C/ · PDF file3 Some Typical Normal Values for Some Key Pulmonary Parameters FRC 2.6 L RV 1.5...
Transcript of C/ · PDF file3 Some Typical Normal Values for Some Key Pulmonary Parameters FRC 2.6 L RV 1.5...
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Trachea(Generation #1)
Primary Bronchi (Generation #2)
Conducting Airways Generations 1-16
2o Bronchi (Generation #3)
Respiratory ZoneGenerations ~17-23
Alveoli
Respiratory Bronchioles
O2
CO2
venous arterial
PB=0
PA<0
Atmospheric AirHigh O2 (150 mmHg)
CO2 ~ 0
Inspiration
O2
CO2
venous arterial
PB=0
PA>0
Alveolar AirO2 ~100 mmHgCO2 ~ 40 mmHg
Expiration
Fick’s lawJ = DA (ΔC/ ΔX)
LungChest Wall
StuckTogether
Lung
Air leakPneumothoraxLung collapses& Chest expands
Hemoglobin-O2 Binding Curve
0 20 40 60 80 1000
20
40
60
80
100
0
5
10
15
20
Venous
Arterial
↑CO2
PaO2 (mm Hg)
% H
b Sa
tura
tion
HbO
2 content (ml O
2 /dl)
2
PO2=100 mm Hg14 ml O2/dL
PO2=100 mm Hg0.3 ml O2/dL
O2
O2
PO2=100 mm Hg14 ml O2/dL
PO2=100 mm Hg0.3 ml O2/dL dissolved20 ml O2/dL HB-O2
O2
O2
VT
Tota
l Lun
g C
apac
it y
ExpiratoryReserve
InspiratoryReserve
FRC
InspiratoryCapacity
ResidualVolume
VitalCapacity
1 s
FEV1.0
VT
Tota
l Lun
g C
apac
it y
ExpiratoryReserve
InspiratoryReserve
FRC
InspiratoryCapacity
ResidualVolume
VitalCapacity
500 ml
2.6 L
1.5 L
4.5 L
~6 L
Forced Vital CapacityTLC
FEV1.0 FVC
1 secFEV1.0 = 4 LFVC = 5 L
% = 80%
RV
TLC RV
Exp
irato
ry F
low
Rat
eLung 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)
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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
ChestWall
RecoilForce
Lung Wall
RecoilForce
Normal
Balance of Forces Determines FRCHooke’s Law: F = -kx
Fibrosis↑ lung recoil
Ppl= -8
Intrapleuralspace
Ppl = -2
Emphysema↓ lung recoil
Incr
easi
ngvo
lum
eD
ecre
asin
gvo
lum
e
Ppl = 0
Pneumo-thorax
NormalFRC
Ppl = -5
LungChest Wall
StuckTogether
Lung
As we remove airfrom pleural spacethe lung expands& the chest wallgets pulled in.
ChestWall
RecoilForce
Lung Wall
RecoilForce
NormalFRC
Ppl = -5
Normal
Balance of Forces Determines FRCHooke’s Law: F = -kx
Intrapleuralspace In
crea
sing
volu
me
Dec
reas
ing
volu
me
Ppl = 0
Ppl = -2
Emphysema↓ lung recoil
Fibrosis↑ lung recoil
Pneumo-thorax
Ppl= -8
4
Sur
face
Are
a (r
elat
ive)
Surface Tension (dynes/cm)30 60
WaterDetergent
LungSurfactant Plasma
80
↑Surface Area ∝ ↑Surface Tension
Surfactant40% Dipalmitoyl Lecithin25% Unsaturated Lecithins
8% Cholesterol27% Apoproteins, other
phospholipids, glycerides,fatty acids
Hystere
sis
Sur
face
Are
a (r
elat
ive)
Surface Tension (dynes/cm)30 60
WaterDetergent
LungSurfactant
80
↑Surface Area ∝ ↑Surface Tension
1. Reduces Work of Breathing2. Increases Alveolar Stability
(different sizes coexist)3. Keeps Alveoli Dry
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Normal
VTFRCN
PIP (cm H2O)
Lung
Vol
ume
Expiration
Inspiration
Hysteresis Occurs During Dynamic Air FlowDue to Surfactant reorientation & Airway Resistance
Static Lung Compliance Curve
Static Compliance Curves
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Fibrosis(low compliance)
Normal
Emphysema(high compliance)
VT
FRCN VTFRCF
VT
FRCE
Intrapleural Pressure, PIP (cm H2O)
Lung
Vol
ume
ChestWall
RecoilForce
Lung Wall
RecoilForce
NormalFRC
PIP = -5
Normal
Balance of Forces Determines FRCHooke’s Law: F = -kx
Intrapleuralspace In
crea
sing
volu
me
Dec
reas
ing
volu
me
PIP = 0
PIP = -2
Emphysema↓ lung recoil
Fibrosis↑ lung recoil
Pneumo-thorax
PIP= -8
5
Lung has weight
-8
PIP = -2
-5
Apex
Base
Chest Wall
Regional- Apex to Base Differences
-14-12-10-8-6-4-202
Apex
Base
Norm Lung Volume
Alveolar VolumeAlve Ventilation
Apex Base
++ ++
Inspiration
Inspiration
PIP (cm H2O)
Lung
Vol
ume
Regional- Apex to Base Differences
-14-12-10-8-6-4-202
ApexΔV
Base
Low Lung Volume(shifts to lower V)
Alveolar VolumeAlve Ventilation
Apex Base++++
PIP (cm H2O)
Lung
Vol
ume
Apex to Base Differences
-14-12-10-8-6-4-202
ApexΔV
Base
Low Lung V
Normal Lung V
PIP (cm H2O)
Lung
Vol
ume
The dashed trace is the PIPrequired to overcome recoil forces(ot PTP taken from compliance curve).More PIP (solid curve) is required toovercome airway resistance to flow.N.B. ΔP = PA-PB ∝ Resist•Flow.
Air Flow (L/s)
+1
-1
0
+0.6
-0.6
0
PA(cm H2O)
1 2 3 4time (sec)
-5
-8
cmH
2O
VT (L)0.4
0
0.2
Respiratory Cycle
Inspiration Expiration
PTP
PIP
PTP
PIPPB=0
-5
-7
-8
-6
-5
Rest FRC
Inspiration
End Inspiration
+
0
0
-AirFlow
PA= 0
PIP
End Expi-ration-FRC
Expiration
time
Respiratory CycleSingle VT Breath
Static Compliance Curves
-18-16-14-12-10-8-6-4-202
Normal
VT
FRCN
Pleural Pressure, Ppl (cm H2O)
Lung
Vol
ume
Expiration
Inspiration
6
PA (cm H2O)+1
-1
0
+0.5
-0.5
0
Air Flow (L/s)
1 2 3 4time (sec)
-5
-8
Ppl (cm H2O)
Case of ZERO Resistance
VT (L)0.4
0
0.2
Respiratory Cycle
Inspiration Expiration
-5
-8
-8
-6
-5
Rest FRC
Inspiration
End Inspiration
+
0
0
-Air
Flow
PA= 0
Ppl
End Expi-ration-FRC
Expiration
time
Respiratory CycleSingle VT Breath
PB=0
PA (cm H2O)+1
-1
0
+0.5
-0.5
0
Air Flow (L/s)
1 2 3 4time (sec)
-5
-8
Ppl (cm H2O)
The linear Dashed trace is the Pplrequired to overcome recoil forces.More Ppl (solid curve) is required toovercome airway resistance to flow.N.B. ΔP = PA-PB ∝ Resist•Flow.
VT (L)0.4
0
0.2
Respiratory Cycle
Inspiration Expiration
-5
-8
-8
-6
-5
Rest FRC
Inspiration
End Inspiration
+
0
0
-Air
Flow
PA= 0
Ppl
End Expi-ration-FRC
Expiration
time
Respiratory CycleSingle VT Breath
PB=0
PA (cm H2O)+1
-1
0
+0.5
-0.5
0
Air Flow (L/s)
1 2 3 4time (sec)
-5
-8
Ppl (cm H2O)
VT (L)0.4
0
0.2
Respiratory Cycle
Inspiration Expiration
-5
-8
-8
-6
-5
Rest FRC
Inspiration
End Inspiration
+
0
0
-Air
Flow
PA= 0
Ppl
End Expi-ration-FRC
Expiration
time
Respiratory CycleSingle VT Breath
PB=0
Case of HIGH Resistance
Airway Generation5 1 0 15
Tota
l Cro
ss S
ectio
nal A
rea
ConductingZone
RespZone
v = Flow/A
NR= ρDv/ηρ=densityD= diameterv= velocityη= viscosity
Airway Generation
Res
ista
nce
SubsegmentalBronchi
5 1 0 15
Resistance
8ηlR= ———
πr4
k•numberR= —————
A2
N.B. this is total x-sectional area (AT
2 =n2An2)
Lung Volume
Airw
ay R
esis
tanc
e
Normal↓RecoilEmphysema
Fibrosis
Mild Expiratory Effort (P+13)
0
Normal at FRC-5
0
Dynamic Compression of Airways
PTP=+5PPl - PA= -5
7
+28
30 25 20 15 10 5 0
EPP
Emphysema
in unsupported airways
Dynamic Compression of Airways
EPPEqual Pressure Point(in supported airways)
Low VL&Basal Alv
also like this
+13
Mild Expiratory Effort (P+13)
+8
8 4 0
Normal at FRC-5
0
+13
+13
PTP=+5PPl - PA= -5
+8
13 10 8 6 4 2 0
EPP
Emphysema+11
PPl-PA=-2
-2
0+11
Strong Expiratory Effort (P+30)
+25
30 25 20 15 10 5 0
EPP
Normal
+25
13 10 8 6 4 2 0
EPP
Emphysema+11
PPl-PA=-2
-2
0
Dynamic Compression of Airways
EPPEqual Pressure Point(in supported airways)
+13
Mild Expiratory Effort (P+13)
+8
8 4 0
Normal at FRC-5
0
+13
+13
PTP=+5PPl - PA= -5
Low VL&Basal Alv
also like this
Strong Expiratory Effort (P+30)
+25
30 25 20 15 10 5 0
EPP
Normal
+25
+28 Emphysema
30 29 28 27 25 20 0
Pursed-lipsHi Resist
EPPMoves toward the mouth
& supported airways
Normal
↑ResistanceObstructive
↑ RecoilRestrictive
time (sec)
Vol
ume
FRC
InspirationForced Vital Capacity
TLC
FEV1.0 FVC
1 sec
FEV1.0 = 4 LFVC = 5 L
% = 80%
RV
NormalTLC
FEV1.0
FVC
1 sec
FEV1.0 = 1.2 LFVC = 3.0 L
% = 40%
RV
Obstructive↑airway resist
Restrictive↑lung recoil
TLCFEV1.0 FVC
1 sec
FEV1.0 = 2.7 LFVC = 3.0 L
% = 90%
RV
Effort Independent limbin forced expiration.
TLC RV
Exp
irato
ry F
low
Lung Volume
Flow-Volume Curves
Due to Dynamic Airway Compression and airway collapse.
Inverted Inspiration
RV
Exp
irato
ry F
low Forced expiration
Inspiration
Insp
irato
ry F
low
TLC Lung Volume
8
Normal
Obstructive
Restrictive
9 8 7 6 5 4 3 2 1 Lung Volume (L)
Flow
Rat
e (L
/sec
)
9TLC RV
Lung Volume (L)
6 5 4 3 2 1
3. Alveolar Plateau
1. 2. Dead Space Washout
4.
N2
Con
cent
ratio
n (%
)
20
40
Critical Closing Volume Test
ClosingVolume
Apex to Base Differences
-14-12-10-8-6-4-202
ApexΔV
Base
Pleural Pressure, Ppl (cm H2O)
Lung
Vol
ume
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.N
2C
once
ntra
tion
(%)
20
40
Critical Closing Volume Test
ClosingVolume
IncreasedClosingVolume
Hemoglobin-O2 Binding Curve
0 20 40 60 80 1000
20
40
60
80
100
0
5
10
15
20
26
50
75
9097.5
PaO2 (mm Hg)
% S
atur
atio
n of
Hem
oglo
bin
Hb-O
2 content(m
l O2 /100 m
l blood)
Hemoglobin-O2 Binding Curve
0 20 40 60 80 1000
20
40
60
80
100
0
5
10
15
20
26
50
75
9097.5
PaO2 (mm Hg)
% S
atur
atio
n of
Hem
oglo
bin
Hb-O
2 content(m
l O2 /100 m
l blood)
0 20 40 60 80 1000
1
2
3
Dissolved O2
HbO2
PaO2 (mm Hg)
Hb-O
2 content(m
l O2 /100 m
l blood)
9
PO2=100 mm Hg14 ml O2/dL
PO2=100 mm Hg0.3 ml O2/dL
O2
O2
PO2=100 mm Hg14 ml O2/dL
PO2=100 mm Hg0.3 ml O2/dL dissolved20 ml O2/dL HB-O2
O2
O2
Bohr Shift Hb-02 Curve
0 20 40 60 80 1000
20
40
60
80
100
Normal Hb
Bohr Shift↑[H+], ↑CO2, ↑Temp or DPG
↓[H+],↓CO2
↓Temp
PaO2 (mm Hg)
% S
atur
atio
n of
Hem
oglo
bin
0 20 40 60 80 1000
5
10
15
20Myoglobin
Normal Hb
Anemia
Carbon Monoxide
PaO2 (mm Hg)
Hb-
O2
cont
ent
(ml O
2 /1
00 m
l blo
od)
Capillary Wall
CO2 + H2O —→ H2CO3 → H+ + HCO3-
O2CO2
CO2Cl-
H+ + HbO2 → HHb + O2
CarbaminoHHb-CO2
O2
TissueCO2 Loading & O2 Unloading
c.a.
Alveolar Wall
O2CO2
CO2
Cl-
H+ + HbO2 ← HHb + O2
CarbaminoHHb-CO2
O2
LungsCO2 Unloading & O2 Loading
c.a.
HCO3-
CO2 + H2O ←— H2CO3 ← H+ + HCO3-
O2 curve
Who
le blo
od to
tal C
O 2Co
ntent
(ml C
O 2/dl)
10
↑O2 helps CO2 unloading
Arterial (↑O2)
37 40 43 46 49 52
46
48
50
52
54
Rest Venous
PCO2(mm Hg)
CO
2C
onte
nt(m
l CO
2/1
00 m
l blo
od)
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)
CO
2C
onte
nt(m
l CO
2/1
00 m
l blo
od)
HALDANE SHIFT
XIV. RESPIRATORY GAS CASCADEPO2 PCO2mm Hg mm Hg
⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯Air (dry) 760 × 0.21 160 0Trachea (humidified; 760-47) 713 × 0.21 150 0Alveolus (some O2 absorbed by blood) 100 40Arterial (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 COJCO = 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%
Cap
illary
PX
(% a
lveo
lar)
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
PO
2m
m H
g
20
40
60
80
100
NormalTransit TimeExercise
ShortensTransit
time
Thickened Alveolar
Membrane
O2 Diffusion in Pulmonary Capillaries(transit time)
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Expired Lung Volume (L)0 0.2 0. 4 0.6 0.8
Alveolar Plateau
Inspired O2 dilutedby alveolar N2
N2
Con
cent
ratio
n (%
)
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 or 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
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Zone 1PA>Pa>PvLow Flow
PAPa Pv
PAPa Pv
Zone 2Pa>PA>PvWaterfall
Zone 3Pa>Pv>PAHi Flow
PAPa Pv
PAPa Pv Zone 4Same, but
Hi extra-Alv-R
Flow
of B
lood
or A
ir
Bottom TopDistance up Lung
Ventilation
Perfusion
1
2
3
VA/Q. .
VA /Q
R
atio
.
.PO2 = 40PCO2 = 45
Normal VA/QLow VA/Q High VA/QCO2 = 45
PO2 = 150PCO2 = 0
PO2 = 100PCO2 = 40
PO2 = 150PCO2 = 0
. . .
Ventilation Perfusion Ratios
No flow
. . .
PO2 = 40PCO2 = 45
Low VA/Q.
Normal VA/Q.
PO2 = 100PCO2 = 40
High VA/Q.
PO2 = 150PCO2 = 0
PO2 (mm Hg)
PC
O2
(mm
Hg)
50 100 150
50
Base
Apex
Flow
of B
lood
orA
ir
Bottom TopDistance up Lung
Ventilation
Perfusion
1
2
3
VA /Q
R
atio
.
.
VA/Q. .
Region VA V•A Q• V•A/Q• PCO2 PO2 ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ Apex + + + Base + ++ + ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯
13
Mechanisms of HypoxemiaA. HypoventilationB. Diffusion AbnormalitiesC.Right to Left ShuntD.Ventilation/Perfusion MismatchE. 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. Anemiab. Carbon Monoxidec. Hypoperfusion (CV problem)
Local Controla. Low PAO2 → vasoconstrictionb. Low PVCO2 → bronchoconstriction
Hemoglobin-O2 Binding Curve
0 20 40 60 80 100 120 1400
20
40
60
80
100
0
5
10
15
20
26
50
75
100
(100+75)/2=87.5(20+15)/2 =17.5
PaO2 (mm Hg)
% S
atur
atio
n of
Hem
oglo
bin
Hb-O
2 content(m
l O2 /100 m
l blood)
High
VA/Q.
.
Low
V A/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
0 20 40 60 80 100 120 1400
20
40
60
80
100
0
5
10
15
20
26
50
75
100
(100+75)/2=87.5(20+15)/2 =17.5
87.5
54 m
mH
g
PaO2 (mm Hg)
% S
atur
atio
n of
Hem
oglo
bin
Hb-O
2 content(m
l O2 /100 m
l blood)
High
VA/Q.
.
Low
V A/Q.. High VA/Q
can’t compensateFor Low VA/Q
. .
. .
37 40 43 46 49 52
46
48
50
52
54
PCO2(mm Hg)
CO
2C
onte
nt(m
l CO
2/1
00 m
l blo
od)
30
High VA/Q. .
Low VA/Q. .
44
High VA/Q Compensates For Low VA/Q
. .
. .
Integratorin CNS
(Medulla)
SensorsChemoreceptors
Central &Peripheral
Control VariablesPO2, PCO2, pH
AfferentSensory
info
Efferentto motorneurons
EffectorsRespiratory Muscles
(e.g. Diaphragm)
Simple Negative Feedback System
14
Arterial PO2 (mm Hg)
% m
axim
al fi
ring
rate
50 100 500
50
75
25
Peripheral Chemoreceptor ResponsivenessBBB CSFPlasma
CO2
HCO3
+
H+
CO2 ←→ HCO3 + H+
RespiratoryAcidosis (↑PaCO2)
Pumped
CNS Acidosis then HCO3 is pumped in(& restores pHCNS faster than kidneys can restore pHsystemic)
BBB CSFPlasma
CO2
HCO3
+
H+
CO2 ←→ HCO3 + H+
Metabolic Acidosis
Hyperventilation& ↓PaCO2
CNSAlkalosis !!!!
(then pump HCO3 out)
15
ExpirDRGInspir
Higher Brain CentersPneumotaxic Center
Apneustic Center
–
Periph &CentralChemo-receptors
RespiratoryMuscles
VagusStretch
+
Toni
c In
spD
rive
Cut-off
ThreshAdjust
Cut
-off
+/–
Expiratory effort
+/–
30 60 900
10
20
30
40
50
60
PCO2 = 40 mm Hg
PCO2 = 45 mm Hg
PCO2 = 20 mm Hg
PaO2 (mm Hg)
Vent
ilatio
n (L
/min
)
Ventilatory Response to O2
35 40 45 50 550
20
40
60
PaO2 ≥ 200 mm Hg
PaCO2 (mm Hg)
Vent
ilatio
n (L
/min
)PaO2 ~100 mm Hg
PaO2 ~ 60 mm Hg
Ventilatory Response to CO2
35 40 45 50 550
10
20
30
40
50
NormalMetabolic Alkalosis
Metabolic Acidosis
PaCO2 (mm Hg)
Vent
ilatio
n (L
/min
)
Ventilatory Response to CO2
18,000 32,000 65,000 98,000Altitude (ft)0 10,000 20,000 30,000
0255075
100125150
PIO2
(PB -47)(0.21) -50
Altitude (ft)
P IO
2 (m
mH
g)
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 CSFPlasma
CO2
HCO3
+
H+
CO2 ←→ HCO3 + H+
RespiratoryAlkalosis
high pHCSF limits Hypoxic
Hyperventilation
When pHCNSreturns 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 adjustments1, Polycythemia2. Enhanced Diffusing Capacity3. Imcreased Capillary Density4. Right shift of HbO2 curve
LA
LVRV
RA
Lung
Tissue
Placenta
SVC
IVC
FO
Aorta
DA
Lung
25
15
30
14
19
22
26
Low O2Hi Resist PA
PVPV
0 20 40 60 80 1000
5
10
15
20Myoglobin
Normal Hb
Anemia
Carbon Monoxide
PaO2 (mm Hg)
Hb-
O2
cont
ent
(ml O
2 /1
00 m
l blo
od)
LA
LVRV
RA
Lung
Tissue
Placenta
SVC
IVC
FO
Aorta
DA
Lung
25
15
30
14
19
2226
Hi O2Lo Resist
PVPV
95
95
95
40
40
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