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LEAD POISONING AND LEAD ABSORPTION

September, 1912.

September, 1912.

The use of lead for various industrial processes and for painting was well known to the ancients. Pliny[1] speaks of white lead, and a method of corroding lead in earthen pots with vinegar, sunk into a heap of dung, as the means by which white lead was made for paint. Agricola mentions three forms of lead—white lead, a compound which was probably bismuth, and metallic lead itself. The alchemists were acquainted with the metal under the name of “saturn,” the term signifying the ease with which the nobler metals, silver and gold, disappear when added to molten lead.

Colic caused by lead was also known in ancient times, and is described by Pliny; many other writers refer to it, and Hippocrates was apparently acquainted with lead colic. Not until Stockhusen[2], however, in 1656, ascribed the colic of lead-miners and smelters to the fumes given off from the molten liquid was the definite co-relation between lead and so-called “metallic colic” properly understood, and the symptoms directly traced to poisoning from the metal and its compounds. Æthius, in the early part of the sixteenth century, gave a description of a type of colic called “bellon,” frequently associated with the drinking of certain wines. Tronchin[3], in 1757, discovered that many of these wines were able to dissolve the glaze of the earthenware vessels in which they were stored, the glaze being compounded with litharge.

In our own country, John Hunter[4] describes the frequent incidence of “dry bellyache” in the garrison of Jamaica, caused by the consumption of rum which had become contaminated[2] with lead. Many other writers in ancient and historical books on medicine have written on the causation of colic, palsy, and other symptoms, following the ingestion of salts of lead; and as the compounds of lead, mainly the acetate or sugar of lead, were freely used medicinally, often in large doses, opportunities constantly occurred for observing the symptoms produced in susceptible persons. It is not to the present purpose to examine the historical side of the question of lead poisoning, but those interested will find several valuable references in Meillère’s work “Le Saturnisme”[5].

Lead was used in the seventeenth and eighteenth centuries particularly, and in the earlier part of the nineteenth, for its action upon the blood. In view of experimental evidence of the action of lead on the tissues, particularly the blood, this empirical use has interest. Salts of lead were found to be hæmostatic, and were therefore used for the treatment of ulcers because of the power, notably of lead acetate, of coagulating albuminous tissue. It was also used in the treatment of fevers, where again it is quite possible that the administration of a lead salt, such as an acetate, produced increase in the coagulability of the blood. At the same time spasms of colic and other accidents followed its use. There is practically no disease to which the human body is subject which was not treated by lead in some form or another. Lead, with the addition of arsenic, was given for malaria, while its use in phthisis was also common. The present use of diachylon plaster is an instance of the continuous use of a salt of lead medicinally, as also is the lotion of the British Pharmacopœia containing opium and lead.

The Chemistry of Lead.

Physical Properties.

—Lead belongs to the group of heavy metals, and occupies a position between bismuth and thorium in the list of the atomic weights, the atomic weight being 206·4, and density 11·85. It is blue-grey in colour, and its softness and facility to form a mark upon paper are well known. Lead melts at a temperature of 325° C., and at this temperature a certain (if negligible) amount of volatilization takes place, which vapour becomes reprecipitated in the form of an oxide. Use is made of the volatility of the metal at the higher temperatures, 550° C. and upwards, in the oxidation of lead from a mixture of lead,[3] silver, and gold; the oxide of lead, or litharge, is partially collected and absorbed by the crucible, but the greater part is mainly removed from the surface of the liquid metal as it is formed, while the richer metal is left in the crucible.

Chemically speaking lead is a tetrad, and forms a number of organic derivatives, especially through the intervention of a particular oxide, minium. Lead forms metallic alkalies and alkaline earths, resembling silver in this direction, and also metallic compounds with zinc and copper; in this point it is very similar to silver. Small quantities of lead present in other metals—as, for instance, a small trace in gold—alter its physical qualities to a great extent; whilst the addition of minute traces of other metals to lead—as, for instance, antimony—cause it to become hard, a fact made use of in the manufacture of shot.

A number of oxides of the metal are known: two varieties of protoxides (massicot and litharge), protoxide hydrate, and bioxide. Sulphide, or galena, represents the chief form in which lead is found in Nature, and from which the actual metal is produced by metallurgical processes.

The salts of lead may be divided as follows:

1. The carbonates or hydrated carbonates employed in a large number of industrial and other processes, which are the cause of much lead poisoning.

2. The acetates, both normal and basic, which are particularly concerned in the production of white lead—at any rate in the process of converting metallic lead into the hydrated carbonate through the medium of acetic acid and steam.

3. Chromate of lead, which is used as a pigment, and also in dyeing yarns, etc.

4. The nitrates and chlorides; the chloride particularly is used as an oxidizing agent (plumbing, soldering, tinning of metals).

5. The silicates, silico-borates, silico-fluoborates, which constitute the many varieties of glass and crystals used in optical instruments, and the various glazes and enamel colours used in the potteries.

There are a large number of other derivatives, but these are not of special interest to the subject in hand.

The Action of Water upon Lead.

—The action of water on lead was known even to the ancients, Pliny and Galen having written on the subject. At times, and under certain conditions, as much as 20 milligrammes per litre have been found, as in the[4] Bacup epidemic, and 14 milligrammes per litre in the epidemic at Claremont. Bisserie[6] in 1900 made an exhaustive inquiry into the action of water upon lead; he gives the following conclusions:

1. Water and saline solutions attack lead more or less readily when it is in combination with another metal, such as solder, copper, bronze, iron, or nickel, the result being a hydrated oxide.

2. The maximum effect is produced with water slightly acid and with solutions of chlorides or nitrates. With these it is not necessary to have other metals present, and if the water is thoroughly aerated the pure metal is attacked.

3. Bicarbonates and carbonic acid exercise by themselves an action on wet lead, but the carbonate of lead formed in the process adheres firmly to the surface of the metal, and prevents any further action.

4. Sulphates act in the same way, but in less degree.

5. This protective action is much diminished when the water is even slightly charged with nitrates or organic material. Pouchet has pointed out that lead branch-pipes fixed to iron water-pipes, thus producing an “iron-lead couple,” set up definite electro-chemical changes, and tend to increase the rate at which solution of lead in the pipe water takes place.

Houston[7], in an extensive and very full report on the effect of water upon lead, especially undertaken for the purpose of inquiry into the contamination of supplies of drinking water by means of lead, distinguishes two species of action—namely, plumbo-solvency, which is brought about by the acidity of the water in contact with lead; and a second kind of action, erosion, determined to some extent by the dissolved air in the water. He came to the conclusion that the plumbo-solvency and erosive action of water on metallic lead differed considerably, and that the protective layer or plumbo-protective substance did not always protect lead pipes from the solvent action of water.

Chemical Characters of Lead Salts.

—A short summary of the chemistry of lead salts may not be out of place.

A soluble salt of lead, such as the acetate or nitrate, is precipitated by (1) hydrogen sulphide or alkaline sulphide as a brown or black precipitate, which is insoluble in ammonium sulphide. In dilute solutions this sulphide is, however, appreciably soluble in mineral acids, and may introduce errors in analysis, especially[5] as the solubility is distinctly increased by the presence of certain earthy salts. The sulphide produced through the action of alkaline sulphide on a soluble salt of lead is less soluble than is the corresponding acid sulphide. Soluble salts of lead are at once precipitated by albumin or peptone; the resulting precipitate has no stable composition.

Under certain conditions definite colloidal precipitates are formed, particularly in the presence of sulphide of copper or mercury. (2) Sulphuric acid or soluble sulphates produce a precipitate of lead sulphate insoluble in excess of the precipitating salt or sulphuric acid, and only slightly soluble in alkaline solutions. This method is the one generally adopted for gravimetric determination of a lead salt. (3) Potassium chromate produces a precipitate of chromate of lead very little soluble in acid, but soluble in caustic alkali. (4) Potassium iodide produces a yellow lead iodide, soluble on heating, and reprecipitating and crystallizing on cooling. (5) Alkaline chlorides and hydrochloric acid produce needle-like crystals of lead chloride soluble on heating, and reprecipitating on cooling. (6) Potassium nitrate in conjunction with a copper salt (copper acetate) produces a precipitate of a triple copper, lead, and potassium nitrate, crystallizing in characteristic violet-black cubes. This reaction is one made use of in the qualitative determination of small quantities of lead in organic fluids (see p. 167).

All the precipitates of lead salts, with the exception of the sulphide, are soluble in fixed alkalies, in ammonium acetate, ammonium tartrate, and ammonium citrate. It is possible to determine the presence of lead in a large volume without evaporating down the whole bulk of fluid. By this means liquid containing lead is treated with sulphide of copper, sulphide of mercury, or baryta-water. Meillère states that he has detected the presence of as small a quantity as 1 milligramme of lead in 1,000 c.c. of water in this manner without evaporating the liquid. Where lead is in organic combination, as is the case in the urine of persons suffering from lead poisoning, it is not decomposed by hydrogen sulphide, and the method is therefore not applicable in such cases, but is useful in water examination.

Electrolytic Reactions.

—Solutions of lead are easily electrolyzed, and give a precipitate of lead at the cathode; simultaneously the peroxide is produced at the anode, and the reaction is acid. In nitric acid solutions Riche pointed out that the whole of the lead[6] is carried to the anode, and this is the reaction made use of in the determination of lead present in the urine (see p. 172).

The presence of copper in an electrolyte regulates the precipitation of lead oxide, copper alone being deposited at the cathode, and at the same time the presence of a small quantity of copper promotes the destruction of organic materials.

REFERENCES.

Lead poisoning of industrial origin rarely occurs in the acute form. Practically all cases coming under the notice of either appointed surgeons, certifying surgeons, or even in the wards of general hospitals, are of the subacute or chronic type. There is no reason to suppose that lead compounds are used more frequently by the workers in lead industries as abortifacients than by other persons.

The compounds of lead which are responsible for poisoning in industrial processes are for the most part the hydrated carbonate, or white lead, and the oxides of lead, whilst a comparatively small number of cases owe their origin to compounds, such as chromates and chlorides.

The poisonous nature of any lead compound from an industrial point of view is proportional to (1) the size of the ultimate particles of the substance manufactured, and therefore the ease with which such particles are capable of dissemination in the air; and (2) the solubility of the particles in the normal fluids of the body, such as the saliva, pharyngeal and tracheal and bronchial mucus, etc., and the fluids of the stomach and intestine. An instance of the variation in size of the particles of lead compounds used industrially is the difference between ground lead silicate (fritted lead) used in the potteries, and the size of the particles of ordinary white or “raw” lead. By micrometric measurements one of us [K. W. G.[1]] found the average size of the particles of fritt to be ten times that of the white lead particles. Further, direct experiment made with equal masses of the two compounds in such a manner that the rate of settling of the dust arising could be directly compared in a beam of parallel light showed presence of dust in the white lead chamber fifteen minutes after the fritt chamber was entirely clear. It is found as a matter of[8] practice that where dust is especially created, and where it is difficult to remove such dust by exhaust fans, the greatest incidence of lead poisoning occurs. The association of dusty processes and incidence of lead poisoning is discussed in relation to the various trades in Chapters XV. to XVII. Fume and vapour given off from the molten metal or compounds, such as chlorides (tinning), are only a special case of dust.

The channels through which lead or its compounds may gain entrance to the animal body are theoretically three in number:

For many years most authorities have held that industrial poisoning by means of compounds of lead takes place directly through the alimentary canal, and that the poison is conveyed to the mouth mainly by unwashed hands, by food contaminated with lead dust, and by lead dust suspended in the air becoming deposited upon the mucous membrane of the mouth and pharynx, and then swallowed. As evidence that lead dust is swallowed, the classical symptom of colic in lead poisoning has been adduced, on the supposition, in the absence of any experimental proof, that the lead swallowed acted as an irritant on the gastro-intestinal canal, thus causing colic, and, on absorption from the canal, setting up other general symptoms. Much of the early treatment of lead poisoning is based upon this assumption, and the administration of sulphuric acid lemonade and the exhibition of sulphate of magnesia and other similar compounds as treatment is further evidence of the view that the poisoning was considered primarily intestinal.

One of the chief objections to this view, apart from the experimental evidence, is that in those trades where metallic lead is handled, particularly lead rolling, very few hygienic precautions have ever been taken in regard to washing before meals, smoking, etc. Although in these trades the hands become coated with a lead compound (oleate), and the workers frequently eat their food with unwashed hands, thus affording every opportunity for the ingestion of lead, the incidence of poisoning is by no means as high or so pronounced in these occupations as in those giving rise to lead dust, such as the white lead industry, where special precautions are taken, and where the incidence of poisoning is always related to the dust breathed.

[9]

Respiratory Tract.

—In a report on the incidence of lead poisoning in the manufacture of paints and colours, one of us [T. M. L.[2]] in 1902 laid stress on the marked incidence of poisoning in the specially dusty lead processes. Following on that report special attention was given to the removal of dust by means of exhaust ventilation. With the introduction of precautionary measures, the incidence of poisoning underwent a marked decrease, this decrease being most definite in those industries where efficient exhaust ventilation could be maintained (see p. 47). Experience shows that cases of poisoning in any given trade or manufacturing process are always referable to the operations which cause the greatest amount of dust, and where, therefore, the opportunity of inhaling lead dust is greatest.

The investigations of Duckering[3], referred to on p. 203, show the amount of dust present in the air in certain dangerous processes. His results clinch the deductions made from general observation, that dusty processes are those especially related to incidence of industrial poisoning. Ætiologically, therefore, the relationship of dust-contaminated air and poisoning is undeniable, and in not a few instances on record persons residing at a distance from a lead factory have developed poisoning, although not employed in any occupation involving contact with lead, aerial infection through dust remaining the only explanation. The actual channel through which the lead dust suspended in the air gains entrance to the body is, therefore, of especial importance; one of two channels is open—gastro-intestinal and respiratory.

The investigations of one of us (K. W. G.) on the experimental production of lead poisoning in animals has shown conclusively that the dust inhaled was far more dangerous, and produced symptoms far earlier than did the direct ingestion of a very much larger quantity of the same compound by way of the mouth and gastro-intestinal canal. There is no doubt whatever that the chief agent in causing lead poisoning is dust or fume suspended in the air. That a certain amount finds its way into the stomach direct is not denied, but from experimental evidence we consider the lung rather than the stomach to be the chief channel through which absorption takes place (see p. 81).

The following table gives a specific instance of the incidence of lead poisoning in a white lead factory, and demonstrates clearly the ætiological importance of dust. The increase in reported cases, as well as in symptoms of lead absorption not sufficiently[10] severe to prevent the individual from following his usual occupation, was associated with the rebuilding of a portion of the factory in which the packing of dry white lead had been carried on for a large number of years. The alterations necessitated the removal of several floors, all of which were thoroughly impregnated with lead dust. Before the alterations were undertaken it was recognized that considerable danger would arise; stringent precautions were therefore taken, and the hands engaged in the alterations kept under special observation. Notwithstanding this there was an increase in the number of reported cases, which were all mild cases of colic; all recovered, and were able to return to their work in a short time.

Table I.—Lead Poisoning in a White Lead Factory.

The figures refer to the weekly examination of the whole of the men. For example, if a man was returned as suffering from anæmia on three occasions, he appears as three cases in Column 7.

Meillère[4] goes to considerable trouble to show that absorption of lead dust by the lung is hypothetical; that it may take place, but that it is not a channel of absorption of practical importance. He cites a number of opinions and experiments by various observers on the absorption of lead through the mucous membrane of the mouth, alimentary canal, conjunctiva, etc., and he regards the absorption of lead as one peculiarly confined, in the majority of instances, to the intestinal canal.

The usual view is that, in the passage of the respired dust-laden air through the nose, the larger particles of dust are deposited first of all upon the mucous membrane in the interior chambers of the nose; further, a second deposit takes place on the posterior wall of the pharynx and in the throat, where the eddies produced[11] by the current of air inhaled through the nostrils allow the finer particles to become more easily deposited. Finally, should a small trace gain access to the larynx, it is said to be deposited there upon the mucous membrane, to be subsequently ejected, and only a very small proportion of the total may ever find its way into the lung.

In all arduous labour, directly the respiration rate rises through extra calls made upon the muscles of the body, an increase in the depth of respiration takes place; yet even under these circumstances Meillère and others incline to the view that the dust is deposited on the mucous surfaces of the mouth and swallowed. Experimental evidence is entirely opposed to these suppositions. In the first place, unless particles of dust readily find their way into the lung, it is difficult to understand how the lung itself becomes the site of so much deposit of carbon, and of flinty material in stonegrinder’s pneumokoniosis. The staining of the lung by means of carbon particles, particularly in dwellers in cities, is too well known to warrant more than a passing reference. Moreover, experimental work has shown that fine powders suspended in the air easily reach the lung. Armit[5] has shown that the nickel in nickel carbonyl poisoning gains direct access to the lung, and becomes deposited there, the metallic particles being readily demonstrated in the lung tissue itself. Further, the experiments (see p. 84) demonstrate that white lead dust and other forms of lead dust definitely gain access to the lung, and thus inhaled produce all the symptoms of lead poisoning in animals subjected to the inhalation. White lead, litharge, or red lead, are not easily suspended in water, and long-continued mixing is necessary to make a suspension. Great difficulty is found in “laying” lead dust by water, as the following experiment demonstrates: Five wash-bottles are arranged in series; in the first ground dry white lead is placed, and the other three bottles are filled with water, and a tube laid under the surface of the water in such a way that the air from the first bottle must pass the whole of the water seals in each subsequent bottle. In the last bottle is dilute nitric acid saturated with sulphuretted hydrogen. If the series is now attached to an aspirating jar, and air drawn slowly over at the rate of ordinary respiration, the white lead powder in the first bottle being at the same time shaken so that the air is fully charged with finely powdered dust, lead is quickly detected in the air passing through the last bottle of the series, by[12] the darkening of the solution. In this way the presence of lead dust has been demonstrated after passing through four 2-inch water seals and 8 feet of ¹⁄₄-inch wet rubber tubing. Such an experiment negatives the theory that all, or even a large quantity, of a finely divided powder becomes deposited on the upper portion of the respiratory tract.

Particles of lead present in the air in industrial processes are exceedingly minute, and even in ground white lead the average size of the particle is under 1 μ. Finally, Tanquerel[6] and Stanski[7] succeeded in producing lead poisoning experimentally by blowing lead dust through a tube inserted in a tracheotomy opening. There remains, therefore, no room for doubt that the lung is the pre-eminent portal for lead absorption, particularly in industrial processes; from which it follows, as has been extensively shown in actual practice, that the diminution of dust in workshops and factories by means of exhaust ventilation is invariably followed by a diminution in the number of cases of plumbism.

Gastro-Intestinal.

—We have dealt with absorption by way of the lung, and have insisted that such inhalation of dust is of greater importance in giving rise to industrial lead poisoning than gastro-intestinal absorption. Gastro-intestinal absorption can take place, and is by no means negligible, in ordinary industrial conditions. One of the most interesting and important confirmatory evidences of the absorption of lead by the gastro-intestinal canal is to be found in the large outbreaks of poisoning in which water-supplies have been contaminated, either at their source or locally. We have already seen that electrolysis may play an important part in the solution of lead in water, and also learnt from Gautier[8] that the carbon dioxide content of water is not necessarily the sole predisposing element in the solution of lead. In this connection an important case is described by Thresh[9], where water by no means soft, but holding some 30 degrees of hardness, produced lead poisoning in an isolated family. The water in question was distinctly acid to litmus-paper, and contained a very high percentage of nitrates; the compound or salt of lead present was therefore one easily absorbed from the alimentary canal (see p. 86).

In all instances of water-borne lead poisoning the amount of lead present in the water was small; but as such lead would not be removed by boiling, the amount of water consumed per person from the contaminated source was probably large. As the signs[13] of poisoning did not appear until a considerable time had elapsed, a much larger quantity of lead was probably absorbed than would appear from the simple statement that the water contained ¹⁄₁₀ grain per gallon.

A number of cases have been reported from use of diachylon as an abortifacient, and the symptoms in these cases are invariably those which occur in other severe forms of poisoning such as are met with in industrial processes. In nearly every case colic was the first symptom, followed later by paresis of various types—amaurosis, albuminuria, albuminuric retinitis, melancholia, encephalopathy—and not a few of the persons succumbed. In most of the reported cases abortion was produced, but in some, particularly in one[10], three dozen pills containing diachylon were taken in a month, producing acute lead poisoning, colic, and paresis, but not abortion.

In fifteen recorded cases of the use of diachylon, fourteen showed a lead line, in many cases distinct and broad. This point has considerable interest, as such a line cannot have been produced by oral contact. The drug in the form of pills would be rapidly swallowed, and little opportunity afforded for particles to remain in the mouth. Its presence, therefore, suggests excretion from circulating blood of lead which has been absorbed in the intestine. The blue line will be referred to again later (see p. 122).

Practically all cases of water poisoning and of swallowing of lead compounds have developed colic. Further, colic is cited in all the early recorded cases, even in the very earliest cases referred to in the historical note, of lead poisoning; and as poisoning in those cases had invariably taken place by swallowing the drug, it may be presumed from this association has arisen the belief that lead must be swallowed to produce gastro-intestinal symptoms. No attention has been paid to the fact that a few cases of definite cutaneous absorption of lead from the use of hair lotions have been followed by colic. Gastro-intestinal symptoms, therefore, can be produced without the direct ingestion of the drug, and colic is a symptom of generalized blood-infection rather than a localized irritative action on the intestinal mucosa. This question, again, is more related to pathology than ætiology, and is dealt with in that section. But mention may be made here of the fact that a number of observers, more lately Meillère, have laid it down as an axiom that experimental production of lead poisoning in animals gives no criterion[14] or evidence of lead poisoning produced in man industrially. Very grave exception must be taken at once to such a statement. In the majority of experiments quoted by Meillère the quantity of lead given for experimental purposes has been large—much larger, indeed, than is necessary to produce small and characteristic effects—and instead of chronic poisoning an acute lead poisoning has generally been set up; and even where chronic poisoning has supervened, the condition has as a rule been masked by the severer initial symptoms. On the other hand, the evidence to be derived from comparison of the various observations from animal experiments brings out with remarkable unanimity the similarity of the symptoms to those produced in man, and, as will be seen later in the section devoted to Pathology, experiments by one of us (K. W. G.) have so far confirmed this surmise; in fact, a description of a case of encephalopathy coming on after lead poisoning of a chronic nature, described by Mott, agrees in practically every particular with the train of symptoms as observed in these experimental animals. Certain slight differences as to the muscles first affected are observed, but it is practically always the homologous muscle (the physiological action of which more nearly resembles the human muscle) which is the one to be affected in the animal, not the anatomical homologue. Thus, for instance, in the cat the spinal muscles, and particularly the quadriceps extensor, is the muscle which is first affected through the medium of the anterior crural nerve. This extensor muscle is one which only performs a slight amount of work in extending the knee-joint, the amount of work being, however, disproportionate to the size of the muscle. The extensors of the fore-feet ultimately do become weakened, but it is the hind-limb upon which the stress first falls.

Attention has been given to the solubility of lead salts in gastric juices, the majority of such experiments having been performed with artificial gastric juice. The method at present in use, prescribed by the amended rules of August, 1900, for earthenware and china factories, is based on some, if slight, consideration of the physiology of digestion. The method described by Rule II. states that the estimation of the quantity of lead present in the lead fritt shall be performed as follows:

A weighed quantity of dry material is to be continuously shaken for one hour at room temperature with one thousand times its weight of an aqueous solution of hydrochloric acid, containing[15] 0·25 per cent. of HCl. This solution is thereafter to be allowed to stand for one hour, and to be passed through a filter. The lead salt contained in a portion of the clear filter is then to be precipitated as lead sulphide, and weighed as lead sulphate.

This method has been adopted on the supposition that the solubility of a lead salt in the gastric juices is the chief source of the lead poisoning in the Potteries, and that the hydrochloric acid content of the solution determines, for practical purposes, the quantity of lead dissolved out of a given sample. The temperature, however, at which this estimation is made—namely, room temperature—is one considerably lower than that of the body, and the quantity of lead taken up into solution at this temperature is less than that which occurs at the ordinary temperature of the body—37° C. Practically twice as much lead is dissolved out of fritt at 37° C. for an hour as is rendered soluble at the ordinary temperature of the room—about 15° C. Thomason[11], who made some experiments in this direction, gives a figure of 2·35 lead oxide dissolved at 15° C. and 4·54 at 37° C. In another estimation—a matter, too, of some considerable importance—it was found that acetic acid dissolved 1·97 per cent, at 15° C., and 3·27 at 37° C. In lactic acid the figure was 2·28 at 15° C., and 3·53 at 37° C. It is therefore a low estimation of the solubility of any substance by the gastric juices if the substance is operated on at a temperature below that of the body.

The question of the solubility of a lead salt in the gastric contents is important in view of the small quantities of dust swallowed; and in addition to hydrochloric acid, other substances are also present in the gastric juice, which is by no means a simple aqueous solution of the mineral acid. Further, the gastric juice, except in cases of pathological type, is not acid in periods of gastric rest, unless such acidity may be represented by the presence of fermentative acids—acetic, lactic, and butyric.

The activity of the gastric juice on lead is directly caused by the quantity of organic acids present in addition to the hydrochloric acid, and by the presence of foodstuffs—(1) in the undigested and (2) in the semidigested condition. In considering the absorption of lead products from the gastro-intestinal canal, the normal digestive processes should not be lost sight of—that is, the sequence of events which occur during digestion of food. On swallowing food, no definite acidity is present in the stomach for fifteen to twenty minutes, and even after that time the[16] hydrochloric acid is only commencing to be secreted. As digestion proceeds, and the whole mass becomes partially dissolved, such portions as are in a soluble condition are passed through the pyloric opening at intervals, and the whole contents of the stomach do not pass straight through the pyloric opening as through an ordinary straight drain-pipe. As each mass of food passes onwards through the pylorus, it comes into contact in the duodenum with pancreatic juice, and with the bile, these alkaline fluids rapidly change the reaction, and allow the other ferments, trypsin, etc., to become active. As the mass proceeds onwards through the intestine, the succus entericus also exerts its function. Finally the fluid contents of the intestine are passed onwards through the ileo-cæcal valve. During the passage from the pylorus to the ileo-cæcal valve, the reaction of the intestinal contents undergoes variations, from an alkaline in the duodenum or upper parts of the jejunum, to acid at the ileo-cæcal valve. Practically no absorption takes place from the stomach itself; a small quantity of water and such highly volatile fluids as alcohol may be absorbed, but the main absorption is not commenced until the food has left the stomach; in fact, the stomach contains no mechanism for food absorption. The work of absorption of the products of digestion is carried on actively through the small intestine until finally the materials have reached the large intestine through the ileo-cæcal valve; water is then mainly absorbed, and albuminous fluids and substances in solution to some extent, but the amount of absorption which takes place is infinitesimal as compared with that of the small intestine.

These points in the physiology of digestion require to be taken into account when discussing the absorption of lead salts in the gastro-intestinal canal.

When human gastric juice is obtained direct from the stomach in man, and lead is submitted to its action, definite quantities of lead pass into solution; and, curiously enough, in the normal gastric juice lead sulphate is as soluble as both white lead and litharge. The following two tables give the results of the estimation of the direct action of human gastric juice upon lead. The particular point is that the juice was obtained by the stomach tube from persons who had been given a simple test meal preceded by a twelve hours’ fast; the juice was therefore in a normal condition. The tests gave the following results in the normal stomach:

[17]

In the second digestion, in which the analysis of the contents showed the patient to be suffering from the condition known as “hyperhydrochloridia,” the results were—

A very large number of experiments have also been performed for the purpose of determining the solubility of raw lead glaze, and white lead, in artificial digestions, the digestions having been made up in such a way that they resembled as far as possible in every particular the ordinary stomach contents. The type of digestion used was as follows:

Digestions were performed with this mixture, and in every case the digest was divided into two portions; each portion was retained at body temperature, with agitation for a couple of hours, and at the end of that time one portion was submitted to analysis. The second portion was neutralized, sodium carbonate and pancreatic ferment added, and digestion carried on for another two and a half hours at body temperature. At the end of this time the pancreatic digest was examined.

Thirty-five digestions were performed. When 1 gramme of white lead was used—that is, 0·01 per cent., containing 0·75 per cent. of lead oxide—the quantity of lead found as lead oxide in the acid digest varied from 2 to 3 per cent., whilst the amount found in the pancreatic digest varied from 4 to 6·5 per cent. of the added salt. On increasing the amount to 12 grammes—that is, 1 per cent.—the quantity returned in the digest only increased from 1·5 to 2 per cent. In other words, in the addition of larger quantities of material the ratio of solubility did not rise in proportion to the quantity added. Where a direct pancreatic digestion was performed without the preliminary digest of the gastric contents, the amount of lead present in the digest was only about 0·2 per cent. of the quantity added; indeed, it was very much smaller than the amount dissolved out after preliminary acid digestion—that[18] is, if the normal sequence of digestion is followed, the solubility progresses after the gastric digest has been neutralized and pancreatic ferment has been added, whereas very slow action indeed occurs as the result of action of the pancreatic digest alone. Some experiments described by Thomason[12], although carried out without special regard to the physiological question of the progressive nature of digestion, distinctly confirm the point raised. Thus, in a digest of gastric juice, milk, and bread, 5·0 per cent. of lead was dissolved, whereas when pancreatic juice alone was used only 0·4 per cent. was found to be dissolved, a remarkable confirmation of the point under discussion.

The difficulty of estimating lead present in these gastric digestions is a very real one, as, owing to the precipitation of lead by various fluids of an albuminoid nature, it is difficult to determine the amount of lead present in a given quantity of digest; moreover, in making such a digest, much of the material may become entangled among the clot of the milk in a purely mechanical fashion, and, in attempting to separate the fluid from the other portion of the digest, filtration no doubt removes any lead which has been rendered soluble first of all, and reprecipitated as an albuminate. An albuminate of lead may be formed with great ease in the following way: A 5 per cent. solution of albumin in normal saline is taken, 0·02 per cent. of hydrochloric acid is added, and 10 per cent. solution of lead chloride added as long as a precipitate is formed. The precipitate is then filtered off, and washed in a dialyser with acidulated water until no further trace of lead is found in the washings. A portion of this substance taken up in distilled water forms a solution of an opalescent nature, which readily passes through the filter and gives the reaction of protein with Millon’s reagent, and the lead reaction by means of caustic potash and sulphuretted hydrogen, but very large quantities of mineral acid are required to produce any colour with hydrogen sulphide. Lead which gains access to the stomach, either dissolved in water or swallowed as fine dust, becomes in all probability converted first into a soluble substance, chloride, acetate, or lactate, which compound is then precipitated either by the mucin present in the stomach, or by the protein constituents of the food, or by the partially digested food (peptonate of lead may be formed in the same way as the albuminate described above). In this form, or as an albuminate or other organic compound, it passes the pylorus, and becomes[19] reprecipitated and redigested through the action of the pancreatic juice. A consideration of the action of artificial gastric juices and the properly combined experiments of gastric and pancreatic digestions suggest that the form in which lead becomes absorbed is not a chloride, but an organic compound first formed and gradually decomposed during the normal process of digestion, and absorbed in this manner from the intestine along with the ordinary constituents of food. Dixon Mann[13] has shown that about two-thirds of the lead administered by the mouth is discharged in the fæces, and that the remaining one-third is also slowly but only partially eliminated. This point is of very considerable importance in relation to industrial poisoning of presumably gastro-intestinal origin, and consideration of the experiments quoted suggests that the digestion of albuminate or peptonate may to some extent be the basis which determines the excretion of so much of the lead via the fæces. This alteration of solubility has no doubt a bearing on the immunity exhibited by many animals when fed with lead, and probably explains the fact that many of the experimental animals fed with lead over long periods exhibited no symptoms of poisoning (see p. 85), whereas control animals, given a far smaller quantity of lead by other means and through the lung, rapidly developed symptoms of poisoning. A diversity of opinion exists as to the effect of pepsin upon the solubility of lead. Oliver[14] considers that the pepsin has a retarding influence on the solubility of lead in the gastric juice, and Thomason’s experiments also support this view, although it is difficult to see why the action of pepsin alone should be of such extreme importance. There is also the complicating fact that other added substances in the food may mask any direct pepsin factor that may be present. Albumose and peptone rather than pepsin are to be regarded as the more important substance physiologically in their reaction with lead, and it is interesting to note that Schicksal[15] found that by exposing lead in the form of white lead in a 1 per mille solution of hydrochloric acid in the presence of peptone produced a greater solvent effect on white lead than did the diluted acid alone, and the same effect was also seen on metallic lead.

[20]

Table II.—Schicksal’s Table.

The experiments referred to on p. 18 undoubtedly agree with those of Schicksal. In addition to the presence of peptones, the effect of carbonic acid must be also considered, as increase in solubility in gastric and pancreatic digestions was produced when carbonic acid gas was bubbled through the digest during the period of action. The whole question of solubility of many materials in the fluids of the stomach and intestinal canal requires entire revision, not only as regards lead, but as regards a number of other metals, including arsenic.

The Mechanism of Lead Absorption.

—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[21] 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[22] 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[23] 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[24] 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.

In the absorption of the substance from the intestine, it may go direct into the blood-stream in a similar fashion through the lacteals along the lymph channels, and so into the thoracic duct, and finally into the general circulation. On the other hand, a certain amount, probably not an inconsiderable portion, is taken up by the portal circulation and transferred direct to the liver itself. Chemical analysis of the liver supports this view, as does also the considerable amount of stress thrown upon the liver when poisoning has taken place from the intestinal canal on administration of massive doses of a highly soluble lead compound. According to Steinberg[16], excretion of lead takes place partly from the liver by the bile. This is probable, but there is no experimental evidence at the present time to support the view. If such an excretion does take place, the form in which the lead is excreted is probably one in which it is no longer soluble by digestive action. On the other hand, it may be in so soluble a form as to become reabsorbed from the intestine, thus setting up a constant cycle. But such a theory is one that would require a considerable amount of experimental evidence to support it before it could be relied on.

There is no doubt that, however absorbed, lead remains stored up in the body in minute quantities in many places, and the close analogy to arsenic is met with in the curious elimination of the metal by the fæces. Cloetta[17], quoted by Dixon Mann, discovered that, although dogs were unable to take a larger dose of arsenic than 0·0035 gramme per day without exhibiting toxic results, they could nevertheless take arsenic in much larger doses if it were given in the solid form, and he was able to increase the dose to as much as 2 grammes per diem without showing any toxic symptoms. Examination of the urine and fæces showed that as the amount of urinary excretion of arsenic diminished, so that in the fæces increased, and in lead poisoning, even in massive doses swallowed in error, the amount of lead excreted by the urine rapidly diminishes in quantity, although the patient may be still suffering from the effects of lead poisoning. The experiments, also, quoted on p. 100 constantly pointed to the elimination of lead by way of the intestine,[25] and in practically all the animals that had suffered from chronic poisoning well-marked dark staining of the upper part of the cæcum due to lead was invariably present. This staining and excretion of lead of the large intestine undoubtedly takes place in man. In a case described by Little[18], where diachylon had been administered, the administration of a large enema containing sulphate of magnesium came away black. A more detailed result of the experiments and a consideration of the elimination of lead are reserved for another chapter, but it is impossible to consider the ætiology of the disease without some reference to the general histological channels of absorption and excretion.

Cutaneous Absorption of Lead.

—A considerable amount of controversy has centred on the question of the absorption of lead through the unbroken skin. It has been shown that such drugs as belladonna applied to the skin alone may produce dilatation of the pupil; an ointment containing salicylic acid spread upon the skin and thoroughly rubbed in is followed by the appearance of derivatives of salicylic acid in the urine; mercury may be applied to the skin, and rubbed in, in sufficient quantities to produce salivation; and a very large number of other drugs may be cited, all of which when applied to the unbroken epidermis with friction produce the physiological action of the drug.

There is no reason to exclude lead from the category of drugs which may be absorbed through the medium of the skin, and, as several observers have shown, animals may be poisoned by lead on applying a plaster of lead acetate to the skin. Amongst these experiments may be quoted those of Canuet[19] and Drouet[20] on rabbits. Some observers, among whom may be mentioned Manouvrier[21], have attempted to prove that paralysis of the hands occurs more often in the right hand in right-handed people, in the left hand with left-handed people, and from the various experiments showing absorption of lead through the unbroken skin they seek to connect the lesion of the nerve with absorption direct through the skin of the hands.

Many objections can be urged against acceptance of this theory. Lead workers who are constantly manipulating lead in a state of solution with bare hands do not appear as a class to be more subject to wrist-drop than do persons who are exposed to inhalation of fumes or dust of lead; in fact, incidence of paralysis and of nerve lesions generally is more severe among persons[26] exposed to prolonged inhalation of minute quantities of lead through the respiratory tract. The greater the exposure to dust, the greater the number of cases of anæmia and colic, whilst in other industries, as has already been stated, where lead exists as an oleate on the hands of the workers day in and day out for many years, paralysis and even colic are of rare occurrence; in other words, persons especially exposed to the absorption of lead through their hands show a much smaller incidence of lead poisoning of all types than do those exposed to lead dust. Further, the pathology of wrist-drop and similar forms of paresis tends to show that the nerve supplying the affected muscles is not affected primarily, but that the initial cause is hæmorrhage into the sheath of the nerve, producing ultimate degenerative change. The hæmorrhage, however, is the primary lesion.

REFERENCES.

A large number of poisonous substances, among which lead may be included, are not equally poisonous in the same dose for all persons. It is customary to speak of those persons who show a diminished resistance, or whose tissues show little power of resisting the poisonous effects of such substances, as susceptible. On the other hand, it is possible, but not scientifically correct, to speak of immunity to such poisonous substances. Persons, particularly, who resist lead poisoning to a greater degree than their fellows are better spoken of as tolerant of the poisonous effects than as being partially immune.

The degree of resistance exhibited by any given population towards the poisonous influence of lead shows considerable variation. Thus, in a community using a water-supply contaminated with lead, only a small proportion of the persons drinking the water becomes poisoned. There are, of course, other factors than that of individual idiosyncrasy which may determine the effect of the poison, as, for example, the drawing of the water first thing in the morning which has been standing in a particular pipe. But even if all disturbing factors are eliminated in water-borne lead poisoning, differing degrees of susceptibility are always to be observed among the persons using the water.

Lead does not differ, therefore, from any other drugs to which persons show marked idiosyncrasies. Thus, very small doses of arsenic may produce symptoms of colic in susceptible persons; a limited number of individuals are highly susceptible to some drugs, such as cannabis indica, while others are able to ingest large doses without exhibiting any sign of poisoning; and it is well known that even in susceptible persons the quantity of a particular drug which first produces symptoms of poisoning may[28] be gradually increased, if the dosage be continued over long periods in quantities insufficient to produce marked symptoms of poisoning. In this direction a number of experiments have been performed with arsenic, particularly those of Cloetta[1], who found that the dose of arsenic for dogs could be gradually raised, if given by the mouth, to many times the ordinary fatal dose, but that if at this point a subminimal fatal dose was injected beneath the skin acute symptoms of arsenic poisoning followed.

We show in a later chapter that the excretion of lead in persons tolerant of the metal takes place through the medium of the bowel, and that probably those individuals who are engaged in what are recognized as dangerous processes in lead industries, and yet show no signs of illness, have established a kind of balance between the intake of the poison and its excretion by the bowel. It is rarely possible in such persons to find any lead excreted through the kidney. Occasionally, however, such persons, after working a considerable time in a dangerous lead process, become suddenly poisoned, and inquiry frequently discloses the fact that some disturbing factor, either intercurrent illness, alcoholic excess, etc., has occurred, or that the breathing of a big dose of dust has precipitated the symptoms of general lead poisoning. On the other hand, the experience of all persons engaged in the routine examination of lead workers is that, although a worker may show signs of lead absorption as distinguished from definite lead poisoning during the earlier period of his employment, he later shows less and less signs of the influence of the poisonous substance; even a mild degree of definite poisoning in the early stages of work in a lead process does not seriously militate against this gradually acquired tolerance, whilst careful treatment during such a time as the man is acquiring tolerance to the poison frequently tides him over the period, and enables him to withstand the ordinary dangers attached to his work.

The earliest symptom of lead absorption is anæmia. The anæmia is not very profound, and the diminution in the red blood-cells rarely reaches as low as 2,000,000 per c.c., the hæmoglobin remaining somewhere between 75 and 80 per cent. Some loss of orbital fat, as well as fat in the other parts of the body, occurs, but beyond this no obvious clinical signs of poisoning exist. Should such persons possess unhealthy gums, a blue line rapidly makes its appearance, but where the gums are healthy it is unusual to see any sign of deposit in this prodromal stage.

[29]

Persons who gradually acquire tolerance go through the stage of anæmia without exhibiting any symptoms of colic or paresis, and without any treatment the hæmoglobin and the number of red cells gradually pass back to a more or less normal condition. During this period—that is, whilst the blood shows signs of a diminution in its corpuscular and colour content—basophile granules may always be found if sought for, but disappear as a rule when the blood-count has returned to about 4,000,000 per c.c. and an 80 per cent. hæmoglobin. Such a man has now developed tolerance to the poisonous influence of lead, a tolerance which may be described as a partial immunity produced by recurrent subminimal toxic doses. On the other hand, in a number of persons who show definite susceptibility, the blood-changes are progressive, and do not show signs of automatic regeneration. In such persons, even after so short time as four to six weeks’ exposure to lead absorption, definite symptoms of colic may make their appearance. The removal of such an individual from the poisonous influence of lead generally clears up the symptoms in a short time, but the symptoms may occasionally continue for several months after removal from the influence of the poison. An individual of this type is to be looked upon as showing peculiar susceptibility, and should not be employed in any lead process where there is risk.

Such statistics as are available on this point show that an increased tolerance to the poisonous influence of lead is gradually acquired during periods of work, in that the number of attacks of poisoning diminish in frequency very considerably in relation to the number of years worked. As will be seen on reference to the chapter dealing with the statistics of lead poisoning (p. 46), the greatest number of cases occur in persons who have only worked a short time in lead. On the other hand, the sequelæ of lead poisoning only make their appearance, as a rule, after long-continued exposure. It is important to bear in mind that the various forms of paresis rarely make their appearance unless the subject has been exposed to long-continued absorption of lead, and, further, that the blood of such persons will as a rule show, on careful examination, evidences of the long-continued intoxication. If measures, therefore, were taken to determine the presence of such continued intoxication, and to diminish the amount of poison absorbed (subjecting the individual at the same time to a proper course of treatment), a large number of the cases of[30] paralysis, encephalopathy, and death, incidental to the handling and manufacture of lead, could be eliminated.

Susceptibility may at times be shown by several members of one family. Oliver[2] says that he has known many members of one family suffer from and die of lead poisoning. In our experience several instances of this susceptibility have been noticed. In one case two brothers, working in one shift of men, developed poisoning, although no other persons in that shift showed any signs of it. A third brother, who came into the works after the other two had left, and who was placed under special supervision on account of the susceptibility exhibited by his two brothers, although given work which exposed him to the minimal degree of lead absorption, developed signs of poisoning six weeks after his entrance into the factory. In another factory, three sons, two daughters, and the father, all suffered from lead poisoning within a period of four years: the father had three attacks of colic, ultimately wrist-drop in both hands; one daughter had one attack of colic, and the other three attacks; whilst the three brothers all suffered from colic and anæmia, and one had early signs of weakness of the wrist. There was no evidence at all to show that these persons were more careless, or had been more exposed to lead dust, than any other of the persons with whom they worked, or that the work they were engaged upon was more likely to have caused illness to them than to other workers. Persons with a fresh complexion and red hair have been noted to be more susceptible to lead poisoning than dark-haired persons.

In one factory with which we are familiar, a number of Italian workmen are employed; these show considerably less susceptibility to lead poisoning than do their English comrades as long as they adhere to their own national diet. When, however, they give this up, and particularly if they become addicted to alcohol, they rapidly show diminished resistance; in fact, all the cases of plumbism occurring among the Italians in this factory during the last ten years have been complicated with alcohol. It is possible that the relatively large quantity of vegetables in the diet of these Italians influences the elimination of absorbed lead. There is some reason to suppose, however, that there may be racial immunity to lead poisoning.

The following case in the same factory illustrates a point already mentioned—namely, the gradually acquired tolerance to poisoning,[31] and the unstable equilibrium existing. The individual was a man of twenty years of age. He commenced work on August 2, 1905. Six weeks later he was under treatment for seven weeks, for lead absorption, and had a peculiarly deep blue line round his gums, and a diminished hæmoglobin of 75 per cent. The symptoms disappeared with ordinary routine treatment, and his work was shifted to a position in the factory where he was exposed to the minimum amount of lead absorption, at which work he continued during the rest of the time he remained in the factory. He continued quite well until June, 1906, when he was again under treatment for two weeks, with the same blue line and anæmia, and his blood showed the presence of basophile granules. He was under treatment again in January and February, 1909, for five weeks, had again a deep blue line and basophile staining of his blood. On November 7, 1911, having had no anæmia and no blue line, he had a slight attack of colic. During this period of work his blood had been examined on eight occasions, and on each occasion it had shown basophile granules. The attack of colic was an exceedingly mild one. There is no reason to suppose that he had indulged in alcoholic excess, but there was some reason to think that for about a month he had been subjected to increased lung absorption. No other persons working in the same shift at the same work developed poisoning during the whole of this period. This case illustrates initial susceptibility, partial tolerance, and ultimate breaking down of such partially established tolerance.

During the experimental inquiry on lead poisoning by one of us [K. W. G.[3]], the question of the subminimal toxic dose and the minimal toxic dose was under consideration. Animals subjected to inhalation of lead dust invariably succumbed to the effects of the poison when the dose given represented from 0·0001 to 0·0003 gramme per litre of air inhaled, the period of inhalation being half an hour three times a week. On the other hand, when the lead content of the air was as low as 0·00001 gramme per litre, the symptoms of poisoning were long delayed, and in more than one instance, after an early diminution in weight, recovery of the lost weight took place, and the animals, whilst showing apparent symptoms of absorption, had no definite symptoms of paresis. These observations tend to confirm such clinically observed facts as are given in the case cited above, but they, of course, do not form a criterion as to the[32] amount of lead dust which may be regarded as innocuous to man.

Lead is peculiarly a cumulative poison, and post-mortem analyses of viscera show that it may be stored up in certain parts of the body, more especially in the bone and red bone marrow and brain, and to some extent in the liver, spleen, and kidneys. Any circumstance, therefore, that temporarily interferes with the ordinary channels through which lead is excreted may determine the presence of a much larger quantity than usual of the metal in circulation in the body; and if in addition an increased quantity of the poison be inhaled, more or less acute symptoms follow. The localization of the deposit of lead is therefore of some importance.

Meillère and Richer[4] give an analysis of various organs of the body, but their results are not in accord with the majority of other observers. They found that the hair particularly contains a large quantity of lead. They do not seem to have examined the bones. Next to the hair, the liver seems to have contained the largest amount. Wynter Blyth[5] found 117·1 milligrammes of lead in the brain of a person who died of encephalopathy. In another case he found 0·6 gramme in the liver, 0·003 in the kidney, and 0·072 in the brain. Hougounencq[6] examined the organs of a person who died from lead poisoning, and found the largest amount of lead in the large intestine.

In the lung, stomach, kidney, and heart, only traces were found.

Dixon Mann[7] describes some experiments in which potassium iodide was given in cases of chronic poisoning, and during the whole of the experiments the fæces and urine were analyzed three times a week. He found by this means that a considerable amount of lead was being eliminated by the intestine. He therefore administered 2 grammes of lead acetate three times a day for five days to a patient, and he found that the fæces contained 0·1762 gramme the first day, 0·17411 gramme the second day; the fourth day it had fallen to 0·0053 gramme, and on the sixth day to 0·0006 gramme. The largest amount at any one time in a day obtained from the urine was only just over 0·001 gramme; the average amount found in the case of chronic poisoning was[33] about 3 milligrammes, whereas the greatest amount at any one time in the urine was only 0·9 milligramme.

The quantity of lead present in the brain necessary to determine acute poisoning is not known, and it is probable that an extremely minute quantity will produce very serious effects; and in support of this may be quoted a number of observations in which search has been made for the metal in persons who have died of diseases affecting the brain associated with other symptoms of poisoning, and yet post-mortem examination of the brain by chemical methods has not revealed the presence of any lead whatever. In the case reported by Mott (see p. 71), no lead at all was recognized in the brain.

There are no reasons, therefore, for supposing that the immunity to lead poisoning depends on the fixation and storing up of the poisonous metal in a non-poisonous form in some special situation in the body, and, further, the particular situation in the body richest in lead in any given case of poisoning will depend rather on (1) the type of compound causing the poisoning, and (2) the portal through which such poisoning occurs.

The question of the detection of lead in the body is referred to in the chapter dealing with Chemical Examination. It is as well to point out in this connection that chemical investigation of the amount of lead present in the organs of persons dying from lead poisoning should, if possible, always be made where there is any doubt as to the diagnosis.

Certain observers—amongst them Gautier[8]—are of opinion that traces of lead may be found in normal persons. Thus, in a rat (Mus decumanus) Gautier found 2 milligrammes of lead in 60 grammes of liver. He considers that in many persons at least 0·5 milligramme of lead may be swallowed daily incorporated with the food, as a number of foods are liable to contamination by lead. Tinned foods, particularly those which are soldered up after the materials have been placed in the tin, certain tinned fruits with acid juices, often contain small masses of solder loose in the tins; in the case particularly of fruits the natural acid may slowly dissolve the lead from the solder. The amount of so-called “normal” lead, if it is to be found at all, must be very small, and would certainly be much smaller in the case of a normal person than in one who had been subject to definite lead poisoning. Such experimental evidence as is forthcoming supports[34] the clinical observations that persons exposed to small doses of lead eventually develop tolerance of the metal, so that they may ultimately withstand many times the dose sufficient in the first instance to produce poisoning.

Such circumstances are the natural factors in the prevention of poisoning, and if due care be given to their significance, the surgeon in charge of any lead works may by judicious treatment and alternation of employment so assist and strengthen the natural defensive forces that susceptibility may be diminished, and the degree of tolerance increased to a very considerable extent. We do not imply that efficiency in the exhaust ventilation can be in any way relaxed; all we desire to emphasize is that certain natural defensive forces of the body do undoubtedly exist by which susceptible persons ultimately become less susceptible, and that by appropriate means these defensive forces may be augmented.

Susceptibility and immunity to poisoning by lead may be considered, according to the type of lead compound absorbed, further in its relation to age and sex. All compounds of lead are not poisonous in the same degree; the more easily soluble compounds are more poisonous than the less soluble. On the other hand, compounds which appear at first sight unlikely to produce poisoning may do so; for instance, fritted lead or lead silicate, a substance largely used in the potteries as a glaze, and manufactured by fusing together litharge and a silicate, would appear at first sight to be quite an innocuous substance. Owing to its method of preparation, however, it is not a pure compound of lead and silica, but contains lead oxide, metallic lead, etc., entangled in its meshes, and experimentally one of us (K. W. G.) has demonstrated that such a compound may be acted on by the tissues of the body, both when injected subcutaneously and even when inhaled, and so gradually produce definite symptoms of lead poisoning, but at a much slower rate than the more poisonous lead compounds. The fineness of division in which the compound of lead exists is another factor affecting its poisonous nature; the more finely divided particles find their way into the lung more easily than the coarser particles. Various subsidiary matters may also determine the susceptibility in a given individual, and of these a certain number require mention, as they probably act as definite predisposing factors. Age and sex may be regarded as predisposing factors to lead poisoning, and certain diseases also.

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Age.

—Young persons are regarded as more liable to lead poisoning than adults, although it is difficult to obtain definite figures on the point, the duration of employment acting as a disturbing factor in estimating the susceptibility of young persons. They may have worked in a lead works for a year or more without showing any signs of poisoning, but develop them later in adult life, although it is very likely that absorption had taken place during the earlier period. In the Report of the Departmental Committee on the Use of Lead in the Potteries (Appendix XII.), the attack rate for the period 1899 to 1909 for young persons is 19·3 per 1,000, and for adults 18·8 for the same period, but the figures upon which these attack rates are based are too small to build any conclusion. The general clinical conclusions of appointed surgeons and certifying surgeons in the various lead factories would be, we believe, that the susceptibility of young persons is at least twice that of adults, and there is some ground for supposing that the tissues of an adult when growth has ceased more readily adapt themselves to deal with the absorption and elimination of poisonous doses of lead than do the tissues of a young person.

Sex.

—Women are more susceptible to poisoning by lead than men, and in lead poisoning from drinking water the proportion of women (especially pregnant women) and children attacked is stated to be higher than in men, and one such epidemic is quoted by Oliver where the rise in the number of miscarriages and premature births led to the discovery of the fact that the water-supply was contaminated with lead. The close relationship of lead poisoning to miscarriage has been repeatedly made out, especially by Oliver, in the white lead industry as carried on twenty years ago. Oliver also quotes the effect upon rabbits[9], Glibert upon guinea-pigs[10], and in the experiments of one of us (K. W. G.), referred to on p. 99, all the animals to which lead was given during pregnancy aborted; and, further, with one exception out of eight animals, all died of lead poisoning, not as the result of the abortion, but some time later, although no further administration of lead was made. This confirms the well-known abortifacient effect of diachylon, and there is no doubt that the lead circulating in the maternal blood determines the abortion. Further, observers who have examined the fœtus in such cases have demonstrated the presence of lead in the fœtus itself. Oliver[11] found that eggs painted with lead nitrate did not[36] hatch out, and on opening the eggs the embryos were found to have reached only a limited stage of development, and to have then died, whereas control eggs painted with lime produced live chicks. From what is stated later with regard to the curious action of lead upon the blood, the mechanism of abortion is easily understood; it is probable that placental hæmorrhages are produced, as in other organs of the body. But the effect of lead on the female is not only apparent during pregnancy. A considerable number of women working in lead processes suffer from amenorrhœa, and often from periods of menorrhagia and dysmenorrhœa, which as a rule is the more striking symptom. The effect of lead on the uterine functions, however, only exists so long as the constant intake of the poison is taking place, and many cases are recorded where women, after having had successive abortions while working in lead factories, have ultimately gone through a normal pregnancy and given birth to a living child. This circumstance bears a strong analogy to the similar train of events in syphilis.

In the Report of the Committee on the Use of Lead in the Potteries, some inquiry was made with regard to the possible association of lead absorption on the male side as a predisposing cause of infant mortality and premature birth. The tables given are not very conclusive, and from our own observations there seems to be very little evidence for supposing that a male lead worker is less likely to beget children, or that his children are more likely to be unhealthy than those of men working in any other industrial process. We are here speaking of the effect of lead under the conditions of its general use in this country now. In the absence of any precautions whatever as to daily absorption of dangerous dust, the effect on the offspring, even in the case of male lead workers, may well be evident, as has been shown by Chyzer[12] in the manufacture of pottery as a home industry in Hungary. One greatly disturbing factor in estimating the greater susceptibility of the female than the male in many lead industries is that the more dangerous work is performed by the women, such, for instance, in the Potteries, as the process of colour-blowing and ware-cleaning.

Predisposing Causes of Lead Poisoning.

—In lead poisoning, as in many other diseases, a number of predisposing and contributory causes may be cited which tend to lower the susceptibility of the individual to the poisonous effect of the metal and[37] its compounds, or to so modify the functions of the body that a smaller dose of poison may produce more profound changes than would otherwise be the case.

Certain diseases may be regarded as predisposing causes by lowering the general resistance of the body tissues to the influence of lead, and a consideration of the chapter on Pathology will at once demonstrate how seriously certain diseases may contribute in this way.

The peculiar effect of lead is upon the blood and the walls of the bloodvessels, and it will therefore follow that any disease which may affect the intima of the bloodvessels may predispose to lead poisoning; and, further, as the elimination of lead takes place to a certain extent through the kidney, any disease which affects either the renal epithelium or the general maintenance of the excretory function of the kidney may predispose that organ to the irritative effects of the lead circulating in the blood. In the same way, the condition of lead absorption in which the balance of absorption and elimination of lead remains in such a ratio that no definite symptoms of lead poisoning appear may have that delicate balance easily upset by the introduction of some secondary cause, which, when operating in association with lead absorption, may precipitate symptoms attributable to poisoning by that metal. Chronic alcoholism especially, producing as it does definite changes in the kidney of itself—changes which it is impossible to distinguish by the naked eye from the effects of lead poisoning—must clearly act as a predisposing, if not even an exciting, cause of lead kidney infection. In experiments upon animals, it was found that the addition of alcohol to the diet of an animal which was the subject of chronic lead absorption precipitated the attack of definite poisoning; in other words, the latent period of lead poisoning—that is to say, the resistance exhibited by the tissues to the toxic influence of lead—was considerably diminished by this addition of a second irritant, alcohol. In several experiments, also, where the form of lead experimented with was one of the least toxic of the lead compounds, the animals subjected to such a compound alone did not become poisoned, but succumbed if alcohol were added to their diet. This experimental work is amply borne out by the clinical evidence of all persons who have had experience of industrial lead poisoning, as cases of colic and wrist-drop are frequently observed in lead workers shortly after alcoholic[38] excesses. Individuals, therefore, who are suspected of the alcoholic habit should not be employed in any process where they are likely to run risk of absorption of lead dust.

Such diseases as syphilis and gout, by causing a heightened arterial tension or definite disease of the intima of the bloodvessels themselves, tend to weaken the arteries in much the same manner as does lead circulating in the blood, and must on that account act as predisposing causes.

In persons employed in lead trades some species of tolerance is generally developed, and if the functions of the body progress in the normal way the balance of elimination and absorption are equal, and, as will be seen later, the chief channel for the elimination of lead from the body is through the bowel. It follows, therefore, that any disease which tends to produce constipation or chronic inactivity of the normal intestinal functions will also tend to lower the resistance of the individual to lead poisoning.

Of the various types of intestinal disease of a chronic nature—such, for instance, as chronic dysentery, colitis, and the like—little need be said; but the predisposing effect of diseased conditions of the upper portion of the alimentary canal must not be overlooked, more particularly affections of the oral cavity itself. This special type of infection, often included under the term of “oral sepsis,” besides producing anæmia, is also a constant cause of intestinal disturbance, and as such operates as a particular predisposing cause of lead poisoning.

With regard to gout the evidence is not so clear. It was pointed out by Garrod[13] that gout was common among house-painters, and it has been generally stated that lead poisoning predisposes to this complaint. In the opinion of a considerable number of observers, however, gout is by no means common among persons working in white lead factories or lead-smelting works, but there seems to be some reason to suppose that it is somewhat common among those persons employed in the painting trades, but not among those employed in the manufacture of paints and colours. From the experiments carried out by one of us [K. W. G.[13]]. it seems probable that the occurrence of gout among painters may be associated with the use of turpentine, largely employed in the ordinary processes of painting, as this substance in particular is not one that is used by workers in[39] other lead trades, and, from experiments performed on animals, the inhalation of turpentine vapour was found to produce very definite changes both in the kidney and the general metabolism of the body.

Malnutrition.

—Malnutrition is recognized as a predisposing cause of practically all forms of disease, and with a chronic intoxication, such as lead poisoning, malnutrition and starvation, with its attendant depression of all the vital forces of the body, is essentially a predisposing cause of poisoning, so much so that even the fact of commencing work without previously partaking of food may operate directly as a cause of poisoning. It has been found, moreover, experimentally by one of us [K. W. G.[14]] that an animal fed with milk containing lead nitrate did not develop poisoning, though the control animal developed well-marked symptoms of poisoning with a much smaller dose given in water.

Anæmia.

—Anæmia has already been referred to as occurring with great frequency in persons who are absorbing lead, and it usually forms one of the chief factors in the symptom-complex of lead cachexia. As the action of lead is particularly upon the blood and the hæmopoietic organs, diminishing the number of red cells and the amount of hæmoglobin, and impairing the organs from which fresh blood-cells are produced, a disease or state associated with anæmia other than of lead origin acts as a definite predisposing cause in the development of toxic symptoms in a worker in an industrial lead process.

Among the anæmias, two particular types may be referred to as of chief importance. In the first place, chlorosis, the anæmia occurring particularly in young women, is often associated with intestinal stasis. Lead anæmia occurring in a chlorotic person is always more severe than simple lead anæmia. Young persons suffering from chlorosis, therefore, should not be employed in a dangerous lead process until the anæmia has been treated. The second type of anæmia, which, from its frequency, may be also regarded as a predisposing cause of lead poisoning, is chronic secondary septic anæmia. Anæmias of this type, as was pointed out by William Hunter[15], resemble in many points the original idiopathic or Addisonian anæmia, often termed “pernicious anæmia,” and one of us has had occasion to inquire into the curious type of secondary anæmia associated with septic affections of the upper respiratory tract, particularly those related[40] to chronic suppurative affections of the accessory sinuses of the nose, of the gums, of the mucous membrane of the mouth and the throat. The commonest forms of this secondary anæmia are those due to chronic post-nasal discharge, and to chronic infections of the gums and alveolus of the jaws, the latter often classed together under the term “pyorrhœa alveolaris.” This term is an exceedingly clumsy one, indicating a discharge of pus from the gum edges and sockets of the teeth, which are often loose. The disease commences as an infective gingivitis along the edges of the gum, and progresses to rarefying osteitis of the alveolar process, and often of the body of the bone. The affection rarely gives rise to pain, and as a rule the individual is entirely unaware that any chronic suppuration is present, and little or no notice is therefore taken of the disease. Progressive anæmia may thus be set up without any knowledge of its cause, partly by absorption of the actual bacteria and their products through the alveolar bloodvessels, and partly by the fact of the constant swallowing of pus and bacterial products, which set up various forms of chronic gastro-intestinal incompetence. From the discharges of the mouth, and issuing from the gum edges, numerous bacteria have been isolated, and in more recent work one of us [K. W. G.[16]] has succeeded in isolating and identifying certain bacteria as a direct cause of arthritis deformans, a malady occasionally, but without sufficient grounds, ascribed to lead poisoning. Arthritis of various types may occur in persons engaged in lead trades, but in all such cases we have had the opportunity of examining there has been some obvious source of septic infection, and no evidence that the arthritis was due to the action of lead. It is most important to draw the attention of those engaged in the protection of lead workers from the dangers of their occupation to these chronic septic conditions of the mouth, and it may be taken as a general rule that, wherever the blue line makes its appearance along the gums, such gums are in a state of chronic infection, and the appearance of the blue line is merely a secondary effect. It is exceedingly rare to find the blue line in persons with intact gums and clean teeth; and although attention is frequently drawn to the fact that a lead line exists in a person whose teeth are normal, little or no notice is taken of the presence or absence of a suppurative condition of the gum margins. Moreover, such a suppurative condition does not always result in obvious inflammation of the gum edges,[41] and very considerable destruction of the alveolus and the interdental bone may exist without any obvious signs of its presence, unless the case be examined carefully with a fine probe. This particular point has been the subject of experiment by one of us. Animals exposed to the influence of air laden with lead dust never develop a blue line, although all the usual symptoms of lead poisoning make their appearance. When, however, some slight suppurative lesion of the gums was produced by an inoculation into the gum tissue of organisms isolated from a case of infective gingivitis in a human being, the site of inoculation and any suppurative lesion that resulted locally at once allowed the development of a blue line, and it was only in animals so treated that it was possible to produce experimentally the Burtonian line.

There is no doubt that any chronic septic infection may predispose to lead poisoning through the production of a secondary anæmia, and it is therefore inadvisable to pass for work in a lead process of a dangerous nature any persons suffering from an infected condition of the mouth. It follows also that the care of the mouth and gums should be rigorously enforced upon all persons employed in lead trades, as the mere mechanical facilities for the accumulation of débris around the individual teeth tends to increase the quantity of lead dust that may be retained in the mouth. This is gradually rendered soluble and absorbed, through the action of the bacterial acids which are always produced along the gum margins when any entangled food is retained in the interdental spaces.

One further point of importance attaches to the infections of the upper respiratory tract—namely, the constant ingestion of bacteria of a fermentative type. By this means the contents of the stomach may be maintained in a state of hyperacidity, and any small quantities of lead which become swallowed are thereby at once rendered soluble in the intermeal periods.

Of the other types of anæmia which may act as predisposing causes of lead poisoning, little need be said, as they are either associated with other grave symptoms or are rare in this country. But as all forms of anæmia, particularly septic anæmia, malarial fever, etc., are associated with destruction of the blood-cells, the presence of basophile staining granules in the red corpuscles of such persons is a constant feature, and must not be confounded[42] with the basophile staining owing its origin to the effect of lead.

In addition to the diseases mentioned which may be said to predispose to lead poisoning, certain other diseases have been stated to be predisposed to by the action of lead. It is no doubt a fact that where chronic anæmia, wasting, loss of subcutaneous fat, decreased muscular power, and general lowering of the metabolic activity of the body, are produced, an individual so affected may be supposed to be more susceptible to certain infectious diseases, and among these stress has been laid on the alleged association of phthisis with lead absorption. This point is discussed in the next chapter.

In summing up the difficult question of predisposition to lead poisoning, together with the correlated questions of susceptibility and immunity, certain facts may at any rate be clearly stated:

1. Undoubted individual susceptibility and immunity exist with regard to lead poisoning in exactly the same way as individual susceptibility and immunity may be shown to exist towards poisoning by many other metals and drugs. Therefore, given the same opportunities for infection, a person showing early signs of lead absorption may be regarded as susceptible.

2. Females are at least twice, and probably three times, as susceptible to lead poisoning as are males. Much of this susceptibility is determined by the extra stress thrown upon the female generative organs.

3. Certain diseases predispose to lead poisoning mainly by nature of the alterations in metabolism produced—chiefly anæmia.

4. Many persons engaged in lead industries become gradually tolerant of the absorption of lead, and in time resist much larger doses than would have been possible at the commencement of exposure, but in such persons the balance between absorption and excretion upon which that tolerance depends may become easily disturbed by intercurrent disease or sudden increase in absorption.

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REFERENCES.

Classification of notified cases of lead poisoning was carried out on practically the same lines between the years 1900 and 1909, and comparison of the data so collected has interest, in view of their large number—nearly 7,000—in respect of (1) increase or decrease in recorded amount in each one of eighteen classes of industries; (2) severity and number of attack—i.e., whether first, second, third, or chronic; and (3) main symptoms.

Notification was first enjoined by Section 29 of the Factory and Workshop Act, 1895, which subsequently, on consolidation of the Factory Acts, became Section 73 of the Act of 1901. This enactment requires every medical practitioner, attending on, or called in to visit, a patient whom he believes to be suffering from lead poisoning contracted in a factory or workshop, to notify the case forthwith to the Chief Inspector of Factories at the Home Office; and a similar obligation is imposed on the occupier of a factory or workshop to send written notice of every such case to the certifying surgeon and inspector of factories for the district. In form there is close similarity between this section and that requiring notification under the Infectious Diseases (Notification) Act; but whereas the symptoms of these diseases are, within well-recognized limits, precise, in lead poisoning the differential diagnosis has not infrequently to be made from a variety of common ailments—headache, anæmia, rheumatism, abdominal pain; and there is no precise standard of what constitutes lead poisoning.

The notification of the practitioner as a rule gives no information beyond the belief that the case is one of lead poisoning. As a matter of routine the notification is followed up by an inquiry[45] by the certifying surgeon and inspector to see whether regulations already in force have been infringed in the particular work-place or not, and as to how far there may have been contributory negligence on the part of the sufferer. The data supplied on the surgeon’s report form the basis of the tabulation[1]. Brief explanation is wanted of the method adopted in classification. Cases represent all attacks reported within a year, and not previously reported within the preceding twelve months, so as to make the number of persons and cases in a year the same. Where the interval between two reports on the same person was more than twelve months, the fresh attack was again included. The number of such second reports on persons already included in a return numbered 284 (4·2 per cent.), and a portion of these certainly, probably not more than 100, have been included twice or thrice in the total 6,638 cases. Cases in which there was obvious error in diagnosis, or in which the opinion of the certifying surgeon was very strongly against the diagnosis (especially when the report had been made in the first instance by the occupier alone, and not by a medical practitioner), were excluded from the return. These numbered 458 (6·8 per cent.). Others, again, where there was a strong element of doubt, but not to be regarded as more than a difference of opinion between two medical men, were marked doubtful and included. Of these there were 424 (6·3 per cent.).

The classification of industries was designed to represent the way in which the poisoning may be supposed to originate from (a) lead fumes (1 to 4), (b) handling metallic lead (5 and 6), (c) dust from lead compounds (7 to 14), and (d) lead paint (15 to 17). We attach now only slight importance to this attempt to define causation, as it will appear from our survey that we regard almost all cases as the result of inhalation either of fumes or dust.

The reports describe not only the particular attack, but also the general condition of the patient at the time of the attack. Very frequently a combination of symptoms—colic, anæmia, and varying degree of paralysis—are described as present, and when this is the case each one of them has been entered under the appropriate heading. The total number of symptoms, therefore, greatly exceeds the number of cases, but this does not affect the correctness of the estimate of each one as a proportion on the total number reported. The reports do not give detailed[46] information such as can be gained from hospital records. Especially is this the case with the symptoms of paralysis and encephalopathy.

Table III. shows the number of reported cases included in returns for each of the years 1900 to 1909. On the total figures there has been a reduction of 47·7 per cent. In the several industries the salient feature is that the considerable diminution achieved is limited to industries—notably white lead, earthenware and china, litho-transfers, and paints and colours—in which, under regulations or special rules, locally applied exhaust ventilation for the removal of dust, and periodical medical examination of the workers, have been required. Where, owing to the nature of the processes carried on, it has been found impracticable, in the present state of knowledge, to apply local exhaust ventilation, and where periodical examination of the workers is lacking, as in smelting of metals[A] and industries using paint, there has been tendency to increase in the number of cases. In coach-building the increase is in part due to activity in the motor-car industry.

[47]

TABLE III.—NOTIFICATION OF POISONING BY LEAD (under S. 73, 1901), 1900-1909.

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49]

TABLE IV.—ANALYSIS OF REPORTS ON LEAD POISONING BY CERTIFYING SURGEONS FROM JANUARY 1, 1900, TO DECEMBER 31, 1909.

[50]

Table IV. shows the severity of the attacks as stated by the surgeon, the number of attack, and the main symptoms. The personal element enters into the character of the reports, and symptoms which one surgeon might describe as slight another might regard as moderate, or even severe. In general, however, “slight” includes cases of (1) colic without complication, and of comparatively short duration; (2) anæmia in adolescence aggravated by employment; and (3) either of the above with tendency to weakness of the extensors. “Moderate” includes (1) a combination of colic with anæmia; (2) profound anæmia; (3) partial paralysis; and (4) cases in which there is constitutional debility. “Severe” includes (1) marked paralysis; (2) encephalopathic conditions—convulsions, optic neuritis, and mental affections; (3) grave undermining of the constitution associated with paralysis, renal disease, and arterio-sclerosis. The reports are made during the attack, and information is not received of the sequelæ which may supervene, except in the event of a later report as the result of fresh exposure to lead. Number of attack has reference to definite occurrence of disability. Transient attacks which have preceded the disabling condition have been usually disregarded. It was necessary to limit the number of attacks which might be regarded as indicating chronic plumbism, and all those included in Column 10 are either third attacks or cases of chronic lead poisoning. Among the main symptoms, the headings “Gastric,” “Paretic,” “Encephalopathic,” and “Rheumatic or Arthralgic,” represent fairly accurately the relative incidence of these in cases of lead poisoning in this country; those under the headings “Anæmia” and “Headache” are useful in comparing relative incidence on the two sexes, but they occur, probably, much more frequently than the figures would indicate; those under “Tremor” and “Other” are less valuable. Under “Other” are included “Gout,” “Nephritis,” or “Cerebral Hæmorrhage,” so that entry under this head indicates chronic, rather than mild, lead poisoning. The conclusions from the table are easy to draw, as, in general, the feature which causes severity of symptoms to be prominent leaves its mark also on “Number of Attack” and “Main Symptoms.” Thus, in the industries in which severe cases exceed the average (brass, plumbing, printing, file-cutting, tinning, glass-cutting, ship-building, paints used in other industries, and other industries), the chronic nature of the plumbism is markedly above the average, and some severe symptom, usually paralysis, is also above the average. An exception to this rule is china and earthenware, where severity is considerably below the average, but where, among men, the figures for chronic lead poisoning and paralysis are distinctly high. It will be seen, however, that the proportion of slight cases even in this industry is below the average. On the other hand, severity is below the average in smelting, white lead, red lead, litho-transfers, enamelling, electric accumulators, paints and colours, and coach-painting, and the symptoms in these industries are, in general, colic rather than high degree of paralysis; but in them a severe symptom which is above the average, in general, is encephalopathy. The explanation of these differences depends, we believe, on two factors: (1) Duration of employment, with which, naturally, the age of the worker is associated; (2) opportunity of inhaling lead dust. The longer the employment, the more likely, naturally, if absorption goes on, is the plumbism to become chronic, and to be associated with paralysis, its prominent sign. Duration of employment among males in file-cutting and china and earthenware, as contrasted, for instance, with that in white lead, is very much longer, and the same could be shown of comparatively[51] new industries, such as electric accumulators and litho-transfers. Thus, in one year the age distribution and duration of employment of those attacked in three of these industries was as follows:

Persons employed in the manufacture of white and red lead, electric accumulators, paints and colours, and the others named, are exposed essentially to dust from salts of lead, which are readily absorbed. Poisoning, therefore, if precautions are inadequate, will quickly show itself, causing certain workers to seek other employment after one attack. Poisoning thus produced is more likely to induce colic, or, if the dose has been large or the individual markedly susceptible, encephalopathic symptoms, than paralysis. On the other hand, the slowness of the onset of symptoms in the case of brass workers, plumbers, printers, file-cutters, and tinners, is more the result of inhalation of fumes or of dust of metallic lead than of salts of lead; or if the inhalation be of salts of lead, then of these in less amount and over a long period, with, as a result, gradual undermining of the constitution, showing itself in paralysis, arterio-sclerosis, and renal disease. The two factors indicated obviously account for the differences in severity and number of attack between males and females. If second and third attacks are comparatively fewer in females than in males, it follows that, in general, the attack will be less severe also, and this is brought out in the figures. Cerebral symptoms—encephalopathy, to which headache may be added—are more than twice as frequent in females as males. This may be due to idiosyncrasy, but it may very possibly be simply the result of short duration of employment of young workers in processes where dust of salts of lead is incidental.

Attacks generally are most frequent in the first or second year of employment. Thus, of 2,195 attacks reported in the four years 1904 to 1907, as to which sufficient data are given, 898[52] occurred in the first two years of employment, and of these 672 occurred in the first year—that is, three-sevenths of all the cases were reported during the first two years, and four-sevenths in the whole of the remaining years of employment. It is, unfortunately, impossible to say what is the proportion of attacks among those employed for any given age period. In some factories—as, for example, lead smelting works—the average duration of employment is about thirteen years. The length of employment preceding an attack was made out from reports on cases which occurred in the white lead industry in 1898—a time when a number of new workers were taken on to replace the female labour abolished in June of that year, and conditions as regards removal of dust were entirely different from what they are now. The figures, therefore, can only be considered to have bearing upon incidence under almost the worst possible circumstances. Of 155 attacks, duration of employment was stated to have been less than 1 week in 3, from 1 week to 1 month in 8, from 1 to 3 months in 62, from 3 to 6 months in 44, from 6 to 12 months in 12, and 1 year and over in 26.

Attempt has been made to discredit the value of Section 73 of the Factory Act, 1901, on the ground that the proportion of cases in which some degree of paralysis is present is very high as compared with the extent found by other observers. The points we have laid stress on—(1) duration of employment, (2) varying kinds and amounts of lead dust and fumes—are, we believe, quite sufficient to account for, and give value to, the figures dealt with. To them should be added another factor, though one of less account—namely, the extent to which particular muscles are used. In the case of file-cutters, for instance, there is no doubt that the cramped position of the left hand holding the chisel, and the work thrown on the right in holding the heavy mallet, determine the direction of the paralysis, especially on to the muscles of the thenar and hyperthenar eminences and of the fingers.

There is, however, difficulty in deciding whether such entries on reports as “weakness of arms and legs,” “weakness of arms,” “muscular weakness,” etc., should be interpreted as incipient paralysis.[A] With a disease like lead poisoning showing[53] marked tendency to affect the muscles supplied by the musculo-spiral and other nerves, the only safe course was to include all these terms as equivalent to partial paralysis. Table V. on p. 54 shows close parallelism for the six years.

If it is difficult to distinguish rightly all the cases classed as “paralysis,” it is even more difficult to determine what should be included under the term “encephalopathy.” We have limited it to epileptiform seizures, optic neuritis (uncomplicated by epilepsy), and various forms of insanity. Table VI. on p. 54 is interesting as showing how fairly constant the numbers are from one year to another.

Except in the one industry of earthenware and china, in which a return of the number of persons employed according to process and kind of ware has been made on three separate occasions, and in which the reports of the certifying surgeons enable the cases of poisoning to be classified in the same way, it is difficult to determine accurately the attack rate of lead poisoning. Even in the earthenware and china trade many things have to be borne in mind. The poisoning which occurs is not distributed evenly over all the factories. Thus, among the 550 potteries, in the years 1904 to 1908, five potteries were responsible for 75 cases, and 173 for the total number of cases (517), leaving 377 factories from which no cases were reported.

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Table V.—Forms of Paralysis: 1904-1909.

Table VI.—Encephalopathy.

The same state of things is found in all the other industries. Particular factories, owing to special method of manufacture or special manner of working, may have an incidence out of all proportion to that prevailing in the trade generally. And it is, of course, control of these more obvious sources of danger by the efforts of manufacturers and the factory inspectors that[55] has led to the notable reduction recorded—e.g., in white lead works and the pottery industry.

Returns of occupiers do not lend themselves readily to exact estimate of the number of persons exposed to risk of lead poisoning, as they do not differentiate the processes, and in nearly all factories in which lead is used some of those returned will not come into contact with it.

In industries, however, in which there is periodic medical examination of persons employed in lead processes an attack rate can be made out. It must be regarded as approximate only, as in the manufacture of electric accumulators, for instance, medical examination is limited to persons employed in pasting, casting, lead-burning, or any work involving contact with dry compounds of lead, whereas the reported attacks include a few persons engaged in processes other than those named.

Table VII.—Attack Rate from Lead Poisoning in the Year 1910 in Certain Industries.

As has been mentioned above, the accurate information we have of the numbers employed in the several processes in the earthenware and china industry enable us to use the figures for that industry to illustrate, what is certainly true of all other lead industries also, the fact of the relative greater degree of risk in one process than another.

The fall in the number of fatal cases attributed to lead poisoning, as is perhaps to be expected, seeing that the great majority are deaths from chronic lead poisoning, does not run parallel with the diminution in the number of cases. Thus, in the five years 1905 to 1909 the deaths numbered 144, as compared with 131 in the previous five years, although the cases fell from 3,761 to 3,001. We believe this is due to an increasing inclination to[56] attribute chronic nephritis, and even (without sufficient justification in our opinion) phthisis and pneumonia, to lead poisoning on the death certificates of lead workers. Copies of all death certificates on which lead poisoning is entered as directly or indirectly a cause are received by the Chief Inspector of Factories. All of industrial origin are included in the return. Of a total of 264 which could be followed up, encephalopathic symptoms appeared on the death certificate in 38 (10·6 per cent.); Bright’s disease, cerebral hæmorrhage, paralysis, or chronic lead poisoning either alone or as a combination of symptoms closely connected, in 188 (71·2 per cent.); phthisis in 13 (5·0 per cent.); and other diseases, such as pneumonia, etc., in 25 (9·4 per cent.). Table IX. brings out the relative frequency in the several groups of industries, and, as is to be anticipated, the different average age at death when due to acute and chronic lead poisoning.

TABLE VIII.—LEAD POISONING IN EARTHENWARE AND CHINA WORKS

(China, Earthenware, Tiles, Majolica, Jet and Rockingham, China Furniture and Electrical Fittings, Sanitary Ware).

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The statistical evidence from death certificates published in the decennial supplements of the Superintendent of Statistics[2] is of significance, not only in enabling comparison to be made between one industry and another, in regard to mortality from lead poisoning, but also in determining the other causes of death most frequently entered on death certificates of lead workers, and therefore, if they are in high excess, as compared with male workers generally, they are to be ascribed with some degree of certainty to deleterious effects of lead on some of the principal organs. Thus, in Table X. a list of occupations is given in which the mortality from plumbism in the years 1900 to 1902 was double or more than double the standard. It represents the mortality which would occur if the male population in the particular industry had exactly the same age population as that of “all males.” Further, the annual mortality among “all males” is taken as 1,000, and that of males engaged in the several industries is stated as a proportion of this. This “mortality figure” of 1,000 is made up of the mortality from various causes (of which only those considered to bear upon lead poisoning are given in the table) in the proportion stated.

The contention that, because lead workers die from certain diseases more frequently than “all males,” such diseases must be the sequelæ of lead poisoning is untenable unless other recognized causes of the diseases in question have been excluded. For excess of deaths from phthisis and respiratory diseases the conditions of work and exposure to inhalation of mineral and metallic dust or vitiation of atmosphere, in pottery, spelter, printing works, and file-cutting workshops, sufficiently account. The figures, indeed, take no account of this, and their value, in some at any rate, is still further diminished by the very large number of occupations (several involving no contact at all with lead) included in the headings. With exception of the strikingly greater proportion of deaths among lead-workers from Bright’s disease, the figures are too contradictory to draw deductions from as to what are “sequelæ” of lead poisoning. But this figure—160, as compared with 35 for all males—is confirmatory evidence, if any were needed, that chronic Bright’s disease is a sequela. And, from the pathology of lead poisoning, we believe that the granular condition of the kidney is due to the sclerotic change brought about in its substance by microscopic hæmorrhages. We have very little evidence indeed in man that this interstitial change is set up or preceded by an acute tubal nephritis. While we do not deny that there may be some parenchymatous change associated with lead poisoning, we do not believe that it is of the kind which gives rise to the large white kidney, and we should therefore exclude such disease as a sequela. But if chronic Bright’s disease is admitted, the train of symptoms associated with it—notably arterio-sclerotic changes resulting in cerebral hæmorrhage and albuminuric retinitis—must be admitted also. Unless it were established that granular nephritis were present in a lead-worker before commencement of lead employment, we think it would be useless to endeavour to prove that the condition was independent of lead, despite its comparative frequency as a cause of death apart from employment.

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TABLE IX.—MAIN SYMPTOMS APPEARING AS THE CAUSE IN 264 DEATH CERTIFICATES OF LEAD POISONING.

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TABLE X.—COMPARATIVE MORTALITY FROM SPECIFIED CAUSES AMONG MALES ENGAGED IN CERTAIN OCCUPATIONS: 1900-1902.

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Other conditions which might readily be admitted as sequelæ are optic neuritis, following on an attack of encephalopathy. No general statement can be made in regard to mental and nervous diseases, gout, pernicious anæmia, as sequelæ, as each must be considered in relation to the evidence adduced in the particular case, and after exclusion, in the first two, of syphilis as a cause.

The distinction between causation and association has to be borne in mind before admitting as sequelæ of lead poisoning diseases of bacterial origin, such as phthisis or pneumonia, or any disease to which the affected person may be thought to have been rendered more prone by reason of lead employment. The contention that a person may have been debilitated by lead poisoning is no proof that the enfeeblement of the constitution was the cause either of the bacillus gaining entrance into the lung or of the ultimate fatal issue from the engrafted disease. Such assertion in every case must rest on supposition. Evidence that lead employment predisposes to phthisis is not necessarily made[61] stronger, in our opinion, by existence during life of clinical symptoms, or, in their absence, of detection of lead in the tissues post mortem.

In classifying causes of death, the general rule should be to select, from the several diseases mentioned in the certificate, the disease of the longest duration. Exceptions to this rule are that definite diseases ordinarily known as constitutional diseases should have preference over the other diseases mentioned. After thirty-five years of age, certificates of death from lead poisoning are almost always filled in in association with other diseases which are the usual causes which lead to mortality generally. But neither phthisis, nor pneumonia, nor any acute disease of the heart or lungs, nor valvular disease of the heart, nor, indeed, any acute febrile condition, can have direct relation with—i.e., be a sequela of—lead poisoning.

REFERENCES.

The pathology of lead poisoning has formed the subject of scientific inquiry from the time that the association of certain pathological symptoms was definitely correlated with poisoning by means of the metal or its salts.

Acute poisoning, due to accidental swallowing of large doses of lead salts or to use of lead salts criminally, generally produces a train of symptoms different from those met with in chronic industrial poisoning. But it is difficult to understand why so many writers upon the subject of lead poisoning should have attempted to draw a hard-and-fast line between the pathological symptoms in acute and chronic poisoning. This is especially the case when the after-history of cases of acute poisoning is traced, for in a large number of instances a case of acute poisoning drifts on into a subacute, and finally a chronic, stage. All the symptoms of paralysis, encephalopathy, and even kidney degeneration, have been described in persons who were first of all the subjects of acute poisoning.

The direct effect of a lead salt, such as the acetate, upon the mucous membrane of the stomach, is a caustic one, and the attention of observers seems to have been focussed on what is really a secondary effect of the lead salt, and not one intrinsically associated with actual poisoning by the metal itself.

A good deal of experimental work has also been performed in one way or another—mainly by feeding with, or inoculation of, considerable quantities of soluble lead salts—but, with one or two notable exceptions, such experiments have not carried the knowledge of the true pathology of lead poisoning very much farther. The statement is not uncommonly made that no definite correlation exists between the symptoms observed in animals and those observed in man, the reason being that the[63] massive doses given to animals cannot be similar to, nor can they produce results comparable with, the slow intoxication taking place in man; although the after-history of the majority of cases of acute poisoning shows that the symptoms suffered are generally identical with the severer symptoms seen in cases of chronic poisoning of industrial origin. One of the chief reasons explaining this remarkable point of view arises from the fact that the tissues which come into the hands of the pathologist for post-mortem and histological examination are as a rule derived from cases of chronic poisoning, cases in which the acute symptoms have drifted into the subacute or chronic stage, when any minute changes existing in the initial stages of the poisoning have long since disappeared, or their significance has been so far obscured by secondary changes that the primary lesions are lost sight of.

A critical examination of the very large amount of literature published on lead poisoning negatives the idea that acute and chronic poisoning differ fundamentally in their pathology, and observers are found describing identical pathological lesions resulting from acute or chronic industrial poisoning. It is impossible to review the whole of the existing literature. Kobert[1], in summing up the general effect of lead upon the animal body, makes the following general statement: “Lead affects especially the striped and unstriped muscles, the epithelium of the excretory glands, the neuroglia of the central nervous system, and is essentially a protoplasmic poison.”

We base our knowledge on definite experiments, so arranged that the method of exposure was in every way similar to that in lead industries. The only point of difference that can be urged against them is one of degree; but as the train of symptoms produced was in every way comparable with those suffered by man, this objection cannot be sustained. The fact that the symptoms develop in a shorter time than they do in industrial processes is merely a function of the intensity of the poisoning.

An attempt will be made first to summarize the literature on the pathology of lead poisoning, and, as such literature covers an immense amount of ground, to group the pathological findings of various observers, as far as possible, under four main headings—namely:

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Gastro-Intestinal.

—As the chief early symptom of all types of chronic poisoning is abdominal colic, early investigators turned their attention to the pathology in this region, and ascribed the colic to various causes.

Oliver[2] noted that, in animals poisoned with lead, the intestine was found to be irregularly contracted, and ascribed the pain in abdominal colic to the irregular contraction of the intestines themselves, supposing that the effect of lead was on the muscular tissues. He also noted the presence in the intestine, both large and small, of staining due to lead, and the considerable amount of lead to be found in the large intestine. We have only met with staining by lead in the large intestine.

Dixon Mann[3] pointed out that the fæces contain two-thirds of the amount of lead taken by the mouth in experimental cases, and considered that the lead was re-excreted into the intestine; and a number of other observers hold this view. Recent work confirms the supposition, and there is no doubt that lead is eliminated in this way.

Stockvis[4] has occasionally seen small ulcers or abrasions in the small intestine; these he thinks may be due to small hæmorrhages.

Ménétrier[5], quoted by Meillère, describes a form of glandular atrophy of the stomach which is met with in chronic lead poisoning. He states that the alcoholic gastritis generally present in persons the subject of saturnine gastritis renders the differentiation exceedingly difficult. This observer is also in complete agreement with many others who associate much of the chronic lead poisoning to association with alcoholic intemperance. The particular type of gastric degeneration Ménétrier regards as due to the effect of lead is “une sclérose regulière, inter-tubulaire, se recontrant d’une manière diffuse et générale dans le muqueuse gastrique.”

He further considers that this gastric sclerosis occurs earlier than the disease of the kidneys.

Kussmaul and Meyer[6] describe a chronic intestinal catarrh with chronic degenerative changes in the intestinal mucosa very similar to the changes described by Ménétrier.

Tanquerel[7] inclined to the view that the colic was not associated with spasm of the intestines, and states that no clinical evidence could be found of intestinal spasm by rectal examination during a spasm of colic. But, as Bernard[8] points out, intestinal spasm may occur with “ballonment” of the rectum.

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Another cause of colic is suggested by Bokai[9]—namely, hypersensibility of the intestinal nerves—and he cites as evidence the diminution in pain produced by the administration of morphine; and it is not improbable that some hypersensibility of the nervous system of the intestine goes hand in hand with the vaso-constriction that has been shown to exist, while, in addition, many observers have found degenerative and even subacute inflammatory changes in the sympathetic nervous system of the abdomen, mainly in the splanchnic area and the solar ganglion. The action of vaso-dilator drugs on the pain of colic demonstrates the close association of vaso-motor changes with the acute paroxysmal pain.

Riegels[10] investigated the cause of colic in 200 cases. He found that in every instance there was reason to suppose that toxic vaso-constriction of the vessels in the splanchnic area, due to irritation in the vaso-constrictor nerves, was brought about by the action of lead.

Definite gastritis has also been described in some way simulating that caused by arsenic, with thickening in the submucosa of the stomach and intestine. Associated with this enteritis is endarteritis, atrophy of the glands, and Lieberkühn’s follicles. In the colon as well as the ileum was a well-marked enteritis involving the muscular lesions of the gut.

Various other authors describe degenerative processes with cirrhotic changes in the gastro-intestinal tract. Amongst these, Galvini[11] describes, in a case of death from very chronic lead poisoning, extreme cachexia, perihepatitis, perisplenitis, atrophy of the stomach, liver, and spleen, and chronic sclerosing peritonitis (saturnine peritonitis). Associated with general changes in the abdominal cavity, marked inflammation and sclerosis was found in the solar plexus. There is said to be a very considerable correspondence between the condition of the peritoneal cavity and its contents in lead poisoning and barium poisoning. In some of the animals referred to in the description of the experiments, marked inflammatory conditions of the small intestines and colon were found, and in not a few instances definite ulceration and signs of recent hæmorrhages were found scattered along the intestinal tract. No sclerosis was found, however, in the peritoneal cavity, though a common symptom of all the animals, whether poisoned by inhalation, inoculation, or feeding, was the absence of practically all fat from the peritoneal cavity, the[66] omentum being represented by an exceedingly thin membrane without any traces of fat whatever.

Nervous System.

—Perhaps the oldest classical symptom of lead poisoning is the potter’s palsy or wrist-drop due to interference with the nerve-supply of the extensor muscles of the hand, leading to inability to extend the wrist or the fingers on the arm, wasting of the affected extensor muscles, and finally a claw-shaped hand due to contractions produced by the pull of the unopposed flexor groups.

The origin of this extensor paralysis has been the subject of much controversy. One party regards the lesion as of central origin, affecting the upper motor neurons or their connections in the spinal cord; the other takes the view that paralysis is mainly of a peripheral type. Tanquerel[12], whose classical work on lead poisoning still contains one of the best descriptions of the disease from the clinical standpoint, describes an associated affection of the peripheral sensory nerves resulting in definite anæsthesia and hyperæsthesia, and there is no doubt that sensory nerve affection, although not very common in lead poisoning, does occur occasionally, and is due to peripheral affection of the nerves. Occasionally generalized peripheral neuritis is to be met with, but even this is much less common than in alcoholism or other toxic forms of peripheral neuritis.

In the opinion of most of the observers who regard the neuritis as of peripheral origin, the ultimate interference with the motor nerves is due to an ascending neuritis of the peripheral nerves affecting the spinal ganglia, and Pal and Mannaberg[13] have described polyneuritis; whilst Westphal[14], Dejerine[15], Eichhorst[16], Ramond[17], and others, support particularly the primary lesion of the peripheral nerves as the cause of the disease. Marie and Babinski[18] in 1894 evolved the central theory, and supported it by reference to the apparent bilateral occurrence of the paresis and the analogy with many examples of polymyelitis. Vulpian and Steiglitz[19], examining cords of animals poisoned by lead, described vacuolation of the cells in the anterior cornua of the cord.

The original suggestion of the spinal origin of the disease was enunciated by Erb[20], who, without particular reference to either the electrical or histological changes to be found in lead poisoning, based his theory on the similarity of the lesions to polymyelitis.[67] A few cords of persons who have died of lead poisoning do show slight changes in the anterior cornua.

One other theory of the nerve affections in plumbism is that advanced first of all by Hitzig[21], and later by Boerwinkel[22] and Eichhorst[23], who regard the initial disease as one related to the circulation, and not necessarily to the nerve lesions themselves. Potain[24], basing his observations on the anatomical distribution of the blood vessels, points out that the flexor muscles, excluding the supinator longus, are drained by the median cephalic vein, whilst the extensors are drained by the interosseous—a peculiarity of considerable importance, as the supinator longus escapes paralysis in the majority of cases of wrist-drop.

The presence of paralysis in the muscles and the association of nerve lesions to muscular paralysis led investigators to examine the nervous system, and probably more attention has been paid to the pathology of poisoning in this direction than in any other. Many records of isolated cases are to be found in the literature of the subject, and the examination of the spinal cord has been carried out in many instances; several have been cases of generalized paralysis or dementia, with involvement of the trunk muscles as well as those of the extremities in the paresis.

Many observers who have made histological examinations in such cases have found nuclear changes in the anterior columns of the cord suggesting polymyelitis. A small number only of the total cases of paresis, however, come under this heading. Vulpian[25], Oppenheimer[26], Oeller[27], and others, described degenerative and proliferative changes in the grey matter of the cord. Steiglitz[28] by animal experiments produced inflammatory processes in the anterior grey substance, vacuolations in the ganglion cells, and degeneration in the anterior root ganglia. In the paralyzed muscles the changes of degeneration are found: the muscle nuclei become spindle-shaped, the interstitial tissue undergoes degeneration, the muscle becomes atrophied, takes the stain badly, shows irregular striation, and the muscle bundles become ill-defined and fused.

Scarcely any two observers are agreed as to the exact nerve lesions which are to be found, and so at variance are the various theories based upon the pathological findings that it is by no means uncommon to find two sets of observers quoting the same electrical reactions and histological appearances as proving in[68] the one case peripheral, and in the other the central, origin of the paralysis. On the other hand, in the quite early observations of Hitzig[29] particular attention was called to the bloodvessels and their possible association with the disease. Moreover, as has been already cited, ancient physicians were in the habit of making use of lead as a styptic and hæmostatic because of its peculiar action on the blood.

Probably as a result of improved histological methods of examining the nervous tissue, renewed attention was given to the nerve fibres and nerve cells, with the result that, in the very large number of observations recorded, many different nerve lesions are described as the sequelæ of lead intoxication.

On the other hand, Hitzig’s observations on the associated inflammation of the bloodvessels has received confirmation by several independent workers. Westphal[30] cites a case of chronic lead poisoning resulting in death from encephalopathy, and describes degeneration and œdema of the brain following a process of chronic inflammation in the smallest and minute bloodvessels, and also associated with degeneration of the ganglion cells in the vicinity. Chvostek[31] also publishes a similar case where cerebral degeneration and some œdema had occurred. Kolisko[32], in examining the brain of a girl who had died of encephalopathy, found chronic œdema of the brain and spinal cord, the condition closely resembling that described by Hitzig as chronic cerebral hypertrophy.

Quensel[33], in a man who had died of encephalopathy, found leptomeningitis, atrophy of the cortex with degeneration of the parenchymatous elements of the cells and nerve fibres, degenerative changes in the vessels, nuclear destruction and pigmentation of the cells, and œdema. Nissl[34] described granules, which bear his name, present in the ganglion cells in the cortex, with parenchymatous degeneration. These cases were not associated with paralysis, nor is encephalopathy by any means always complicated with paralysis of muscles.

Berchthold[35] describes a case of typical spastic paraplegia due to lead, and states that the cortical neurons were but little damaged, the weight of the poison having fallen upon the peripheral segments.

Sorgo[36] describes a case of progressive spinal muscular atrophy traced to lead, in which degeneration of the spinal cord was a marked feature.

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Steiglitz[37], in describing the inflammatory processes produced in animals poisoned by lead, makes special mention of a distinct minute inflammatory change in the grey matter of the brain, with vacuolation occurring in the ganglion cells in the anterior horns of the spinal cord. Prévost and Binet[38], on the other hand, describe an inflammation of the peripheral nerves occurring after administration of lead to rabbits for one month. They produced what they describe as “a lead polyneuritis,” with primary affection of the motor nerves. With the brain, as with other parts of the body, various writers describe widely differing changes. Experimentally, when the doses have been massive and the animals rapidly poisoned, very little has been found, and some regard this as evidence against the central origin of lead paresis. On the other hand, in cases of chronic poisoning (mainly chronic industrial poisoning), where an opportunity of post-mortem examination has been afforded, marked atrophic changes have been discovered both in the brain and spinal cord, in the motor nerves supplying the affected muscles, and throughout the nervous system generally, so much so that anterior polymyelitis of old origin is described, vacuolation and degeneration of the ganglion cells, and various other pathological changes associated with nerve degeneration.

On reviewing the literature, it becomes practically certain that in the old and advanced cases of poisoning lesions are invariably found in the central nervous system, while in the less advanced cases the most marked change has been found in the peripheral nerves. In only a very few instances have any observers noted the fact of hæmorrhages occurring in the nervous tissues, and one of the most important observations on this point is the careful description by Mott[39], of a fatal case of lead poisoning in an asylum, in which distinct yielding of the vessel walls with minute hæmorrhages was present in the cerebral cortex. This case is quoted in full on p. 71.

In the record of the experiments by one of us (K. W. G.) on p. 95 are described the hæmorrhages occurring in the anterior crural nerves of cats poisoned by lead. These animals showed most distinct loss of power in their hind-limbs, as was evidenced by their inability to jump, and other symptoms homologous to wrist-drop in man. In these animals no nerve degeneration or alteration in the spinal cord was found sufficiently gross to account for the paralysis, whereas the amount of pressure produced[70] by the yielding of the vessel walls on the nerve bundles and the associated exudation was evidently sufficient to cause compression, and thereby loss of function in the nerve in question.

Now, the pathological changes described by numerous observers, such as parenchymatous and interstitial changes in the brain, destruction of the anterior grey matter, and, finally, the degenerative changes in the muscle groups, the macroscopical and microscopical atrophy of the muscle bundles with the fibrillation and other changes, are none of them opposed to the view that hæmorrhage and exudation are the earliest and initial change; in fact, in experimental animals minute hæmorrhages could always be traced in the earliest stages of poisoning, frequently before definite symptoms appeared.

Confirmation of this theory is seen in the work of Glibert[40], and the drawings he gives showing fibrous changes in the lungs, hyperplasia, congestion, and emphysema, cirrhotic conditions of the liver, and, as he describes it, blood-stasis caused by elongation and dilatation of the capillaries, are all of them highly confirmatory of the hæmorrhage theory. Further confirmation is also afforded by the observations on the action of lead salts upon the blood itself. From the earliest days lead has been used as a styptic, and its empirical use has been shown by later observation to be due to its power of readily coagulating albumin and peptone. Further, in chronic lead poisoning there is a marked increase in the coagulation time of the blood. Glibert, in the work already referred to, points out the increased ductility of the red blood-cells in lead poisoning. Quite apart from this, there is no doubt that definite alterations in the red blood-cells occur; a species of icterus is common in lead poisoning, the anæmia of lead poisoning is of a destructive type, increased urobilin may occur in the urine, and in some instances hæmatoporphyrin is present in considerable quantities. The bone-marrow in cases of lead poisoning undergoes distinct inflammatory change, and may possibly be the cause of some of the curious aching arthralgias often noted as a clinical symptom. All the pathological evidence that can be adduced points unmistakably to the blood as suffering the initial stress in lead poisoning, and it is therefore by no means surprising that the blood vessels should be the next in order to undergo degenerative changes. It is probably this degenerative change, particularly associated with the increased coagulability, alteration[71] in viscosity, the destruction of the blood-cells themselves, and the permeation of the vessel walls by definite, if exceedingly minute, quantities of lead salts, that determines the yielding of the smaller and generally the weaker bloodvessels. In the histological examination of the experimental animals there was considerable evidence that the venules, rather than the arterioles, are the first to yield.

The following case of chronic lead encephalitis, with the examination of the nervous system described by Mott[41], is a case that has a large bearing on the general pathology of lead poisoning, and has the merit of being so carefully described that we cite it at length, as bringing out some of the special features connected with the pathology of lead poisoning.

Excretory System.

—A large number of observers have shown that great stress is thrown on the kidney in the excretion of lead. Discussion has taken place as to whether the effect is a primary interstitial or a parenchymatous nephritis. Most observers are agreed that the histological changes found in the kidneys of lead workers have very little by which they may be differentiated from the effects of alcohol.

Although the kidney suffers directly from the effect of circulating lead, the amount of lead excreted by the kidney in chronic cases is usually small, variable in quantity, and very rarely exceeds more than 5 milligrammes in the twenty-four hours.

The chemical estimations of the quantity of lead found in the kidney of persons who have died of lead poisoning given by different observers, vary exceedingly. Even in cases of definite lead poisoning, where there can be no reasonable doubt as to[73] the diagnosis, many cases are on record where no lead at all has been discovered in the kidney.

It is not acute nephritis which is seen in lead poisoning, but the chronic cirrhotic variety. This probably takes a very long time to develop; indeed, animals kept under the influence of lead for two years show very little kidney destruction. It is quite possible that in the kidney disease met with in lead-workers the combined effect of alcohol with lead is really the causative factor. There is not sufficient statistical evidence to make a definite statement on this point, and it would only be possible by comparing the records of the autopsies of a number of persons working in lead who do not die from lead poisoning, and who were non-alcoholic, with a similar number of persons who, in addition to their lead absorption, were alcoholic subjects.

It is unusual to find blood in the urine, and the condition of the kidney does not suggest that it would be present.

Gull and Sutton[42] have described arterio-capillary fibrosis in which the intima of the larger vessels became greatly hypertrophied, and many of the smaller vessels are practically destroyed by obliterative arteritis. The production of arterio-sclerosis, with attendant thickening of the vessel walls and with the various symptoms commonly associated with arterio-sclerosis, were regarded as secondary symptoms of lead poisoning. The action of lead on the vessel walls themselves thus independently proved by a large number of observers working at different aspects of the problem suggests the pathological change in the vessels as the common element in the cause of these diverse symptoms of lead poisoning—colic, paralysis, mania. Generally speaking, however, the attention of most has been rather focussed on the kidney and the degenerative changes occurring in that organ due to the irritative action of lead in the process of excretion than on the vessels themselves.

Lead in the urine is by no means so common nor so definite a symptom of lead poisoning as might be supposed, considering the extreme manner in which the kidneys suffer in old-standing cases. Of particular importance in this respect is the case referred to by Zinn[43], where a woman aged thirty-three received 20 grammes of lead acetate in error. After the first acute symptoms had passed off, the case drifted on to one of chronic poisoning, with the usual symptoms of colic, anæmia, and cachexia. During the whole period of the disease, both acute and chronic[74] stages, examinations of the urine for lead were made, using the method of Fresenius Babo[44]; yet lead was only detected in the urine during the early stages, and directly the acute symptoms had passed off no further lead could be detected. This point is of some importance, particularly when taken together with the experiments quoted by Blum[45], who, injecting animals with lead iodide, was unable to recover lead from the urine. The iodide only passed through the kidney, the lead being retained in the body.

Jaksch[46] states very definitely that lead is not found in the urine in chronic cases, but only in the acute cases, and then quite early.

With regard to the kidney two views are held—the one regarding the disease of the kidney as primarily affecting the bloodvessels, and the other as an initial parenchymatous change causing secondary obstruction and alteration in the vessels themselves. There is therefore much evidence to show that, whether the bloodvessels be primarily or secondarily affected, almost all observers are in accord in the opinion that at one time or another, either sooner or later, the bloodvessels become affected through the action of lead.

Kobert[47] points out that in no case was distinct cirrhosis of the kidney produced in experimental lead poisoning in animals; inflammation certainly was to be seen, either interstitial or parenchymatous, but apparently the poisoning had not progressed a sufficient length of time for definite cirrhosis to be produced. On the other hand, kidney changes have been found of various types, all of which may be the precursors of the ultimate cirrhotic and fibroid change occurring in the kidneys seen in chronic poisoning by lead as well as in chronic alcoholism. Particular stress must be laid on the fact that cirrhotic kidneys are so frequently the direct result of long-continued alcoholic excess, and, from what has been demonstrated in the experimental researches on predisposition to lead caused by alcohol, the condition of cirrhosis of the kidney in a lead-worker is by no means indicative of lead poisoning, as it may be an old alcoholic effect long antedating that due to lead.

Oliver[48], Charcot[49], Gombault[50], Hoffer[51], and others, found a certain amount of parenchymatous degeneration. Von Leyden[52], however, was able to produce a granular condition of the kidney with glomeruli shrunken and an arterio-capillary[75] fibrosis. Gayler[53], on the other hand, thinks that the arteritis of the smallest arteries is the preliminary effect upon the kidney, whereas more recently Glibert[54] published plates of the kidney showing definite sclerosis as well as interstitial nephritis.

Cornil[55] and Brault[56] think the vessels are affected only secondarily, and that parenchymatous changes are the primary lesion. Hoffer[57], by feeding guinea-pigs with lead, produced very definite obliterative arteritis. Klemperer[58] claims to have produced inflammation and definite necrosis of portions of the kidney substance.

The whole of the kidney is not necessarily affected. Only portions of it may show changes, while Kleinenberger[59] notes that in chronic lead poisoning, at the time of acute exacerbation of the disease, granular casts as well as red blood-cells are found; and, further, that in cutting through them crystallized masses are occasionally found, consisting of urates, and sometimes containing lead.

Gayler[60] considers that the effect on the kidney commences in the muscular coats of the smaller vessels, in which endarteritis followed by obliterative arteritis is set up.

Practically all observers, therefore, are in agreement that the kidney suffers to a very considerable extent in chronic poisoning, and the majority of observers are also in agreement that the bloodvessels themselves are the primary seat of the change. Further, the presence of blood in the urine is exceedingly rare in chronic lead poisoning, despite Kleinenberger’s[61] statement to the contrary. It certainly may occur during a very acute attack, but we have never seen this symptom.

Circulatory System.

—Arterio-sclerosis occurring in lead-workers has been known for some time, and the anæmia of saturnism has been known for an even longer period. For some time no definite type of anæmia was associated with lead cachexia, and the anæmia was generally regarded as one arising from general malnutrition. Here and there through the literature of the pathology of lead poisoning are to be found remarks which suggest that the action upon the bloodvessels may be a primary instead of a secondary effect. Obliterative arteritis is described by Uhthoff[62], Pflueger[63], Oeller[64], and Pal[65], and in other cases obliterative retinitis has been considered to be associated with the action of the lead upon the vessel walls.

Heubel[66], and later Rosenstein[67], found that, in dogs[76] poisoned with lead, definite cerebral anæmia was produced, due to vaso-constriction, and consider it to be due to the direct action of lead upon the intima of the vessel walls. Associated with such poisoning were symptoms of eclampsia and uræmia, and the latter author considers that the uræmia is due to vaso-constriction of the kidney vessels.

Oliver[68] and others have also pointed out the alteration in the pulse-rate associated with exacerbations of colic, and a number of observers have noted that certain drugs, such as atropin and amyl nitrite, which are known vaso-dilators, have a distinctly calming effect upon the paroxysms of pain.

One or two other observers have actually noted the presence of hæmorrhages in the lesions; thus, in the case quoted by Mott[69] definite yielding of the vessel walls and signs of old hæmorrhage are described amongst other lesions in the brain. Seifert[70] also describes the presence of hæmorrhages amongst the ganglion cells in the anterior columns of the cord, both in the case of persons who have died of lead poisoning and animals to which lead had been given experimentally. In addition, Sajous[71] describes a case of paralysis of the superior laryngeal nerve, associated with hæmorrhages, in the region of the abductor muscles of the larynx. Mott’s case also showed this laryngeal hæmorrhage.

More recently Elschnig[72], in his observations upon the eye, has determined a close association between vaso-motor affections, constrictions, and dilatations, and various eye lesions, such as amaurosis and amblyopia, occurring in lead poisoning. Rambousek[73], in summing up Elschnig’s work, points out how much his observations tend to bridge over the gap between the action of lead upon the blood, the bloodvessels, and the nerves. He points out that the eye is a peculiarly favourable organ for watching the effect of a poison so insidious as lead. The bloodvessels, the nerves, and the muscles, are all open to inspection and actual observation to a degree not to be found in any other part of the body. Elschnig[74], in a typical case of sudden lead amaurosis associated with acute lead colic, found that very definite motor spasm of the vessels of the eye, conjunctiva, and the retina, were associated with the amaurosis. He argues from this that the action of lead is probably directly upon the unstriped muscular fibre of the vessel walls; that such an action may, and does, extend to the vessels of the eye muscles, producing[77] paralysis of the muscles of accommodation, and a dilatation of the pupil, which may be observed in a large number of persons employed in conditions subjecting them to lead absorption. Elschnig further considers that the transitory amaurosis which is often associated with lead poisoning may be due to vaso-motor disturbances in the brain itself, as well as in the eye.

Still more recently, and due, no doubt, to a great extent to the work of Elschnig, further attention has been drawn to the vascular system in lead poisoning. Elschnig’s work has carried the question another stage forward by showing the association of vaso-motor disturbances with eye disease, whilst in this country Oliver[75] pointed out the effect upon the pulse of abdominal colic.

At the beginning of the researches on this point described in the next chapter, this clue running through the whole of the pathology of lead poisoning was not appreciated. At the commencement of the investigations there seemed to be no main general line of symptoms or histological findings that could be adduced as characteristic of lead poisoning; in fact, the initial experiments were performed, with the object of examining the association of lung-absorbed lead compounds as a possible cause of lead poisoning, as against the entrance of lead by the alimentary canal; but as the experiments proceeded it became clear that the stress of the initial intoxication was undoubtedly falling upon the bloodvessels, and more particularly upon the minuter bloodvessels, and less on the arterial side of the capillaries (although the capillaries were to a large extent associated with the process) than upon the venous radicles.

A general consideration of the pathology shows that lead causes changes in the nervous system affecting both upper and lower segments, degeneration of the ganglion cells in the cord and in the brain, interstitial inflammation of the neuroglia, cortical degeneration, distinct neuritis, both axial and peri-axial, of the peripheral nerves, and also signs of change in the sympathetic nervous system in chronic lead poisoning. Later work has, however, all tended to point out that the chief and first effect of lead is upon the blood.

Moritz[76] first pointed out the presence of basophile granules in the red blood-cells. The work was followed up by Emden[77], Gravitz[78], Zinn[79], Otto[80], Silbert[81], and by Escherich[82]. All these authors found basophilic erythrocytes in the[78] blood associated with blood-destruction, and Escherich in addition describes early changes taking place in the intima of the bloodvessels associated with vaso-constriction. The Italian author Mattirolo[83], as well as Marchet[84] and Jores[85], came to a similar conclusion. Glibert of Brussels[86], carrying the observations somewhat farther, and although working with guinea-pigs, which normally show basophilic staining in their blood-cells, was able to demonstrate one further point of considerable value—namely, the increase in the viscosity of the blood, with blood-corpuscles of greater toughness, elasticity, and power to resist destruction when making films, than in normal blood.

There is thus very striking continuity in the observations of all the various observers, despite the fact that at first sight their descriptions may appear discordant. There seems no doubt that practically all authors who have given attention to the subject are agreed that the circulatory system, and primarily the blood circulating in the vessels, is affected by lead, and, further, that the vessels themselves undergo degeneration of various types, many of the cases examined showing complete obliterative arteritis as the result of long-standing irritation. Others describe no obliterative changes of this type in the vessels, because attention was given mainly to the nervous system, where the cells were found degenerated and showing chromatolysis. But, on the other hand, careful observers, such as Mott, have noted the presence, in passing, of these apparent yieldings of the vessels here and there in the region of the degenerated nervous tissue. Again, even the histological action of a drug such as amyl nitrite points to involvement of the vaso-motor system. Perhaps this curious association through all the described pathology and bloodvessel infection would not appear so clear but for the more recent investigations described in the following chapter.

REFERENCES.

It was thought that some light might be thrown on chronic intoxication produced by lead salts if direct experiment were made upon animals, resembling in the arrangement of such experiments, as far as possible, the industrial conditions under which human beings contract lead poisoning.

The animals chosen for the experiments were cats, as it is a fact of common knowledge that it is impossible to keep cats in lead works, particularly white-lead, because they rapidly become poisoned if allowed to stray about the works. The same holds good in the case of dogs.

From the statistics already given in Chapter IV., and from the remarks in the chapter on Ætiology, there was no doubt whatever that dust played a most important rôle in the production of industrial lead poisoning. In attempting, therefore, to copy the industrial conditions, it is essential to submit the animals experimented upon to infection by means of air in which lead dust is suspended. A large number of experiments have been carried out in the first place, by myself[1], and later in conjunction with Dr. Goodbody[2], and another series of experiments were also undertaken by myself[3]. Further experiments are still in progress in this and other directions.

1. Breathing Experiments

—First Series.—A. The animals experimented upon were placed in a large closed chamber at one end of which an electric fan was fitted in such a way that the air was kept in constant motion. The lead dust was introduced by means of a funnel through the roof in a definite quantity during timed intervals. By means of an aspirating jar and[82] a tube inserted into the side, samples of air were withdrawn from time to time during the experiments, and submitted to chemical analysis to determine the quantity of lead circulating in the air. These samples were drawn off at the level of the animals’ heads. Great care was taken to eliminate any swallowing of dust by the animals during the experiments, by protecting their coats from the dust and carefully brushing them at the conclusion of each exposure.

Second Series.—B. In other experiments a chamber containing two separate compartments was constructed, and lead dust suspended in air was blown into the two compartments by means of an electric fan situated outside. The apparatus was so arranged that the draught of air from the fan passed through two separate boxes, in which the lead compound under experiment was kept agitated by means of small fans situated in the boxes and driven by a second electric motor. In this way two different samples of lead were experimented on at one and the same time, the air current driving in the dust through the two boxes being equal on the two sides; the quantity of dust was therefore directly proportional to the compound used. Samples of the dusty air were aspirated off and subjected to analysis, as in the first series. In this series of experiments the animals were so arranged that only their heads projected into the dust chamber during exposure.

2. Feeding Experiments.

—Feeding experiments were carried out by mixing a weighed dose of the lead compound experimented with, and adding this to a small portion of the animal’s first feed in the morning. It was found that unless the lead was well incorporated with the animal’s food it would not take the lead in the dry form; and in dealing with white lead and other dust, it was necessary to give the compound in a similar form to that in which a man would obtain it under industrial conditions, which of course precluded the use of a solution.

The amount of lead given by the mouth as a control to the inhalation experiments was from seven to ten times the dose which could be taken by the animal during its exposure in the cage, and the dose was given daily, and not every third day as in the inhalation experiments. All the compounds used in the inhalation experiments were given to animals by the mouth, the animals’ weights being carefully noted.

In a further series of feeding experiments a soluble salt of[83] lead was added to the animals’ food (water or milk), the salt in this case being the nitrate. The quantity added was much smaller than in the dust experiments. 0·1 gramme was given daily.

3. Inoculation Experiments.

—As a further control to both the breathing and feeding experiments, the various lead compounds similar to those used in the other experiments were inoculated into animals. The insoluble salts gave some difficulty in the technique of injection, but by using a large needle, and making the suspension of the material in the syringe, the difficulty was overcome. The quantity of material inoculated varied; it was calculated in fractions of a gramme per kilogramme body weight, the quantity of fluid used being the same in all cases—namely, 10 c.c.—and inoculations were made subcutaneously and intramuscularly in the muscles of the back after previous shaving. In only one case was localized inflammation produced, and this was when the acetate was the salt employed.

None of the animals exhibited any signs of discomfort during the experiments from the presence of lead dust in the air; once or twice sneezing was noticed, but this was an uncommon occurrence. This point is of practical importance, as the lead dust contained in the air in white-lead and other factories is not of itself irritating to the mucous membrane of the lung. The animals subjected to this form of experiment were no doubt absorbing much larger doses of lead than are persons engaged in the manufacture of lead compounds.

The only ascertainable difference in the ultimate pathological lesions produced in animals, whether inhaling large quantities or minimal quantities of dust, was the rate at which the poisoning took place. In certain experiments it was found that the animals maintained a kind of equilibrium, much as do workmen engaged in dusty lead processes. It was found, moreover, that some animals showed a certain amount of tolerance to the effect of lead dust, in that their weights remained almost constant, but an increase in the quantity of lead present in the air immediately produced progressive diminution in the body weight; and as this diminution in the body weight approached to one-third of the animal’s initial weight, so symptoms of chronic poisoning supervened.

In addition to the animals inhaling lead dust over prolonged periods, certain other inhalation experiments were made for the determination of lead dust in the lung as opposed[84] to the stomach. In the inhalation experiments proper, where the animals were exposed to inhalation every other day or every third day, for only an hour at a time, the quantity of lead present in the air was not very large, and it was thought essential to determine if, in exceedingly dusty atmospheres, any appreciable amount of lead could be found in the stomach. Ten animals were submitted to the inhalation of air heavily charged with various types of lead dust. The animal was exposed to the dust for an hour and a half to two hours; at the end of this time it was anæsthetized, and when the respirations had ceased, and the animal was dead, sulphuretted hydrogen was blown into the lung and into the stomach. The animal was then rapidly dissected and staining looked for. The tissues were further treated with acid and re-exposed to sulphuretted hydrogen gas. In one animal only out of the ten was any staining noticed in the stomach. In none of the others was any such staining found, but very definite blackening was found in the larynx, trachea, and macroscopically even in some of the bronchioles. Sections of the lung were further submitted to histological examination, and by means of micro-chemical tests with chromic acid and with iodine, and also by comparing sections of the experimental animals and animals which had not been subjected to lead dust inhalations, a very much larger quantity of material was found present in the lungs of the inhalation animals than in the normal animal. The dust was situated in the alveoli and the alveolar cells, and often in the lymphatics. On examining microscopically sections of the lungs of those animals exposed to graduated inhalation over extensive periods, a far larger number of blackened granules, dust, pigment, and other substances, was found than in similar sections of animals which were under normal conditions and had not been exposed to lead dust, although it is true such animals show a very fair proportion of carbon particles taken up by the lung tissue.

A further important fact was noticeable in animals Nos. 21 and 22 (see p. 101), which had been exposed to a low solubility glaze such as is used in the Potteries. Low solubility glaze is compounded with lead frit—that is to say, a lead glaze (or lead silicate) which has been finely ground. The particles of this substance are much larger than those of ordinary white lead, and in addition they are much more angular. Of three animals exposed to this glaze, one actually died of pneumonia (acute),[85] and the other two suffered from some bronchial trouble, both of them showing distinct signs of pneumonic patches and old and chronic inflammation when examined histologically; whereas in none of the other animals exposed to white lead dust or to the high solubility glaze, which contained white lead as opposed to lead frit, no such pneumonic or fibroid changes were found. This point is of some pathological importance.

The inhalation experiments also throw some light on the quantity of lead necessary to produce poisoning. The animals in the inhalation experiments were exposed for varying periods, and constant estimations made of the lead present in the air. In a number of instances samples were taken from the cage air during the whole of the experiment, as rapidly as possible. The quantity of lead floating in the air was found to increase as the experiment progressed, although a large amount of the lead introduced was caught on the side of the cage and deposited on the floor.

In the later experiments the method of taking the samples continuously during the experiment was abandoned, and four samples only were taken, and the average recorded. A simple calculation will give the quantity of lead dust it would be possible for an animal to inhale during the whole of this period of exposure. The utmost tidal air in the case of a cat would be taken at 50 c.c. Taking the average, about 0·27 gramme of lead was inhaled during the half-hour of exposure.

Feeding Experiments.

—Twelve feeding experiments of various types are recorded. The method of experiment was as follows:

The compound under investigation was carefully weighed out each day (0·5 to 1·0 gramme), the substance being some of the same compound that was being made use of for inhalation experiments. In the case of the white lead it was found essential to mix it with the animals’ food; they were given white lead in a small amount of their food, and no further food was given for some little time after the dose of lead had been swallowed. Low and high solubility glazes were also made use of for feeding, and as a further experiment alcohol was given to the animals in addition to the previous course of lead inhalation or feeding, and the exposure to lead continued after the alcohol was given. In addition to high solubility glazes, white lead, and flue dust, a soluble salt of lead was also used, in one series the salt being the nitrate. 0·1 gramme was given daily; and it is[86] these two nitrate animals (46 and 47) which showed distinct differences from the white lead and other feeding experiments. In one case the lead was given mixed with water, in the other mixed with milk. The animal which was fed with the nitrate dissolved in water developed encephalopathy, whereas the one in which the substance was mixed in milk exhibited no signs, though fed for a similar period. Both the animals increased in weight, which is an unusual effect in experimental lead poisoning. The question of the addition of milk, which apparently prevented the absorption of lead, is of very considerable importance, as it is highly probable, as has been pointed out with regard to the precipitation of lead by means of organic substances, that the albuminoid substances in the milk precipitate the nitrate already in a state of solution; and it may be argued from these experiments that mixing the white lead with the food would tend to prevent the lead having a toxic or deleterious effect, but even when the lead was given in the form of pills between meals no poisonous effect was noticed. Further, the quantity of white lead given was considerable, and it is highly questionable whether the quantity of lead so taken would be dissolved by the gastric juice excreted under normal circumstances in its entirety, as a very considerable quantity would pass onwards through the pylorus undissolved. Until the lead compound has become soluble it cannot react with the albuminoid constituent of the food. Ordinary dry white lead or litharge does not combine directly with albumin.

The majority of the experimental animals showed alteration in weight. The most important point which is brought out by these experiments, considering them from the point of view of inhalation, is the enormous quantity of white lead the “feeding” animals swallowed without producing any apparent symptoms. The quantities cited are the amounts given per diem, whereas in the inhalation experiments the animals were rarely exposed more than three days a week for an hour at a time (see table, p. 101). The quantity of lead, therefore, given by the gastro-intestinal canal was at least ten times as much, in many cases fifteen or twenty times as much, as could be taken by the other animals via the lung during inhalation, and yet these animals showed little or no susceptibility to poisoning when fed with white lead or other lead compounds, unless alcohol was given in addition.

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An examination of the stomach after death showed, in the case of the alcoholic animals, distinct evidence of gastritis, and there is some reason to suppose that in such animals a degree of hyperacidity may have existed, thereby promoting the rate of solution of the lead.

The increased susceptibility to lead poisoning through the agency of alcohol is interesting. No. 6 received, in addition to its inhalations or period of exposure in the dusty air, 50 c.c. of port wine per diem. Symptoms of lead poisoning appeared a day sooner than in any other animal, and if we eliminate this experiment, as the dust (flue dust from blast-furnace) contained also arsenic and antimony, three days sooner than the litharge animal, and twenty-five days sooner than the other animals exposed to white lead dust. In addition, this animal was the only one which actually died during the period of experiment; all the other animals were killed at the end of two months and submitted to histological examination; but the animal which had received alcohol died with symptoms closely simulating lead encephalopathy in man. The predisposing action of alcohol is still further emphasized by the subsequent experiments with three animals exposed to white lead dust; one was exposed thirty-seven and the other thirty days before symptoms appeared, whereas when alcohol was given poisoning was apparent within twelve days, and after only four inhalations.

In the case of animals fed with white lead, one after eight months, and the other a year and a half, showed no signs of lead poisoning at all, while the weights remained constant. At the end of this time alcohol (50 c.c. of port wine) was added to the animals’ diet, and one month after the addition of alcohol to the diet, the dose of white lead being continued constant, encephalopathy ensued. In a second case the animal was started on alcohol in addition to the white lead. In a month it was showing signs of slight paresis. Again, an animal fed on a low-solubility frit consisting of ground-up lead silicate, showed no ill-effects after receiving a daily dose of this compound. At the end of this time alcohol was added to its diet, and six months later the animal developed symptoms of cerebral involvement, which continued at intervals until a fatal attack of encephalopathy at the end of a year. There is thus definite evidence to show that the addition of alcohol to the animal’s diet undoubtedly hastened and determined the appearance of[88] lead poisoning, and this, taken in conjunction with the inhalation experiments previously cited, is very strong evidence of the increased susceptibility to lead poisoning produced by alcohol. This supersensitiveness to lead through the medium of alcohol is a matter of clinical experience to most persons who have had experience of industrial lead poisoning, particularly those who have been engaged in the routine examination of persons working in factories.

Inoculation Experiments.

—In order to control both the feeding and the inhalation experiments, and more particularly to obtain direct information of the effect of lead upon the body tissues, resource was had to the inoculation of the various lead compounds tested—namely: (1) White lead, (2) litharge, (3) lead frit. These three compounds are the three types of lead salt which are used in the Potteries, whilst white lead and litharge are the compounds causing industrial poisoning in the largest proportion of cases in other industries. As a further control, the more soluble lead salts were also made use of—namely, acetate, nitrate, and chloride—mainly for the purpose of establishing some standard of poisoning both in rate and dose.

Several rather unexpected results were derived from the inoculation experiments, which will be referred to.

The method of inoculation was to suspend the lead compound to be tested in normal saline solution or distilled water. The animal was then shaved, and the lead compound inoculated into the muscles of the back. The corrosive action of these lead salts was avoided by using a considerable quantity of diluent.

Lead frit is a constituent of low-solubility glaze—that is to say, a glaze which has not more than 5 per cent. soluble lead when subjected to the standard test of exposing 1 gramme of the glaze to a litre of 0·04 per cent. hydrochloric acid for an hour at room temperature. The frit which was the constituent of this glaze is produced by heating together litharge or lead and silica, the production being a yellow, hard, glaze-like material looking very much like sugar-candy. It is not by any means a compound of lead and silica of simple composition, as different samples show a wide variation in their lead content; whilst, in addition, the mode of its formation closely resembles that of an alloy or amalgam, and allows of the formation of a eutectic entangling in its meshes both of the constituents of which it is formed, so that a certain amount of free lead, in addition to the[89] silicates of various descriptions, are present. At the same time the compound is highly resistant to the action of mineral acids, and, of course, much more insoluble and refractory than white lead, litharge, or other lead oxides. The body fluids, however, particularly the fluids in the subcutaneous and muscular tissue, definitely exert some action upon this fritted lead, and it was found experimentally that symptoms of poisoning could be produced in the experimental animals when even small doses were administered. A gramme of frit was inoculated, and in all but one case the animals showed definite signs of lead poisoning, and in two instances actually died with symptoms of encephalitis.

By washing the frit with distilled water, a slight diminution in the poisonousness was found, but by washing the frit with two or three changes of dilute acetic acid (3 per cent.), and then with distilled water, no pathological results followed inoculation. Water-washing frit alone definitely reduces the poisonous effect, but not to the same extent as the preliminary washing with acetic acid. On the other hand, washing with hot water had a much greater effect than cold-water washing.

Further evidence given by the inoculation experiments shows the relationship between the more soluble and the insoluble lead salts. The dose of acetate required to kill an animal was about 0·1 gramme of acetate per kilogramme body weight. On the other hand, 0·1 gramme of white lead produced no ill-effects, 0·5 gramme per kilogramme body weight produced death in about two months. In addition, those animals suffering from the more acute forms of poisoning developed definite eye changes and retinal hæmorrhages. Tortuosity and increased size of the retinal vessels were observed in several instances.

Besides controlling the experiments of feeding and inhalation, the inoculation experiments play a still more important part, as they furnish the correlation, necessarily, of the histological changes found as the result of poisoning by means of lead. In all the animals which have died of poisoning, certain definite trains of symptoms made their appearance. These symptoms were in practically all particulars similar to those observed in industrial lead poisoning in man, the onset of the affection and its clinical course corresponding to the symptom-complex in man, including those of cortical involvement, and often similar to the classical Jacksonian variety.

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Throughout these experiments the animals exhibited no signs of irritation, and during the initial period, even, when loss of weight was a noticeable feature, their appetites remained exceedingly good; they were quite friendly, and purred loudly when stroked; but when symptoms of poisoning became manifest, particularly the onset of paralysis, a definite change in mental phenomena took place: the animals became quarrelsome, highly apprehensive of danger without cause, morose and lethargic by turns. At this stage, in more than one instance, acute encephalopathy supervened. The mental change was peculiarly striking in reference to Mott’s case, quoted on p. 71, as in all respects it was exactly analogous with the train of symptoms recorded in that case. To sum up, the symptoms produced in the experimental animals by the lead compounds inoculated and respired, no matter what the particular compound of lead experimented was, were as follows:

1. Slight preliminary rise in weight at the commencement of the experiment, lasting from one to two weeks.

2. Progressive loss of weight, mainly due to the disappearance of all fat, subcutaneous, kidney, mesenteric, etc., with associated anæmia, and the curious sunken and pinched faces commonly associated with saturnine cachexia.

3. Paresis of various types.

In the cat the muscles first affected are those of the back and the quadriceps extensor of the hind-limbs. The onset of the paralysis is slow and insidious, but may be acute; as a rule weakness in the muscles of the lumbar region and the spine are the first symptoms; secondly, inability to jump, owing to the weakness of the quadriceps extensor, while the animal tends to fall over when turning round quickly. Encephalitis occurs, and is frequently fatal. As a rule the affection is unilateral; complete loss of consciousness may occur, followed by slow but complete recovery. The animals gave no evidence of suffering pain, and, when recovered from an attack of encephalopathy, would at once take milk, but seemed dazed and uncertain in their movements. When the animals reached the stage of paralysis, they were destroyed under anæsthetics, and subjected to post-mortem examination. The post-mortem findings of a typical case were as follows:

The animal was emaciated, the fur easily pulled out, and the muscles were exceedingly flaccid.

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Rigor mortis was slow in making its appearance; the blood remained fluid for a considerable time.

Practically no fat was to be found in the whole of the mesentery, and the omentum was devoid of fat and shrivelled. The fat around the kidneys had entirely disappeared. There was little orbital fat.

The peritoneum was thin and glistening, and very frail.

The whole of the mesenteric vessels, particularly in the region of the large intestine and the ileo-cæcal valve, were engorged with blood; whilst in the lower part of the small intestine, and often in the duodenum, occasionally in the whole of the jejunum and ileum, traces of minute hæmorrhages were found along the intestinal wall.

The liver was engorged with blood, as was the spleen.

The kidney capsule stripped easily, but was occasionally adherent here and there. The whole of the cortical vessels were injected with blood, the branching showing most distinctly.

A good deal of serous fluid was at times found underneath the kidney capsule.

On section the cortex appeared engorged with blood, and showed here and there, even to the naked eye, small hæmorrhages.

In the region of the appendix a few large mesenteric glands were invariably found, whilst a few glands might also be found in the wasted mesentery of the small intestine. In the region of the appendix the glands were frequently dark in colour. On opening the gut, minute hæmorrhages and ulcerated patches were to be found in the lower part of the ileum; the ileo-cæcal valve, and the whole of the large intestine, extending right up to the end of the appendix, was covered with a dark slate-blue slime, in which lead could be easily recognized by chemical processes.

Ulceration of the gastric mucous is uncommon, and only on one occasion were any hæmorrhages found. In the thoracic cavity the lungs were generally found to be emphysematous, and particularly in those animals subjected to inhalation of lead frit containing angular particles of lead glaze broncho-pneumonia was found.

The heart was flabby, and occasionally distinct roughening and thickening of the valves was seen.

Nervous System.—On opening the skull, hæmorrhages were[92] frequently found at the base of the brain, occasionally situated over the surface of the cerebrum. Minute hæmorrhages were found often underneath the arachnoid membrane, but the largest hæmorrhages were always found at the base of the brain, and spreading down into the spinal canal along the medulla.

On removing the cord, minute hæmorrhages were found along the surface, irregular in distribution, and never very large. On section the brain and cord appeared normal.

Histology.

—A large number of sections were prepared from the animals developing symptoms of poisoning; the various tissues are described seriatim:

Muscles.—These appear to have undergone general fatty degeneration. The individual muscle fibres are indistinct in outline, and show irregular areas stained by hæmatoxylin. Some infiltration may be seen here and there between the muscle fibres, and minute hæmorrhages are occasionally detected, the chief appearance being that of general atrophy. The heart muscle shows similar degeneration, and the tendency of the sarcolemma to break down and stain irregularly is apparent. In many areas the muscle fibres stain poorly, if at all. Occasionally minute hæmorrhages are found, passing between the muscle fibres.

Liver.—The hepatic cells show varied degeneration; the vessels passing between the cells are engorged with blood, the cells being frequently much distorted from their general arrangement, and here and there completely obliterated by small areas of exudation as well as actual hæmorrhages.

Spleen.—The parenchyma shows masses of irregular spaces filled with recently-shed blood; the individual cells show a granular degeneration, with occasional basophile staining, the general appearance being one of chronic congestion. Here and there cloudy swelling may be seen.

Intestine.—Sections across the small intestine show atrophy of the intestinal wall, slight degeneration of the muscular coats, with infiltration and minute hæmorrhages.

Large Intestine.—Here similar minute hæmorrhages are found, in no case large enough to be seen by the naked eye. Areas of necrotic tissue are also seen in which considerable quantities of lead sulphide particles are found.

PLATE I

Fig. 1.—Section of Large Intestine of Animal poisoned by Inhalation of White Lead, showing Excretion of Lead by Tissues. (Stained Eosin and Hæmatoxylin.) × 250.

The whole of the large intestine was stained black, the staining commencing at the ileo-cæcal valve. No staining is observable in the small intestine; the line of demarcation is sharp.

 

Fig. 2.—Intestinal Ulceration in Turpentine Poisoning. (Stained Eosin and Hæmatoxylin.) × 250.

 

Fig. 3.—Section of Anterior Crural Nerve from Animal poisoned by Inhalation of White Lead Dust, showing Hæmorrhage in Nerve. (Stained Hæmatoxylin and Eosin.) × 250.

There was paralysis of the quadriceps extensor on the right side; the left leg was unaffected and the left anterior crural nerve was unaffected.

 

PLATE II

Fig. 1.—Section of Lung of Animal exposed to Inhalation of White Lead Dust, showing Mass of Lead in the Lung Substance. (Stained Hæmatoxylin and Eosin, and treated with H₂S.) × 250.

 

Fig. 2.—Lung of Animal exposed to Turpentine Vapour. (Stained Hæmatoxylin and Eosin.) × 250.

 

Fig. 3.—Lung of Animal exposed to Inhalation of White Lead Dust, showing Chronic Inflammation with Exudation and Capillary Leakage and Hæmorrhage. (Stained Hæmatoxylin and Eosin.) × 250.

 

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Lung.—Red or grey hepatization may be found, or a general appearance of broncho-pneumonia, where the dust used contained angular or insoluble substances. In animals subjected to prolonged inhalation, particles of lead could be demonstrated in the alveolar cells, and in the tissue beyond, either by staining with chromic acid or by means of iodine. Staining by sulphuretted hydrogen is not very satisfactory, as most animals resident in a large city show masses of carbon situated in various parts of the alveolar cells. If, however, a section be treated by means of iodine or chromic acid, and watched under the microscope during the process, the particles of carbon are easily differentiated from those of lead compounds.

Nervous System.—Sections of the brain and spinal cord, and of the nerve supplying the paralyzed muscles, all exhibited the same phenomena of minute hæmorrhages. In later cases some change in the cells is found, but as a rule, beyond a slight increase of the intracellular substance, little or no change is found in the cellular elements of the brain; but in the region of the surface minute hæmorrhages may be constantly traced, spreading over the surface of the cortex. In the cord, sections made in various situations failed to show any very definite degeneration, and little or no hæmorrhage was observed amongst the cells of the cord. Hæmorrhages could occasionally be seen on the surface.

In a number of animals the anterior crural nerves supplying the paralyzed quadriceps extensor muscles were examined carefully both for degeneration and for hæmorrhages. Very few degenerated nerve fibres were found, not more than would be accounted for by the minute hæmorrhages, which were found passing in between the nerve bundles, and here and there producing pressure on the nerve bundles themselves.

Kidney.—In the kidneys minute microscopical hæmorrhages, some of them quite large, were found in the cortex. The hæmorrhages are diffuse and irregular, and apparently due here, as in other situations in the body, to the breaking down of minute venioles rather than arterioles. In many cases the change is capillary. Parenchymatous nephritis may be seen, probably resulting from the transudation taking place from the vessel walls.

The chief view brought out in the histological examination of the various organs is one of capillary hæmorrhage. This phenomenon is not peculiar to lead poisoning, but, from the work of Moore of Liverpool[4], it would seem that all[94] heavy metals, such as bismuth, mercury, not excepting iron, tend to produce a curious generalized yielding of the minuter vessel walls. Armit[5] has demonstrated a similar effect with nickel. The phenomena is, however, typically associated with lead poisoning, and may, we think, be regarded as the definite factor of chronic lead poisoning.

For the purposes of controlling the experiments of inhalation, two other series of experiments were undertaken. In one instance an animal was fed for two years on white lead; the animal was given 0·1 gramme per day, and this was increased up to 0·5 gramme, and ultimately 1 gramme. This animal exhibited no symptoms whatever of lead poisoning, and when it was killed, at the end of the time of experiment, showed no apparent lesion, with the exception of very marked staining of the colon and vermiform appendix. This staining of the large intestine and the appendix, the engorgement of the vessels, particularly of the omentum and mesentery, the enlargement of the lymphatic glands in the neighbourhood of the colon, ileo-cæcal valve, and appendix, suggest the absorption of lead in the upper part of the intestine, and its discharge or elimination into the large intestine. That lead is absorbed into the upper part of the intestine was demonstrated in the following manner:

An animal was anæsthetized, an incision made, and a loop of intestine pulled up and clamped off, a solution of lead chloride being run into the loop by means of a hypodermic syringe. The mesenteric vein passing from this loop of intestine was then carefully secured, a small opening made in it, and the blood collected drop by drop until some 40 c.c. had been collected, the time occupied being about three-quarters of an hour. The blood thus collected was submitted to chemical examination, and lead was demonstrated to be present. Lead therefore passes direct from the intestine into the portal circulation.

In only one of the feeding experiments with solid compounds of lead was any definite symptom of lead poisoning produced, and in this instance the compound used was dust collected from the flues of a blast-furnace. This dust was afterwards found to contain a considerable quantity of arsenic. The experiment cannot therefore be regarded as conclusive. With the more soluble salts of lead, however, such as the acetate, lead poisoning may be set up by means of lead administered via the intestinal canal: 1 gramme of lead acetate administered by means of a hypodermic syringe through a catheter passed into the stomach of a cat produced abortion in ten days, and death in three weeks. Four grammes of acetate produced a similar effect in a dog in four weeks.

[95]

PLATE III

Fig. 1.—Kidney of Animal poisoned with White Lead (Inhalation), showing Microscopical Hæmorrhages. (Stained Hæmatoxylin and Eosin.) × 250.

 

Fig. 2.—Kidney of Man dying of Chronic Lead Poisoning. (Stained Hæmatoxylin and Eosin.) × 250.

 

Fig. 3.—Brain of Young Woman dying of Acute Lead Encephalopathy, showing Small Cerebral Hæmorrhages. (Stained Hæmatoxylin and Eosin.) × 250.

 

The two following cases, in which both chemical and histological examination has been carried out on the tissues of persons who had been employed in occupations which rendered them exposed to absorption of lead, and who died with symptoms directly suggestive of lead poisoning, may be added, as they confirm the experimental results given above in all particulars:

Case 1.—A woman aged twenty-one, employed in a litho-transfer works, who died after a short illness during which the chief symptoms were headache and mental clouding.

At the post-mortem examination no pathological lesions were discoverable with the exception of a small gland which had become calcareous, situated near the right bronchus. The brain was injected over the left cerebral hemisphere, but no hæmorrhages were to be seen with the naked eye. There were no other pathological signs. A portion of the brain showing the injection and congestion were submitted to histological and chemical analysis. Histologically the brain tissue was found to be normal, with the exception of slight chromatolysis of some of the larger cells; but interspersed about the whole section in the slides examined, but more particularly in the area of the cortex, minute microscopical hæmorrhages were found (see Fig. 3). Here and there these hæmorrhages were seen related to the expanded capillaries, all of which showed considerable engorgement with blood. The arteries and veins themselves were, in addition, considerably distended. There was no interstitial degeneration of the neuroglia noticed. A few patches were found which apparently represented old hæmorrhages undergoing gradual fibroid degeneration. In no case were the hæmorrhages of a size that could be detected by the naked eye.

Two hundred and fifty grammes of the injected area of the brain were submitted to chemical examination by the moist process described in the chapter on Chemical Analysis. The nitric acid filtrate from the electrolytic deposition gave a well-marked precipitate with sulphuretted hydrogen, which was filtered off and recognized as lead. There was only the merest trace of iron present. By colorimetric estimation the quantity[96] of lead found present in the brain estimated as Pb was 0·0143 gramme. The quantity found in 250 grammes of brain substance examined from the injected area was 0·0041 gramme.

Case 2.—A man who had been employed in an electrical accumulator works for a considerable time, and who had had a history of several attacks of lead colic and one of lead paresis affecting both hands.

The man’s work in connection with lead ceased from the time of the paresis, but some three years subsequently he died with cerebral hæmorrhage.

Portions of the organs, brain, kidney, liver, and spleen, were examined histologically, stained in the ordinary way with hæmatoxylin and eosin. In the brain the same marked microscopical hæmorrhages were observed as described in the previous case, and in addition many more areas of old fibroid scars, very minute, but apparently corresponding to earlier minute hæmorrhages. The kidney showed definite interstitial hæmorrhage (see Plate III., Fig. 2), as did the liver and spleen.

A portion of the brain was further submitted to chemical examination, and 0·0014 gramme of lead was determined as present.

The importance of this confirmatory evidence is undoubted, as the presence of the capillary hæmorrhage existing in the tissues of a person dying under suspicious circumstances when employed in a lead process is confirmed by the chemical determination of lead in the tissues.

The following tables, arranged under three headings, give some of the experimental results obtained by submitting animals to the effect of compounds of lead.

Table XI. gives the inoculation experiments.

The materials used in these experiments were those used in the inhalation and feeding experiments. The experiments are also arranged in such a manner that each series is a control one of the other.

The amount of substance used for the inoculation gives some rough idea of the dose required to produce poisoning in an animal; but even this question of dose in absolute quantities, administered hypodermically, shows considerable variation in the degree of poisonous effect. The first animal in Table XI. was inoculated with acetate, this being one of the more soluble lead compounds, and was given it in three small doses. The animal[97] received 0·3 gramme per kilogramme of body weight, whereas in No. 35 2 grammes of washed frit—that is to say, lead glaze formed by fusing together litharge and silica—actually did produce symptoms, but of a mild nature. Animal No. 33 only had 0·16 gramme, being 0·05 gramme per kilogramme of body weight; and this caused acute symptoms. 0·35 gramme of white lead in a 3·500 kilogramme animal (No. 31) produced no symptoms at all. In the list of the inoculation experiments, three animals only exhibited no symptoms—one of these (No. 31) which was given white lead hypodermically, and Nos. 41 and 42, which were inoculated with lead silicate or lead frit, which had been previously treated with acetic acid or water.

Several practical points arise from these experiments, notably with regard to the frits, as it is seen that a considerable amount of the toxic properties contained in frit are removed by washing—most by washing with acetic acid and water, but also to some extent by washing with hot water alone, showing that in the ordinary production of lead frit for pottery purposes a certain amount of lead in a soluble condition as regards the body tissues was still present. This is no doubt entangled in the true silicates in the forms of oxides, or even as carbonate. Further, the toxicity of the lead compounds used may certainly be arranged in the order of their solubility with regard to the animal tissues, the acetate being the most poisonous, and the frit, when washed, the least; but unwashed frit, even in relatively small doses, may produce poisoning. This point is still further emphasized in Table XIII. Animal No. 42, four months after previous inoculation, showed no signs of poisoning. Lead nitrate in water was therefore given in quantities of 0·01 gramme per diem; one month later this animal developed poisoning.

Table XII. deals with the feeding experiments.

In these experiments acetate was given in one case only, and then in the form of pills coated with keratin. It is impossible to say, however, whether the animal ever received any soluble lead, as on one or two occasions the keratin pills passed right through the animal without dissolving. On the other hand, feeding with nitrate of lead in water produced symptoms, but when the nitrate was given in milk no symptoms appeared. It will be noticed it took a cat four months to show any signs of poisoning taking 0·1 gramme per day; whereas the animal receiving subcutaneous doses of 0·16 gramme of acetate[98] showed paralysis in fifteen days, and in twenty-two days was so ill that it had to be destroyed under an anæsthetic. The same relationship in time also obtains in the case of the animals fed on dry white lead. In practically no instance did definite or severe poisoning follow the feeding on dry white lead alone, even when quite large quantities were taken. On reference to the inoculation experiments of Table XI., it will be seen that the inoculation of 2 grammes of dry white lead produced definite symptoms, although the feeding cats had an amount very largely in excess of this. The only animals fed on white lead or frit exhibiting signs of lead poisoning were those which were given alcohol in addition to the lead compound.

A comparison of the results given in Tables XI. and XII. shows that animals which received lead compounds subcutaneously suffered much more than the animals which received the lead via the gastro-intestinal canal, even when the doses given via the mouth were exceedingly large. It will follow, then, that the actual contact with the more intimate fluids of the body, rather than the digestive juices, determines the solubility and general distribution of the lead compound in the body. This is confirmed by a recent paper by Straub[6].

The animals experimented upon by feeding were kept in the laboratory under the same conditions as the inhalation animals, but were so placed that under no circumstance could they obtain any lead dust by inhalation. These animals were used as control to the breathing experiments, the substance fed to the animals being in all cases the same substance as was used for the various inhalation experiments; but in addition a certain number of the animals were given alcohol, which are referred to in Table XII. Alcohol was also given to animal No. 6 in the inhalation series.

The animals fed with lead were fed with the same compound which was used for the inhalation experiments, 0·4 to 1 gramme being given daily; so that during the period these animals were exposed to lead dust the other animals were taking the same compound via the intestinal canal, but in much larger quantities, and yet they exhibited no signs of lead poisoning.

[99]

TABLE XI.—INOCULATION.

[100]

TABLE XII.—FEEDING EXPERIMENTS.

[101]

TABLE XIII.—INHALATION EXPERIMENTS.

[102]

The experiments definitely bring out one all-important fact—namely, that lead dust circulating in the air is many times more dangerous than lead actually swallowed; for even if the animals which were exposed to the inhalation of dust swallowed the whole of the quantity contained in the respired air, they would only obtain one-tenth of the amount the other fed animals were getting. It is, of course, impossible to suppose that the whole of the lead contained in the inhaled air reached the lung. It can only have been the smaller particles which did so. Therefore the ratio is many more than ten times between the fed and the inhaling animal; in all probability only one-tenth of the contained lead in the respired air reaches the lung. Under these circumstances the ratio of poisoning via the lung to poisoning via the intestinal canal is as 100 : 1.

Table XIII. deals with the question of inhalation.

Every care was taken during these experiments to avoid any vitiation of such experiments by the actual swallowing of lead dust by the animals exposed to breathing. Moreover, all the animals were carefully controlled, in that an animal of somewhat similar weight at the same time was subjected to the ingestion of the same lead compound, but in much bigger quantities, via the mouth.

It will be seen immediately, on comparing Tables XI. and XII. with Table XIII., that the rate of poisoning by means of dust is greatly in excess of the rate of poisoning by feeding, even where poisoning by feeding actually occurred. Also that the amount of dust present in the air inhaled shows a marked correlation with the date of appearance of the first symptoms of poisoning, and that where the quantity of dust is very much reduced the poisoning was delayed longer than might have been expected, and that when poisoning did appear the symptoms were much less pronounced than with the more dusty atmospheres; and this although the quantity of lead obtained would be relatively the same over the range of time the animals were exposed.

The knowledge gained in dealing with industrial poisoning clinically receives very strong corroboration from these inhalation experiments, for it is a well-known fact that many persons engaged in dusty trades exhibit a species of immunity to lead poisoning. It is true that some susceptible persons, as has already been pointed out, very rapidly show signs of poisoning, even with a dosage producing no effect in other persons working under similar conditions; and it is highly probable that these persons have arrived at a species of equilibrium by which they are able to excrete the lead ingested, and so prevent any accumulation and general damage to their tissues. Directly, however, the dosage is increased, signs of poisoning come on, as in the[103] case of animals Nos. 10 and 11. For some seventy to eighty days little or no sign of poisoning was seen with the small dosage commenced with. At the end of this time, as no symptoms appeared, the quantity of lead in the air was increased, with the result that poisoning rapidly became manifest.

We have also in these inhalation experiments, in Cases 21 and 22, definite evidence that a low-solubility glaze—that is to say, glaze containing fritted lead—is capable of setting up lead poisoning when taken via the lung, as when such glaze is inoculated, although it produces no such symptoms when given via the mouth, except, perhaps, when it is complicated by excessive alcohol.

Symptoms exhibited by Experimental Animals.

—The cat is peculiarly susceptible to lead poisoning. In lead works it is impossible to keep a cat any length of time, as it rapidly dies of poisoning.

All the animals subjected to lead absorption, and definitely suffering from symptoms of lead poisoning, exhibited the following symptoms:

1. Slight increase of weight over the first period of poisoning, lasting from one to three weeks.

2. A progressive diminution in weight, progressing until the animal exhibited definite signs of poisoning.

3. Wasting, especially of the spinal muscles (the erector spinæ and in the lumbar region), out of proportion to the determined loss of weight; pinched facies, with frequent exhibition of running from the eyes and nose, even when not exposed to the action of lead dust, merely by inoculation.

4. Various types of paralysis, particularly in the cat; the muscles of the back and of the quadriceps extensor of the hind-legs show signs of paralysis. In the cat the quadriceps extensor is paralyzed sooner than the extensor communis digitorum in man. The cats show loss of power in the hind-limbs by inability to jump. The reflexes, particularly the knee-jerks and elbow-jerks, are first of all increased, and latterly become lost.

The chief and main sign which was noted in the histological examination of the animals inoculated was one of minute microscopical hæmorrhages (this has already been referred to); these hæmorrhages were not confined to any particular position in the body nor to any one organ. In the animals which showed symptoms of epilepsy, occasionally thickening of the pia mater[104] was found, but invariably in such cases small hæmorrhages were found immediately under the arachnoid, not covering any great area, but apparently causing pressure upon small areas of the cortex. In others, again, the hæmorrhages were found lower down in the brain, and a few in the spinal cord. At times a large amount of hæmorrhage was to be found present at the base of the brain, spreading downwards from the medulla into the spinal canal, but this only occurred in such animals as died with encephalopathic symptoms. In animals which had signs of more chronic poisoning—that is to say, gradual loss of body weight, emaciation, constipation, contraction of the abdomen, and paresis, particularly of the hind-limbs and the muscles of the back—hæmorrhages were found in the muscles, liver, spleen, lung, heart, various positions in the abdomen, in the spinal cord, in the nerve-supply of the affected muscle, and even in the brain, none of them large enough to produce absolute destruction of more than a very minute portion of the organ in which they were situated.

Now, all these symptoms, and, more important still, the phenomena of hæmorrhage, were found in all the animals which exhibited similar symptoms, whether they were poisoned by inhalation of dusty lead compounds or fed upon lead compounds associated with alcohol; but even in some of the animals which were fed upon lead compounds—particularly white lead—and which had exhibited no definite symptoms of paralysis, or, for that matter, any symptom referable to poisoning, here and there slight histological changes which were referable to minute hæmorrhages.

The experimental work therefore carries us very considerably forward in correlating the symptomatology and pathology of lead poisoning. The symptoms produced in susceptible animals by the actual inoculation of a lead compound differ only in degree and rapidity of onset from those produced in animals submitted to inhalation with similar compounds. Feeding, on the other hand—that is, ingestion by way of the gastro-intestinal canal—even in large quantities, did not produce poisoning to any great extent, except when some material such as alcohol was added, thereby breaking down the animal’s resistance. Another interesting fact is given—that if lead is taken by the mouth in addition to milk a great deal of the poisonous effect is got rid of; thus of two animals—Nos. 46 and 47—which received[105] lead nitrate in their food, the one in water and the other in milk, the one which received it in milk showed no effects even after four months’ experiment, whereas at the end of four months the animal which was receiving the compound in its water died. This brings out a point already insisted upon—namely, that in all lead factories it is highly important that no work should be undertaken first thing in the morning, before the workers have had a proper meal, and that in the absence of a proper meal milk is the best substitute. It is highly probable that the soluble lead salt becomes united in some form of albuminate which is dealt with later, and perhaps turned into a sulphide and excreted without absorption. There is no possible doubt, from the large series of experiments which I have performed, that lead inhaled is far more poisonous than when absorbed in any other way; further, that the amount of poisoning produced differs somewhat according to the type of compound inhaled, and the experiments, moreover, give some suggestion as to the dose which is likely to produce poisoning. It is seen, where the animal is inoculated with white lead, the dose required to produce symptoms is below 1 gramme per kilogramme of body weight, but above 0·2 gramme per kilogramme of body weight. In feeding, 0·8 gramme, and even 1 gramme, per diem for eighteen months produces no effect, although the same quantity plus an excess of alcohol rapidly produces the disease. On the other hand, as small a dose as 0·1 gramme of nitrate of lead given in water for four months produced death.

Turning to the inhalation experiments, the quantity of dust breathed when as high as 0·0007 gramme per litre produced symptoms after only twelve inhalations for a period of about thirty-seven days; whereas when the dose was reduced to 0·0001 gramme per diem the time required to produce symptoms of poisoning was 120 days; in fact, this last dose (0·0001) for the animal under experiment was almost the lower limit, as this animal showed an almost steady line of weight for a considerable time, the weight remaining up for the first hundred days, a slight variation taking place from week to week until a progressive diminution set in.

Practically all the animals poisoned manifested a very distinct diminution in body weight; in four only other symptoms of poisoning appeared first. This is a fact that is often to be noted amongst lead-workers, and if a progressive diminution in weight[106] takes place, there is strong reason for supposing that a considerable alteration in the metabolism of the body has taken place; but it does not follow that microscopical hæmorrhages or other definite effects of poisoning are present, although such is probable.

Finally, in summing up the conclusions to be drawn from the above experiments, it has been suggested that such experiments as inoculation, experimental inhalation, or even feeding, are no criterion of the circumstances under which industrial workers become infected with lead. It is perhaps hardly necessary to refer to this point, but for the fact that it is possible this book may be made use of by those who are not in the habit of dealing with experimental pathology. One of the first and most important matters in dealing with any form of poisoning is to obtain knowledge of the actual symptoms both clinically and physiologically, as well as pathologically, of the effects of any drug, and to determine if the symptoms so produced in an experimental animal conform to the symptoms as seen in man. For the purpose, therefore, an animal is required which is susceptible to the poison, and therefore cats were used in the foregoing experiments, as it is absolutely impossible to keep a domesticated cat in any white lead works, for the animals invariably become poisoned by lead.

The second point in prosecuting an inquiry into the pathology of any disease is to determine the train of poisoning when definite dosage, both in quantity and compound, is made use of. By feeding an animal with a compound only, the absorption through the gastro-intestinal canal could be studied; whereas by inoculating some of the compound—in suspension if it be insoluble, or in solution if it be soluble—into the subcutaneous or muscular tissue, the direct action of the body fluids on the compound may be studied; and, furthermore, its absorption by the membranes—that is, the cell membranes and the animal tissues—are determined. It is necessary to give at first a dose big enough to produce definite symptoms, and then to gradually decrease the dose to find the minimum amount producing symptoms within a reasonable amount of time. Inoculation experiments therefore give an answer to a number of these questions, and are the basis upon which further inquiry is conducted; they form a criterion from which it is possible to judge the effect of inhalation, and the same remarks which have been made with regard to inoculation refer to inhalation experiments. It is essential first[107] of all, in the experimental animals, to subject them to rigorous enough conditions to obtain definite symptoms, and then, by varying the experiments, to study the amount, entrance, and general behaviour, of the poison, correlating the evidence so obtained from the definite knowledge already gained with the previous experiments.

It is hoped that this brief note on experimental evidence will assist in the elucidation of the foregoing experiments to those who are not conversant with the application of experimental evidence.

Further Experiments relating to Lead Poisoning amongst Painters.

—A series of further experiments were made, with particular reference to lead poisoning exhibited by painters; and as these experiments and their results could not have been undertaken without the previous knowledge gained of the pathology of lead poisoning due to the inhalation of particles of dust floating in the air, their discussion has been reserved until the previous section had been dealt with.

It has been supposed by some that surfaces painted with lead paint give off certain emanations containing the metal lead as an organic compound. As the incidence of lead poisoning amongst painters is exceedingly high, as far as any statistical evidence can be obtained (see p. 48), it would seem that the painter is peculiarly exposed to infection by lead dust; and if, in addition, organic compounds of lead were given off, he would be still more liable to lead poisoning.

Two methods of experiment were used:

1. The exposure of animals to the fumes given off from freshly painted surfaces, the paints used being compounded with white lead, lead sulphate, zinc sulphide, and zinc oxide.

Animals were exposed in a cage similar to that used in the inhalation experiments previously described, but, instead of blowing in the contaminated air, the cages were so arranged that boards freshly painted with the special paint under experiment were introduced into the cage daily, the animals remaining the whole time in the chamber. Special precautions were taken with regard to ventilation.

2. An animal was placed in a chamber, and the compound to be tested was heated electrically by means of a coil surrounding the glass tube in which the compound was placed. The current was regulated by means of resistances, so that the thermo-couple and galvanometer gave a constant reading of 59° C. Air was constantly[108] passed through the tube over the heated substance and into the animal’s cage, which was efficiently ventilated. In this way any emanations which were given off from the normal room temperature or up to 59° C. were carried over into the animal’s cage, and there breathed. The apparatus was so arranged that the heating coil extended close to the point of delivery into the cage.

The result of these experiments showed that the animals confined in cages and exposed to freshly painted surfaces, where the paint used was white lead, zinc oxide, or lead sulphate, very soon showed signs of poisoning, and they became emaciated and suffered from recurrent attacks of salivation. The animals exposed in the cages in which air was passed over either white lead paste, zinc paste, or lead sulphate paste, showed no signs of illness, although kept in the cage and subjected to the inhalation of any fumes which might be given off for three months, spending the whole of the day in the cage, but being removed during the night to separate cages.

It therefore seemed clear that, whatever illness was produced in the animals exposed to fresh paint, they were not suffering from absorption of lead, but of some other compound of which the paint was made. Various constituents of the paint were therefore tried—namely, the metallic bases, lead or zinc, and linseed-oil, with turpentine and lead acetate mixed with turpentine. The animal exposed to the turpentine alone very rapidly showed signs of disease—salivation, a tendency to diarrhœa, strabismus, but the latter only after a two-hour exposure, whilst the quantity of turpentine present in the cage air did not exceed 10 milligrammes per litre.

The animal exposed to turpentine and lead acetate exhibited few symptoms, but the same in kind as the animal exposed to turpentine alone. The linseed-oil animal showed no signs of disease whatever. The animals exposed to the metallic bases of the paint—namely, zinc oxide or white lead—showed no signs of poisoning as long as the compound itself was not thrown into the air in the form of dust; but when lead dust was present in the air the animal rapidly showed the ordinary signs of lead poisoning. The animal exposed to zinc oxide dust showed very little sign of discomfort, but by prolonged exposure early kidney disease was produced, and signs of chronic inflammation were detectable in the lung.

It is interesting to note in this connection that Lehmann[7] describes symptoms produced in cats when exposed to the vapour[109] of turpentine. The animals which I exposed to turpentine vapour exhibited the same symptoms as those described by Lehmann. He gave no result of the histological inquiry of the animals so exposed, but in no case, apparently, was the animal killed after exposure. In my animals exposed to the vapour of turpentine very definite disease of the kidney was produced, the inflammation tending rather to the tubular than the interstitial variety of nephritis. The tubules were found blocked with débris, their contour irregular and destroyed, and their substance pale and almost hyaline; whilst areas of cloudy swelling, together with small hæmorrhages, were to be found scattered about the kidney. The heart muscle was flabby, and the heart tending to dilatation; whilst microscopically hæmorrhages could be found throughout the organ of a minute capillary nature, and passing between and disturbing the muscle bundles.

No changes of any sort were found in the tissues of the animals exposed to the emanations given off from white lead paste. By analyses these emanations were found to contain no lead, but traces of aldehyde, formic acid, and CO₂. It follows, therefore, that the effect of turpentine when inhaled by the painter must be to act as a contributory cause of lead poisoning, and it is interesting in this connection to recall the fact noted on p. 38, that Garrod has described gout as occurring constantly among painters. The statement already quoted, that gout is not common among workers in white lead factories, where the exposure to lead is very much greater than among painters, points to turpentine as the cause of the increased incidence of gout among house-painters rather than lead absorption. The importance of dust containing lead as a source of illness and lead poisoning in painters must not be minimized, as in sand-papering, etc. (see p. 137). The importance of lead dust inhaled in this way is perfectly understood. It is, however, highly probable that the combined action of the turpentine with the lead accounts for the fact that headache is a common symptom of early disease in painters, which is not the case among white-lead workers.

REFERENCES.

Acute Poisoning.

—Acute poisoning by lead is not common. Industrially it hardly ever occurs. Zinn[1] states that, out of 200 cases of industrial lead poisoning in his clinic in Berlin, only one was to be regarded as an acute case. In most instances the poisoning is due to swallowing some compound of lead, either as an abortifacient or to commit suicide.

The pathology and symptoms of such acute lead poisoning depend in the first place upon the nature of the salt of lead swallowed, as, for instance, after swallowing sugar of lead a burning taste is complained of, with acute gastric pain, generally coming on within an hour of taking the poison, salivation, metallic taste in the mouth, acute hiccough, and griping pain in the abdomen. The mouth is stained a whitish-grey. Later there is a great fall in blood-pressure, the skin becomes moist, or a cold sweat may appear. The respiration and pulse drop; finally comes vertigo, acute headache, coldness of the extremities, anæsthesia, and death in one or two days, or the case passes on to one of chronic poisoning. If the patient survives for the first two or three days, retinal changes frequently make their appearance, and occasionally acute fever may supervene. Various paralyses also appear, and the case then becomes one of subacute or chronic poisoning.

The lethal dose for healthy adults is probably as large as 50 grammes for lead acetate, for lead carbonate 25 grammes; these doses are, of course, only approximate.

Post mortem in a case of acute lead poisoning by ingestion, the mouth and stomach show the presence of a lead salt in the mucous exudation, together with corrosive gastritis and considerable swelling and œdema of the mucous membrane. The large intestine is generally stained darkly, from a light brown[111] to a deepish black; this staining may not appear until quite low down in the intestine. There is hyperæmia of the liver, much engorgement of the vessels in the mesentery, the kidney, and the brain. The rest of the intestinal viscera show signs of engorgement. Fluid may be present in the peritoneal cavity, and occasionally in the other serous cavities.

The histological examination of the various organs exhibits the same microscopical hæmorrhages as are found in the cases of chronic poisoning to be described later.

Although acute lead poisoning is rare in industrial experience, it may occur from time to time. Several cases are on record where a workman developed an acute attack of poisoning as a result of immersion in a white lead beck; another case is described which followed immersion in a tank of solution of lead acetate.

An accident of this description may conceivably occur; the treatment of such a case should be energetic, as the poisoning is chiefly due to lead swallowed. An emetic should be given, followed by sublimed sulphur, or, better still, the stomach washed out with dilute hydrogen sulphide water slightly acidulated with sulphuric acid, so as to change any lead present in the stomach into the least soluble form. A brisk purge should be given, and the patient encouraged to drink considerable quantities of lemonade containing sodium or potassium citrate. Alcohol, even during collapse, should be avoided; a hypodermic injection of strychnine is preferable. It must be borne in mind that lead is absorbed in the upper part of the intestine, and only in a minute degree, if at all, from the stomach; it is re-excreted mainly by the large bowel and by the urine; to some extent also by the sweat and saliva. Treatment is therefore directed towards (a) forming an insoluble compound as far as possible; (b) promoting the elimination of the poison; (c) placing as little work as possible upon the tissues most affected. Only milk should be given as food for two to three days.

The diagnosis of lead poisoning is not in itself of any great difficulty where any one of the classical symptoms of lead poisoning is present, such as lead colic, paresis, or the characteristic lead anæmia or cachexia. On the other hand, the premonitory symptoms of poisoning, as seen by a club doctor, particularly in persons engaged in industrial processes, are more difficult to determine; but for the appointed surgeon, who has an opportunity[112] of watching them from week to week, the gradual development of anæmia, extensor weakness, and other early symptoms, should give no difficulty. The clinical diagnosis requires to be made earlier by the appointed surgeon than by the general practitioner; for the appointed surgeon’s duty in a white lead works is not only to treat lead poisoning when it is once established, but, by carefully noting premonitory signs, to avoid the development of actual symptoms in susceptible persons. It is convenient, therefore, to divide the diagnosis of lead poisoning, from the clinical standpoint, into two divisions—incipient and pronounced. Such incipient changes are for the most part noticed amongst lead-workers, and in many cases are more strictly signs of lead absorption than signs of lead poisoning.

The earliest symptoms of poisoning are found in the vascular system, and the curious pallor of the face in persons who have worked in lead for a considerable period is often pronounced, although the conjunctiva may not show such a diminution in colour as might be expected from the facial change, while the actual determination of hæmoglobin may be almost normal. In addition to this, a person of fresh colour working in lead, if susceptible, very quickly loses his florid appearance, often heightened by the colour of the face only remaining on the cheek-bones as a hectic flush. Such a person will also show diminution in the colour of the conjunctival vessels, and invariably a distinct yellowish appearance of his sclerotics, due to the pigmentation of that tissue by broken-down blood-pigment. The yellow colour of the eyes is definite evidence that blood-destruction is in progress.

Following on the anæmia, or, more strictly speaking, the pallor of the face, a well-marked wasting of the subcutaneous fat takes place. In animals poisoned with lead in small or large doses—particularly in small doses given over a considerable period—this wasting of all subcutaneous and other fat is a very marked feature, so much so that practically no kidney, mesenteric or abdominal fat is to be found. The fat is lost in a greater proportion than other body tissues. In man the infra-orbital fat, together with the fat about the buccinator muscle, suffers early, and a curious facial contour is produced, two well-marked folds being seen—one the ordinary naso-labial fold, and the other situated at the anterior margin of the masseter. This, together with the loss of the orbital fat, gives the face a curious pinched appearance.[113] Such a pinched appearance is also to be found in animals (cats) poisoned by lead. The wasting frequently precedes any other symptoms, and it is no uncommon thing to find that a man who has been working in a lead process exposing him to inhalation of dust for a year is losing weight. In one case a man of 10 stone 7 pounds was reduced in weight to 9 stone 2 pounds in fourteen months, during the whole of which time he showed no signs at all of lead poisoning, and only towards the latter end of the time did he exhibit any blue line on his gums; there were no symptoms referable to lead poisoning. Such a case is typically one of lead absorption, which, if continued, would ultimately result in pronounced anæmia with either colic or paralysis, probably the former. The man in question was not engaged in any lead process, but was an electrician attending to the electric light and motors in a smelting works. His occupation necessitated work above the general ground-level, and therefore he inhaled the fumes and finer dust particles detached especially from the arc lamps which required adjustment.

In many persons who have worked in lead for long periods, wasting does not progress beyond a certain point, and these persons may be regarded as having established a certain degree of immunity. Men are met with who have worked in white lead factories and in smelting works for periods of from twenty to, in one case, forty-three years, a considerable portion of such period being antecedent to the time at which the regulations in force for dust removal and general protection of the workers were established, and they must have been exposed to much lead dust. Nevertheless they were less emaciated than many who have only worked a year or two years in a factory under modern hygienic conditions and special regulations. Such persons are either immune from the commencement, or they have established a certain degree of tolerance towards the metal; the latter supposition is the more probable, as there is reason to think several of them suffered from a mild degree of poisoning during the earlier years of their employment.

The rate of development of pallor and wasting are the important facts in incipient poisoning. Anæmia, together with the presence of basophile granules in the red cells, in a previously healthy person, and diminution in the hæmoglobin to 75 per cent., is definite evidence that absorption is leading on to poisoning—that is, blood-destruction—and coincidently insidious damage to[114] the finer bloodvessels and their nerve-supply (see Chapter V.). Such a person may at any moment develop a sudden attack of colic or paresis.

Associated with the wasting and pallor comes wasting of the muscles themselves, quite apart from any nerve lesions, and with it a certain degree of mental lethargy, slowness in comprehension, and loss of power over individual muscles or groups of muscles, more usually the latter. The mental lethargy shows itself in many ways—amongst others, heaviness and drowsiness—and careful examination should be made of any man who, previously a good time-keeper, commences somewhat suddenly to be late in the morning. The muscles of the hands and the arms, may show no definite wasting as compared one with another; but early loss of power, particularly of the extensors of the wrist or fingers, may be present for six months to a year before definite wrist-drop makes its appearance. In two cases under our own observation, loss of power of the extensor muscles of the wrist was present—in the one case for eight, and in the other case eleven, months before definite paresis occurred. In the one case the first symptom of paralysis was inability to extend the little fingers of both hands; the case was at once suspended from work, and was given treatment. Within forty-eight hours both wrists were so far affected that they could not be extended. In the second case the first symptom of paresis other than the loss of extensor power was the inability to oppose the thumb to the first index-finger of the left hand; within seven days complete wrist-drop of the left hand, partial drop of the right hand, including the middle and ring fingers, occurred. Both cases made a complete recovery.

By no means all wrists which show weakness of the extensor muscles ultimately develop paralysis; for, on looking through the records of the examination of three factories, only 4 per cent. of persons whose wrists were noted as showing loss of extensor power ultimately developed definite paralysis. In the extended position of the hands, when the surgeon is examining for extensor weakness, note should be made of any tremor, as fine tremor is frequently an early symptom of ensuing paralysis. The tremor is generally fine, increased on attempting to perform concerted acts (intention tremor); some loss of co-ordination may be found.

Where the nerve supplying the muscle has suffered alteration in its conductivity, as by the occurrence of a small hæmorrhage in[115] its sheath, gradual diminution in the nutrition of the muscle takes place; but whether or not this is sufficient explanation for the chronic wasting which is seen in the hands is not yet definitely proved.

In examining the hands outstretched for tremor and loss of muscular power, wasting of the interossei may be seen before any definite evidence of paralysis supervenes. On the palm of the hand both the thenar and the hypothenar eminences may show flattening, and attention should always be paid to this portion of the hand, as an early flattening of the hypothenar eminence particularly is one of the earlier symptoms of wrist paralysis.

Constipation.

—Constipation is a well-known precursor of colic in lead poisoning cases, but is by no means an invariable rule. About 15 per cent. of cases of lead colic suffer from intermittent diarrhœa.

A number of cases (see the table on p. 49) show that “rheumatic” symptoms are amongst those associated with lead poisoning. Some of these rheumatic symptoms, as has been explained, may be due to minute hæmorrhages, in the muscle or elsewhere, setting up the pains of a rheumatic nature in the part affected. One other symptom occurs with considerable frequency both as a precursor of colic and as an associated symptom in constipation, and even in diarrhœa associated with lead poisoning, and often regarded as of rheumatic origin—namely, lumbago. Complaints of lumbago in lead-workers should always be regarded seriously, as they may be a guide in discovering an early intoxication.

From what has been said of the excretion of lead into the large intestine in poisoned animals, the symptom of lumbago often complained of by lead-workers may, in some instances at any rate, owe its origin to overloading of the large intestine, due to the inhibitory action of lead on the intestinal muscles. It has been seen that excretion of lead into the large intestine is the normal method of excretion of the metal, and that concomitant congestion of the vessels in the corresponding mesenteric area is an associated symptom in poisoned animals. Local vasomotor spasm may also contribute.

The Pulse.

—The pulse in lead poisoning in the incipient stage is perhaps not so important as when poisoning has become pronounced. Considerable variation exists amongst different observers with regard to the blood-pressure of lead-workers. Our experience is, on the whole, that it tends to be high,[116] and pressures of 150 to 170 mm. Hg are common. In an average of 100 cases we found the highest pressure to be 178, and the lowest 115, the mean 150.

Collis[2], in a special report on smelting of materials containing lead, gives the average blood-pressure of 141 smelters as 148·2, and of 38 white lead-workers as 156·5.

Increase of tension undoubtedly takes place as lead absorption becomes more established, and the well-known high arterial tension of arterio-sclerosis is to be found in most workers employed in lead for any considerable period. Even in the cases quoted above showing no signs of lead poisoning, notwithstanding long duration of employment in lead factories, there was a distinct increase of arterial tension, not necessarily attributable to lead alone, but possibly also to such incidental causes as gout, alcoholism, syphilis, etc. When colic is present, marked diminution in the pulse-rate may be noticed during the spasms, and even without the presence of colic a diminution in the pulse-rate, with a definite increase of tension, as estimated by the finger, is a matter of practical importance in the diagnosis of absorption.

In quite early stages the pulse may be increased, and a small, rapid pulse should be regarded as a suspicious sign. Only in the later stages of the disease do alterations in the heart-sounds take place.

Sphygmograph tracings of the pulse of lead-poisoned persons shows the well-marked high tension type.

Lead Colic.

—Probably the commonest symptom, and the one for which first and foremost relief is sought, is abdominal colic. The colic of lead poisoning, when once seen, is rarely mistaken a second time. The pain is generally referred to the lower portion of the abdomen, low down, and often the sufferer points to a position immediately above the pubes; pain may often be referred also to the right iliac fossa, and on this account the possibility of appendicitis, or even perityphlitis or chronic colitis, must not be forgotten.

Colic, as shown in the statistics on p. 49, is the chief symptom complained of. No doubt, as has been previously suggested, the fact that colic is so common a symptom induced earlier pathologists to regard the entrance of lead through the gastro-intestinal canal as being the portal of lead infection. We have, however, demonstrated in the chapter on Pathology that the absorption[117] of lead, particularly in industrial processes, is mainly by way of the lung, and in the résumé of the literature it has already been pointed out that strong evidence exists for regarding colic and other abdominal symptoms associated with pain as due to vaso-motor disturbances in the splanchnic and mesenteric areas.

Lead colic is usually irregular, with marked exacerbations and remissions, and in the acute form the legs are drawn upwards towards the abdomen, the body is flexed at the hips, the face anxious and drawn, whilst the body is covered with a cold sweat, the eyes are staring, and convulsive movements of the limbs occur. The sufferer often finds relief from firm pressure upon the abdomen, a point of considerable importance in diagnosis; the pain is not increased, but distinctly relieved, by firm pressure.

If the abdomen be digitally examined during a paroxysm of pain, the intestines will be found contracted under the fingers, often in an irregular fashion. In an animal acutely poisoned with lead the intestines are found irregularly contracted during a very large portion of their length, and when removed from the body have the appearance of a string of sausages. There is evidence that spasmodic contraction of the circular fibres of the muscles of the mucosa has taken place, and the wave of peristalsis, moving forward, meets with a block at these points of constriction, thereby causing pain.

The colic affecting the lower part of the abdomen may possibly be related to the excretion of lead into the large intestine, and the affection of the bloodvessels in the mesentery, and in animals poisoned by means of lead the vessels in the mesentery, particularly in the region of the ileo-cæcal valve and the large intestine, are engorged with blood.

During a paroxysm the patient frequently screams in agony and rolls about upon the bed or the floor. Temporary relief may be obtained by leaning upon a pillow placed upon the back of a chair. The relief afforded by such procedure is also strongly in favour of the vaso-motor origin of the pain. During the spasm the abdomen is retracted, and fibrillary twitching of the abdominal parietes may often be seen; a constant desire to go to stool is generally present, but only results in straining and, perhaps, the passage of a little mucus and blood.

Vomiting is often associated with this stage, and the patient frequently vomits a considerable amount of thick, tenacious mucus. The vomit is not uncommonly regarded by the patient[118] as composed of white lead, if he has been working in that industry. Tanquerel in 1,217 cases noted vomiting 400 times, and marked retraction of the abdomen 649 times. Occasionally the patient complains of a sense of great weight in the abdomen, particularly in the intervals between the spasms of pain.

During the exacerbations of colic very marked diminution in the pulse-rate takes place, a fact that has already been referred to in the section dealing with vaso-motor disturbances. The pulse may be as low as 20 beats per minute, but it varies generally between 40 and 50 per minute.

Very occasionally the first stage of colic is associated with a slight rise of temperature. This must be regarded as an intercurrent affection rather than as one definitely associated with lead poisoning. Probably in such circumstances a gastritis other than the lead vaso-motor colic is the reason for the elevation of temperature, but it may confuse the diagnosis, suggesting rather an acute gastritis than lead colic. Under normal conditions the temperature falls during the colic, the extremities are cold, and the body is covered with a moist perspiration, the temperature dropping to 96°, and even lower.

On palpating the abdomen during these acute exacerbations, it is found that not only the gastric region, but the whole of the abdomen, is affected. Occasionally the acute pain is referred to the navel, but generally to the lower region of the abdomen; and very frequently the pain is described as running down into the scrotum, whilst there may also be pain complained of as far as the knee-joint, but this last is unusual. There may or may not be well-marked peristalsis taking place, but quite commonly large hardened tumours can be felt in various situations in the abdomen, corresponding to the contracted intestinal walls. Shifting tumours, then, may be regarded rather as a diagnostic sign of the acute forms of lead colic.

The colic rarely commences without some slight prodromal symptoms of dyspepsia or gastric discomfort; generally for two or three days preceding the attack there is loss of appetite, with a distaste for food, and obstinate constipation, particularly a general feeling of languor associated with an unpleasant taste in the mouth. Tanquerel, and later Grissolle[3], among others, described a form of stomatitis which they thought was a prodromal symptom of an attack of lead colic. Our own experience, however, does not at all coincide with these statements.

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Very occasionally the sufferer from acute colic may die during a paroxysm due to heart failure, but we have had no experience of such a fatality, although such an occurrence has been recorded on more than one occasion.

After the first acute attack of colic, which generally commences suddenly, often without previous warning, but is as a rule ushered in by irregular and finally complete constipation, or with diarrhœa alternating with constipation, the colic still occurs at irregular intervals; and although the constipation be relieved by enemata or the use of strong purgatives, paroxysmal pain will recur for days, and even weeks. In one particular case colic recurred at intervals for eight weeks, although the bowels were open each day and the patient had been under regular treatment, whilst the anæmia and other general symptoms of poisoning had disappeared.

According to the researches of Meillère[4] and others, lead is stored up in the body in various situations, and is gradually eliminated, such elimination taking place mainly through the fæces, and only to a limited extent through the urine. Probably the elimination of lead through the lower part of the intestine accounts for the recurrent attacks of colic.

Amino[5], Chatin[6], and Harnack[7], regard this colic as due to vaso-constriction taking place in the splanchnic area, and the rapid action of such drugs as atropin, chloroform, and nitroglycerine, support this view. In fact, Mayer[8] in 1881 demonstrated that in lead colic the splanchnic vessels undergo well-marked minute inflammatory changes. Others, from investigations carried on in persons who had died of lead poisoning, regard the acute pain as set up by irritation of the sympathetic nervous system, particularly of the solar plexus, irritation of the nerves in this region presumably setting up reflex colic.

The inhalation of amyl nitrite during an attack of colic will often entirely relieve it, and the pulse will immediately rise to the normal rate. It is difficult, however, in observing a case of colic, to determine whether the colic is preceded by slowing of the pulse and the rise of blood-pressure, or whether the colic is the immediate exciting cause of the constriction of the vessels and the alteration of the pulse-rate.

Chronic Colic.

—The acute form of lead colic frequently passes on to a chronic condition; the attacks become much less intense, and may at times only amount to general discomfort in the abdomen,[120] but the symptoms may last for several weeks, and even months, with no abdominal discomfort for a period of a week or ten days, then recurrence of pain, gradually increasing until it has attained a considerable degree of intensity, and then passing away, only to reappear in two or three days’ time. In such cases of prolonged colic after an interval of two or three weeks, small doses of strychnine or tincture of nux vomica will determine the onset of an attack of colic, showing that the intestinal muscular tissue remains in a state of hypersensibility long after the attack appears to have passed away.

A particular form of colic of long duration with exacerbations and remissions has been known for many years in the French navy, called “seamen’s colic.” Before this time outbreaks had occurred in various parts of the world, and John Hunter[9] described a form of dry bellyache occasioned by drinking certain West Indian wines, the wines in question having been stored in contact with lead—in fact, the vigorous Saxon of John Hunter peculiarly describes this chronic form of lead colic.

Although the prodromal stages of malaise, lassitude, loss of appetite, nausea, etc., generally precede both the acute and the chronic forms, colic often commences suddenly. Men may be examined in the factory in the morning, when the ordinary routine examination has elicited no symptoms, and yet cases of acute colic have occurred later in the same day in the very men examined.

The chief points associated with lead colic are—

1. The intermittent character.

2. The relation of the colic mainly to the lower part of the abdomen.

3. The slowing of the pulse.

4. The relief afforded by firm pressure on the abdomen.

To which may be added the action of amyl nitrite and other drugs of a similar physiological action.

Headache.

—Persistent headache is another of the symptoms associated with lead poisoning, but it is not common as an early symptom. The headache complained of by painters is probably not due to lead poisoning, but, as has been suggested, to turpentine. The headache of lead poisoning is invariably a later symptom, and frequently follows an attack of colic a week or more after the abdominal pain has ceased. The position of the headache varies; it may be of the vertex type, almost entirely[121] confined to the vertex and occipital regions. On the other hand, it is frequently irregular, and neuralgic in type; but in this type, frontal and temporal, more particularly temporal, the patient describes the pain as if a blunt instrument were being pushed through his head from both temporal regions at the same time. Earache, or pain in the region of the petrous portion of the temporal bone, may at times suggest ear disease, but this situation is not so common as suboccipital or temporal pain.

The headache in these situations is no doubt associated with the meningeal artery in the temporal region, and with the sinuses in the occipital region. The headache, not unlike the colic, undergoes remissions and exacerbations. With the exacerbations vertigo is common, and on more than one occasion in our experience a person suffering from persistent lead headache and vertigo has been arrested as suspect of alcoholism. Headache and vertigo without either colic or paresis is by no means uncommon, and may be associated with pains in the arms and legs. These pains are generally referred to by the patient as rheumatic, and it is a little interesting to call to mind the number of instances in which rheumatic symptoms are returned as associated with lead poisoning in the statistics given on p. 48. It is probable that these pains are neither muscular nor purely nervous in origin, but are primarily due to small lesions of the bloodvessels, as described in the chapter on Pathology, occurring in various parts of the body, and thereby setting up localized irritation, too minute to form an area which can be discovered by palpation, but sufficiently pronounced to produce irritation and reflex pain, in some respects similar to “bends” in compressed air disease. This special type of rheumatic pain differs, of course, from the lumbago associated with constipation.

Persistent headache is an exceedingly grave feature, and although it may at times disappear quickly on treatment, mental clouding and alteration of the higher functions is always to be feared; not infrequently persistent headache ushers in a final and fatal encephalopathy. In such a case the headache persists, becomes more and more excruciating, the patient rapidly shows loss of mental power, and may gradually sink into a condition of delirium. On the other hand, an attack of acute delirium may suddenly supervene, commencing with sudden loss of consciousness, followed by irregular movements of all the limbs, frothing at the mouth and nose, and finally mania. Recovery[122] is by no means uncommon, and after a sudden attack of this description the patients are entirely ignorant of the whole circumstance; they may occasionally recover powers of locomotion, and wander to long distances, unable to give an account of themselves or to remember their names, and only after a considerable time recover consciousness of their identity; but this type of case is comparatively rare.

The case quoted by Mott[10] gives a typical history of mental affection due, no doubt, to lead, but partially complicated by alcohol.

The Burtonian Line.

—Much controversy has raged around the significance of the blue line on the gums to be seen in certain persons working in lead, as to whether this particularly well-marked sign is to be regarded as a diagnostic symptom of lead poisoning or not.

For a long time it was regarded, and by many is still regarded, as sufficient evidence in itself to determine that a person is suffering from lead poisoning. On the other hand, those who have had considerable experience of industrial lead poisoning, particularly in the routine examination of workmen occupied in various lead industries, do not regard the occurrence of the Burtonian line as of more value than that the person showing such pigmented gums has been exposed to lead absorption.

There are two kinds of Burtonian line:

1. A fine bluish line is seen around the gingival margins, more pronounced on the interdental papillæ of the gum, and always more marked around such teeth as are coated with a deposit of tartar than around teeth which are clean. This line is undoubtedly due to the decomposition of the lead salts which have gained access to the mouth, by the sulphuretted hydrogen produced by the decomposition and putrefaction of food, epithelial débris, and other materials, which have accumulated around the edges of the teeth and in the interdental spaces. Peculiar evidence of this may often be seen in the mouths of certain persons whose parotid glands are discharging saliva which promotes deposits of calculus. Thus, one may often find merely the two first upper molar teeth on both sides of the upper jaw coated with tartar, no other teeth in the upper jaw being similarly affected. This deposit of calcium phosphate and carbonate is exceedingly porous, and becomes saturated with the products of decomposition, evolving sulphuretted[123] hydrogen in fairly large quantities. In the mouths of such persons working in lead factories a dark bluish staining of the cheek in apposition to the filthy tooth may be frequently seen, and where the rest of the teeth are free from deposit no such staining is observable. Viewed with a hand-lens, the blue line is seen to be made up of a large number of minute granules of dark colour which are deposited, often deeply, in the tissue. It is a matter of importance to note that a blue line is rarely seen in the mouths of those persons who pay attention to dental hygiene; where the teeth are clean, the gums closely adherent to the teeth, and entire absence of pus and freedom from deposit we have never seen a Burtonian line produced. Many of the so-called healthy mouths with perfect teeth have yet infected gums.

On examining sections of such a line, it is interesting to note that at first sight the particles appear to be situated deeply in the tissue, and mainly in relation to the bloodvessels supplying the gum. A little closer attention shows that the particles are really aggregated, particularly in the deficiencies between the epithelial cells which are constantly thrown off from the surface of the gum, a process which has its origin in an inflammatory condition, the whole gum becoming hypertrophied, with numerous small areas of ulceration. In these positions a certain amount of direct absorption of dust and fine particles takes place from the ulcerated surface, and becomes converted into lead sulphide by the sulphuretted hydrogen produced locally from the decomposing tissue. A certain amount of pigmentation is also referable to the mucous glands. It is well known that, in infections of the mouth of the type of pyorrhœa alveolaris or of rarefaction of the alveolar process, a good deal of infection coexists in the mucous glands of the buccal membrane, especially along the gum margins themselves, and the lead dust also becomes deposited in these glands, and later forms a sulphide. It is possible that some blue lines are due to excretion of lead from the blood.

Some little care is required to differentiate between the early lead Burtonian line and the curious bluish-grey appearance of the gum edges in cases of pyorrhœa alveolaris; when once the two conditions have been studied, little difficulty exists, but the use of a hand-lens will at once settle the matter. The bluish appearance of the gum in many cases of gum disease is due to local cyanosis. A few other forms of pigmentation of the gum[124] edges exist, such as an occasional blue line seen in workers with mercury, a black line in coal-miners, and so on, but these hardly call for discussion in the present instance. Any pigmentation of the nature discussed above is to be regarded as a sign that the worker has been subjected to the inhalation of lead dust, and is therefore suspect of lead absorption, in whom definite symptoms of lead poisoning may be expected to occur if the exposure to the harmful influence be long-continued.

2. In the second variety of blue line the pigmentation is not confined to the gum edge or to a band rarely exceeding a millimetre in width, as is the ordinary common blue line. In this case the whole of the gingival mucous membrane from the edges of the teeth, and extending some way into the buccal sulcus, five or six millimetres or even a centimetre wide, may be seen.

When this phenomenon is present, it is always associated with a marked degree of pyorrhœa alveolaris, the gums are soft, œdematous, and pus oozes from their edges, the teeth are frequently loose, and the other symptoms of disease of the os marginum are present.

Sections made from such a case suggest still more that some excretion of lead has taken place from the bloodvessels, as the lead particles may be seen closely related to the capillaries; but here again there is little doubt that it is due to absorption from the externally inflamed surfaces of the gum rather than excretion of the vessels themselves. It is interesting to note that, in all the experimental animals, in no instance has any Burtonian line been observed, although the animals (cats and dogs) have been fed upon cat’s meat, which readily undergoes putrefaction, and organisms capable of producing sulphuretted hydrogen are invariably present in the mouths of such animals. Notwithstanding this, the blue line has not been observed, because the animals’ gums were entirely free from infection or pathological changes. By causing an artificial inflammation around the canine teeth of an animal exposed to lead infection, a definite blue line was produced in two weeks. This line had all the characteristics of the common Burtonian line.

This form of blue line with a deep pigmentation of the whole of the gums, although in itself not to be regarded as diagnostic of lead poisoning alone, rarely occurs unless the person has been subjected to such long-continued poisoning that other symptoms have already made their appearance.

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The blue line, then, whichever type is observed, cannot in our opinion be regarded as a diagnostic sign of lead poisoning, but is merely an indication that the person who exhibits the phenomenon has been at some time or other subjected to lead absorption.

There is no evidence to show that lead is excreted by the salivary glands. A number of cases of poisoning certainly complain of a metallic taste in the mouth, and, judging from the analogy of mercury, it is possible that excretion of small quantities of lead may take place through the saliva; but such a point is merely of scientific interest, and has no practical bearing on the question of lead poisoning. Pigmentation in the salivary glands suggesting excretion of lead has not been observed, notwithstanding the constant presence of potassium sulphocyanide in the parotid saliva. The blue line of Burton may occasionally be observed, in other regions of the body. From time to time the intestine is found stained with a bluish-black deposit of lead sulphide, and in a case of acute poisoning following the ingestion of a large quantity of lead acetate, and in the cases described by Oliver of the ingestion of lead oxide (litharge), black staining of the intestines was peculiarly well marked. In all the animals referred to it forms a constant feature in the large intestine, and in the chapter on Pathology this blue staining of the large intestine is more minutely described. We have met with it once in the post-mortem examination of a man who died of lead poisoning, and when found it may, we think, be regarded as a diagnostic sign. Macroscopical evidence is not sufficient; it is necessary to make a histological examination of the tissues, when the stained areas are seen to be associated with the lymphoid tissue in the intestinal wall, and not only interstitial portions, but actually the interior of the cells themselves, are found to be packed with small bluish granules. Such a histological finding would be highly characteristic of an extreme case of lead poisoning.

Where considerable quantities of lead have been taken into the gastro-intestinal canal, a blue ring has occasionally been described surrounding the anus.

About 85 per cent. of cases of lead poisoning with colic show obstinate constipation as a leading symptom. The constipation generally exists for several days preceding the onset of the colic, and may persist for as long as twelve to fourteen days,[126] while six to seven days is a common period. There is very little that is characteristic about the constipation other than its intractability; indeed, it is frequently of the greatest difficulty to relieve this symptom. No doubt the direct origin is due to the excretion of lead into the large intestine (see p. 94).

Palpation of the colon often shows distension, with a good deal of pain on pressure at both the hepatic and splanchnic flexures, more particularly the latter. Distinctly painful spots may be found in the length of the intestine, due to small ulcers, or more probably to the minute hæmorrhages which we have elsewhere described as associated with lead poisoning. The remaining 15 per cent. of cases have as a prodromal symptom diarrhœa. Further, diarrhœa is not uncommon amongst persons who are working in a lead factory, and who do not show other signs of poisoning; and as lead taken into the body in various ways is excreted through the fæces in common with other heavy metals, such as iron, bismuth, nickel, as well as arsenic, the occurrence of diarrhœa should suggest to the surgeon the possibility of considerable lead absorption having taken place.

REFERENCES.

Symptomatology and Diagnosis (Continued)—Excretion of Lead.

—The two chief channels for excretion of lead are the urine and the fæces, while some include the saliva and the sweat.

In the case of the sweat there is not much evidence, but a few observers, mainly French, claim to have discovered traces of lead in the skin of lead-workers. In such a case, however, it is exceedingly difficult to eliminate the question of surface contamination; and although brisk peripheral circulation and transudation may possibly carry off a certain amount of lead, the chance of this is highly improbable.

There seems rather more evidence that the salivary glands may eliminate lead, as a number of other substances are undoubtedly passed in this way. Mercury certainly undergoes excretion through the salivary glands and the mucous glands of the mouth, and it is therefore not improbable that a metal so closely related in its chemical, and perhaps physiological, relations may be excreted in a similar fashion. Meillère[1] cites three instances of parotitis which were considered to be of lead origin, and further quotes an instance where, in chemical examination of the salivary glands after death, lead was found in small quantities.

Chronic parotitis is not infrequently cited as a symptom in cases of reported industrial lead poisoning, and may owe its origin to impairment of the salivary gland by the passage of the metal. Chronic parotitis, or even tenderness of the parotid glands, does not occur frequently among lead-workers with symptoms of lead absorption. Excretion, however, of lead through the salivary glands is not of great importance, except from the occasional complaint of a metallic taste in the mouth in chronic[128] lead poisoning, and in such instances possibly definite excretion of lead is taking place through the parotid glands. A case may be cited which rather supports the view that lead may be excreted through the salivary glands. A certain worker engaged in a dangerous lead process from time to time, but never as a constant symptom, showed distinct pigmentation in the internal surfaces of both cheeks in the region of the buccal papillæ of the parotid duct. The pigmentation was intermittent; at times a large patch of deep blue-black pigmentation was found in the situation on both sides, with no staining of the cheeks around or of the gum margins, although his teeth in these regions were coated with foul tartar. If the lead in this instance gained access through the mouth, why should it have been deposited merely upon the cheek in this one situation, despite the fact that several other situations in the mouth exhibited the same conditions of bacterial decomposition for the production of sulphuretted hydrogen? We have not observed this pigmentation in the neighbourhood of the ducts of the submaxillary and sublingual glands, but only in the parotid.

By far the most important organ in the excretion of lead, from the point of view of symptomatology and diagnosis, is the kidney. Lead is not uncommonly found in the urine of lead-workers and in the urine of those suffering from lead poisoning. The quantity present is usually small and in a form in which it is exceedingly difficult to detect. Yet very pronounced changes in the kidneys may take place, with little evidence in the urine itself that pathological changes are taking place.

The urine of workers in lead factories is frequently high-coloured; in fact, as a general rule the degree of pigmentation is greater than is normal, and in those persons who show some degree of icterus, with the curious yellowish-brown colour of the conjunctivæ, hæmatoporphyrin may be detected on applying suitable tests.

In well-established cases of chronic poisoning, albuminuria as a rule is found, together with certain alterations in the other constituents of the urine, such alteration frequently making its appearance before the definite onset of albuminuria. Further, the changes in the eye, referred to under a special heading, have been frequently described as albuminuric retinitis of lead origin, it being true that eye changes are often associated with chronic changes in the kidney.

[129]

In acute poisoning lead is generally found in the urine, but in chronic poisoning it is by no means a common occurrence. From time to time small quantities are excreted, and in the chemical analysis made of the kidneys in cases of fatal lead poisoning a certain amount of lead has frequently been noted. Wynter Blyth[2] found in the kidneys of two white lead workers a total of 0·003 gramme. Peyrusson and Pillault[3], quoted by Meillère, found a similar quantity, 0·003 gramme, while in experimental animals Meillère himself found considerably less, only 0·0001 gramme; Stevenson, in a case reported by Newton Pitt[4], 0·0086 per cent. of lead in the cæcum and colon. Notwithstanding a small quantity of lead which may be determined by chemical methods as present in the urine or the kidney, very definite nephritis is set up in these organs, obviously due to the irritative effect of the metallic poison.

The Kidneys.

—Kidney disease of several types has been described as associated with poisoning by lead, particularly with chronic lead poisoning, where large quantities of a soluble lead salt have been ingested. Very considerable strain is thrown upon the kidney, with the result that the lead salts themselves are passed through; but, as has been pointed out when dealing with acute poisoning, the passage of lead through the kidneys does not continue for any considerable time, and in lead poisoning of an industrial and chronic nature no lead at all has been found in the urine in undoubted cases. Even when present, it may be difficult to detect unless the electrolytic method is used (see p. 174). At the same time kidney disease undoubtedly does occur in a very large number of workers.

All heavy metals, of which silver, mercury, iron, zinc, and finally lead, may be quoted as examples, appear to be eliminated by the kidney when they are present in the body in toxic doses, and often when in small non-toxic doses, but in the latter case to a greater extent through the bowel than through the kidney. The lead circulating in the blood, in common with other heavy metals, may be found chemically in the kidney, but the quantity recovered is not as large as one would expect from the considerable amount of inflammation often present.

In the experiments on animals, subjected to poisoning over considerable periods, the condition of the kidney in every instance showed distinct histological changes; and the longer such animals had been subjected to the poisonous effects of the[130] metal, the more advanced were the signs of degeneration in its structure. In the earliest cases the disease partook much more of the nature of an interstitial nephritis, and it was in the later and more chronic stages only that changes in the glomeruli and fibroid degeneration were to be found, but in even these earliest cases of poisoning definite minute interstitial hæmorrhages were to be found scattered about the kidney. These minute hæmorrhages did not cause symptoms of hæmaturia, as in none of the experimental animals was bloody urine observed. On the other hand, besides definite small areas of hæmorrhage, patches were discoverable, indicative of hæmorrhage which had undergone fibroid change. Even in the illustrations given by Glibert[5], there appears to be evidence that hæmorrhage had taken place and had undergone fibroid degeneration, and there is very little doubt that in cases of kidney disease, the preliminary action of the poison determines small local yieldings of the vessel walls, with leakage, often hardly amounting to true hæmorrhage, at such spots. There is nothing opposed to the theory in the findings of other observers; in fact, if the preliminary gross effect be leakage of the description given, all the other lesions described by various observers follow as a corollary.

In the kidney, as in the other regions of the body, the venioles rather than the arterioles appear to be the preliminary site of destruction, and microscopical observation of the sections leads to the view that the intima of the vessels and not the media or the muscular coat is the one affected in the first place. Capillary hæmorrhages under these conditions are easier to understand than if the arterioles themselves or their muscular or middle coats were primarily affected. As degenerative changes progress, the whole of the vessel—external and middle coats and intima—undergoes change, ultimately resulting in the extreme narrowing and consequent blocking of the vessels themselves. Further shrinkage taking place in this area produces the shrunken sclerosed kidney.

Zinc in the form of oxide behaves in very much the same way upon the kidney as does lead. An experimental animal, which was given 0·2 gramme of zinc oxide per kilogramme body weight by hypodermic injection in the muscles of the back, died in fifteen days, and the kidneys showed extensive hæmorrhages—not merely the minute and capillary hæmorrhages found in lead[131] poisoning, but hæmorrhages extending right through from the cortex.

Clinically, kidney disease, unless albumin be detected in the urine, is not a prominent symptom during the progress of an attack of chronic lead poisoning, and is to be regarded as a late symptom, developing as the result of long-continued irritation. The difficulty of eliminating alcoholic complication has been discussed, and there are no specific symptoms or post-mortem signs which enable one to distinguish alcoholic nephritis from the nephritis of lead poisoning.

In the chapter on Pathology, the effect of alcohol on the kidney was cited as a common predisposing cause of kidney disease in lead-workers, and the effect of alcoholic excess in the case of a person who is already the subject of chronic lead absorption may determine the change from absorption to definite poisoning, because of alteration in the excreting-power of the kidney. So long as the ratio between ingestion and excretion is maintained the balance is kept up, and, although the tissues of the body may show signs of a certain amount of degeneration, no definite disease is produced; but the gastric irritation and the work thrown upon the kidney in removing from the blood large quantities of alcohol may be sufficient to alter this absorption-excretory balance and determine the attack of poisoning.

Acute nephritis is rare, and cannot be regarded as a sequela of chronic lead poisoning. Acute nephritis occurring in a lead-worker, with the associated symptoms of general œdema of the face, eyes, hands, feet, is of the gravest possible moment, and such a sudden appearance of nephritis is almost invariably fatal. In chronic nephritis, to which most of the lead cases belong, the usual signs are to be found in the urine. Pain is rarely a symptom; and although pain in the back is often complained of by lead-workers, examination rarely suggests that the backache is of kidney origin, but rather the lumbago type associated with chronic constipation. Care, however, must be taken, when backache is complained of, in eliminating kidney disease as a possible origin of the pain. A quantitative examination of the urine, with reference to the total acidity and phosphate excretion, may assist; and although this is not possible in a routine examination of cases of lead absorption, it may be useful in cases of suspected poisoning, especially where there are evidences of a good deal of blood-destruction.

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For convenience of description, it is better to consider the action of lead upon the blood under two headings:

1. That of the corpuscular and other changes.

2. The action on the vessel walls, and pathological changes secondary to disease of the vessels.

The Anæmia of Lead Poisoning and Saturnine Anæmia.

—From the early days of medicine it has been known that lead produces poverty of the blood, and the white or yellowish-white appearance of persons who have been subjected to long-continued inhalation of lead dust or fumes constitutes striking evidence of blood-alteration. At the same time it is a common fact that the facial pallor does not always go hand in hand with diminution in the hæmoglobin. The conjunctiva may be observed as a test for colour, and here may be seen the curious vaso-motor disturbances which are partially responsible for the facial pallor.

Facial pallor in some forms of lead cachexia owes its origin to interference with the nerve-supply to the vessel walls, and it is a noticeable fact that a lead-worker whose face shows unmistakable signs of pallor rapidly flushes when spoken to suddenly or if mentally disturbed. The anæmia of lead poisoning is, however, a very definite fact. All observers are agreed that a marked diminution in the hæmoglobin of the blood takes place, to as low, often, as 35 per cent., without necessitating abstention from work, and without any serious interference with respiration, even when performing heavy manual labour.

In persons in whom the hæmoglobin is diminished there is frequently a yellowish or icterous hue of the skin, particularly the conjunctiva, due to staining of the tissues with altered blood-pigment. The hæmoglobin derivative—hæmatoporphyrin—can also be found in the urine of persons suffering from a marked degree of reduction in the blood-pigment, and may be taken as confirmatory evidence of destructive or hæmolytic anæmia. The symptom is, however, a later one than is frequently stated by the French observers, and can only be regarded as a later and confirmatory symptom, and not as an early one of diagnostic importance.

As would be expected from the destruction of blood-pigment, the morbid process leaves its imprint upon the individual red cells, and basophile staining of a number of the red corpuscles is to be found in a very large proportion of persons[133] poisoned by lead. Moritz[6] first pointed out that these alterations in the red cells were present in lead poisoning. The basophile granules are by no means confined to lead anæmia, but are to be found in any severe secondary anæmia where hæmolysis has taken place, as in nitrobenzene and aniline poisoning, carbon bisulphide, etc. In addition to the basophile-staining granules in the blood-cells, the whole corpuscle may take on a bluish-grey tint when stained. The best stain to demonstrate these bodies is Leishman’s modification of Romanowski’s, and there is no occasion to stain the blood in the fresh condition, as the presence of the granules may be demonstrated easily, even after two or three months. Schmidt[7] thinks that if the basophile corpuscles reach 100 per million red cells the cause is undoubtedly lead poisoning.

Alterations are also to be observed in the structure of the red blood-cells in addition to the basophile staining. Distinct vacuoles appear, but as a general observation—first noted by Glibert[8]—the blood appears to be more resistant to damage when making the films, and the red corpuscles themselves seem to be more elastic than normal (increased viscosity). Alteration in the shapes of the corpuscles also takes place, and not only small varieties—microcytes—but also the large macrocytes are to be found. Nucleated red cells are rare.

The diminution in the number of the red cells is not so pronounced as would be supposed from the diminution in the quantity of hæmoglobin; but in the later stages, as in other secondary anæmias of toxic origin, the total quantity of red cells sinks to a count of a million or less per cubic millimetre.

According to Garrod, etc., the alkalinity of the blood is decreased in lead absorption.

The white blood-corpuscles do not show any change in their structure by the ordinary methods of staining, but they apparently show, as do the red cells, more resistance to injury in spreading blood-films—that is to say, the viscosity of the blood, which is apparently increased in lead poisoning, is also exhibited by the white cells. In the early stages of lead poisoning, more especially in acute lead poisoning, distinct leucocytosis may be observed, such a leucocytosis showing itself rather in relation to the lymphocytes than to the polymorphonuclear cells. In addition, the large mononuclear cells are also greatly increased, and a differential blood-count from a case of lead poisoning which[134] also shows the presence of basophile granules in the cells invariably brings to light a definite increase in the percentage number of lymphocytes, and a decrease in the number of polymorphonuclears, and this even when the total leucocyte count is not outside the ordinary limit of normal variation. On the whole, the number of leucocytes present in the blood of persons suffering from lead absorption will always be found to tend rather towards the higher than the lower limit of normal variation.

At times a considerable increase in the number of eosinophile cells is found in films made from persons suffering from lead poisoning, particularly when there has been prolonged obstinate constipation. The count is never high, and is rarely more than 5 or 6 per cent. It is not usual to find any of the other forms of white cells in the blood, and in this way the anæmia of lead poisoning may be easily differentiated from the other forms, such as pernicious anæmia, lymphatic leucæmia, spleno-medullary lymphocythæmia. By examining a number of blood-films derived from persons subjected to lead absorption, and shuffled with a number of films from normal persons, one of us (K. W. G.) has been able to separate out, by the above method, the blood-films taken from the suspected persons. The criteria in the determination were—

1. The presence of basophile granules.

2. Total basophile staining and size of corpuscles—poikilocytosis.

3. Differential count, showing increase in a number of lymphocytes and large mononuclear cells.

Determination of the presence of lead poisoning from the examination of the blood, therefore, receives considerable support; but at the same time it is open to some objection from the fact that it is not in lead poisoning alone that basophile granules make their appearance in the blood. Any cause producing destruction of the red blood-cells, and even their depletion by prolonged hæmorrhage, is followed by an increase in the output of the red cells from the bone-marrow[9]. During this output of extra blood-cells from the bone-marrow, numerous cells gain entrance to the blood, in which the nuclei are not entirely degenerated; and it is these particular cells which give the phenomena of basophile staining, and their presence is rather indicative of the increased blood-formation that is progressing,[135] following blood-destruction, rather than direct evidence of blood-destruction itself.

In a number of forms of anæmia—in fact, in almost all forms of severe secondary anæmia, and certainly all forms of anæmia associated with hæmolysis—the presence of basophile granules may be demonstrated. They are commonly found in pernicious anæmia, secondary septic anæmia, and the anæmia of malaria. Practically, the use of basophile granules in the presence of the blood of lead-workers is being utilized in Leipzig for the early detection of lead poisoning. By means of the Zeiss eyepiece enumeration disc the relative number of basophile granule cells to normal red cells is determined; and when the number of red cells containing basophile granules exceeds 100 per million red cells, the individual from whom the blood is derived is regarded as in a presaturnine condition, and given proper treatment. By this means it has been found possible to diminish the number of persons actually suffering from lead poisoning.

The adoption of such a method has some drawbacks, especially in view of the fact that substances other than lead may cause the basophilia. At the same time there is no doubt that, if all persons employed in lead trades who showed basophilia were suspended from their employment at the present time, a very large number of persons would be dealt with. Yet the practical application of this method is by no means impossible under industrial conditions, and would at any rate give a definite test upon which diagnosis could be made, though it would be quite impossible to expect the general practitioner or the certifying surgeon to estimate the basophilic content. All such estimations would necessarily have to be performed at some properly equipped pathological laboratory, such as at the present time many municipal authorities possess.

These facts are of importance, as a differential count of the white cells, together with a careful inspection of a blood-film for basophile staining and alteration in the red cells, as well as other phenomena noted, together with an estimation of the hæmoglobin contained in the blood, are to our mind of considerably more value in the diagnosis of lead poisoning than is the quantitative estimation of the red or white cells. The following tables give a certain number of enumerations, etc., made from the blood of lead-poisoned persons:

[136]

BLOOD-EXAMINATION OF LEAD ANÆMIA—DIFFERENTIAL COUNT PER CENT.

• A = Polymorphonuclears.
• B = Lymphocytes.
• C = Large hyaline.
• D = Eosinophile.
• E = Transitional.
• F = Basophile.
• G = Microcytes.
• H = Megalocytes.
• I = Poikilocytes.
• J = Nucleated red.
• K = Plehn’s bodies.
• Corpuscles, Thoma-Zeiss.
• Hæmaglobin, Haldane’s instrument.
• Films, stained Leishman.

[137]

The form of lead inhaled is immaterial, and definite poisoning with alteration in the blood may be occasioned, not only with white lead and lead fume, but also even with lead sulphate and lead silicate.

The following table gives the result of blood-counts performed upon the blood of persons employed in the manufacture of a paint erroneously supposed to be innocuous, as the base consisted of lead sulphate and oxysulphate:

Differential Counts per Cent. of Blood-Films from Lead Sulphate Workers.

Sand-papering surfaces of painted objects, walls, coaches, etc., also throws a definite amount of lead dust into the air whenever the sand-papered paint contains lead. The following table gives the differential counts of the blood of persons employed in the furniture-painting trades:

Differential Counts per Cent. of Blood-Films from Furniture-Makers (Sand-Paperers).

Circulatory System.

—A very large number of the symptoms referable to chronic and well-defined lead poisoning are referable to circulatory lesions, and, as has been elsewhere pointed out, the ultimate nerve degeneration occurring in various parts of[138] the body is probably but a final symptom of the earlier hæmorrhage which has taken place. Certain symptoms are, however, more closely related to the circulation than others, and may therefore be more conveniently grouped together under the present heading. The smaller changes, many of them connected with special organs (such, for instance, as the eye) or particular regions (as the mesenteric vessels), have been already referred to in dealing with colic and eye changes. Vaso-motor changes precede the actual change in the vessel walls themselves. On the other hand, the alterations in the structure of the liver, lung, spleen, and more especially the kidney, are secondary to change in the structure of the walls of the vessels themselves.

Vaso-motor disturbances may or may not be of nervous origin, although the former view is probably correct, and it is also equally possible that the direct affection of the vessels is associated with the nerve irritation. On the other hand, direct inflammation of the vessel walls, resulting in obliterative arteritis, in arterio-sclerosis, and degeneration and exudation in the kidney, lung, and liver, are practically due to degenerative changes either in the intima or the middle coats of the finer vessels. The common symptoms of arterio-sclerosis, vertigo, headache, and pulsation in the vessels, and of the persistent headache already referred to, all suggest changes taking place in the vessels complicated by œdema. In the early stages of kidney degeneration, however, it is common to find an interstitial nephritis due apparently to exudation from the vessel walls. Such an hypothesis is to some extent supported by the somewhat allied condition of engorgement and fibroid change in the liver and lung, and to a lesser extent in the spleen. In the lung, even in persons not exposed to inhalation of lead, and in animals, as pointed out by Glibert, secondary changes in the lung follow lead intoxication, such changes taking the form of emphysema and generalized fibrosis; whilst the liver is engorged with blood, and later undergoes similar degenerative changes. The bloodvessels in these organs are found to have lost a considerable amount of their elasticity, to have yielded here and there, and in other places to be completely closed by obliterative arteritis. Microscopical hæmorrhages are to be found mainly in the veins leading from the capillaries. In the kidney such vessel changes as are outlined are the precursors of disease, and albumin is found in the urine, but the quantity is rarely very large. Casts[139] are not common, and the amount of lead present in the urine may be exceedingly small, difficult to trace, and in many cases entirely absent.

In the later stages of chronic saturnism the heart may show degenerative changes. Microscopical examination of the heart muscle shows that alteration of the fibres of the muscles takes place in a manner similar to that of the voluntary muscles. Disease of the heart valves is uncommon; alterations in the heart sounds are infrequent; the clinical picture of the cardiac condition is that of a “flabby” heart.

REFERENCES.

Symptomatology and Diagnosis (Continued)—The Nervous System.

—The most definite objective symptoms of chronic poisoning by means of lead are those of the nervous system. From the time of Tanquerel[1] affections of the hands and fingers and the muscles of the back have all been well known. Associated with the paralysis are local vaso-motor effects, such as cyanosed condition of the skin over the paralyzed muscles, cold hands, etc.; whilst later, if the paralysis be severe and persists, atrophic changes take place in the skin, muscles, bone, whilst definite contracture occurs from unopposed contraction of the unaffected muscles. Paralysis will therefore be associated with two of the great systems into which the body is divided for the purposes of medical and physiological description—namely, the muscular and the nervous—and, on account of the similarity of the clinical symptoms of lead paralysis, attention has been drawn rather to the nerve changes preceding muscular paralysis and degeneration than to other influences affecting the nerve inflammation.

Lancereaux[2] considered that lead poisoning resulting in paralysis takes the form of a gradual impregnation of the nervous tissue with lead salts, until such a time as degenerative effects are set up, and with it muscular paralysis.

Meillère[3], who has given much attention to the ætiology of lead poisoning, as well as to the clinical study of the disease, considers that plumbism may be divided into three periods:

(a) Impregnation of the tissues of the body, the nervous tissue being the chief one affected by lead salts.

(b) Retardation of the general oxidation changes of the body, resulting in malnutrition and general loss of tone.

[141]

(c) Establishment of intoxication, with the generalized affections, paresis, etc.

If three such periods can be recognized, as no doubt they can, as divisions of the time during which lead gradually affects the tissues, the symptoms in the more severe cases would be expected to be those associated with the more prolonged exposure. This, no doubt, is true to a limited extent, more particularly in industrial poisoning, depending for its development on a long-continued dosage of lead in minute quantities, and for the most part of metallic lead. On the other hand, with some of the salts of lead, notably the hydrated carbonate, acute disease may take place during the first stage—namely, impregnation of lead—the determining factor then being either the retardation of the elimination of lead, or a suddenly increased quantity in lead dosage, or some intercurrent disease, or even alcoholic excess, whereby a sudden large excess of the poison is thrown into the general circulation.

The commonest type of paralysis occurring is the one affecting the muscles of the hands, which may for a considerable time show some diminution in their extensor power before the actual onset of the disease takes place. The onset of paralysis is practically always unaccompanied by pyrexia; the only occasions in which pyrexia may be associated with the onset of the attack are those cases in which some secondary cause determines the paralysis, and the pyrexia in these instances is due to the intercurrent disease, and not to the lead infection.

Although weakness of the extensor muscles of the hands may be present in persons subjected to lead absorption for a considerable time, the actual onset of the disease itself is frequently sudden; but in the majority of cases it is distinctly chronic, and is rarely, in the case of paresis, associated with any definite prodromal symptoms. Prodromal symptoms have been noted, such, for instance, as lassitude, general debility, and more especially loss of weight. Cramps of the muscles the nerve-supply of which is becoming affected, alteration of the skin over areas corresponding to definite cutaneous nerves, hyperæsthesia, anæsthesia, or analgesia, may occasionally be present. Neuralgic pains have also been described, but these are inconstant, and generally of the arthralgic type related to the periarticular tissues of joints rather than to pain in the course of the nerves. The pain is rather of the visceral referred type[142] than a definite neuralgia. Tremor is, however, frequently associated with the preliminary condition of paresis, and in several cases variations in the amount of weakness of the extensor muscles of the wrist have been noticed, as far as can be estimated clinically without the use of a dynamometer. Associated with this weakness is tremor of a fine type, often increased by movement (intention tremor), and in every case more marked during the periods of increased weakness. Instances have occurred where definite wrist-drop followed after a prolonged period of weakness; in others the weakness has temporarily cleared up for six months, and no difference could be determined in the extensor power of the two wrists; while in others, again, the weakness is progressive, but slight, and insufficient to warrant the removal of the workman from his occupation. Again, progressive weakness may remain a symptom of the wrists of workmen for years.

The Forms of Lead Paresis.

—The paralysis may be partial or generalized, but the chief muscles affected are the extensors of the wrists and the forearm, and the interossei of the hand. As a rule, the first muscles to be affected are the extensor communis digitorum and the extensor indicis. The muscles of the shoulder—mainly the deltoid—come next in order, followed by the muscles of the leg, particularly the peroneus longus and brevis, with occasionally the interossei of the foot; the muscles of the back, neck, and abdominal walls, are occasionally affected, as are those of the larynx and diaphragm, and it is of interest to note that Trousseau pointed out that among horses employed in lead works paralysis of the superior laryngeal nerve often occurred.

Considerable difficulty is experienced in estimating the reason of the predilection of lead for the musculo-spiral nerve, this being the nerve mainly affected in wrist-drop. Owing to the fact that the supinator longus receives an additional nerve-supply to the musculo-spiral, this muscle frequently escapes paralysis when the whole of the other extensors of the hand are involved. Moreover, the predilection for given nerves differs in different animals, and one of us (K. W. G.) has found experimentally that in cats the first nerve to be affected is the anterior crural supplying the quadriceps extensor, whilst the second group of muscles affected are the spinal muscles, particularly in the lumbar region.

[143]

Among the speculations which have been made with regard to this predilection for definite groups of muscles supplied by one nerve, Teleky[4] examined forty cases of paralysis with special reference to Edinger’s theory—namely, that the function of muscles (and of other organs) breaks down under certain circumstances before the strain set upon them. In this way Edinger explains paralysis following lead poisoning as being due to excessive strain on the particular group of muscles affected, based on a consideration of the relative volumes and weights of the muscles of the hand and forearm, and the demands made on the several groups, flexors, extensors, supinators, etc., by the coarse or fine work respectively demanded of them in industrial employment. He concludes that—

1. Of the forearm, the flexors (triceps, anconeus, extensors, biceps, brachialis anticus, and supinator longus) possess a high degree of capacity for work, but are not called into play mainly in the execution of fine work; while the supinators are characterized by great mass, and are brought into play mainly in work of coarse and heavy nature, and not during fine manipulations.

2. The muscles concerned in pronation are of small capacity for work, and are not called on for sustained work.

As for the muscles acting on the wrist and hand, he concludes that the extensors (carpi radialis longior and brevior, carpi ulnaris, and the extensors of the fingers) are powerful, and much exceed in capacity for work the flexors (flexor carpi radialis, flexor carpi ulnaris, the flexors of the fingers, etc.), but in all fine manual work, and specially where close grasping movements enter into association with the flexors, external strain is put upon them, whilst the flexors merely support their action.

The extensor communis digitorum is the weakest of all the long finger muscles; its volume is hardly one-fourth that of the corresponding flexors, and while it acts only on the first of the phalanges, the flexors act on all three. In all fine work they are called on for heavy strain, especially the interossei and the lumbricals, but in harmony with the long flexors when grasping movements are performed. The small muscles of the fingers have nearly the same mass as the extensor communis, and in all fine movements the grasping efforts are taxed severely; but their play is under considerably more favourable physical relations than that of the extensors, whilst in addition they are aided in[144] their work at times by the long flexors. The chief adductor muscle of the thumb (extensor metacarpi pollicis) is particularly powerful; the other extensors of the thumb are very weak, and work under unfavourable physical conditions, but are supported in their action by the strong abductor muscle. The muscles of the abductor, opponens and flexor brevis, in the complicated work thrown on the thumb in manipulation, are much exerted, so that the effects of overexertion show themselves first in this region.

Thus, Edinger maintains that the muscle-supply of the arm is designed for coarse heavy work, the muscles of the fingers and the hand having to carry out more work than can be expected of them from a consideration of their volume and their physical action.

The commonest form of lead palsy, the antibrachial type of Déjerine-Klumpke[5], is explicable from consideration of overexertion of the particular group of muscles named. The supinator muscle, supplied also by the musculo-spiral nerve which serves the paralyzed muscles, escapes because of its size, and the fact that functionally it belongs to the flexor group, and the first-named reason also, explain the frequent escape of the long abductor of the thumb.

Teleky[6] investigated thirteen slight cases of the antibrachial type. In one both hands were affected, in one the left only, and in all the others the right only—facts which he thinks bring out the rule of causation by employment. Of fourteen painters, three had the right forearm affected only, the other eleven both right and left, but always more marked in the right. Amongst them he cites cases where the shoulder muscles were paralyzed, which he considered was due to the extra strain of unusual employment, involving a raising of the arms above the head, or lying on the back painting the under parts of carriages. In several of the painters the index-finger was the least affected, by reason of the less exertion thrown on it by the position assumed in holding the brush between the second and third fingers. The long abductor, probably because of its size and power, is in no case completely paralyzed.

In file-cutters he insists that the predominant share, falling on a single or on several small muscles of the hands, makes the early appearance of paralysis of the small muscles the characteristic sign. In this connection we have frequently observed[145] decrease in the size of the thenar and hypothenar eminences amongst lead rollers; in fact, in the majority of lead rollers who have followed their occupation for a large number of years the flattening of both thenar and hypothenar eminences is well marked, but it is only fair to point out that in these cases very considerable stress is thrown on the muscle of this part of the hand by the pressure of the lead plate in pushing it inwards into the roller and grasping it on its appearance back again through the roller, and that, further, the use of large and clumsy gloves with all the fingers inserted into one part, and the thumb only into the other, tends to produce inaction of portions of the lumbricals and of the opponens pollicis, and may, therefore, from purely mechanical reasons cause damage to this part of the hand.

Teleky[7] cites cases of right-sided paralysis of the adductor brevis pollicis supplied by the median nerve, and partial paralysis of the long extensors and of the extensor ossis metacarpi pollicis supplied by the radial nerve, and in one or two cases complete paralysis of the thenar muscles and adductor, whilst the extensors of the fingers and wrists were only partially paralyzed. The cases all occurred in lead capsule polishers. This particular selection of muscles is clearly the result of the peculiar movement necessary in polishing the capsules of bottles on a revolving spindle, involving specially the use of the opponens muscle.

This observation of Teleky’s is in direct accord with the observation quoted above of the hands of persons engaged in lead rolling.

In the lower extremity, paralysis of the muscles associated also with paralysis of the adductor and extensors of the thumb was found by Teleky in a shoemaker who had contracted plumbism by the use of white lead. He explains this lower extremity paralysis by the exertion thrown on the adductor muscles of the thigh whilst holding the shoes.

In children affected with lead palsy the lower extremities are more frequently paralyzed than the upper, due to the relatively greater strain in childhood on the legs than on the arms.

Edinger’s theory, supported as it is undoubtedly by Teleky’s observations, is a matter of the greatest importance in the production of paralysis; for if we accept the view that lead is a poison that has a selective power on certain nerves, we have still to consider which is the greatest force, the selection[146] of certain groups of muscles or the effect of functional action. The theory of muscular overexertion certainly falls in with the type of paralysis, and Teleky has undoubtedly shown that under certain circumstances, by special exertion of other muscle groups not usually affected, these muscles alone, or to a greater extent than those usually affected, are involved in the paresis. If, therefore, lead has a selective action, which is exceedingly doubtful, it must be very slight.

Such selective action is, of course, exceeded by a functional activity which brings about the affection of those nerves which supply the muscles most used. If, therefore, we judge of paralysis as being due to the selective action of lead on certain nerves, we are met at once with the objection that the muscles affected do not always correspond to such a nerve distribution, and that muscles supplied by other than the musculo-spiral nerve are affected by paralysis.

Careful consideration of the chapter on Pathology, and more particularly of the histological findings described, in which the preliminary action of lead is found to be typically and invariably on the blood, setting up degenerative changes microscopical in size and limited in area, affecting the vessel walls and producing a yielding of the vessel, determining minute microscopical hæmorrhages distributed, not necessarily in one position of the body, but all over the body, and peculiarly in the case of the cat affecting those muscles called upon to perform sudden and violent movement—namely, jumping—enables us to regard such microscopical hæmorrhages as an adequate explanation of the association of paralysis in muscle groups, functionally related to various trades and industrial processes.

It may be argued, and we think with considerable reason, both from pathological and clinical findings, that, as muscular exertion is apparently associated with the onset of paralysis, particularly in those muscles which may be regarded as physically somewhat inadequate to the work they have to perform, and that, as the paralysis is associated with definite functional groups of muscles, and to a curious extent varies according to the trade in which the sufferer is engaged, therefore greater stress thrown upon the muscular tissue at some period or another during occupation determines the microscopical hæmorrhage in the nerve supplying the muscles, or in the muscle itself, so that[147] the paralysis affects just such muscles as have an increased strain thrown upon them. It does not necessarily follow that the preliminary initial hæmorrhage occurring should be a large one—in fact, from the whole of the histological history, hæmorrhages are exceedingly minute; neither does it follow that it is essential for such hæmorrhages to take place in the whole length of the nerve itself; but it is only necessary that the finer branches of the nerve should have their venioles or arterioles affected, and it is of course in the finer branches particularly, as has been pointed out in relation to the venioles, that degeneration of the intima of the vessels takes place.

Finally, the effect of early treatment on lead palsy tends to bear out this theory. If a case of lead palsy be treated in the early stages, the clinical course of the case is good; increased paralysis generally takes place in the first week, and, where, perhaps, only two or three fingers are involved when the case is first seen, spreads generally to other regions within a week, and the whole hand is affected; but from this moment onwards improvement takes place on the application of suitable treatment, and, if continued, almost invariably results in the entire recovery from the paresis.

There is little doubt that this is the true explanation of the ordinary paresis of lead poisoning, and a very great deal more evidence is required to combat it and to prove the selective action of lead upon individual nerves, since the theory of hæmorrhage does not owe its origin to conjecture, but is based on clinical and histological examination of early cases of poisoning.

In attempting to find a cause for the paralysis of the hands so commonly present in painters, it has been suggested that lead is absorbed through the skin, and affects the nerves at their junction with the muscles, setting up a peripheral neuritis [Gombault[8]]. The theory breaks down at once when such commonly-occurring affections as paralysis of the ocular muscles, paralysis of the peroneal type, paralysis of the muscles of the shoulder, etc., are considered.

For the convenience of description lead paralyses are generally divided into a series of groups, the grouping varying according to the function of the various muscles rather than to their anatomical grouping. The various types of paralysis have to be considered in detail:

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1. Antibrachial Type (Déjerine-Klumpke—Remak).

—The first muscle affected is the extensor communis digitorum, with dropping of middle and ring fingers, while extension of the first and fourth is possible because of their separate muscles of extension (extensor minimi digiti and extensor indicis). Paralysis may be limited to these, and not advance farther, but it is common to see these two muscles primarily affected, and for other muscles to become involved after the patient is put on treatment, although exposure to lead has ceased. Usually, however, the paralysis advances, involving the extensors of the index and little fingers, so that the basal phalanges of the four fingers cannot be extended. The long extensor of the thumb is next involved, but this may be delayed. The two terminal phalanges are still able to be extended by the interossei (as shown by Duchenne) when the basal phalanx is passively extended on the metacarpal. Abduction and adduction of the fingers also remain unaffected. The wrist muscles are affected next. The hand remains in semi-pronation, and when hanging down forms a right angle with the forearm, the fingers slightly flexed with the thumb towards the palm, and the hand deflected to the ulnar side. In grasping an object the flexors remain unaffected, the wrist is much flexed owing to the shortening of the flexors in consequence of the extensor paralysis. The hand cannot pass the median line. The long abductor of the thumb—that is, the extensor ossis metacarpi pollicis, also known as the “extensor primi internodii pollicis”—is only very rarely involved, but has been described as being the muscle alone involved in the paralysis affecting persons engaged in polishing lead capsules.

2. The Superior or Brachial Type (Remak).

—The muscles affected are those of the Duchenne-Erb group—namely, the deltoid, biceps, brachialis anticus, and supinator longus. The supra- and infrascapular muscles are also as a rule involved, but the pectoralis major rarely. This type of paralysis is usually found in old cases associated with other forms of paralysis, but may be found as a primary affection (as already noted amongst painters); sometimes the deltoid is the only muscle affected, with diminution in electrical contractility of the other muscles of the group.

The arm hangs loosely by the trunk, with the forearm semi-pronated. The arm cannot be raised, nor can the forearm be[149] bent on the upper arm. Extension is unaffected, as the triceps is never involved. Supination is impossible because of paralysis of the supinator brevis. Movement effecting rotation of the shoulders is involved, due to the paralysis of the supra- and infra-spinatus. Electrical reactions are said to be less marked in the brachial than the antibrachial type, and complete loss of faradic contractility is rare; but in one of the three cases described below, in which electrical reactions were carefully tested, the right deltoid showed entire loss of contractility to faradism.

3. Aran-Duchenne Type.

—The muscles of the thenar and hypothenar eminences and interossei are affected. This type of lead paralysis may be distinguished from progressive muscular atrophy by the electrical reactions, and the fact that the atrophy is accompanied by more or less pronounced muscular paralysis. The atrophy is almost always most marked, and advances pari passu with the paralysis. This form may occur alone, or be complicated with the antibrachial type, which is the most common. It is seen in file-cutters as the result of overstrain of the muscles in question. Moebius[9], in his observations on file-cutters, noted in one case paralysis of the left thumb, with integrity of the other muscles of the left upper extremity. Opposition of the thumb was very defective; there was paralysis of the short flexor and of the adductor and atrophy of the internal half of the hypothenar eminence. Reaction of degeneration was noted in the muscles named, but not in the extensors of the fingers and wrist. In another case, in addition to feebleness of the deltoid, flexors of forearm on the upper arm, and small muscles of hand, there was paralysis and atrophy of the adductor of the thumb and first interosseous and paralysis of the opponens.

4. Peroneal Type.

—This is a rare type, and nearly always associated with the antibrachial or with generalized paralysis. In the former the paralysis is slight, especially when it affects the psoas; but there is predilection for certain groups of muscles, especially the peroneal and extensor of the toes, while the tibialis anticus escapes. Hyperæsthesia, or more rarely anæsthesia, precedes the onset.

The patient walks on the outside of the feet, has difficulty in climbing stairs, and cannot stand on the toes. The toes drag on the ground in walking, so that the foot has to be swung round[150] at each step, and the inner side is lifted in excess by the action of the tibialis anticus, with uncertainty in gait. If walking is continued, the toes drag more, and “stepping” gait is assumed by bringing into action the muscles of the thigh. The foot cannot be flexed on the leg; abduction of the foot and extension of the basal phalanx of the toes is impossible. Later the peroneal muscles, extensor communis of toes, and extensor of great toe, are paralyzed, from which fact arises the difficulty of walking and of descending stairs, as the whole weight of the body is supported then by the tibialis anticus. This type corresponds with the antibrachial type of the upper extremity. If the tibialis anticus is paralyzed, it is in association with the gastrocnemius.

5. Paralysis of Special Sense Organs.

—Tanquerel[10] called attention to the aphonia of horses in lead works, necessitating tracheotomy, and Sajous[11] described adductor paralysis of the glottis in a house-painter. Morell Mackenzie[12] also described unilateral paralysis of the adductors in persons suffering from lead poisoning, whilst Seifert[13] particularly describes a curious case in which paralysis of the transverse and oblique arytenoid muscles prevented contraction of the cord in its posterior quarter, and in a second case of paralysis, affecting the posterior crico-arytenoid muscles on both sides, the adductors remained unaffected. What is still more interesting in Seifert’s case is the fact that at the post-mortem old hæmorrhages were found in the mucosa of the arytenoids and aryepiglottidean folds. Occasionally sensory paralysis may be found in the special sense organs—such, for instance, as loss of taste, loss of smell, and, in addition, diminished power of hearing—but these defects rarely if ever occur unless accompanied by distinct mental changes and generalized paralysis.

6. Eye.

—Poisoning affects the eye in two ways:

• (a) Defects of the visual mechanism.
• (b) Defects of the muscular mechanism of the eye.

Lockhart Gibson[14] describes a large number of cases of paralysis of the muscles of the eye met with amongst children in Queensland. The cause was traced to the painted railings near which the children had been playing. The white lead paint had somewhat disintegrated under the action of the sun’s rays, forming an efflorescence; the children admitted to have rubbed the paint and then sucked their fingers.

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Between July, 1905, and 1908, sixty-two cases of plumbism in children were admitted to the children’s hospital, and of these sixty-two cases thirteen had well-marked ocular symptoms. The paralysis of the muscles of the eye was almost invariably one of the external rectus, but other muscles were at the same time affected; occasionally paralysis of the whole of the oculo-motor muscles was seen with the exception of the superior oblique. It is worthy of note that amongst these children a very large number suffered, in addition to their eye paralysis, with foot-drop and wrist-drop, and, on the whole, suffered from foot-drop to a much larger extent than from paralysis of the hands.

Galezowski[15] describes paralysis of accommodation of the eye, and in cases described by Folker[16] some amount of orbital paralysis was also present.

7. Generalized Paralysis.

—These types do not differ in form from the previously described types, except, perhaps, as regards their rapidity of onset. Where the onset is slow (chronic) the subject is usually one who has been previously affected with paralysis of the extensors of the hand, followed by development of the paralysis in the shoulders, hand, leg, thorax. In the acute form, paralysis may affect all the muscles in a given limb or group, and reduce them in a few days to a complete condition of paralysis. In extreme cases the patient lies on the back and is incapable of rising, and sometimes even unable to eat. The intercostals, diaphragm, and larynx, are also affected, while there is generally dyspnœa and aphonia. The muscles of the head and neck appear to escape. In these acute cases, pyrexia may be a common symptom.

Electrical Reactions.

—The diagnosis of the affected muscle is greatly assisted by careful examination of all the muscles in the affected physiological group by means of the galvanic and faradic currents. The battery for the purpose of testing the electrical reactions must have an available electromotive force of over 40 volts. A battery of thirty-two Leclanché dry cells is ample. For the faradic current, a small induction coil operated by two Leclanché cells is sufficient. One large, flat electrode should be used, and several smaller ones.

The faradic current should be used first, as it stimulates the nerves directly, and the muscles only indirectly, through their nerve-supply. Each nerve trunk should be examined systematically. The motor points correspond for the most part[152] with the points of entry of the motor nerves into the muscles which they supply. A small electrode, either a button or a small disc about the size of a sixpence, should be used for the examining electrode, while the larger electrode should be placed either on the abdomen or between the shoulders. The electrodes should be well soaked in normal saline.

The intensity of the minimum current required to produce a contraction for each point should be noted, and compared with the effect of a similar current on the opposite side of the body.

The reaction of degeneration of the faradic current consists in no contraction at all being elicited, even when a very strong current is employed. If there be unilateral wrist-drop in the left hand, consisting of loss of power of the extensor communis digitorum on that side, no movement of the muscle is produced at all when the electrode is placed across the motor points of the muscle. These are situated to the outer side of the arm when the dorsum of the hand is uppermost, about 1¹⁄₂ to 2 inches below the olecranon. The same quantity of current, when applied to the unaffected muscle on the opposite side, produces a brisk reaction.

Having observed the effect with the faradic current, and the results having been recorded, the continuous current is used, and the electrodes made use of in an exactly similar fashion. When a small electrode is used, the superficial nerves and muscles are more stimulated than those lying deeply. It is necessary, therefore, to begin with a small current and gradually increase it until the individual muscle responds.

The strength of the current employed is registered by means of a milliampèremeter.

With the continuous current quantitative as well as qualitative alterations may be determined, and with the quantitative change of the galvanic current the muscular excitability is increased, contraction following the application of a weaker current than is necessary to produce it in health or in the sound muscle on the other side of the body.

With the qualitative change, the contraction is no longer sharp, but sluggish. The anodal closing contraction is elicited with a weaker current than kathodal closing contraction, so that ACC>KCC.

The quantitative change depends partly on the nutrition of the muscle; the qualitative change depends on the fact that[153] the nerve no longer regulates the character of the contraction, and also to a small extent is the result of changes in the muscle itself.

In a complete reaction of degeneration in an affected muscle, reaction to the faradic current is absent, contraction to the galvanic current is sluggish, and is produced with a smaller current in the anode than the kathode.[A]

As the nerve lesion passes away, the voluntary contraction generally begins to return before the nerves show any reaction to electrical stimulus.

The following three cases in which the electrical reactions of the muscles were determined, give examples of typical cases of lead paresis. In No. 3, owing to the fact that the case was treated immediately the paralysis occurred, complete recovery had taken place, and, as will be seen, the electrical reactions have again become normal.

Case 1.—Litharge and blast-furnace worker. Employed in lead works, where a large number of different metallurgical processes associated with the recovery of lead from the ore were carried on. Double wrist-drop, existing for eight years, untreated until some four years after paralysis took place, when slight improvement occurred. The electrical reactions show that the extensor communis digitorum on the right side is completely degenerated, whilst the first interosseous of the right side show reactions of degeneration. On the left side the extensor communis digitorum showed normal but very feeble reaction. This latter point is one of considerable importance if early hæmorrhage accounts for lead paralysis, for if the nerve itself was completely destroyed, or if, as was the case, the muscle appeared completely paralyzed on inspection, obviously the nerve-supply must be completely cut off if the lesion was due to destruction of the nerve of the spinal cord or to the destruction of the lower motor neuron. On the other hand, the presence of small localized fibrillar contraction, found by the galvanic current, together with the presence of a slight reaction to faradism, suggests that some small portion of the nerve has remained unaffected, and that for this reason certain portions of the muscle have not undergone degeneration—a circumstance which can hardly be expected if the cause of the paralysis is in the destruction of the whole of the nerve-supply.

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[156]

This case is a typical one of the anterior brachial type, showing partial recovery of function. The man is able to grasp, although the wrist becomes strongly flexed in so doing.

Case 2.—We are indebted to Dr. Gossage for this case, which was presented at the Out-patients of the Westminster Hospital; and to Dr. Worrell, who made the electrical investigations. We are further indebted to Dr. Worrell for the reports which are given in tabular form of the electrical reactions of these three cases.

This is a case of brachial type, with weakness of both deltoids, and the patient was unable to raise his right arm at the shoulder. It will be seen that there is here also evidence that the electrical contractility diminishes before the entire loss. It will be also noticed that the supinators are unaffected.

Case 3.—These are the electrical reactions of a case which had recovered. This man showed the ordinary anterior brachial type, which came on suddenly, although he had shown distinct weakness of wrists when forcible flexion was performed for nine months previously, but there had been no obvious increase in the weakness. He was immediately removed from his work, and within seven days paralysis, which at first only affected the extensor communis digitorum, had spread to the minimi digiti and the extensor indicis, the opponens pollicis being also involved on the right side. He was treated from the start with faradic current, and was instructed to use the battery himself, which he did twice a day for a year. At the end of two months he was sufficiently recovered to be given light work, and at the time of taking the reactions his wrists have so far recovered their power that we were unable to flex them forcibly.

The progressive weakness noted in the three cases has already been referred to, and may be a prodrome of paralysis, but there may be recovery without paralysis supervening.

Tremor.

—Tremor may be observed in a large number of cases of lead poisoning, and is invariably associated with paralysis, although the symptom of tremor by no means always progresses to definite palsy. Two types of tremor are described—fine and coarse—and Gübler further describes a type of tremor which is both rhythmic and intermittent. The tremor is usually distinctly increased on attempting to grasp or point the hand (intention tremor), but it is difficult to separate tremor from alcoholic tremor, and, further, it must not be forgotten that[157] persons engaged in arduous work may show a certain amount of tremor due to muscular fatigue. Persistent tremor, however, is a symptom that is always to be noted and carefully watched.

Of the types of paralysis, the antibrachial is the most common, and, secondly, probably the brachial. The least common is the peroneal. The table on p. 54 shows the distribution of cases of paralysis, so far as they can be made out from reports received since 1904.

Closely associated with paralysis are affections involving the brain. Tanquerel, in his classical description of affections of the brain associated with lead poisoning, gives the following classification:

• 1. Delirium.
• 2. Lead mania.
• 3. Psychic depression.
• 4. Coma.
• 5. Convulsions, saturnine eclampsia, or epilepsy.

There is probably a very considerable relationship between insanity and lead poisoning, as pointed out by Robert Jones[17], the resident physician and Superintendent of Claybury Asylum.

Rayner[18] remarked that the compulsorily careful habits of life of painters and lead-workers ought to protect them against vicious habits, and should protect them against a too free indulgence in the use of alcohol! Our own experience is that paralysis, and particularly affections of the brain, occur in the majority of cases in persons who are addicted to alcohol, and the experiments quoted in the chapter on Pathology on the influence of alcohol in the production of encephalitis in animals is strong presumptive evidence that alcohol is one of the chief predisposing causes in the determination of saturnine encephalopathy.

Encephalitis is given as a cause of death in the report already referred to in 14·3 per cent. of 264 fatal cases. Amongst this number encephalopathy accounted for 14·3 per cent., cerebral hæmorrhage 9·8 per cent., and paralysis 9·2 per cent. Now, all these are cases in which cerebral lesions may be confidently stated to have existed, which brings the total to 34·4 per cent. of deaths at least due to brain involvement. We have already referred to the high incidence of paralysis amongst file-cutters—40 per cent. as against 21·1 per cent. for all industrial forms of poisoning.

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When encephalitis occurs, it is usually an acute symptom, and often develops before paralysis is set up, but as a rule is preceded by a period of persistent headache, such headache being invariably temporal or occipital.

Robert Jones, in his paper, states that of the 133 cases who, from the nature of their work (painters, plumbers, etc.), were liable to lead impregnation, 19 had signs of poisoning upon admission, whilst 22 had a distinct history of lead poisoning at some time or other. He gives the following analysis of the mental condition:

Savage[19] is of opinion that lead will produce any of the symptoms of general paralysis of the insane, and may even be a contributory cause of the disease, but no statistics are available of the Wassermann reaction in these cases. Goodall[20] refers to the fact that nerve poisons, such as syphilis, alcohol, and fevers, injury or sunstroke, which are intermediate in fixity between alcohol and lead, seem to have an intermediate influence in the production of general paralysis.

Jones states that the mental symptoms found in the cases are to be grouped amongst one or other of the following varieties:

1. Of a toxæmic nature, with sensory disturbances, which tend to get well rapidly.

2. Hallucinations of sight and hearing, more chronic in nature, which may be permanent. The delusions in this class are almost invariably those of being poisoned or followed about, and are in the main persecutory.

3. Those resembling general paralysis with tremors, increased knee-jerk, inco-ordination, accompanied with listlessness amounting to profound dementia, but which tend to get well.

Eye Changes.

—Two main forms of eye change are to be found amongst lead-workers. In the first place, temporary and sudden amaurosis makes its appearance, due no doubt to vascular change,[159] either vaso-motor or hæmorrhagic. The trouble may occur in one or both eyes, may come on gradually, the patient merely being unable to distinguish letters or faces at a distance, or he may become suddenly totally blind. In the majority of cases the affection disappears under treatment, but in a small number of cases total blindness persists.

Occasionally nystagmus may be seen, but is not a common symptom; but dilatation of the pupils, quite apart from retinal changes, is not unusual. Inequality of the pupils may be observed, but partial dilatation of both pupils is more common, and is often associated with early anæmia. Conjunctival hæmorrhages are to be noted from time to time, without obvious cause, such as injury, etc., but in the majority of cases these have been associated with other symptoms.

The first feature noticed in the eye is loss of brightness, and a curious lack-lustre of the eyes of persons intoxicated by lead is one of the general features making up the saturnine cachexia. Loss of brightness of the eye is associated in many other diseases with anæmia, but is particularly prominent in lead poisoning, much more so than is to be accounted for alone by the degree of blood-destruction, and is a point of which the examining surgeon should always take notice.

One other form of eye change requires attention—namely, retinal changes due to circulatory disturbances. In an advanced case the whole picture is one of severe albuminuric retinitis, but in the earlier stages some engorgement of the vessels without alteration of the surrounding tissue is seen. Elschnig[21] associated this alteration in the vessels of the eye with vaso-motor changes caused by direct action of the poison, producing a vascular constriction or dilatation, and is inclined to regard the kidney disease frequently associated with this condition of the eye as something quite apart. He would regard the two affections as independent, and merely correlated through their common origin—lead intoxication. It has even been suggested by some observers that the change in the eye is secondary to cerebral œdema. Thus Mannaberg[22] regards the encephalitis of saturnine origin as associated with chronic œdema of the brain and spinal cord, which thus produces reflex irritation of the nervous system of the eye. Bikler[23] and Weber[24] consider the symptoms as circulatory. From whatever cause the disease is set up, sooner or later changes in the[160] form of obliterative arteritis take place, with gradual but ultimately complete loss of vision.

There are said to be no characteristic eye symptoms in acute cases of lead poisoning, whereas with chronic lead poisoning in many cases there is central and peripheral affection. The affections may be further divided into subjective and objective. Many of the subjective symptoms, such as loss of sight and blindness, are associated with definite eye lesions, which may be seen with the ophthalmoscope, but other definitely objective lesions may be present without any influence on sight to commence with. Folker[25] describes five cases of lead amblyopia in lead-workers from a pottery district, in all of which there was a peculiar symptom—the gradual failing of sight associated with colour flashes. When examined, the discs were described as white, and the vessels small.

Lockhart Gibson[26], in describing the cases of eye disease amongst the children in Queensland, found one symptom apparently in all the eyes examined—namely, great swelling of the discs. This swelling of the discs might be accompanied with no loss of sight whatever, and at other times had been accompanied with defective sight for many months previously. Some of the discs were excessively swollen. There were also to be seen patches of pigment and irregular swelling of the vessels, but no definite hæmorrhages. In the more acute cases, and particularly those associated with complete paralysis of the ocular muscles, total blindness usually followed.

As a rule, when complete amaurosis occurs in lead poisoning, blindness follows through double optic neuritis or neuro-retinitis, but amblyopia may be present without fundus changes. Occasionally the loss of sight may be regarded as of central origin. The renal disease so often associated with lead poisoning may cause the retinal changes accompanying it. An albuminuric neuro-retinitis may occur without albumin in the urine. As a rule, the eye of a lead-worker reacts to light and accommodation. Ophthalmoscopic examination may show very pink discs, patches of pigment scattered about irregularly outside the discs, with occasional definite hæmorrhage. The edge of the discs may show blurring, with further sclerosis and peri-arteritis of the vessels, a white sheath around the arteries being often visible. The neuritis on one or both sides may be associated with disturbances of sight, and diffusely red and cloudy papilla,[161] with swelling or hæmorrhages. In choroidal atrophy pigmentation may also be seen.

Muscular System.

—One further point may be referred to in relation to the muscular system—namely, the occurrence of pain of a rheumatic type. Quite a number of cases of mild degrees of lead poisoning complain of arthralgic symptoms—that is to say, “rheumatism.” Careful examination of such cases shows no evidence that the pain is a true arthralgia, neither does it seem to have a true relation to gout. The pain as a rule is referable to the muscles themselves, and in such instances digital examination of the muscle in the region of the pain generally exhibits deep-seated tenderness. There does not appear to be any special marked tenderness along the trunks of the nerves supplying the muscle, nor is there evidence of hyperæsthesia of the skin. Such hyperæsthesia does occur in lead poisoning, but is generally associated with cerebral lesions. The pain, therefore, must be regarded rather as myalgic, and intercostal distribution of the pain is not infrequent; but although the symptom is one that is often complained of, it is an exceedingly difficult one to differentiate from other myalgias as a definite symptom of lead poisoning. The chief point in favour of the inclusion of this so-called lead rheumatism as a symptom of lead poisoning is the frequency with which it is noted in the reports by certifying surgeons. While, therefore, having no evidence to regard it as necessarily a definite symptom of poisoning, it is one which has been recorded in a considerable number of cases. As has been already suggested, there is some reason to think these myalgic pains may be due to minute hæmorrhages taking place in the muscles, thereby producing localized irritation to some extent comparable with the “bends” of divers.

Post-Mortem Signs of Plumbism.

—Very real difficulty exists in determining from naked-eye appearances at a post-mortem examination whether the cause of death be due to chronic plumbism or not. The changes produced by several other forms of intoxication, notably chronic alcoholism, produce many of the same changes in the tissues as lead. Inspection of the organs in the case of plumbism can only give rise to a surmise that the cause of death is due to lead poisoning.

There are, however, certain macroscopical appearances at an autopsy in the case of saturnism which should be carefully noted,[162] and although alone they do not constitute sufficient evidence upon which to pass a definite opinion, they are still important as diagnostic signs in the light of histological and chemical examination.

Particular note should be paid at an autopsy of a case of suspected lead poisoning to the following points:

1. Mouth, for the presence or absence of blue line, which, if present, must be examined with a lens.

2. General condition of the abdominal viscera, and particularly of the mesenteric and perinephritic fat. In plumbism this is invariably reduced in quantity.

3. The condition of the mesenteric vessels, as to whether or not they are engorged with blood, or whether or not leakage appears to have taken place.

4. General condition of the arteries, for the presence of atheroma, etc.

5. The heart muscle, which in plumbism is generally pale, flabby, and with a tendency to general dilatation of the cavities.

6. Intestines.

(a) The presence of injection of the muscular coat, particularly the lower portion of the intestine, and about the ileo-cæcal valve.

(b) The presence or absence of minute ulcerations, or even hæmorrhages along the intestine, even in the mucosa of the stomach.

(c) The presence of dark staining in the coats of the lower intestine, not altogether disappearing when washed under a gentle stream of water. Should there be any evidence of this staining, it is highly important to remove some of the fæces, as well as a portion of the intestine, for chemical examination.

7. The condition of the liver, which in poisoning by lead, as by alcohol, frequently shows a considerable amount of enlargement, and may even show patches of perihepatitis due to secondary causes. But the cirrhosis occurring in lead poisoning is not so great as in alcohol. In lead poisoning the liver as a rule is large and soft, and engorged with blood.

8. The kidney, for signs of interstitial rather than tubular nephritis, adherent capsule, and blood-stained exudate.

9. If paresis of any sort has been present during the illness, examination of the cord and brain should be made with especial[163] care, and in addition the nerves on the affected side supplying the affected muscles should also be examined. In the brain definite small but coarse hæmorrhages may be occasionally observed, but as a rule the only signs to be found are injection of the cortical vessels, frequently over certain definite areas, and not involving the whole of the vascular system of the brain. Minute hæmorrhages may be also found in the spinal cord.

For the purposes of histological examination, a portion of the following organs should be removed and placed in a 5 per cent. formalin solution at once: Liver, spleen, kidney, intestine, the last-named specimen being selected from any area which shows injection, or ulceration, or dark staining.

Smears may also be made from the bone-marrow, as in prolonged anæmia of saturnine origin definite changes may at times be found in the bone-marrow cells.

Where paresis has existed, a portion of the particular nerve supplying the muscles should be obtained, and histological examination made, as well as a portion of the cord above the lesion, and where cerebral symptoms have been present, a portion of the brain, the portions taken being part of that showing engorgement of the vessels. For the nervous tissue generally, it is better to place some of the specimens in Müller’s solution, and others in spirit. Equal parts of Müller’s solution and formalin may be used if desired.

Material for Chemical Examination.

—For the purposes of chemical examination, any of the organs which appear to be mainly affected by chronic inflammation may serve, but it is usually important to examine the brain, kidney, and liver. If any dark staining exist in the intestine, a portion of this, together with the contained fæces, should be removed. It is better to tie ligatures round the intestine, and divide the coat between the ligatures, and place the whole of the specimen in dilute formalin. Specimens thus obtained should be sent off for examination at once. The whole of the organ need not necessarily be despatched for examination in every case, but if only a portion is sent, it is essential that the weight of the whole organ be accurately taken before any portion is removed, and the total weight noted with the specimen when sent.

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REFERENCES.

Very great assistance is afforded by chemical and histological diagnosis in the determination of cases of lead poisoning, especially when the case is likely to involve proceedings under the Workmen’s Compensation Act. In addition, a large amount of information is afforded to the certifying or appointed surgeon and the medical practitioner by adoption of certain easily carried out methods of diagnosis. It will be our purpose in the present chapter to describe as far as possible methods by which chemical or other investigation of a case of lead poisoning can be pursued, and the clinical methods of diagnosis which are applied in ordinary routine.

The majority of the methods described, especially the chemical investigation of material obtained from alleged fatal lead poisoning for the purpose of determining the presence or absence of lead, the histological examination of such tissues, and the examination quantitatively of excretions for lead, are processes which can only be carried out in a fully equipped laboratory, and certainly do not belong to the ordinary routine of medical work. The medical practitioner cannot be expected in the ordinary course of his routine work to examine blood-films for basophile staining or to make differential blood-counts. Especially is this the case in the routine examination of large numbers of factory hands. Further, many of the processes involved in either the chemical or histological examination of the tissues require so much special apparatus, without which such work cannot be undertaken, that the mere cost of the necessary instruments precludes the investigation being carried on except in special laboratories. At the same time, our purpose is to point out how additional methods of research may be made use of in obscure cases, and how recourse should be had to a well-equipped[166] laboratory in doubtful cases. Further, the coroner, when ordering a post-mortem examination, may ask for a histological and chemical examination.

Methods of Chemical Diagnosis.

—The presence of lead may require to be determined qualitatively and quantitatively, and the procedure may differ slightly as to which process it is necessary to adopt. The quantitative determination of the amount of lead present in organs or excretions of the body is of far more importance than the estimation or determination of the fact of its presence. We have already referred to the work of Gautier[1], who has found lead present in the tissue of normal persons with such constancy that French observers, at any rate, now speak of “normal lead,” to distinguish it from lead which may be found in pathological conditions. There is, however, little doubt that the quantity of lead existing in the human body is exceedingly small. It is possible, with certain refined methods of chemical examination, that qualitative traces of this substance might be found. On the other hand, the methods of determination of lead are some of the most difficult in toxicological analyses, on account of the presence of other metals, particularly iron, which are exceedingly difficult to get rid of, and may easily lead to errors.

1. Qualitative Tests.

—The group reagent for lead is sulphuretted hydrogen in acid or alkaline solution. Lead is precipitated by this reagent as a black precipitate. Where no other metals are present, and where no organic matter is present at the same time, there is very little difficulty, and the usual method of the determination of lead in water by means of sulphuretted hydrogen is exceedingly easy.

Potassium iodide gives a yellow precipitate soluble on warming, and forms large crystals on the tube. Hydrochloric acid and chlorides give needle-shaped crystals, soluble in heat, and crystallizing out when cold. But the double chloride of potassium and lead is more soluble in heat, and still more soluble in cold, than is the pure chloride. This fact is made use of in the process to be described presently in separating lead from organic mixtures.

The direct examination is rarely possible or satisfactory, but the potassium cupric acetate method is one that may be applied to the qualitative estimation of lead in the tissues.

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Method for detecting Small Quantities of Lead qualitatively.

—Dry and incinerate the material to be tested. Extract with hot dilute nitric acid, after repeated incinerations, finally extracting with ammonium acetate. Filter, incinerate, and take up the residue in dilute nitric acid. Evaporate to dryness and add a few drops of dilute acetic acid, and transfer drop to microscope slide.

To the drop on the microscope slide add one drop of dilute copper acetate solution, and two to three drops of saturated solution of potassium nitrate. Stir up the drops and well mix with a platinum wire, allow to stand for a few minutes, and then examine with a two-thirds objective. If lead is present, violet-black cubes of potassium copper lead nitrate appear (K₂CuPb[NO₃]).

This test is said to give a reaction in the presence of 0·00003 gramme.

Determination of Lead in the Urine.

—The quantity of lead passed by the kidneys into the urine is always small, even in acute lead poisoning. Further, the lead is excreted in organic combination, and is therefore difficult to detect. For absolute quantitative examination it is essential to evaporate the whole bulk, using at least ¹⁄₂ gallon of the fluid, and proceeding with the concentrate in the manner indicated in the estimation of lead.

For the qualitative examination many methods have been suggested, but all of them are more or less fallacious.

In certain instances in acute lead poisoning, or where a relatively large quantity of lead is excreted by the kidney, acidulation of the fluid with strong sulphuric acid direct will at times produce a precipitate of lead sulphate, which may be filtered off and the filtrate examined by the usual tests—namely:

A white precipitate with dilute sulphuric acid.

A yellow precipitate with potassium chromate, hardly soluble in nitric acid, but soluble in alkalies.

A blue flame on heating on a platinum wire, and finally, if sufficient substance is present, the reduction to metallic form with the blowpipe flame.

A method has been recommended of suspending a small bag of calcium sulphide in the sample to be examined, the supposition being that, if the calcium sulphide in the bag showed blackening, it would be due necessarily to lead. This is highly questionable,[168] and in the hands of one of us (K. W. G.) has not given satisfactory results.

A further method, which is quite simple in application, and occasionally gives confirmatory results, may be applied in the following manner: The urine to be examined is inoculated with the Bacillus coli communis. For this purpose a small quantity of fæces may be used. The B. coli in its growth makes use of the organic substances in the urine, and at the same time sets free sulphuretted hydrogen. The urine left is filtered, the filtrate dissolved in 10 per cent. nitric acid (minimal quantity), and the filtrate examined by the usual tests. This method has occasionally given quite good results in the hands of one of us (K. W. G.), and is, moreover, an exceedingly easy one to carry out.

Passing sulphuretted hydrogen direct through the fluid is of no value, as it is necessary first of all to split up the organic compound before it will react to sulphuretted hydrogen.

Electro-Chemical Methods.

—Of all the methods at present in use for the estimation of the presence of lead in the urine, the electro-chemical gives by far the most satisfactory results. Several methods are described:

The first method consists in using magnesium, which is left for some hours in the urine, which has been previously strongly acidulated. In this manner Marsden and Abram[2] say that they have been able to detect 1 part in 50,000 in the urine without difficulty. The method adopted is as follows:

“A strip of pure magnesium is placed in the fluid to be examined. Ammonium oxalate in the proportion of about 1 gramme to 150 c.c. is added. If lead is present, it is deposited on the magnesium. A deposit is seen within half an hour, but we have usually left it twenty-four hours. The slip is then washed with distilled water and dried. Confirmatory tests: (1) Warm the slip with a crystal of iodine (yellow iodide proves lead, cadmium may be ignored); (2) dissolve deposit in HNO₃, and apply usual tests. The magnesium can be used again after careful washing with acid and distilled water. The surface of the magnesium, when used, must be bright and free from oxide. The delicacy of the method has been tested with aqueous solutions containing known quantities of lead, also with normal urine to which known quantities of lead have been added. In all cases a control experiment was performed to insure the freedom of the materials[169] from lead. Lead has been detected when present in the proportion of 1 part to 50,000, whether in simple aqueous solution or in urine.”

Shufflebotham and Mellor[3] describe the following method as one by which lead may be detected in organic tissue, and in each case this necessitated a large amount of evaporation. The method has value, but the difficulty of dealing with large quantities of fuming nitric acid, and the addition of this acid from time to time during the operations, render it difficult unless a good fume chamber is at hand. Shufflebotham and Mellor state that they obtained no reaction with the potassium chloride-hydrochloric acid method suggested by Dixon Mann.

A method has recently been described by Hebert[4]—a modification of Trillet’s. This method is based upon the fact that peroxide of lead, when mixed with tetramethyl of diphenyl-methylen, gives in acetic acid solution a fine blue coloration. Unfortunately, a number of other peroxides give the same blue coloration, amongst them manganese, potash, copper, magnesium. In addition, the sodium peroxide used to convert the lead present into the peroxide also gives a bright blue coloration with the reagent, even if present in minute quantities.

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The test is made in the following manner: The substance is incinerated, sulphuric acid added in the usual way, and the substance evaporated to dryness. It is treated with a cold solution of sodium hypochlorite. The hypochlorite is then removed partly by washing and partly by heating, and the reagent is then added directly to the substance in the capsule, and if a peroxide is present the blue colour results.

Unfortunately, this dissociation-point of the hypochlorite and the temperature at which peroxide of lead is changed back again to the oxide are very close together, being only about 25° C. In addition, it is very difficult to remove the last traces of the substances which give a blue coloration in addition to lead. One of us (K. W. G.) has made extensive trials with this method, as, if it had been a reliable process, it would have been one which would have considerably facilitated the estimation of lead in small quantities. The method has been adopted by certain French observers, who by drawing 2 c.c. of blood from the median basilic vein, and estimating the lead present in this small amount by means of the blue coloration, have sought to show that at least 25 milligrammes of lead were circulating in the blood of the body. In addition to other grave considerations, the fact that the reagent itself is colourable by certain other peroxides which exist in the blood-ash renders these figures entirely untrustworthy.

2. Quantitative Methods of Estimation.

—Two methods may be used in the detection of lead in organic substances, either in organic fluids or in solids, and are generally termed the “wet” and “dry” methods, from the original treatment of the substance.

In the dry method the substance is incinerated with or without the addition of sulphuric and nitric acid; in the wet the material is treated with hydrochloric acid and potassium chlorate. Subsequent treatment in both cases is on the same lines.

Method of Fresenius and Von Babo[5]

—Moist Method.—The substance which is suspected to contain the poison, if solid, is reduced to a pulp, and is mixed with sufficient water until of the consistency of thin gruel. The urine should be evaporated to one-fourth or one-sixth of its volume. Fæces should be well stirred up with distilled water. The substance is then placed in a large flask together with crystals of potassium chlorate; each 100 grammes of the substance require[171] 3 to 4 grammes of potassium chlorate. Pure HCl of the same weight as the original substance is then added, the flask is placed on a water-bath and gently heated. Care must be taken that the heating is not too brisk, as otherwise the evolution of the chlorine peroxide takes place too rapidly. If necessary, additional crystals of potassium chlorate are added from time to time until the fluid becomes limpid and of a slight yellow colour, or, if there is much organic matter, until it assumes the appearance and colour of thin oatmeal gruel. On account of more gradual evolution of chlorine, the chlorate that is present before the flask is heated acts much more energetically, weight for weight, than fragments added after the liquid is heated, as a great deal of the gas then escapes without rendering any service. If the substance contains sugar, starch, or alcohol, extra care must be taken to avoid frothing over. When the fluid contents are clear or reduced to a thin consistency, the liquid is transferred to an evaporating basin, and allowed to remain on a water-bath until the smell of chlorine has disappeared; it is then filtered while hot. The whole of the organic matter is not destroyed by this process, fatty substances especially being resistant; but if the organic matter is reduced to small fragments, any mineral poison present will be liberated.

The objections raised against this process are that some important poisons—such, for instance, as arsenic and antimony, specially the former—are liable to escape partially in the form of vapour, and that others, such as lead and silver, may remain as insoluble precipitates on the filter. As regards the first objection, it is to be observed that, when the hydrochloric acid is diluted with water (as in a moist method of destroying organic matter), any arsenic which may be present in the hot solution is not given off with its acid aqueous vapour, arsenious chloride dissolved in hydrochloric acid being volatile only when the solvent is concentrated. Any possibility of loss may be avoided, however, by furnishing the flask, in which the organic matter is being destroyed, with a condenser and receiver. The second objection, as far as lead is concerned, is met by taking care to filter the solution whilst hot; if only a limited amount of lead is present, it then remains in solution as chloride so long as the liquid is hot, and will consequently pass through the filter. A considerable quantity is kept in solution in the cold, as it forms a combination with potassium chloride, which is more soluble[172] than lead chloride alone. If a large amount is present, it will not all be found in the filtrate; the substance left on the filter, therefore, must always be tested for lead. In toxicological work, however, the amount of lead present is not as a rule more than will remain dissolved in the cold. Silver chloride, being insoluble either in hot or cold water, will not pass through the filter; consequently the salts of silver require dealing with in a special manner.

Dry Method.—This is effected by heating the finely divided substance to redness, so that it is either carbonized or completely incinerated. When cold, the residue is drenched with nitric acid, and sufficient heat is afterwards applied to drive off the free acid. The nitrate of the metal is then dissolved in water, filtered, and dealt with according to the kind of metal present.

The dry method is unsuitable in the case of the more volatile metals, as arsenic, antimony, and, in a lesser degree, lead, tin, and zinc. Further, it is extremely difficult and troublesome to carry out with large masses of organic matter. It is convenient with small amounts, and in the absence of the more volatile metals yields good results.

The following two methods are given by Glaister[6] on the one hand, and Dixon Mann[7] on the other. Both methods are good. It will be seen that Glaister recommends the estimation of the lead as sulphide.

When minute quantities of lead are present in combination with large amounts of organic matter, the dry process is tedious, difficult to carry out, and uncertain in its results. The plan adopted in the elimination of lead by Dixon Mann is as follows:

The urine is evaporated down to the consistency of gruel, and the fæces mixed in distilled water to a like consistency. They are then treated by the wet method, as given above. The filtrate after cooling is placed in a glass cell, the bottom of which consists of a sheet of vegetable parchment; the cell is immersed to such a depth in a deeper cell, containing distilled water acidulated with a few drops of sulphuric acid, that the liquids in the inner and outer cells stand at the same level. A piece of platinum-foil enclosing a surface of about 50 square centimetres, constituting the kathode, was submerged in the liquid contained in the inner cell, a similar piece of platinum-foil, constituting the anode, being immersed in the outer cell. The pieces of foil are so placed as to be opposite each other,[173] separated by the parchment diaphragm. A current, 3 or 4 volts, is then passed through for from six to eight hours, after which the foil is removed from the inner cell and gently washed and dried. The metallic lead is dissolved off the foil with dilute nitric acid aided by heat, and after driving off most of the free acid the solution is decomposed with dilute sulphuric acid with an equal volume of alcohol added. It is then set aside for twenty-four hours. The precipitate of lead sulphate is washed with water containing 12 per cent. of alcohol, until all the free acid is removed; it is then separated by decantation, ignited, and weighed. The amount of lead is calculated from the weight of the sulphate; 100 parts of sulphate are equal to 68·319 parts of metallic lead.

Whether the moist or the dry process is used, the residue after the primary filtration should be tested for lead, which may be present as sulphate and remain undissolved. If the original substance contains lead as sulphate, the salt should be dissolved with heat in an aqueous solution of ammonium tartrate to which a little free ammonia has been added, then precipitated with sulphuretted hydrogen (100 parts of lead sulphide equal 86·61 parts of metallic lead). It is better, however, to convert the sulphide into sulphate by treating it with nitric and subsequently sulphuric acid, after which it is ignited, weighed, and the amount of the metal calculated by the lead sulphate factor.

Having obtained the substance by decomposing the organic matter, two methods of estimation may be made use of:

(1) Colorimetric; (2) gravimetric.

Where the estimation is to be made gravimetrically, the substance is always obtained as a sulphate, and the lead estimated by weighing as a sulphate. This process is an exceedingly tedious one when a large number of small samples have to be estimated, as in the determination of the amount of lead dust present in the air. On the other hand, it is probable that the use of the balance in the estimation of lead as sulphate is more accurate where larger quantities up to 10 milligrammes are present; but where only 2 or 3 milligrammes are present in the amount of substance examined, the experimental error in washing is too large to warrant the expenditure of time required in this form of estimation, and the colorimetric method is used.

Detection of Lead in Organic Mixtures.

—Acidulate the organic substances, reduced to fine proportions, with nitric acid, heat[174] for some time, then permit to cool; filter, wash residue, and mix washings with filtrate; concentrate filtrate; pass H₂S; place mixture in warm place to allow precipitate to settle; after which decant supernatant fluid, collect precipitate on tared filter, thoroughly wash, dry on water-bath, and weigh. One part of sulphide is equivalent to 0·9331 part of lead oxide and 1·5837 parts of acetate of lead.

The electrolytic method is better adapted for the detection of minute quantities of lead, as, for example, in the urine or fæces or in vomited matter. The urine may be evaporated to a viscous state; the others, finely broken up, are treated in the same way, after HCl is added, as recommended above, the mixture heated, and pinches of powdered chlorate of potash added, as necessary, to break down organic matter. The heating is continued until the odour of chlorine disappears, after which it is filtered and the filtrate allowed to cool. The filtrate is then placed in the outer cell of a two-celled arrangement, not unlike a dialyser, the bottom of which is formed of vegetable parchment, the outer cell containing distilled water acidulated with H₂SO₄. Into the inner cell is placed a piece of platinum-foil measuring about 50 square centimetres of exposed surface, which is connected with the kathode or negative pole of four Grove cells, and into the outer cell is placed a like-sized piece of platinum-foil connected with the anode or positive pole. These pieces of foil are so placed in relation to one another that they are only separated by the parchment. The galvanic circuit being now closed for some hours, any lead in the filtrate will be deposited on the platinum-foil connected with the kathode in the inner cell. The foil is then removed, carefully washed, and the metallic lead dissolved by dilute nitric acid aided by heat, after which the solution is concentrated until most of the free acid is driven off; dilute sulphuric acid is added to throw down the sulphate, alcohol being also added to expedite precipitation. The precipitate is allowed to settle for twenty-four to thirty-six hours, filtered on a tared filter, washed with water containing 12 per cent. of alcohol, dried, ignited, and weighed. One part of sulphate is equivalent to 0·68319 part of metallic lead and to 1·25 parts of acetate of lead.

The estimation of the lead, especially if the amount be small, may be more accurately made by the volumetric colorimetric[175] method. The metallic lead deposited on the platinum-foil is dissolved in nitric acid, and distilled water added, and an aliquot portion placed in a Nessler glass. A few drops of freshly-prepared H₂S water, or H₂S gas itself, may be added to or bubbled through the contents of the glass so as to form lead sulphide. The colour formed is now matched in a similar glass, using a standard solution of lead nitrate, and forming the lead sulphide as before.

Some have advocated the magnesium wire deposition test, originally devised by von Jaksch, and modified by Hill Abram, for the detection of lead in the urine of persons who are suspected to be suffering from chronic lead poisoning (see ante).