The importance of determination...

INTRODUCTION

Celiac disease represents by definition a hypersensitivity of In patients with liver cirrhosis and prominent hypoxemia, the IPVD and right-to-left shunts represent the major pathogenic mechanism in the development of severe respiratory disorders (1–3).

The most common pulmonary symptom in IPVD is dyspnea, affecting almost 40% of patients. If questioned, up to 70% of candidates for liver transplantation complain of dyspnea (4). Another typical manifestation of IPVD in cirrhosis is platypnea, specifying that dyspnea is more pronounced in the upright and sitting position than in a recumbent one (5). Orthodeoxia is another clinical sing in IPVD, representing the decrease of partial oxygen pressure more then 10% when patient is changing the position from a recumbent to a sitting one.

Hypoxemia with partial oxygen pressure (Pa,O2) less than 8 kPa without any other cardiorespiratory diseases suggests the presence of IPVD (6,7).

The determination of P(A-a)O2, is the simplest method of assessment the ratio of ventilation and perfusion of the lungs. It is demonstrated that P(A-a)O2 ≥ 2 kPa with or without hypoxemia indicates the IPVD (8).

PATIENTS AND METHODS

The prospective study analyzed results of 70 patients with liver cirrhosis which were treated at the Institute of Digestive Diseases and Institute of Pulmonary Diseases, Clinical Centre of Serbia.. Gas analyses were carried out using Blood Gas Manager IL 1312 equipment, while predicted values for the partial oxygen pressure in blood were calculated using Sorbini equation (Pa,O2 =103.5 - 0.42 x years) (9). Arterial blood gases analysis were performed in both supine and sitting positions while exposed to the room air and after 15 minutes of breathing of hyperoxic mixture using a direct method, which includes arterial blood sample with a heparinized syringe.

Spirometric measurements in our study were performed by open spirometric system with pneumotachograph (Pneumoscreen II spirometer) for determination: vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume during the first second (FEV1). Body plethysmograph (Bodyscreen II) was used for measurement of total lung capacity (TLC), thoracic gas volume (TGV), residual volume (RV), and air volume resistance in the airways (RaW).

The alveolo-arterial gradient of oxygen pressure (P(A-a)O2=PA,O2-Pa,O2) was calculated in the way usually used in practice. The oxygen pressure in the alveolar gas is calculated on the basis of the measured atmospheric pressure and carbon-dioxide in the exhaled air (PA,O2= Fio2 x (Pb – PaH2O) – PA,CO2 (Fio2 + 1 – Fio2 / Ra) ( Fio2-fractional inspiratory concentration of oxygen; Ra-respiratory quotient), while Pa,O2 is measured directly in the arterial blood (10).

Given to the variations of respiration changes in cirrhotics while assuming different body positions, arterial blood gas changes occurred, the change of P(A-a)O2 for at least 0.66 kPa is a sign of significant alteration of IPVD with the assumption of different body positions (11).

Pulmonary function tests were used to determine the transfer factor (TL,CO) and transfer coefficient (KCO = TL,CO divided by the effective alveolar volume), as the indicators of alveolo-capillary diffusion state. Diffusion parameters were measured by carbon monoxide, using the one-inspiration method, with Transferscreen machine. Lower normal limit of transfer factor was determined by mathematics in the way that the expected values of TL,CO were subtracted by SD of 1.64 (SD of 1.42 for males, SD of 1.17 for females). The expected values of TL,CO were calculated on the basis of valid standards (in males, expected TL,CO = 11.11 x height in meters -0.066 x years - 6.03; in females, expected TL,CO = 8.18 x height in meters - 0.049 x years - 2.74) (11).

Restrictive ventilatory disorders were defined on the basis of spirometric parameters: VC, index 100 x FEV1/VC (Tiffeneau) and TLC. Lower normal limit was determined as the expected value – 1.64 SD (in males, SD for FVC = 0.61, SD for TLC = 0.70, and for Tiffeneau SD = 7.17; in females, SD for FVC = 0.43, SD for TLC = 0.60, and for Tiffeneau SD = 6.51) (12).

Statistical analyses were performed using χ2 and t-test.

RESULTS

Orthodeoxia was confirmed in 10 (14.3%) hypoxemic and 4 (5.7 %) normoxemic patients. When room air was breathed, the average Pa,O2 value in a supine position was 9.40 ± 1.74 kPa, while in a sitting position the average Pa,O2 value was 7.41 ± 1.81 kPa. When 100% oxygen was breathed, the average Pa,O2 value in supine position was 35.49 ± 17.95 kPa, while in the sitting position the average Pa,O2 value was 21.07 ± 14.41 kPa (Table 1).

In our series, 30 (42.8%) patients had P(A-a)O2 over 2 kPa. All patients with orthodeoxia had higher P(A-a)O2, whose mean value in the supine position was 4.03 ± 2.36 kPa while it was 5.73 ± 2.65 kPa in the sitting position. The patients with orthodeoxia and higher P(A-a)O2 had IPVD. The patients with orthodeoxia and normoxemia also had higher P(A-a)O2, ranging from 2.1 to 2.37 kPa and presented subclinical IPVD.

The diagnosis of ascites was made in 43 (61%) patients. Restrictive ventilatory disorders and higher P(A-a)O2 were diagnosed in 16 (37.2%) patients with ascites. Mean value of restriction parameters was: VC 73.0 ± 14.4, TLC 83.7 ± 13.5, and Tiffeneau index 78.3 ± 3.37.

Among the patients with restrictive ventilatory disorders and without orthodeoxia, the mean value of P(A-a)O2 was 2.77 ± 1.12 kPa in the supine position while it was 1.80 ± 1.04 kPa in the sitting position. Comparing patients with and without orthodeoxia, the significant difference in P(A-a)O2 (p=0.001, t-test) was found, especially in the sitting position (Table 2).

Lower transfer factor (TL,CO) was found in 38 (54%) patients, while lower transfer coefficient (KCO) was noted in 46 (66%) patients. The mean value of transfer factor was 6.24 (65.72%). All patients with IPVD and subclinical IPVD manifested reduced values of transfer factor and transfer coefficient.

Higher P(A-a)O2 and normal values of transfer factor were recorded in 11 (16%) (patients with restrictive ventilatory disorders), while the increased P(A-a)O2 and lower transfer factor were found in 14 (20%) patients (patients with IPVD). Lower transfer factor and normal P(A-a)O2 were recorded in 17 (24%) patients. No statistical significance between the increase of P(A-a)O2 and diffusion impairment was found (χ2 – test, p=0.62) (Table 3).

DISCUSSION

In their study of 26 patients with liver cirrhosis, Bashour and Cochran (1966) obtained the mean gradient value of 5.97 kPa (13).

In the group of patients who were candidates for portocaval shunt, Naeije et al (1985) measured the mean value of P(A-a)O2 of 4.58 kPa (14).

In 1991, Hourani and associates reported the increased gradient of oxygen pressure in 45% of patients who were candidates for liver transplantation, and the mean value of gradient was 4.89 kPa (4).

Stressing the significance of this functional disorder, Fahy and associates (1992) stated that 69% of patients, being the candidates for liver transplantation, had higher P(A-a)O2 (15).

In 1998, Behera et al found hypoxemia with the increased P(A-a)O2 in 26.7% of patients with liver cirrhosis. Better findings were manifested in patients with extrahepatic obstruction of portal vein (16).

In Fallon’ cohort of 207 consecutive liver transplant candidates who underwent arterial blood gas screening, 66% had P(A-a)O2 higher than 2 kPa (17).

In our series, 30 (42.8%) patients had P(A-a)O2 over 2 kPa. The increased P(A-a)O2 (5.73 kPa ± 2.65), particularly in the sitting position, was recorded in all patients with orthodeoxia, which indicates the IPVD.

Frequently, the hyperventilation of patients with liver cirrhosis may increase P(A-a)O2 values even in the case of normoxemia. Therefore, P(A-a)O2 is sensitive parameter of pulmonary gas exchange disorder. High diagnostic significance of these tests has been corroborated by findings of the unchanged basal partial oxygen pressure in the presence of subclinical IPVD, in spite of the increase of P(A-a)O2 (18).

Subclinical IPVD, as specific entity, present the transitory phase in the development of hepatopulmonary syndrome (HPS). In spite of IPVD and the increased P(A-a)O2, the partial arterial oxygen pressure may stay unchanged for a long period of time. This is caused by alveolar hyperventilation, hyperdynamic circulation, and an increase of cardiac output characteristic for cirrhotic (19,20).

Subclinical lung vasculature vasodilatation, with concomitant normoxemia may be found in the early phases of liver cirrhosis. With the progression of pulmonary changes, the hypoxemia becomes increasingly present. During the course of the disease, the impairment of oxygenation may be intensified even without the aggravation of liver function (21).

In our series, all four patients with subclinical IPVD were normoxemic despite increased P(A-a)O2, ranging from 2.1 to 2.37 kPa.

Among the patients with restrictive ventilatory disorders caused by ascites and without orthodeoxia, the mean value of P(A-a)O2 was 2.77 ± 1.12 kPa in the supine position while it was 1.80 ± 1.04 kPa in the sitting position.

Patients with abundant ascites, in standing position, usually have normal results of respiratory gasses of arterial blood, while partial insufficiency of respiration is manifested in recumbent position. Early closing of the airways makes the large areas in lower lung regions not to participate in ventilation while having maintained perfusion, and, accordingly, the ventilation-perfusion ratio is substantially worse. Perfusion of non-ventilated regions causes the situation that a large quantity of blood flows through lungs without being oxygenated (22).

Chang and associates (1997) published the results of their study where the effect of ascites to pulmonary function was monitored in two groups of patients, by comparison of therapeutically effects of paracentesis and diuretics. In distinction from patients treated by paracentesis, the patients administering diuretic therapy manifested significant improvement of gas exchange, along with PaO2 increase and large reduction of P(A-a)O2. The improvement of oxygenation following the diuretics suggests that, other than mechanical effect of ascites, the interstitial pulmonary edema and fluid retention contribute additionally to more difficult gas exchange (23).

Studies using 100% oxygen are also commonly used in patients with documented or suspected IPVD. On the basis of response to exposure to 100% oxygen, two types of vascular abnormalities in patients with hepatocellular insufficiency have been described. Type-1 is characterized by diffuse vascular dilatation at precapillary level, while, type-2 is defined by true anatomic pulmonary arterio-venous shunting. The application of 100% oxygen leads to significant increase of partial oxygen pressure in the type-1, while the effect is minimal in the type-2 (7).

The incomplete response with partial correction of hypoxemia was obtained in some patients following the inspiration of 100% O2. The impairment was recognized as the result of IPVD, what also contributed to shunt fraction and it was designated as diffusion-perfusion defect or alveolo-capillary oxygen disequilibrium (24,25).

In 1991, Hourani and associates described that, out of 116 patients with liver cirrhosis, 60 (52%) cases manifested reduced diffusion capacity. The increased capillary plasmatic volume and alveolar capillary dilatation give rise to the increase of diffusion distance, representing the basic mechanism of the impaired carbon monoxide and oxygen transfer in liver diseases. The reduction of diffusion capacity in regularly oxygenated cases may be also explained by IPVD, and subclinical intrapulmonary arterio-venous shunts, respectively. It was significant that 40% patients in this study, who manifested diffusion impairment, were not found to have the increase of P(A-a)O2. The authors consider that TL,CO may be more sensitive indicator of minor IPVD than the increase of P(A-a)O2 (4).

Krowka and Cortese, reported, in 1994, that in isolated reduction of TL,CO commencement together with the IPVD, other pathogenetic mechanisms were taking part, such as: diffuse interstitium pulmonary diseases, causing no restrictive disorders in the early phase, flow through non-ventilated alveoli, ventilatory-perfusion imbalance and/or other pulmonary vascular conditions (7).

In our study, lower transfer factor and normal P(A-a)O2 were noted in 17 (24%) patients. Higher P(A-a)O2 and normal transfer factor were found in 11(16%) patients, while the increased P(A-a)O2 and decreased transfer factor were recorded in 14 (20%) patients (cases with IPVD). There was no significant difference in comparison of these two groups, suggesting that the isolated reduction of TL,CO could not be explained only by IPVD.

Orthodeoxia and higher P(A-a)O2 are sensitive functional parameter in diagnostic IPVD, which represent, the major pathogenic mechanism in the development of severe respiratory disorders in liver cirrhosis.

1. Edell ES, Cortese DA, Krowka MJ, Rehder K. Severe hypoxemia and liver disease. Am Rev Respir Dis 1989; 140:1631–5.

2. Andrivet P, Cadranel J, Housset B, Herigault R, Harf A, Adnot S. Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of mdomethacin. Chest 1993; 103:500 –7.

3. Robert V, Chabot F, Vial B, et al. . Hepatopulmonary syndrome physiopathology of impaired gas exchange. Rev Mai Respir 1999; 16:769 –79.

4. Hourani JM, Bellamy PE, Tashkin DP, Batra P, Simmons MS. Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. Am J Med 1991; 90:693 – 700.

5. Robin ED, Laman D, Horn BR, Theodore J. Platypnea related to ortodeoxia caused by true vascular lung shunts. N Engl J Med 1976; 294:941 –3.

6. Rodriguez-Roisin R. The hepatopulmonary syndrome: new name, old complexities.Thorax 1992; 47:897– 902.

7. Krowka MJ, Cortese DA. Hepatopulmonary syndrome: Current concepts in diagnostic and therapeutic considerations. Chest 1994; 105:1528 –37.

8. Rodriguez-Roisin R. The hepatopulmonary syndrome: new name, old complexities. Thorax 1992; 47:897 – 902.

9. Sorbini CA, Grassi V, Solinas E, Muiesan G. Arterial oxygen tension in relation to age in healthy subjects. Respiration 1968; 25:3 – 13.

10. Rebic P. Merenje odnosa ventilacije i perfuzije u plucima. U: Sekulic S (urednik) Plućne bolesti. Elit Medica. Beograd 2000:79 – 81.

11. Cotes JE: Standardisation of the measurement of transfer factor (diffusing capacity).The European Respiratory Journal 1993; 6:5 – 40.

12. Quanjer PH. Lung volumes and forced ventilatory flows. The European Respiratory Journal 1993; 6:5- 40.

13. Bashour A, Cochran P. Alveolar-arterial oxygen tension gradients in cirrhosis of the liver. Further evidence of existing pulmonary arteriovenous shunting. Am Heart J 1966; 71:734 – 40.

14. Naeije R, Melot C, Hallemans R, Mols P, Lejune P. Pulmonary hemodynamics in liver cirrhosis. Seminars in Respiratory Medicine 1985; 7:164 –70.

15. Fahy JV, Kerr KM, Lake JR, Gold WM. Pulmonary function before and after liver transplantation (abstract). Am Rev Respir Dis 1992; 143:A303.

16. Behera D, Singh M, Chawla Y, Dilawari JB. Pulmonary function abnormality in patients with portal hypertension with or without chronic liver disease. Indian J Chest Dis Allied Sci 1998; 40:33 –9.

17. Fallon MB, Abrams GA. Pulmonary dysfunction in chronic liver disease. Hepatology 2000; 32:859 –65.

18. Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Int Med 1995; 22:521 – 9.

19. Agusti AG, Roca J, Rodriguez-Roisin R. Mechanisms of gas exchange impairment in patients with liver cirrhosis. Clin Chest Med 1996; 7:49 – 66.

20. Miki K, Shinohara T, Ogushi F, et al. Hepatopulmonary syndrome-discussion of cardiopulmonary parameters. Med Invest 2000; 47:164 – 9.

21. Mimidis KP, Karatza C, Spiropoulos KV, et al. Prevalence of intrapulmonary vascular dilatations in normoxemic patients with early liver cirrhosis. Scand J Gastroentrol 1998; 33: 988 –92.

22. Gupta D, Lalrothuama S, Agrawal PN, et al. Pulmonary function changes after large volumen paracentesis.Trop Gastroentrol 2000; 21:68-70.

23. Chang SC, Chang HI, Juh F, Shiao GM, Wang SS, Lee SD. Therapeutic effects of diuretic and paracentesis on lung function in patients with non-alcoholic cirrhosis and tense ascites. J Hepatol 1997; 26:833-8.

24. Davis HH, Schwartz DJ, Lefrak SS, Susam N, Schainker BA. Alveolar-capillary oxygen disequilibrium in hepatic cirrhosis. Chest 1978; 73:507 –11.

SAŽETAK

Uočeno je da alveolo-arterijski gradijent ≥ 2 kPa sa ili bez hipoksemije ukazuje na intrapulmonarnu vaskularnu dilataciju. Za procenu značaja alveolo-arterijskog gradijenta kod pacijenata sa cirozom jetre analizirali smo 70 pacijenata. Pritisak kiseonika u alveolarnom vazduhu izračunat je na osnovu izmerenog atmosferskog pritiska i ugljen-dioksida u izdahnutom vazduhu, dok je vrednost Pa, 02 bila izmerena direktno u arterijskoj krvi. Ortodeoksija je potvrđena kod 10 (14,3%) hipoksemičnih i 4 (5,7%) normoksemiča pacijenta. U našoj studiji 30 (42.8%) pacijenata imali su alveolo-arterijski gradijent preko 2 kPa. Svi pacijenti sa ortodeoksijom imali su povišene vrednosti alveolo-arterijskog gradijenta, čija je srednja vrednost u ležećem položaju bila 4.03 ± 2.36 kPa, dok je u sedećem ta vrednost iznosila 5.73 ± 2.65 kPa. Kod pacijenata sa restriktivnim ventilatornim poremećajima izazvanim ascitesom, koji nisu imali ortodeoksiju, srednja vrednost P(A-a) 02 u ležećem položaju iznosila je 2.77 ± 1.12 kPa, dok je u sedećem iznosila 1.80 ± 1.04 kPa. Rezultati ukazuju da su ortodeoksija i povećan alveolo-arterijski gradijent senzitivni funkcionalni parametri u diagnostici intrapulmonalne vaskularne dilatacije koja predstavlja glavni patogenetski mehanizam u nastanku teških respiratornih poremećaja u cirozi jetre.

UVOD

Kod pacijenata sa cirozom jetre i izraženom hipoksemijom, IPVD i desno-levi šantovi, predstavljaju glavni patogenetski mehanizam u nastanku teških respiratornih poremećaja (1-3).

Najčešći plućni simptom jeste dispnea koja se javlja kod skoro 40% pacijenata sa IPVD. Preko 70% pacijenata predviđenih za transplantaciju jetre žali se na dispneu (4). Druga tipična manifestacija IPVD u cirozi je platipnea, koja označava dispneu izraženiju u stojećem ili sedećem u odnosu na ležeći položaj (5). Ortodeoksija je još jedan klinički pokazatelj IPVD, koja predstavlja pad parcijalnog pritiska kiseonika za više od 10%, kad pacijent pređe iz ležećeg u sedeći položaj.

Hipoksemija sa parcijalnim pritiskom kiseonika (Pa,02) manjim od 8 kPa u odsustvu drugih kardio-respiratornih bolesti ukazuje na postojanje IPVD (6,7).

Određivanje P(A-a)02 najjednostavniji je metod za procenjivanja ukupnog odnosa ventilacije i perfuzije u plućima. Uočeno je da P(A-a)02 ≥ 2 kPa sa ili bez hipoksemije ukazuje na postojanje IPVD (8).

PACIJENTI I METODE

U prospektivnoj studiji analizirali smo 70 pacijenata sa cirozom jetre, koji su lečeni na Institutu za digestivne bolesti i Institutu za plućne bolesti Kliničkog centra Srbije. Gasne analize rađene su aparatom Blood Gas Manager IL 1312, dok su predviđene vrednosti za parcijalni pritisak kiseonika u krvi izračunate pomoću Sorbinijeve jednačine (Pa,02 =103,5 -0,42 x godine) (9). Anallizu gasova u arterijskoj krvi vršili smo u ležećem i sedećem položaju, pri udisanju sobnog vazduhu i nakon 15 minuta udisanja hiperoksične smese, direktnom metodom, koja podrazumeva uzimanje aretrijskog uzorka krvi hepariniziranim špricem.

Spirometrijska merenja u našoj studiji su bila izvedena pomoću otvorenog spirometrijskog sistema sa pneumotahografijom (Pneumoscreen II spirometar) za određivanja: vitalnog kapaciteta (VK), forsiranog vitalnog kapaciteta (FVK) i forsiranog ekspirijumski volumen u prvoj sekundi (FEVı).

Telesnom pletizmografija (Bodyscreen II) merili smo: totalni plućni kapacitet (TPK), toraksni gasni volumen (TGV), rezidualni volumen (RV) i otpor strujanju vazduha u disajnim putevima putevima (RaW).

Alveolo-arterijski gredijent pritiska kiseonika (P(A-a)02 = PA02 – Pa,02) izračunavali smo na način koji se uobičajeno koristi u praksi. Pritisak kiseonika u alveolskom vazduhu izračunat je na osnovu izmerenog atmosferskog pritiska i pritiska ugljen-dioksida u izdahnutom vazduhu (PA02 = Fi02 x (Pb –PaH2O) – PA,co2 (Fio2 + 1 – FiO2/ Ra) (FiO2 – frakciona inspiratorna koncentracija kiseonika; Ra – respiratorni količnik), dok je Pa,02 meren direktno u arterijskoj krvi (10).

S obzirom na promenjivost respiracijskih gasova arterijske krvi kod obolelih od ciroze jetre pri promeni položaja tela, promene P(A-a)02 pri prelasku iz ležećeg u sedeći položaj, za najmanje 0.66 kPa, predstavljaju signifikantan znak IPVD (11).

Plućnim funkcionalnim testovima određivali smo transfer faktora (TL,CO) i koeficijent transfera (KCO = TL,CO podeljen sa efektivnim alveolarnim volumenom), kao pokazatelje stanja alveolo-kapilarne difuzije Parametre difuzije merili smo ugljen-monoksidom metodom jednog udaha, sa Transferscreen aparatom. Donju granicu normale za transfer faktora dterminisali smo matematičkim putem tako što smo od predviđenih vrednosti za TL,CO oduzeli 1.64 SD (SD za muškarce 1.42, SD za žene 1.17). Predviđene vrednosti TL,CO računali smo na osnovu usvojenih standarda (za muškarace predviđeni TL,CO = 11.11 x visina u metrima - 0.066 x godine – 6.03; za žene, predviđeni TL,CO = 8.18 x visina u metrima – 0.049 x godine – 2.74) (11).

Restriktivne ventilatorne poremećaje određivani su na osnovu spirometrijskih parametara: VK, indeksa 100 x FEVı / VK (Tiffeneau) i UPK. Donja granica normale determinisana je kao predviđena vrednost – 1.64 SD (za muškarace SD za FVK = 0.61, SD za UPK =0.70, i za Tiffeneau SD =7.17; za žene SD za FVK = 0.43, SD za UPK = 0.60, i za Tiffeneau SD = 6.51) (12).

Statističke analize izvedene su korišćenjem x2 i t-testa.

REZULTATI

Ortodeoksija je potvrđena kod 10 hipoksemičnih (14.3%) i kod 4 (5.7%) normoksemična pacijenata. U uslovima udisanja sobnog vazduhom srednja vrednost Pa,02 u ležećem položaju iznosila je 9.40 ± 1.74 kPa, dok je u sedećem položaju prosečna vrednost Pa02 bila 7.41 ± 1.81 kPa. U uslovima udisanja 100% kiseonika srednja vrednost Pa02 u ležećem položaju iznosila je 35.49 ± 17.95 kPa, dok je u sedećem položaju prosečna vrednost Pa02 bila 21.07 ± 14.41 kPa (Tabela 1).

U našoj studiji 30 (42.8%) pacijenata su imali P(A-a)02 preko 2 kPa. Svi pacijenti sa ortodeoksijom imali su povećan P(A-a)02, čija je prosečna vrednosti u ležećem položaju iznosila 4.03 ± 2.36 kPa, dok je u sedećem položaju bila 5.73 ± 2.65 kPa. Pacijenti sa ortodeoksijom i povećanim P(A-a)02 imali su IPVD. Pacijenti sa ortodeoksijom i normoksemijom takođe su imali povećanu vrednosti P(A-a)02, koja se kretala od 2.1 do 2.37 kPa što prezentuje subkliničku IPVD.

Dijagnoza ascitesa potvrđena je kod 43 (61%) pacijenata. Restriktivni ventilatorni poremećaji i povećan P(A-a)02 dijagnostikovani su kod 16 (37.2%) pacijenata sa ascitesom. Srednja vrednost parametara restrikcije iznosila je: VK 73.0 ± 14.4, UPK 83.7 ± 13.5, a Tiffeneau indeks 78.3 ± 3.37.

Kod pacijenta sa restriktivnim ventilatornim poremećajem, bez ortodeoksije, srednja vrednost P(A-a)02 u ležećem položaju iznosila je 2.77 ± 1.12 kPa, a u sedećem 1.80 ±1.04 kPa. Upoređujući pacijente sa i bez ortodeoksije, uspostvaljena je statistički značajna razlika u vrednostima P(A-a)02 (p = 0.001, t-test), posebno u sedećem položaju (Tabela 2).

Snižen transfer faktor (TL,CO) registrovan je kod 38 (54%) pacijenata, dok je snižen koeficijent transfera (KCO) zabeležen kod 46 (66%) pacijenata. Srednja vrednost transfer faktora bila je 6.24 (65.72%). Kod svih pacijenata sa IPVD i subkliničkom IPVD manifestovale su se snižene vrednosti transfer faktora i koeficijenta transfera.

Povećan P(A-a)02 i normalan transfer faktor imalo je 11 (16%) (pacijenati sa restriktivnim disajnim poremećajima), dok je povećan P(A-a)02 i snižen transfer faktor imalo 14 (20%)) pacijenata (pacijenti sa IPVD). Snižen transfer faktor i normalan P(A-a)02 registrovan je kod 17 (24%) pacijenata. Nisu pronađene statistički signifikantne razlike između povećanih vrednosti P(A-a)02 i poremećaja difuzije (x2 - test, p =.62) (Tabela3).

DISKUSIJA

Bashour i Cochran, 1966. godine, ispitujući 26 pacijenata sa cirozom jetre, izmerili su srednju vrednost alveolo-arterijskog gradijenta 5.97 kPa (13).

U grupi pacijenata predviđenih za proto-kavalni šant, Naeije i saradnici (1985) nalaze srednju vrednost P(A-a)02 od 4.85 kPa (14).

Hourani i saradnici, 1991. godine, saopštavaju povećan gradijent pritiska kiseonika u 45% pacijenata predviđenih za transplantaciju jetre, sa srednjom vrednosti P(A-a)02 4.89 kPa (4).

Ističući značaj ovog funkcionog poremećaja, Fahy i saradnici (1992), navode da je 69% pacijenata, predviđenih za transplantaciju jetre, imalo povećan P(A-a)02 (15).

Behera i saradnici, 1998. godine, nalaze hipoksemiju s povećanjem P(A-a)02 u 26.7% pacijenata sa cirozom jetre. Bolje rezultate imali su pacijenati sa ekstrahepatičnom opstrukcijom portne vene (16).

U Falonovoj studiji od 207 kandidata predviđenih za transplantaciju jetre 66% su imali vrednost P(A-a)02 veću od 2 kPa (17).

U našoj studiji 30 (42.8%) pacijenata je imalo P(A-a)02 preko 2 kPa. Povećana vrednost P(A-a)02 (5.73 kPa ± 2.65), posebno u sedećem položaju, bila je zabeležena kod svih pacijenata sa ortodeoksijom, što ukazuje na IPVD.

Često hiperventilisanje pacijenata s cirozom jetre može da poveća vrednosti P(A-a)02 čak i u slučaju normoksemije. Zbog toga je, P(A-a)02 senzitivan parametar poremećaja gasne razmene u plućima. Veliki dijagnostički značaj ovih testova potvrđuje i nalaz neizmenjenog bazičnog parcijalnog pritiska kiseonika pri postojanju subkliničke IPVD nezavisno od povećanja P(A-a)02 (18).

Subklinička IPVD, kao poseban entitet, predstavlja tranzitornu fazu u razvoju hepatopulmonalnog sindroma (HPS). Uprkos IPVD i porastu P(A-a)02 parcijalni pritisak kiseonika u arterijskoj krvi može dugo vremena da ostane nepromenjen. Ovo je rezultat alveolne hiperventilacije, hiperdinamske cirkulacije i porasta minutnog volumena srca što je karakteristično za cirozu (19,20).

Subklinička vazodilatacija u plućima, praćena normoksemijom, može biti otkrivena u ranoj fazi ciroze jetre. Sa progresijom plućnih promena hipoksemija se sve više ispoljava. Tokom bolesti, oksigenacija može da se pogoršava i bez pogoršavanja funkcije jetre (21).

U našoj studiji, sva četiri pacijenta sa subkliničkom IPVD bili su normoksemični nezavisno od povećane vrednosti P(A-a)02 koja se kretala od 2.1 do 2.37 kPa.

Kod pacijenata sa ventilatornim restriktivnim poremećajima izazvanim ascitesom, koji nisu imali ortodeoksiju, srednja vrednost P(A-a)02 u ležećem položaju bila je 2.77 ± 1.12 kPa dok je u sedećem iznosila 1.80 ±1.04 kPa.

Pacijenti sa izraženim ascitesom u stojećem položaju obično imaju normalne vrednosti respiratornih gasova u arterijskoj krvi, dok se parcijalna insuficijencija respiracije manifestuje u ležećem položaju. Prerano zatvaranje disajnih puteva uslovljava da veliki delovi donjih plućnih regiona ne učestvuju u ventilisanju, dok u isto vreme imaju očuvanu perfuziju, tako da se bitno pogoršava ventilaciono-perfuzioni odnos. Perfuzija u neventilisanim delovima, uslovljava da znatna količina krvi prolazi kroz pluća a da se ne oksigeniše (22).

U studiji, Changa i saradnika (1997), ispitivan je efekat ascitesa na plućnu funkciju kod dve grupe pacijenata, upoređivanjem terapijskih efekata paracenteze i diuretika. Za razliku od pacijenata lečenih paracentezom, pacijenti koji su lečeni diuretskom terapijom pokazali su znatno poboljšanje gasne razmene uz povećanje Pa,02 i veliko smanjenje P(A-a)02. Poboljšanje oksidenacije upotrebom diuretika pokazuje da osim mehaničkog efekta ascitesa intersticijalni plućni edem i retencija tečnosti dodatno doprinose pogoršavanju gasne razmene (23).

Ispitivanja zasnovana na udisanju 100% kiseonika takođe često se koriste kod pacijenata sa dokazanom ili suspektnom IPVD. Na osnovu oksigenacionog odgovora nakon udisanja 100% kiseonika, opisana su dva tipa vaskularnih abnormalnosti kod pacijenata sa hepatocelularnom insuficijencijom. Tip-I karakteriše difuzna vaskularna dilatacija na prekapilarnom nivou, dok je Tip-2 definisan pravim anatomskim plućnim arterio-venskim šantovima. Primena 100% kiseonika dovodi do značajnog povećanja parcijalnog pritiska kiseonika kod Tipa-I, dok je efekat minimalan kod Tipa-2 (7).

Nakon udisanja 100% kiseonika, kod nekih pacijenata, postiže se nepotpuni oksigenacioni odgovor sa parcijalnom korekcijom hipoksemije. Poremećaj je shvaćen kao posledica IPVD, što takođe doprinosi povećanju šantne frakcije, a označava se terminom difuziono-perfuzioni defekt ili alveolo-kapilarni disekvilibrijum kiseonika (24, 25).