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Trachea (Generation #1) Primary Bronchi (Generation #2) Conducting Airways Generations 1-16 2o Bronchi (Generation #3) Respiratory Zone Generations ~17-23 Alveoli Respiratory Bronchioles

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**Zone 1 PA>Pa>Pv Low Flow Flow=P/R Zone 2 Pa>PA>Pv**

Waterfall Zone 3 Pa>Pv>PA Hi Flow O2 CO2 venous arterial PB=0 PA<0 Flow=P/R

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**Atmospheric Air High O2 (150 mmHg) CO2 ~ 0 Inspiration Expiration**

PB=0 PB=0 Inspiration Expiration Alveolar Air O2 ~100 mmHg PA<0 PA>0 CO2 ~ 40 mmHg O2 O2 venous arterial venous arterial CO2 CO2

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**Fick’s law J = DA (C/ X) Chest Wall Lung Lung Stuck Together**

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

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

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**IR IC VC TLC VT ER FRC RV RV Inspiratory Reserve Inspiratory Capacity**

Vital Capacity VC Total Lung Capacity TLC VT VT Expiratory Reserve ER FRC FRC Residual Volume RV RV

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**V1 V1 C1V1=N C2(V1 +VL) =N VL VL VL=(C1/C2)V1 –V1 C1V1= C2(V1 +VL)**

Equilibrate Concentration C1V1=N C2(V1 +VL) =N VL VL VL=(C1/C2)V1 –V1 C1V1= C2(V1 +VL)

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

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

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**Balance of Forces Determines FRC**

Hooke’s Law: F = -kx Chest Wall Recoil Force Increasing volume Intrapleural space Ppl = -2 Normal FRC Ppl = -5 Ppl= -8 Lung Wall Recoil Force Decreasing volume Ppl = 0 Emphysema lung recoil Fibrosis lung recoil Pneumo- thorax Normal

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**LaPlace 2T=Pr P=2T/r For same T, P1>P2 (I.e. 2T/r1 > 2T/r2) P1**

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**Surface Area (relative)**

Surface Area Surface Tension Lung Surfactant Plasma Surfactant 40% Dipalmitoyl Lecithin 25% Unsaturated Lecithins 8% Cholesterol 27% Apoproteins, other phospholipids, glycerides, fatty acids Surface Area (relative) Detergent Water 30 60 80 Surface Tension (dynes/cm)

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**Surface Area (relative)**

Surface Area Surface Tension Lung Surfactant Reduces Work of Breathing Increases Alveolar Stability (different sizes coexist) Keeps Alveoli Dry Surface Area (relative) Detergent Water 30 60 80 Surface Tension (dynes/cm)

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**Static Compliance Curves**

Expiration Inspiration

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**Static Compliance Curves**

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**Balance of Forces Determines FRC**

Hooke’s Law: F = -kx Chest Wall Recoil Force Ppl = 0 Ppl = -2 Emphysema lung recoil Fibrosis lung recoil Pneumo- thorax Ppl= -8 Increasing volume Intrapleural space Normal FRC Ppl = -5 Lung Wall Recoil Force Decreasing volume Normal

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Chest Wall Apex -8 -5 Lung has weight Base Ppl = -2

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**Regional- Apex to Base Differences**

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**Regional- Apex to Base Differences**

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**Apex to Base Differences**

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**Respiratory Cycle - Ppl time Respiratory Cycle Single VT Breath -5**

VT (L) 0.4 Respiratory Cycle Single VT Breath 0.2 -5 Rest FRC Air Flow Inspiration Expiration -8 Inspiration - -5 Ppl (cm H2O) End Inspiration PB=0 -8 PA= 0 + -6 Expiration -8 +0.5 End Expi- ration-FRC Air Flow (L/s) -5 The linear Dashed trace is the Ppl required to overcome recoil forces. More Ppl (solid curve) is required to overcome airway resistance to flow. N.B. P = PA-PB Resist•Flow. -0.5 +1 PA (cm H2O) -1 time (sec)

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**Static Compliance Curves**

Expiration Inspiration

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**Respiratory Cycle - Ppl time Respiratory Cycle Single VT Breath -5**

VT (L) 0.4 Respiratory Cycle Single VT Breath 0.2 -5 Rest FRC Air Flow Inspiration Expiration -8 Inspiration - -5 Ppl (cm H2O) End Inspiration PB=0 -8 PA= 0 + -6 Expiration -8 +0.5 End Expi- ration-FRC Air Flow (L/s) -5 Case of ZERO Resistance -0.5 +1 PA (cm H2O) -1 time (sec)

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**Respiratory Cycle - Ppl time Respiratory Cycle Single VT Breath -5**

VT (L) 0.4 Respiratory Cycle Single VT Breath 0.2 -5 Rest FRC Air Flow Inspiration Expiration -8 Inspiration - -5 Ppl (cm H2O) End Inspiration PB=0 -8 PA= 0 + -6 Expiration -8 +0.5 End Expi- ration-FRC Air Flow (L/s) -5 The linear Dashed trace is the Ppl required to overcome recoil forces. More Ppl (solid curve) is required to overcome airway resistance to flow. N.B. P = PA-PB Resist•Flow. -0.5 +1 PA (cm H2O) -1 time (sec)

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**Respiratory Cycle - Ppl time Respiratory Cycle Single VT Breath -5**

VT (L) 0.4 Respiratory Cycle Single VT Breath 0.2 -5 Rest FRC Air Flow Inspiration Expiration -8 Inspiration - -5 Ppl (cm H2O) End Inspiration PB=0 -8 PA= 0 + -6 Expiration -8 +0.5 End Expi- ration-FRC Air Flow (L/s) -5 Case of HIGH Resistance -0.5 +1 PA (cm H2O) -1 time (sec)

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**Dynamic Compression of Airways**

Mild Expiratory Effort (P+13) -5 Normal at FRC PTP=+5 PPl - PA= -5

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**Dynamic Compression of Airways**

+13 Mild Expiratory Effort (P+13) +8 8 4 Normal at FRC - 5 PTP=+5 PPl - PA= -5 Strong Expiratory Effort (P+30) +25 30 5 EPP Normal EPP Equal Pressure Point (in supported airways) 4 2 EPP Emphysema +11 P Pl - A = +28 EPP Emphysema in unsupported airways Low VL& Basal Alv also like this

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**Total Cross Sectional Area**

Airway Generation Resistance Subsegmental Bronchi 8l R= ——— r4 k•number R= ————— A2 Airway Generation Total Cross Sectional Area Conducting Zone Resp v = Flow/A NR= Dv/ =density D= diameter v= velocity = viscosity

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Lung Volume Airway Resistance Normal Recoil Emphysema Fibrosis

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

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**Forced Vital Capacity Obstructive Restrictive Normal TLC**

FEV1.0 FVC 1 sec FEV1.0 = 1.2 L FVC = 3.0 L % = 40% RV Obstructive airway resist Restrictive lung recoil TLC FEV1.0 FVC 1 sec FEV1.0 = 2.7 L FVC = 3.0 L % = 90% RV Normal TLC FEV1.0 FVC RV 1 sec FEV1.0 = 4 L FVC = 5 L % = 80%

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**Flow-Volume Curves Expiratory Flow Lung Volume TLC RV**

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

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**RV TLC Forced expiration Expiratory Flow Lung Volume Inspiratory Flow**

Inspiration Inspiratory Flow TLC Lung Volume Inverted Inspiration

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

Lung Volume (L)

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**Critical Closing Volume Test TLC RV**

4. 40 1. 2. Dead Space Washout 3. Alveolar Plateau N2 Concentration (%) 20 Closing Volume Lung Volume (L)

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**Apex to Base Differences**

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**Critical Closing Volume Test TLC RV**

Increased Closing Volume 4. 40 1. 2. Dead Space Washout 3. Alveolar Plateau N2 Concentration (%) 20 Closing Volume Lung Volume (L)

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PO2=100 mm Hg 21 ml O2/dL PO2=100 mm Hg 21 ml O2/dL O2 O2 PO2=100 mm Hg 0.3 ml O2/dL PO2=100 mm Hg 0.3 ml O2/dL dissolved 20 ml O2/dL HB-O2 O2 O2

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**Expired Lung Volume (L) N2 Concentration (%)**

Alveolar Plateau Inspired O2 diluted by alveolar N2 N2 Concentration (%) 20 40 A B Fowler’s Test Area A = Area B Vd

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**E.Alveolar Ventilation . . . VE = VD + VA = VT frequency **

The Bohr Equation VD1 (PACO2 – PECO2) = VT PACO2 VD2 (PaCO2 – PECO2) = VT PaCO2 D. Sample Calculation VT = 600 ml PACO2 = 38 mmHg PECO2 = 28 mmHg PaCO2 = 40 mmHg VD1 = 600(38 – 28)/38 = 158 ml VD2 = 600(40 – 28)/40 = 180 ml E.Alveolar Ventilation VE = VD + VA = VT frequency VA = VE - VD . 1.For VT = 500 ml, f = 10/min, VD = 150 ml, what is VA? . VA = = 3500 ml/min If VE is doubled by increasing VT what is VA? = 10, = 8500 ml/min If the same VE is obtained by doubling frequency, what is VA? = 10, = 7000 ml/min . Thus increasing VT rather than frequency is more effective for VE.

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**F. Alveolar Ventilation and CO2 production**

VCO2 = Expired CO2 - Inspired CO2 . =VA FACO2 VA x PACO2 = PA . .VCO2 K VA = PACO2

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**XIV. RESPIRATORY GAS CASCADE**

PO2 PCO2 mm Hg mm Hg Air (dry) 760 Trachea (humidified; ) 713 Alveolus (some O2 absorbed by blood) Arterial (R-L Shunt) Mixed venous (O2 absorbed by tissues) 40 46

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**O2 Diffusion in Pulmonary Capillaries**

(transit time) 100 Thickened Alveolar Membrane 80 60 PO2 mm Hg Normal Transit Time 40 Exercise Shortens Transit time 20 0.25 0.5 0.75 time in Capillary (sec)

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**CO2 Loading & O2 Unloading**

Tissue CO2 Loading & O2 Unloading CO2 O2 Capillary Wall Cl- O2 CO2 c.a. CO2 + H2O — H2CO3 H+ + HCO3- H+ + HbO2 HHb + O2 Carbamino HHb-CO2

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**CO2 Unloading & O2 Loading**

Lungs CO2 Unloading & O2 Loading CO2 O2 Alveolar Wall O2 CO2 HCO3- Cl- c.a. CO2 + H2O — H2CO3 H+ + HCO3- H+ + HbO2 HHb + O2 Carbamino HHb-CO2

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**HALDANE SHIFT Rest Venous P (mm Hg) CO Content (ml CO /100 ml blood)**

37 40 43 46 49 52 48 50 54 Rest Venous P CO2 (mm Hg) CO 2 Content (ml CO /100 ml blood) HALDANE SHIFT Exercise Venous O2 helps CO2 unloading Arterial (O2)

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**Ventilation Perfusion Ratios**

PO2 = 150 PCO2 = 0 PO2 = 40 PCO2 = 45 PO2 = 100 PCO2 = 40 PO2 = 150 PCO2 = 0 No flow CO2 = 45 . . . Low VA/Q Normal VA/Q High VA/Q

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**50 Low VA/Q Base Apex Normal VA/Q PCO2 (mm Hg) High VA/Q 50 100 150**

PO2 = 40 PCO2 = 45 PO2 = 100 PCO2 = 40 50 Low VA/Q . Base Apex PO2 = 150 PCO2 = 0 Normal VA/Q . PCO2 (mm Hg) High VA/Q . 50 100 150 PO2 (mm Hg)

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**Perfusion Flow of Blood or Air VA/Q VA/Q Ratio Ventilation Top Bottom**

3 Perfusion . VA/Q 2 Flow of Blood or Air . VA/Q Ratio Ventilation 1 Distance up Lung Bottom Top . .

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**Mechanisms of Hypoxemia**

PaO2 PaCO2 PO2 (A-a) PaO2 with 100% O2 Hypoventilation low High Norm >550 Diffusion low norm-low high >550 R-L Shunt low norm-low high < VA/Q Imbalance low norm-lo-hi high >550 Other Hypoxemias (without low PaO2) Anemia Carbon Monoxide Hypoperfusion (CV problem) Local Control Low PAO2 vasoconstriction Low PVCO2 bronchoconstriction

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**C A B Pneumotaxic Center – + Apneustic Center Periph & Central Chemo-**

Fourth Ventricle Nucleus retroambiguous (ventral) 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 signal thresh

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**Peripheral Chemoreceptor Responsiveness**

75 50 % maximal firing rate 25 50 100 500 Arterial PO2 (mm Hg)

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**Plasma BBB CSF CO2 HCO3 + H+ CO2 HCO3 + H+ Pumped CNS Acidosis**

then HCO3 is pumped in (& restores pHCNS faster than kidneys can restore pHsystemic) Respiratory Acidosis (PaCO2)

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**Plasma BBB CSF CO2 HCO3 + H+ CO2 HCO3 + H+ CNS Alkalosis !!!!**

(then pump HCO3 out) Metabolic Acidosis Hyperventilation & PaCO2

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**Ventilatory Response to O2**

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**Ventilatory Response to CO2**

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**Ventilatory Response to CO2**

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**Plasma BBB CSF CO2 HCO3 + H+ CO2 HCO3 + H+ When pHCNS**

returns to norm (HCO3 pumped out) VE is less restrained Respiratory Alkalosis high pHCSF limits Hyperventilation

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