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F U R T H E R S T U D I E S O N T H E C H E M I S T R Y O FB L O O D S E R U M . *

B e A L B E R T A . E P S T E I N , M .D .(Fro m the Laboratory of Physiological C hemistry of the Pathological Depart-ment of Mount Sinai Hospital, New York.)

In a recen t pub l icat ion 1 the au tho r recorded the resu l t s o f achemica l ana lys is o f b lood sera f rom d i f fe ren t d iseased cond i t ions .I t was observed tha t the p ro te ins o f the serum are sub jec t to ex ten-sive variations, and in certain diseases the globulin fraction in theserum is g rea t ly increased . In the serum of cases o f chron ic par -enchymatous nephr i t i s the increase in the g lobu l in con ten t i s mostp ronounced , and the g lobu l in may const i tu te n ear ly a l l o f the p ro te inpresent . On the o ther hand , the p ro te in f rac t ions o f se ra f rom casesof chronic interst i t ial nephrit is present, in their quanti tat ive rela-t ions , li t tle o r no change f rom the normal . In cer ta in cases o f thelatter group, there appears to be a tendency for the globulin in theserum to fa ll be low the no rmal percen tage .

Fo r reasons which wi l l be g iven in a fu tu re pub l ica tion the au tho ris o f the op in ion tha t the changes occur r ing in the p ro te in compo-sit ion of blood serum in different diseases are not accidental , butare the results of well defined inf luences acting upon the blood andi ts se rum. In con t ras t ing the f ind ings in the sera o f pa tien ts wi thchron ic in te r s t i t ia l nephr i t i s and wi th chron ic parenchymatous ne-phr i ti s , the conclus ion i s reached tha t the two d iseases a re gene t ica l lyd i f fe ren t in respec t to the b lood , and tha t the change in the p ro te incomposi t ion o f the b lood seru m p lays a d i rec t par t in the p roduct ionof some of the c l in ica l manifes ta t ions o f the two types o f rena ld isease. The composi t ion o f the u r ine and the b lood serum ( thech lor ides and n i t rogenous waste p roducts) in chron ic in te r s t i t ia lnephr i t i s depends upon the degree o f impairment o f the rena l func-t ion ; whereas in the chron ic parenchymatous nephr i t i s the chemist ry

* T h i s w o r k w a s d o n e u n d e r t e n u r e o f t h e G e o r g e B l u m e n t h a l J r . F e l l o w -ship i n Pa thology . Rece ived for publ i ca t i on , Jan uary 21, 1913.1 Epstein, A. A., Jour. Exper. Med., 1912, xvi, 719.

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A l b e r t A . E p s t e i n . 4 4 5of the urine, the retention of fluid and salt in the body, and in alarge measure the character of the disease in the kidneys, are dueto changes occurring in the blood.

Since his last publication on the subject, the author has had theopportunity of examining a number of other blood sera from casesof genito -urinary disease. The particular object aimed at in thestudy of these cases was to ascertain to what extent localized renalaffections react upon the composition of the blood, especially uponthe protein content of the serum.

The cases studied are divisible into three groups. The first ofthese is comprised of minor surgical cases which may be regardedas normal. The second group consists of cases of hyp ertro phy ofthe prostate gland. Apart from the chronic interstitial nephritisfound in many cases, this group is of interest because of the allegedeffect upon the renal pathology and function of prostatic hyper-trophy and the consequent retention of urine. The third seriescontains cases of localized renal affections, such as hydronephrosis,pyonephrosis, pyelonephritis, and nephrolithiasis. This group is.important because ~he disease concerns the kidneys alone. What-ever changes arise in the composition of the blood can be definitelyascribed to disease of the kidneys.

Of the substances determined in the sera, mention will be madeonly of the total protein, of the incoagulable and non-protein nitro-gen, and of the albumin and globulin contents.

T h e s e v e n s e r a f r o m t h e g r o u p o f n o r m a l c a s es ( t a b l e I ) p r e s e n t v a lu e s f o rt h e d i ff e r e n t s u b s t a n c e s w h i c h a r e i n k e e p i n g w i th s t a n d a r d n o r m a l f i g ur e s. T h et o t a l p r o t e i n i n t h e s e s e r a r a n g e s f r o m 6 .. ! t o 8 .2 g in . p e r IO O c .c . o f s e r u m . T h ea v e r a g e o f t h e s e f ig u r e s a m o u n t s t o 7.3 g i n . T h e a l b u m i n p r e s e n t i n a l l t h e s es e r a i s g r e a t e r i n a m o u n t t h a n t h e g l o b u l i n , w h i c h r a n g e s f r o m 2 .1 t o 3. 2 g m .p e r IO O c .c . o f s e r u m , a v e r a g i n g 2.7 g m . p e r IOO c .c ., o r 3 7 p e r c en t . o f t h e t o t a lp r o te i n . I n t h r e e s e r a t h e g l o b u li n c o n t e n t is s o m e w h a t h i g h e r t h a n t h e a v e r a g ef i g u r e g i v e n ; b u t i n n o n e d o e s i t r i s e a b o v e t h e q u a n t i t y o f a l b u m i n

T h e i n c o a g u l a b l e a n d n o n - p r o t e i n n i t r o g e n i n t h i s g r o u p o f s e r a i s v a r i a b l e ,r a n g i n g f r o m o . o 55 t o o. 17 3 g m . o f n i t r o g e n p e r IO O c .c . o f s e r u m . T h i s c o n -s t i t u e n t, e v e n i n n o r m a l s e r u m , i s m o r e v a r i a b l e t h a n t h e r e l a t i o n o f t h e a l b u m i na n d g l o b u l i n t o t h e t o t a l p r o te i n . I n t w o o f t h e c a s e s ( M . C . a n d H . G . )d u p l i c a t e a n a l y s e s o f t h e s e r a w e r e m a d e a t i n t e r v a l s o f a fe w d a y s . T h er e s u l t s a r e o f i n t e r e s t i n s h o w i n g t h e v a r i a b i l i t y o f t h e in c o a g u l a b l e n i t r o g e na n d t h e c o n s t a n c y o f t i l e p r o t e i n c o n s t i t u e n t s o f t h e s e r u m .

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4 4 6 Studies on the Chemistry of Blood Serum.T A B L E I . z

Normal Cases.Case. Date. Diagnosis.

M. C. Nov. 21 VaricoceleM. C. Nov. 24 VaricoceleS.L . Nov. 7 VaricoeeleH.S. Oct. I FistulaA.S. Oct. 8 Perineal sinusH. G. Oct. 4 HemorrhoidsH. G. Sept. 29 HemorrhoidsJ. A. Oct. 7 OrchitisS.S. Sept. I5 Varicocele

Average . . . . . . . . . . . . . . . . I

[ Incoag-Total ulable Albu-protein, nitro- mitt.gen.7.169 o.o7o 4.5447.175 o.o57 4.7447.319 o.094 4.8oo7.o94 o.o55 4.1698.19o o.o9o 5.1347.675 0.072 4.45o7.619 o.o766.969 O.l O7 4.8446.48I o.173 2.5317.30o 4.4o4

PerGlob- cent.ulin. of glob-ulin.2.625 36.62.431 34.02.519 34.42.925 4I .23.056 37.33.225 42.0

2.125 30.52-95 45.72 . 7 2 37-7

T A B L E I I .Prostatic Cases.

Case.

I .S .H.S .I,Z.E . P .I . S .S.G.A.W.

Date.

Oct. 17Oct. 29Sept. 4Sept. 4

Nov. 19Nov. 25

A.L. Oct. 4A.L. Oct. 29M.R . Oct. 8M. R. Oct. 1i

Diagnosis.

HypertrophyHypertrophyHypertrophyHypertrophy

Total Incoag- Globu- Perulable Albu- cettt.protein, nitrO-gen, r a in . . l i n " ofulin.glob-4.600 2.363; 33.9

Hypertrophy

6.963 0.056 4.600 33.97.294 0.079 4.541 2.753 37.77-550 0.257 2.225 4.325 57.26.938 0.227 3.096 3.842 55-35.887 o.114 2.900 2.917 49.5

R6.894 0.067 3.969 2.925 I 47.74.5IO 3.275 I 41.4

HypertrophyHype rtr ophy 7.787 IHy per tr oph y 7.531 Io.o55 4.194 3.337 44.3Hy pe rt ro ph y 7.469 0.080 3.869 3.600 48.0Hy per tr oph y I 7"225 "154 3.600 3.625 49.0Hyp er tr oph y 6.750 I o.125 3.338 3.412 51.o

Average .. .. . . . . . . . . . . . . ? I ? ? ? 41.62 In tables I, II, and I II the values are given in gra ms per IOO c.c. of se rum.

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A l b e r t A . E p s t e i n . 447B l a d d e r T u m o r .

M. WoM . W .

H . P .

S e p t . 2 2 P a p i l l a r y c a r c i n o m a o fb la dde r 6 .756 3 .181 3 .575O c t . 8 P a p i l l a r y c a r c i n o m a o fb la dde r 6 .719 3 .4o7 3 .3x2O c t . 1 5 C a r c i n o m a o f b l a d d e r a n dpro sta te 7 .938 0 .060 4 .776 3 .x62

I n t h e s e c o n d g r o u p ( t a b l e I I ) e l e v e n s e r a a r e f r o m c a s es o f p r o s t a t i c h y p e r-t r o p h y , o n e i s f r o m a c a s e o f c a r c i n o m a o f t h e b l a d d e r a n d p r o s t a t e , a n do n e f r o m a p a p il l a ry c a r c i n o m a o f t h e b l a d d e r T h e p r o t e i n c o n t e n t o f th i sg r o u p o f s e r a i s a l m o s t n o r m a l i n a m o u n t . T h e f i g u r e s r a n g e f r o m 5 . 88 7 t o7 . 5 5I g i n . p e r I o o c. c. o f s e r u m . T h r e e o f t h e s e r a ( f r o m c a s e s I. S ., H . S . , a n dH . P . , t a b l e I I ) p r e s e n t a l s o n o r m a l r e l a t i o n s o f t h e s e r u m p r o t e i n s . I n t h er e m a i n i n g s e r a t h e g l o b u li n c o n t e n t i s a b o v e t h e n o r m a l a m o u n t , b u t t h e i n -c r e a s e i n t h e p e r c e n t a g e o f t h i s p r o t e i n i s m o d e r a t e .

C l i n i c a l ly a l l t h e c a s e s o f t h i s g r o u p s h o w e d m a r k e d v a s c u l a r a n d p u l m o n a r yc h a n g e s . I n t w o o f t h e c a s e s ( E . P . a n d I . S . ) t h e r e w a s a p r o n o u n c e de m p h y s e m a o f t h e l u n g s , a n d i n a n o t h e r ( I . Z .) a d i f fu s e p u r u l e n t b r o n c h i t i sw a s a l s o p r e s e n t . A t t e n t i o n i s c a ll e d p a r t i c u l a r l y t o t h e s e c l i n ic a l f e a t u r e s ,b e c a u s e , a s p o i n t e d o u t i n t h e p r e v i o u s c o m m u n i c a t i o n , ~ t h e g l o b u l i n c o n t e n t i nt h e s e r u m o f s u c h c a s es i s u s u a l l y a b o v e t h e n o r m a l a m o u n t . I n t h e s e r a o f t h ec a s e s p r e s e n t e d t h e g l o b u l i n c o n t e n t a v e r a g e s 41 .6 p e r c e nt . T h i s m o d e r a t ei n c r e a s e i s n o t t o b e a t t r i b u t e d t o a n y a l t e r a t i o n o f t h e k i d n e y s , b u t r a t h e r t ot h e o t h e r c o n d i t i o n s a c c o m p a n y i n g t h e r e n a l c h a n g e s ; n a m e l y , e m p h y s e m a ,b r o n c h i t i s , e t c .

D u p l i c a t e a n a l y s e s w e r e m a d e o n t h e s e r a f r o m t w o o f t h e a b o v e c a s e s ( A . L .a n d M . R . ) . I n o n e i n s t a n c e ( A . L . ) t h e b l o o d s p e c i m e n s w e r e w i t h d r a w n a t a ni n t e r v a l o f t w e n t y - f i v e d a y s ; i n t h e o t h e r c a s e ( M . R . ) t h r e e d a y s e l a p s e db e t w e e n t h e r e m o v a l o f t h e t w o s p e c i m e n s o f b l o o d . T h e f i n d i n g s s h o w a s l i g h tf l u c t u a t i o n i n t h e p r o t e i n c o n t e n t o f t h e s e r a .

T h e v a r i a t i o n i n t h e a m o u n t o f i n c o a g u l a b le n i t r o g e n o f t h e s e r a o f t h e s ec a s e s is v e r y g r e a t, b u t w h e n c o m p a r e d w i t h t h e u r i n a r y f i n di n g s in t h e c o r -r e s p o n d i n g c a s e s , i t a p p e a r s t h a t t h e a m o u n t o f i n e o a g u l a b l e n i t r o g e n v a r i e sw i t h t h e d e g r e e o f i m p a i r m e n t o f t h e r e n a l f u n c t i o n ?

T h e t w o c a s e s o f n e o p l a s m o f t h e b l a d d e r ( M . W . a n d H . P . ) p r e s e n t n on o t e w o r t h y f e a tu r e s . T h e s e r u m o f o n e o f t h e s e ( M . W . ) w a s e x a m i n e d o nt w o o c c a s i o n s s e p a r a t e d b y a n i n t e r v a l o f f o u r t e e n d a y s ; t h e r e s u l t s o f t h es e c o n d e x a m i n a t i o n d o n o t d i f f e r f r o m t h o s e o f t h e f i r s t .

O f t h e g r o u p o f s i x c a s e s o f l o c a l i z e d r e n a l a f f e c t i o n s ( t a b l e I I I ) ,t w e l v e s e r u m e x a m i n a t i o n s w e r e m a d e . T h e f i n d in g s i ll u s tr a t e t h e

s E p s t e i n , A . A . , l o c . c i t .* T h e d e d u c t i o n s d r a w n c o n c e r n i n g t h e r e n al a c t i v it y a r e b a s e d u p o n f u n c -

t i o n a l t e s t s , th e r e s u l t s o f w h i c h w i l l a p p e a r i n a p u b l i c a t i o n b y D r . L e oB u e r g e r , D r . L a n t m a n , a n d t h e a u t h o r .

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448 Studies on the Chemistry of Blood Serum.p o i n t i n q u e s t i o n ; n a m e l y , t h a . t d i s e a s e o f t h e k i d n e y s p r o p e r d o e sn o t a f f e c t t h e c o m p o s i t i o n o f t h e s e r u m p r o t e i n s .

TABLE I I I .Loca l i z ed Rena l Af f ec t ions .

Case. Date. Diagnosis.

L . G . S e p t . l O C o i n c i d e n th y d r o p y o n e p h r o s i s ; h o r s e -s h o e k i d n e yG . T . S e p t . 3 0 H y p e r t r o p h y o f p r o s t a t eG . T . O c t . 2 R e n a l c a lc u l iG . T . O c t . 1 4 P y o n e p h r o s i sG . T . N o v . 2 1 P e r i n e p h r i t ic a b s c e s sM . G . O c t . 7 D o u b l e k i d n e yM . G . O c t . I I H y d r o n e p h r o s i sT . B . A u g . 3 1 P y e l o n e p h r i t i sB . H . A u g . 2 4 P y e l o n e p h r i t i sB . H . A u g . 3 o P y e l o n e p h r i t i sC D .C . D . D e c . s oJ a n . I I U n i l a t e r a l t u b e r c u l o s i s o ft h e k i d n e y

Tota lprotein.

6 . 8 7 5

8 . 5 0 67 . 6 0 66 . 5 1 36 . 8 1 27 . 3 4 47 . 3 1 28 . 2 5 08 . I 2 58 . I 4 4

7 . 1 o 6

i I n c o a g -u I a b l en i t r o -g e ~ .o . I 6 5

O.lO90 . 0 9 30 . 0 6 3o . o 6 o0 . 2 6 5O . O I l

0 . 1 1 2

o . 1 4 90 . 3 3 50 . 0 6 5o . 1 2 3

P e rAlbu- I Gl ob - cent.min. I ulin. ofglob-I ulin.i _ _

3 . 1 6 3 3 . 7 1 2 5 3 . 8

4 . 8 8 I 3 . 6 2 5 I 4 2 . 64 . 1 5 6 3 . 4 5 0 4 5 . 23 . 3 2 6 3 . 1 8 7 4 8 . 62 . 9 6 2 3 . 8 5 0 5 6 . 54 . 2 0 7 L3 . 1 3 7 4 2 . 64 . 3 5 6 I 2 . 9 5 6 4 0 . 44 .991 t 3"269 39 .63 . 0 3 8 5 . 0 8 7 6 2 . 63 . 4 5 8 5 . 6 8 6 6 9 . 8

I3 . 9 6 0 3 . 2 0 o 4 5 . 0

T h e c a s e s r e f e r r e d to r e p r e s e n t i n t h e m a i n p y o g e n i c i n f l a m m a -t i o n s o f t h e k i d n e y s . T o a p p r e c i a t e t h e n e t e f f e c t o f s u c h a p r o c e s su p o n t h e b l o o d s e r u m i t is n e c e s s a r y t o c o n s id e r , o n t h e o n e h a n d ,t h e e f f e c t o f t h e i n f e c t i o n u p o n t h e b l o o d s e r u m , a n d o n t h e o t h e r ,t h a t o f t h e d e s t r u c t i o n o f k i d n e y t i s s u e a n d t h e i m p a i r m e n t o f t h er e n a l f u n c t i o n .

P a t h o l o g i c a l l y c o n s i d e r e d t h e i n f e c t i o u s p r o c e s s i n t h e k i d n e y s i ss i m i la r t o t h a t w h i c h m a y o c c u r i n a n y o t h e r p a r t o f t h e b o d y . I t se f f e c t u p o n t h e c h e m i c a l c o m p o s i t i o n o f t h e b l o o d s e r u m m u s t b e i na l l r e s p e c t s l i k e t h a t o f a c i r c u m s c r i b e d i n f e c t i o n o r a b s c e s s f o r m a -t i o n in a n y o t h e r p a r t o f t h e b o d y . A s i s w e l l k n o w n , i n a ll c a s e so f p y o g e n l c i n f e c t i o n , b u t t o a l e s s e x t e n t i n t u b e r c u l o s i s , t h e g l o b u -l in s i n t h e b l o o d s e r u m a r e i n c r e a s e d . 5 T h u s w e f i n d in t h e s e c a s e st h a t t h e g l o b u l i n c o n t e n t i n t h e s e r u m i s i n c r e a s ed . T h e i n c r e a s e int h e p e r c e n t a g e r e l a t i o n s o f t h e g l o b u l i n t o t h e a l b u m i n a n d t h e t o t a l

5 E r b e n , F . , Ztschr . f . k l in . Med., 19o3, I , 450 .

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Albe r t A . Eps te in . 4 4 9p r o t e i n a p p e a r s t o b e p r o p o r t i o n a t e t o t he d u r a t i o n a n d t h e e x t e n to f t h e in f e c t i o u s p r o c e ss . T h i s i n f e r e n c e , it s e e m s , m a y b e d r a w nf r o m t h e r e s u l t s o f th e r e p e a t e d e x a m i n a t i o n s o f ~t he s e r a o f t w oc a s e s (B . H . a n d G . T . ) .

In the firs t case (B. H.) the blood serum was examined twice at an intervalof s ix days. Th e clinical feature s in this case pointed to a rapidly progre ssingpyelonephritis . Th e chemical findings show that although the total proteinin the serum rema ins constant, th e globulin conten t rises f rom 6~.6 per cent. to69 .8 pe r cent . The e ffec t o f the func t iona l impa irment a r is ing fro m the de -struction of renal tissue is manifested in the marked rise of incoagulable andnon-pro te in n i t rogen (f ro m o . I49 to 0 .335 g in. pe r Ioo c .c . o f se rum ).In the second case (G. T . ) the obse rva t ions ex tended over a pe r iod o f twomonths , and in a ll , four examina t ions o f the b lood se rum were made . Theclinical data in this case show that the disease progressed in two phases , oneof which s tands in relation to the protein composition of the serum, the otherto the non-pro te in cons ti tuen ts o f the se rum. Th is pa t ien t had hypert rophy ofthe prostate , unilateral urethral and renal lithiasis , and pyonephrosis with asecondary perinephritic abscess , and in the course of the illness an extensiveeffusion on the chest developed. Disease in the second kidney was not demon-strable.

O n t h e b a s i s o f w h a t h a s b e e n s t a t e d b e f o r e , t h e r e s u l t s i n t h i sc a s e sh o w t h a t t h e p r o t e i n c o m p o s i t i o n o f t h e s e r u m i s a f f e c t e d b yt h e p y o g e n i e p r o c e ss , b u t i s i n d e p e n d e n t o f t h e e l i m i n a t o r y f u n c -t i o n o f th e k i d n e y ; w h e r e a s t h e n o n - p r o t e i n c o n t e n t i s r e l a t e d tot h e a c t i v i t y o f t h a t o r g a n .

I t i s s e e n f r o m t h e f i g u r e s i n t a b l e I I I t h a t t h e t o t a l p r o t e i n i n t h es e r u m f a l ls p r o g r e s s i v e l y ( 8 . 5 0 6 , 7. 6 06 , 6 . 5 1 3 , a n d 6 . 8 1 2 g r a m sp e r i o o c .c . o f s e r u m ) , a n d t h e a m o u n t o f g lo b u l in r e m a i n s c o n -s t a n t ; t h u s t h e p e r c e n t a g e r e l a t i o n o f t h e g l o b u li n s t o t h e to t a l p r o -t e i n i s p r o g r e s s i v e l y i n c r e a s e d .

T h i s r e s u l t m a y b e d u e t o o n e o r m o r e o f s e v e r a l c a u s e s : i . Ag r a d u a l i n c r e a s e i n t h e g l o b u l i n c o n t e n t w i t h a p r o g r e s s i v e d i l u t i o no f t h e b l o o d ( h y d r e m i a ) . T h e p r o g r e s s i v e l o ss o f w e i g h t o n t h ep a r t o f th e p a t i e n t a r g u e s a g a i n s t s u c h a n o c c u r r e n c e . 2 . A g r e a t e rl o ss o f a l b u m i n t h a n g l o b u l i n i n t h e p u r u l e n t e x u d a t e d i s c h a r g e d b yt h e k i d n e y s . T h e a n a l y s e s o f t h e u r i n e s m a d e a t d i f f e r e n t ti m e ss h o w , h o w e v e r , t h a t a g r e a t e r l o s s o f a l b u m i n i n t h e p u s c o u l d n o ta c c o u n t f o r th e m a r k e d d e c r e a s e i n th e t o t a l p r o t e i n o f t h e s e r u ma n d t h e g r e a t r i s e i n t h e p e r c e n t a g e o f g l o b u l i n. 3 - A g r e a t e r l o s so f a l b u m i n i n t h e s e ro u s e f f u s i o n w h i c h o c c u r r e d i n t h e c h es t m a y

Published April 1, 1913

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4 5 0 S t u d i e s o n t h e C h e m i s t r y o f B l o o d S e r u m .h a v e c o n t r i b u t e d t o t h e n e t r e s u l t o b t a i n e d . T h e t o t a l v o l u m e o ff l u id r e m o v e d o n a s p i r a t i o n o f t h e c h e s t a m o u n t e d t o 2 5 0 c. c. T h i sf l u i d , u n f o r t u n a t e l y , w a s n o t s u b m i t t e d t o c h e m i c a l e x a m i n a t i o n .4 . A g r e a t e r d e s t r u c t i o n o f s e r u m a l b u m i n i n t h e c o u r s e o f th ep r o t e i n m e t a b o l i s m i n t h e b o d y . T h i s i s a p o s s i b l e c a u s e o f t h ec h a n g e o b s e r v e d i n t h e c o m p o s i t i o n o f t h e s e r u m , f o r t h e p a t i e n tw a s k e p t f o r a l o n g t i m e o n a d i e t r i c h i n f a t s a n d c a r b o h y d r a t e sb u t p o o r i n p r o t e i n s .

T a b l e I I I s h o w s t h a t i n t h i s c a s e t h e b e h a v i o r o f t h e n o n - p r o t e i nn i t r o g e n o u s s u b s t a n c e s i s t h e i n v e r s e o f t h a t o b s e r v e d i n t h e p r e -c e d i n g c a se . T h e v a l u e s d r o p g r a d u a l l y f r o m o . I o 9 t o 0 .0 6 0 o f ag r a m o f n i t ro g e n p e r I OO c u b i c c e n t i m e t e r s o f s e ru m . T h i s d e c r e a s eb e c o m e s i n t el l ig i b l e u p o n c o n s i d e r a t i o n o f t h e c l in i c al d a ta . A ss t a t e d a b o v e , t h e i n f e c t i o u s p r o c e s s w h i c h o r i g i n a t e d i n t h e k i d n e ye x t e n d e d t o t h e s u r r o u n d i n g t is s u es , s o t h a t p u s f o r m a t i o n c o n t i n u e du p to an d b e y o n d th e t im e o f th e l as t s e r u m e x a m i n a t io n . T h ee f f e c t o f a p y o g e n i c p r o c e s s u p o n t h e p r o t e i n c o m p o s i t i o n o f s e r u mh a s a l r e a d y b e e n d i s c u s s e d . O n th e o t h e r h a n d , th e r e n a l f u n c t i o ni m p r o v e d i n c o n s e q u e n c e o f s u r g i c a l i n t e r f e r e n c e a t t h e s e a t o fd i se a se . T h a t a n i m p r o v e m e n t in t h e r e n a l f u n c ti o n o c c u r r e d w a se s t a b l i s h e d b y a s t u d y o f t h e u r i n e m a d e a t t h e s a m e t i m e t h a t t h ed i f f e r e n t s p e c i m e n s o f b l o o d w e r e e x a m i n e d . T h e f a c t t h a t t h ep a t i e n t w a s k e p t p e r s i s t e n t l y o n a lo w p r o t e i n a n d h i g h f a t a n d c a r -b o h y d r a t e d i e t m a y a l s o h a v e h e l p e d t o re d u c e t h e n o n - p r o t e i n n i t r o -g e n o u s b o d i e s i n t h e s e r u m .A t h i r d c a s e o f t h e s a m e s e r i es ( M . G . ) s h o w s e v e n m o r e s t r i k -i n g l y th e r e l a ti o n o f th e r e n a l f u n c t i o n t o t h e n o n - p r o t e i n c o m p o -s i t i o n o f t h e s e r u m , a n d t h e t o t a l l a c k o f s u c h r e l a t i o n s h i p t o t h ep r o t e i n c o n st it u e n ts . T h e t w o e x a m i n a t i o n s o f t h e b l o o d s e r u mw e r e m a d e f o u r d a y s a p a r t ; t h e f i r s t p r i o r t o , a n d t h e s e c o n d a f t e ra n o p e r a t i o n u p o n t h e k i d n e y . T h e r e s u l t s s h o w ~th at t h e p r o t e i nc o n t e n t t o g e t h e r w i t h t h e r e l a t i v e a m o u n t s o f a l b u m i n a n d g l o b u l i na r e w i t h i n th e n o r m a l ra n g e a n d r e m a i n c o n s t a n t . T h e n o n - p r o t e i nn i t r o g e n d r o p s f r o m 0 . 2 6 5 t o o . I I O o f a g r a m p e r I O O c .e . o f s e r u m .T h i s r e s u l t i s i n a c c o r d w i t h t h e c l i n i c a l d e v e l o p m e n t s o f t h e c a s e .

W e h a v e t h u s a n i n d ic a t io n o f t h e t w o f o l d c h a r a c t e r o f t h e c h em i -c a l c h a n g e s i n t h e s e r u m , r e s u l t i n g f r o m l o c a l iz e d d i s e a s e o f t h e

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A l b er t A . E p s t e i n . 451k i d n e y s. T h e c h a n g e s b r o u g h t a b o u t b y t h e i n f e c t io u s p r o c es sa f f ec t t h e p r o t e in c o m p o s i t i o n o f t h e s e r u m , w h e r e a s t h a t w h i c hi n t e r f e r e s w i t h t h e r e n a l f u n c t i o n a f f e c t s t h e n i t r o g e n o u s w a s t ep r o d u c t s .

A n o t h e r i n s ta n c e o f t h e e f fe c t o f t h e i n t e r f e r e n c e w k h t h e r e n a lf u n c t i o n u p o n t h e n o n - p r o t e i n c o m p o s i t i o n o f t h e b l o o d s e r u m i sf o u n d i n t h e a n a l y s i s o f t h e s e r u m o f a c a s e o f u n i l a t e r a l r e n a lt u b e r c u l o s is ( C . D . ) . I n th e f ir s t e x a m i n a t i o n w h i c h w a s m a d ep r i o r t o t h e o p e r a t i o n u p o n t h e d i s e a s e d k i d n e y t h e a m o u n t o f n o n -p r o t e i n n i t r o g e n i n t h e s e r u m w a s 0 . 0 6 5 o f a g r a m p e r I O O c .c .A f t e r t h e r e m o v a l o f t h e d i s e a s e d k i d n e y t h i s c o n s t i t u e n t t~ f t h es e r u m r o s e t o o . 1 2 3 g r a m p e r IO O c .c . D e t e r m i n a t i o n s o f t h e u r i -n a r y n i t r o g e n m a d e a t th e s a m e t i m e s h o w e d t h a t t h e e li m i n a ti o no f t h e s e s u b s t a n c e s a f t e r t h e o p e r a t io n w a s c o n s i d e r a b l y l es s t h a nt h a t a t t h e t i m e o f t h e f i r s t e x a m i n a t i o n o f t h e b l o o d s e r u m .

T h e o t h e r c a s e s i n t h i s g r o u p s h o w s i m i l a r re s u l t s . T h e n i t r o g e n -o u s w a s t e p r o d u c t s v a r y c o n s i d e r a b l y in th e d if f e r e n t s e r a. T h ep e r c e n t a g e o f g l o b u l i n i s e l e v a t e d i n m o s t o f t h e m , b u t t h i s i s a t t r i b u -t a b l e t o t h e i n f e c t i o u s p r o c e s s a n d n o t t o a n y o t h e r c a u s e w i t h w h i c ht h e k i d n e y s a r e f u n c t i o n a l l y c o n c e r n e d . I f w e c o n t r a s t t h e r e s u l t so b t a i n e d i n t h e s e c a s e s w i t h t h o s e f o u n d i n t h e s e r a o f c a s e s o fc h r o n ic p a r e n c h y m a t o u s n e p h ri ti s , r e p o r t e d i n t h e c o m m u n i c a t i o na l r e a d y r e f e r r e d t o , w e f i n d t h a t i n t h e c a s e o f l o c a l i z e d r e n a l a f f e c -t i o n s th e c o m p o s i t i o n o f t h e s e r u m i s e n t i r e l y d i f f e r e n t . T h e g l o b u -l i n c o n t e n t i n n o n e o f t h e l a t t e r c a s e s r e a c h e s s o h i g h a l e v e l a s t h a to b s e r v e d i n t h e s e r a o f p a r e n c h y m a t o u s n e p h r i , t i s .

SUMMARY.T h e f o l l o w i n g c o n c l u s io n s m a y b e d r a w n f r o m t h e r e s u lt s o b t a i n e d

in t h i s s t udy .I . I n t h e m i n o r s u r g i c a l c a s es ( c o n s i d e r e d n o r m a l ) t h e ch e m i c a l

c o m p o s i t i o n o f t h e b l o o d s e r u m a g r e e s , a s f a r a s i t s p r o t e i n s a r ec o n c e r n e d , w i t h ,t he u s u a l s t a n d a r d v a l u e s . W h e n e x a m i n e d a t d i f -f e r e n t t i m e s, t h e s e r u m o f s u c h c a s e s s h o w s n o v a r i a t io n i n th e t o t a lp r o t e i n c o n t e n t o r i n i t s i n d i v i d u a l f r a c t i o n s . T h e i n c o a g u l a b l en i t r o g e n , h o w e v e r , v a r i e s c o n s i d e r a b l y i n t h e t o t a l a m o u n t i n t h ed i f f e r e n t c a s e s , a s w e l l a s i n i t s p e r c e n t a g e r e l a t i o n s t o t h e o t h e rc o n s t i t u e n t s o f t h e s e r u m .

Published April 1, 1913

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4:52 S t u d i e s o n t h e C h e m i s t r y o f B l o o d S e r u m .2. The cases of prostatic hypertrophy, with or without chronic

interstitial nephritis, show no change from the normal in the char-acter of the protein composition of the serum, nor in the ratio whichthe individual fractions bear to each other. On the other hand, theincoagulable and non-protein nitrogen of the serum show markedfluctuations, some of which correspond to the degree of functionaldeficiency of the kidneys.

3. In cases of localized infections of the kidneys, ,the changes inthe blood serum are twofold. One concerns the proteins, and istraceable to the infection; and the other concerns the non-proteinnitrogen, results from functional impairment, and varies with theamount of destruction of the kidney substance. Thus an increase inthe globulins is observed in these sera similar to that occurring ininfect ions in other localities ; the non-protein content increases appar-ently in direct proportion to the degree of deficiency of the kidney,and becomes diminished when the function of :the kidneys improves.

The author wishes to acknowledge his indebtedness to Dr. LeoBuerger for the privilege of studying the cases, and to Dr. Lautman,of the House Staff of Mount Sinai Hospital, for assistance in pro-curing the samples of blood.

Published April 1, 1913