PULMONARY GAS EXCHANGE IN HEALTH AND DISEASE

PETER D. WAGNER, M.D.

UCSD, La Jolla, California

Antalya, Turkey, April 2006

GAS EXCHANGE IN HEALTH AND DISEASE

ASTHMA

COPD

INTERSTITIAL FIBROSIS

PULMONARY THROMBOEMBOLISM

NORMAL

MEASURING VENTILATION / PERFUSION MISMATCH

MIGET PRINCIPLES

INERT GAS ELIMINATION FROM THE BLOOD

BLOOD FLOW

INERT GASIN VENOUS BLOOD

VENTILATION

SOME MOLECULES ELIMINATED BY VENTILATIONSOME RETAINED IN BLOOD

RETENTION DEPENDS ON :

PARTITION COEFFICIENT ()

RETENTION DEPENDS ON :

PARTITION COEFFICIENT ()

VENTILATION/PERFUSION RATIO (VA/Q)

RETENTION IS HIGH WHEN VA/Q IS LOW

RETENTION IS LOW WHEN VA/Q IS HIGH

RETENTION = / ( + VA/Q)

RETENTION = / ( + VA/Q)

PARTITION COEFFICIENT ()

RE

TE

NT

ION

(

)HOMOGENEOUS LUNG, VA = QT = 6.0 L/min VA/Q RATIO = 1.0

RETENTION = / ( + VA/Q)

0.0

0.2

0.4

0.6

0.8

1.0

0.001 0.01 0.1 1 10 100 1000

.

SF6Ethane

Cyclopropane

Enflurane

Ether Acetone

IN A HOMOGENEOUS LUNG WITH ANATOMIC DEADSPACE (VD/DT),

EXCRETION = (1 – VD/VT) x RETENTION

- FOR ALL INERT GASES

EXCRETION = MIXED EXPIRED/VENOUS RATIO

RETENTION = MIXED ARTERIAL/VENOUS RATIO

0.0

0.2

0.4

0.6

0.8

1.0

0.001 0.01 0.1 1 10 100 1000

.

PARTITION COEFFICIENT ()

RE

TE

NT

ION

(

);

EX

CR

ET

ION

(

)

HOMOGENEOUS LUNG, VA/Q RATIO = 1.0 AND 30% ANATOMIC DEADSPACE EXCRETION = 70% OF RETENTION

HOMOGENEOUS LUNG

VA/Q RATIOPARTITION COEFFICIENTV

A (

)

AN

D

Q (

)

R (

)

AN

D

E (

)

0.0

0.2

0.4

0.6

0.8

1.0

0 0.01 0.1 1 101000 1000.001 0.01 0.1 1 10 100/ /

0.0

0.2

0.4

0.6

0.8

1.0

0 0.01 0.1 1 101000 1000.001 0.01 0.1 1 10 100/ /

NORMAL LUNGR

(

) A

ND

E

(

)

PARTITION COEFFICIENT VA/Q RATIOV

A (

)

AN

D

Q (

)

No shunt orLow VA/Qalveoli

No highVA/Qalveoli

R

E

/ /00.01 0.1 1 10 100

0.0

0.2

0.4

0.6

0.8

1.0

0.001 0.01 0.1 1 10 1001000

LUNG WITH 50% SHUNT (VA/Q = 0)R

(

) A

ND

E

(

)

PARTITION COEFFICIENT VA/Q RATIOV

A (

)

AN

D

Q (

)

0.0

0.2

0.4

0.6

0.8

1.0

0.001 00.01 0.1 1 10010 100 1000 0.01 0.1 1 10/ /

LUNG WITH 50% LOW VA/Q AREASR

(

) A

ND

E

(

)

PARTITION COEFFICIENT VA/Q RATIOV

A (

)

AN

D

Q (

)

0.0

0.2

0.4

0.6

0.8

1.0

0.001 00.01 0.1 1 10010 100 1000 0.01 0.1 1 10/ /

LUNG WITH HIGH VA/Q AREASR

(

) A

ND

E

(

)

PARTITION COEFFICIENT VA/Q RATIOV

A (

)

AN

D

Q (

)

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

NORMAL SUBJECTV

EN

TIL

AT

ION

(

),

BL

OO

D F

LO

W (

)

VENTILATION / PERFUSION RATIO

NORMAL VA/Q

NOSHUNT

NOLOW VA/Q

NOHIGH VA/Q

VENTILATION / PERFUSION MISMATCH IN CHRONIC LUNG DISEASE

ASTHMA

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

SEVERE, CHRONIC ASTHMA,

PaO2 = 53; FEV1 = 35% PredictedV

EN

TIL

AT

ION

(

),

BL

OO

D F

LO

W (

)

VENTILATION / PERFUSION RATIO

NOSHUNT

LOW VA/Q

NORMAL VA/Q

NOHIGH VA/Q

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

ASYMPTOMATIC ASTHMA,

PaO2 = 79; FEV1 = normalV

EN

TIL

AT

ION

(

),

BL

OO

D F

LO

W (

)

VENTILATION / PERFUSION RATIO

NOSHUNT

LOW VA/Q

NORMAL VA/Q

NOHIGH VA/Q

PATHOPHYSIOLOGICAL INFERENCES

1. Even mild, asymptomatic asthma creates significant VA/Q mismatch -

in spite of a normal FEV1

3. Despite this significant VA/Q mismatch, PaO2 remains high

4. PaO2 remains high because cardiac output is elevated

5. VA/Q pattern is similar in severe asthma - Bimodal distribution with normal and low VA/Q modes

6. Shunt is rarely present despite VA/Q regions as low as 0.01 - suggesting a role for collateral ventilation in preventing shunt

2. VA/Q mismatch with normal FEV1 suggests small airway obstruction

7. Bimodality suggests small airways either badly obstructed or little obstructed

VENTILATION / PERFUSION MISMATCH IN CHRONIC LUNG DISEASE

ASTHMA

COPD

NORMAL LUNG EMPHYSEMATOUS LUNG

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

COPD: PREDOMINANT EMPHYSEMAV

EN

TIL

AT

ION

(

),

BL

OO

D F

LO

W (

)

VENTILATION / PERFUSION RATIO

NOSHUNT LOW VA/Q

NORMAL VA/Q

HIGH VA/Q

MECHANISMS OF AIRWAY OBSTRUCTION

MUCUSPLUGGING

AIRWAY WALL THICKENING, BRONCHO-CONSTRICTION

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

COPD: PREDOMINANT CHRONIC BRONCHITISV

EN

TIL

AT

ION

(

),

BL

OO

D F

LO

W (

)

VENTILATION / PERFUSION RATIO

NOSHUNT

LOW VA/Q

NORMAL VA/Q

NOHIGH VA/Q

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

COPD: CHRONIC BRONCHITIS AND EMPHYSEMA

VENTILATION / PERFUSION RATIO

VE

NT

ILA

TIO

N (

),

B

LO

OD

FL

OW

(

)

NOSHUNT

LOW VA/Q

NORMAL VA/Q

HIGH VA/Q

PATHOPHYSIOLOGICAL INFERENCES

1. COPD causes extensive VA/Q mismatch

3. Patients with a high VA/Q mode are clinically emphysematous

4. Patients with a low VA/Q mode are often clinically bronchitic

5. However, such patients commonly also have emphysema

6. The high VA/Q mode probably represents ventilation in poorly perfused destroyed emphsyematous regions

2. Three characteristic patterns are seen

7. The low VA/Q mode probably represents peripheral airway obstruction due to mucus/remodeling/bronchoconstriction

8. Despite a low DLCO, hypoxemia is due only to VA/Q mismatch

VENTILATION / PERFUSION MISMATCH IN CHRONIC LUNG DISEASE

ASTHMA

COPD

INTERSTITIAL FIBROSIS

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

INTERSTITIAL FIBROSIS

VENTILATION / PERFUSION RATIO

VE

NT

ILA

TIO

N (

),

B

LO

OD

FL

OW

(

)

SHUNT

LOW VA/Q

NORMAL VA/Q

NOHIGH VA/Q

PATIENTS WITH MODERATE TO SEVERE INTERSTITIAL FIBROSIS

MEASURED ARTERIAL PO2, mm Hg

0 20 40 60 80 1000

20

40

60

80

100

PR

ED

ICT

ED

AR

TE

RIA

L P

O2,

mm

Hg

EVIDENCE OF DIFFUSION LIMITATION FOR O2

BUT ONLY DURING EXERCISE

RESTEXERCISE

PATHOPHYSIOLOGICAL INFERENCES

1. Interstitial Fibrosis causes extensive VA/Q mismatch

3. Hypoxemia is variable, due at rest wholly to VA/Q mismatch

4. - Unless DLCO < 50% Predicted, when diffusion limitation occurs

5. Diffusion limitation during exercise causes hypoxemia

6. Limited cardiac output response to exercise worsens hypoxemia

2. A characteristic pattern is seen: Shunt + very low VA/Q areas

7. Shunt + low VA/Q areas probably represent perfusion of capillaries buried in thick fibrotic alveolar walls – extreme diffusion limitation

VENTILATION / PERFUSION MISMATCH IN CHRONIC LUNG DISEASE

ASTHMA

COPD

INTERSTITIAL FIBROSIS

PULMONARY THROMBOEMBOLISM

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

PULMONARY EMBOLISM

VENTILATION / PERFUSION RATIO

VE

NT

ILA

TIO

N (

),

B

LO

OD

FL

OW

(

)

NOSHUNT

NOLOW VA/Q

NORMAL VA/Q

HIGH VA/Q

0.0

0.3

0.6

0.9

1.2

1.5

1.8

.

0 0.01 0.1 1 10 100

PULMONARY EMBOLISM

VENTILATION / PERFUSION RATIO

SHUNT

VE

NT

ILA

TIO

N (

),

B

LO

OD

FL

OW

(

)

NOLOW VA/Q

NORMAL VA/Q

HIGH VA/Q

PATHOPHYSIOLOGICAL INFERENCES

1. Pulmonary thromboembolism causes extensive VA/Q mismatch

4. Hypoxemia is variable; hypercapnia would occur without hyperventilation

5. Hypoxemia is explained by VA/Q mismatch

6. Diffusion limitation is not seen

2. A characteristic pattern is seen – very high VA/Q areas

7. Shunt occurs in some patients. It probably represents one of:

a) perfusion through a patent foramen ovale b) scattered microatelectasis (? Due to loss of surfactant activity)

3. High VA/Q areas are due to low blood flow in embolized vessels