Η διαχυτική ικανότητα σε απόλυτη τιμή ή ως προς τον κυψελιδικό αερισμό

Size: px

Start display at page:

Download "Η διαχυτική ικανότητα σε απόλυτη τιμή ή ως προς τον κυψελιδικό αερισμό"

Barnaby Brooks
5 years ago
Views:

1 Η διαχυτική ικανότητα σε απόλυτη τιμή ή ως προς τον κυψελιδικό αερισμό Αθηνά Γόγαλη ΜD, PhD Eπιμελήτρια Α Πανεπιστημιακή Πνευμονολογική Κλινική Ιωαννίνων

3 Bulk Flow vs. Diffusion Trachea 0 Main Bronchi 1 Lobar Bronchus 2 Segmental Bronchus 3-4 Bronchioles 5-15 Terminal Bronchioles 16 Resp. Bronchioles Alveolar Ducts Alveolas Sacs 23 The cross sectional area increases with airway generation. Large volume/time, with decreasing velocity at any point. Imagine a fast flowing river reaching a delta. The velocity of gas during inspiration becomes tiny at the level of the respiratory bronchiole- at this level diffusion becomes the chief mode of gas movement.

4 Diffusion of Oxygen Across the Alveolar Wall Pulmonary Surfactant Alveolar Epithelium Alveolar Interstitium Capillary Endothelium Plasma Red Blood Cell Hemoglobin Diffuses/Dissolves Diffuses/Dissolves Diffuses/Dissolves Diffuses/Dissolves Diffuses/Dissolves Binds

6 Fick s Law for Diffusion. Vgas = volume of gas diffusing through the tissue barrier per time, in ml/min 0,3μm A = surface area available for diffusion D = diffusion coefficient of the gas (diffusivity) T = thickness of the barrier P1 P2 = partial pressure difference of the gas

7 Diffusivity D Solubility/ MW O 2 has lower MW than CO 2 Solubility of CO 2 is 24x that of O 2 CO 2 diffuses 20x more rapidly through the alveolar capillary barrier than O 2

8 Limitations of Gas Transfer Diffusion Coefficient. Different gases behave differently. Surface Area and Thickness of the alveolar wall. Partial Pressure Gradient across the alveolar wall for each individual gas. Depends on both alveolar and mixed venous partial pressure (start of capillary).

9 Diffusivity of CO 2 is 20x > than that of O 2 Partial pressure gradient of CO 2 is Partial pressure gradient of O 2 is Normally: Perfusion limited ( Α, Τ abnormality): Diffusion limited Cause of low PO2, most usually in exersice It never causes high PCO2

10 MESUREMENT OF DIFFUSING CAPACITY Change in Blood Partial Pressure of Three Gases with Time in the Capillary Carbon monoxide Levitzky. Pulmonary Physiology, 6 th ed. McGraw-Hill. 2003

11 N 2 O is Perfusion Limited N 2 O is very soluble in biological tissues and diffuses rapidly. PcN 2 O rises rapidly in the alveolar capillary. Quickly have PcN 2 O =PAN 2 O. Because there is no pressure gradient, no diffusion occurs after about 0.1 sec. Increased blood flow will increase gas transfer. Transfer of N 2 O is perfusion limited.

12 Measurement of DIO2 is difficult O2 transfer limited by: diffusion ventilation-perfusion mismatching Shunting Changing capillary PO2 CANNOT BE ACCURATELY DETERMINED

WHY Carbon Monoxide? CO is Diffusion Limited CO is present in minimal amounts in the blood. SOLco~SOL O2 Blood PCO rises very slowly because CO is bound to Hgb, with very little dissolved.

13 WHY Carbon Monoxide? CO is Diffusion Limited CO is present in minimal amounts in the blood. SOLco~SOL O2 Blood PCO rises very slowly because CO is bound to Hgb, with very little dissolved. Capillary PcCO does not approach PACO. Partial pressure gradient is maintained throughout the time the blood is in the capillary. Diffusion continues throughout this time. Transfer of CO is limited by diffusivity, surface area, and thickness of the wall. Harmless in low concentrations.

14 Carbon Monoxide is an Ideal Gas for Measuring Diffusing Capacity CO binds avidly to hemoglobin. While CO content of the blood rises, the PCO in blood rises very slowly. Carbon Monoxide The gradient of partial pressures from alveolus to blood remains almost constant during test Levitzky. Pulmonary Physiology, 6 th ed. McGraw-Hill. 2003

15 What is DLCO? The DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries DLCO OR TLCO? North America: Diffusing capacity Europe : Transfer factor because: It is usually obtained at rest when the index is submaximal so it is not a capacity measurement Several processes contribute to the rate constant, not only diffusion TERMINOLOGY VA: The alveolar volume (VA) can be considered the number of contributing alveolar units and is measured during the single breath DLCO by use of a tracer gas (eg, helium). kco: The permeability factor is the rate constant for alveolarcapillary CO transfer. KCO: The carbon monoxide transfer coefficient (KCO is approximately kco/barometric pressure in ml/minute/ mmhg/l), often written as DLCO/VA.

17 Carbon Monoxide Measurement of Diffusing Capacity DLCO = V CO P A CO - P c CO PcCO 0 Normal DLCO = ml/min/mmhg

18 DLCO Has Two Components Diffusion across the alveolar membrane. Reaction with hemoglobin. 1 DL = 1 Dm + q 1 xvc

19 Resistance Dm = membrane conductance Qc = effective capillary blood volume, in ml Hb = Hemoglobin concentration as a fraction of normal θ = constant for the rate of CO uptake by the erythrocytes per ml normal blood Vc =capillary blood volume

20 Measurement of diffusing capacity Methods Single breath-holding method Single expiration method Rebreathing method Steady state method

21 Almost all pulmonary function laboratories use a single-breath method Preparation No cigarette smoking on the day of the test (or note the timing of the last cigarette smoked). No supplemental oxygen for at least 15 minutes prior to and during the test (use of supplemental oxygen can decrease DLCO by approximately 0.35 percent per mmhg change in arterial oxygen tension (PaO 2 ). The DLCO test cannot be performed in patients who are unable to discontinue supplemental oxygen for at least 15 minutes) The updated standards no longer recommend against use of bronchodilators before DLCO testing. The patient is: seated has a nose clip and mouthpiece in place is instructed to adhere to tidal volume breathing without deep inspirations until instructed

DLCO maneuver A full exhalation to residual volume (RV) The mouthpiece is connected to the test gas (0.3 percent carbon monoxide [CO], tracer gas [eg, 10 percent helium or 0.

22 DLCO maneuver A full exhalation to residual volume (RV) The mouthpiece is connected to the test gas (0.3 percent carbon monoxide [CO], tracer gas [eg, 10 percent helium or 0.3 percent methane], oxygen, and nitrogen) The subject inhales rapidly to total lung capacity in <4 seconds Following a 10±2 second breath hold, the subject exhales quickly and completely to RV. An alveolar sample of the exhaled gas is collected immediately following dead space washout and analyzed for calculation of the dilution of the tracer gas and the uptake of CO. Most DLCO instruments are unable to measure the DLCO when the patient's vital capacity is less than approximately 1.5 L.

Single breath DLCO maneuver The patient quickly inhales a deep breath of test gas, holds his or her breath for 10 seconds, and then exhales quickly.

23 Single breath DLCO maneuver The patient quickly inhales a deep breath of test gas, holds his or her breath for 10 seconds, and then exhales quickly. The Jones method measures breathhold time (BHT) starting at 30 percent of inspiratory time (ti) and extending to half of sampling time. RV: residual volume; TLC: total lung capacity. Adapted from Am J Respir Crit Care Med 1995; 152:2185.

24 Calculation of DLCO and VA DLCO testing equipment calculates the DLCO and VA from the measured volumes and fractions of inspired and expired CO and tracer gas (such as helium) during the DLCO maneuver. During breath holding, CO leaves alveolar gas at an exponential rate. The rate constant kco is the measured logarithmic change in CO concentration per minute. VA is the alveolar volume (accessible during a 10 second breath hold), which is calculated by knowing the fractional concentration of the tracer gas in the inhaled and exhaled gas and also volume of gas inhaled. F1V1 = F2V2 VA = VI x (FI tracer/fa tracer) VA x kco = V CO (ml/min) Dividing both sides of the equation by P B (barometric pressure water pressure) gives the DLCO: (VA x kco)/(p B -P H2O ) = V CO /P B -P H2O = DLCO ml/min per mmhg As KCO = kco/(p B -P H2O ), the relationship can be simplified to: DLCO (gas exchange capacity) = KCO (efficiency per lung unit) x VA (number of lung units).

25 Not more than five tests should be done in the course of one session, as five tests can decrease the measured DLCO by 3 to 3.5%. ATS : DLCO in ml (at standard temperature, pressure, and dry [STPD])/min per mmhg, ERS :uses SI units mmol/min per kpa. (Values in SI units are multiplied by to obtain values in traditional units)

27 Copyrights apply

28 ADJUSTMENTS Anemia Decrease in hemoglobin from 16 down to 8 g/dl results in a decline in DLCO from 100% to 75% predicted. The DLCO falls about 9 % during menstruation. DLCO pred.corr = DLCOpred X [1.7Hb/(10.2+Hb)] (Men) DLCO pred.corr = DLCOpred X [1.7Hb/(9.4+Hb)] (Women) Carboxyhemoglobin and cigarette smoking An increase of 1 percent in COHb results in a proportionate 1 percent decrease in the measured DLCO. High altitude The lower arterial oxygen concentration results in less competition for CO binding to hemoglobin, increased CO uptake, and higher measured DLCO compared to a test done at sea level. Patients living at high altitude also have slightly higher hemoglobin levels, resulting in increased DLCO values. (reference equations from the study of Crapo and coworkers). Volume correction the volume inspired (VI) should be >90 percent of the largest vital capacity (VC) to show that any reduction in VA is not due to poor inspiratory effort.

29 Volume correction In the past, the term DLCO/VA (also known as KCO) was misinterpreted as a correction factor for low lung volume, leading to potential misinterpretation of DLCO results. The nonlinear relationship between KCO and lung volume precludes KCO from being a correction factor for DLCO when lung volumes are reduced. DLCO/VA (KCO) reflects alveolar CO uptake efficiency at a given volume. DLCO/VA and DLCO are affected by changes in lung volume (eg, DLCO falls and KCO rises as lung volume becomes smaller in healthy subjects). However, applying DLCO/VA as the correction factor is a misinterpretation of this value.

30 Conditions that Impact Diffusion Capacity for CO DLCO = AxD

31 Interpretation Low DLCO due to cigarette smoking The DLCO is substantially lower in current smokers than in nonsmokers. ( Since the reduction of DLCO partially resolves after smoking cessation, the reduction of DLCO in current smokers cannot be attributed entirely to emphysema and can be influenced by increased carboxyhemoglobin levels.) Low DLCO with obstruction due to emphysema. There is little evidence that a lower DLCO predicts increased morbidity or mortality from COPD (for a given baseline FEV 1 and degree of airway hyperreactivity). --Cystic fibrosis and alpha-1 antitrypsin deficiency (children and young adults). --This pattern can also be seen in adults with bronchiolitis obliterans bronchiectasis H. Langerhans lymphangioleiomyomatosis

32 Interpretation Low DLCO with restriction interstitial lung disease (IIPS, CTD, HF, Granulomatous Disease, drug indused disease, AP, asbestosis). Low DLCO plus both restriction and "small airways" obstruction is also seen in: Sarcoidosis (stage II through IV) Asbestosis Miliary tuberculosis Heart failure Normal DLCO with restriction extrapulmonary cause of the restriction, such as pleural effusion, pleural thickening, neuromuscular weakness, or kyphoscoliosis.

33 Interpretation Low DLCO with normal spirometry: Pulmonary vascular disease (mild to severe decrease in DLCO), such as chronic recurrent pulmonary emboli, idiopathic pulmonary arterial hypertension, and pulmonary vascular involvement with rheumatic diseases and vasculitides Early interstitial lung disease Anemia Hepatopulmonary syndrome An increased carboxyhemoglobin level due to cigarette smoking Increased DLCO Pulmonary hemorrhage Obesity Asthma High altitude Polycythemia Left-to-right intracardiac shunting Mild left heart failure (due to increased pulmonary capillary blood volume) Exercise just prior to the test session (due to increased cardiac output) Supine position

34 Copyrights apply

35 How should the KCO be defined? Krogh: k (kco) permeability, KCO has been referred to as the Krogh factor Cotes : transfer coefficient Hughes and Pride essentially the rate constant for alveolar CO uptake. (ATS/ERS) Task Force KCO or DLCO/VA, like most authors, as diffusing capacity per unit alveolar volume. DLCO reductions greater than VA reductions reflect pulmonary vascular problems. DLCO reductions comparable to VA reductions reflect pulmonary parenchymal problems. DLCO reductions less than VA reductions reflect extrapulmonary problems such as obesity, neuromuscular disease, pleural disease, or resection of pulmonary tissue. Copyrights apply

36 Copyrights apply

37 Copyrights apply

38 Copyrights apply

39 Copyrights apply

Prior to lung resection surgery predicting patients at higher risk for postoperative complications following lung resection for lung cancer and lung volume reduction surgery (LVRS).

40 Prior to lung resection surgery predicting patients at higher risk for postoperative complications following lung resection for lung cancer and lung volume reduction surgery (LVRS). A very low DLCO increases the risk of postoperative morbidity and mortality in patients with lung cancer, although there is no consensus regarding the threshold below which surgery is contraindicated Disability evaluation in patients with severe COPD or interstitial lung disease. A DLCO below 40 percent predicted (or less than 9 ml/min per mmhg) may qualify a patient for total disability according to Social Security standards. Copyrights apply Need for oxygen therapy A low DLCO (eg, 50 percent of predicted) is the major predictor of oxygen desaturation during exercise, so a DLCO test may be worthwhile as a screening test in patients presenting with dyspnea on exertion.

41 FUTURE DIRECTIONS real time gas analyzers: Continuous measurement of carbon monoxide (CO) and the tracer gas (eg, methane) Use of small sample volumes This technology may allow for visual assessment of dead space clearance to ensure alveolar gas sampling and provide a means to measure DLCO among patients with lower vital capacities (DLNO): Since NO has a much faster rate of reaction with hemoglobin and the red blood cell resistance approaches zero, DLNO remains unaffected by fluctuations in pulmonary capillary blood volume and reflects the alveolar-capillary membrane diffusing capacity. The DLNO/DLCO ratio can be measured in a single maneuver and is inversely related to the thicknesses of the alveolar membrane and capillary sheet At present, this measurement is not widely available in clinical laboratories and is mostly used in research settings.

42 Take home message 'Obstructive disease The DLCO is decreased in patients with emphysema, bronchiolitis obliterans, and lymphangioleiomyomatosis, whereas it tends to be normal or high in patients with asthma. Among patients with COPD, a low DLCO predicts oxygen desaturation during exercise and long-term outcome of lung volume reduction surgery. 'Restrictive disease' A low DLCO combined with reduced lung volumes suggests interstitial lung disease. A normal DLCO associated with low lung volumes suggests an extrapulmonary cause of the restriction, such as pleural effusion, pleural thickening, neuromuscular weakness, or kyphoscoliosis. 'Low DLCO with normal spirometry Pulmonary vascular diseases (eg, pulmonary hypertension, thromboembolic disease), early interstitial lung disease, anemia, hepatopulmonary syndrome, and carboxyhemoglobinemia. Follow up A change in the DLCO is a good index of disease progression in ILDs or response to therapy.

43 ΕΥΧΑΡΙΣΤΩ

Diffusion. Dr. Gyanendra Agrawal Senior Resident Deptt. of Pulmonary Medicine PGIMER, Chandigarh

Diffusion. Dr. Gyanendra Agrawal Senior Resident Deptt. of Pulmonary Medicine PGIMER, Chandigarh Diffusion Dr. Gyanendra Agrawal Senior Resident Deptt. of Pulmonary Medicine PGIMER, Chandigarh Diffusion Primary function of lung gas exchange Movement of gas across the blood gas interface is by simple