Diffusion Capacity of Diffusion Capacity of LungsLungs

DR.LAXMAN KUMAR SONIDR.LAXMAN KUMAR SONI Dept. of Pulmonary Medicine, Dept. of Pulmonary Medicine,

Dr.SNMC , JODHPURDr.SNMC , JODHPUR

Physiology of diffusion Terminology Measurement of diffusion capacity Importance in respiratory diseases

PhysiologyPhysiology

Primary function of lung: gas exchange by Simple passive diffusion followingFick’s law of diffusion

TerminologyTerminology•North America: “Diffusing capacity”historical term

•Europe: “Transfer factor” beacause measurment of CO uptake reflects a no. of process(not just diffusion ) and its submaximal value and thus,not truly a capacity.

Components of diffusion pathway

• Gas space within the alveolus • Alveolar lining fluid – surfactant

rich • Tissue barrier – alveolar capillary

membrane • Plasma layer • Diffusion into and within the RBC • Uptake of CO by hemoglobin

Pathway for diffusionPathway for diffusion

Why CO is preferred?

Gas used for measure diffusion capacity have :

1.Lower solubility in pulmonary membrane and 2.High capacitance in blood. these gases include Oxygen ,NO and CO.

• Oxygen In addition to perfusion oxygen transfer limited by such as ventilation perfusion mismatching , shunting , and there is also accurately measurement of Po2 during capillary transient is very difficult .

• NO NO is highly reactive with oxygen so requires special equipment, and have potential cardiovascular side effect and still NO is under research setting.

CO

Not normally present in alveoli/blood Transfer is diffusion limited rather

than perfusion limited Avidly binds to Hb(210 times of

Oxygen) Less affected by other factors

DLO2=1.23 * DLco

Determinats Of CO uptakeDeterminats Of CO uptake

1/DLCO=(1/DM)+(1/QVc)1/DLCO=(1/DM)+(1/QVc)

DM-Membrane condunctivity(reflects DM-Membrane condunctivity(reflects diffusion properties of alveolar diffusion properties of alveolar capilary membrane)capilary membrane)

Factors affecting carbon monoxide diffusion Factors affecting carbon monoxide diffusion capacity of the lung (DL,CO)capacity of the lung (DL,CO)

Extrapulmonary reduction in lung Extrapulmonary reduction in lung inflation (reduced VA) producing inflation (reduced VA) producing changes in DM or QVc that reduce changes in DM or QVc that reduce DLCO DLCO • Reduced effort or respiratory muscle Reduced effort or respiratory muscle

weakness weakness • Thoracic deformity preventing full Thoracic deformity preventing full

inflation inflation

Diseases that reduce QVc and thus reduce Diseases that reduce QVc and thus reduce DL,CO DL,CO

• Anaemia Anaemia • Pulmonary emboliPulmonary emboli

Other conditions that reduce QVc and thus Other conditions that reduce QVc and thus reduce DL,COreduce DL,CO

• Hb binding changes (e.g. HbCO, increased Hb binding changes (e.g. HbCO, increased

FI,O2) FI,O2) • Valsalva manoeuvre (increased intrathoracic Valsalva manoeuvre (increased intrathoracic

pressure) pressure)

Diseases that reduce (in varying Diseases that reduce (in varying degrees) DM and QVc and thus reduce degrees) DM and QVc and thus reduce DL,CO DL,CO

• Lung resection (however, compensatory Lung resection (however, compensatory

recruitment of QVc also exists) recruitment of QVc also exists) • Emphysema Emphysema • Interstitial lung disease (e.g. IPF, Interstitial lung disease (e.g. IPF,

sarcoidosis) sarcoidosis) • Pulmonary oedemaPulmonary oedema• Pulmonary vasculitisPulmonary vasculitis• Pulmonary hypertensionPulmonary hypertension

Diseases that increase QVc and Diseases that increase QVc and thus increase DLCO thus increase DLCO

• Polycythemia Polycythemia • Left-to-right shunt Left-to-right shunt • Pulmonary haemorrhage (not Pulmonary haemorrhage (not

strictly an increase in QVc, but strictly an increase in QVc, but effectively an increase in lung Hb) effectively an increase in lung Hb)

• AsthmaAsthma

Other conditions that increase QVc and Other conditions that increase QVc and thus increase DLCO thus increase DLCO

• Hb binding changes (e.g. reduced FIO2) Hb binding changes (e.g. reduced FIO2) • Muller manoeuvre (decreased intrathorasic Muller manoeuvre (decreased intrathorasic

pressure as in asthma) pressure as in asthma) • Exercise (in addition, a possible DM Exercise (in addition, a possible DM

component) component) • Supine position (in addition, possibly a slight Supine position (in addition, possibly a slight

increase in DM) increase in DM) • Obesity (in addition, a possible DM component) Obesity (in addition, a possible DM component)

VA: alveolar volume; DM: membrane conductivity; Vc: volume of VA: alveolar volume; DM: membrane conductivity; Vc: volume of pulmonary capillary bloodpulmonary capillary blood

Physiological Factors influencing DLCOPhysiological Factors influencing DLCO

Hb levelHb level

DLCO directly correlates with Hb DLCO directly correlates with Hb

1g/Dl decrease Hb – 4% decrease DLCO1g/Dl decrease Hb – 4% decrease DLCO

1g/Dl increase Hb – 2% increase DLCO1g/Dl increase Hb – 2% increase DLCO

COHb levelCOHb level Increase in COHb reduces DLCO in two ways Increase in COHb reduces DLCO in two ways

• Decreases available binding sites on Hb Decreases available binding sites on Hb

• Reduces differential driving Pressure across ACM Reduces differential driving Pressure across ACM

1% Increase in COHb decreases DLCO by 1% 1% Increase in COHb decreases DLCO by 1%

Alveolar volume (VA) •increase in LV - increase in DLCO

expansion of lung - thinning of ACM, increase

in diameter of corner vessels

therefore correct DLCO for volume•KCO=DLCO/VA ( KCO-trasfer cofficient of lung)

Ex.. COPD, Asthma (“increased” DLCO)

Circadian rhythm DLCO drops 1-2%/hr between 9.30am-9.30pm

Gender & Ethnicity lower in women for a given height lower in African-Americans, Asians

Body size: DLco varies with BSAbetter predicted by height & weight 2DLcO=BSA(M) (18.84) -6.8

Age: DLco declines in linear fashion with age

Exercise 30-40% increase recovery after high-intensity ex - 24 hrs

Body position increase on supine

Menstrual cycle highest just before, least 5-10 days after

Measurement of diffusing capacityMeasurement of diffusing capacityMethods Single breath-holding method Single expiration method Rebreathing method Steady state method Riley-Lilienthal method

Indications Specific indications not defined

• variety of testing procedures in use• complexity of physiologic determinants

of CO uptake Most commonly used in evaluation of

• diffuse interstitial lesions• suspected emphysema• pulmonary vascular obstruction

Useful in diagnosis as well as follow up

Single breath method

• Most widely used and best standardized of the various methods

ProcedureProcedure Unforced exhalation to RVUnforced exhalation to RV

(limited to 6 seconds)(limited to 6 seconds)

Rapid inhalation of a diffusion gas mixture to Rapid inhalation of a diffusion gas mixture to TLC TLC (from spirometer/demand valve/reservoir)(from spirometer/demand valve/reservoir)• 0.3% CO0.3% CO• 10% He 10% He (tracer gas)(tracer gas)• 21% O221% O2• Balance NitrogenBalance Nitrogen

Breath hold at TLC for 10 Breath hold at TLC for 10 +/-+/- 2 seconds 2 seconds

Rapid exhalationRapid exhalation(should not exceed 4 sec)(should not exceed 4 sec)

Alveolar gas is collected after a washout Alveolar gas is collected after a washout volume (0.75-1.0 L) has been discardedvolume (0.75-1.0 L) has been discarded(If VC is <2.0 L, washout volume may be reduced to 0.50L)(If VC is <2.0 L, washout volume may be reduced to 0.50L)

Sample gas volume should be 0.50 – 1.0 LSample gas volume should be 0.50 – 1.0 L(If VC <1.0L, a sample of <0.50L can be analyzed if deadspace (If VC <1.0L, a sample of <0.50L can be analyzed if deadspace volume has been cleared)volume has been cleared)

Sample is analyzed for the fractional CO and He Sample is analyzed for the fractional CO and He (tracer (tracer gas)gas) concentration concentration

Change in He concentration reflects dilution by gas in lungs at RVChange in He concentration reflects dilution by gas in lungs at RV

This change is used to determine the initial CO concentrationThis change is used to determine the initial CO concentration

Summary of the procedureSummary of the procedure

Spirometry, lung volumes

Acceptability CriteriaAcceptability Criteria Volume-Time tracing should show smooth, Volume-Time tracing should show smooth,

rapid inspiration rapid inspiration (<4 sec) from RV to TLC(<4 sec) from RV to TLC

Expiration should be rapid Expiration should be rapid but not forced; 4 but not forced; 4 seconds or lessseconds or less

Dead space washout should be 0.75 – 1.00 L Dead space washout should be 0.75 – 1.00 L (0.5 L if VC is less than 2.0 L)(0.5 L if VC is less than 2.0 L)

Alveolar sample volume should be 0.5 to 1.0 LAlveolar sample volume should be 0.5 to 1.0 L

Inspired volume should be at least Inspired volume should be at least 85% 85% of of previously recorded best VCpreviously recorded best VC

Breath hold time should 10 sec +/- 2 sec (No Breath hold time should 10 sec +/- 2 sec (No Valsalva or Mueller maneuver)Valsalva or Mueller maneuver)

Expiration in <4 s (and sample collection time Expiration in <4 s (and sample collection time <3s)#, with appropriate clearance of VD and <3s)#, with appropriate clearance of VD and proper sampling/analysis of alveolar gas proper sampling/analysis of alveolar gas

The average of two or more acceptable test The average of two or more acceptable test should be reported. Duplicate determinations should be reported. Duplicate determinations should be within 10% of highest value or 3 ml should be within 10% of highest value or 3 ml CO/min/mm HgCO/min/mm Hg

Repeatability and Number ofTests

Obtain at least 2 acceptable tests Repeatability requirement – 2 acceptable

tests• within 3 units, OR• 10 % of the highest value

Report the average of 2 acceptable tests that meet repeatability requirement

More than 5 tests are not recommended

Eur Respir J 2005; 26: 720–735

• Average DLAverage DLcocosb valuesb value

25 ml CO/min/mm Hg (STPD)25 ml CO/min/mm Hg (STPD)

Inspiratory maneuver 14%He, 18%O2, 0.27%CO)

breathhold

Deadspace washout(0.75 L)If VC<2L, reduce to 0.5L

Sample collection volume0.5-1LIf VC<2L, reduce to 0.5L

AdvantagesAdvantages

No invasive measuring proceduresNo invasive measuring procedures Analysis of only two gases is requiredAnalysis of only two gases is required Test is easily and rapidly performedTest is easily and rapidly performed

DisadvantagesDisadvantages

Difficult breathing maneuverDifficult breathing maneuver Not practical during exercise testingNot practical during exercise testing Less than maximal inspired VC Less than maximal inspired VC

volumes affect measurement volumes affect measurement accuracyaccuracy

V/Q mismatches can affect the V/Q mismatches can affect the resultsresults

Calculation of DLCOCalculation of DLCO

DLCO = VA X ln FACOi

T X (PB-47) FACOF

T = time of breath holdPB = barometric pressure47 = water vapour pressure at 37oC

KCO = DLCO VA

Technical factors influencing DLCO

PIO2• Inversely related• DLCO increases by 0.31% per mm Hg decrease in PIO2• USA:FiO2 0.21• Europe: FiO2 0.17• Discontinue suppl. O2 > 5 min before procedure

Other Technical variables

•Inspired volume•Duration and condition of breath hold•Deadspace washout volume•Method of gas analysis•Method of measuring VA

Equipment quality controlEquipment quality control

Gas-analyser zeroing Done Gas-analyser zeroing Done before/after each test before/after each test

Volume accuracy Tested daily Volume accuracy Tested daily Standard subject or simulator testing Standard subject or simulator testing

Tested at least weekly Tested at least weekly Gas-analyser linearity Tested every 3 Gas-analyser linearity Tested every 3

months months Timer Tested every 3 months Timer Tested every 3 months

Reporting

Average of at least 2 acceptable and repeatable tests

Report includes:• Measured DLco• Predicted and percent predicted DLco/VA or

Kco• Any adjustments for Hb, COHb or VA

If using continuous analyzers, manual adjustments must be noted on report so interpreter can review and verify the adjustments

Eur Respir J 2005; 26: 720–735

Severity for diffusion disordersSeverity for diffusion disorders

% of predicted% of predicted

NormalNormal 80 – 10080 – 100

MildMild 60 – 7960 – 79

ModerateModerate 40 – 5940 – 59

SevereSevere 20 – 3920 – 39

Very severeVery severe < 20< 20

The The ReportReport

Unit of DLco

Traditional: mL (STPD).min‐1.mmHg‐1 SI units: mmol.min‐1.kPa‐1

Traditional = SI x 3

Eur Respir J 2005; 26: 720–735

Diseases causing alterations in DLCODiseases causing alterations in DLCO

Increased DLCO True increase Polycythemia Alveolar haemorrhage L-R shunts Exercise Pseudo-increase Bronchial asthma

Decreased DLCO

ILD• early though nonspecific manifestation• monitoring progress & Rx• monitoring people at risk COPD• of emphysema• correlates with severity• predicts exercise limitation• predicts mortality

Pulmonary embolism• unexplained dyspnoea + reduced DLCO• correlates with severity of obstruction• reductions persist for 3 yrs

CCF• Increased in early CCF• Decreased in advanced & chronic cases• correlates with NYHA class

Misc Anemia, CRF Alcoholism, smoking RHD, PPH etc.

Steady‐State Method Pt. breathes a mixture of 0.1% CO in air

for several min through one way valve system

During last 2 min exhaled gas is collected and analyzed

ABG also drawn and analyzed for Pco2 Can be measured during tidal breathing,

anesthesia,sleep, and exercise Results are markedly affected by uneven

distribution of ventilation or V/Q abnormalities

AdvantagesAdvantages• Natural breathing maneuverNatural breathing maneuver• Allow greater variety of clinical Allow greater variety of clinical

conditionsconditions DisadvantagesDisadvantages

• More complex and difficult to perform More complex and difficult to perform (PACO)(PACO)

• PPCCCO back pressureCO back pressure

• More affected by V/Q abnormalitiesMore affected by V/Q abnormalities

Rebreathing Method Pt rebreathes the test gas from reservoir,

the volume of which equals pt’s FEV1

Rebreathing continues for 30‐45 s, at controlled rate of 30 per min

More variable

Requires considerable patient cooperation to attain rapid respiratory rate required

AdvantageAdvantage

Least affected byLeast affected by• V / Q abnormalitiesV / Q abnormalities• Changes in the subject’s lung volume at the Changes in the subject’s lung volume at the

time of measurement time of measurement

DisadvantagesDisadvantages

Complexity of the instrumentation Complexity of the instrumentation and equations requiredand equations required

Affected by PAffected by PCCCO buildupCO buildup Need for subject cooperation with Need for subject cooperation with

breathingbreathing PPCCCO back pressureCO back pressure

Interpretation

• Relationship between DLCO and lung volume is not linear, so DLco/VA or DLco/TLC do not

provide an appropriate way to normalize DLco for lung volume

• Conceptually, low DLco but high DLco/VA: extraparenchymal abnormality (e.g. pneumonectomy or chest wall restriction)

• Low DLco and low DLco/VA: parenchymal abnorm

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