breath for the full 14 sec. Forcing expiration causes more airway closure and true residual volume is easier to each with a relaxed expiration. In normal subjects FVC is the same as VC or better according to the equipment used. When both are measured, FEV1/vital capacity i s the taken to be the lower of the estimates. However, most COPD guidelines have employed F EV1/FVC for simplicity. In most healthy subjects this ratio is greater than 70%. 14 sec for ced expirations are uncomfortable. 6-sec readings of FVC, yielding FEV1/FEV6, are receiving increasing attention; the lower limit of normal being 73%. Why are DL/VA (diffusion or tra nsfer coef \201 cient) and DLco both used? As shown in the calculation, diffusing capacity is the prod- uct of the diffusion coef \201 cient (uptake per liter of lung vol- ume) and the lung volume at which the measurement was made. In normal subjects the pulmonary capill ary blood is distributed to the alveoli which are ventilated; as a result the diffusion coe f \201 cient is much higher than in full inspira- tion. As the lung volume is increased th e coef \201 cient falls but proportionally less than the rise of lung volume. Therefore, o verall, diffusing capacity is higher near TLC. When TLC is high, as in pulmonary emphysema, DL/VA is found to be more sensitive to changes in pulmonary vascu- larity than DLco. In re strictive alveolar diseases such as advanced pulmonary \201 brosis, diffusing capacity is low but the coef \201 cient DL/VA is usually within or near normal limits. If it were not , the gas exchanging capacity might be insuf \201 - cient to sustain life. When restrictio n to inspiration is caused by pleural or chest wall disease, without lung dis- ease, transf er coef \201 cient is high as it is in normal subjects who have taken an incomplete inspir ation; this can be used to help determine whether there is underlying lung disease. Practice points: frequently asked questions What are reference (normal) values? Lung volume s and diffusing capacity are dependent on height, age, sex, and sometimes in \202 uenced b y body mass. There are substantial published racial differences. The most striking of these is the relatively lower lung volumes seen in those of black African descent; their higher diffusing capac- ity and coef \201 cient result in an overall advantage in athletics. A re ading of 1.64 standardized residual deviations from the predicted population mean can be in terpreted as abnor- mal in that only 5% of a healthy population will be below this reading; greater deviations obviously can be inter- preted with greater con \201 dence. The use of \200\230% predicted \200\231 is helpful in giving a feel for the size and shape of the lu ngs and in tables describing the abnormalities found among groups of patients with speci \201 c disorders. The common assumption that 80% usually de \201 nes the lower limit of no r- mal is highly misleading and often leads to over-reporting of abnormalities. COPD guidel ines use FEV1/FVC rather than FEV1/VC; does this matter? Physiologists prefer FEV1/VC becau se it is a better diag- nostic tool. In obstructive diseases, FVC almost always underestima tes VC even if care is taken to continue the Further reading Hughes JMB, Pride NB. (eds). Lung Function Tests: Physiological Principles and Clinical Applications. London: Saunders, 1999. MacIntyre N, Crapo RO, Viegi G, et al. Standardization of the single- breath determination of carbon monoxide uptake in the lung. Eur Resp J 2005; 26: 720 \200\223735. Miller MR, Crapo RO, Hankinson J, et al. General considerations for lung function testing. Eur Resp J 2005; 26: 153 \200\223161. Miller MR, Hankinson J, Brusaco V, et al. Standardization of spirometry. Eur Resp J 2005; 26: 319 \200\223338. Pellegrino R, Viegi G, Brusaco V, et al. Interpretative strategies for lung function tests. Eur Resp J 2005; 26: 948 \200\223968. Wanger J, Clausen JL, Coates A, et al. Standardization of the measurement of lung volumes. Eur Resp J 2005; 26: 511 \200\223522. Vital capacity (VC) VC low VC normal FEV1/VC not low FEV1/VC low FEV1/VC normal FEV1/VC low TLC not low TLCO low TLC not low TLC low TLC low Dyspnoea appropriate to FEV Yes No Basal crackles Basal crackles Airflow obstruction Mixed Restrictive ventilatory defect Yes C H A P T E R No Yes Yes No No ? Evidence of pulmonary vascular disease Spontaneous variation or response of PEF and FEV1 >15% after bronchodilators P1 max normal P max low 2 ? Fibrosis, alveolitis, heart failure or chronic infection . Assess options 2 Yes L u n g No Yes No 1 2 3 Lung/thoracic disease Neuromuscular disease 15% variation in PEF or FEV1 over 24 h period, after vigorous exercise at 80% maximal or af ter specific challenge f u n c t i o n ? Evidence of pulmonary vascular disease: ECG, pulmonary artery pressure, mismatched perfus ion defect, abnormal dead space Pulmonary vascular disease Yes No Yes Irreversible airflow obstruction Asthma Mixed ? All options 1-3 assessed? No No t e s t s : a Chronic bronchitis Unexplained dyspnoea No Yes Yes ? PEF (litres/min) < FEV. (litres) x 100 Low PCO2, irregular breathing, frequent sighs, background of anxiety or bereavement Pulmonary vascular disease considered Yes g u d e Improvement afterr steroids No Yes i 2 No Yes Sputum > 5 ml P1 max low? No No Yes t o No ? Yes 50% chance of central airway obstruction 1 i No n t e r p r e t a t i o n 2 1 Central airway obstruction Diffuse airways obstruction Major component of emphysema Look for evidence of thyroid or heart disease, with or without lung disease Look for evidence of neuromuscular disease, with or without lung disease Psychogenic dyspnoea with or without lung disease Low TLCO/VA \200\231 Obliterative bronchiolitis Flow at 50% VC PEF No Yes Yes Fig. 2.2.5 2 3 P PALANGE 24 2.3 Exercise testing The ability to exercise largely depends on the ef \201 ciency of the integrated physiologi c responses of the cardiovascular and respiratory systems to couple the metabolic needs of contracting skeletal muscles. In healthy subjects, exercise tolerance is largely in \202 u enced by age, gender, level of day life activity and \201 tness. In patients with heart o r lung diseases, exercise tolerance is limited by symptoms (e.g. dyspnoea, leg fatigue) cau sed by abnormal cardiovascular, ventilatory and metabolic responses to exercise load. The c auses of exercise intolerance can classified as \200\230central \200\231 (e.g. ventilatory limitation, circulatory limitation) and \200\230peripheral \200\231 (e.g. muscle dysfunct ion). In patients with chronic pulmonary or heart diseases, central and periph- eral abnorm alities often co-exist. Suggested exercise duration: 10 \200\22312 minutes. Pulmonary gas exchange should be measur ed breath-by-breath. EKG and blood pressure are monitored. Symptoms (e.g. dyspnoea and leg fatigue) are recorded at the end of exercise by the use of dedicated scales (e.g. Borg scal e). Constant work rate (CWR). CWR protocols, on a cycle ergometer or on a treadmill, are ut ilized for the meas- urement of exercise \200\230endurance \200\231 tolerance, pulmonary g as exchange kinetics, arterial blood gasses and \202 ow-vol- umes curves during exercise. CWR exercise results in steady-state responses when work rate is of moderate intensity (i. e. below the lactate threshold, L); conversely, high intensity CWR exercise (i.e. above t he L) results in continually changing in most physiologic variables. 6MWT. The object of this test is to walk as far as possible for 6 minutes. The test should be performed indoors along a 30 m long, \202 at, straight corridor; encouragement signi \201 cantly increase the distance walked. Safety. Careful selection of patients prevents serious complications during maximal incremental exercise. Myocardial infarction (within 3 \200\2235 days), unsta ble angina, severe arrhythmias, pulmonary embolism, dissecting aneurism, respiratory failur e, and severe aortic stenosis represent absolute contraindication to CPET. The principal causes of reduced exercise tolerance that can be ruled out at cardiopulmonary exercise testing (CPET) are the following: \200 \200 \200 \200 \200 Reduced oxygen (O2) delivery to exercising muscles. Ventilatory limitation to exercise. Pul monary gas exchange abnormalities. Muscle dysfunction including deconditioning. Excessive p erception of symptoms. Protocols and variables CPET is considered the gold standard for evaluating the causes of e xercise intolerance in lung and heart diseases. CPET comprises the imposition of symptom-li mited incre- mental exercise in combination with comprehensive breath-by-breath monitoring of cardiopulmonary variables (e.g. ventilation (V \200\231E), heart rate (HR), oxygen uptak e (V \200\231O2), CO2 output (V \200\231CO2)), perceptual responses (e.g. dyspnoea, leg dis comfort) and, as needed, measurements such as exercise-related arterial O2 desaturation, dy namic hyperin \202 ation and limb-muscle strength. Variables: key points \200 V O2-work rate relationship (ZV O2/ZWR). In normal sub- jects, the slope of the linear phas e from \200\230unloaded pedal- ing \200\231 to peak cycle ergometer exercise is 9 \200 \22312 ml/min/watt. This index is used as an approximate index of work ef \201 ciency. ZV \200\231O2/ZWR is relatively independent of age, gender, \201 tness and body mass. 5.0 V O2 peak 4.0 ) n m i AUTHOR \200\231S TIP There are some CPET response patterns (e.g. ventila- tory limitation, circulatory limitation) that are not dis- ease-speci \201 c but point to particular sites of system dysfunction, narrowing the differential diagnosis. The absence of these response patterns can be taken as evi- dence against a signi \201 cant involvement of these systems in the exercise limitation. 3.0 / l ( 2 2.0 O V 1.0 0.0 0 50 100 150 200 250 300 350 Work rate (W) The classical criterion for de \201 ning exercise intolerance and classifying degrees of i mpairment is V \200\231O2 peak standardized by body mass (mlV \200\231O2/min/kg). Values be low 80% pre- dicted should be considered abnormal while values below 40% of the predicted i ndicate severe impairment. Walking tests, such as the 6-minute walking test (6MWT) and the \200\230shuttle \200\231 walking test, are increasingly utilized for the assessment of exe rcise tolerance in chronic diseases; measurement of arterial O2 saturation by pulse oxymetr y (SpO2), HR and exertional symptoms are recommended during these tests. Fig. 2.3.1 V O2 peak. Is the highest V O2 value (ml/min or cor- rected for body mass, ml/min/kg) measu red at peak exer- cise. With good subject effort, V O2 peak reflects subject \200\231s maxi mal aerobic capacity ( \200\230maximum \200\231 V \200\231O2). This index is taken to re \202 ect the attainment of a limita- tion in the O2 conductance pathway from the lungs to t he mitochondria. Lactic threshold (qL). The lactate threshold is the highest WR or V O2 at which arterial lactate is not systemati- cally increased; it is considered an important fun ctional demarcator of exercise intensity. Sub- L work rates can normally be sustained for prolonged periods. L is dependent on age, gender, body mass and fitness. Protocols: key points \200 CPET. It is a symptom-limited incremental protocol, per- formed on a cycle ergometer or on a treadmill. Work rate is increased every minute or in a ramp fashion. CHAPTER 2.3 Exercise testing 25 Non-invasive estimation of L requires the demonstra- tion of an augmented V \200\231CO2 i n excess of that produced by aerobic metabolism. Ventilatory equivalents for CO2. Measured as the slope of the increase of V \200\231E over V \200\231CO2 (ZV \200\231E/ZV \200\231CO2 ) from \200\230unloaded pedaling \200\231 to the respiratory compensation point (RCP) or a s the value at L (ZV \200\231E/ZV \200\231CO2 @ L). It is considered a non invasive ind ex of \200\230ventilatory ef \201 - ciency \200\231. In normal individuals ZV \200\231E/Z V \200\231CO2 values of 25 \200\22328 have been reported. Several factors may increase ven tilatory response to exercise, namely hypoxemia, acidosis, increased levels of wasted venti lation and pulmonary hypertension. Breathing reserve (BR). BR provides an index of the prox - imity of the ventilation at the limit of tolerance (V \200\231E max) to the maximal achie vable ventilation (MVV, estimated from the subject \200\231s resting FEV1 x 40). BR can be de \201 ned as V \200\231E max as a percentage of MVV (i.e. 1 \210\222V \200\231E max/MVV) . In chronic lung diseases BR is reduced or absent at peak CPET exercise. Dynamic hyperin \202 ation (DH). In normal subjects end- expiratory lung volume (EELV) decreases with incre asing WR by as much as 0.5 \200\2231.0 litres below functional resid- ual capacity (FRC). C hanges in EELV during exercise can be estimated by asking the subject to perform an inspira - tory capacity (IC) maneuver at a selected point in the exercise test. In obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD), EELV increases during exer cise in spite of expiratory muscle activity. Arterial O2 desaturation. During exercise arte rial O2 satu- ration (SpO2) is maintained in the region of 97 \200\22398%. However, it is n ot uncommon for highly- \201 t endurance athletes and women to exhibit arterial desaturati on at peak exercise. Arterial oxygen desaturation can be observed in patients with moderate \200\223severe interstitial lung disease (ILD) and in patients with primary pulmo- nary hy pertension (PPH). A more pronounced arterial O2 desaturation as been reported during walkin g com- pared to cycling in patients with COPD. TLIM and \200\230isotime \200\231 measureme nts. TLIM is the tolerable limit of exercise, expressed as function of time (e.g. minutes) measured during CWR protocols. In clinical practice high intensity ( \210 80% watt max) CWR protocols are utilized for the evaluation of interventions. In addition to TLIM, measureme nt of pertinent physiologic variables (e.g. V \200\231E, IC, dyspnoea) at standardized time ( \200\230isotime \200\231) are obtained. The principal indications to exercise testing in clinical practice are the following: 1 Pro vide an objective measure of exercise capacity. 2 Identify the mechanisms limiting exercise tolerance. 3 Establish indices of the patient \200\231s prognosis. 4 Monitor disease progr ession and/or the response to interventions. AUTHOR \200\231S TIPS \200 V O2 peak, L, oxygen pulse (V O2/HR), BR, ZV E/ ZV CO2, DH, SpO2 are the exercise variabl es/indexes that have been shown to be particularly useful in the functional and prognostic evaluation of patients with chronic heart and lung diseases. V O2 peak values of <14 ml/min /kg, V O2 values at L of <11 ml/min/kg and ZV \200\231E/ZV \200\231CO2 slopes of >34 all sug- gest poor prognosis in patients with CHF V O2 peak has also been utilized as a prognos tic variable in patients with COPD, ILD, CF and PPH. High intensity CWR tests, performed on a cycle ergometer or on a treadmill, to the TLIM seems to pro- vide the best information o n the effects of therapeutic interventions. Further reading ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003; 167: 211 \200\223277. ATS statement: guidelines for the six-minute walking test. Am J Respir Crit Care Med 2002; 166: 111 \200\223117. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting the anaerobic threshold by gas exchange. J Appl Physiol 1986; 60: 2020 \200\2232027. Casaburi R, Kukafka D, Cooper CB, et al. Improvement in exercise tolerance with the combina tion of tiotropium and pulmonary rehabilitation in patients with COPD. Chest 2005; 127: 809 \200\223817. ERS task force on standardization of clinical exercise testing. Clinical exercise testing w ith reference to lung diseases: indications, standardization and interpretation strategies. Eur Resp J 1997; 10: 2662 \200\2232689. Gitt AK, Wasserman K, Kilkowski C, et al. Exercise anaero- bic threshold and ventilatory ef \201 ciency identify heart failure patients for high risk of early death. Circulation 200 2; 106: 3079 \200\2233084. Myers J, Prakash M, Froelicher V, et al. Exercise capacity and mortal- ity among men referr ed for exercise testing. N Engl J Med 2002; 347: 288 \200\22390. O \200\231Donnell DE, Revill SM, Webb KA. Dynamic hyperin \202 ation and exercise intolera nce in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 770 \200 \223777. Exercise testing in clinical practice Evaluation of heart and lung functional reserves measured at rest (e.g. spirometry, lung di ffusion for CO, echocardiog- raphy) do not allow accurate prediction of the level of exerci se tolerance in health and disease states such as COPD and chronic heart failure (CHF). Imp ortantly, exer- cise intolerance predicts poor prognosis in chronic dis- eases. Well establ ished indications for exercise testing are the diagnosis of myocardial ischaemia and exerci se-induced bronchoconstriction. In the last decade, however, exercise testing has been incr easingly utilized for the functional and prognostic evaluation of patients with chronic lun g and heart diseases and for the evaluation of the effects of inter- ventions. CPET variabl es as well as distance covered during walking tests have proven to be useful in the functio nal and prognostic evaluation of pati ents with COPD, CHF, ILD, PPH and cystic \201 brosi s (CF). O \200\231Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperin \202 ation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004; 23: 832 \200\223840. Oga T, Nishimura K, Tsukino M, et al. The effects of oxitropium bromide on exercise perform ance in patients with stable chronic obstructive pulmonary disease. A comparison of three d ifferent exercise tests. Am J Respir Crit Care Med 2000; 161: 1897 \200\2231901. Palange P, Crimi E, Pellegrino R, et al. Supplemental oxygen and heliox: \200\230new \200 \231 tools for exercise training in chronic pulmonary diseases. Curr Opin Pulm Med 2005; 11 : 145 \200\223148. Palange P, Valli G, Onorati P, et al. Effect of heliox on lung dynamic hyperin \202 ation, dyspnoea, and exercise endurance capacity in COPD patients. J Appl Physiol 2004; 97: 1637 \200\2231642. P PALANGE 26 Singh SJ, Morgan MDL, Scott S, et al. Development of a shuttle walking test of disability i n chronic airways obstruction. Thorax 1992; 47: 1019 \200\2231024. Palange P, Forte S, Onorati P, et al. Ventilatory and metabolic adap- tation to walking and cycling in patients with COPD. J Appl Physiol 2000; 88: 1715 \200\2231720. Wasserman K, Hansen JE, Sue DY, et al. Principles of Exercise Testing Palange P, Ward SA, Carlsen K-H, et al. Recommendations on the use of exercise testing in c linical practice. Eur Respir J 2007; 27: 529 \200\22341. and Interpretation, 4th edn. Philadelphia: Lea & Febiger, 2004. This page intentionally left blank M KOHLER & J STRADLING 28 2.4 Interpretation of arterial blood gasses and acid/base balance This chapter describes a simple approach to interpreting PaO2, PaCO2, pH, and Hb, as obtain ed from standard blood gas machines. The information is divided into what can be learned ab out gas exchange, and what can be learned about acid/base balance. Considering that only fo ur numbers are actually measured by blood gas machines (the rest are cal- culated), a consi derable amount of information can be derived. use a small magnetic \200\230 \202 ea \200\231 in the tube to mix the blood with the hepa rin, by sliding an external magnet up and down the tube immediately after obtaining the sam ple. The blood gas machine must be able to take microsamples (most do). Although the sample is only an \200\230arterialised \200\231 capillary sample, and not pure arterial, PaCO2 l evels are accurate enough for clinical practice. However, with good arterialisation, with r ubefacients (Algipan \204 /Deep Heat \204 ) or heat and vigorous rubbing, a reasonably accu rate PaO2 is obtainable: the accuracy of the latter is less important as arterial oxygenati on can also be assessed by oximetry. This ear lobe technique is easily performed by nursing staff, for example, to monitor PaCO2 response to non-invasive ventilation (NIV) and O2 the rapy. The three main things blood gasses tell you about gas exchange. 1 How much is the pat ient ventilating their alveoli? This is derived from the PaCO2. PaCO2 \211 6 kPa is due t o underventilating the alveoli, PaCO2 \211 4.5 kPa is due to overventilating the alveoli. This is not the same as total ventilation, which includes dead-space of course. Interpretation of arterial blood gasses \200\223gas exchange Normal ranges Breathing air: P aO2 > 12 kPa (>10 kPa in normal elderly), PaCO2 4.6 \200\2235.9 kPa. How to take an arteria l sample Arterial blood gasses are best taken from the radial, rather than the brachial, ar tery due to the dual radial/ulnar supply to the hand. Occasionally the radial and ulnar art eries do not anastomise in the hand and damage to the radial artery can lead to infarction of the thumb and \201 rst \201 nger. In reality this is not a problem if \201 ne need les (22 or 23G) are used to sample the arterial blood, but is an issue when an indwell- ing radial artery cannula is to be inserted. The presence of an adequate anastamosis can be pr oven by pressure occlu- sion of the radial and ulnar arteries, while asking the patient to make a tight \201 st (to squeeze out blood from the super- \201 cial capillaries), then release the pressure on the ulnar artery and show that the whole palm becomes pink again w ithin a few seconds, despite continuing radial artery pres- sure (Allen test). Cock the wri st back, use quick vertical penetration of the skin (to lessen pain), followed by slower pe netration down to the artery at a slight angle along the line of the artery towards the elb ow. Use a specific heparinised syringe designed for arterial use which should only self \201 ll if in the artery. Analyze immediately, or within 30 minutes if kept cool on ice. Al ways record date, time, and the % inspired O2 (FiO2) during sampling. 2 Is the PaO2 high enough to adequately oxygenate tissues and thus prevent anaerobic metabo lism? PaO2 > 6 kPa (SaO2 8 80%) is probably adequate; PaO2 > 7 kPa (SaO2 8 87%) is de \201 nitely adequate. 3 I s there any evidence of V/Q mismatch? Evidence of low V/Q units is derived from the cal culated alveolar to arterial (A \200\223a) gradient for oxygen. 4 16 28%O2 24%O2 14 Air 12 a P k 10 2 8 O C P 6 6 5 A 7 4 2 3 1 2 0 0 2 4 6 8 10 12 14 16 18 20 22 24 PO2 kPa Fig. 2.4.2 Alveolar air line graph showing the graphical derivation of the A \200\223a grad ient for O2. The A \200\223a gradient calculator graph (Fig. 2.4.2) sets out the graphical representatio n of gas exchange. \200 Point \235 = the pO2 and pCO2 of alveolar air. (Atmospheric pressure 8 100 kPa, water vap or pressure in warm/ humi \201 ed air 8 7 kPa, and 21% of (100 \210\222 7) 8 20.) Point \235 = the pO2 and pCO2 when breathing 24% O2 via a Ventimask. (24% of (100 \210\222 7) 8 23.) Point \235 = the pO2 and pCO2 when breathing 28% O2 via a Ventimask. (28% of (100 \210\222 7) 8 26.) Point \235 = the theoretical pO2/pCO2 of alveolar gas when breathing a ir, if all the O2 were removed and replaced by CO2 (equivalent to extreme hypoventilation a nd of course impossible!), when the respiratory quotient (RQ = CO2 produced/O2 consumed) is 0.8 (usual value). Fig. 2.4.1 Taking an arterialised sample of capillary blood from an earlobe. An alternative is an arterialised capillary sample, an under- used technique. This techniqu e utilizes a small glass pre- heparinised tube to draw up blood milked from a lancet punctu re on the end of the ear lobe (Fig. 2.4.1). Some units CHAPTER 2.4 Interpretation of arterial blood gasses and acid/base balance 29 Use of A \200\223a gradient diagram: examples (Fig. 2.4.3) Case 1. Consider point (W) in th e pO2/pCO2 graph, the blood gasses on air of a young non-smoker complaining of chest pain 7 days postop. The PaO2 of 13 is normal; does this reassure you, or does it provide supporti ng evidence for a pulmonary embolus? PaCO2 = 2. Ask the following questions: \200 The line between \235 and \235 with a gradient of 0.8 describes all possible combinatio ns of alveolar gas: moving towards \235 if ventilating more, and towards \235 is ventil ating less - called the alveolar air line. Point \235 = is the area in which PaO2 and PaC O2 of arte- rial blood normally sit. If the lungs are perfect gas exchangers, then blood le aving the lungs and entering the systemic arterial circulation ( \235 ) should be perfectly equilibrated with the alveolar gas (A). Point \235 = However, the mixed venous point (th e pulmo- nary arterial blood) is well to the left of the alveolar air line, because capilla ry PO2 falls more kPa (87) than the PCO2 kPa rises (81 to 2) during gas exchange in the tis sues (because the CO2 solubility curve is steeper than the PaO2/SaO2 dissociation curve). I f the lungs fail to oxygenate mixed venous blood prop- erly (e.g. pneumonia, or low V/Q fro m asthma/COPD) then it is as if mixed venous blood has bypassed the lung and spilled into t he systemic arterial blood, which there- fore moves the eventual arterial PaO2/PaCO2 point to the left of the alveolar air line, point \235 . The horizontal distance that the actual arterial point is to the left of the \200\230ideal \200\231 alveolar air line is called t he alve- olar to arterial (A \200\223a) gradient and is a measure of how ef \201 ciently m ixed venous blood is being equilibrated with alveolar gas, i.e. it is a measure of V/Q mism atch and right-to-left shunts. How much is the patient ventilating? PaCO2 \211 4.5 kPa; therefore there is hyperventilati on. Is the patient adequately oxygenated? PaO2 > 7 kPa; therefore OK. Is there an abnormal A \200\223a gradient? Measure the hori- zontal line between W and the alveolar line off the graph, or calculate: 20 \200\223 (13 + 2 ) = 4.5 kPa 0.8 >2 kPa, hence yes; the V/Q matching is not normal. Thi s provides supporting evidence for a pulmonary embolus, but could also be due to consolidat ion from a pneumonia, for example. This makes the point that PaO2 cannot be used to assess V/Q matching in the lung without an associ- ated PaCO2 to tell you \200\230what the PaO2 o ught to be \200\231. 16 28%O2 24%O2 14 Air 12 As well as being read from the graph, the A-a gradient can be calculated. The following for mula essentially adds the RQ-corrected PaCO2 to the PaO2, and \201 nds out how far away f rom the inspired PO2 (PIO2) this number is. a P k 10 2 O C P 8 6 4 Arterial PO2 Arterial PCO2 2 Aa gradient = PIO2 \200\223 (PaO2 + PaCO2) 0 0.8 0 14 16 18 20 22 24 2 4 6 8 10 12 PO2 kPa Inspired PO2 Respiratory quotient Fig. 2.4.3 Examples of the use of the A \200\223a gradient for O2 when interpreting blood g asses. Calculation of inspired PO2 breathing either air, 24% or 28% O2: Air: 21% of (100 \210\222 7) 8 20 kPa, (where 100 kPa = atmos- Case 2. Consider point (X) on the pO2/pCO2 graph. These gasses are on air from a young man following an overdose of methadone tablets, PaO2 = 6, PaCO2 = 11. \200 pheric pressure, 7 kPa = H2O vapor pressure) 24%: 24% of (100 \210\222 7) 8 23 kPa 28%: 28% of (100 \210\222 7) 8 26 kPa How much is the patient ventilating? PaCO2 > 6 kPa; therefore he is hypoventilating Is the patient adequately oxygenated? PaO2 only 6 kPa, therefore no, he needs added O2. Has the pa tient got an increased A \200\223a gradient? Measure the horizontal line between X and the alveolar line off the graph, or calculate: On the graph, the position of the \200\230alveolar air \200\231 line depends on the inspir ed %O2, and the two extra lines, for 24% and 28% O2, are shown approximately. In the calcul ation the PIO2 has to be adjusted accordingly, see above*. In normal lungs, matching of V/Q is not totally perfect, and this is due to relative under-perfusion of the apices and over -perfusion of the bases (gravity effects on pulmonary arterial blood \202 ow, not fully c ompensated for by hypoxic vasoconstriction of pulmonary arterioles). These imper- fections in V/Q, and direct drainage of some of the cardiac muscle \200\231s venous blood into the l eft ventricular cavity (and thus systemic arterial circulation), lead to a small A \200\223 a gra- dient of 1 to 2 kPa in the young and middle aged, and 2 to 3 in the elderly. Figures in excess of these values are abnor- mal and indicate areas of low V/Q or increased right- to-left shunt. 20 \200\223 (6 + 11 ) = 0.8 kPa 0.8 <2 kPa, hence no; therefore there is nothing wrong with the lungs, despite the abnormal gas ses, this therefore represents pure hypoventilation. After a messy stomach wash-out he is s ent to the ward and 24 h later is febrile. Blood gasses on 24% O2 are point (Y) on the grap h, thus both PaCO2 and PaO2 are better. \200 How much is the patient ventilating? PaCO2 just >6 kPa; therefore is still hypoventilating a bit. M KOHLER & J STRADLING 30 The two main things blood gasses tell you about acid/base balance. \200 Is the patient adequately oxygenated? PaO2 > 7 kPa; therefore adequately oxygenated. Has th e patient got an A \200\223a gradient? What is the respiratory (or ventilatory) component to an abnormal pH? This is derived from the PaCO2. What is the metabolic component to an abnormal pH? This is derived from the calc ulated standard base excess/ de \201 cit. 23 \200\223 (11 + 6.5) = 4.2 kPa 0.8 Z (23, not 20, because on 24% O2, not air) >2 kPa so yes; may now have an aspiration pneumoni a. Relationship between SaO2 and PaO2 \200\223 \200\230discrepancies \200\231 between oximet ry and blood gasses 100 pH = 7.5, 7.4, 7.3 80 ) % ( 2 O S 60 n o i t a r u t a s Right shift caused by:- fall in pH rise in temperature increase in 2,3-DPG 50% 40 n e g y x O 20 Fig. 2.4.5 Relationship between pH and PaCO2 (log scale) with calculated iso [HCO3 ] lines added. P 50 at pH 7.40 0 2 4 6 8 60 PO2 10 12 14 16 120 kPa mmHg Interpretation of acid/base relationships are best plotted as a log PaCO2 versus pH graph ( Fig. 2.4.5), because these are the two primary measurements made by blood gas machines (eve rything else to do with acid/base balance, except the Hb, is calculated). Normality lies in the area labeled (N), the pH between 7.37 and 7.43, and the PaCO2 around 5 kPa. As ventila tion is decreased or increased (PaCO2 going up or down respectively), the pH will change; t he amount depends on the buffering capacity of the blood (CO2 is an acid gas, combining wit h water to give [H+] and [HCO3 ] ions). 20 0 40 80 100 Fig. 2.4.4 Hemoglobin dissociation curve. A fall in pH (more acidotic), or a rise in body temperature, will move the dissociation cur ve to the right. This has the effect of making the PaO2 higher for any given SaO2, e.g. at pH 7.20, a measured saturation (e.g. by oximetry) of 90% is equivalent to a higher PaO2 of 9.7 kPa than the usual 7.7 kPa: a rise in body temperature to 41 C will do the same, and t he effects of pH and temperature are additive. Conversely, for a given PaO2, pyrexia and ac idosis will lower the SaO2 and thus oxygen carriage to the tissues, e.g. a PaO2 of 7.7 kPa will normally give an SaO2 of 90%, but if the temperature rises to 41 C, and pH falls to 7 .20, then the SaO2 falls to 70%. Increasing 2,3-DPG levels shift the curve to the right, bu t levels \202 uctuate unpredictably and any changes are small. Changes in body temperatur e are often the reason why measured pulse oximetry saturations apparently \200\230do not a gree \200\231 with the measured blood gasses (pH is taken into account in the theoretical c alculation of SaO2 by blood gas analysers, but the patient \200\231s correct body temperatu re is rarely entered and thus not taken into account). This is particularly important in hy pothermia when the curve is left shifted leading to impaired oxygen unloading anyway. Furth ermore, an apparently adequate oximetry reading can mask a low PaO2, which will further les sen oxygen availability to the tissues (although somewhat mitigated by the reduced metaboli c rate of hypothermic tissues). CO2 + H2O n HCO3 + H+ Removed by combination with Hb and other proteins Following small rises in PaCO2, the pH wo uld fall disas- trously without buffering of H+ ions. This buffering capacity depends mainl y on Hb (hence an estimate is made of Hb by the blood gas machine) and other proteins, prod ucing the normal buffer line running through (N) on the graph (Fig. 2.4.5). This line would be much \202 atter without buffering. Therefore acute hypoventilation and hyperventilati on will move the patient up and down this line, in directions b or c, respectively. If hypo ventilation at point b becomes chronic (e.g. as it may in COPD), then the kidney retains HC O3 (by excreting H+) to try and correct the pH towards nor- mal, and the patient moves on to a new iso HCO3 buffer line displaced to the right, e.g. the one labeled +10 meq/l (35 meq/l). The degree of displacement represents the metabolic component to the acid/base stat us and, in this case, because the [HCO3 ] has risen, will be higher than the normal \201 gure of about 25 meq/l. When the raised \201 g- ure is quoted relative to the normal 25 meq/l (by subtract- ing 25), this is called the \200\230base excess \200\231. Thus buffer lines to the right of the normal buffer line represent a metabolic alkalosis or base excess . These \201 gures are calculated assuming a normal or \200\230stand- ard \200\231 PaCO2 (i.e. not using the patient \200\231s real value), called Interpretation of arterial blood gasses \200\223 acid/ base balance Normal ranges pH 7.37 \200\2237.43 (H+ 37 \200\22343 nmol/l), PaCO2 4.6 \200\2235.9 kPa, base excess 3 mmol/l. CHAPTER 2.4 Interpretation of arterial blood gasses and acid/base balance 31 the \200\230standard bicarbonate \200\231 (SBC on the blood gas machine printout), or \200\230standard base excess \200\231 (usually SBE). Two other similar \201 gures on some printouts (usually HCO3 and TCO2) are calculated at the patient \200\231s actual PaCO2 a nd are not much use. They will be higher when the real PaCO2 is above normal (thus more HCO 3 made), and lower when below normal, as HCO3 will fall having com- bined with H+ to re place the CO2. Chronic hyperventilation (e.g. at altitude due to the hypoxia) produces the opposite, a resorption of [H+] by the kidney, and thus the buffer line shifts to the left g iving a negative value for the \200\230base excess \200\231, a \200\230base de \201 cit \200\231. Thus a metabolic acidosis compensates for a respiratory alkalosis. Note that thes e homeostatic corrections do not bring the pH back to normal as there needs to be an error signal to keep the correction process going. A metabolic acidosis (such as in ketoacidosis) will also move the line to the left (a), producing a base de \201 cit (or negative base e xcess \200\223 a curious invention!), followed by hyperventilation to try and correct the pH (i.e. a respira- tory alkalosis to correct a metabolic acidosis). This pure ventilatory stimulation in the absence of abnormal lungs often produces deep breathing with little incr ease in rate and is called Kussmaul \200\231s breathing. Thus lines to the left of the norm al buffer line represent a metabolic acidosis or base de \201 cit. A metabolic acidosis du e to anaerobic metabolism (and hence lactic acid production) can reverse the compensa- tory metabolic alkalosis secondary to chronic hypercapnia during a severely hypoxic COPD exacer bation, removing the evidence for chronic CO2 retention. Thus a fall in pH during a COPD ex acerbation re \202 ects not only impaired alveolar ventilation (increased airways obstruct ion) but also reduced PaO2 (anaerobic metabolism) \200\223 hence a low pH is the best guid e to how sick such a patient is. Finally, metabolic alkalosis e.g. during hypokalaemia (whe n the kidney is forced to use H+ ions, instead of potassium ions, to swap for the sodium th at needs resorbing from the tubular \202 uid, [H+] is lost in the urine and HCO3 return ed to the blood). This will move the buffer line to the right (d), but only limited hypoven tilation is available to compensate, due to the inevitable ventilatory stimulation that the attendant hypoxaemia produces. Thus the mixture of respiratory and metabolic contribu- tio ns to a patient \200\231s acid/base disturbance can be established by plotting the PaCO2 an d pH on the graph (Fig. 2.4.5). exist, and helps differentiate the cause of any metabolic acidosis. Depending on methods of measurement, the nor- mal value is between 8 and 16mmol/l (or meq/l) and mainly due to alb umin. A high anion gap indicates that there is loss of HCO3 without a subsequent increase in Cl . Electroneutrality is maintained by the increase in anions such as ketones, lactat e, PO4 , and SO4 . Because these ani- ons are not part of the anion-gap calculation a hig h anion gap results. An acidosis with a normal anion gap will be a simple HCO3 /Cl excha nge such as might occur, for example, in: \200 \200 \200 renal tubular acidosis; acetazolamide therapy; HCO3 loss from profuse diarrhea. An anion gap is likely to be present, for example, when the metabolic acidosis is due to: \200 \200 \200 \200 \200 \200 diabetic ketoacidosis (ketones are acids); renal failure (although can be in the normal ran ge too); lactic acidosis; salicylate poisoning; methanol poisoning; ethylene glycol (antifr eeze) poisoning. AUTHOR \200\231S TIPS There are only three main things to think about when assessing gas ex change: \200 \200 How much is the patient ventilating their alveoli? Is the PaO2 high enough to adequately ox ygenate tissues and thus prevent anaerobic metabolism? Is there any evidence of a V/Q misma tch, assessed from the A \200\223a gradient for oxygen? There are only three main things to think about when assessing acid/base: \200 Is there a ventilatory/respiratory contribution from an abnormally high or low PaCO2? Is th ere a metabolic component evidenced by a shift of the buffer line to the left or right, num erically the base excess (or de \201 cit)? If there is an acidosis, is there an increased anion gap? Further reading Williams AJ. http://www.bmj.com/cgi/content/ full/317/7167/1213 Anion gap The anion gap [(Na+ + K+) - (Cl + HCO3 )] shows you the amount of other anions , apart from Cl + HCO3 , that M MASOLI & P HUGHES 32 2.5 Respiratory muscle function Overview of function \200 Causes of respiratory muscle weakness