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 Ancient Factors in the Relations between 
 the Blood Plasma and the Kidneys 
 
 BY 
 
 A. B. MACALLUM, M.D., F.R.S. 
 noTMMM or Koomunnvr w nn VNimMrrr «m kmomto 
 
 PUM THE 
 
 AMERICAN JOURNAL OF THE MEDICAL SCIENCES 
 July, 1918, No. 1, \-oi. dvi, p. 1 
 
Estnrtcd from the AmnieMi Journal of th* Medical B e teneee, 
 July, 1«18. No. 1, vol. elv4, p. t 
 
 AHcmn VACTOBS nr the ULAnom bbtwihi 
 
 BLOOD FLABMA AMD TBI KDlfin.' 
 
 Bt a. B. Macallum, M.D., F.R,S., 
 
 niorEaaoB or ■looiBiiianiT m nn umvaMrrr of Toaoirro. 
 
 The -'^nism, excq>t that of the unicellular type, is a 
 
 congerii - whose history, individually considered, as it is 
 
 thus i. i, constitutes the sciences we call onnparative 
 
 embry) .jmpar»tive physiology and which we must know, 
 
 not only . . oipreht . ' the full significance of the work they now 
 perform, but aba to leoognize and interpret the possible variants 
 from the norma' in function and structure which they may manifest. 
 This history, in invertebrates as in vertebrates, is one of change 
 either in structure, or in function, or, often, in both structure and 
 function, and, accordingly, frequently confusing and difficult to 
 follow m any attonpt to gain a full comprehenaon of the conditions 
 and forces tiiat determined the diaracter of etidi organ. 
 
 One needs but to scan the list of the organs of the vertebrate 
 body to illustrate how true this is. The nervous system with its 
 protean numifestations in the line of evolution, the thyroid, the 
 thymus, the suprarenals, the pituitary body, the pineal gland, the 
 gills, the lungs, the alimentary canal with its accessiny structives 
 and even the liver, all have a past in which the dominant feature has 
 been changed in structure and fimction with the result that the 
 final stage in each transcends the eariier ones and so obscures their 
 characters that it is- now difficult to determine the earlier history 
 except in some cases from the structural side. 
 
 One thing is mdeed certain. The' change has never been of the 
 ■per aaUum type. But it has been unceasing, without pause, and it 
 b progressmg today as it has been in the long past. The Hera- 
 deitan flux therefore plays its part in organogenic evolution as 
 distinctly as it does in the physiod world. 
 
 Among all the organ? with their varied history as to structure 
 and their variations L. fxmction, there is, however, one whose 
 function in one particular respect has not changed from the time 
 
 ■ The Hatfield Lecture delivered l>afora the CoUcfe of Phjrsiriau, PhOadelpbia, 
 April 10, 1017. 
 
2 iiACALum: TBI BLO<» nuMJL Am TBI xmNxn 
 
 when it first began to evdve in the very far past Thia wgan is 
 the kidney and the function ^;hid) it performs, as it has performed 
 it far back in the very beginning of the history of vert<^te life, 
 is the regulation of the inwganic composition of the internal 
 medium (rf the body, whidi we know as tlw Mood idasma. 
 
 Hus organ was am<Hig the very first to appear in the prutoverte- 
 brate, or in the first invertebrate type whidi hegta to (Merentiate 
 along the line of devdoixnent whidi resulted in the aiq>earanoe 
 of th^. protovertebrate in the Cambrian, at it may be pre^^ambrian 
 times. If vre may rdy on the order in whidh the organs appear 
 in the euibryologiad history of the vertebrate, the renal organ is as 
 ancient as the neural canal, a.nd its otypn would appear to antedate 
 by a long period the dosure of this canal and the disappearance of 
 the coelomic cavity into which the primitive nephric tubules opened. 
 If the latter are, as has been claimed, derived by differentiation fr(»n 
 the coxal ^ands of a crustaoean<4ike form, they are of more andent 
 origin than the neural canal itsdf . 
 
 What the kidney of the protovertdnate was we may gather firom 
 the eariiest imm of the vertebrate kidney, which consisted of 
 three divisions, arranged in order frmn before badcward: the pro- 
 nephros, the mesonephros and the metanqdiros. One of tb<se, the 
 mesonephros, becomes the adult kidney in fishes and ^phibia; 
 ano^er, the metanephros, becomes the functional kidney m other 
 vertebrate classes, reptiles, birds and mammals. This is of sig- 
 nificance, as I shall show later, in indicating that the regulation of 
 the inorganic composition of the blood plasma exercised by the 
 adult kidney must have been exercised also by the kidney of the 
 protovertebrate. 
 
 In order to understand what thb regulation involves we must 
 for a moment consider what the inorganic OMnposition of the bk)od 
 plasma is. The salts of the blood plasnw in amount range between 
 0.78 and 0.88 per cent, of the weight of the plasma, and they consist 
 of the chlorides, phosphates, carbonates and sulphp'^es of sodium, 
 potassium, caldum and magnesium. The salts of sodium are by 
 far the most abundant, after which come those of potassium, cal- 
 cium and magnesium in the order mentioned. Tk j salts of sodium, 
 chiefly the chloride, amount to more than 90 per cent, of the total 
 inorganic solids of the plasma. 
 
 The composition in detail has been determined by Bunge for the 
 horse, ox and pig, and by Abderhalden for the ox, horse, pig, sheep, 
 dog, cat. 
 
 lie composition of human plasma has not been redetermined 
 since 1850 when Carl Schmidt published the results of a number of 
 analyses which are quoted now m all the text-books. They were 
 obtained by the methods in use seventy to eighty years ago, which 
 gave less exact determinations than those now followed in making 
 such analyses, and, consequently, the percentages, notably those 
 
macallvm: tbb blood plasma and thb eonibtc 
 
 of potMunn, cmldum, magnetium and dilorine, whidi Sdunidt'i 
 deteraunatioBS yield, ue open to quettion. 
 
 Hie inorganic oompoMtion of the plaana in binU, reptiles and 
 amphibia has not been ascertained, but the total peroentacs of tho 
 ash has been ascertained to range between 0^ and 0.9 in birds and 
 reptiles, while b the frog it has been estimated to be as km as 0.46, 
 but this may possibly be due to the diflkuHy of getting enou^ of 
 the idasma of the frog fr«e from admoture with water or lymph. 
 The fact that in birds and reptiles the percentage ct the salts is 
 as hi^ as in mammals is an indicatitm that the details of the 
 composition are not widdy different from those of the plasma 
 of the nuunmsis abovo mentioned. 
 
 The analyses of ttie bloc ! plasma m fishes whidi we have today 
 are only those of thu cod, ptjlock and dogfish, which I made dght 
 years ago, and they are of q)ecial interest in connection with the 
 aniJyses (rf the Mood pUsma of mammals. 
 
 If one examine*- Bunge's and Abderiialden's tables, giving the 
 results <k their analyses, one is impressed only with the fact that the 
 detsils obtrude themselves to the exdiision of all else, that in fact 
 one does not see the woods for the trees, and, in consequence, the 
 ngnificanoe of the results are obscured. 
 
 If, however, one selects the catiimic elements and arranges them 
 in values proportional to the most abundant one, sodium, which 
 may be made equal to 100, order is obtained frran the mase of 
 details in these uudyses, a^d one finds surprising reaemUanoes in 
 the ■wdues obtained frwn plasmas (rf all the mammals. FurthCT,the 
 proportions obtained frran the analyses of the {dasLja of the fishes 
 referred to fall bto lice witl t tne fran mammalt, in such a way as 
 to suggest that we have thus revealed a cardinal feature in the 
 inorganic compositiob of the blood pbuma ci \-^tebrates. 
 
 TUs feature is indicated in the fdkr. ing table of ratios in which 
 Na - 100. 
 
 
 Nk. 
 
 K. 
 
 Ck. 
 
 Ml. 
 
 DucSdi UeanOtiat lulaaru) 
 
 100 
 
 4.01 
 
 3.71 
 
 3.40 
 
 
 100 
 
 0.600 
 
 3.03 
 
 1.47 
 
 FoUoek (PsBcmMiu tireiu) . 
 
 100 
 
 4.SS 
 
 3.10 
 
 IM> 
 
 Do* 
 
 100 
 
 «.8S 
 
 3. S3 
 
 0.81 
 
 MMDBUd (•«•««•) . . . 
 
 lOO 
 
 e.oo 
 
 3.68 
 
 o.ao 
 
 Man (C. Schmidt) . . . 
 
 100 
 
 9.23 
 
 3.37 
 
 1.7S 
 
 Mu (A. B. M-) . . . . 
 
 100 
 
 S.U 
 
 8.71 
 
 0.86 
 
 The ratios for man are -derived from Schmidt's analyses carried 
 out, as already stated, with methods which wer ^ less exact than those 
 which are employed today, and, in consequence, they are accepted 
 with reserve, more especially as in my own determinations on the 
 blood plasma of man the values for potasaum, calcium and mag- 
 nesium are much lower than those given by Schmidt and in general 
 accord with those of Abderhalden and Bunge for manmuls. 
 
 Tlie ratio of potassium in the blooid plasma of the cou, as Jeter- 
 
macaixom: thk vumd plasma and the kidnsts 
 
 mined in my own anaiyMB. is hif^, but this may fomAhky be due 
 to hemolysis, the prepantion of serum which I used having • red- 
 dish tinge and therefore probably contained the potassium ol the 
 hemolyud oorpuacles, which thus would give a higher ratio for 
 this element tlwn would be given by pure plasma or serum. The 
 fact tint so near a relative of the cod, as is the pollock, gives less 
 than half ^ ratio of the cod and approadies vtry closely that of 
 the do(^ supports the view that the ratio in the cod is less than 
 that given above. 
 
 Apart from these exceptions, if they are to be ranked as such 
 and not due to errors in analysis or to abnormal composition, the 
 striking feature is the very extraordinary parallelism between the 
 ratios in mammals and those in fishes. Thb parallelism appears 
 enhanced when one consklers that the concentrations of inorganic 
 salts in both classes c^ vertebrates differ. The concentrati- i in the 
 serum of the mammal, lis already stated, ranges from 0.78 to 0.88 
 per cent, in the sera of the cod anti pollock, from 1.282 to 1.20:i, 
 respectively, while in the dogfish it is 1.774, or {wactically, double 
 what it is in the serum of a mammal. 
 
 The parallelism in the ratios of the individual elements in the 
 highest as well as in the lowest vertebrates is a cardinal fact, some- 
 thing more fundamental than the total concentration of the salts 
 in the plasma. Its occurrence in two such widely separated classes 
 of vertebrates suggests that it is an endowir -xt received from the 
 common ancestor of both, the protrvertcbrate, which must have 
 existed in the early CamlHian or pre-Cambrian times. 
 
 What is the explanation of these ratios between the sodium, 
 potassium, calcium, and magnesium? 
 
 The answer tc this question I obtained some fourteen years ago 
 when determining the inorganic composition of certain medusae 
 and comparing it with the composition of the ocean water of their 
 habitat. Aurelia flavidula, the common jelly fish of our coasts in 
 July and August, when it is liquefied, whidi happens when it is 
 allowed to stand in a dry dish, furnishes a liquid in which, besides 
 organic constituents, is contained a concentration of inorganic salts 
 like that of the ocean water from which the animal was taken. 
 From the analyses of its salts, compared with those of ocean water, 
 ratios between the sodium, potassium, calcium and magnesium 
 (with Na - 100) were obtained which revealed a very striking 
 parailel. 
 
 Ocean water (Dittmar) . 
 Aurelia flavidula (Macallum) 
 
 The parallelism betw^een the two series of ratios is very close and 
 the conclusion follows the' : fluid in the tissues of Aurelia is 
 but very slightly modified t .^-n water and of the same concentration 
 as the latter. 
 
 Na. 
 
 K. 
 
 Ck 
 
 Mg 
 
 100 
 
 3.03 
 
 3.01 
 
 12.10 
 
 100 
 
 S.18 
 
 4.13 
 
 11.43 
 
MACALLVM: the BLUUD FLMUU and tub KlbNEYH O 
 
 It WM, however, when the ntkw for w» water were com|Nired 
 with the ratios c f the blood piMn» of • .unnul, for enmi^. the 
 dog. that one obtained a chie to iK orif . of the rathm in the blood 
 pbunia of vertebrates. We we in tH' ^tter: 
 
 
 N*. 
 
 K. 
 
 Ol». 
 
 Mfl 
 
 OoMM w«tMr (DitUBu) . . . 
 
 100 
 100 
 100 
 100 
 
 I.ftl 
 
 e.w 
 i.ta 
 a.TS 
 
 a. 01 
 a.sa 
 
 4.00 
 4.85 
 
 13.10 
 0.81 
 
 n.ao 
 
 1.73 
 
 Jiat the ratios are parallel to thoee of ocean water, except b regard 
 to magneshim. Were the ratio of the hitter reduced to 1, or thnc- 
 abouta, the paralleliam between the two awies would be so striking 
 as to render unneoesaary further diacuasion of th* queation of th^ 
 origin of the ratio* in the blood i^aama. 
 
 That these ratios are of oceanic wigin can admit of no dou 
 when we cmnpare them with thoee of the horseshoe crab ardlobntt.. 
 
 The horseshoe crab. Limulus fdyphemua, whidt b<<s kid its 
 habitat in the ocean aince its origin in the early por«.'>n of the 
 Pabeozoic age, has a jJaama in vhidi the pa -^ . Jisni betw •: v \t and 
 ocean water is uncontrovertible. Thu b nc '..bt due to ;he fact 
 that the osmotic preaui .' of the ocean has been acting on its plasma 
 through the many milUons of years which have elapsed since the 
 Cambrian age, and, jdiough unquesticmably the ocean has been 
 undergoing, in all that time, changes, not only in concentration but 
 also in the ratios of its salts, the Mood plasma of the horseshoe crab 
 has kept pace wiUi it and today the concentration of its salts equals 
 that of tlue ocean water in whidi it lives, and the ratios in its pUuma 
 are practically l^ose of ocean water. We thus see that ocean water 
 does in diis one case determine the inorganic composition of the 
 blood plasma. 
 
 In the plasma of the lobster, Homarut ammcanut, whK'h has been 
 associated with He ocean only since the Cretaceous pe lod, though 
 the concentration of the inorganic salts b as hi^ as the ocean 
 water of its habitat, the ratio of the magnesium only is different 
 from that of the ocean. 
 
 In both the lobster and the horseshoe crab the concentration of 
 the inorganic salts of the plasma appears to vary with the concen- 
 tration of the ocean water of their habitat, and in brackish water 
 it falls to that of the latter. The concentration of the salts of the 
 plasma in these forms follows the concentration of the medium, 
 whereas in the Seladiians, which include the shark: and \be dogfish 
 and which have had their habitat in the ocean ever smce the early 
 part of the Pabeozoic age, the concentration of the plasma salts 
 exceeds half that of ocean water to a slight extent, although the 
 osmotic pressure of the uoean has been exerting its effect on the 
 Selachian plasma for at least several scores of millbns of years. 
 
6 iiACALum: ih> blood flabma and the kidnitb 
 
 In the marine Teleosteui fishes, whidi, like the ood, have been 
 denizens <rf the ocean for a time, periiaps, not. half as long, the 
 concentration in the i^asma is but little more than a third of 
 the concentration rf the salts m *iie ocean. 
 
 In the marine invotebrates of today the circulatory fluid is but 
 a more or less modified form rf sea water. In some the circulatory 
 channels fiedy communicate with the exterior with the result that 
 the circulatory fluid is pure sea water, but, even wbea the circu- 
 lation is closed as it is in the horseshoe crab, the blood plasma is 
 sea water with protons and other organic constituents. 
 
 There is then a jwofound difference between the blood plasma 
 oi vwtebrates and that of invertebrates. That of the latter varies 
 more or less readily with an immediate change in the medium of 
 the habitat, while that of the former is affected, and then but 
 appreciably, only after milBons <rf years. 
 
 Ate we then to condude that the plasma of vertebrates was 
 primarily of wigin different from that of the plasma of inver- 
 
 tebmtes? .... . . , . 
 
 If we scan the tables of ratios for the sodium, potassium, cakaum 
 and magnesium in the i^asanas 6t the different forms of vertebrates 
 and invertebrates, we see m the paraUeliam already rderred to an 
 unmistakable indication that the blood plasma of vertebrates was 
 also originally sea water, not indeed the aea water of the present 
 age, but of a far past when the concentration of its salts was less than 
 one-third of what it is now and when also the potassium was rela- 
 tively more a^ the magnesium rdativdy less abundant than m the 
 
 ocean of today. ...... , . . -. 
 
 The sea b tiie ori^nal home of all life on our ^obe, and it was 
 m the sea that the differentiation between amnua and vegetable 
 life as well as the evdution of tiie great divisbns of the annual 
 kingdom were effected. Indeed, the great events in the evdu- 
 tion of animal forms have been roidered posnble by dianges which 
 have taken iJace in the composition of the ocean. Among the fun- 
 damental results of these changes was the devdoiMnent of a closed 
 circulatory system of vertebrates, the fluid contained m which 
 became henceforth independent of the ocmipoation of the contempo- 
 rary ocean, and, as we have seen, of the ocean of subsequent periods 
 even after many millions of years, as in the case of the Seladiians 
 (sharks), marine Teleosts (cod, herring) and the Cetaoea (whales). 
 
 The sea ever since the first condensation of water on the ongmal 
 cooled rock crust of our ^obe has be«a changing in composition by 
 the leaching out of its bed the salts it contained and by receiving 
 salts in the river discharge, also leached frwn the land areas of 
 the globe. The quantity of salts annually disdiarged from the 
 land areas is enormous and it is estimated by 'Joly at about one 
 hundred and fifty-seven nullions of tons (157,270,000), which, if 
 divided into the amount of salts which he calculates as contained in 
 
I 
 
 I 
 
 macallum: the blcxh) plasma and tbb ramsTS 7 
 
 the ocesn today, mundy, 14,151,000,000,000,000 tons, would ^e 
 the age of the ocean as aj^roximatdy ninety million yean. The 
 concentration has theief(»e been slowly dianpng and it must have 
 been in the far past much less than it is now. 
 
 The idative propcHlions of the various salts must have duuged 
 dso. AH the salts discharged in the ocean by the rivers have not 
 been retuned, for, woe they retained, the potassium and the 
 calcium salts would be very greatly nuwe abuiulant than they are 
 now. Indeed the caldum salts in the ooean would have long ago 
 reached a degree (rf high supersaturation quite impossible to con- 
 cave of, since the Ume saks in the calcareous rocks of the earth's 
 crust, depodted from sea water in the past ages, woidd thus be in 
 sdution in the sea. The potasdum was, <moe, rdativdy to the 
 sodium, more abundant than the i»esent ratio indicates, and it 
 has been and is being constantly -xtracted fr«n the ocean in the 
 formation oi such minerals as glaiuionUe apparentiy at a rate whidi 
 keeps its concentration over long ages f airiy constant. The mag- 
 nedum salts also have bem concentrating slowly, for the dinuna- 
 tion of magnedum as cubonate in the formation of ddomitic lime- 
 stone has been proceeding at a rate less than that of the constant 
 addition throu^ the river water. This wouM postulate that mag- 
 nedum b not only absdutdy but also relatively more abundant 
 in the ocean of today than it was in that of the far past 
 
 The only constituemts that are not extracted from the ocean are 
 the sodium salts. TTirae have always therefcwe been on the increase 
 from a time in the eariy pre-Cambiian when they were periiaps but 
 slightiy in excess of those of potasdum. Their increase will proceed 
 in the ages to come and findly produce such a d^ree of concen- 
 tration and, consequentiy sudi a speca&c dendty that will, as in 
 the water of the Dead Sea, pwmit tiie human body to float because 
 d its lower spedfic gravity. .... 
 
 The differences in the series of ratios exhibited by the sodium, 
 potasdum, calcium and magnesium in the blood plaana of verte- 
 brates on the one hand and in the sea wat» of today, on the other, 
 parallel as these two series so strikingly are, can be e^)lained as 
 due to the blood plasma reproducing, ai^roximately, the ratios 
 obtaining m the ocean of the time when the ori^nal ancestral form 
 of vertebrates, the i»otovortebrates, ot eovertd)rate8, arose. The 
 total concentration of the salts in the blood plasma can also be 
 explained as due to a reproducti<m of the ooncratration <rf the sea 
 water of the same age, that is, when it had less than 1 per cent, of 
 
 salts. 
 
 How far back in geolo^l time this poiod was it is difficult to 
 detomine exactiy. It must have been eariier than the earliest w 
 most ancient fosnl ronains of vertebrates indicate, that is, in the 
 eariier Cambrian or even pre-C«nbrian, for the |m>tovatdi>rate 
 must have l<Mig preceded the vtftdmtes to which, throuf^ evdu- 
 
8 
 
 hacallvm: the blood plasma and the kidnets 
 
 tion, it gave origin. How long the intervening period has been is 
 also difficult of detennination. Estimates made on various bases 
 give different results and the only satisfaction that one obtains from 
 them is the recognition of their extreme limits, the maximal and 
 minimal. Prof. Strutt in determining the content in helium of a 
 nuneral derived from Cambrian rocks of Renfrew Coimty, Ontario, 
 Canada, calculates that it was over seven hundred million years old. 
 If, on the other hand, one follows Joly's method, based on the 
 amount of salts in annual river discharge into the ocMn, and the 
 amount now in the ocean, and also acceptmg as approximatdy co> 
 rect the percentage of salts in the ocean when the protovertdbrate 
 arose as less than 1 per cent., and therefore less than one-third of 
 the concentration in the ocean of today, it follows that more than 
 sixty millions of years must have elapsed since the protovertebrate 
 appeared and disappeared on the geological horizon. 
 
 Whether we accept the higher or the lower estiouite, or even a 
 lower one still, the enormously long period during which the blood 
 plasma has been simulating Palseo-oceanic conditions in the con- 
 centration of its salts and in the ratios of the sodium, potassium, 
 calciiun and magnesium it contains, emphasizes the importance in 
 one respect of ^e organ which has maintamed through the long 
 ages of vertebrate history this concentration and these ratios, prac- 
 tically unchanged. 
 
 Thia organ is the kidney. There is m invertebrates no structure 
 with a similar function or with a function even distintiy approaching 
 that of the vertebrate kidney. It is this organ that has made a 
 fundamental difference between the vertebrate and the inverte- 
 brate, not only in the struggle for existence but also in the capacity 
 to evolve higher forms of animal life. The animal form that must 
 accommodate its internal medium to that of its habitat has an 
 enormous handicap when it changes its environment, from ocean 
 to fresh water or to land, as compared with one whose internal 
 luediimi, under all circumstances, is constant in composition. With 
 such a handicap vertebrate life and all that it involves would have 
 been impossible. 
 
 This function of the kidney is fundamental and is more ancient 
 than that of excreting the waste products of the tissues of the 
 body. In the dogfish, as in Saladiians generally, whose history 
 has been associated with the ocean since their origin in the Silurian 
 period and in whose blood plasma the concentration of salts has in 
 consequence been incr«i^ed to only about half that of the sea, the 
 difference between tiie osmotic pressure of the ocean water and 
 that given by the salts of the blood plasma is equalized by urea 
 which amounts to more than 2 per cent^, and by ammonium salts, 
 which amounts to more than -^ reckoned as NH,. This retention 
 of urea and ammonium salts undoubtedly developed as a result of 
 the tendency of the blood to balance the slowly increasing osmotic 
 
IIACAIXUII: THB BLOOD PLASMA AND THE KIDNITB 
 
 9 
 
 pressure of the sea water. The very fact that the kidneys in these 
 forms exhibit inertness in the dinunation of urea while they are 
 extremely active in the diminatibn of salts is extremely significant. 
 What th^r do most rigorously is the regulation of tiie inorganic 
 composition of the blood, theiefore the more firmly fixed physio- 
 logical habit must be tiw more ancient one and, consequently, their 
 earliest function was not the elimmation of ^mtste metabolic products 
 but the regulation of the morganic compoation of the blood plasma. 
 The function of excreting waste products developed later and in 
 Selachians never acquired the fixity that diaracterizes the other 
 function. . 
 
 In the long ages the kidney has thus performed a function wtudi 
 for constancy and unvarying regularity is unrivalled in the world 
 of life. This constancy, this unvarying regularity contrasts strik- 
 ingly with the variation in function which the other organs have 
 undergone and indicates how basic the kidney is in the vertebrate 
 system and why it takes precedence in the body as a vertebrate 
 organ par excellence. 
 
 How it happened that the kidney in the protovertebrate acquired 
 this fixity of function we do not know. Geologists concede a 
 very long time to the pre-Cambrian, a duration which, according to 
 different estimates, ranged from one-third to nine-tenths of the whole 
 geological period. In this long cycle of time many things could 
 have happened and conditions must have obtained which impressed 
 on the primitive kidney of tiie protovertebrate an abiding character, 
 not to disappear even though the original organ underwent a 
 marked transformation in structure before it devel<q)ed into the 
 renal organ of the vertebrate of today. 
 
 The question now arises, whether this PaUeo-oceanic character 
 b ever disturbed in disease of the kidney and, if it is, what are the 
 
 results. ... 
 
 To this question there is not much to offer m the form of an 
 answer. There have been very few investigations of the morganic 
 composition of the blood plasma in disease, and these only of a 
 very limited scope, bearing abnost whdly on the chlmine content, 
 t-e amount of which was supposed to give an indication of the total 
 concentration and of tiie sodium present. The conclusions based 
 on such analyses are, of course, accepted only with reserve amply . 
 because of the tenuity of the data on which they are based. Plasma 
 that are accessible are those of Schmidt. 
 
 Believing that the subject had possibilities m a clinical line, I 
 undertook during the last five years investigations on the inorganic 
 compoation of normal human plasma, with a view to comparison 
 of the same with the blood plasma in cases of Bright's disease, and, 
 more especially, in cases Of puerperal eclampaa. These investiga- 
 tions are not yet completed, owing to the time-devouring character 
 
10 ILXAIXUU: THI BLOOD FLA81IA AND THB KIDNKT8 
 
 of the work involved, buc ;KHne of the results so far obtained are 
 c^nite and interesting »ud they may be mentioned here. 
 
 It is to be premised, first of all, that the determinations m 
 Sdmudt's analyses, so far as sodimn, potastdum, cakaum and mag- 
 nesimn are conconed, give too high values. Those for sodium 
 range from 0.3173 to 0.3438 per cent, and for potassiiun from 0.0314 
 to 0.0332, while in my analyses the range of sodium is from 0.29 to 
 0.316 and <rf potassium frwn 0.019 to 0.0212. It may thus be seen 
 that Sdmudt's value»are quite too hi^, and especially in the case 
 of potasfflum, his average fw the ktter b«jng 60 p« coit in excess 
 of mine. The results obtained for the plasma in Biij^t's disease 
 are quite incomi^ete, but those for puerperal edampua are far 
 enough advanced to enable me to give some points of interest. 
 
 In 4 cases the ratios on the bases of Na - 100 were: 
 
 Qmm N». K. C». Mr 
 
 1 ... 100 17. 68 4.02 3.42 
 
 2 *'.... 100 28.70 3.27 2.37 
 
 3 ' ' .... 100 10.(10 
 
 4 ■ ■ ■ .... 100 10.10 2.58 0.68 
 [SCnonniU) ! .... 100 S.U 2.71 0.861 
 
 The magneaum and caldum content b high in Cases 1 and 2 
 and normal in No. 4, but in all the potassium is in excess and m 
 No. 2 extraordinarily so, as much as four tiries the normal, while 
 in No. 1 it is nearly three times the normal. 
 
 There was a minute quantity of hono^obin in the serum of all 
 the four cases, as revealed by the spectroscope, and srane of the 
 potassium found in excess of the normal Jiay have beta denved 
 from hemolyzed red corpusdes which are rich m potasrium salts, 
 but this would not explam the excess in No. 2, in whidi the amount 
 of hemoglobin in the swum did not exceed that in Nos. 3 and 4. It 
 b possible that hemolysb in the circulating blood may be responabl^ 
 ultimately for thb excess, but thb does not explain the non-elinuna- 
 tion of the potassium in excess above normal by the kWnj^. 
 Temporarily, at least, in edampaa the cdlular elements of the kid- 
 ney concerned in maintaimng the normal ratio of potassium in the 
 blood plasma must suffer a partial or total eclipse of function. 
 
 I am inclined to infer from the results of my observations that 
 the very first change from the normal to the definitely established 
 primary condition in some of the forms of Bright's dbease b a loss 
 of the power to mabtam the Pateo-oceanic ratios. 
 
 The structures in the kidney involved in maintaining these ratios 
 are the proximal convoluted tubules, which, with the glomendi, 
 are derived from and therefore represent the oripnal parts of Ae 
 kidney of the eariiest vertebrates and of the protovcr*ebrates. The 
 proximal convoluted tubules are also concerned i^ reducing the 
 H-ion concentration of the blood, for they secrete add, not acid salts, 
 into the urine, a function which is also very andent, a function per^ 
 
macallum: the blood vaaua ajid the kidneys 
 
 11 
 
 f<«ined in mvertebrates by «U the ce'S of the body sitimted near 
 the body surface, and still pcrfonned intennittently and with a 
 hi^ decree of spedalization by the gastric i^ands of vert< ates. T-^ 
 aome invertebrates other tissues have spedaUzed in this oi.itter also, 
 as for example, in the sdivary glands of the carnivorous moUuM 
 DoHum galea, the concentration of the sulphuric add of the " saliva " 
 of wluch exceeds 4 per cent. 
 
 It may be that the function of preventing the ever-tending-to- 
 mcrease of the H-ion concentration of the blood plasma is as andent 
 as the Palieo^)ceanic function, i view which their common localiza- 
 tion in tbe Droximal tubules supports. 
 
 Enough has been said here to emphasize the view that behind 
 the functions of the renal organ is a history which links up tiie 
 human body with the far past^th an age of the earth when ite 
 oceans contained caly what 'wuld now be regarded as brackish 
 water and the earliest type of vertebrate life was just beginning to 
 appear as a marine form. From the facts advanced it will be 
 gathered also that the blood jdasma, so far as its inorganic salts are 
 concerned, is but a reproduction of the remotdy andeut ocean, and 
 that it is an heirloom from the life in 
 
 "that immortal IM 
 Whic*. brousht us thiilMr," 
 
 not indeed in the Words^ orthian sense, but in the literal one, for 
 the sea b the original home of aU life on the ^obe and gave our 
 blood, and, accordiugly, the tissues of our bodies, a character that 
 long ages have not ^aced and will not efface. 
 
 '/ 
 
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