REFERENCES.
[1] Annual Reports of the Chief Inspector of Factories since 1898, especially for 1909, p. 19.
[2] Supplement to the Sixty-fifth Annual Report of the Registrar-General on the Mortality in Certain Occupations in the Three Years 1900, 1901, 1902, by Dr. John Tatham, pp. cxix-cxxii, Cd. 2619.
CHAPTER V
PATHOLOGY
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 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:
[Gastro-intestinal] system.
[Nervous] system.
[Excretory] system.
[Circulatory] system.
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.
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 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. 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 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.
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 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 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.
The patient was a coach-painter, aged forty-four. Family history of no particular interest. Had been a painter since a boy. No specific history. Treated for enlargement of liver at one time. Married. No children. His wife a widow; four children before married to him.
Before the attack of encephalitis, which ultimately resulted in his death, he suffered from colic and obstinate constipation. The commencement of the final attack of lead infection was associated with an epileptiform fit, from which he recovered and resumed his work, but from this time onwards he suffered from progressive weakness and progressive inability to perform his ordinary work. Constant indulgence in alcohol did not pull him together as before; and although previously he had been able to indulge in large quantities of alcohol, a very little now affected him adversely.
The first epileptiform attack was in July, and in November he commenced to have delusions, was restless, suspicious.
On admission to the asylum he showed marked cachexia. Weight, 8 stone 7 pounds; height, 5 feet 9 inches. There was present well-marked oral sepsis and blue line.
Mental Condition.—Restlessness; disorientation; remitting delirious state; periods of shouting coincident with colic, worse at night; auditory hallucinations.
Physical Condition.—Bilateral wrist-drop; extensor paralysis of the fingers; hand-grip and gait impaired; reaction of degeneration of paralyzed muscles; coarse tremors; fibrillary twitching; staccato articulation.
Sensory.—No definite change.
Reflexes.—Pupils normal. Sluggish reaction to light and accommodation.
Organic.—Deglutition difficult. Micturition and defæcation not under control.
Vaso-motor.—Tâche cérébrale marked.
Eye neuro-retinitis. Unequal amaurosis.
Heart.—Increased action, variable; alteration during exacerbations of colic. Second sound in aortic area accentuated. High pressure, variable. Majority of arteries thickened.
He suffered gradual mental change; the whole of the mental symptoms increased in severity until the patient looked like the final stages of a case of general paralysis. He died on December 1. Colic was present at intervals during the whole time.
Post-mortem made the next day. Septic bronchitis. Hæmorrhage at the base of epiglottis and left vocal cord.
Lungs.—Septic broncho-pneumonia.
Pericardium.—Small amount of fluid.
Heart.—Striated, bluish. Weight 11¹⁄₄ ounces.
Ventricles.—Slight hypertrophy of left ventricle.
Valves.—Competent.
Aorta.—Atheroma near its bifurcation.
Arteries.—All more or less thickened.
Peritoneum.—Retroperitoneal hæmorrhage in region outside pancreas. Mesenteric glands enlarged, indurated, bluish on section.
Stomach.—Normal.
Intestines.—Vessels congested. Large bowel constricted at irregular intervals.
Cæcum.—Mucosa slate-coloured.
Colon.—Dark-greenish mass.
Liver.—Blue on section; pale yellow areas; soft in consistency. Weight, 47³⁄₄ ounces.
Spleen.—Normal.
Kidneys.—No fat. Cirrhotic, adherent, atrophic cortex, granular.
Muscles.—Generally dark in colour; wasted.
A very complete histological examination was made of the brain and spinal cord, and throughout the particular changes noticed were proliferation of the glia, hyaline thickening of the walls of the vessels, both arteries and veins, and presence of congestion; and here and there rupture of the smallest vessels, causing miliary microscopic hæmorrhages into the perivascular sheaths and the substance of the brain. There was no infiltration with lymphocytes and plasma cells, as is found in general paralysis. The neuroglia showed a formative hyperplasia resulting from chronic irritation.
In the cortex there was neuroglia proliferation in the polymorpho layer and the molecular layer. Changes were seen in the Betz cells, particularly in the Nissl substance, with perinuclear chromatolysis, such as is generally found in chronic peripheral neuritis, whether due to lead, alcohol, or other toxic causes.
There was no coarse atrophy or degeneration of the fibres of the cortex. Neither the cerebellum nor the spinal cord at any of the levels examined showed fibre atrophy or degeneration, except possibly a slight diffuse sclerosis in the crossed pyramidal tracts of the lumbar region.
Microscopical examination was made of the heart, spleen, kidney, liver, lung, and suprarenal gland. There was a general condition of angiosclerosis; in the liver a fibrotic overgrowth around the vessels; in the kidneys well-marked interstitial fibrosis.
A chemical examination of the brain was also conducted by the copper potassium nitrite method, but no lead was found.
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 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 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 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 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 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 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.