Download Respiratory Physiology

Trachea
(Generation #1)
Conducting Airways
Generations 1-16
Primary Bronchi
(Generation #2)
2o Bronchi
(Generation #3)
Respiratory Zone
Generations ~17-23
Respiratory
Bronchioles
Alveoli
Pa
PA
Pv
PA
Pa
Pv
PB=0
Zone 1
PA>Pa>Pv
Low Flow
Flow=P/R
Zone 2
Pa>PA>Pv
Waterfall
PA<0
PA
Pa
Pv
Zone 3
Pa>Pv>PA
Hi Flow
venous
O2
CO2
arterial
PB=0
Atmospheric Air
High O2 (150 mmHg)
CO2 ~ 0
Inspiration
Expiration
PA<0
venous
PB=0
O2
CO2
Alveolar Air
O2 ~100 mmHg
CO2 ~ 40 mmHg
arterial
venous
PA>0
O2
CO2
arterial
Chest Wall
Lung
Lung
Stuck
Together
Fick’s law
J = DA (C/ X)
Air leak
Pneumothorax
Lung collapses
& Chest expands
Hemoglobin-O2 Binding Curve
% Hb Saturation
Venous
80
60
20
15
CO2
10
40
5
20
0
0
0
20
40
60
PaO2 (mm Hg)
80
100
HbO2 content (ml O2 /dl)
Arterial
100
Inspiratory
Reserve
Inspiratory
Capacity
Vital
Capacity
VT
Expiratory
Reserve
FRC
Residual
Volume
Inspiratory Inspiratory
Reserve
Capacity
IR
IC
Vital
Capacity
TLC
VC
VT
VT
Expiratory
Reserve
FRC
FRC
Residual
Volume
RV
ER
RV
V1
V1
C1V1=N
VL
Equilibrate
Concentration
C2(V1 +VL) =N
VL=(C1/C2)V1 –V1
C1V1= C2(V1 +VL)
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
~6.5 L
Inspiratory
Reserve
Inspiratory
Capacity
Vital
Capacity
5L
VT
600 ml
Expiratory
Reserve
FRC 2.5 L
Residual
Volume
1.2 L
Chest Wall
Lung
Stuck
Together
As we remove air
from pleural space
the lung expands
& the chest wall
gets pulled in.
Lung
Balance of Forces Determines FRC
Intrapleural
space
Ppl = -2
Ppl = -5
Normal
FRC
Ppl= -8
Lung
Wall
Recoil
Force
Ppl = 0
Normal
Emphysema
 lung recoil
Fibrosis
 lung recoil
Pneumothorax
Decreasing
volume
Chest
Wall
Recoil
Force
Increasing
volume
Hooke’s Law: F = -kx
LaPlace
2T=Pr
P=2T/r
P1
P2
For same T, P1>P2
(I.e. 2T/r1 > 2T/r2)
Surface Area (relative)
Surface Area  Surface Tension
Lung
Surfactant
Plasma Surfactant
40%
25%
8%
27%
Detergent
Dipalmitoyl Lecithin
Unsaturated Lecithins
Cholesterol
Apoproteins, other
phospholipids, glycerides,
fatty acids
Water
30
60
Surface Tension (dynes/cm)
80
Surface Area (relative)
Surface Area  Surface Tension
Lung
Surfactant
1. Reduces Work of Breathing
2. Increases Alveolar Stability
(different sizes coexist)
3. Keeps Alveoli Dry
Detergent
Water
30
60
Surface Tension (dynes/cm)
80
Static Compliance Curves
Lung Volume
Normal
Expiration
VT
FRCN
2
0
Inspiration
-2
-4
-6
-8
-10
-12
-14
Pleural Pressure, Ppl (cm H2O)
-16
-18
Static Compliance Curves
Lung Volume
Emphysema
(high compliance)
Normal
VT
FRCE
Fibrosis
(low compliance)
VT
FRCN
VT
FRCF
2
0
-2
-4
-6
-8
-10
-12
-14
Pleural Pressure, Ppl (cm H2O)
-16
-18
Balance of Forces Determines FRC
Lung
Wall
Recoil
Force
Intrapleural
space
Ppl = -2
Ppl = -5
Normal
FRC
Ppl= -8
Ppl = 0
Normal
Emphysema
 lung recoil
Fibrosis
 lung recoil
Pneumothorax
Decreasing
volume
Chest
Wall
Recoil
Force
Increasing
volume
Hooke’s Law: F = -kx
Apex
-5
Base
Chest
Wall
-8
Lung has weight
Ppl = -2
Regional- Apex to Base Differences
Norm Lung Volume
Inspiration
Lung Volume
Apex
Inspiration
Apex
Base
2
0
-2
-4
-6
Alveolar Volume
Alve Ventilation
-8
-10
Pleural Pressure, Ppl (cm H2O)
-12
-14
Base
++
++
Regional- Apex to Base Differences
Lung Volume
Low Lung Volume
(shifts to lower V)
Apex
V
Apex
Alveolar Volume
Alve Ventilation
++
++
Base
2
0
-2
-4
-6
-8
-10
Pleural Pressure, Ppl (cm H2O)
-12
-14
Base
Apex to Base Differences
Lung Volume
Normal Lung V
Low Lung V
Apex
V
Base
2
0
-2
-4
-6
-8
-10
Pleural Pressure, Ppl (cm H2O)
-12
-14
Respiratory Cycle
0.4
Ppl
VT (L)
Respiratory Cycle
Single VT Breath
0.2
0
Inspiration Expiration
-5
Ppl (cm H2O)
Air Flow
(L/s)
0
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)
0
-1
1
2
3
time (sec)
4
Rest FRC
-8
Inspiration
-8
End
Inspiration
+
-6
Expiration
0
-5
Air
Flow
-8
+0.5
-5
0
PB=0
time
PA= 0
End Expiration-FRC
Static Compliance Curves
Lung Volume
Normal
Expiration
VT
FRCN
2
0
Inspiration
-2
-4
-6
-8
-10
-12
-14
Pleural Pressure, Ppl (cm H2O)
-16
-18
Respiratory Cycle
0.4
Ppl
VT (L)
Respiratory Cycle
Single VT Breath
0.2
0
Inspiration Expiration
-5
Ppl (cm H2O)
-8
+0.5
Air Flow
(L/s)
Case of ZERO
Resistance
0
-0.5
+1
PA (cm H2O)
0
-1
1
2
3
time (sec)
4
-5
Rest FRC
-8
Inspiration
-8
End
Inspiration
+
-6
Expiration
0
-5
0
Air
Flow
PB=0
time
PA= 0
End Expiration-FRC
Respiratory Cycle
0.4
Ppl
VT (L)
Respiratory Cycle
Single VT Breath
0.2
0
Inspiration Expiration
-5
Ppl (cm H2O)
Air Flow
(L/s)
0
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)
0
-1
1
2
3
time (sec)
4
Rest FRC
-8
Inspiration
-8
End
Inspiration
+
-6
Expiration
0
-5
Air
Flow
-8
+0.5
-5
0
PB=0
time
PA= 0
End Expiration-FRC
Respiratory Cycle
0.4
Ppl
VT (L)
Respiratory Cycle
Single VT Breath
0.2
0
Inspiration Expiration
-5
Ppl (cm H2O)
-8
+0.5
Air Flow
(L/s)
Case of HIGH
Resistance
0
-0.5
+1
PA (cm H2O)
0
-1
1
2
3
time (sec)
4
-5
Rest FRC
-8
Inspiration
-8
End
Inspiration
+
-6
Expiration
0
-5
0
Air
Flow
PB=0
time
PA= 0
End Expiration-FRC
Dynamic Compression of Airways
Mild Expiratory Effort (P+13)
Normal at FRC
-5
0
PTP=+5
PPl - PA= -5
0
Dynamic Compression of Airways
Mild Expiratory Effort (P+13)
Strong Expiratory Effort (P+30)
+13
-5
Normal at FRC
+8
Normal
+25
+13
0
+13
PTP=+5
PPl - PA= -5
-2
8
4
0
30 25 20 15 10 5
EPP
0
EPP
Equal Pressure Point
(in supported airways)
+11
0
PPl-PA=-2
13
Emphysema
10 8
6
4
+28
2
Low VL&
EPP Basal Alv
also like this
0
Emphysema
30 25 20
EPP
15
10
in unsupported airways
5
0
v = Flow/A
Resistance
8 l
R= ———
r4
k•number
R= —————
A2
5
10
15
Airway Generation
Total Cross Sectional Area
Resistance
Subsegmental
Bronchi
NR= Dv/
=density
D= diameter
v= velocity
= viscosity
Conducting
Zone
5
10
Resp
Zone
15
Airway Generation
Airway Resistance
Normal
 Recoil
Emphysema
Fibrosis
Lung Volume
Volume
Normal
Inspiration
 Recoil
Restrictive
Resistance
Obstructive
FRC
time (sec)
Forced Vital Capacity
Obstructive
Normal
Restrictive
airway resist
TLC
TLC
lung recoil
TLC
FEV1.0
FEV1.0
FVC
FVC
RV
RV
FEV1.0
FVC
1 sec
RV
1 sec
1 sec
FEV1.0 = 4 L
FVC = 5 L
% = 80%
FEV1.0 = 1.2 L
FVC = 3.0 L
% = 40%
FEV1.0 = 2.7 L
FVC = 3.0 L
% = 90%
Expiratory Flow
Flow-Volume Curves
TLC
Effort Independent limb
in forced expiration.
Due to Dynamic
Airway Compression
and airway collapse.
Lung Volume
RV
Expiratory Flow
Forced expiration
Inverted
Inspiration
Inspiratory Flow
TLC
Lung Volume
Inspiration
RV
9
Flow Rate (L/sec)
Normal
Obstructive
Restrictive
9
8
7
6
5
4
Lung Volume (L)
3
2
1
Critical Closing Volume Test
N2 Concentration (%)
TLC
RV
4.
40
1.
3. Alveolar
Plateau
2. Dead Space
Washout
20
Closing
Volume
6
5
4
3
Lung Volume (L)
2
1
Apex to Base Differences
Lung Volume
Normal Lung V
Low Lung V
Apex
V
Base
2
0
-2
-4
-6
-8
-10
Pleural Pressure, Ppl (cm H2O)
-12
-14
Critical Closing Volume Test
N2 Concentration (%)
TLC
RV
4.
40
1.
3. Alveolar
Plateau
2. Dead Space
Washout
Increased
Closing
Volume
20
Closing
Volume
6
5
4
3
Lung Volume (L)
2
1
O2
PO2=100 mm Hg
21 ml O2/dL
O2
PO2=100 mm Hg
0.3 ml O2/dL
O2
PO2=100 mm Hg
21 ml O2/dL
PO2=100 mm Hg
O2 0.3 ml O /dL dissolved
2
20 ml O2/dL HB-O2
N2 Concentration (%)
40
Alveolar
Plateau
A
20
Vd
Inspired O2 diluted
by alveolar N2
Fowler’s Test
Area A = Area B
B
0
0.2
0. 4
0.6
Expired Lung Volume (L)
0.8
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 = 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
Alveolar
Membrane
PO2 mm Hg
80
60
Normal
Transit
Time
40
Exercise
Shortens
Transit
time
20
0.25
0.5
time in Capillary (sec)
0.75
Hemoglobin-O2 Binding Curve
80
97.5
90
20
75
15
50
10
60
40
5
20
26
0
0
20
0
40
60
PaO2 (mm Hg)
80
100
Hb-O2 content
(ml O2 /100 ml blood)
% Saturation of
Hemoglobin
100
Bohr Shift Hb-02 Curve
% Saturation of
Hemoglobin
100
H+],CO2
Temp
80
Normal Hb
60
Bohr Shift
H+], CO2, Temp or DPG
40
20
0
0
20
40
60
PaO2 (mm Hg)
80
100
Normal Hb
Hb-O2 content
(ml O2 /100 ml blood)
20
Myoglobin
15
Carbon Monoxide
10
5
Anemia
0
0
20
40
60
PaO2 (mm Hg)
80
100
CO2
Tissue
CO2 Loading & O2 Unloading
O2
Capillary Wall
CO2
Cl-
O2
CO2 + H2Oc.a.
— H2CO3  H+ + HCO3H+ + HbO2  HHb + O2
Carbamino
HHb-CO2
CO2
Lungs
CO2 Unloading & O2 Loading
O2
Alveolar Wall
CO2
O2
HCO3Clc.a.
CO2 + H2O —
H2CO3  H+ + HCO3-
H+ + HbO2  HHb + O2
Carbamino
HHb-CO2
HALDANE SHIFT
54
CO2 Content
(ml CO 2 /100 ml blood)
Exercise Venous
Rest Venous
52
50
Arterial (O2)
48
O2 helps CO2 unloading
46
37
40
43
46
PCO2 (mm Hg)
49
52
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
PO2 = 40
PCO2 = 45
PO2 = 100
PCO2 = 40
50
PCO2 (mm Hg)
.
Low VA/Q
Base
.
Normal VA/Q
PO2 = 150
PCO2 = 0
Apex
.
High VA/Q
50
100
PO2 (mm Hg)
150
Perfusion
.
VA/Q
2
VA/Q
Ratio
Flow of Blood or Air
3
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
.
VA/Q Imbalance
low
norm-low
high
<550
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
Pneumotaxic
Center
Medulla
Oblongata
Apneustic Center
Fourth
Ventricle
+
Cut-off
signal
C
Nucleus
tractus
Solitarius
(dorsal)
–
Cut-off
A
+
Insp
Dors ts
+
Nucleus
retroambiguous
(ventral)
thresh
+
B
+
C1
vent
Vagus
Stretch
Respiratory
Muscles
Periph &
Central
Chemoreceptors
Peripheral Chemoreceptor Responsiveness
% maximal firing rate
75
50
25
50
100
Arterial PO2 (mm Hg)
500
Plasma
BBB
CSF
CO2  HCO3 + H+
CO2
HCO3
Pumped
+
CNS Acidosis
then HCO3 is pumped in
H+
(& restores pHCNS faster than
kidneys can restore pHsystemic)
Respiratory
Acidosis (PaCO2)
Plasma
CO2
BBB
CSF
CO2  HCO3 + H+
HCO3
+
H+
Metabolic
Acidosis
Hyperventilation
& PaCO2
CNS
Alkalosis !!!!
(then pump HCO3 out)
Ventilatory Response to O2
Ventilation (L/min)
60
50
40
PCO2 = 45 mm Hg
30
20
PCO2 = 40 mm Hg
10
0
30
PCO2 = 20 mm Hg
60
PaO2 (mm Hg)
90
Ventilation (L/min)
Ventilatory Response to CO2
60
PaO2 ~ 60 mm Hg
40
PaO2 ~100 mm Hg
PaO2  200 mm Hg
20
0
35
40
45
PaCO2 (mm Hg)
50
55
Ventilatory Response to CO2
Ventilation (L/min)
50
Metabolic Acidosis
Normal
Metabolic Alkalosis
40
30
20
10
0
35
40
45
PaCO2 (mm Hg)
50
55
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
CSF chemoreceptors no longer limiting hyperventilation.
Norm.

-
2-4 days
low
low
Norm.
Peripheral alkalosis no longer restraining hyperventilation.
Norm.


30 Yrs.
low
Norm.
Hypoxic response of chemoreceptors lost.
Norm.
-
-
Norm.
Plasma
CO2
BBB
CSF
CO2  HCO3 + H+
HCO3
+
H+
Respiratory
Alkalosis
high pHCSF limits
Hyperventilation
When pHCNS
returns to norm
(HCO3 pumped out)
VE is less restrained