volumes (6 mL/kg) IL-1, IL-8 Increased permeability and consolidation Pathophysiology Widespread alveolar and dependent consolidation Loss of surfactant and increased permeability Alveolar flooding NO increases blood flow past ventilated alveoli Consolidated alveoli NO NO Back Front Reduces shunt Consolidated lung (a) Acute respiratory distress syndrome (b) Ventilator-induced lung damage (c) Common causes of ARDS (d) V/Q matching CXR of aspiration-induced ARDS 1. Loss of surfactant Repeated alveolar collapse and re-expansion cause damage. Aim to prevent alveolar collapse and encourage alveolar recruitment This is achieved with PEEP and increased mean airways pressure (i.e. reverse I:E ratio) to hold open alveoli Direct pulmonary 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 multiorgan failure MOF Pathogenesis (Fig. 41a and b) and causes (Fig. 41c) acute inammatory phase healing broproliferative phase Clinical features acute inammatory phase healing broproliferative phase Investigations Monitoring: to assess uid balance and ensure adequate tissue oxygen delivery Radiological: diffuse bilateral pulmonary inltrates diffuse patchy inltrates dependent consolidation pneumothoraxes pneu- matoceles brosis Management establish and treat the underlying cause F o > limit pressure- induced damage, optimize oxygenation avoid circulatory com- promise < Alveolar recruitment > Excessive uid loading must be avoided Essential general measures No drug therapy has been consistently benecial Inhaled nitric oxide prone position Extracorporeal membrane oxygenation (ECMO) Acute respiratory distress syndrome Diseases and treatment 91 91. r42 Mechanical ventilation (a) Indications for mechanical ventilation or support in adults Surgery General anaesthesia with neuromuscular blockade Postoperative management following major surgery Respiratory centre depression Usually when PaCO2 >78kPa (5060mmHg) Head injury Drug overdose, e.g. opiates, barbiturates Raised intracranial pressure: cerebral haemorrhage/ tumours/meningitis/encephalitis Status epilepticus Lung disease Pneumonia Acute respiratory distress syndrome (ARDS) Severe asthma attack Acute exacerbation of chronic obstructive pulmonary disease (COPD), cystic fibrosis Traumalung contusion Pulmonary oedema Cervical cord damage above C4 Neck fractures Neuromuscular disorders when VC Non-invasive respiratory support continuous positive airway pressure (CPAP) obstructive sleep apnoea ARDS non-invasive intermittent positive pressure ventilation (NIPPV) CPAP NIPPV Weaning Complications of mechanical ventilation Mechanical ventilation Diseases and treatment 93 93. r43 Oxygenation and oxygen therapy (a) Indications for acute oxygen therapy (d) Oxygen delivery devices (c) Risks associated with high-dose oxygen therapy 1. Cardiac and respiratory arrest 2. Hypoxaemia (PaO2 30 L/min). Consequently, FiO2 is less affected by the breathing pattern. The resulting masks are high flow, low concentration and fixed performance Figure (iv) illustrates that a fixed O2 flow through a Venturi valve entrains the correct proportion of air to achieve the required O2 concentration 2. Fixed performance devices Air is entrained during breathing whilst oxygen is delivered from a reservoir (i.e. mask, reservoir bag, nasopharynx) e.g. Figure (i) Low-flow face masks, O2 flows at ~210 L/min into the mask and is supplemented by air drawn into the mask. The FiO2 achieved depends on ventilation Examples of variable performance devices are low-flow facemasks (see i), nasal cannulae (see ii) and non- rebreathing face masks with reservoir bags (see iii) These devices cannot be used if accurate control of FiO2 is desirable, e.g. COPD with hypercapnia 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% 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% The FiO2 delivered to the lungs depends on the oxygen flow rate, the patients inspiratory flow, respiratory rate and the amount of air entrained 1. Variable performance devices Continuous positive airways pressure (CPAP) masks Use a tight fitting mask and a flow generator to deliver a fixed FiO2 with a positive pressure (510 cm/H2O) throughout the respiratory cycle Venturi valves are colour coded and deliver 24, 28, 31, 35, 40 or 60% FiO2 for a fixed flow rate 28 L/min entrained air 5 L/min inspired 5L/min inspired Venturi Valve (iv) High-flow (Venturi), low concentration face mask (iii) Non-rebreathing and anaesthetic masks (i) Low-flow facemask (ii) Nasal cannulae High (1015 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 FiO2 is 60100% at O2 flow rates of 1015 L/min FiO2 can be 60% at 15 L/min O2 FiO2 is between 24 and 35% One-way valve stops exhaled air entering reservoir bag Reservoir bag O2 flow 1015 L/min O2 flows at ~215 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 3 L/min air drawn into mask 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 O2 flow rates up to 4 L/min. Higher rates dry mucosa 30 L/min into mask at FiO2 24% 25 L/min escapes from mask 2 L/min jet of oxygen 30 L/min total gas flow at fixed O2 concentration 2L/min oxygen into mask 2 L/min oxygen 94 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 94. Tissue hypoxia low arterial Po blood O2 content tissue blood ow haemoglobin concentration oxygen dissociation curve poisoning of intracellular oxygen usage Measuring tissue hypoxia S o pulse oximeter P o blood gas analysis S P o S o mixed venous oxygen partial pressure P o Po P o S o P o Oxygen therapy type 2 (hyper- capnic, CO2 retaining) respiratory failure r In normal patients S > P r In patients at risk of type 2 respiratory failure S S r High-dose supplemental oxygen (>60%) S r Moderate-dose supplemental oxygen (4060%) S r Low-dose (controlled) supplemental oxygen (2428%) CO2 retaining, type 2 respiratory failure S P co S P co S P co > < CO poisoning P Stop oxygen therapy S S Other techniques to improve oxygenation 1 Anaemia: 2 Block of airways by mucus and retention of secretions 3 Fluid restriction 4 Alveolar recruitment 5 Ventilatory support Oxygenation and oxygen therapy Diseases and treatment 95 95. r44 Sleep apnoea EOG (eye movement) EEG SaO2 (blood O2 saturation) Thoracic movement Airflow (a) Normal (b) Obstructive sleep apnoea (c) Central sleep apnoea Desaturation Arousal No airflow Continued effort Desaturation No effort Arousal No airflow Polysomnogram (simplified) (e) Cheyne-Stokes respiration Time VentilationO2saturation Cheyne-Stokes respiration occurs in heart failure and at altitude, and is characterized by slowly increasing and decreasing depth of each breath Pharynx Blocked airway Tongue Uvula (d) Obstructive sleep apnoea Normal airflow Obstructed airflow 96 The Respiratory System at a Glance, 3e. By J.P.T. Ward, J. Ward, R.M. Leach. Published 2010 Blackwell Publishing Ltd. 96. Sleep apnoea obstructive sleep apnoea central sleep apnoea (CSA) polysomnogra- phy REM NREM P o P co Obstructive sleep apnoea loud snoring daytime hypersomnolence gain weight nocturnal hypoxia apnoea plus hypopnoea index AHI obesity hypoventilation syndrome pulmonary hypertension Therapy nasal continuous positive airway pressure CPAP Central sleep apnoea loss or inhibition of central respiratory drive Cheyne-Stokes respiration Therapy NIPPV Sleep apnoea Diseases and treatment 97 97. Case studies: questions Case 1 Questions 1 You are worried whether either or both could have a pulmonary embolus (PE). From the history and ndings 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 o2? 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? Case 2 Questions 1 Is this peak ow normal? Apart from the nomogram values, can you think of any other peak ow reading with which it would be useful to compare todays clinic reading? 2 If you measured the following: r FEV1/FVC r Airway resistance r Functional residual capacity (FRC) r Lung compliance r Arterial o2 and arterial co2 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 eld. 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 ow rate r Airway resistance r Functional residual capacity r Lung compliance r Arterial o2 and arterial co2 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 rst 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 nds 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 ow 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 o2 and co2, 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 trafc 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 ow reading. The Accident and Emergency 98 Cases and self assessment Case studies: questions 98. ofcer notices he is now cyanosed, although the widespread rhonchi noted in the GPs letter have now disappeared. Arterial blood gases show arterial o2 = 7 kPa and arterial co2 = 5.5 kPa while breathing 60% oxygen. 8 Discuss the features that suggest this asthma attack is life- threatening. Do the reduced rhonchi on auscultation contradict the other ndings? 9 What is the cause of the low arterial o2? Was the inhaled oxygen helpful, and if so was the correct concentration used? Is this co2 normal, and how does it affect your assessment of the severity of this attack? Case 3 Physical examination Chest radiograph D co Questions 1 What would you expect the patients 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 Lco low? 5 What will happen to the patients oxygenation with exercise? Why? 6 Why is the patients jugular venous pressure elevated? 7 What are the most likely diagnosis and pathophysiology of his disease? Case 4 D co 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 patients 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? Case 5 Figure 45 Case studies: questions Cases and self assessment 99 99. < 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 classied? 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? Case 6 P 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? Case 7 Questions 1 What are the risks associated with cigarette smoking? 2 Why is smoking addictive? 3 How would you advise the wife regarding smoking cessation? 4 Following smoking cessation what is the risk of developing cancer? 5 What are the effects of passive smoking on children? Case 8 Questions: 1 What brings you to suspect PSP? 2 How do you conrm your diagnosis? 3 What causes PSP, and is it likely to happen to James again? 4 What treatment would you prescribe? 5 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? 100 Cases and self assessment Case studies: questions 100. Case studies: answers Case 1: Pulmonary emboli 1 2 P o 3 Po P co 4 5 d d d 6 7 8 Case 2: Asthma 1 2 Case studies: answers Cases and self assessment 101 101. 3 r r > r r > r 4 Pco 5 6 7 Pco Po Pco 8 9 P o Pco Pco Pco Case 3: Severe breathlessness 1 2 3 4 D co 5 D co < 6 7 102 Cases and self assessment Case studies: answers 102. Case 4: Restrictive ventilatory defect 1 D co 2 D co D co 3 4 5 r r r r 6 Case 5: Haemoptysis 1 2 < > 3 bronchiectasis Aspergillus 4 d Case studies: answers Cases and self assessment 103 103. Figure 46(a) Aspergillus Aspergillus > 5 6 Immediate Bronchial angiography embolization Aspergillus < Final diagnosis: Case 6: Oxygenation and oxygen therapy Patient 1 1 P co P o = P o P co R P o P o = P o = F o = = R P co = co F o P o = F o = . = P o P o = . . = 2 P co P o P co Patient 2 1 P o P o P co P o F o = P o P o = . = P o 104 Cases and self assessment Case studies: answers 104. 70.0 14.0 7.0 PaO2(kPa) 0.2 0.6 1.0 FiO2 Hypoxaemia caused by true right to left shunt is refractory to supplemental O2 when shunt fraction exceeds 30% Shunt fraction = QS/QT (%) Effect of true shunt (QS/QT) on the arterial oxygen tension (PaO2) response to inspired oxygen fraction (FiO2) 50% shunt 30% shunt 10% shunt Figure 47 2 F o type 1 respiratory failure P co Patient 3 1 P o F o P o P o F o P o 2 P o F o Case 7: Smoking cessation 1 2 3 A A A A A Nico- tine replacement therapy Bupropion (Zyban) Varenicline (Champix) 4 5 Case studies: answers Cases and self assessment 105 105. Case 8: Primary spontaneous pneumothorax 1 2 3 > 4 5 106 Cases and self assessment Case studies: answers 106. Self-assessment questions best Chapter 1: Structure of the respiratory system: lungs, airways and dead space 1.1 The pulmonary nerve plexus 1.2 The pleural space 1.3 Type II pneumocytes 1.4 Alveolar dead space Chapter 2: The thoracic cage and respiratory muscles 2.1 Intercostal spaces 2.2 The diaphragm 2.3 Accessory inspiratory muscles include all of the following EX- CEPT 2.4 Paradoxical breathing Chapter 3: Pressures and volumes during normal breathing 3.1 Functional residual capacity 3.2 Intrapleural pressure 3.3 From the trace produced when a subject breathes in and out of a simple water-lled spirometer, it is possible to measure 3.4 The predicted lung volumes for a subject Chapter 4: Gas laws 4.1 Fractional concentration of oxygen in the air = 4.2 Saturated water vapour pressure Self-assessment questions Cases and self assessment 107 107. 4.3 A man has eaten a lunch of baked beans on toast and drunk a bottle of cola after which he goes on a hot air balloon ride. As he ascends he experiences abdominal pain. The gas law that best explains his problem is = 4.4 When the lid was removed from the bottle of cola, bubbles formed in the liquid and rose to the surface. = Chapter 5: Diffusion 5.1 Diffusion through the alveolarcapillary membrane 5.2 Diffusion-limited uptake of a gas through the alveolar capillary membrane 5.3 Carbon monoxide (CO) diffusing capacity (transfer factor) P P 5.4 One condition that does NOT reduce the carbon monoxide diffusing capacity (transfer factor) is Chapter 6: Lung mechanics: elastic

respiratory system at aglance

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