1 Inspiratory Inspiratory Reserve Capacity P O2 =100 mm Hg P O2 - - PDF document

SLIDE 1

1

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

O2 CO2

venous arterial

PB=0 PA<0

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

O2 CO2

venous arterial

PB=0 PA>0

Alveolar Air O2 ~100 mmHg CO2 ~ 40 mmHg Expiration

Fick’s law J = DA (ΔC/ ΔX)

Lung Chest Wall Stuck Together Lung Air leak Pneumothorax Lung collapses & Chest expands

Hemoglobin-O2 Binding Curve

20 40 60 80 100 20 40 60 80 100 5 10 15 20

Venous Arterial

↑CO2

PaO2 (mm Hg) % Hb Saturation HbO2 content (ml O2 /dl)

SLIDE 2

2

PO2=100 mm Hg 14 ml O2/dL PO2=100 mm Hg 0.3 ml O2/dL O2 O2 PO2=100 mm Hg 14 ml O2/dL PO2=100 mm Hg 0.3 ml O2/dL dissolved 20 ml O2/dL HB-O2 O2 O2

VT T

• t

a l L u n g C a p a c i t y Expiratory Reserve Inspiratory Reserve FRC Inspiratory Capacity Residual Volume Vital Capacity

1 s

FEV1.0

VT T

• t

a l L u n g C a p a c i t y Expiratory Reserve Inspiratory Reserve FRC Inspiratory Capacity Residual Volume Vital Capacity 500 ml 2.6 L 1.5 L 4.5 L ~6 L

Forced Vital Capacity

TLC

FEV1.0 FVC

1 sec

FEV1.0 = 4 L FVC = 5 L % = 80% RV

TLC RV Expiratory Flow Rate

Lung Volume

Flow-Volume Curves

V. A Few Terms (for Your Convenience) Eupnia - Normal breathing. Apnea - cessation of respiration (at FRC). Apneusis - cessation of respiration (in the inspiratory phase). Apneustic breathing – Apneusis interrupted by by periodic exhalation. 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 - Intrapleural pressure (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) V

• E – ventilation (liters/min) (V
• = dV/dt)

V

• A – Alveolar ventilation (liters/min)

Q

• – Blood Flow (liters/min)

SLIDE 3

3

Some Typical Normal Values for Some Key Pulmonary Parameters FRC 2.6 L RV 1.5 L TLC 6.0 L VT 500 ml FVC 4.5 L FEV1.0 / FVC >75% Frequency 10-12/min V

• A (norm)

5 ± 0.5 L/min V

• E (norm)

7 ± 0.7 L/min V

• E (max)

120-150 L/min

• Max. insp flow

7-10 L/sec

• Max. exp flow

6-9 L/sec Compliance 60-100 mL/cm H20 PAO2 100 mm Hg PaO2 (21% O2) 90-95 mm Hg PaO2 (100% O2) >500 mm Hg PaCO2 40 ± 3 mm Hg Arterial pH 7.37-7.43 PvO2 40 mm Hg PvCO2 46 mm Hg [Hb] 14-15 g/dL

Chest Wall Recoil Force Lung Wall Recoil Force

Normal

Balance of Forces Determines FRC

Hooke’s Law: F = -kx

Fibrosis ↑ lung recoil Ppl= -8

Intrapleural space

Ppl = -2 Emphysema ↓ lung recoil

Increasing volume Decreasing volume

Ppl = 0 Pneumo- thorax

Normal FRC

Ppl = -5

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

Ppl = -5 Normal

Balance of Forces Determines FRC

Hooke’s Law: F = -kx

Intrapleural space Increasing volume Decreasing volume

Ppl = 0

Ppl = -2

Emphysema ↓ lung recoil Fibrosis ↑ lung recoil Pneumo- thorax

Ppl= -8

SLIDE 4

4

Surface Area (relative) Surface Tension (dynes/cm) 30 60

Water Detergent Lung Surfactant Plasma

80

↑Surface Area ∝ ↑Surface Tension Surfactant

40% Dipalmitoyl Lecithin 25% Unsaturated Lecithins 8% Cholesterol 27% Apoproteins, other phospholipids, glycerides, fatty acids

Hysteresis

Surface Area (relative) Surface Tension (dynes/cm) 30 60

Water Detergent Lung Surfactant

80

↑Surface Area ∝ ↑Surface Tension

• 1. Reduces Work of Breathing
• 2. Increases Alveolar Stability

(different sizes coexist)

• 3. Keeps Alveoli Dry
• 18
• 16
• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Normal

VT FRCN

PIP (cm H2O)

Lung Volume

Expiration Inspiration

Hysteresis Occurs During Dynamic Air Flow Due to Surfactant reorientation & Airway Resistance Static Lung Compliance Curve

Static Compliance Curves

• 18
• 16
• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Fibrosis (low compliance) Normal Emphysema (high compliance) VT FRCN VT FRCF VT FRCE Intrapleural Pressure, PIP (cm H2O) Lung Volume

Chest Wall Recoil Force Lung Wall Recoil Force Normal FRC

PIP = -5 Normal

Balance of Forces Determines FRC

Hooke’s Law: F = -kx

Intrapleural space Increasing volume Decreasing volume

PIP = 0

PIP = -2

Emphysema ↓ lung recoil Fibrosis ↑ lung recoil Pneumo- thorax

PIP= -8

SLIDE 5

5

Lung has weight

• 8

PIP = -2

• 5

Apex Base Chest Wall

Regional- Apex to Base Differences

• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Apex Base

Norm Lung Volume

Alveolar Volume Alve Ventilation Apex Base ++ ++ Inspiration Inspiration PIP (cm H2O) Lung Volume

Regional- Apex to Base Differences

• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Apex ΔV Base

Low Lung Volume (shifts to lower V)

Alveolar Volume Alve Ventilation Apex Base ++ ++ PIP (cm H2O) Lung Volume

Apex to Base Differences

• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Apex ΔV Base Low Lung V Normal Lung V PIP (cm H2O) Lung Volume

The dashed trace is the PIP required to overcome recoil forces (ot PTP taken from compliance curve). More PIP (solid curve) is required to

• vercome airway resistance to flow.

N.B. ΔP = PA-PB ∝ Resist•Flow. Air Flow (L/s)

+1

• 1

+0.6

• 0.6

PA (cm H2O)

1 2 3 4

time (sec)

• 5
• 8

cm H2O

VT (L)

0.4 0.2

Respiratory Cycle

Inspiration Expiration

PTP PIP PTP PIP PB=0

• 5
• 7
• 8
• 6
• 5

Rest FRC Inspiration End Inspiration +

• Air

Flow PA= 0 PIP End Expi- ration-FRC Expiration time Respiratory Cycle Single VT Breath

Static Compliance Curves

• 18
• 16
• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Normal VT FRCN Pleural Pressure, Ppl (cm H2O) Lung Volume

Expiration Inspiration

SLIDE 6

6

PA (cm H2O)

+1

• 1

+0.5

• 0.5

Air Flow (L/s)

1 2 3 4

time (sec)

• 5
• 8

Ppl (cm H2O)

Case of ZERO Resistance

VT (L)

0.4 0.2

Respiratory Cycle

Inspiration Expiration

• 5
• 8
• 8
• 6
• 5

Rest FRC Inspiration End Inspiration +

• Air

Flow PA= 0 Ppl End Expi- ration-FRC Expiration time Respiratory Cycle Single VT Breath PB=0

PA (cm H2O)

+1

• 1

+0.5

• 0.5

Air Flow (L/s)

1 2 3 4

time (sec)

• 5
• 8

Ppl (cm H2O) The linear Dashed trace is the Ppl required to overcome recoil forces. More Ppl (solid curve) is required to

• vercome airway resistance to flow.

N.B. ΔP = PA-PB ∝ Resist•Flow. VT (L)

0.4 0.2

Respiratory Cycle

Inspiration Expiration

• 5
• 8
• 8
• 6
• 5

Rest FRC Inspiration End Inspiration +

• Air

Flow PA= 0 Ppl End Expi- ration-FRC Expiration time Respiratory Cycle Single VT Breath PB=0

PA (cm H2O)

+1

• 1

+0.5

• 0.5

Air Flow (L/s)

1 2 3 4

time (sec)

• 5
• 8

Ppl (cm H2O) VT (L)

0.4 0.2

Respiratory Cycle

Inspiration Expiration

• 5
• 8
• 8
• 6
• 5

Rest FRC Inspiration End Inspiration +

• Air

Flow PA= 0 Ppl End Expi- ration-FRC Expiration time Respiratory Cycle Single VT Breath PB=0 Case of HIGH Resistance

Airway Generation

5 1 0 15

Total Cross Sectional Area

Conducting Zone Resp Zone v = Flow/A

NR= ρDv/η ρ=density D= diameter v= velocity η= viscosity

Airway Generation Resistance

Subsegmental Bronchi

5 1 0 15

Resistance 8ηl R= ——— πr4 k•number R= ————— A2

N.B. this is total x-sectional area (AT

2 =n2An 2)

Lung Volume Airway Resistance Normal ↓ Recoil Emphysema

Fibrosis

Mild Expiratory Effort (P+13) Normal at FRC

• 5

Dynamic Compression of Airways

PTP=+5 PPl - PA= -5

SLIDE 7

7

+28 30 25 20 15 10 5 0 EPP Emphysema

in unsupported airways

Dynamic Compression of Airways

EPP

Equal Pressure Point (in supported airways)

Low VL& Basal Alv also like this +13 Mild Expiratory Effort (P+13) +8 8 4 Normal at FRC

• 5

+13 +13

PTP=+5 PPl - PA= -5

+8 13 10 8 6 4 2 EPP Emphysema +11

PPl-PA=-2

• 2

+11 Strong Expiratory Effort (P+30) +25 30 25 20 15 10 5 EPP Normal +25 13 10 8 6 4 2 EPP Emphysema +11

PPl-PA=-2

• 2

Dynamic Compression of Airways

EPP

Equal Pressure Point (in supported airways)

+13 Mild Expiratory Effort (P+13) +8 8 4 Normal at FRC

• 5

+13 +13

PTP=+5 PPl - PA= -5

Low VL& Basal Alv also like this Strong Expiratory Effort (P+30) +25 30 25 20 15 10 5 EPP Normal +25 +28 Emphysema 30 29 28 27 25 20 0

Pursed-lips Hi Resist

EPP

Moves toward the mouth & supported airways

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

Forced Vital Capacity

TLC

FEV1.0 FVC

1 sec

FEV1.0 = 4 L FVC = 5 L % = 80% RV

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

Effort Independent limb in forced expiration.

TLC RV

Expiratory Flow Lung Volume Flow-Volume Curves

Due to Dynamic Airway Compression and airway collapse. Inverted Inspiration

RV

Expiratory Flow Forced expiration Inspiration Inspiratory Flow

TLC

Lung Volume

SLIDE 8

8

Normal Obstructive Restrictive

9 8 7 6 5 4 3 2 1

Lung Volume (L) Flow Rate (L/sec)

9

TLC RV Lung Volume (L)

6 5 4 3 2 1

• 3. Alveolar

Plateau 1.

• 2. Dead Space

Washout 4.

N2 Concentration (%)

20 40

Critical Closing Volume Test

Closing Volume

Apex to Base Differences

• 14
• 12
• 10
• 8
• 6
• 4
• 2

2

Apex ΔV Base Pleural Pressure, Ppl (cm H2O) Lung Volume Low Lung V Normal Lung V

TLC RV Lung Volume (L)

6 5 4 3 2 1

• 3. Alveolar

Plateau 1.

• 2. Dead Space

Washout 4.

N2 Concentration (%)

20 40

Critical Closing Volume Test

Closing Volume Increased Closing Volume

Hemoglobin-O2 Binding Curve

20 40 60 80 100 20 40 60 80 100 5 10 15 20

26 50 75 90 97.5

PaO2 (mm Hg) % Saturation of Hemoglobin Hb-O2 content (ml O2 /100 ml blood) Hemoglobin-O2 Binding Curve

20 40 60 80 100 20 40 60 80 100 5 10 15 20 26 50 75 90 97.5

PaO2 (mm Hg) % Saturation of Hemoglobin Hb-O2 content (ml O2 /100 ml blood)

20 40 60 80 100 1 2 3

Dissolved O2 HbO2 PaO2 (mm Hg)

Hb-O2 content (ml O2 /100 ml blood)

SLIDE 9

9

PO2=100 mm Hg 14 ml O2/dL PO2=100 mm Hg 0.3 ml O2/dL O2 O2 PO2=100 mm Hg 14 ml O2/dL PO2=100 mm Hg 0.3 ml O2/dL dissolved 20 ml O2/dL HB-O2 O2 O2

Bohr Shift Hb-02 Curve

20 40 60 80 100 20 40 60 80 100

Normal Hb

Bohr Shift ↑[H+], ↑CO2, ↑Temp or DPG ↓[H+],↓CO2

↓Temp

PaO2 (mm Hg) % Saturation of Hemoglobin

20 40 60 80 100 5 10 15 20

Myoglobin Normal Hb Anemia Carbon Monoxide PaO2 (mm Hg) Hb-O2 content (ml O2 /100 ml blood)

Capillary Wall

CO2 + H2O —→ H2CO3 → H+ + HCO3

• O2

CO2 CO2 Cl- H+ + HbO2 → HHb + O2 Carbamino HHb-CO2 O2

Tissue CO2 Loading & O2 Unloading

c.a.

Alveolar Wall

O2 CO2 CO2 Cl- H+ + HbO2 ← HHb + O2 Carbamino HHb-CO2 O2

Lungs CO2 Unloading & O2 Loading

c.a.

HCO3

• CO2 + H2O ←— H2CO3 ← H+ + HCO3
• O2 curve

Whole blood total CO2 Content (ml CO2/dl)

SLIDE 10

10

↑O2 helps CO2 unloading Arterial (↑O2)

37 40 43 46 49 52 46 48 50 52 54

Rest Venous PCO2(mm Hg) CO2 Content (ml CO 2 /100 ml blood)

HALDANE SHIFT

↑O2 helps CO2 unloading Arterial (↑O2) Exercise Venous

37 40 43 46 49 52 46 48 50 52 54

Rest Venous PCO2(mm Hg) CO2 Content (ml CO 2 /100 ml blood)

HALDANE SHIFT

• XIV. RESPIRATORY GAS CASCADE

PO2 PCO2 mm Hg mm Hg ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Air (dry) 760 × 0.21 160 Trachea (humidified; 760-47) 713 × 0.21 150 Alveolus (some O2 absorbed by blood) 100 40 Arterial (R-L Shunt) 90 40+ Mixed venous (O2 absorbed by tissues) 40 46

CO is Diffusion Limited (soaked up by Hb immediately) Uptake depends on Diffusing Capacity CO+Hb=Hb-CO [CO]=“0” NO2 is Perfusion Limited (Blood is quickly “saturated”) Uptake depends on how much blood goes by NO2 doesn’t bind [NO2]i= [NO2]o

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)

Distance along Capillary (%)

33% 67% 100%

Capillary PX (% alveolar)

20 40 60 80 100

Diffusion in Pulmonary Capillaries

O2 CO N2O

Diffusion Limited Perfusion Limited time in Capillary (sec)

0.25 0.5 0.75

PO2 mm Hg

20 40 60 80 100

Normal Transit Time

Exercise Shortens Transit time

Thickened Alveolar Membrane

O2 Diffusion in Pulmonary Capillaries (transit time)

SLIDE 11

11

Expired Lung Volume (L)

0 0.2 0. 4 0.6 0.8

Alveolar Plateau Inspired O2 diluted by alveolar N2

N2 Concentration (%)

20 40

A B Fowler’s Test Area A = Area B

Vd

The Bohr Equation VD1 (PACO2 – PECO2) ⎯⎯⎯ = ⎯⎯⎯⎯⎯⎯⎯⎯ VT PACO2 PCO2 values are measured by a CO2 electrode. Sometimes PaCO2 is used. 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 V

• E = V
• D + V
• A = VT × frequency

V

• A = V
• E – V
• D

1. For VT = 500 ml, f = 10/min, VD = 150 ml, what is V

• A?

V

• A = 5000 - 1500

= 3500 ml/min 2. If V

• E is doubled by increasing VT what is V
• A?

= 10,000 - 1500 = 8500 ml/min 3. If the same V

• E is obtained by doubling frequency, what is V
• A?

= 10,000 - 3000 = 7000 ml/min Thus increasing VT rather than frequency is more effective for ↑ V

• E.

F. Alveolar Ventilation and CO2 production V

• CO2 = Expired CO2 - Inspired CO2

= V

• A × FACO2

V

• A × PACO2

= ⎯⎯⎯⎯⎯⎯ PA V

• CO2 × k

V

• A = ⎯⎯⎯⎯⎯⎯⎯

PACO2 Where k= 863 mmHg

• r 0.863 (mmHg•L/ml)

So, for a given rate of CO2 production, steady state PACO2 is inversely related to V

• A.

Thus, if V

• A is decreased by 1/2, PACO2 is doubled.
• XIX. RESPIRATORY EXCHANGE RATIO

RQ = V

• CO2/V
• O2

The relative amounts of O2 consumed and CO2 produced depends upon the fuel. Carbohydrate RQ = 1 Fat RQ = 0.7 Protein RQ = 0.8 A typical "normal" RQ is 0.8 The partial pressures of O2 and CO2 are also affected. V

• CO2

PACO2 40 RQ = ⎯⎯⎯ = ⎯⎯⎯⎯⎯ = ⎯⎯⎯ V

• O2

PIO2 - PEO2 50 Study Questions/ Exercises Q: Why does this ratio necessarily reflect the RQ? Alveolar Gas Equation – Allows you to estimate PAO2 – PaO2 gradient. PAO2 = FIO2 (PATM – PH2O) – PaCO2/RQ + K PAO2 = PIO2 – PaCO2/RQ e.g. = 150 – 40/0.8 = 100 mmHg K = PACO2 •FIO2 • ({1-RQ}/RQ) a small correction (2 mmHg) usually ignored

SLIDE 12

12

Zone 1 PA>Pa>Pv Low Flow

PA

Pa Pv

PA

Pa Pv

Zone 2 Pa>PA>Pv Waterfall Zone 3 Pa>Pv>PA Hi Flow

PA

Pa Pv

PA

Pa Pv

Zone 4 Same, but Hi extra-Alv-R

Flow of Blood or Air Bottom Top Distance up Lung Ventilation Perfusion

1 2 3

VA/Q

. .

VA/Q Ratio

. . PO2 = 40 PCO2 = 45

Normal VA/Q Low VA/Q High VA/Q

CO2 = 45

PO2 = 150 PCO2 = 0 PO2 = 100 PCO2 = 40 PO2 = 150 PCO2 = 0 . . .

Ventilation Perfusion Ratios

No flow

. . .

PO2 = 40 PCO2 = 45

Low VA/Q

.

Normal VA/Q

.

PO2 = 100 PCO2 = 40

High VA/Q

.

PO2 = 150 PCO2 = 0

PO2 (mm Hg) PCO2 (mm Hg) 50 100 150 50 Base Apex

Flow of Blood or Air Bottom Top

Distance up Lung

Ventilation Perfusion

1 2 3

VA/Q Ratio

. .

VA/Q

. .

Region VA V

• A

Q

• V
• A/Q
• PCO2

PO2 ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Apex + + + Base + ++ + ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯

SLIDE 13

13

Mechanisms of Hypoxemia

• A. Hypoventilation
• B. Diffusion Abnormalities

C.Right to Left Shunt D.Ventilation/Perfusion Mismatch

• E. Low inspired PO2

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 <550 . VA/Q Imbalance low norm-lo-hi high >550

Other Hypoxemias (without low PaO2) a. Anemia b. Carbon Monoxide c. Hypoperfusion (CV problem) Local Control a. Low PAO2 → vasoconstriction b. Low PVCO2 → bronchoconstriction

Hemoglobin-O2 Binding Curve

20 40 60 80 100 120 140 20 40 60 80 100 5 10 15 20

26 50

75 100

(100+75)/2=87.5 (20+15)/2 =17.5 PaO2 (mm Hg) % Saturation of Hemoglobin Hb-O2 content (ml O2 /100 ml blood)

High VA/Q

. .

Low VA/Q

. .

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?.

Hemoglobin-O2 Binding Curve

20 40 60 80 100 120 140 20 40 60 80 100 5 10 15 20

26 50

75 100

(100+75)/2=87.5 (20+15)/2 =17.5

87.5 54 mmHg

PaO2 (mm Hg) % Saturation of Hemoglobin Hb-O2 content (ml O2 /100 ml blood)

High VA/Q

. .

Low VA/Q

. .

High VA/Q can’t compensate For Low VA/Q

. . . .

37 40 43 46 49 52 46 48 50 52 54

PCO2(mm Hg) CO2 Content (ml CO2 /100 ml blood)

30 High VA/Q

. .

Low VA/Q

. .

44 High VA/Q Compensates For Low VA/Q

. . . . Integrator in CNS (Medulla) Sensors Chemoreceptors Central & Peripheral Control Variables PO2, PCO2, pH Afferent Sensory info Efferent to motor neurons Effectors Respiratory Muscles (e.g. Diaphragm)

Simple Negative Feedback System

SLIDE 14

14

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

Peripheral Chemoreceptor Responsiveness

BBB CSF Plasma CO2 HCO3 + H+ CO2 ←→ HCO3 + H+ Respiratory Acidosis (↑PaCO2) Pumped CNS Acidosis then HCO3 is pumped in

(& restores pHCNS faster than kidneys can restore pHsystemic)

BBB CSF Plasma CO2 HCO3 + H+ CO2 ←→ HCO3 + H+ Metabolic Acidosis Hyperventilation & ↓PaCO2 CNS Alkalosis !!!!

(then pump HCO3 out)

SLIDE 15

15

Expir

DRG Inspir Higher Brain Centers Pneumotaxic Center Apneustic Center

–

Periph & Central Chemo- receptors Respiratory Muscles Vagus Stretch

+

Tonic Insp Drive

Cut-off

Thresh Adjust

Cut-off +/–

Expiratory effort

+/– 30 60 90 10 20 30 40 50 60

PCO2 = 40 mm Hg PCO2 = 45 mm Hg PCO2 = 20 mm Hg PaO2 (mm Hg) Ventilation (L/min)

Ventilatory Response to O2

35 40 45 50 55 20 40 60

PaO2 ≥ 200 mm Hg PaCO2 (mm Hg) Ventilation (L/min) PaO2 ~100 mm Hg PaO2 ~ 60 mm Hg

Ventilatory Response to CO2

35 40 45 50 55 10 20 30 40 50

Normal Metabolic Alkalosis Metabolic Acidosis PaCO2 (mm Hg) Ventilation (L/min)

Ventilatory Response to CO2

18,000 32,000 65,000 98,000

Altitude (ft)

10,000 20,000 30,000 25 50 75 100 125 150

PIO2 (PB -47)(0.21) -50 Altitude (ft) PIO2 (mmHg)

SLIDE 16

16

EFFECTS OF HIGH ALTITUDE A. At 10,000 ft PB=525 mmHg inspired PO2 is ~100 mmHg ⇒PAO2 is ~50 mmHg. 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. At 63,000 ft PB=47 mmHg, inspired PO2 is ~0 mmHg ⇒ tissues boils, H2O vapor. B. Acclimatization and hyperventilation at 10,000 ft Time at High Alt. PaO2 PaCO2 pH blood pH CSF VE [HCO3] ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ 1 Hr low low high high ↑

• 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. ↑↑↑ ↓ Peripheral alkalosis no longer restraining hyperventilation. 30 Yrs. low Norm. Norm. Norm.

• Hypoxic response of chemoreceptors lost.

BBB CSF Plasma CO2 HCO3 + H+ CO2 ←→ HCO3 + H+ Respiratory Alkalosis high pHCSF limits Hypoxic Hyperventilation When pHCNS returns to norm

(HCO3 pumped out) 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] ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ 1 Hr low low high high ↑ Normal Hypoxic drive is restrained by low PaCO2 and high pH. 1-2 day. low low high Norm. ↑↑ ↓[HCO3]CSF CSF chemoreceptors no longer limiting hyperventilation. 2-4 days low low Norm. Norm. ↑↑↑ ↓[HCO3]Syst Peripheral alkalosis no longer restraining hyperventilation. 30 Yrs. low Norm. Norm. Norm.

• Hypoxic response of chemoreceptors lost.
• C. Other adjustments

1, Polycythemia

• 2. Enhanced Diffusing Capacity
• 3. Imcreased Capillary Density
• 4. Right shift of HbO2 curve

LA LV RV RA Lung Tissue

Placenta

SVC IVC FO Aorta DA

Lung

25 15 30 14 19 22 26

Low O2 Hi Resist PA

PV PV

20 40 60 80 100 5 10 15 20

Myoglobin Normal Hb Anemia Carbon Monoxide PaO2 (mm Hg) Hb-O2 content (ml O2 /100 ml blood) LA LV RV RA Lung Tissue

Placenta

SVC IVC FO Aorta DA

Lung

25 15 30 14 19 22 26

Hi O2 Lo Resist

PV PV

95 95 95 40 40

SLIDE 17

17

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 = V

• CO2/V
• O2

Respiratory Quotient 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 Nitrogen Washout New Ones! VD2 (PaCO2 – PECO2) ⎯⎯ = ⎯⎯⎯⎯⎯⎯⎯⎯ Bohr Eqn VT PaCO2 V

• A = V
• CO2 × k / PACO2

Alveolar Ventilation-PACO2 PAO2 = PIO2 – PaCO2/RQ Alveolar Gas Eqn