Document 6R9ZrMOQyL466eMG3k5KYdvq4

-fief - Journal of Medicine.-34:. 3-11 March-1930. March, 1930 LEAD POISONING--XEHOE 3 On the Diagnosis and Treatment of Lead Poisoning* ' Ro b e r t A. Ke h o e , M. D., Cin c in n a t i, Oh io - Front the Eichberg Laboratory of Physiology in the University of . _ . .' Cincinnati, Cincinnati, Ohio _ - The essential nature of lead poisoning,, ' Ex p o s u r e , l as well as thatof the other heavy, metal Measurements of exposure have become ' intoxications, remains S matter of specu a matter of necessity, not only in intelli lation and hypothesis. Despite the large, gent efforts fo prevent lead poisoning but amount of valuable clinical-and expert" .also irt diagnosis, .A considerable amount mental information which is available, our. of information has been collected, not knowledge is -scanty at certain critical jjoints, and much of'the information which has been.used to explain-the entire-picture is at best controversial. -In.this situation, it-is well to recognize the difference be tween facts and. working hypotheses. When facts, even those at the inost "em pirical type, are made the basis of pro cedure and practice, we cannot criticize,, even when; these facts are seen to.be in adequate. -But when hypotheses are con verted into gospels to be passionately held or just as passionately-condemned, we. are in danger of using them to conjure lip - wish fulfilment knowledge .on the one hand,-and to obscure and hinder the de velopment of new'tacts on the other. ably, byv Legge. in- 'England, and - Teleky in Germany, indicating-the qtlan..tity of lead exposure which i3 capa ble of producing, lead intoxication over a period of -time.'. With the -tremen dous. increase in industrial use of lead compounds, it becomes increasingly im portant to assess the significance of the" exposure to lead associated with various industries. By -far the commonest arid most imjxjrtant exposures are due to the contamination of the air . with finely ` divided lead compounds, it is a simple matter fa measure the extent of such con-lamination of the. air in the immediate. vicinity of workers. Thusjjriost of the - occupations in a particular industry have their own hazards, qualitatively and quan- - It is with these ideas in mind that I - titatively. The toxicity-of the lead-com -present some new .facts which are of fin pounds varies with their physical and clin- - - portance in the diagnosis and the treat - ical characteristics, but it 'may be said that - ment of lead poisoning. If these facts are . any type of lead dust, regardless of its not discussed in relation-to existing inter solubility or particulate size is capable of pretations of the character of lead poison producing lead-poisoning if present in stif-~ ing, ir is because adequate interpretations ficicnt concentration in the air- inhaled by -must come_more from-the future than 'animals or'man. It has been'established ~ from the present or past, and because the on a fairly sound basis, that the- regular facts by themselves are sufficiently im inhalaition through the usual working day portant to occupy flie time-at our dis -of air containing less than five miligrams' posal. .- - ' of lead per ten cubic meters of air does - The diagnosis of lead poisoning rests on- not produce-serious lead intoxication in si proper evaluation of the following mat- individuals of a representative group..1 A . -ters: (1) Exposure talead compounds; lower figure than this should be main f2) susceptibility to lead; (3) symp tained in-all industrial plants where lead tomatology;. (4) physical-findings; and- compounds are used. One .can only be J Ti') laboratory findings specifically related- sure that this is done by means of repeated to lead to agreater or les.ser degree. Such examinations - of the air- breathed by experimental evidence as follows is pre workers. - _ -" " "' '. . sented with the purpose-of clarifying In the non-industrial population poison- somewhat the means and the limitations ing is most-frequently occasioned by.the involved in such an evaluation.' . -. . `Read at a meeting of The-Academy of Medi cine of Cincinnati, December 9, 1929. , 1 Legge, Thomas M, and Goadby,. Kenneth W.: Lead Poisoning and Lead Absorption, London,"1912, page 207;' ' ' ; -- . - . *7ZJuLA^j** '--f Mit t 4 ". ' THEJOUBNAIOF MEDICINE March, ]:mh TABLE I -COMPARISON OF MEAN VALUES OF.GROUPS - WITH VARIABLE EXPOSURE " Subjects Lead in Faeces Lead in Urine Number u{ MeVGm Ash - Mgs/Liter . Persons Children -- .OST .068 . 88 Medical Students.-. .060 - .080 - it Workmen--No Known Exposure. ,074 .096 84 Same Type - Workmen*-- exposure. Thus We have a valuable meth od of determining the relative magnitude of .exposure in a particular occupation, liy making a study of the lead excretion oi ;i representative group large enough to take into account the sampling error occasioned by individual -variation. On the other hand, with these data, we are able to das- . Previous Exp.... .100 Carafe Mechanics .180 .130 - ,120 114 sify future" subjects as to tlje significance - fo of their exposure to lead, by merely study posed Workmen .192 Severely Exposed' - Workmen........... .780 _ .181 . .210 . 106 ing their excreta. " 132 In the individual case in-which the diag nosis is at state the examination of a sin gle sample of faeces or urine or both does ingestion of lead with drinking water and .not yield adequate information. This is Wines and food, and in the case of'chil especially true if the exposure has been dren especially, by chewing or sucking discontinued for some days or weeks prior toys,= furniture, or other objects painted, to examination. In the latter situation \ve with lead paints: That cases of the latter must study the individual's excretion long" type occur is sufficient reasoH for abolish enough to determine the average rate ot ing the use of lead paints on toys, beds, his- excretion, and whether it is on the playpens, and furniture commonly used decrease.' " . . . . bychildren. . , -- In the latter -instances there is' no sim ple way of determining the extent'of ex posure,' and even"under industrial" condi - tions the ordinary methods of measuring Table II shows the continuous lead ex cretion in the' "faeces and urine of one subject, J. F., whose lead exposure has, been- moderate. The initial drop in excre tion is most significant. It is a character exposure fire inadequate in_ that they do istic feature of the excretion of all lead not indicate the extent- of absorption of workers in a dusty atmosphere if observed lead which results from carelessness or immediately after removal from exposure. the improper use or inadequacies of'res- The first figure in the curve of faecal ex pirators and bathing and washing facili cretion represents -largely lead inhaled ties. ": A better measure of the total pic- - during the previous day while at work, and ture may be obtained b"y-a study of the subsequently carried from the upper res excretion, of lead Occurring among per piratory" passages with mucus, etc., to 4 sons Who arc experiencing lead exposure. the intestinal tract,1 where most of it is - Table I illustrates the variation- in the excreted -without haying been absorbed. extent of lead excretion "shown by repre With the clearing of the nose and throat sentative groups selected because of ob-" and alimentary tract, the excretion falls served, variationsrin degree'of lead'ex to the level occasioned by the magnitude- posure.' It is clear that the exposure to of lead which is actually absorbed into the lead on the-part of most non-industrialized -persons) is smali. Nevertheless the con ditions of life oft an earth-consisting part ly of lead and in an environinent in which, lead is used for-many purposes, presup pose some degree of-lead absorption on the part, of everyone. That such a small ab sorption produces a regular excretion of lead, militates against our -ancient concept of an almost quantitative accumulation of. lead in the tissues, and equally strongly ' 'against the notion that lead may exist in an-immobile state in the'body. It demon- . strates also that the toxicity of lead has a quantitative aspect.- The table shows that lead excretion increases with increased DUP050332405 March, 1930 -LEAD POISOHISG--XEHOE ` 5 TABLE HI ~ Umw j Cml-- * U4 severe. None of these men was ill at the time of study but all of them except the first, showed such signs pf lead absorption, as lead .line,-considerable stippling of the - erythrocytes and high faecal and urinary lead excretion. It would appear that even under conditions of severe exposure, measurable quantities of lead in the circu-' latihg blood are inconstantly found. The variation -in this -respect probably repre sents both sampling error and variation in the quantity of lead in the'tissues.- Thai - is to say,-a single subject may show lead- in his blood at certain_titn.es and not at - others, while one with a large lead content is likely to show a blood, lead higher than - tissues. - Now asexcretion continues, the one with a small lead content.- Thislpoint . amount of -leadrin the body diminishes, will be referred to later. . ' "" : and the rate of. excretion- drops. -Table HI shows the results" of similar",observa4 tions on the urinary excretion on this sub ject and another, R. S., whose exposure i was more severe--in fact 'enough to pro* duce actual intoxication in" a -short time. " The height and slope of the curves tell the story of the relative magnitude of the pre vious lead exposure. One cannot ignore the fact that the lungs probably contain lead in these cases, and that this lead is being continually absorbed into the blood and distributed in the tissues. Thus ab sorption is not entirely complete, and urrtil it is complete we cannot obtain-the true picture of the relationship^ excretion to the lead content -of the body. It would appear, however, that this factor is not of sufficient importance to seriously inter fere with the drop in-excretory rate. It may be possible to take this factor into raccount by a study of the lead in the blood, Another means of obtaining informa tion as to" the extent of lead exposure and absorption is found in the various methods - ' of recognizing the. histological changes in the blood. I have 'not found any great " superiority displayed by any one of these." over the other.- Variations in-the reticu- ' lated and basophilic erythrocytes are ap parently indicative of the same general type of change in the blood,-as-is shown by variation in the number of erythrocytes showing punctate basophilic stippling. Examination of the.blood'smears for stip pling is somewhat .easier than any other . method. Its sensitivity for "the purpose " for which it is used is entirely satisfactory! As a matter of fact- all the "microscopical ' blood changes used to estimate the extent of lead- absorption show a significant change prior to the development of symp toms of intoxication, except in instances nferences to which will be made further in inr our discussion. ' .. " TABLE IV - l e a d in - CIRCULATING BLOOD I The lead content of the blood, has not, o my knowledge, been used'as a means of finical interpretation. In the present late of our information, one must-be cauious in arriving at conclusions as to its" Present 'Haemo* Srmo* Subject Exposure globIn toms W.B.M..... Slight E.B___ ...... None L.McD.....slight . None so None None 00 None 03- None fib 1 Pb/ilg. % 1 . Trace 6 ., Nit -6 Nil 6 Trace 'TABLE V -- - - LEAD IN CIRCULATING BLOOD . Present Subject Exposure O.O. F..... Moderate M.M.___ -Heavy flr- Heavy Heavy J.S------- Heavy 1V.D....... Heavy pj.j.... Heavy E.M.__ Heavy J.F........ Moderate Haemo- Syxnp- Pb/Mgs ' g-lobin toms Stip/OOF . % - 82 None 26 Nil 74 ' None *51 0.10 73 None 71 . 'Trace ' 70 ' None 85- -Trace' 70 None 89 Trace 73 None o.i y 70 None .0.42 74 None 43 '67 None 40 0.13 0.15 - tsefnlness. It is entirely safe tosay that ead in any considerable amount found in - r he circulating blood, furnishes evidence I>f significant lead'exposure at some time;. fable-lV shows the result of analysis of - he blood in a number of subjects with lit- !e -or no exposure to lead. Table V ^represents a number :of similar observa.- stions on a group of- subjects whose ex- "posure to lead at the time of-sampling was } J I DUP050332406 6. THEJOUBNAL OF MEDICINE. "March, j k k i of sudden absorption of overwhelming lead .intoxication in an individual case,"by amounts. Therefore it is merely a matter . means of these or any other known meth of convenience and experience as to which ods of observation. It can be said only is used in following a group of workmen, .. that, under a certain set- of conditions cf or in arriving af a diagnosis; The only exposure, "cases of intoxication are-certain necessity in the use. of these methods' is. to occur in time. Armed with this infor- " that they be applied uniformly and quanti mation the industrial physician Can dem tatively. in relationship to known stand onstrate the need of limiting the exposure ards. Table. VI shows a comparison of of the men under, his care. stippling count s, made by a standard meth This -brings us to consider a" question od, for several groups of men under ob that has been at issue many times. When served variation of exposure. The sig- - does lead absorption develop into lead in - nificance of the figures shown is unques toxication? What are the earliest evi tionable. In I ascribing significance to dences of intoxication?' In my experience microscopic Wood changes, however, it is the earliest signs of lead intoxication usu necessary to recognise that none of them ally appear in the form of blood changes, is specifically due to lead absorption. One except in those instance's in which a sud must rule out"other anemias and leukemias den and large increase in exposure or a as well as the effects of the continued in-, complicating illness bring about the sud- - halation of benzolr gasoline, and perhaps- den .development of gastro intestinal ot certain other volatile solvents. Even vari nervous system symptoms. - If the ex ations in exposure to sunlight involve his posure. is comparatively regular and quailtological changes in the formed elements tftatively constant, the first"signs are like of the blood, and the limits of normal variation must be known more accurately than they, are now, before we attempt to make refined conclusions on such findings. The foregoing evidences of exposure to lead, and Consequent absorption," may-not be used as a means of recognizing the presence or the. likelihood of lead intoxi cation. All that can be established by the study of lead excretion, lead content of the blood, and histological variations on the ly to be a drop in the-haemoglobin con tent of the blood. This is usually preced ed by a progressive rise in the number of stippled erythrocytes, and followed by a diminution in the erythrocyte count. These -occur very frequently without any subjective symptoms^ or any other phys ical signs. Oh this basis, a steady rise in. the number of stippled erythrocytes in any lead worker is to be regarded as a sug gestive sign of impending intoxication, blood is the extent of the individual's ex while a progressive diminution of. the posure,- Obviously if his exposure can be .haemoglobin "content of the blood is to be shown to be of a type associated with the regarded" as an actual evidence of intoxi occurrence of-lead poisoning, one may ex cation,- with or without associated sub plain readiiy, perhaps too readily, the jective symptoms, except in those instances . background of characteristic symptoms in which the blood changes are due to and physical findings.- " - ' In industrial practice, however; it is not possible to anticipate- the development of other causes. .' Su s c e p t ib il it y . " Very little can be said about the under lying nature of susceptibility to lead.cum- TABLE VI pounds as it is so dramatically observed COMPARISON OF MEAN VALUES OF STIPPLING in the case of certain individuals.' With OF ERYTHROCYTES OF GROUPS WITH VARIABLE EXPOSURE - out attempting any explanation" of the. facts, it should-be pointed out that there Stippled Erythrocytes Subject ' per.50 fields Medicst Students............ 0,95" . Workmen--No Known Exposure ................. .. 1,35 Seme Type Workmen-- - History of Previous * Exposure _.................... 1.6S Auto Mechanics ............ 1.70 Larue Group Persons In - - - . Dusty Lead Industry.... 1T.0 . Selected Persons with __ . Heavy Exposure........ . 9S.00 - Number ol Subjects -71 are certain conditions which are known to influence susceptibility. The most im 84 portant of these are, (1) general vascular -disease, (2) general hepatic disease, (3) " 114 tuberculosis, (4) active chronic infections .- 70 in general, (5) starvation, and (6) fa - 122 .. 11 tigue. In addition to these,.immaturity in both animals and men is an important i * '" DUP050332407 If " litfOitti&W s- ; March, 1930 LEAS POISOSTtSTG--t -KEHOE 7 factor.' Any explanation of- the median-. TABLE VIII ism concerned with lead .poisoning must THE FIXATION OF LEAD IN THE CENTRAL" account for these facts. I mention them at this time only to point out the ncces- NERVOUS SYSTEM ' '. - - Ratio of Conc^ in Brain to ". - -: - - " sity'.for care in the exclusion from lead Rabbit ` - Lead in Brain Cone, in Entire Time in Days .- " occupations, , of persons in whom any of No. 86 M/% ' 1.62 Carets* After Treatment 4.0 4 . r these factors are at.work. In.connection' IS . - 0.72- with vascular disease I cannot but state 38 - . . 1.15 *r - 1J5 0.6 . .o 10.0 - 8 ' 150 830 v _ my tentative conclusion that lead intoxi ao T4 , 1.81 2.08 - 1&0 52.0 -270 420 -- ' cation is only doubtfully to be regarded as 75 ! 1.86 ' 23.0 240 - a cause of vascular disease. It rather : e 76 appears; that the incidence .of arterio LOS 1.27 42.0 53.0 800 no - _ ,,- sclerosis among lead workers is little if any higher than it is in a corresponding said that more than: traces of lead in. the age group of the general population. On blood indicate the strong probability of the other hand; the occurrence of lead' recent exposure of a significant type. . intoxication in persons with arterio- -The seriousness of nervous- system- ; sclerosis is high indeed. I suspect that it symptoms as a result of lead absorption is only because so many lead cases have -justifies some special consideration. Lead arterio-sclerosis that the" orthodox cause encephalopathy is the - most dangerous and effect relationship has' been said to "manifestation of lead intoxication, and -exist. -. the most unsatisfactory from the point -- Sy mp t o ma t o l o g y . . of view Of treatment. Furthermore lead - It has -been' stated by many persons that the symptoms in lead poisoning are l .due' to lead in the circulating blood. Up to the present there has been no direct evidence that such is the case. In fact, previous attempts to discover lead in the palsy, while'usually-not serious, as to life, presents-a gloomy...prognosis as to the return of normal function. . It is prob-. . able that this is due to ' a quality of ner vous tissue,- which is apparently not shared by any'other tissue of the body. blood have: failed because of a lack of analytical methods of sufficient sensitiv ity. If the symptoms are due to lead in the blood if' should be possible to find lead present. Furthermore, the continual Nervous tissue has a striking ability of fixing such lead-as reaches-it. This is' shown in Table VIII, in which a series of rabbits treated in various ways, but with considerable quantities of lead, have excretion of lead-in the urine presiipI poses some quantity of lead in the blood. been killed for analysis after .various per iods of time. Even after seventeen | Accordingly we have attempted to find months, during which practically all the fwhat quantity of lead is present in the other lead of the body has been lost, the blood. The previous tables (IV and V) brain of Rabbit No. 78 still retains an have shown that it may be found. Table VII. further illustrates the point, and amount which is almost as great as that, found in the brain of any animal of-the shows that in all the cases of acute ill ness studied by us to the present, lead is uniformly found in" the blood in measur series. - It is interesting to note that the skeleton of this animal contained no de tectable quantity of blood. . able quantities. It may well.be that a range of concentration may be found con stantly .associated with the presence of The imooTtance of this lies in the factthat if one has absorbed lead into the ' brain, he. may presumably deyelOp en symptoms. At present it may only be cephalopathy at any time afterward. Thus may be explained the occasional develop ment of central nervous-signs of lead in - TABLE VII ' toxication years after lead exposure has LEAD IN CIRCULATING BLOOD . been discontinued. ' " -' Vitsmt Hacmo- Sjrmp- ' Ph/Ms Subject- _ Exposure "globra- toms Stip/50F - % ' Just wfiat occurs to enable lead in the - Heavy * 56 -Slight - -24? 040 brain "to produce symptoms may-not be t J.C.B... SI.Prolonged 75 Slight 0 C.G.H.._ Heavy --Encephalopathy --. 042 0,21 stated with any certainty, but that, symp C.G.fl.-., Heavy - C.G.H..... Heavy R.S____ Heavy. -- Encephalopathy-- 042 toms are associated with lead in the brain . -- CoKc 70 Colic --149 0.04 0.37 -tissue is shown .by the-following-table - -_ - - - t DUP050332408 X issm, tiHum i kaii >i rt W 'iir' ijiM^T' r a THE JOURNAL OF MEDICINE March, 103a TABLE IX " Tr e a t me n t . DISTRIBUTION OF LEAD ICLINICAL ENCEPHALOPATHY) CASE J. C. _ It has been my observation that in most - Lead Lead Mgs- Ma%* instances of early lead intoxication, re 1 Tissue " Weiebt Foilmi per 100 ems MFs% an Crams Milligrams tissue in carcass covery occurs spontaneously -when ex \ - lib Bone------ 15.00- U5 13.000 i.n posure to lead compounds.is discontinued. - - - ft . ' -1 . - l A -j . .. -. - 5 - Long Booe.-- - Bone Marrow CartUare -- Sapraroul H _- Ft --------Patterns -Spleen_____ - Heart______ 12.23 6.505.00 . . 5.00 .oo 50.00 150.00 . 025.00 - 0.980.18 0.23 Nil Nil 0.1S l. 0.58 8.000 - 2469 *4.800 - -Nil . Nil 0.300 0.860 - 0.13? 19.51 - 6.75 - 11.22 Nil NU 0*68 2.10 0.88 Most- cases which do -not respond thu>are" either complicated by ailments, which need medical attention, or are the result of repeated or prolonged injury from ex posure over a considerable period of time. - - 1 . - 1- .. - :. . --- - j1 - i Kidneys 500.00 .Liver * . 1300.00 .. Lent (rt)___ 050.00 _,.---1. Aon* tit) ` 800.00 - Brain 1250.00 ' Spinar fluid.. 13.75 Blood 75.30 0.65 -9.20 0.6S 0.44. iiSS, "Nif -0.1Q 0.217 0.708 0.105 -0;055 0.348 Nil 0.183 OiSS - 1o.i7o3 -.0.13 0.85 NU 0.83 -The first requirement of good therapy, then, is to avoid doing anything which may interfere-with the normal processes of recovery. To accomplish even this re- =. 6077.80 ; 20.81. 0.110 LOO Thia talio between the concentration in a particular .quires some understanding of the nature of these processes.. Gne. of the important: tuiue aad that in the earcaaa a" whole represents a factors in recovery has to do with- the elective affinity for lead, which we have called _an "index of selective absorption". - -. elimination of lead from.the body.. Alien-' tion has been called to the fact that lead is steadily eliminated in both the faeces (Table IX) illustrative-of the distribu . and urine, and that the rate of excretion tion. of lead-in the tissues of a typical bears a relationship to "exposure, or pre- . fata] case. It should be noted1 that the sumably, to "the amount of lead in the small amount of spinal fluid contained no body. Thus the patient, left alone, will -lead, or .at most an amount too small, to tend to eliminate from his body the of- . defect. A terminal lobar pneumonia in fending agent. In time he will excrete all the necropsy findings in this instance, of the lead except that portion which is does not -exclude lead- intoxication as a firmly bound in his tissues. ' At present, primary'cause,-though it may be supposed there is no evidence that lead is fixed in _ that-the pneumonia contributed to the, pic any tissue of the body, with the exception ture; In fact there is quite commonly a of.the central nervous system. Therefore Icontributing factor in the-develqpment of there is no need for'the use of therapeutic lead enoephalopathy. I have seen lead measures which will aid in the elimination encephalopathy- develop after prolonged of lead from the tissues, except in the case x anaesthesia, and again what appeared ta of the brain. Here unfortunately, no be lead encephalopathy followed an illness such, measures are -known, though it is ' resembling epidemic influenza,. Here the likely that experimentation will discover differential diagnosfs fs a matter of some- them. - doubt, but the cerebral symptoms were However, it is possible to remove unab distinctly more.characteristic of lead than sorbed lead" from the alimentary tract, of a post influenzal- encephalitis. That such conditions as produce cerebral anox emia are effective in influencing'the de . " TABLE X _ " velopment of acute: brain' symptoms due - - - " rwT () Uwi jr to lead is strongly suggested by these faets. . = - It-is not ray purpose to discuss the symptomatology of lead intoxication, ex .cept to-the extent that it is possible to in troduce new experimental evidence relat ing to it. The clinical picture -in' lead poisoning is too well known, and too read- iiy-available to justify -further discussion. Accordingly I pass over the protean tnan- ifestations of lead intoxication to touch'- briefly on certain considerations as to the treatment. "' :' "' T-- V DUP050332409 mmimin .m Marcia JB30 _ LEAD POISONING--XEHOB - _ 9 TABLE XI . TABLE XII - DISTRIBUTION OF LEAD \ . -. Tissue- . Rabbit No. 243 - . ' Lead:: Lead Mgi Wt. of tissue Found per 100 gni -9|t% in Grams Milligrams tissue fa carcase 13.0 . Nil Nil . mi Liver 102.0 025- 0.246 1.00 Spleen ........ . 1.5 NU - a - Nil - 29.0 Lost in Frqnrstka - C.-N. S._....... U.0 0.13 0.039 -4.1* - Skin and Hair,, 283.5 0.00 0.210 0*8 - - Bkjod..... ..... . 92.0 - 0.17 - '0.18$ - 082 Meade __ ........ 704.0 O.R5 0.044 0*0 Remainder.__ 425.0 o.n 0.187 0.74 227.0 8.85- 1.475 - 6.55 Int, Tract....--.. 255.0 0.14 0.055 0*6 - Contents of - Int.. Tract...-- *07.0 0.21 -0.GS5 OB* - _ 2633.0 " 5.01 0.22$ 1*0 Total leju! excreted------ 5.18 Total lead recovered-- 1L07- and also-to maintain rapid evacuation oj Total lead injected------12.00 ? such-lead as is excreted into the intestinal j tract, so as-to'avoid its re-absorption, which compares, the' distribution of lead- j Magnesium sulphate has. long been used; in a series of animals treated intraven | orally in cathartic doses for this purpose, ouslyWith lead and killed at variable pe f Table X shows its effectiveness for this riods after treatment. The eventual dis-. [ purpose. - = " . . tribution'is the same as if the lead bad " The use of the generally recommended - .been administered rally except that cer measures for increasing lead elimination tain tissues, notably the Brain, have ab f from the tissues during the period-of lead _ sorbed lead brought to it by blood which f intoxication, is dangerous "and unneces- had not passed through the liver. Under s' sary. There is one means which may be conditions, which permit of the carrying' t employed effectively and without risk,. out of this normal type of distribution of which has not received attention. Table lead in the tissues, symptoms of intoxica 'i XI shows the extent to which lead excre- tion are likely, to disappear rapidly. In | tion by the kidneys depends upon water fact it is' doubtful.if symptoms occur so * excretion- - - - long as lead .is distributed jn this normal : The diminution of the symptoms of fashion,: It would be of the utmost im r lead intoxication which usually follows on portance, therefore, to understand fully f removal from exposure is not due solely the factors necessary for thirnormal dis to the excretion of lead. On the contrary, tribution. The existing data are inade much of the effect is due to factors which quate to define these factors; We must work to some extent in the opposite di rection. Under normal conditions lead .- TABLE XIII ' - disappears out of the circulating blood RELATIVE DISTRIBUTION OF LEAD*-- very rapidly. -There is evidence that this - . _ " TIME EFFECT - - -- .occurs initially through the influence of . - \|f " ' g* the liver. However, whatever - be the mechanism-a' large amount of absorbed lead appears -shortly in the bones, with - s. If 8 8 3 E Is - Jjj 2sjl 5?| <[ smaller amounts in the liver, muscles, con 0& . ftf!4- 8 Kn M*h nective tissue and fat. The normal type Kidney .... 2&70 -trace 3.22 1.64 O' 0-_ 0 Liver ..... 4.28 8.24 2.85 4.73 8.00 1.00 "1.68 of distribution isiljustrated in Table XII. Spleen------ Nil .74.07 1S.83 0 --0 trace Fat ............ 0.47 trace 0.86 -0 -- --O The speed wi.th which the lead is re-, C. N. S..-. 0.48 1.23 G.45 trace 0 "4.18 0 moved from the blood--this being done Bleed ..... - 2.68 ' 3.70 12.40 trace- -- 0.82 0 Muscle .... 0.-20 0.2T 0.38 0.12 --. --0.20- 040 almost quantitatively, when lead is ab Bone ------- 0.98 3.28 1.48 3.66 3.00 8.55 &22 InL Tract 0.43 2.19 1.47 1.78 -- 0.25 0.34 sorbed by way of the alimentary tract- -The figures above represent the ratio-between the. saves the other tissues from the effects, of concentration in any ou* organ and that m the total ' carcass, in each-instance. Thus one can see the shift* high-concentration over long periods of -ing which occurs with time. Thus the lead is out of the time. -This is shown by Table XIII, blood after 16 hours. It has reached practically the , normal distribution after 85 hours. I i >' I * DUP050332410 IVSi.n*lB i- 10 . . _ THE JOUENAL OP MEDICINE . - .March, 1030 -content ourselves,- for the: moment, with" the recognition, of certain things - which It is plain-from, the Combination of modify the-normal processes. -. in general if may be said that an-in-: blood and excretory findings .following the effect of exercise, that a condition of rest : crease in the lead content of the blood, is favorable to the distribution of lead in and in the excretion of lead, indicates the the tissues, wHHe exercise promotes ex . existence of conditions- which operate cretion. Some interesting. speculations against the normal distribution of lead in are prompted by these observations. The the tissues. Table XIV shows a number most characteristic physiological responses of factors which influence the iead. con-- in exercise are ah increased utilization of centration of -the blood. The broken line oxygen and an increased production of shows the drop in the' blood concentra lactic acid. One can scarcely refrain from tion following cessation of exposure, in' ' relating the increased output of lead to one an untreated subject. The solid line or the other of these factors. It is espe-. shows the variations coincident with sev dally-significant that lead compounds are eral types of treatment of another subject. peculiarly soluble in lactic .acid. It seems Table II shows the variation in the faecal likely that the increased lactic acid in the and urinary excretion of lead under these same influences,. . - - Tables XV and XVI show the influence of activity on lead excretion. The heavy tines in the horizontal axis on Table XV tissues brings about an increased solubil ity of lead, which escapes into the blood, to be subsequently removed by' the liver and excreted after some delay into the alimentary tract. indicate.;night, the thin lines-daytime. Whatever be the explanation, we cannot' Lead is thus'excreted more rapidly during but conclude that exercisers bad for the the activity of the day. . patient suffering- from lead intoxication. On the other hand the activities of the lead TABLE'XV worker promote elimination and combat accumulation. In the same terms, fatigue doubtless contributes to the production of symptoms. '; The foregoing facts, although present-ed very briefly, permit the-laying down of J a few-general principles for the treatment ; of lead-poisoning,. The patient should be : removed from all exposure to lead com- ! pounds, and he should be put in a condi- .' tion of rest.' The alimentary tract should ' be freed of its unabsorbed lead through ' the use of such a cathartic as Epsom ' Salts. - The free emptying of the alimen tary tract should be mantained throughout DUP050332411 I i March, 1930 I.KAD rOISONINO--XEHOE 11 tlie .duration of the symptoms-, to prevent r -most important measure is to eliminate . "reubsorption of lead excreted into-it any chronic disease which may be present Water should be given inrlarge quantities Especially'important is the cleaning up of : j k promote excretion of lead, Aid a suffi cient amount of calcium, potassium, and Mxiium salts should be given to maintain a proper salt balance in the tissues, during the-badly infected mouth that is' so com monly seen. Chronic infections in gen eral arc serious obstacles to complete" re covery and shouldbe4reated-ascotnptetdjy the high water intake. Large quantities as is possible: ' ' " .- ' 'of citrus fruit juicea are particularly ad Even at this time, attempts to eliminate . vantageous in obtaining both: increased lead rapidly from the tissues are unneces water and salt intake. . A full mixed diet sary. lithe patient is let alone the lead . .should be. provided so" as to promote and - will be eliminated, and without the neces-'." -maintain as nearly, normal physiological' sity. of constant medical care: The latter . state of. toe-body as possible; All agents which are believed or knowti to promote a quick-release of lead from the-tissues should be strictly avoided. " - - ~ : - In die case of cerebral involvement,, the" 'above regime is not likely to prove success ful. Here, one must resort to procedures. Avhichare to some degreeempirical Have -regarded this condition as due impart to" edema of the brain, "and, in one or two cases, I have had encouraging results from . - intravenous injections of hypertonic salt solutions. Twpjiercent Magnesium Sul-1 phate was especially effective in" one" case, ':in. that" it suppressed a" delirium and re-_stored normal consciousness reach time it was used. That edema-is usually present is often impossible, while without it, rapid lead 'elimination is unsafe. There is usur ally no advantage in sacrificing safety for' speed .in these cases. . .The patient should be cautioned agamsfexcesses ineffort, and- ' in. his' use of alcohol. He-should be ad vised as to toe danger ofrecurrence of Ins symptoms as a result of undueTatigue. or toe occurrence of acute infections within -. toe. succeeding few months. Thus: he : should avoid exposure to cold and unclear-- ent weather conditions,, and in every re spect he should-live a.s 'carefully'as is.pos- sjble,: He'should understand .that it is in-" advisable-for him to resume his exposure . to lead compounds.' . -_ . iipthesecases is not to be doubted, and al __ With the .above attention, the typical though combatting the. edema does not ease of lead poisoning without involve constiiute.an entirely adequate, treatment, . ment of the central nervous system, will it-is the best I can recommend on present recover uncventually, 'and in. most, in- . information, v - stances will show little or no residual ef When the acute symptoms subside, the fects from his experience, . : . -. : , " Extrinsic- Nervous Control of - - eral end of-toe hypogastric .nerves has - - Large Bowel . - -opposite effects orr.the ascending and - A. jr Carlson, Chicago (Journal A. M. -transverse-colon. If this portion of. the - A-, January-11,' 1930), has investigated, colon is relatively atonic at the. time; the " stimulation- induces -a powerful contrac this ptoblonJii dogs and monkeys. He tion of both the circular'and the longi is convinced, on-thebasis of many ereperi- tudinal jnusculatiire.'- On toe 'otherhand, - iuents, that vagus efferent fibers do. not - -.fl"this portion of the intestine is.in a rcach.or influence the"large"bowel in the. -farrdegree of tonus or rhythmic contrac-" dog, but vagus motor fibers-seem to teach tions -at the time of the stimulation, the tire cecum and "the appendix in a- small tonus and motility "are inhibited. Irri region of the-large bowel, close to-toe tation of .the sacral sympathetics. in the" cecum-in the monkey. The vagus motor dog produces a motor effect on the cir- .and inhibitory fibers reach, and influence - cular and longitudinal musculature-over- the whole length of" the small .intestine the. entire large bowel. This- region, in- - in the dog, not through toe. wall of the -stead of-haying no motor innervation, has intestine but bv- wiy .of the mesentery -a.double- motor innervation (sacral and connections. Stimulation of the periph hypogastric). s - - = . . ", ", rm. . ~ .-= = "ir . DUP050332412