Trachea (Generation #1)

Conducting Airways Generations 1-16 Primary Bronchi (Generation #2)

2o Bronchi (Generation #3)

Respiratory Zone Generations ~17-23

Respiratory Alveoli

Atmospheric Air

PB=0 High O2 (150 mmHg) PB=0 CO2 ~ 0

Inspiration Expiration

Alveolar Air

O2 ~100 mmHg PA<0 PA>0 CO2 ~ 40 mmHg O O venous 2 arterial venous 2 arterial

CO2 CO2

Hemoglobin-O2 Binding Curve

100 Arterial 20 HbO Chest Wall 2 80 Venous (ml O content Lung 15

60 Stuck ↑CO2 10 Together 40

Air leak 2

% Hb Saturation % Hb 5 Pneumothorax 20 /dl) Fick’s law Lung collapses & Chest expands 0 0 J = DA (ΔC/ ΔX) 0 20 40 60 80 100

PaO2 (mm Hg)

1 Inspiratory Inspiratory Reserve Capacity PO2=100 mm Hg PO2=100 mm Hg

O2 O2 y

t 14 ml O2/dL 14 ml O2/dL i

c

a Vital

p

a Capacity

C

g

n FEV

u 1.0

L VT

l

a

t

o

T Expiratory PO2=100 mm Hg PO2=100 mm Hg O O Reserve 1 s 2 0.3 ml O2/dL 2 0.3 ml O2/dL dissolved FRC 20 ml O /dL HB-O 2 2 Residual Volume

Inspiratory Inspiratory Forced Flow-Volume Curves Reserve Capacity TLC

y

t

i

c

a Vital FEV1.0 p FVC a Capacity

C

g 4.5 L

n

u ~6 L

L VT

l RV a 500 ml 1 sec

t

o Expiratory Flow Rate Flow Expiratory

T FEV1.0 = 4 L Expiratory FVC = 5 L TLC RV Reserve % = 80% FRC 2.6 L Lung Volume Residual Volume 1.5 L

V. A Few Terms (for Your Convenience) Eupnia - Normal . - cessation of (at FRC). Apneusis - cessation of respiration (in the inspiratory phase). Apneustic breathing – Apneusis interrupted by by periodic . Hyperpnea – increased breathing (usual ↑VT). Tachypnea – increased frequency of respiration. Hyperventilation – increased alveolar ventilation (PACO2 <37 mm Hg). Hypoventilation – decreased alveolar ventilation (PACO2 >43 mm Hg). Atelectasis – closed off alveoli, typically at end exhalation. Cheyne-Stokes Respiration – Cycles of gradually increasing and decreasing VT. Dyspnea- Feeling of difficulty in breathing. Orthopnea- Discomfort in breathing unless standing or sitting upright.

PIP - (pressure in space between visceral and parietal plurae) PTP - Transpulmonary pressure (distending pressure of airway) PACO2 - Alveolar PCO2 (partial pressure of CO2). PaCO2 - arterial PCO2. PvCO2 - venous PCO2 PAO2 - Alveolar PO2 PaO2 - arterial PO2 PvO2 - venous PO2 PECO2 - PCO2 of exhaled air FECO2 – fraction of exhaled air which is CO2 (i.e. A= Alveolar, a= arterial, v= venous, E = exhaled, I = inspired) VE – Expired volume (liters) • • VE – ventilation (liters/min) (V = dV/dt) • VA – Alveolar ventilation (liters/min) • Q – Blood Flow (liters/min)

2 Some Typical Normal Values for Some Key Pulmonary Parameters FRC 2.6 L Max. exp flow 6-9 L/sec

RV 1.5 L Compliance 60-100 mL/cm H20 TLC 6.0 L

VT 500 ml FVC 4.5 L PAO2 100 mm Hg PaO2 (21% O2) 90-95 mm Hg

PaO2 (100% O2) >500 mm Hg FEV1.0 / FVC >75% Frequency 10-12/min PaCO2 40 ± 3 mm Hg • Arterial pH 7.37-7.43 VA (norm) 5 ± 0.5 L/min • PvO2 40 mm Hg VE (norm) 7 ± 0.7 L/min • PvCO2 46 mm Hg V (max) 120-150 L/min E [Hb] 14-15 g/dL Max. insp flow 7-10 L/sec

Balance of Forces Determines FRC Hooke’s Law: F = -kx Chest Chest Wall Wall Recoil Lung Lung volume

Force Intrapleural Increasing space P = -2 pl Normal Stuck FRC P = -5 Together pl Ppl= -8 Lung P = 0 As we remove air Wall pl Recoil volume from pleural space Force Decreasing the lung expands & the chest wall gets pulled in. Normal Emphysema Fibrosis Pneumo- ↓ lung recoil ↑ lung recoil thorax

Balance of Forces Determines FRC Hooke’s Law: F = -kx

Chest Wall Recoil Intrapleural space volume

Force Increasing P = -2 pl Normal FRC P = -5 P = -8 Lung pl pl Wall Ppl = 0 volume Recoil Decreasing Force

Normal Emphysema Fibrosis Pneumo- ↓ lung recoil ↑ lung recoil thorax

3 ↑Surface Area ∝ ↑Surface Tension

Lung Surfactant Plasma Surfactant s 40% Dipalmitoyl Lecithin si re 25% Unsaturated Lecithins te 8% Cholesterol ys H 27% Apoproteins, other phospholipids, glycerides, fatty acids

Surface Area (relative) Detergent Water

30 60 80 Surface Tension (dynes/cm)

Hysteresis Occurs During Dynamic Air Flow ↑Surface Area ∝ ↑Surface Tension Due to Surfactant reorientation &

Lung Static Curve Surfactant Normal 1. Reduces Work of Breathing 2. Increases Alveolar Stability Expiration (different sizes coexist) 3. Keeps Alveoli Dry VT Lung Volume FRCN Inspiration

Surface Area (relative) Detergent Water 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 30 60 80 PIP (cm H2O) Surface Tension (dynes/cm)

Static Compliance Curves Emphysema (high compliance) Balance of Forces Determines FRC Hooke’s Law: F = -kx Chest Wall Normal Recoil Intrapleural VT space volume

Force Increasing PIP = -2 FRCE Normal Fibrosis FRC (low compliance) P = -8

Lung VolumeLung P = -5 VT Lung IP IP

FRCN Wall V PIP = 0 volume

T Decreasing FRC Recoil F Force

2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18

Intrapleural Pressure, PIP (cm H2O) Normal Emphysema Fibrosis Pneumo- ↓ lung recoil ↑ lung recoil thorax

4 Regional- Apex to Base Differences Norm Lung Volume Apex Chest -8 Wall Inspiration Apex

Lung Volume Lung Inspiration Apex Base -5 Lung has weight Base Alveolar Volume ++ Alve Ventilation ++

2 0 -2 -4 -6 -8 -10 -12 -14

PIP (cm H2O)

Base PIP = -2

Regional- Apex to Base Differences Apex to Base Differences Low Lung Volume (shifts to lower V)

Normal Lung V

Apex ΔV Apex ΔV Low Lung V Lung Volume Lung Lung Volume Lung Apex Base Alveolar Volume ++ Alve Ventilation ++ Base Base

2 0 -2 -4 -6 -8 -10 -12 -14 2 0 -2 -4 -6 -8 -10 -12 -14

PIP (cm H2O) PIP (cm H2O)

Respiratory Cycle Static Compliance Curves VT (L) PIP time 0.4 Respiratory Cycle Single V Breath T -5 Rest FRC 0.2 0

Air -7 Inspiration Flow - 0 Inspiration Expiration End -5 P PB=0 P = 0 -8 IP A Inspiration Normal PTP O 2 + -6 Expiration PTP cm H P End Expi- IP 0 -5 Expiration -8 The dashed trace is the PIP ration-FRC required to overcome recoil forces +0.6 (ot P taken from compliance curve). P TP Lung Volume VT A More P (solid curve) is required to (cm H2O) IP 0 overcome airway resistance to flow. N.B. ΔP = P -P ∝ Resist•Flow. FRCN A B Inspiration -0.6 +1 Air Flow (L/s) 0 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -1 1 2 3 4 Pleural Pressure, P (cm H O) time (sec) pl 2

5 Respiratory Cycle Respiratory Cycle P time P time V (L) pl V (L) pl 0.4 T 0.4 T Respiratory Cycle Respiratory Cycle

Single VT Breath Single VT Breath 0.2 0 -5 Rest FRC 0.2 0 -5 Rest FRC

Air Air 0 Inspiration Expiration -8 Inspiration 0 Inspiration Expiration -8 Inspiration Flow - Flow - -5 Ppl (cm H2O) -5 Ppl (cm H2O) End End PB=0 -8 PB=0 -8 PA= 0 Inspiration PA= 0 Inspiration

+ -6 Expiration + -6 Expiration -8 -8 +0.5 End Expi- +0.5 End Expi- Air Flow 0 -5 Air Flow 0 -5 (L/s) ration-FRC (L/s) ration-FRC 0 0 Case of ZERO The linear Dashed trace is the Ppl Resistance required to overcome recoil forces. -0.5 -0.5 More Ppl (solid curve) is required to overcome airway resistance to flow. +1 +1 N.B. ΔP = PA-PB ∝ Resist•Flow. PA (cm H2O) PA (cm H2O) 0 0

-1 1 2 3 4 -1 1 2 3 4 time (sec) time (sec)

Respiratory Cycle P time V (L) pl 0.4 T Respiratory Cycle Subsegmental v = Flow/A Single VT Breath Bronchi 0.2 0 -5 Rest FRC NR= ρDv/η ρ=density Air D= diameter 0 Inspiration Expiration -8 Inspiration Flow - v= velocity -5 Ppl (cm H2O) η= viscosity End PB=0 P = 0 -8 A Inspiration Resistance

+ -6 Expiration 8ηl -8 R= ——— πr4 +0.5 End Expi- Air Flow 0 -5 Conducting Resp (L/s) ration-FRC Resistance k•number Zone Zone 0 Case of HIGH R= ————— Resistance A2 -0.5 +1 Total Cross Sectional Area Sectional Cross Total

PA (cm H2O) 0 5 1 0 15 5 1 0 15 Airway Generation Airway Generation -1 1 2 3 4 time (sec) N.B. this is total x-sectional area 2 2 2 (AT =n An )

Dynamic Compression of Airways Mild Expiratory Effort (P+13)

-5 Normal at FRC

0 0

↓ Recoil PTP=+5 PPl -PA= -5 Normal Emphysema Airway Resistance Airway Fibrosis

Lung Volume

6 Dynamic Compression of Airways Dynamic Compression of Airways Mild Expiratory Effort (P+13) Strong Expiratory Effort (P+30) Mild Expiratory Effort (P+13) Strong Expiratory Effort (P+30) +13 +13 -5 +8 Normal at FRC +25 Normal -5 +8 Normal at FRC +25 Normal +13 +13 +8 +25 +25 0 +13 840 30 25 20 15 10 5 0 0 +13 840 30 25 20 15 10 5 0

PTP=+5 PTP=+5 P -P = -5 EPP EPP P -P = -5 EPP EPP Pl A Equal Pressure Point Pl A Equal Pressure Point (in supported airways) (in supported airways)

-2 +11 Emphysema +28 Emphysema -2 +11 Emphysema +28 Emphysema Pursed-lips +11 Hi Resist 0 13 10 8 6 4 2 0 30 25 20 15 10 5 0 0 13 10 8 6 4 2 0 30 29 28 27 25 20 0

PPl-PA=-2 Low VL& PPl-PA=-2 Low VL& EPP EPP Basal Alv EPP EPP Basal Alv Moves toward the mouth also like this in unsupported airways also like this & supported airways

Normal Forced Vital Capacity Inspiration Obstructive Restrictive Volume Normal ↑airway resist ↑lung recoil ↑ Recoil TLC TLC TLC FEV1.0 FEV1.0 Restrictive FEV FVC FVC 1.0 FVC RV 1 sec RV 1 sec

↑Resistance RV 1 sec Obstructive FRC time (sec) FEV1.0 = 4 L FEV1.0 = 1.2 L FEV1.0 = 2.7 L FVC = 5 L FVC = 3.0 L FVC = 3.0 L % = 80% % = 40% % = 90%

Flow-Volume Curves Forced expiration

Inverted Effort Independent limb Inspiration in forced expiration. Expiratory Flow Expiratory

TLC Lung Volume RV Due to Dynamic Airway Compression and airway collapse. Expiratory Flow Expiratory

Inspiration

TLC Lung Volume RV Flow Inspiratory

7 Critical Closing Volume Test TLC RV 9 Normal 4. 40 1. 2. 3. Alveolar Washout Plateau

Obstructive 20 Restrictive

Concentration (%) Closing 2 Volume N Flow Rate (L/sec)

9 8 7 6 5 4 3 2 1 6 5 4 3 2 1 Lung Volume (L) Lung Volume (L)

Critical Closing Volume Test Apex to Base Differences TLC RV

4. 40 1. 2. Dead Space 3. Alveolar Normal Lung V Washout Plateau

Increased Apex Closing ΔV Low Lung V 20 Volume Lung Volume Lung Concentration (%) 2 N Closing Base Volume

2 0 -2 -4 -6 -8 -10 -12 -14 6 5 4 3 2 1 Pleural Pressure, Ppl (cm H2O) Lung Volume (L)

Hemoglobin-O2 Binding Curve 100 97.5 20 (ml O Hemoglobin-O2 Binding Curve 90 Hb-O 80 75 15 2 100 97.5 20 blood) ml /100 (ml O

90 2 60 content

Hb-O 50 10 80 75 15 2 40 /100 ml blood) Hemoglobin 2 % Saturation of Saturation % 5 60 content 20 50 10 26 40 0 0 0 20 40 60 80 100 Hemoglobin

3 (ml O % Saturation of Saturation % 5 P (mm Hg) aO2 HbO

20 2 Hb-O 2 /100 ml blood) ml /100

2 2 26 content 0 0 0 20 40 60 80 100 1 Dissolved O PaO2 (mm Hg) 2 0 0 20 40 60 80 100 PaO2 (mm Hg)

8 Bohr Shift Hb-02 Curve

100 + ↓[H ],↓CO2 PO2=100 mm Hg PO2=100 mm Hg O O 80 ↓Temp 2 14 ml O /dL 2 14 ml O /dL 2 2 Normal Hb 60

40 Bohr Shift

Hemoglobin + ↑[H ], ↑CO2, ↑Temp or DPG % Saturation of 20

PO2=100 mm Hg PO2=100 mm Hg O O 0 2 0.3 ml O2/dL 2 0.3 ml O2/dL dissolved 0 20 40 60 80 100 20 ml O2/dL HB-O2 PaO2 (mm Hg)

CO Tissue 20 Normal Hb 2 O2 CO2 Loading & O2 Unloading Myoglobin Capillary Wall 15 Cl- O CO2 2 Carbon Monoxide content 10 2 CO + H Oc.a. —→ H CO → H+ + HCO - /100 ml blood) /100 ml 2 2 2 3 3 2

Hb-O 5 H+ + HbO → HHb + O Anemia 2 2 (ml O (ml Carbamino 0 HHb-CO 0 20 40 60 80 100 2

PaO2 (mm Hg)

CO 2 O2

CO Unloading & O Loading /dl) 2 2 2

Alveolar Wall

- O CO2 HCO3 2 Content (ml CO Content

Cl- 2 c.a. + - CO2 + H2O ←—H2CO3 ← H + HCO3

+ H + HbO2 ← HHb + O2 O2 curve Carbamino Whole blood total CO Whole blood HHb-CO2

9 HALDANE SHIFT HALDANE SHIFT 54 54 Exercise Venous

Rest Venous Rest Venous 52 52

Content 50 Arterial (↑O2) Content 50 Arterial (↑O2) /100 ml blood) /100 ml blood) 2 2 2 2 CO CO 48 ↑O2 helps CO2 unloading 48 ↑O2 helps CO2 unloading (ml CO (ml CO

46 46

37 40 43 46 49 52 37 40 43 46 49 52

PCO2(mm Hg) PCO2(mm Hg)

CO is Diffusion Limited (soaked up by Hb immediately) Uptake depends on XIV. RESPIRATORY GAS CASCADE

PO2 PCO2 mm Hg mm Hg ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ CO+Hb=Hb-CO [CO]=“0” Air (dry) 760 × 0.21 160 0 Trachea (humidified; 760-47) 713 × 0.21 150 0 NO2 doesn’t bind [NO2]i= [NO2]o Alveolus (some O2 absorbed by blood) 100 40 Arterial (R-L Shunt) 90 40+

Mixed venous (O2 absorbed by tissues) 40 46

NO2 is Limited (Blood is quickly “saturated”) Uptake depends on how much blood goes by

Measuring Diffusion capacity, DL ( or Transfer capacity) with CO JCO = DCOA ΔP/ Δx ΔP = PACO –PaCO and PaCO=0 and DCO, A & Δx are lumped into DL DL = JCO /PACO (where JCO is the rate of CO uptake measured)

Diffusion in Pulmonary Capillaries O2 Diffusion in Pulmonary Capillaries (transit time)

100 Perfusion Limited 100

N O Thickened 80 2 80 Alveolar Membrane

(% alveolar) O2 60 60 X mm Hg

O2 Normal 40 40 P Transit Exercise Time Capillary P Capillary 20 20 Shortens Transit CO Diffusion Limited time

33% 67% 100% 0.25 0.5 0.75 Distance along Capillary (%) time in Capillary (sec)

10 40 Alveolar Plateau

A Inspired O2 diluted by alveolar N2

20 Vd Fowler’s Test Area A = Area B Concentration (%) 2 N

B

0 0.2 0. 4 0.6 0.8 Expired Lung Volume (L)

The Bohr Equation

VD1 (PACO2 – PECO2) ⎯⎯⎯ = ⎯⎯⎯⎯⎯⎯⎯⎯ VT PACO2

P values are measured by a CO electrode. Sometimes P is used. CO2 2 aCO2 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 = 5000 - 1500 = 3500 ml/min • • 2. If VE is doubled by increasing VT what is VA? = 10,000 - 1500 = 8500 ml/min • • 3. If the same VE is obtained by doubling frequency, what is VA? = 10,000 - 3000 = 7000 ml/min • Thus increasing VT rather than frequency is more effective for ↑ VE.

F. Alveolar Ventilation and CO2 production • VCO2 = Expired CO2 - Inspired CO2 XIX. RESPIRATORY EXCHANGE RATIO • • RQ = VCO2/VO2 • = VA × FACO2 The relative amounts of O2 consumed and CO2 produced depends upon the fuel. • Carbohydrate RQ = 1 VA × PACO2 Fat RQ = 0.7 = ⎯⎯⎯⎯⎯⎯ Protein RQ = 0.8 PA A typical "normal" RQ is 0.8

The partial pressures of O2 and CO2 are also affected. •

• VCO2 × k • VCO2 PACO2 40 VA = ⎯⎯⎯⎯⎯⎯⎯ RQ = ⎯⎯⎯ = ⎯⎯⎯⎯⎯ = ⎯⎯⎯ • PACO2 V O2 PIO2 - PEO2 50

Where k= 863 mmHg Study Questions/ Exercises or 0.863 (mmHg•L/ml) Q: Why does this ratio necessarily reflect the RQ?

Alveolar Gas Equation – Allows you to estimate PAO2 – PaO2 gradient. P = F (P – P ) – P /RQ + K So, for a given rate of CO2 production, AO2 IO2 ATM H2O aCO2 • P = P – P /RQ steady state PACO2 is inversely related to VA. AO2 IO2 aCO2 • e.g. = 150 – 40/0.8 = 100 mmHg Thus, if VA is decreased by 1/2, PACO2 is doubled. K = PACO2 •FIO2 • ({1-RQ}/RQ) a small correction (2 mmHg) usually ignored

11 Zone 1

PA PA>Pa>Pv P P a v Low Flow

Zone 2 PA P P a v Pa>PA>Pv Waterfall

Zone 3 PA P P a v Pa>Pv>PA Hi Flow

P P A P a v Zone 4 Same, but Hi extra-Alv-R

Ventilation Perfusion Ratios 3 PO2 = 150 P = 0 Perfusion CO2 .. VA/Q 2 V Ratio . A PO2 = 40 PO2 = 100 PO2 = 150 /Q . PCO2 = 45 PCO2 = 40 PCO2 = 0 Ventilation No flow

1 CO = 45 2 ...... Flow of Blood or Air Low VA/QNormal VA/Q High VA/Q

Top Bottom Distance up Lung

3

P = 40 Air Perfusion O2 .. PCO2 = 45

or V /Q PO2 = 100 A P = 40 50 CO2 2 V . Ratio . Low VA/Q A /Q Base Blood . . Ventilation Normal VA/Q P = 150 O2 1 PCO2 = 0 (mm Hg) Flow of

CO2 Apex P

Distance up Lung Top . Bottom • • • • High VA/Q Region VA VA Q VA/Q PCO2 PO2 ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Apex + + + 50 100 150 Base + ++ + ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ PO2 (mm Hg)

12 Mechanisms of Hypoxemia

PaO2 PaCO2 PO2 (A-a) PaO2 with 100% O2 ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Hypoventilation low High Norm >550 Mechanisms of Hypoxemia Diffusion low norm-low high >550 R-L Shunt low norm-low high <550 A. Hypoventilation . V /Q Imbalance low norm-lo-hi high >550 B. Diffusion Abnormalities A Other Hypoxemias (without low P ) C. Right to Left Shunt aO2 a. Anemia b. Carbon Monoxide D. Ventilation/Perfusion Mismatch c. Hypoperfusion (CV problem)

E. Low inspired PO2 Local Control

a. Low PAO2 → vasoconstriction b. Low PVCO2 →

Hemoglobin-O2 Binding Curve Hemoglobin-O2 Binding Curve 100 100 100 20 100 20 (ml O 87.5 (ml O /Q /Q A A .. .. Hb-O Hb-O 80 75 80 75 15 2 15 2 /100 ml blood) /100 ml blood) High V High V 2 2

60 content 60 .. content 50 50 High VA/Q /Q 10 /Q 10 A A .. .. can’t compensate.. 40 40 For Low VA/Q Hemoglobin Hemoglobin Low V Low V

% Saturation of Saturation % 5 of Saturation % 5 20 20 54 mmHg 26 26 0 0 0 0 0 20 40 60 80 100 120 140 0 20 40 60 80 100 120 140 P (mm Hg) P (mm Hg) aO2 (100+75)/2=87.5 aO2 (100+75)/2=87.5 (20+15)/2 =17.5 (20+15)/2 =17.5 Study Questions/ Exercises: Consider ½ of pulmonary blood flow going to regions where PAO2 is 150 mm Hg and the other ½ to a region of PAO2 = 40 mm Hg. Assume PACO2 is 30 and 50 mm Hg in these respective regions. How does PaO2 become less than normal while PaCO2 is normal?.

Simple Negative Feedback System 54 .. Integrator Low V /Q A in CNS 52 (Medulla) Afferent Sensory info 50 Efferent .. to motor Sensors 48 High VA/Q /100 ml blood) Content Compensates neurons 2 2 .. For Low V /Q Central & A Effectors CO Peripheral 46 Respiratory Muscles

(ml CO (e.g. Diaphragm) 44 .. High V /Q A Control Variables 30 37 40 43 46 49 52 PO2, PCO2, pH PCO2(mm Hg)

13 Peripheral Responsiveness Plasma BBB CSF

+ 75 CO2 CO2 ←→ HCO3 + H

Pumped HCO3 50 CNS Acidosis + then HCO3 is pumped in (& restores pHCNS faster than + H kidneys can restore pHsystemic) 25 % maximal firing rate firing maximal %

Respiratory Acidosis (↑P ) 50 100 500 aCO2 Arterial PO2 (mm Hg)

Plasma BBB CSF

+ CO2 CO2 ←→ HCO3 + H

HCO3

+

H+

CNS Metabolic Hyperventilation Alkalosis !!!! Acidosis & ↓PaCO2 (then pump HCO3 out)

14 Higher Brain Centers Pneumotaxic Center Apneustic Center

+/–

Cut-off DRG Inspir Expir – Thresh Adjust +/–

E x e Cut-off p + v i i r r Periph & a t D o Central r p y s

e n Chemo- I f f c o i Vagus receptors r n t o T Stretch

Respiratory Muscles

Ventilatory Response to O2 Ventilatory Response to CO2 60 60 PaO2 ~ 60 mm Hg

50

40 40 P ~100 mm Hg PCO2 = 45 mm Hg aO2 30

PaO2 ≥ 200 mm Hg 20

Ventilation (L/min) 20 Ventilation (L/min) Ventilation 10 PCO2 = 40 mm Hg

PCO2 = 20 mm Hg 0 30 60 90 0 35 40 45 50 55 PaO2 ( mm Hg) PaCO2 ( mm Hg)

Ventilatory Response to CO2

50 Metabolic Acidosis Normal 40 Metabolic Alkalosis

30 150

20 125 100 P

Ventilation (L/min) IO2 75

10 (mmHg) 50 IO2 P 25 0 (PB -47)(0.21) -50 35 40 45 50 55 0 18,000 32,000 65,000 98,000 0 10,000 20,000 30,000 P (mm Hg) Altitude (ft) aCO2 Altitude (ft)

15 EFFECTS OF HIGH ALTITUDE

A. At 10,000 ft PB=525 mmHg inspired PO2 is ~100 mmHg ⇒PAO2 is ~50 mmHg. Plasma BBB CSF At 15,000 ft PB=380 mmHg inspired PO2 is ~70 mmHg ⇒PAO2 is ~20 mmHg. At Mt Everest PB=250 mmHg, inspired PO2 is ~42 mmHg ⇒PAO2 is ~0 mmHg. + CO2 CO2 ←→ HCO3 + H At 63,000 ft PB=47 mmHg, inspired PO2 is ~0 mmHg ⇒ tissues boils, H2O vapor.

B. Acclimatization and hyperventilation at 10,000 ft HCO3

Time at High Alt. PaO2 PaCO2 pH blood pH CSF VE [HCO3]

⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ + 1 Hr low low high high ↑ - H+ Hypoxic drive is restrained by low PaCO2 and high pH.

1-2 day. low low high Norm. ↑↑ - CSF chemoreceptors no longer limiting hyperventilation.

2-4 days low low Norm. Norm. ↑↑↑ ↓ When pHCNS Peripheral alkalosis no longer restraining hyperventilation. Respiratory high pHCSF limits returns to norm Alkalosis Hypoxic (HCO pumped out) 30 Yrs. low Norm. Norm. Norm. - - . 3 Hypoxic response of chemoreceptors lost. Hyperventilation VE is less restrained

EFFECTS OF HIGH ALTITUDE B. Acclimatization and hyperventilation at 10,000 ft

Time at High Alt. PaO2 PaCO2 pH blood pH CSF VE [HCO3] Aorta Low O2 25 ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Hi Resist PA 1 Hr low low high high ↑ Normal

SVC 15 19 DA Hypoxic drive is restrained by low PaCO2 and high pH. PV PV RA LA 1-2 day. low low high Norm. ↑↑ ↓[HCO3]CSF FO 22 CSF chemoreceptors no longer limiting hyperventilation. IVC Lung Lung 2-4 days low low Norm. Norm. ↑↑↑ ↓[HCO3]Syst 26 Peripheral alkalosis no longer restraining hyperventilation. RV LV

30 Yrs. low Norm. Norm. Norm. - - Hypoxic response of chemoreceptors lost. 14 Tissue C. Other adjustments 1, Polycythemia 30 2. Enhanced Diffusing Capacity 3. Imcreased Capillary Density 4. Right shift of HbO2 curve Placenta

Normal Hb 20 95 Hi O Aorta Myoglobin 2 25 Lo Resist 40 15 DA 95 SVC 15 19 PV PV RA Carbon Monoxide FO LA content 10 40 2 IVC /100 ml blood) /100 ml

2 Lung Lung 26 RV LV Hb-O 5 22 Anemia 95 (ml O (ml

14 0 Tissue 0 20 40 60 80 100 30 PaO2 (mm Hg)

Placenta

16 Equations Old ones you already knew ΔP=QR Ohm’s Law J=DA(ΔC/Δx) Fick’s Law JCO=DL-COPCO PV=nRT Universal Gas Law (Boyle’s & Charles’ Laws) Px= P Fx Dalton’s Law of Partial Pressures Cx = Px kSolubility Henry’s Law P=2T/r Law of LaPlace F= –kx Hooke’s Law R = 8ηl/πr4 Tubular resistance NR= ρDv/η Reynold’s Number – + CO2 + H2O ↔ H2CO3 ↔ HCO3 + H • • RQ = VCO2/VO2 PTP= PAirway – PIP Transpulmonary P (Transmural)

Derivable (simple algebra word problem) VL = VS([He]in – [He]fin)/[He]fin Helium Dilution VL = VS FEN2/FN2-air

New Ones!

VD2 (PaCO2 – PECO2) ⎯⎯ = ⎯⎯⎯⎯⎯⎯⎯⎯ Bohr Eqn VT PaCO2

• • VA = VCO2 × k / PACO2 Alveolar Ventilation-PACO2

PAO2 = PIO2 – PaCO2/RQ Alveolar Gas Eqn

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