Lead poisoning and lead absorption

by Sir Thomas Morison Legge; Kenneth Weldon Goadby

—The final method of absorption of lead particles or lead solution into the animal body remains to be considered. Experimental phagocytosis of lead particles—as, indeed, of any minute particles of substance—suspended in an isotonic solution, may be observed directly under the microscope. Lead particles show no exception to the rule, and white blood-corpuscles in a hanging-drop preparation, made by suspending them in an isotonic salt solution and serum, may be watched englobing particles of lead, and by appropriate means the ingested lead may be afterwards demonstrated. In such an experiment, much of the lead absorbed by the individual corpuscles rapidly loses its property of giving a black precipitate with sulphuretted hydrogen, and has apparently become converted into an organic compound, peptonate or albuminate.

In the section devoted to the Chemistry of Lead, it has been noted that the colloidal solutions of lead are not precipitated by sulphuretted hydrogen, and that albuminates and peptonates of lead are presumably of colloidal form. There seems evidence, therefore, that the direct absorption of lead takes place by means of the phagocytes of the body, and that in them it becomes converted into a colloidal form, in which it is probably eliminated through the kidney and intestine, mainly the latter.

Further evidence of the englobement of lead particles by amœbic cells may be gained if sections of the intestines of experimental animals are examined; in the lymphoid glands particles of lead may be seen situated in the interior of the walls, and even in the cells. It does not by any means follow that these particles of lead sulphide present in the cells have been formed in situ; more probably the lead has been converted into a sulphide in the intestinal lumen itself, and subsequently taken up by the amœbic cells situated in its periphery.

Another solution is possible—namely, that the particles seen in the intestinal wall are particles of lead in process of excretion into the intestine itself, and that the pigmentation of the vessel walls and cells is caused by the staining of the particles of lead passing from the blood into the lumen of the tube, which have been converted into a sulphide during their passage.

The localization of the staining in the large intestine, especially in the region of the appendix in animals (cats), tends to support this theory. The large bowel near the ileo-cæcal valve, the appendix, and even the glands in the immediate neighbourhood, are found to be discoloured, and to contain lead in larger quantities than any other portion of the intestine. In extreme cases the whole of the large intestine may be stained a greyish-blue. The bloodvessels in the mesentery in this region are also engorged. When, however, a salt of lead, such as lead carbonate or lead oxide, gains access to the stomach, it may be easily converted into chloride by the free hydrochloric acid present in the stomach; and, in addition, should there be any chronic acid-dyspepsia (hyperchlorhydria), particularly of the fermentative type, in which free lactic acid and other organic acids are to be found within the viscus, small quantities of lead swallowed as dust undergo solution and conversion into chloride or lactate. The pouring out of acid gastric juice from the stomach glands does not take place immediately after the first bolus of food is swallowed, and it may be twenty minutes or half an hour before the gastric contents have an acid reaction. During this time any lead salts previously swallowed may become incorporated with the bolus of food and escape absorption.

Lead in solution or suspension in the stomach which becomes mixed up with the food, and at the same time subjected to the action of various albuminous constituents of the food in addition to acids, causes an albuminate or peptonate of lead to be easily formed, and as such can never be absorbed from the stomach direct; practically no absorption takes place in the stomach, and the presence of food containing albuminate precipitates any lead in solution as an organic insoluble salt. The bolus of food impregnated with small quantities of lead passes onwards to the intestine, where further digestion takes place. As the mass passes through the intestine the action gradually results in the reappearance of acidity, but at the same time a certain quantity of sulphuretted hydrogen is produced, some of it from the degradation of the sulphur-containing moiety of the protein molecule by ordinary hydrolytic process and intestinal ferments, quite apart from any bacterial action. A portion of the lead present in the chyme may be set free again for absorption. The bile is said to assist in the solution of lead in vitro.

In experiments made by one of us, which are quoted later, it has been shown that an isolated loop of intestine allows the absorption of a soluble lead salt (chloride) when there is no food present in the loop. As the food mass proceeds through the length of the intestine more and more sulphur is set free, and an opportunity arises for the fixation of the lead as a sulphide, but even as a sulphide it is slightly soluble. Probably, however, most of the lead becomes absorbed long before it reaches the stage at which free sulphur or sulphuretted hydrogen exists for the formation of sulphide. It is highly probable that lead, in common with a number of other heavy metals, including arsenic, is absorbed gradually in the upper part of the intestine, and re-excreted in the lower. Such an hypothesis is undoubtedly strongly supported by the remarkable staining of the large intestine and the ileo-cæcal valve.

The exact mechanism of the absorption of lead from its compound with albumin or peptone as a lead peptonate or albuminate is very difficult to state at present; lead albuminate is undoubtedly insoluble in water or normal saline and in albumin. The process of absorption, then, of the metal lead from the gastro-intestinal canal is very closely related to the absorption of other heavy metals, and the fact that animals after very large doses of lead salts administered via the mouth show hæmorrhages in the intestinal wall, in addition to hæmorrhages in other parts of the body, with occasional distinct ulceration, suggests a localized coagulative action on the vessels in the wall of the intestine as the probable origin of the ulceration. A consideration of this problem of lead absorption from the intestine—probably only the minutest quantity of lead, if any, is absorbed from the stomach direct—is one of considerable importance in the prevention of such lead poisoning as is attributable to swallowing lead. No work in a lead factory should be commenced in the morning without partaking of food, because if food be present the opportunities for absorption of lead are greatly diminished, and of all foods the one to be recommended as the most efficient is milk, or cocoa made with milk.

The absorption of dust through the lung is probably an exceedingly complicated reaction, and Armit’s experiments with nickel carbonyl probably give the clue. He found that in nickel carbonyl poisoning the volatile product was split up on the surface of the lung cells, the metallic portion passing onwards into the lung itself, to be eventually absorbed by the serum.

From the pathological and histological investigations described on [p. 81], and from the fact that particles of lead are very readily taken up by white blood-corpuscles, we can conclude that absorption of the finer lead particles gaining access to the lung takes place through the medium of these phagocyte cells, as such cells are well known to exist within the alveoli of the lung. The stored-up carbon particles found in the lungs in dwellers in cities show that such transference of particles from the alveoli to the inner portions of the lung trabeculæ is a constant phenomenon, and it is therefore easily understood how rapidly any fine particles not of themselves irritant may be easily taken up by the tissues. Once having gained access to the interior of the cells, the particles subjected to the action of the serum of the blood in the ordinary process of bathing the tissues by the exuding lymph—nay, more, actual particles of lead—may thus be actually transferred bodily into the finer blood-spaces, and so be carried forward to the general circulation. Such particles as remain fixed in the lung will undergo gradual absorption, and the constant presence of carbonic acid in the circulating blood brought to the lung undoubtedly largely contributes to their solution, and there is no need to presuppose the necessity of some recondite interaction of organic acid for the solution of the inhaled lead in the lungs.