Document a4ODd7Ex882XaGg2z86OXBEKR

, ,vv*~<r ' ^iie Behavior of Lead in The Animai Organist'aiv''iV5-k- A. It is well known that lead la only slightly tcoflc for animals and m a n when absorbed slowly Many times the single "* lethal dose m y be found in the tissues of apparently normal ani- ; mais Furthermore , experimental animals and men may go through - all the activities of an apparently normal life without showing any evidence of interference with any normal function,.at any time in spite of having taken into their bodies large quantities of ; lead, ~ v \ -;; The explanation of this apparent lack of toxicity in r the case of rabbits is shown by experimental studies on the distri* O bution of lead in the tissues, and the excretion of lead from the body, . . " , ; .. . : . . '' .: : '' Data compiled from the analyses of the tissues of many rabbits which have accumulated lead without developing lead pi sonlng at any time, show a characterist1cdistribution of lead In the tissues ^ Selective .absorption'Is. shown b y the liver , the kid- . .....j ' noys, the central nervous s y s t e m ^ a n d 'the bones. The skeleton does not absorb all the lead. In fact the concentration of lead found in the bones is rarely higher than tliat found in the other tissues mentioned above. But, because of the enormous mas3 of the skeleton as compared with that of the liver, kidney, and central nervous system, most of the lead is found in the skeleton, f% u s this large bulk of comparatively inert tissue, physiologically, 3-y sM' V t;, -`M  2 is able to take up largo quantities of lead, and in so doing maintains a low concentration throughout the entire body. A study of excretion in relation to tho total load content and tho distribution of load in the tissues, shows that thoro is a continuous excretion, the magnitude of which is propor tional to the total load content of tho animal. Furthermore, In spite of a great diminution of the total lead in the body, as a result of prolonged and continuous excretion, the distribution of lead in the tissues remains proportionally constant, oxcept in tho case of the nervous system. ^In thi3 tissue the relative concentra tion steadily increases as load is lost from the body^ '.his can occur only as a result of a continual shifting of lead in tho tis sues, Is tho excretory organs (liver, intestine and kidney) give up load, they absorb lead from the blood, which being depleted as to its load content, takes up more lead from the tissues through which it passes. Tho cyclo continues thus until moat of tho load is lost from tho body. Thus because of its manner of distribution and its continuous excretion load is only slightly toxic, ordinarily, and oven largo amounts may fail to induce poisoning. D. Lead poisoning, hov/over, occurs in experimental ani mais under proper conditions* It nay occur when tho actual quan tity of load in tho animal body Is quite small. Acute symptoms and death from lead poisoning occur as the result of the administration of a single sufficiently largo dose, or following the frequent repetition of doses, one of which is not apparently injurious, also, illness and death from lead poisoning may occur at a time in which no lead is being administered or absorbed* Then this lattor occurs there is always sortie contrlbu- tory factor. Anaesthesia, starvation, difficult parturition, inter current acute infection, or experimental administration of acids, alkalies, and many neutral salts, may precipitate an attack of ill ness and perhaps death as a result of lead poisoning. lio matter how the poisoning is induced certain com mon facts are seen. The rate of excretion of lead is high, the blood content is high, and there is a striking variation in the distribution of lead In the tissues from that found in the leaded but symptomless animal. These facts lead to the following conclusions. Poi soning is produced when the lead concentration in trio blood is high. High concentration in the blood may be produced in any one of throe ways. Lead may be absorbed into the blood from the outside at a more rapid rate than it can bo distributed into the tissues. Or, in spite of the rate of absorption sufficiently slow to allow dis tribution, the total quantity taken in nay bo such as eventually to bring about a high concentration in all the tissues, including the blood. Obviously in both of these cases-excretion does not keep pace with absorption, and if excretion be impaired for any rea son, poisoning will be hastened. Finally, lead may bo poured out of the tissues into the blood, so to speak, as a result of fete changes in the tissues themselves. The data indicate that the tissues most easily sub- jeefc to change in this direction are the liver and kidneys* The skeleton takes part in the process but apparently at a slower rate. The central nervous system, on the other hand, shows a decided ten -4 The variety of the conditions which may precipitate acute poisoning in the 2abbit fluring a period of complete freedom from absorption compels a search for some mechanism common to all '.-/hereby lead may be brought out of the tissues into tho blood* Such a search brings U3 to the recognition of the similarity of behavior of lead in the tissues as compared v/lth that of the lead-protein com pounds under laboratory conditions* In the presence of certain pro teins load i3 bound, so to speak, and is only very slightly soluble. *' , '4 '"4* ft * In the present oFVtTcids, alkalies and neutral salts, however, the heavy metal protein precipitates are seen to resolve and to free the heavy metal from its relatively insoluble and little diffusible state* t is difficult to conceive of any other combination of tho heavy metal in tho tissues which may be affected by so many variables* On this basis the influence of parturition, acute In fection, fatigue and other types of illness with thoir attendant increased production and decreased elimination of acids, together with administered acids, alkalies and many neutral salts may all bo readily understood. Thus becoming freely diffusible and mobile in tho body lead may be expected to enter trie blood stream in high concentration and to be carried into tissues such as the central nervous system which are highly susceptible to injury, a3 '.veil as to bo oneretod at a greatly increased rate. Further evidence of the probable correctness of this interpretation is offered by the relative efficacy of the salts In producing the above effects* hose salts which are most effective in resolving heavy metal-protein precipitates are soen to bo most effective in bringing about changes in distribution of loud in tho tissues, and in promoting excretion* Thus the ammonium salts (includ- ing the carbonate) and certain salts of potassium as the iodide and sulphocyanate are strikingly effective in both* C* A consideration of clinical facts as ' veil as indirect evidence gained by studies on excretion of lead in man indicate the ' great liklihood that the distribution and excretion of lead in man are influenced by the 3ame set of factors as have been observed in the case of rabbits* Direct proof is difficult if not impossi ble to obtain because of the necessity of obtaining human tissues for analysis under conditions which do not allow of tho Influonce of acute illness and disease on the anto-morten distribution of load* Concluding on the basis of the indirect evidence that the facts as regards lead distribution in man are as observed in tho rabbit, the principles on which the treatment of load poison- / ' ing should be based are capable of simple statement, (1)* Persons, without symptoms, but mown to con tain large quantities of load must be regarded as potential cases of lead poisoning* The normal distribution of lead in their tis sues should not be disturbed, except as they are kept under the closest observation, and slow elimination of load should be main tained over a long pei'iod of time, during which further absorption CO ^ is prevented* Intercurrent infections are especially to bo feared, (7 and In the event of their occurrence every effort should be made o to prevent the development of tho starvation or intoxication acid KE 0 accumulation which so frequently results* .. . The use of especially efficacious methods of lead elimination is fraught with grave danger to tho subject ex cept under the most careful observation, and, in general, it is advisable to use materials which produce their effect slowly* 6 (2)* 'he patient with lead poisoning is already suffering as a result of abnormal distribution of lead. In his case every effort iaust bo made to restore the normal relations of lead distribution. He should not bo treated for greater elimi nation of load. Careful observation will usually serve to indicate why his symptoms are present* Several possibilities present them selves, but the most important and more frequently effective means of producing a subsidence of symptoms is to neutralise the acid in toxication which is usually present by proper quantities of alkaline salts. After the disappearance of the symptoms of active poisoning the case of this man is in no wise different from that of the group discussed previously* K 0006574