186 J. Physiol. (I946) I05, I86-I90 6I2.2I5.9 THE ABSORPTION OF FLUIDS FROM THE LUNGS BY F. C. COURTICE AND P. J. PHIPPS From the Experimental Station, Porton and the Laboratory of Physiology, Oxford (Received 16 January 1946) When pulmonary oedema is produced by irritant gases such as phosgene, the oedema fluid is similar to the blood plasma in its protein composition (Cameron & Courtice, 1946). As a result, the removal of this fluid is by way of the lymphatics since the effective osmotic pressure of the plasma proteins is abolished. These authors have shown that, in such cases, there is a considerable increase in the lymph flow from the lungs via the right lymph duct during the acute phase of oedema formation. In animals that survive exposure to phosgene, the oedema fluid is but slowly removed over a period of several days after the cessation of the acute phase. This suggests that, after the acute phase, the lymphatic removal of this fluid is very slow. The present series of experiments was performed to find the rate of removal from the lungs of water, of 0 9% NaCl solution and of serum after they had been introduced into the lungs by way of the trachea. METHODS Dogs and rabbits were used. Dogs were anaesthetized with 'Nembutal', the right lymph duct was cannulated and lymph collected. Water, 0 9% NaCl solution or dog serum was then introduced into the lungs via the trachea and the changes in lymph flow measured. The dogs were then killed and the lung/heart weight ratio determined to estimate the amount of fluid remaining in the lungs. Rabbits were anaesthetized with 'Nembutal', and then water, 0 9% NaCl solution or rabbit serum was introduced into the trachea. The rabbits were then allowed to recover from the anaesthetic and groups were killed at 1, 4, 24, 48 and 72 hr. afterwards. The lung/heart weight ratios were determined and the amount of fluid remaining in the lungs calculated. In another series of rabbits, 15 c.c. serum were introduced into the trachea of two groups. Special tracheal cannulae incorporating inspiratory and expiratory valves of minimal resistance and dead space were inserted. In one group a pressure of 4 or 6 cm. water was placed on the expiratory side while in the other group no pressure was used. These experiments were designed to show whether or not breathing against a pressure would increase the absorption of serum from the lungs. RESULTS Experiments with dogs. Table 1 shows the effects of the introduction of water, of 0 9% NaCl solution and of serum into the lungs of dogs. In each case the fluid was introduced over a period of about 2 hr. From 4 to 5 hr. after the
FLUID ABSORPTION FROM THE LUNGS 187 beginning of the injections, the dogs were killed and the lungs examined. Assuming a normal lung/heart weight ratio of 1F3, the excess fluid in the lungs was calculated. Lymph was collected from the right lymph duct throughout, and the excess over normal determined. TABLE 1. Weight (kg.) 14x5 18-6 14x1 18-0 The absorption of fluids from the lungs of normal dogs anaesthetized with 'Nembutal' Excess lymph flow over Duration of normal experiment (hr.) 4 5 10 15 Fluid introduced Water 350 0.9% NaCl 260 Serum 162 Serum 55 Fluid absorbed 283 156 31-3 The results indicate that water is rapidly absorbed, and 0 9 % NaCl solution relatively rapidly absorbed, directly into the blood capiflaries, since the increase in lymph flow is small. Serum is but slowly absorbed. 100 4. 5 4 80 40 0 10 20 30. 40 50 60 70 Hours Fig. 1. The absorption of water, of 0 9% NaCl solution and of serum from the lungs of rabbits. 10 c.c. were introduced into each rabbit by way of the trachea. Each point represents the average of five experiments. Experiments with rabbits. The rabbits were treated in groups of 5. 10 c.c. of fluid were introduced along the trachea into the lungs of each rabbit. Immediately after killing, the lungs were examined and the lung/heart weight ratio determined. From this ratio the excess fluid in the lungs was estimated, assuming a normal ratio of 1-8. (The mean lung/heart weight ratio of ten normal rabbits was 1.76 + 0.03, S.E. of mean.) The results are plotted in Fig. 1 as the percentage of fluid absorbed. This shows that, with water, nearly 80% was
188 F. C. COURTICE AND P. J. PHIPPS absorbed within 1 hr. and the remainder was then more slowly absorbed. With saline, 23% was absorbed in 1 hr., 36% in 4 hr. and 72% in 24 hr. Serum, on the other hand, was much more slowly absorbed. In two other groups of rabbits, with 5 in each group, 30 c.c. of water or of 0-9% NaCl solution were introduced into the trachea of each rabbit. Of this, 15 c.c. were introduced first and then, 15 min. later, the final 15 c.c. The animals were killed 30 min. after the beginning of the experiment. From the lung/heart weight ratios it was shown that, on an average, 91F6 % of the water was absorbed and 34-5 % of the saline. In a further two groups of rabbits, 20 c.c. of water or of 0 9% NaCl solution were introduced into the lungs of each rabbit and the animals were killed 1 hr. later. At this time 92% of the water and 35-5 % of the saline had been absorbed. In another series of experiments, serum was introduced into the trachea of each of twenty rabbits, two groups of ten. The average weight of the rabbits in each group was 2x8 kg. All the rabbits in this series were kept under 'Nembutal' for 6 hr. when they were killed and the lung/heart weight ratios determined. The experiments were done in pairs, one control expired to atmospheric air and the other expired against pressure. 15 c.c. serum, from the same batch of rabbit serum, were injected into the lungs of each. The average results showed that, in the ten controls, 42 1 % of the serum was absorbed while, in the ten breathing against pressure, 39-4 % of the serum was absorbed. It thus appears that resistance to expiration, causing a more forceful expiratory effort, did not increase the absorption of the serum. The lungs of the rabbits in most of these experiments were examined histologically. The introduction of as much as 30 c.c. of water or of 0-9 % NaCl solution, or of 15 c.c. of serum caused, apart from the presence of fluid in the alveoli, no abnormal changes in the respiratory mucous membrane or lung tissue. The rabbits that were allowed to recover and live for 24-72 hr. behaved normally after the initially increased respiration rate returned to normal. After the introduction of water, this recovery was very rapid. DISCUSSION These experiments show how rapidly water and 0.9 % NaCl solution are absorbed from the normal lungs directly into the blood stream. Very little appears to be absorbed by the lymphatics. Winternitz (1920), while working on the question of pulmonary oedema due to irritant gases, also showed that physiological saline is rapidly taken up by the lungs. The experiments with water are of interest when considering the absorption from the lungs in cases of drowning in fresh water. The problem of the absorption of lung oedema fluid during the recovery phase of phosgene poisoning, however, is not one of absorption of water or of
FLUID ABSORPTION FROM THE LUNGS 189 0 9 NaCl solution from the lungs. Cameron & Courtice have shown that the oedema fluid is rich in protein and is very similar to plasma. Thus, the experiments in which serum was inserted into the lungs give a much better idea of the rate of removal of oedema fluid after the first. acute phase of oedema production is over. It has been seen that serum is very slowly absorbed from the lungs of both dogs and rabbits, and in rabbits it takes about 4 days to remove all the serum introduced. This corresponds to the findings in phosgene poisoning, for, although the animal begins to recover 24-36 hr. after exposure to phosgene, the lungs remain oedematous for about 5 days. The fact that the lymph does absorb serum at all, even though slowly, has been shown by the introduction of Evans Blue dye into the lungs in some of these experiments. Some of the dye is soon absorbed by the lymphatics and appears in the right lymph duct whereas the plasma contains but little. This dye combines with albumin (Rawson, 1943) and is probably absorbed into the lymphatics combined with protein. It seems, therefore, that the proteins of the serum introduced into the lungs are absorbed by the lymphatics, but at a slow rate. The solution of the problem of speeding up removal of oedema fluid from the lungs depends on increasing the lymph flow. As the lymph is driven along the lymph channels mainly by mechanical means, it was hoped that increasing the force of expiration, by introducing a positive pressure on the expiratory side of the tracheal cannula, would increase the lymph flow and so hasten the absorption of oedema fluid. The experiments with rabbits in which serum was introduced into the lungs show, however, that breathing against pressure does not increase absorption of the serum. SUMMARY 1. Water, 0-9 NaCl solution or serum were introduced through the trachea into the lungs of normal dogs and rabbits. The rate of disappearance of these fluids was then estimated. 2. In dogs, the lymph flow from the right lymph duct was measured. Both water and the saline solution passed rapidly from the lungs directly into the blood stream with very little increase in the lymph flow. Serum, on the other hand, was slowly absorbed, probably only by the lymphatics. 3. Similar results were obtained during the absorption of water, of 09 % NaCl solution and of serum from the lungs of rabbits. Whereas water was extremely rapidly absorbed, serum persisted in the lungs for about 4 days. This agrees with the slow absorption of oedema fluid from the lungs during the recovery phase of phosgene poisoning. 4. The introduction of a resistance to expiration of 4 or 6 cm. water pressure did not increase the absorption of serum introduced into the lungs of rabbits.
190 F. C. COURTICE AND P. J. PHIPPS Our acknowledgements are due to the Director-General, Scientific Research and Development, Ministry of Supply, for permission to publish this investigation. We are also indebted to Prof. G. R. Cameron for the histological examination of the lungs. REFERENCES Cameron, G. R. & Courtice, F. C. (1946). J. Physiol. 105, 175. Rawson, R. A. (1943). Amer. J. Physiol. 138, 708. Winternitz, M. C. (1920). Pathology of War Gas Poisoning. Yale University Press.