ON T H E R O L E OF MICROCIRCULATORY DISTURBANCES IN T H E PATHOGENESIS OF H Y A L I N E M E M B R A N E D I S E A S E IN NEWBORNS

M. Gardevski Key-words: microcirculation — hyaline membrane disease — pathogenesis — newborns

Pathogenesis of neonatal hyaline membrane disease (HMD) is not clarified yet. There exist numerous and rather contradictory concepts concerning the patho­genetic mechanism inducing hyaline-like material formation (2—4). The ini­tial enthusiasm to explain HMD pathogenesis with the lack or insufficient surfac-tant secretion dropped off bit by bit. Serious hesitations in this respect were caused by reports of some authors (1 , 10) about HMD in post-mature infants as well as by unsatisfactory results from substitution therapy with artificial surfactant (9, 11—13). That was why it was necessary to investigate also some other factors responsible for HMD development.

The purpose of the present work was to study the microcirculatory distur­bances in lungs from deceased HMD newborns and experimental animals in order to clarify the role of these disturbances in HMD pathogenesis.

Material and methods

Our study covered the lungs of 101 newborn infants died of HMD an d of 40 guinea pigs with experimentally induced HMD. Material from lungs was light and electron microscopically studied. Post-mortem material fixation for electron microscopy of newborn lungs was done according to the method of Bachofen et al. (7). Experimental animals were treated with single s. c. injection of 2 ре r cent paraquat solution. They were divided into two experimental series with diffe­rent dosis: 1 s t — with 20 mg/kg b. w. and 2 n d — with 30 mg/kg b. w. Animals were killed 24 and 48 hours later. Small pieces of pulmonary tissue were fixed in 10 per cent neutral formalin for light microscopic study and in 5 per cent glutaraldehyde for electron microscopic one. The materials were embedded in durcupan, contrasted with uranyl-acetate according to Reynolds' method and nvestigated under transmission electron microscope.

Results and discussion

Main alterations of lung microcirculatory bed in deceased newborns were presented as severe capillary congestion. Capillary loops in alveolar walls were dilatated and filled with erythrocytes. They protruded towards the alveolar lumen (fig. 1). Severe hyperemia with signs of sludging phenomena was present in the terminal branches of venous vessels, too. In contrast to them, arterioles looked purely congested or empty. We could establish in single capillary network seg­ments only plasma fluid and hemolyzed erythrocytes. These disturbances were more severely expressed in newborns died in the first and second day of life. Ca­pillary congestion intensity differed substantially in single cases. Although the process was diffuse it also showed a certain mosaicity: foci with various size took irregularily turns with those with slightlier or more severely expressed capillary dilatation. A more demonstratively expressed stasis was found out in subpleu-ral regions of the lungs and in basally located segments. Newborns of smaller

On the role of.

gestation age and these died in the early hours after birth demonstrated more severe microcirculatory disorders.

We established in 29.06 per cent of autopsies with newborn HMD erythro­cyte microthrombi but in 17.09 per cent fibrin ones in the terminal pulmonary

Fig. 1. Severe hyperemia of lung capillaries in a newborn died of HMD. Stain H . E . Maen

trunc branches. Interesting data was obtained when compared postnatal age of HMD newborns died with pulmonary microthrombi presence. Fibrin microthrom­bi were established in 24.05 per cent amids deceased in the first day after birth while in the next days they reduced down to 2.63 per cent. Diapedesis haemor­rhages in the lungs were observed in 83.13 per cent of HMD newborns, too.

The electron microscopic investigation of lung specimens from deceased new­borns revealed strongly dilatated capillary loops filled with erythrocytes and plasma fluid. Epithelial processes of pneumocytes, type 1 which covered ca­

pillaries towards the alveolar lumen were irregularly thickened. In single seg­ments they were vacuolizated and thickened (fig. 2) but in other areas fine and homogenous. Together with dilatated capillaries loops with unsteadily ondulated walls emerging into alveolar lumen could be seen. Here and there several capil­laries succeeded each other without epithelial cells between them.

f We established a notably interesting phenomenon rather repeated in our material that there was a segmental thickening and looseness of basal capillary membranes. Capillary membrane was 2—3 times more thickened as compared with the rest part in single segments. It had a low electron density and deleted structure. Epithelial cover on these regions looked more dense, thinned and on­dulated.

Similar changes were found out when lungs of experimental animals were histologically examined. There was a picture of a severe stasis. Dilatated capilla­ries were filled with plasma. Basal capillary membrane possessed segmental thickenings and lower electron density in these regions. Both epithelial and endo­thelial coverings were ondulated, strcfngly flattened and with small quantity of

М. Gardevski

pinocytotic vesicles in the places of focal basal membrane thickening. In the close proximity of these lesions, in arteriolan lumen there were electron-dense masses with fine reticular structure and irregular form considered by us parts

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Fig . 2. Vacuolization and pinocytotic vesicles in the cytoplasmic evaginations of pneumocytes type 1 in a newborn died of HMD. Stain H . E . , Magn.x20 000

of hyaline-like material. Hyaline-like material formation in the lungs of deceased newborns and of experimental animals demonstrated an expressed phasic charac­ter. Init ial ly, it consisted in development of intraalveolar oedema followed by precipitation and HM formation and ended with HM fragmentation and resorp-tio n.

Our observations on the microcirculatory disorders allow us to presume that they play an essential role in HMD pathogenesis. We consider the alterations mentioned an expression of an increased vascular permeability. Other investi­gators (6) report an increased capillary permeability, too. On the basis of mor­phological study of the lungs of 11 newborns and 28 adults with HMD E . Nakov and M. Silyanov (5) accept that microcirculatory disorders with an increased

On the role of.. 27

capillary permeability are the main factor in HMD pathogenesis. They assert rather emphatically that congenital lack of surfactant does not cause HMD. Ac­cording to them, HMD is due to unfavourable conditions related to coagulopa­thies and intoxications of the mother or pulmonary hypertension, hypoxemia and acidosis of the fetus. R . D. Bland supposes that any factors inducing pulmonary oedema can be pathogenetically related with HMD development (9).

We establish HMD in 11 cases (6.23 per cent) of the full-term and mature newborns with a post-mortem examination performed. On the other hand, HMD is found out of 11 infants born up to the 28 t h gestational week with a severe pul­monary immaturity in one case only. A l l that allows us to suppose that imma­ture lung presents only an unfavourable predisposition on the basis of wich diffe­rent stress factors easily lead to shock condition with severe microcirculatory disturbances. Most infants have preliminary lesions as shown in our study. Hypo­xemia is the most frequent one — in 64.36 per cent of the cases. The increased capillary permeability induces an intraalveolary oedema followed by precipita­tion and hyaline-like material formation. Therefore, microcirculatory disorders are the initial and main factor in the pathogenesis of pulmonary alterations in newborn HMD.

Our presumption concerning the essential role of capillary congestion and increased vascular permeability has an important theoretical and great practi­cal significance. From this follows that HMD prophylaxis must be directed to­ward reduction of the number of premature births, on the one hand, and towards prevention or timely treatment of any unfavourable factors and pathological conditions damaging the fetus and the newborn before and during delivery, on the other hand. Besides, the main attention should be paid to prevention of ano-xemic and hypoxemic fetal conditions.

R E F E R E N C E S

1. А р н а у д о в а P . , В . М а к а в е е в а , А. К а ч у л о в . Педиатрия (С.) 1981, № 1, 61—66. — 2. Г а н ч е в, С. Перинатална детска смъртност. С , Мед. и ф и з к . 1981. — 3. Е л и з а р о в а , И. П., Н. И. Б у б н о в а , Ю. А. Т и т о в , И. В, Ф е о д о р о в а . Акуш. и гинекол. (М ) , 1982, № 9, 26—30. — 4. И в а н о в с к а я . Т. Е., А. В. Ц и н з е р л и н г. Патологическая анатомия болезней детского возраста, М., Медицина, 1981. — 5. Н а к о в, Е. , М. С и л я н о в . В : Н а ц . конф. патол. , V I I I -Варна, 1981г . Тезиси, 7 9 — 8 1 . — 6. П о л у я х т о в а, М. В . Вопр. охр. матер, и, детства, 1980, № 6, 22—27. — 7. В а с h о f е n, М., Е. R . W f t i b e l , В . R о о s. Amer. Rev. Respir. Dis., I l l , 1975, 247-256. — 8. B l a n d , R . D . Acta Paediatr. Scand., 72, 1983, 305, 92—99. — 9. M i i n е г, А. D. , R . V у a s, I . E . H о p k i n . Arch. Dis. Child., 58, 1983, No 6, 458—460. - 10. P 1 a u с h е, W. C , F . S e b a s t i a n , R . L e-O i l i e r . Amer. J . Obshtr. Gynecol., 144, 1932, No 2, 157-159. — 11. R o b e r t s o n , B . Clin. Physiol., 3, 1983, No 2, 97—110. - 1 2 . S m i t h , L . J . , N . B . K a p l a n , J • B r o d y . Amer. Reo. Respir. Dis., 122, 1980, 947—957. — 13. W a l t e r s , D . V. Brit. Med. J . , 289, 1984, No 6449, 855—856.

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О Р О Л И М И К Р О Ц И Р К У Л Я Т О Р Н Ы Х Н А Р У Ш Е Н И Й В П А Т О Г Е Н Е З Е Г И А Л И Н О - М Е М Б Р А Н Н О Й Б О Л Е З Н И У Н О В О Р О Ж Д Е Н Н Ы Х

М . Гардевски

Р Е З Ю М Е

При помощи светового и электронного микроскопа исследованы легкие 101 умершего новорожденного ребенка с гиалино-мембранной болезнью и 40 морских свинок с экспери­ментально вызванной гиалино-мембранной болезнью. В первые часы заболевания устанав­ливаются острые нарушения микроциркуляции, как капиллярная конгестия, очаговые утол­щения и разрыхление капиллярной базальной мембраны И множество пиноцитозных ве­зикул в эндотелиалькых клетках. Эти изменения оцениваются как выражение повышенного капиллярного пермеабилитета, вызванного предшествующей фетальной аноксией. При : об­разовании гиалинового материала наблюдается выраженная стадийность, которая начина­ется интраальвеолярным отеком, вслед за которым наблюдается преципитация отечной жид­кости; процесс закончивается фрагментацией и резорбцией гиалинового материала.

Результаты исследования показывают, что легочные микроциркуляторные нарушения являются начальным и решающим фактором в патогенезе гиалино-мембранной болезни у новорожденных.

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