Trachea

(Generation #1)

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

2o Bronchi
(Generation #3)

Respiratory Zone
Generations ~17-23

Respiratory
Bronchioles
Alveoli
 Zone 1 PB=0
PA
Pa Pv PA>Pa>Pv
Low Flow
Flow=P/R

PA Zone 2
Pa Pv
Pa>PA>Pv
Waterfall
PA<0

PA Zone 3 O2
venous arterial
Pa Pv Pa>Pv>PA
Hi Flow CO2
 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
venous
O2 arterial venous
O2 arterial

CO2 CO2
 Chest Wall
Lung Lung

Stuck
Together

Air leak
Pneumothorax
Fick’s law Lung collapses
& Chest expands
J = DA (C/ X)
 Hemoglobin-O2 Binding Curve
100 Arterial 20

HbO2 content (ml O2 /dl)

% Hb Saturation

80 Venous
15

60
CO2 10
40

5
20

0 0
0 20 40 60 80 100
PaO2 (mm Hg)
 Inspiratory Inspiratory
Reserve Capacity

Vital
Capacity

VT

Expiratory
Reserve
FRC
Residual
Volume
Inspiratory Inspiratory
Reserve Capacity IR
IC
Vital
Capacity VC
TLC
VT VT

Expiratory
Reserve ER
FRC
FRC
Residual
Volume RV RV
V1 V1 Equilibrate
Concentration

C1V1=N C2(V1 +VL) =N

VL VL
VL=(C1/C2)V1 –V1

C1V1= C2(V1 +VL)

III. 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.

Ppl - Pleural 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)
.
VE – ventilation (liters/min)
.
VA – Alveolar ventilation (liters/min)
Q – Blood Flow (liters/min)
Some Normal Values For Some Key Pulmonary Parameters
FRC 2.5  0.5 L Max. exp flow 6-9 L/sec
RV 1.2  0.3 L Compliance 60-100 mL/cm H20
TLC 6.5  0.5 L
VT 500  100 ml
FVC 4.5  0.5 L PAO2 100 mm Hg
PaO2 (21% O2) 90-95 mm Hg
FEV1.0 / FVC >75% PaO2 (100% O2) >500 mm Hg
Frequency 10-12/min PaCO2 40  3 mm Hg

V A (norm) 5  0.5 L/min Arterial pH 7.37-7.43

V E (norm) 7  0.7 L/min PvO2 40 mm Hg

V E (max) 120-150 L/min PvCO2 46 mm Hg
Max. insp flow 7-10 L/sec [Hb] 14-15 g/dL
 Inspiratory Inspiratory
Reserve Capacity

Vital
Capacity
~6.5 L

5L
VT 600 ml

Expiratory
Reserve
FRC 2.5 L
Residual
Volume
1.2 L
 Chest Wall
Lung Lung

Stuck
Together

As we remove air
from pleural space
the lung expands
& the chest wall
gets pulled in.
 Balance of Forces Determines FRC
Hooke’s Law: F = -kx
Chest

Increasing
Wall

volume
Recoil
Force Intrapleural
space
Ppl = -2
Normal
FRC
Ppl = -5 Ppl= -8

Decreasing
Lung

volume
Wall Ppl = 0
Recoil
Force

Normal Emphysema Fibrosis Pneumo-

 lung recoil  lung recoil thorax
LaPlace
2T=Pr
P=2T/r

P1
P2

For same T, P1>P2

(I.e. 2T/r1 > 2T/r2)
 Surface Area  Surface Tension
Surface Area (relative)
Lung
Surfactant Plasma Surfactant
40% Dipalmitoyl Lecithin
25% Unsaturated Lecithins
8% Cholesterol
27% Apoproteins, other
phospholipids, glycerides,
fatty acids

Detergent Water

30 60 80
Surface Tension (dynes/cm)
 Surface Area  Surface Tension
Surface Area (relative)
Lung
Surfactant
1. Reduces Work of Breathing
2. Increases Alveolar Stability
(different sizes coexist)
3. Keeps Alveoli Dry

Detergent Water

30 60 80
Surface Tension (dynes/cm)
 Static Compliance Curves

Normal
Lung Volume

Expiration

VT
FRCN
Inspiration

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

Pleural Pressure, Ppl (cm H2O)
 Static Compliance Curves
Emphysema
(high compliance)

Normal
Lung Volume

VT
FRCE
Fibrosis
VT (low compliance)
FRCN
VT
FRCF

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

Pleural Pressure, Ppl (cm H2O)
 Balance of Forces Determines FRC
Hooke’s Law: F = -kx

Chest
Wall

Increasing
volume
Recoil
Intrapleural
Force space
Ppl = -2
Normal
FRC
Ppl = -5 Ppl= -8

Decreasing
Lung

volume
Wall Ppl = 0
Recoil
Force

Normal Emphysema Fibrosis Pneumo-

 lung recoil  lung recoil thorax
 Apex Chest
-8 Wall

-5 Lung has weight

Base Ppl = -2
 Regional- Apex to Base Differences
Norm Lung Volume

Inspiration
Apex
Lung Volume

Inspiration Apex Base

Base Alveolar Volume ++
Alve Ventilation ++

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

Pleural Pressure, Ppl (cm H2O)
 Regional- Apex to Base Differences
Low Lung Volume
(shifts to lower V)
Lung Volume

Apex
V

Apex Base
Alveolar Volume ++
Alve Ventilation ++
Base

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

Pleural Pressure, Ppl (cm H2O)
 Apex to Base Differences

Normal Lung V
Lung Volume

Apex
V
Low Lung V

Base

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

Pleural Pressure, Ppl (cm H2O)
 Respiratory Cycle
Ppl time
VT (L)
0.4
Respiratory Cycle
Single VT Breath
0.2 0 -5 Rest FRC

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

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

-1 1 2 3 4
time (sec)
 Static Compliance Curves

Normal
Lung Volume

Expiration

VT
FRCN
Inspiration

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

Pleural Pressure, Ppl (cm H2O)
 Respiratory Cycle
Ppl time
VT (L)
0.4
Respiratory Cycle
Single VT Breath
0.2 0 -5 Rest FRC

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

+ -6 Expiration
-8
+0.5
Air Flow 0 End Expi-
-5
(L/s) ration-FRC
0 Case of ZERO
Resistance
-0.5
+1
PA (cm H2O)
0

-1 1 2 3 4
time (sec)
 Respiratory Cycle
Ppl time
VT (L)
0.4
Respiratory Cycle
Single VT Breath
0.2 0 -5 Rest FRC

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

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

-1 1 2 3 4
time (sec)
 Respiratory Cycle
Ppl time
VT (L)
0.4
Respiratory Cycle
Single VT Breath
0.2 0 -5 Rest FRC

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

+ -6 Expiration
-8
+0.5
Air Flow 0 End Expi-
-5
(L/s) ration-FRC
0 Case of HIGH
Resistance
-0.5
+1
PA (cm H2O)
0

-1 1 2 3 4
time (sec)
 Dynamic Compression of Airways
Mild Expiratory Effort (P+13)

-5 Normal at FRC

0 0

PTP=+5
PPl - PA= -5
 Dynamic Compression of Airways
Mild Expiratory Effort (P+13) Strong Expiratory Effort (P+30)
+13

-5 +8 Normal at FRC Normal

+25
+13

0 +13 8 4 0 30 25 20 15 10 5 0

PTP=+5
PPl - PA= -5 EPP EPP
Equal Pressure Point
(in supported airways)

-2 +11 Emphysema +28 Emphysema

0 13 10 8 6 4 2 0 30 25 20 15 10 5 0

PPl-PA=-2 Low VL&

EPP Basal Alv EPP
also like this in unsupported airways
 Subsegmental v = Flow/A
Bronchi
NR= Dv/
=density

Total Cross Sectional Area

D= diameter
v= velocity
= viscosity
Resistance

Resistance
8 l
R= ———
r4
Conducting Resp
k•number Zone Zone
R= —————
A2

5 10 15 5 10 15

Airway Generation Airway Generation

Airway Resistance

 Recoil
Normal Emphysema

Fibrosis

Lung Volume
 Normal

Volume
Inspiration

 Recoil
Restrictive

Resistance
Obstructive FRC
time (sec)
 Forced Vital Capacity
Obstructive Restrictive
Normal airway resist lung recoil
TLC TLC TLC
FEV1.0
FEV1.0
FEV1.0 FVC FVC
FVC
RV 1 sec RV 1 sec

RV 1 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
Expiratory Flow

Effort Independent limb

in forced expiration.

Due to Dynamic
Airway Compression
and airway collapse.

TLC Lung Volume RV

Expiratory Flow
Forced expiration

Inverted
Inspiration

TLC Lung Volume RV

Inspiratory Flow

Inspiration
 9
Normal
Flow Rate (L/sec)

Obstructive
Restrictive

9 8 7 6 5 4 3 2 1
Lung Volume (L)
 Critical Closing Volume Test
TLC RV

4.
N2 Concentration (%)

40
1. 2. Dead Space 3. Alveolar
Washout Plateau

20

Closing
Volume

6 5 4 3 2 1

Lung Volume (L)

 Apex to Base Differences

Normal Lung V
Lung Volume

Apex
V
Low Lung V

Base

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

Pleural Pressure, Ppl (cm H2O)
 Critical Closing Volume Test
TLC RV

4.
N2 Concentration (%)

40
1. 2. Dead Space 3. Alveolar
Washout Plateau

Increased
Closing
20 Volume

Closing
Volume

6 5 4 3 2 1

Lung Volume (L)

 PO2=100 mm Hg PO2=100 mm Hg
O2 O2
21 ml O2/dL 21 ml O2/dL

PO2=100 mm Hg PO2=100 mm Hg
O2 0.3 ml O2/dL O2 0.3 ml O /dL dissolved
2
20 ml O2/dL HB-O2
 40
Alveolar
Plateau
N2 Concentration (%)

A Inspired O2 diluted
by alveolar N2

20
Vd
Fowler’s Test
Area A = Area B

0 0.2 0. 4 0.6 0.8

Expired Lung Volume (L)

The Bohr Equation

VD1 (PACO2 – PECO2)

 = 
VT PACO2 D. Sample Calculation
VD2 (PaCO2 – PECO2) VT = 600 ml PACO2 = 38 mmHg
 =  PECO2 = 28 mmHg PaCO2 = 40 mmHg
VT PaCO2
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
.
=VA  FACO2
.
VA x PACO2
= 
PA
.
.VCO2  K
VA = 
PACO2
XIII. RESPIRATORY EXCHANGE RATIO
. .
RQ = VCO2/VO2
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.

PACO2 40
RQ =  = 
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 = PIO2 – PaCO2/RQ

K = PACO2 FIO2  ({1-RQ}/RQ) a small correction (2 mm Hg) usually ignored

XIV. RESPIRATORY GAS CASCADE
PO2 PCO2
mm Hg mm Hg

Air (dry) 760  0.21 160 0
Trachea (humidified; 760-47) 713  0.21 150 0
Alveolus (some O2 absorbed by blood) 100 40
Arterial (R-L Shunt) 90 40+
Mixed venous (O2 absorbed by tissues) 40 46
 O2 Diffusion in Pulmonary Capillaries
(transit time)
100

Thickened
80
Alveolar
PO2 mm Hg

Membrane
60

Normal
40
Transit
Exercise Time
20 Shortens
Transit
time

0.25 0.5 0.75

time in Capillary (sec)

 Hemoglobin-O2 Binding Curve
100 97.5 20
90

(ml O2 /100 ml blood)

% Saturation of

80

Hb-O2 content
75
15
Hemoglobin

60
50 10
40

5
20

26
0 0
0 20 40 60 80 100
PaO2 (mm Hg)
 Bohr Shift Hb-02 Curve
100
H+],CO2
% Saturation of

80 Temp
Hemoglobin

Normal Hb
60

40 Bohr Shift
H+], CO2, Temp or DPG
20

0
0 20 40 60 80 100
PaO2 (mm Hg)
(ml O2 /100 ml blood) 20 Normal Hb
Myoglobin
Hb-O2 content

15

Carbon Monoxide
10

5
Anemia

0
0 20 40 60 80 100
PaO2 (mm Hg)
 CO2 Tissue
O2
CO2 Loading & O2 Unloading
Capillary Wall

CO2 Cl- O2

CO2 + H2Oc.a.
— H2CO3  H+ + HCO3-

H+ + HbO2  HHb + O2

Carbamino
HHb-CO2
 CO2 Lungs
O2
CO2 Unloading & O2 Loading
Alveolar Wall

CO2 HCO3- O2

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

H+ + HbO2  HHb + O2

Carbamino
HHb-CO2
 HALDANE SHIFT
54 Exercise Venous
(ml CO 2 /100 ml blood)
Rest Venous
CO2 Content

52

50 Arterial (O2)

48 O2 helps CO2 unloading

46

37 40 43 46 49 52
PCO2 (mm Hg)
 Ventilation Perfusion Ratios
PO2 = 150
PCO2 = 0

PO2 = 40 PO2 = 100 PO2 = 150

PCO2 = 45 PCO2 = 40 PCO2 = 0
No flow

CO2 = 45
. . .
Low VA/Q Normal VA/Q High VA/Q
 PO2 = 40
PCO2 = 45
PO2 = 100
50 PCO2 = 40
.
Low VA/Q Base
PCO2 (mm Hg)

.
Normal VA/Q
PO2 = 150
PCO2 = 0

Apex

.
High VA/Q
50 100 150
PO2 (mm Hg)
 3

Flow of Blood or Air

Perfusion
.
VA/Q
2
.

Ratio
VA/Q
Ventilation
1

Bottom Distance up Lung Top

. .
Region VA VA Q VA/Q PCO2 PO2

Apex + + +
Base + ++ +

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
 Medulla Pneumotaxic
Oblongata Center
Apneustic Center
Fourth
Ventricle +
Cut-off
C signal
Nucleus
Cut-off
– thresh
tractus
Solitarius A +
(dorsal) Insp
+ Dors ts
Nucleus
retroambiguous
(ventral) +
B
vent
C1 +
Periph &
Central
Vagus Chemo-
Stretch receptors
Respiratory
Muscles
 Peripheral Chemoreceptor Responsiveness

75
% maximal firing rate

50

25

50 100 500
Arterial PO2 (mm Hg)
 Plasma BBB CSF

CO2 CO2  HCO3 + H+

Pumped
HCO3
CNS Acidosis
+ then HCO3 is pumped in
(& restores pHCNS faster than
H+ kidneys can restore pHsystemic)

Respiratory
Acidosis (PaCO2)
 Plasma BBB CSF

CO2 CO2  HCO3 + H+

HCO3

H+

Metabolic Hyperventilation CNS

Alkalosis !!!!
Acidosis & PaCO2
(then pump HCO3 out)
 Ventilatory Response to O2
60
Ventilation (L/min)

50

40
PCO2 = 45 mm Hg
30

20

10 PCO2 = 40 mm Hg
PCO2 = 20 mm Hg
0
30 60 90
PaO2 (mm Hg)
 Ventilatory Response to CO2
60 PaO2 ~ 60 mm Hg
Ventilation (L/min)

40 PaO2 ~100 mm Hg

PaO2  200 mm Hg
20

0
35 40 45 50 55
PaCO2 (mm Hg)
 Ventilatory Response to CO2
50
Metabolic Acidosis
Normal
40
Ventilation (L/min)

Metabolic Alkalosis

30

20

10

0
35 40 45 50 55
PaCO2 (mm Hg)
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.
 Plasma BBB CSF

CO2 CO2  HCO3 + H+

HCO3

H+

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