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Trachea (Generation #1) Primary Bronchi (Generation #2) Conducting Airways Generations o Bronchi (Generation #3) Respiratory Zone Generations ~17-23 Alveoli Respiratory Bronchioles

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PAPA PaPa PvPv Zone 1 P A >P a >P v Low Flow PAPA PaPa PvPv PAPA PaPa PvPv Zone 2 P a >P A >P v Waterfall Zone 3 P a >P v >P A Hi Flow O2O2 CO 2 venousarterial P B =0 P A <0 Flow= P/R

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O2O2 CO 2 venousarterial P B =0 P A <0 O2O2 CO 2 venousarterial P B =0 P A >0 Atmospheric Air High O 2 (150 mmHg) CO 2 ~ 0 Alveolar Air O 2 ~100 mmHg CO 2 ~ 40 mmHg InspirationExpiration

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Ficks law J = DA ( C/ X) Lung Chest Wall Stuck Together Lung Air leak Pneumothorax Lung collapses & Chest expands

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VTVT Total Lung Capacity Expiratory Reserve Inspiratory Reserve FRC Inspiratory Capacity Residual Volume Vital Capacity

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Expiratory Reserve Residual Volume Vital Capacity VTVT Total Lung Capacity Inspiratory Reserve FRC Inspiratory Capacity TLC RV IC VTVT IR FRC ER VC

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VLVL V1V1 VLVL V1V1 C 1 V 1 =NC 2 (V 1 +V L ) =N V L =(C 1 /C 2 )V 1 –V 1 Equilibrate Concentration C 1 V 1 = C 2 (V 1 +V L )

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Expiratory Reserve Residual Volume Vital Capacity VTVT Total Lung Capacity Inspiratory Reserve FRC Inspiratory Capacity 600 ml 2.5 L 1.2 L 5 L ~6.5 L

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Lung Chest Wall Stuck Together Lung As we remove air from pleural space the lung expands & the chest wall gets pulled in.

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Chest Wall Recoil Force Lung Wall Recoil Force P pl = 0 P pl = -2 Normal Emphysema lung recoil Fibrosis lung recoil Pneumo- thorax P pl = -8 Balance of Forces Determines FRC Hookes Law: F = -kx Intrapleural space Increasing volume Decreasing volume Normal FRC P pl = -5

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P1P1 P2P2 For same T, P 1 >P 2 (I.e. 2T/r 1 > 2T/r 2 ) LaPlace 2T=Pr P=2T/r

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Surface Area (relative) Surface Tension (dynes/cm) WaterDetergent Lung Surfactant Plasma 80 Surface Area Surface Tension Surfactant 40% Dipalmitoyl Lecithin 25% Unsaturated Lecithins 8% Cholesterol 27% Apoproteins, other phospholipids, glycerides, fatty acids

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Surface Area (relative) Surface Tension (dynes/cm) WaterDetergent Lung Surfactant 80 Surface Area Surface Tension 1.Reduces Work of Breathing 2.Increases Alveolar Stability (different sizes coexist) 3.Keeps Alveoli Dry

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Static Compliance Curves Expiration Inspiration

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Static Compliance Curves

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Chest Wall Recoil Force Lung Wall Recoil Force Normal FRC P pl = -5 Normal Balance of Forces Determines FRC Hookes Law: F = -kx Intrapleural space Increasing volume Decreasing volume P pl = 0 P pl = -2 Emphysema lung recoil Fibrosis lung recoil Pneumo- thorax P pl = -8

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Lung has weight -8 P pl = Apex Base Chest Wall

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Regional- Apex to Base Differences

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Apex to Base Differences

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P A (cm H 2 O) Air Flow (L/s) time (sec) P pl ( cm H 2 O ) The linear Dashed trace is the P pl required to overcome recoil forces. More P pl (solid curve) is required to overcome airway resistance to flow. N.B. P = P A -P B ResistFlow. V T (L) Respiratory Cycle InspirationExpiration Rest FRC Inspiration End Inspiration Air Flow P A = 0 P pl End Expi- ration-FRC Expiration time Respiratory Cycle Single V T Breath P B =0

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Static Compliance Curves Expiration Inspiration

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P A (cm H 2 O) Air Flow (L/s) time (sec) P pl ( cm H 2 O ) Case of ZERO Resistance V T (L) Respiratory Cycle InspirationExpiration Rest FRC Inspiration End Inspiration Air Flow P A = 0 P pl End Expi- ration-FRC Expiration time Respiratory Cycle Single V T Breath P B =0

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P A (cm H 2 O) Air Flow (L/s) time (sec) P pl ( cm H 2 O ) The linear Dashed trace is the P pl required to overcome recoil forces. More P pl (solid curve) is required to overcome airway resistance to flow. N.B. P = P A -P B ResistFlow. V T (L) Respiratory Cycle InspirationExpiration Rest FRC Inspiration End Inspiration Air Flow P A = 0 P pl End Expi- ration-FRC Expiration time Respiratory Cycle Single V T Breath P B =0

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P A (cm H 2 O) Air Flow (L/s) time (sec) P pl ( cm H 2 O ) V T (L) Respiratory Cycle InspirationExpiration Rest FRC Inspiration End Inspiration Air Flow P A = 0 P pl End Expi- ration-FRC Expiration time Respiratory Cycle Single V T Breath P B =0 Case of HIGH Resistance

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Mild Expiratory Effort (P+13) 0 Normal at FRC -5 0 Dynamic Compression of Airways P TP =+5 P Pl - P A = -5

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Strong Expiratory Effort (P+30) EPP Normal EPP Emphysema in unsupported airways EPP Emphysema +11 P Pl -P A = Dynamic Compression of Airways EPP Equal Pressure Point (in supported airways) +13 Mild Expiratory Effort (P+13) Normal at FRC P TP =+5 P Pl - P A = -5 Low V L & Basal Alv also like this

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Airway Generation Total Cross Sectional Area Conducting Zone Resp Zone v = Flow/A N R = Dv/ =density D= diameter v= velocity = viscosity Airway Generation Resistance Subsegmental Bronchi Resistance 8 l R= r 4 knumber R= A 2

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Lung Volume Airway Resistance Normal Recoil Emphysema Fibrosis

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Normal Resistance Obstructive Recoil Restrictive time (sec) Volume FRC Inspiration

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Forced Vital Capacity TLC FEV 1.0 FVC 1 sec FEV 1.0 = 4 L FVC = 5 L % = 80% RV Normal TLC FEV 1.0 FVC 1 sec FEV 1.0 = 1.2 L FVC = 3.0 L % = 40% RV Obstructive airway resist Restrictive lung recoil TLC FEV 1.0 FVC 1 sec FEV 1.0 = 2.7 L FVC = 3.0 L % = 90% RV

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Effort Independent limb in forced expiration. TLC RV Expiratory Flow Lung Volume Flow-Volume Curves Due to Dynamic Airway Compression and airway collapse.

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Inverted Inspiration RV Expiratory Flow Forced expiration Inspiration Inspiratory Flow TLC Lung Volume

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Normal Obstructive Restrictive Lung Volume (L) Flow Rate (L/sec) 9

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TLCRV Lung Volume (L) Alveolar Plateau Dead Space Washout 4. N 2 Concentration (%) Critical Closing Volume Test Closing Volume

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Apex to Base Differences

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TLCRV Lung Volume (L) Alveolar Plateau Dead Space Washout 4. N 2 Concentration (%) Critical Closing Volume Test Closing Volume Increased Closing Volume

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P O2 =100 mm Hg 21 ml O 2 /dL P O2 =100 mm Hg 0.3 ml O 2 /dL O2O2 O2O2 P O2 =100 mm Hg 21 ml O 2 /dL P O2 =100 mm Hg 0.3 ml O 2 /dL dissolved 20 ml O 2 /dL HB-O 2 O2O2 O2O2

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Expired Lung Volume (L) Alveolar Plateau Inspired O 2 diluted by alveolar N 2 N 2 Concentration (%) A B Fowlers Test Area A = Area B VdVd

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The Bohr Equation V D1 (P ACO2 – P ECO2 ) = V T P ACO2 V D2 (P aCO2 – P ECO2 ) = V T P aCO2 D. Sample Calculation V T = 600 ml P ACO2 = 38 mmHg P ECO2 = 28 mmHg P aCO2 = 40 mmHg V D1 = 600(38 – 28)/38 = 158 ml V D2 = 600(40 – 28)/40 = 180 ml E.Alveolar Ventilation... V E = V D + V A = V T frequency... V A = V E - V D. 1.For V T = 500 ml, f = 10/min, V D = 150 ml, what is V A ?. V A = = 3500 ml/min.. 2.If V E is doubled by increasing V T what is V A ? = 10, = 8500 ml/min.. 3.If the same V E is obtained by doubling frequency, what is V A ? = 10, = 7000 ml/min. Thus increasing V T rather than frequency is more effective for V E.

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F. Alveolar Ventilation and CO 2 production. V CO2 = Expired CO 2 - Inspired CO 2. =V A F ACO2. V A x P ACO2 = P A..V CO2 K V A = P ACO2

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XIV.RESPIRATORY GAS CASCADE P O2 P CO2 mm Hgmm Hg Air (dry) Trachea (humidified; ) Alveolus (some O 2 absorbed by blood)10040 Arterial (R-L Shunt)9040+ Mixed venous (O 2 absorbed by tissues)4046

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time in Capillary (sec) P O2 mm Hg Normal Transit Time Exercise Shortens Transit time Thickened Alveolar Membrane O 2 Diffusion in Pulmonary Capillaries (transit time)

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Capillary Wall CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - O2O2 CO 2 Cl - H + + HbO 2 HHb + O 2 Carbamino HHb-CO 2 O2O2 Tissue CO 2 Loading & O 2 Unloading c.a.

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Alveolar Wall O2O2 CO 2 Cl - H + + HbO 2 HHb + O 2 Carbamino HHb-CO 2 O2O2 Lungs CO 2 Unloading & O 2 Loading c.a. HCO 3 - CO 2 + H 2 O H 2 CO 3 H + + HCO 3 -

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O 2 helps CO 2 unloading Arterial ( O 2 ) Exercise Venous Rest Venous P CO2 (mm Hg) CO 2 Content (ml CO 2 /100 ml blood) HALDANE SHIFT

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P O2 = 40 P CO2 = 45 Normal V A /QLow V A /QHigh V A /Q CO 2 = 45 P O2 = 150 P CO2 = 0 P O2 = 100 P CO2 = 40 P O2 = 150 P CO2 = 0... Ventilation Perfusion Ratios No flow

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P O2 = 40 P CO2 = 45 Low V A /Q. Normal V A /Q. P O2 = 100 P CO2 = 40 High V A /Q. P O2 = 150 P CO2 = 0 P O2 (mm Hg) P CO2 (mm Hg) Base Apex

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Flow of Blood or Air V A /Q Ratio Bottom Top Distance up Lung Ventilation Perfusion V A /Q

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Mechanisms of Hypoxemia P aO2 P aCO2 P O2 (A-a)P aO2 with 100% O 2 HypoventilationlowHighNorm>550 Diffusionlownorm-lowhigh>550 R-L Shuntlownorm-lowhigh 550 Other Hypoxemias (without low P aO2 ) a.Anemia b.Carbon Monoxide c.Hypoperfusion (CV problem) Local Control a.Low P AO2 vasoconstriction b.Low P VCO2 bronchoconstriction

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Fourth Ventricle Nucleus retroambiguous (ventral) Nucleus tractus Solitarius (dorsal) C1 Medulla Oblongata C Cut-off B vent A Insp Dors ts Pneumotaxic Center Apneustic Center – Periph & Central Chemo- receptors + Respiratory Muscles + + Vagus Stretch + Tonic Insp Drive + Cut-off signal thresh

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Arterial P O2 (mm Hg) % maximal firing rate Peripheral Chemoreceptor Responsiveness

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BBB CSFPlasma CO 2 HCO 3 + H + CO 2 HCO 3 + H + Pumped Respiratory Acidosis ( P aCO2 ) CNS Acidosis then HCO 3 is pumped in (& restores pH CNS faster than kidneys can restore pH systemic )

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BBB CSFPlasma CO 2 HCO 3 + H + CO 2 HCO 3 + H + Metabolic Acidosis Hyperventilation & P aCO2 CNS Alkalosis !!!! (then pump HCO 3 out)

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Ventilatory Response to O 2

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Ventilatory Response to CO 2

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BBB CSFPlasma CO 2 HCO 3 + H + CO 2 HCO 3 + H + Respiratory Alkalosis high pH CSF limits Hyperventilation When pH CNS returns to norm (HCO 3 pumped out) V E is less restrained

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