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Biochemical Studies in the Toxaemias of Pregnancy

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BIOCHEMICAL STUDIES
21
THE TOXAEMIAS OF PREGNANCY.
By
M.D.
CRAWFORD,
M, B*, Oh. B.
Thesis submitted for the degree of M.D.
U niversity of Glasgow.
January, 1941*
ProQuest Number: 13849772
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(i)
TABLE OF CONTENTS
Page.
1.
PREFACE.................................................................................................
SECTION I:
INTRODUCTION. ..............................................
SECTION II:
THE EFFECT OF LABOUR OK PLASMA URIC ACID
AND UREA.
Introduction.
.......................................................................
7.
8.
Findings before Onset of Labour
Changes during Labour and the Puerperium....................
10.
D iscussion................................................................................
l^j.
Summary.................................................
SECTION III:
21.
CHANGES IN PLASMA URIC ACID AND UREA
IN ECLAMPSIA.
Introduction..........................................................................
2 2.
Uric Acid F in d in gs.....................................................
2 J>•
Findings before Onset of F it s ...............................
2. f.
The E ffect
of F i t s . . .............................................. 2 9.
The E ffect
of Labour...............................
Urea Findings.
32.
......................................................... 34-.
Findings before Onset of F it s .............. ................ 3 4 ,
The E ffect
of F it s .................
35.
The E ffect
of Labour.............................................
J6.
The E ffect o f Convulsions on Plasma Uric Acid
and Urea in Non-PregnantP atien ts and in Animals. 3 7.
D iscussion................................ ............................................ 4 0 .
Summary.................................................................................... 4 4*
(U)
P age.
SECTION IV;
CHANGES IN BLOOD CONCENTRATION IN
NORMAL AND TQXAEMIC PREGNANCY.
Introduction..........................................................................
45 .
Present Technique................................................................ 5 0 .
Ant e-par turn Findings............................................... ..
51.
Changes during Labour and the Puerperium,............. 5 £ •
Factors Influencing ?ost-Partum D ilution. , .......... 5 4 .
Changes in Normal and Toxaemic Cases....................... 5 7*
D iscussion....................... ....................................................... 6 1 .
Summary........................... ....................................................... 6 J .
SECTION V:
A,
VOMITING IN PREGNANCY.
Vomiting of Early Pregnancy or Hyperemesis
Gravidarum.
Introduction....................... ....................................... 6 6 .
Present R esu lts
67-
Wernicke fs Encephalopathy..................................... j q %
Summary......................... ............................................... 73B.
Vomiting of Late Pregnancy.
Introduction
........ ......................................... 7 4 .
Prolonged Hyperemesis............... ............................. 7 4 P y e l i t i s ..................................................................... . ^6 •
“E rythroblastosis Foetal is " ................................. 7 9 .
M iscellaneous Group................................................. £ JL.
Summary..................... ................................................... 8 3 .
(i i i )
P age.
SECTION VI:
JAUNDICE IN PREGNANCY.
I n t r o d u c t i o n ...........................
85-
A.
O b s t e t r i c A cute Y e llo w A troph y.....................
$ 7.
B.
True A cute Y e llo w A trophy.................................
95.
C.
D e la y e d Chloroform P o i s o n i n g ..........................
101.
D i s c u s s i o n .........................................................................................
106.
Summary................................................................................................
10?.
SECTION V II;
CHANGES IN BLOOD BIOCHEMISTRY ABOUT THE
TIME OF DELIVERY WITH SPECIAL REFERENCE TO OBSTETRIC
SHOOK.
I n t r o d u c t i o n ...........................
110.
P r e s e n t I n v e s t i g a t i o n ......................
114.
D isc u ssio n
..........................1 2 4 - .
Summary................................................................................................1 2 8 .
SECTION V I I I : GENERAL SI3MMARY...........................
.1 2 9 .
BIBLIOGRAPHY.................................................................. ............................1 3 7 .
APPENDIX. .......................................................................................................1 4 7
C ase N o te s and B io c h e m ic a l F in d in g s o f a l l
C ases.
1.
PREFAOE
The i n v e s t i g a t i o n s on which t h i s t h e s i s i s
b ased were c a r r i e d ou t i n th e R esea rch Department and
Wards o f t h e R oyal M a te r n ity and Womens H o s p i t a l ,
G lasgow, d u r in g t h e t e n u r e o f t h e F a u ld s F e l lo w s h ip ,
Glasgow U n i v e r s i t y .
Two p a p e r s , e n t i t l e d 11The E f f e c t o f Labour
on t h e Plasm a U r ic A c id and U rea11 and ‘‘Changes i n B lood
C o n c e n t r a t io n i n Normal and Toxaemic P re g n a n cy 11, have been
p u b l i s h e d i n t h e J o u r n a l o f O b s t e t r i c s and G ynaecology o f
t h e B r i t i s h S n p i r e , 1939?
r e sp e c tiv e ly ,
540 and 1 9 4 0 ,
^3?
from d a ta r e c o r d e d i n t h i s work; a t h i r d
paper, e n t i t l e d "Changes i n Plasm a U r ic A cid and Urea i n
Eclam psia", i s a t p r e s e n t i n p r e s s .
I h av e much p l e a s u r e i n a c k n o w le d g in g my
i n d e b t e d n e s s to Dr. H.L. Sheehan f o r h i s c o n s t a n t
encouragem ent and h e l p f u l c r i t i c i s m
c o u r s e o f th e work.
th rou gh o u t th e
Thanks a r e a l s o due to P r o f e s s o r
S. Cameron, P r o f e s s o r J . Hendry, Dr. J . H e w itt and
Dr. R.A. L en n ie f o r p e r m i s s i o n to i n v e s t i g a t e c a s e s i n
t h e i r wards i n t h e Royal M a te r n it y and Women*s H o s p i t a l ,
Glasgow, and t o Dr. A. MacNiven f o r p e r m i s s i o n t o s tu d y
c a s e s i n h i s wards a t G a r tn a v e l M ental H o s p i t a l .
2.
S E C T I O N
I
I N T R O D U C T I O N .
About t e n p e r c e n t o f a l l p r e g n a n t women a r e
found t o s u f f e r from one o r o t h e r o f a group o f d i s o r d e r s
p e c u l i a r t o p r e g n a n c y which a r e r e f e r r e d to a s th e
‘■toxaem ias o f p r e g n a n c y 11.
Under t h i s term ‘‘to x a e m ia s o f
p r e g n a n c y 11 t h e r e a r e i n c l u d e d - v o m itin g o f p regn an cy,
a c u t e y e l l o w a t r o p h y o f th e l i v e r , p r e - e c l a m p s i a , e c la m p s ia ,
lo w r e s e r v e k id n e y , e t c .
The term h y p e r t e n s i v e tox aem ia
d e n o t e s t h o s e c o n d i t i o n s a s s o c i a t e d w ith h ig h b lo o d p r e s s u r e ,
a lb u m in u r ia and oedema, e i t h e r t o g e t h e r or s i n g l y .
be s p e c i f i c a l l y n o t e d t h a t ,
I t i s to
th rou gh ou t th e p r e s e n t work,
th e word " to x a e m ia 11 i s u s e d a s a c l i n i c a l d e s c r i p t i o n
w it h o u t any i m p l i c a t i o n t h a t h y p o t h e t i c a l t o x i n s are
c i r c u l a t i n g i n th e b lo o d .
The h y p e r t e n s i v e to x a e m ia s o f p r e g n a n c y have
been th e s u b j e c t o f e n d l e s s r e s e a r c h and c o n t r o v e r s y f o r
many y e a r s ;
i n many t e x t b o o k s o f o b s t e t r i c s a whole c h a p te r
i s g i v e n to th e d i s c u s s i o n o f t h e v a r io u s t h e o r i e s o f th e
e t i o l o g y o f e c la m p s ia and p r e - e c l a m p s i a .
In 1843 L ever d i s c o v e r e d albumen i n th e u r in e o f
e c la m p t ic women and f o r some y e a r s a f t e r t h i s
was th o u g h t to be a l l i e d t o uraem ia.
th e d i s e a s e
This t h e o r y soon f e l l
i n t o d i s f a v o u r but was su p p o r te d by V olhard ( 1 9 2 4 ) who
reg a r d e d e c la m p s ia a s a form o f a c u t e uraem ia and p rop osed
t h e term “e c l a m p t i c u ra em ia 11.
He c o n s i d e r e d t h a t g e n e r a l
v a s o c o n s t r i c t i o n w it h r e s u l t i n g c a p i l l a r y c h a n g e s was a
prim ary f a c t o r .
Many w orkers a g r e e c o n c e r n in g th e im portance
o f c a p i l l a r y damage; H inselm ann ( 1 9 2 4 ) and Heynemann ( 1 9 2 4 )
have been a b l e t o d e m o n stra te marked c h a n g e s i n th e c a p i l l a r i e s
i n c a s e s o f h y p e r t e n s i v e to x a e m ia and e c la m p s ia ; t h e y found
w id e n in g and l e n g t h e n i n g o f th e s k i n c a p i l l a r i e s w ith
r e s u l t i n g s t a s i s o f b lo o d f l o w - t h e s e ch a n g e s t h e y c o n s id e r e d
were s e c o n d a r y to spasm o f t h e a r t e r i o l e s .
In 1919
Z an geraeister advan ced h i s “Hydrops Gravidarum"
th e o r y which
p o s t u l a t e s i n c r e a s e d c a p i l l a r y p e r m e a b i l i t y a s th e fundam ental
l e s i o n o f e c la m p s ia .
He c o n s i d e r s t h a t oedema, r a i s e d b lo od
p r e s s u r e , a lb u m en u ria and o t h e r s i g n s a r e a l l se co n d a r y to
i n c r e a s e d t r a n s u d a t i o n o f f l u i d t o t h e t i s s u e s and t h a t c e r e b r a l
oedema i s th e c a u s e o f th e c o n v u l s i o n s , h e a d a c h e s and r e t i n a l
changes.
i s w ater”.
He c o n c lu d e s t h a t “th e lo n g so u g h t e c la m p tic t o x i n
F o e t a l e le m e n t s ( V e i t , 1 9 0 5 ) ,
f o e t a l m e t a b o lic
p r o d u c t s ( D i e n s t , 1902 and 1927)> p l a c e n t a l (Liepmann, 1 9 0 6 ;
Young, 1927) C r u ic k sh a n k s, H e w itt and Couper, 1 9 2 7 ) and
i n t e s t i n a l (S o lo m o n s, 1922 and 1 9 3 3 ) t o x i n s h a ve been
s u g g e s t e d a s c a u s a l a g e n t s o f e c la m p s ia w h ile some workers
advance t h e o r i e s r e l a t i n g to e n d o c r in e im b alan ce (H ofbauer,
1918 and 1933) Hoffman and A n selm in o , 19 31 ) C ushing, 1934;
Smith and Smith 1 9 3 3 and 1 9 34) and a n a p h y la x is (R osenau and
Anderson, 1 9 0 8 ).
Almost a l l th e t h e o r i e s h ave one p o i n t i n common
and t h a t i s ,
th ese ca ses.
t h e r e c o g n i t i o n o f a g e n e r a l m e t a b o l ic u p s e t i n
T h is m e t a b o l ic u p s e t i s e v id e n c e d by ch a n g es i n
t h e b io c h e m ic a l f i n d i n g s o f th e v a r io u s body f l u i d s .
I n v e s t i g a t i o n s o f t h e s e ch an ges h a v e thrown some l i g h t on th e
n a tu r e o f th e d i s e a s e ,
but t h e r e h a s been much d iv e r g e n c e o f
o p i n i o n ev en i n r e g a r d t o some o f the f i n d i n g s .
In p a r t i c u l a r ,
r e p o r t e d r e s u l t s from h y p e r t e n s i v e to x a em ic p a t i e n t s d i s a g r e e
w ith r e g a r d t o th e q u e s t i o n o f r e t e n t i o n o f n o n - p r o t e i n
n itro g en fr a c tio n s .
many w o r k e rs,
Low b lo o d u r e a v a l u e s have been found by
( Z a n g e m e is te r , 1903; W illia m s , 1921; H elim uth,
1923; Heynemann, 1924; P l a s s , 1924; S ta n d e r , 1 9 24; S ta n d er,
Duncan and S i s s o n , 1 92 5; C r u ic k sh a n k s, H ew itt and Gouper, 1927;
Dieckmann, 1933;
S ta n d e r and Oadden, 1 9 3 4 b ); w h ile th e r e s u l t s
o f o t h e r s show a c o n s i d e r a b l e r e t e n t i o n i n th e b lo od o f a l l
n o n - p r o t e i n n i t r o g e n f r a c t i o n s ( C a ld w e ll and Lye, 1921;
K i l l i a n and Sherw in, 1 9 21; W althard, 1922; F rey, 1923;
Bokelmann and Rother, 1925 ).
One of the reasons for these
d ifferen ces i s th at, in most cases, determinations were made
on groups of d ifferen t p a tien ts, eith er at d ifferen t stages
in pregnancy or with varying degrees of toxaemia, and the
average r e su lts compared.
When the re su lts are examined in
d e ta il, i t appears that those workers whose average figures l i e
within normal lim its had several p atien ts with values much above
normal and, conversely, in the r e su lts of those workers in
favour of a non-protein nitrogen reten tion , there are p atien ts
with low non-protein nitrogen and urea values.
i n v e s t i g a t o r s h ave a tte m p te d t o f o l l o w ,
Very few
i n any d e t a i l ,
ch a n g es o c c u r r in g i n th e n o n - p r o t e i n n i t r o g e n
th e
5.
fr a c tio n s o f the blood in in d iv id u a l p a tie n ts and thus the
f a c to r s in flu e n c in g the blood n on -p rotein n itro g en fr a c tio n s
in th e se h y p e rten siv e toxaem ic c a ses have not been recogn ised.
Renal fu n c tio n t e s t s in h y p erten siv e toxaemic ca ses
before and soon a f t e r d e liv e r y have been found to be very
u n s a tis fa c to r y both from a d ia g n o s tic and from a p ro g n o stic
p o in t o f view .
Stander, Ashton and Cadden ( 1 9 3 2 ) found the
urea clea ra n ce and c r e a tin in e e x c r e tio n t e s t s o f some value
in d if f e r e n t ia t in g m ild n e p h r itis from low reserv e kidney
c a s e s , but g iv e no r e s u lt s fo r p re-ecla m p tic ca ses.
Dieckmann ( 1 9 3 5 ) > on the o th er hand, in a d e ta ile d in v e s tig a tio n
o f ren al fu n ctio n in c o n v u lsiv e and n o n -co n v u lsiv e, acu te and
chronic h y p e rten siv e toxaem ic p a t ie n t s , found that the urea
clea ra n ce t e s t was o f l i t t l e value during pregnancy or soon
a f t e r d e liv e r y because o f the wide range found in the normal
pregnant c a s e s .
Cadden and McLane (1 9 3 4 ) found that on ly the
urea clea ra n ce t e s t was s e n s it iv e enough to d if f e r e n t ia t e
tru e ch ron ic n e p h r itis from the o th er toxaem ias; the average
r e s u lt s from p re-ecla m p tic and eclam ptic c a se s were lower
than the average r e s u lt s from normal c a s e s , but the range in
each group was so wide th a t th e t e s t was o f no d ia g n o s tic
v alu e.
E lder, S in c la ir and Rogers (193&) in a sim ila r
in v e s t ig a t io n a ls o s tr e s s e d the wide range o f the normal
v alu es fo r ren a l fu n c tio n t e s t s in pregnancy and in d ica ted
th a t t h i s was p a r t ly due to wide v a r ia tio n s in blood urea
valu es in d iff e r e n t c a s e s , the v a lu es in some normal ca ses
being very low.
I t i s , th e r e fo r e , o f great importance th a t
any fa c to r cau sin g changes in the blood urea, in normal and
h y p e rten siv e toxaem ic c a s e s , and so c o n tr ib u tin g to the wide
v a r ia tio n s , should be in v e s tig a te d and elim in a ted .
During recen t years much a t te n t io n has been drawn to
the r a ise d u r ic a c id co n ten t o f the blood in p re-ecla m p tic
and eclam p tic c a s e s .
An in crea sed u r ic a c id co n ten t, decreased
COg combining power and low ered pH o f the blood are now
g e n e r a lly accep ted as being the ou tstan d in g fin d in g s in the
blood ch em istry in eclam psia.
Raised blood u r ic a cid in
c e r t a in c a se s i s o fte n co n sid ered to be d ia g n o stic o f eclam psia
w h ile some workers (Stander and Cadden, 1 9 3 4 b) regard the
h e ig h t o f the u r ic a c id value as an index o f the s e v e r ity o f the
d is e a s e .
I t w i l l be shown h ere, however, th a t se v era l fa c to r s ,
apart from th e toxaem ia, cause marked changes in the blood
u ric a,cid l e v e l , and u n le s s th e se are understood the a ctu a l
u r ic a c id valu e in an in d iv id u a l ca se may be very m islead in g.
7.
S E C T I O N
II
THE EFFECT OF LABOUR ON PLASMA UHIO AOID AND URSA
IK NORMAL AND NON-OONVULSIVE TOXAEMIC PATIENTS.
The p r e s e n t s t u d y d e a l s w ith th e ch a n g es i n u r i c
a c i d and u r e a i n t h e b lo o d o f i n d i v i d u a l p a t i e n t s d u rin g
t h e l a s t few weeks o f p r e g n a n c y , d u rin g la b o u r and th rou gh ou t
th e p u erp eriu m .
B lood sam p les were c o l l e c t e d d a i l y i n most
c a s e s and, d u rin g l a b o u r , a t i n t e r v a l s o f a few h o u rs.
Each sp e c im e n was exam ined f o r plasm a u r i c a c i d c o n t e n t by
B e n e d i c t s d i r e c t c o l o r i m e t r i c method. (1 9 2 2 a and b ).
The a c c e p t e d normal ra n g e by t h i s method i s 2 t o 4 m illig r a m s
p e r 100 c . c .
o f p la sm a , and a l l normal c a s e s , i n n on -pregn ant
p a t i e n t s or i n t h o s e i n e a r l y o r m id -p reg n a n cy , s t u d i e d h er e
have f a l l e n w i t h i n t h i s r a n g e .
B lo o d -u r e a was d eterm in ed by
t h e g a so r a e tr ic m ethod o f Van S ly k e and K ugel.
(1933)*
The s e r i e s c o n s i s t e d o f 9 3 women:
A. T w e n t y - f iv e normal c a s e s .
P a t i e n t s a t term w ith o u t
any a lb u m in u r ia , h y p e r t e n s i o n or oedema a t any tim e d u r in g
pregnancy.
Most were p r i m ig r a v id a e , a few h a v in g s l i g h t l y
con tracted p e lv e s.
B.
(See Avgenri.-: ~ CAoos 1 to
F i f t y - s i x p r e -e cla m p tic c a se s .
t .)
P r a c t i c a l l y a l l th e
p a t i e n t s were p r im ig r a v id a e h a v in g tox a em ic s i g n s o f v a r y in g
d e g r e e s o f s e v e r i t y but w it h o u t any c o n v u l s i o n s .
p r e -e c la m p tic ,
The term ,
i s used h e r e , a s by m ost a u t h o r s , to d e f i n e
a s p e c i f i c t y p e o f h y p e r t e n s i v e to x a em ic p a t i e n t ; i t does
8.
n o t im p ly t h a t t h e s e p a t i e n t s l a t e r d e v e lo p e d c o n v u l s i o n s .
The p a t i e n t s have been s u b - d i v i d e d from a c l i n i c a l p o i n t o f
view a s m ild or s e v e r e .
The m ild p r e - e c l a m p t i c p a t i e n t s
c o r r e s p o n d t o th e low r e s e r v e k id n e y c a s e s o f American
w r ite rs;
t h e y were f r e e from symptoms and had o n l y m ild
h y p e r t e n s i o n , a lb u m in u r ia or oedema.
(C a ses 26 to 6 2 .)
P a t i e n t s w ith e c la m p s ia h av e been e x c lu d e d from
c o n sid e r a tio n in t h i s s e c t io n .
0.
Twelve c a s e s o f c h r o n ic to x a e m ia .
A r a th e r
m i s c e l l a n e o u s group o f m u lt ip a r a e who had to x a em ic symptoms
and s i g n s d u r in g p r e g n a n c y s u g g e s t i v e o f th e c o n d i t i o n s
o f t e n r e fe r r e d to as e s s e n t i a l h y p er ten sio n or n e p h r itic
to x a e m ia .
The d i a g n o s i s was b a sed , among o t h e r t h i n g s , on
th e p r e v i o u s h i s t o r y , m u l t i p a r i t y and advanced a g e .( C a s e s 66-94)
F in d in g s B e fo r e O nset o f Labour.
The f i n d i n g s f o r plasm a u r i c a c i d and u rea i n
t h e s e p a t i e n t s a t term , but b e f o r e th e o n s e t o f la b o u r ,
a r e shown i n T able I .
These f i n d i n g s a r e e s s e n t i a l l y s i m i l a r to t h o s e
o f many o t h e r w orkers (O a ld w e ll and Lye, 1 9 21; K i l l i a n and
Sh erw in, 1921; F re y , 1923; H ellm u th , 1923; P l a s s , 1924;
S ta n d e r , 1 9 2 4 ) ,
t h e o n l y n o te w o r th y d i f f e r e n c e
b e in g t h e
somewhat r a i s e d
u r i c a c i d v a l u e s i n th e normal c a s e s .
Of
th e s e , th e p a t ie n t s
w it h v a l u e s 4 . 0 m i ll i g r a m s or more p er
100 c . c .
o n s e t o f la b o u r were a l l p r im ig r a v id a e .
b efore
the
Many o f them had been exam ined a few weeks e a r l i e r and a t
t h a t tim e th e u r i c a c i d v a l u e s had been w i t h i n normal l i m i t s .
9.
The p r o b a b le c a u se o f t h i s r i s e o f u r i c a c i d i n p r im ig r a v id a e
i n th e l a s t few weeks o f p r e g n a n c y i s d i s c u s s e d l a t e r .
Table
I.
Plasma u ric a c id and urea b efore on set o f labour.
11
ft'
U r ic a c i d
( m i l l i g r a m s p er 100
c u b ic c e n t i m e t r e s
o f p lasm a )
I-
Range
C la ss o f P a tie n t
Urea
( m i ll i g r a m s p e r 100
c u b ic c e n t i m e t r e s
o f plasm a)
Mean
Range
Mean
Normal p a t i e n t s ....................
'2 . 5 t o 5 . 2
3-9
16 to 21
18
M ild p r e - e c l a m p t i c p a t i e n t s
3 .0 to 5 .3
4 .5
1 4 t o 32
21
Severe p r e -e c la m p tic p a t ie n t s
3 .6 to 9 .7
6 .1
14 to 55
30
C hronic to x a e m ic p a t i e n t s . . .
2 .7 to 7 .3
5-3
1 4 to 55
26
In th e p r e - e c l a m p t i c and c h r o n ic to x a em ic p a t i e n t s
g r e a t d i f f e r e n c e i n th e u r i c a c i d c o n t e n t o f th e plasm a was
found from c a s e t o c a s e , d u r in g th e l a s t month o f p regnancy.
I n th e m ild p r e - e c l a m p t i c p a t i e n t s th e v a lu e was r a r e l y much
above normal l i m i t s ( o n l y 5 p a t i e n t s had v a l u e s o v er 5
m i l l i g r a m s p er 100 c . c . ) .
P a t i e n t s w ith h ig h v a l u e s were
u s u a l l y o f th e s e v e r e c l i n i c a l t y p e ,
but th e r e v e r s e d id n ot
h o ld ; n o t a l l p a t i e n t s w ith s e v e r e symptoms had a h ig h u r i c
a c id .
Many o f t h e s e p r e - e c l a m p t i c and c h r o n ic p a t i e n t s were
under o b s e r v a t i o n f o r 2 to 3 weeks b e f o r e the o n s e t o f la b o u r
and i t was found t h a t , a lth o u g h a d e f i n i t e c o n c l u s i o n c o u ld
not be made from a s i n g l e d e t e r m i n a t i o n ,
u r ic a c id v a lu es,
the r i s e and f a l l i n
i n i n d i v i d u a l p a t i e n t s , accom panied changes
10.
i n t h e c l i n i c a l s e v e r i t y o f th e c o n d i t i o n s .
Stan der and
Cadden (1 9 3 4 b ) foun d much t h e same r e l a t i o n .
However, w h ile
a h ig h u r i c a c i d v a lu e was found t o i n d i c a t e a s e v e r e to x a em ia ,
i t d id n o t appear t o have any r e l a t i o n a t a l l t o impending
c o n v u lsio n s.
The b lo o d u r e a v a lu e i n th e normal p a t i e n t s were
found to be v e r y lo w a s shown i n T able I .
In th e m a j o r i t y
o f t h e to x a e m ic p a t i e n t s th e b lo o d u r e a v a l u e s o b t a i n e d l a y
w i t h i n th e normal l i m i t s f o r n on -p regn an t c a s e s , but were
d e f i n i t e l y h ig h e r th a n th e r e s u l t s from th e normal p regn an t
cases.
S i m i la r r e s u l t s h a ve been r e c o r d e d by Z an gem eister
( 1 9 0 3 ) , W illia m s E .C .P .
( 1 9 2 3 ) , H ellm uth ( 1 9 2 3 ) , C ru ick sh an k s,
H e w itt and Couper ( 1 9 2 7 ) , Dieckmann (1 933 )? e t c .
p e r h a p s , been s u f f i c i e n t l y s t r e s s e d t h a t ,
It
n o t,
b ecau se o f th e low
normal v a l u e s i n p r e g n a n c y , any ce.se w ith a b lo o d u rea v a lu e
o f more th a n 25 m i l l i g r a m s p e r 100 c . c .
la b o u r,
b e f o r e th e o n s e t o f
s h o u ld be r e g a r d e d a s abnorm al.
Changes During Labour and the Puerperium.
When t h e s e same p a t i e n t s were f o l lo w e d th rou gh o u t
la b o u r and th e puerperium i t was found t h a t i n p r a c t i c a l l y
e v e r y c a s e a r i s e i n u r i c a c i d , and i n many c a s e s a r i s e i n
u rea a l s o , o c c u r r e d d u rin g la b o u r , w ith a r e t u r n to normal
d u r in g th e p u erp eriu m .
In some p a t i e n t s the r i s e was s l i g h t
and w ould h a ve been o v e r lo o k e d i f b lo o d -s p e c im e n s had n ot
been c o l l e c t e d a t i n t e r v a l s o f a few h ou rs b e fo r e and a f t e r
th e tim e o f d e l i v e r y .
was c o n s i d e r a b l e ,
In o t h e r p a t i e n t s , how ever, th e r i s e
th e v a l u e s m ounting w e l l above normal l i m i t s
1/l.LriJ.l .L' 1 »
*1*
t*a
;
2**
miytAy
13.
2.i«
i
u9
R e l a t i o n o f l e n g t h o f L ab ou r t o R i s e o f U r i c A c i d i n a l l Oases
v111- ««✓
'
w \ j s t n <L v » o o i
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: <£nw
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-ivnj-iy
11.
even i n n o n -to x a em ic p a t i e n t s .
The h ig h e s t v a lu e rea c h e d
among normal p a t i e n t s was 1 0 .4 m illig r a m s o f u r ic a c id and
10 4 m illig r a m s o f u r e a p er 100 c . c , p lasm a. (C ase I)
U r ic A cid F in d in g s .
When th e r e s u l t s from the w hole s e r i e s were s tu d ie d
i t was found t h a t th e e x te n t o f th e r i s e i n u r ic a c id , above
th e a n te -p a r turn l e v e l , depended d i r e c t l y on th e le n g th and
s e v e r i t y o f th e la b o u r .
The e v id en ce fo r t h i s i s shown in
T able I I and C h arts I to IV.
T able
II.
R e la t io n o f le n g t h o f la b o u r to u r ic a c id r i s e .
Hours i n Labour
Mean
Range
Maximal r i s e s i n u r i c a c i d
( m illig r a m s p er 100 c u b ic
c e n t i m e t r e s o f plasm a)
Range
Mean
0 to
4
3
- 0 . 5 to 0 . 5
0 .1
5 to
12
7
- 0 . 1 to 1 . 7
0 .5
13 to
24
18
0 . 1 to 3 .0
1 .1
25 t o
48
35
1 . 0 t o 4 .5
2 .4
49 t o 120
73
3 .1 to 6 . 4
4. 6
In T able I I a l l p a t i e n t s have been arran ged in t o
groups a c c o r d in g t o le n g t h o f la b o u r , w ith o u t r eg a r d to
c l a s s i f i c a t i o n a s normal or to x a e m ic .
The mean r i s e f o r
each o f t h e s e groups a t d i f f e r e n t tim e s th rou gh ou t la b o u r
and e a r l y puerperium i s shown i n Chart I .
The b a se l i n e o f
th e graph r e p r e s e n t s th e o r i g i n a l u r ic a c id v a lu e o f each
12.
group b e f o r e th e o n s e t o f la b o u r , w h ile the p o i n t s p l o t t e d
show th e a c t u a l r i s e ,
i n m illig r a m s o f u r i c a c i d p er 100 c . c .
plasm a, above th e antepartum l e v e l .
The p o i n t o f o r i g i n o f
each cu rv e from th e b ase l i n e i n d i c a t e s th e mean le n g t h o f
la b o u r f o r p a t i e n t s i n t h a t group.
From t h i s c h a r t i t can be se e n t h a t , not o n ly
does th e u r i c a c i d i n c r e a s e d u rin g la b o u r , but t h a t th e
e x t e n t o f th e r i s e i s s t r i c t l y p r o p o r t i o n a l to the l e n g t h
o f th e la b o u r .
I t w i l l be n o t i c e d th a t th e r i s e d u rin g
la b o u r i s grad u al but s l i g h t l y more r a p id towards t h e end,
i.e .
i n th e se co n d s t a g e o f la b o u r .
The maximal va lu e was
u s u a l l y found a t about 4 h o u rs postpartum , a lth o u g h v a r i a t i o n
was found from c a s e t o c a s e ,
some p a t i e n t s r e a c h in g t h e i r
maximum a t d e l i v e r y and o t h e r s c o n t in u in g to r i s e t i l l 24
hou rs p o s t-p a r tu m .
In most p a t i e n t s the v a l u e s r e tu r n e d
to an a b s o l u t e normal betw een the t h i r d and f i f t h days
p o st-p a r tu m ; c a s e s which s t a r t e d w ith h ig h a n t e - p a r turn
v a l u e s th u s show a more r a p id p o st-p a rtu m f a l l , which i s
seen in la t e r ch a r ts.
P a t i e n t s h av in g a s e v e r e la b o u r
showed a g r e a t e r r i s e th a n p a t i e n t s w ith a m ild la b o u r o f
t h e same d u r a tio n ; t h i s f a c t a c c o u n ts fo r the range o f th e
r i s e s i n each group shown i n Table I I .
The e s t i m a t i o n o f
t h e s e v e r i t y o f th e la b o u r depended m erely on c l i n i c a l
o b s e r v a t i o n and, t h e r e f o r e , a c c u r a t e f i g u r e s cannot be
g i v e n to show t h i s p o i n t .
In th e g r e a t m a j o r it y o f p a t i e n t s ,
how ever, t h e l e n g t h o f the la b o u r g i v e s a f a i r l y s a t i s f a c t o r y
in d e x o f i t s s e v e r i t y .
As one would e x p e c t , th e m a j o r it y
. t i o n o f L e n g t h o f L a b o u r t o R i s e o f U r i c A c id i n f o r c e p s and
11on - f o r c e p s e a sea,
wwsy -jJ
o o I V3J
bu
Id O oU O l V O
Mi
'351'a
"J tl p J- ;? !/
o f th e p a t i e n t s h a v in g a l o n g la b o u r were p r im ig r a v id a e
w h ile many o f th e p a t i e n t s w ith a sh o r t la b o u r were m u ltip a r a e ,
but th e r i s e i n plasm a u r i c a c i d was found to be u n a f f e c t e d
by th e p a r i t y o f th e p a t i e n t , depending o n l y on the l e n g t h
o f th e la b o u r .
I n Chart I I t h e p a t i e n t s d e l i v e r e d by f o r c e p s ,
and t h o s e n o t so d e l i v e r e d , a r e p l o t t e d s e p a r a t e l y .
I n th e
group o f p a t i e n t s w ith la b o u r over 48 h o u r s , t h e r e was o n ly
one sp o n ta n eo u s d e l i v e r y and, t h e r e f o r e , a curve f o r th e
p a t i e n t s n o t d e l i v e r e d by f o r c e p s a t t h a t tim e h a s n ot been
drawn.
The r e s u l t s from the o th e r two g ro u p s, how ever, show
a g r e a t e r ante-parturn r i s e i n p a t i e n t s d e l i v e r e d by f o r c e p s
and a s l i g h t d e l a y i n th e poet-partura f a l l to normal.
It is
o b v io u s th a t n e i t h e r d e l i v e r y by f o r c e p s nor th e a d m i n is t r a t i o n
o f an a n a e s t h e t i c can a f f e c t th e ante-parturn r i s e i n u r i c a c id ,
e x c e p t to s h o r t e n i t by t e r m in a t in g t h e la b o u r .
The g r e a t e r
r i s e i n p a t i e n t s d e l i v e r e d by f o r c e p s i s most p r o b a b ly due
t o th e g r e a t e r s e v e r i t y o f the la b o u r ; f o r c e p s were a p p l i e d
i n most c a s e s b ecau se o f a p r o lo n g e d seco n d s t a g e and
m a ter n a l d i s t r e s s .
The d e la y i n the p ost-p artu m f a l l i s not
marked and may be due e i t h e r to the more s e v e r e la b o u r or to
th e a n a e s t h e t i c .
P a t i e n t s who have had a s i m i l a r a n a e s t h e t i c
( g a s - o x y g e n - e t h e r ) a p a r t from la b o u r , e . g .
f o r th e perform ance
o f e x t e r n a l v e r s i o n s , have shown a s l i g h t r i s e i n plasm a u r i c
a c i d (mean 0 . 7 mg. > range 0 . 1 t o 1 . 5 nig. p e r 100 c . c . )
l a s t i n g f o r r a th e r more th an 24 h o u r s.
partum f a l l i s ,
d e liv e r y .
The d e la y e d p o s t ­
t h e r e f o r e , p r o b a b ly due to th e a n a e s t h e t i c a t
h o u r to R ise o f U ric
'k>wsyrj,
tf o t l
Oly n
HI
OOI
g s iy
1WOJ-OU
e l a t i o n o f L e n g t h o f l a b o u r t o R i s e o f u r i c A c i d i n oedem atous j
and n o n - o e derm t o n
V USw1 •o'-y OO1 v 3 ‘bw
(fnw Ol yn Ml 3S<H THrtiOU
14.
In Chart I I I the combined r e s u lt s from chronic
toxaemic and p re-ecla m p tic ca ses have been p lo tte d a g a in st
the normal c a s e s , but s t i l l in groups according to len g th o f
labour.
The toxaemic ca ses have been combined, as th ere i s
not any s ig n if ic a n t d iffe r e n c e between them.
In the lo n g e st
labour groups, on ly p a tie n ts d e liv e r e d by forcep s have been
in clu d ed , so that a f a ir comparison can be made.
I t w ill be
seen th a t, when the mean len g th o f labour i s the same, the
r i s e in u r ic a c id i s not higher in th e se toxaemic ca ses than
in the normals.
The post-partum f a l l in the toxaemic cases
i s greater and more rapid than in normal c a ses because the
u ric a c id i s f a l l i n g from a h igher o r ig in a l ante-partum
value to an a b so lu te normal value a f t e r d e liv e r y .
In Chart IV the r e s u lt s from oedematous p a tie n ts
are charted a g a in st the r e s u lt s from those not oedematous.
The oedematous p a tie n ts form the m ajority o f the se v e r e ly
toxaemic p a tie n t s .
The curves are e s s e n t ia lly sim ila r;
the s li g h t d iffe r e n c e s in h eig h t can be accounted for by
the d iffe r e n c e s in the len g th o f labour o f each group.
I t may, th e r e fo r e , be concluded th at the r i s e in
plasma u r ic a cid which has been shown to occur during labour
i s n eith e r r e la te d in any way to the h eig h t o f the o r ig in a l
ante-partum value nor to the c l a s s i f i c a t i o n o f the p a tie n t
(normal or toxaem ic) nor to oedema, nor to the method o f
d e liv e r y .
I t appears to be r e la te d only to the len g th and
s e v e r ity o f the labour.
Urea F indings.
In most o f the p a tie n ts plasma urea d eterm inations
:a r r v.
01
it)our to R i s e o f I :l '
u3?e
,
Houai
fVNTE-pfl^urv
Hours
'VoS't'rnerfu k \
rl e 1 a t i on o f j- e us
vOB
O
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q
15.
were made a t th e same tim e a s t h o s e o f u r ic a c i d , and a
s i m i l a r r i s e was u s u a l l y found d u rin g la b o u r .
The r i s e was
most marked i n l o n g l a b o u r s , w h ile p a t i e n t s w ith normal
la b o u r s showed l i t t l e
or no r i s e .
Chart V shows th e mean urea r i s e d u rin g la b o u r and
the
e a r l y puerperium i n p a t i e n t s grouped a c c o r d in g to l e n g t h
o f la b o u r .
The s i m i l a r i t y to th e u r i c a c i d changes w i l l be
n o te d , t h e same r e l a t i o n t o th e l e n g t h o f la b o u r b e in g se e n .
The r i s e i n u r e a o c c u r r e d l a t e r i n la b o u r than the u r i c a c id
r is e .
In many p a t i e n t s t h e r e was n o t a c o m p lete r e t u r n to
th e a n te-p a rtu m l e v e l ;
t h i s i s p r o b a b ly due to the f a c t t h a t
an te-p artu m u rea v a l u e s a r e below th e normal non -pregn ant
l e v e l , and t h a t t h e r e i s a p h y s i o l o g i c a l r i s e i n u rea i n th e
puerperium .
( W illia m s , 1923> Cadden and F a r i s , 1 9 3 8 ) .
I t was foun d,
u r ic a c id
how ever, t h a t , a lth o u g h the u r e a and
both showed changes i n the same d i r e c t i o n and a t
th e same tim e i n i n d i v i d u a l p a t i e n t s , a c o n s t a n t p r o p o r t io n
d id n ot e x i s t between t h e i r v a l u e s from c a s e to c a s e .
As
w ith u r i c a c i d th e r i s e was n ot o b v i o u s l y r e l a t e d t o to x a em ia ,
f o r c e p s , o r a n a e s t h e s i a , though th e d a ta a r e l e s s com p lete i n
t h e c a s e o f u r e a th a n i n t h a t o f u r i c a c i d .
D isc u ssio n .
The f i n d i n g s r e c o r d e d h e r e show t h a t la b o u r can
produce a marked e l e v a t i o n o f the u r ic a c i d and u r e a i n t h e
p lasm a.
I t i s o b v io u s ,
th erefore,
t h a t any e s t i m a t i o n s o f
th e se su b sta n ces, or oth er n o n -p r o tein n itr o g e n f r a c t io n s
r e p o r te d i n women a t or about d e l i v e r y or i n the e a r l y
16.
puerperium, have l i t t l e s ig n ific a n c e u n less the len g th o f the
labour i s known and the appropriate r is e accounted fo r.
The r is e in u r ic a cid and urea during labour i s
probably due to dim inished e x c r e tio n by the kidney, and
r e la te d to the o lig u r ia which occurs so commonly during labour.
The impairment o f renal fu n ctio n i s presumably due m ainly to
the p ressu re o f the c h ild * s head on the base o f the bladder
and lower end o f the u r e te r s .
Such a lo c a l pressure e f f e c t
i s o f course to be expected from a p r io r i c o n sid er a tio n s, and
i t i s proved p a th o lo g ic a lly by the in v a r ia b le fin d in g on
post-mortem exam ination o f oedematous, haemorrhagic or
u lce ra ted areas a t the base o f the bladder in f a t a l ca ses
fo llo w in g a p ro tra cted labour.
The r is e in u r ic a cid to valu es above normal, which
was noted in some non-toxaemic prim igravidae during the la s t
few weeks before term, may a lso be due to pressure on the
lower u r e te r s sin c e i t occurs a f t e r the f ix in g o f the head in
the p e lv is .
A survey o f the lit e r a t u r e on b lo o d -n itro g en , in
normal and toxaem ic p a tie n ts a t about the time o f d e liv e r y ,
or in the puerperium, r e v e a ls that only a few workers made
s e r ia l in v e s t ig a t io n s on in d iv id u a l p a tie n t s , and o f those
none made exam inations of the blood r e g u la r ly at short
in te r v a ls o f tim e.
As a r e s u lt , the e f f e c t of labour on
the n on -p rotein n itro g en fr a c tio n s o f the blood has not been
c le a r ly shown and a referen ce has not been found which r e la t e s
ra ised n on -p rotein n itro g en valu es to the len g th o f labour.
17.
In most c a s e s th e e s t i m a t i o n s were made o n ly a t i n t e r v a l s o f
2 to 7 d a ys, and f i g u r e s a r e n o t g i v e n f o r d u r a t io n o f la b o u r.
Owing to l a c k o f in fo r m a tio n on t h i s p o i n t , and a l s o i n view
o f th e r e l a t i v e l y i n f r e q u e n t e x a m in a tio n s , i t i s d i f f i c u l t to
a s s e s s th e s i g n i f i c a n c e o f t h e s e f i n d i n g s i n g e n e r a l.
The most d e t a i l e d work i n t h i s c o n n e c t io n ap p ears
t o be t h a t o f Oadden and F a r i s ( 1 9 3 8 ) , who s t u d i e d t o t a l
n o n - p r o t e i n n i t r o g e n , u r e a n i t r o g e n and r e s t n i t r o g e n i n 40
p a t i e n t s d u rin g th e f i r s t s t a g e o f la b o u r , a t d e l i v e r y and on
a l t e r n a t e days through out th e puerperium .
They found a s l i g h t
i n c r e a s e i n th e mean r e s u l t s fo r the s e r i e s during la b o u r and
i n t h e f i r s t day p o s t —par turn.
During the 2nd and 3rd day p o s t ­
partum t h e l e v e l s rem ained s t e a d y or showed a s l i g h t f a l l ;
t h i s was f o l lo w e d by a r i s e o f a l l v a lu e s r e a c h in g normal
non -pregn ant l e v e l s by t h e 1 0 th day p o st-p a r tu m .
When t h e i r
f i n d i n g s i n i n d i v i d u a l c a s e s a r e s t u d i e d , how ever, wide
v a r i a t i o n s a r e found; 8 out o f 40 c a s e s showed a d e c r e a s e i n
t o t a l n o n - p r o t e i n n i t r o g e n from b e fo r e d e l i v e r y to a f t e r
d e liv e r y ,
5 out o f 40 c a s e s showed a d e c r e a s e i n urea n i t r o g e n
and 14 o u t o f 40 showed a d e c r e a s e i n r e s t n i t r o g e n , w h ile
1 c a s e showed an i n c r e a s e i n n o n - p r o t e i n n i t r o g e n .f r o m 2 4 .2
t o 48 mg. p e r 100 c . c . ,
p er 100 c . c .
100 c . c .
i n urea n i t r o g e n from 8 . 2 to 2 5 .6 mg.
and i n r e s t n i t r o g e n from 16 to 2 2 .4
du rin g la b o u r .
Pe ^
T h eir mean r e s u l t s te n d to a g r e e
w ith th e p r e s e n t f i n d i n g s , how ever, and i t i s l i k e l y th a t
t h e f a c t o r o f l e n g t h o f la b o u r i s r e s p o n s i b l e fo r th e changes
d e s c r i b e d and would e x p l a i n th e wide range o f the f i n d i n g s
r e p o r te d .
18.
Stander sand Cadden ( 1 9 3 4 b ) > p u b l i s h e d b io c h e m ic a l
f i n d i n g s from many p r e - e c l a m p t i c and e c la m p tic c a s e s .
D e te r m in a tio n s on p r e - e c l a m p t i c s were made “im m ed ia te ly b e fo r e
d e l i v e r y 11 and “a f t e r r e c o v e r y ” .
The r e s u l t s show h ig h e r u r i c
a c i d v a l u e s b e f o r e d e l i v e r y w ith normal v a l u e s a t t h e secon d
e x a m in a tio n ; t h e y do n o t r e c o r d the time o f o n s e t or the l e n g t h
o f la b o u r , how ever, and t h e r e f o r e t h e i r c o n c l u s i o n s cannot be
a c c e p t e d a t t h e i r f a c e v a lu e .
A r i s e i n u r i c a c i d d u rin g
la b o u r can be s e e n i n s e v e r a l o f t h e i r c h a r t s , but no m en tion
i s made o f i t i n t h e i r p ap er.
S ie d e n t o p f ( 1 9 3 2 ) , i n an i n v e s t i g a t i o n on changes
i n b lo o d c h e m is tr y d u rin g th e th r e e s t a g e s o f la b o u r ,
d eterm in ed t o t a l n o n - p r o t e i n n i t r o g e n o f th e b lo o d in s e v e r a l
women.
In most o f h i s c a s e s he found a s l i g h t r i s e du rin g the
f i r s t and e a r l y secon d s t a g e and a g r e a t e r r i s e d u rin g th e
l a t e seco n d s t a g e o f la b o u r , but t h e r e were s e v e r a l marked
ex cep tio n s:
11 ou t o f 12 p a t i e n t s showed a f a l l i n t o t a l
n o n - p r o t e i n n i t r o g e n i n th e t h i r d s t a g e o f la b o u r w h ile 12
out o f 1 4 c a s e s showed a r i s e betw een the end o f la b o u r and
th e
or 6th day o f the puerperium .
The i n v e s t i g a t i o n
ap p ears to have been c a r r i e d ou t on groups o f d i f f e r e n t
women'at t h e v a r io u s s t a g e s o f la b o u r and t h e r e f o r e the
changes i n i n d i v i d u a l p a t i e n t s cannot be f o l lo w e d .
H is
f i n d i n g s p r i o r t o d e l i v e r y a g r e e w ith the p r e s e n t r e s u l t s
but no n o t i c e i s ta k en o f the l e n g t h o f la b o u r , and t h i s
p r o b a b ly a c c o u n t s f o r th e in c o n s is te n c ie s i n h i s r e s u l t s .
The r a p id f a l l i n n o n - p r o t e i n n i t r o g e n f r a c t i o n s
which he f i n d s im m e d ia te ly a f t e r d e l i v e r y h as not been
19.
found i n the p r e s e n t stu d y and i s i n d i r e c t d isa greem en t
w ith the f i n d i n g s o f P l a s s .
H is method o f r e c o r d in g changes
a s a p e r c e n t a g e o f t h e i r o r i g i n a l v a lu e makes even sm a ll
changes appear s t r i k i n g and e x a g g e r a t e s any e x p e r im e n ta l e r r o r .
P l a s s in 1924 examined a s e r i e s of 24 p a t i e n t s ,
7 norm al, 7 e c la m p tic and 10 n o n - c o n v u ls iv e to x a e m ic , f o r
n o n - p r o t e in n i t r o g e n f r a c t i o n s du rin g la b o u r and the
puerperium .
In some c a s e s the f i r s t specim en was taken o f f
d u rin g l a b o u r , but i n o t h e r s the f i r s t specim en was ta k e n o f f
a fte r d e liv e r y .
A s l i g h t r i s e i n a l l f i g u r e s f o r t o t a l non­
p r o t e i n n i t r o g e n , u r i c a c i d and u r e a was found t o o ccu r p o s t ­
partum (maximum l e v e l s r ea c h e d on 2nd or 3rd day p o s t - p a r t urn)
w ith a su b seq u en t f a l l to norm al.
The r i s e was g r e a t e s t i n
tox a em ic c a s e s and was u s u a l l y found to c o i n c i d e w ith the
c l i n i c a l improvement o f the p a t i e n t .
P l a s s s u g g e s t e d th a t
t h i s i n c r e a s e i n n o n - p r o t e i n n i t r o g e n f r a c t i o n s was due to
d i l u t i o n o f the b lo od by t i s s u e f l u i d c o n t a i n i n g h ig h e r non­
p r o t e i n n i t r o g e n , urea and u r i c a c i d c o n t e n t .
r e su lts,
The p r e s e n t
e s p e c i a l l y t h a t from oedematous c a s e s , do not support
t h i s t h e o r y and i t seems l i k e l y t h a t the r i s e which he
d em on strated was m e r e ly the end o f th e r i s e which had o c cu rr ed
d u rin g la b o u r .
H ellm uth ( 1 9 2 3 ) examined a s e r i e s o f normal p a t i e n t s
i n la b o u r and a g a in once or t w ic e in the puerperium , u s u a l l y
about the 7^
day p o st-p a r tu m .
He found v a lu e s r a i s e d during
la b o u r and normal a t l a t e r e x a m in a tio n s .
In 12 o f h i s normal
c a s e s th e u r i c a c i d was found to be o v e r 3*5 mS« Per 100 c «c .
( h i g h e s t 5 .0 mg. p e r 100 c . c . ) .
He e x p l a i n s t h e s e f i n d i n g s
20.
a s due to a m e t a b o lic u p se t i n p r im ig r a v id a e a t term c a u s in g
d i f f i c u l t y i n com p lete o x i d a t i o n o f p r o t e i n s .
Frey ( 1 9 2 3 ) determ ined b lo od n o n - p r o t e i n n i t r o g e n
f r a c t i o n s i n a s e r i e s o f normal and toxa em ic pregnant women
a t d e l i v e r y and l a t e r i n the puerperium .
In normal c a s e s a t
d e l i v e r y he found n o n - p r o t e i n n i t r o g e n , u r e a and u r ic a c i d
a t th e upper l i m i t o f normal but w e ll w i t h i n normal l i m i t s
l a t e r i n the puerperium .
In toxa em ic c a s e s he found t h a t the
n o n - p r o t e i n n i t r o g e n and u r e a were o f t e n much i n c r e a s e d a t
d e l i v e r y , but th e v a lu e s v a r ie d g r e a t l y from c a s e to c a s e .
H is u r i c a c i d f i n d i n g s were v e r y i n c o n s i s t e n t .
It is lik e ly
t h a t th e h ig h v a l u e s found by t h e s e two w orkers, Hellmuth
and F rey , i n t h e i r normal and i n many o f t h e i r toxaem ic
c a s e s can be a c c o u n te d f o r by l e n g t h o f tim e i n la b o u r.
The r e l a t i o n between the l e n g t h o f la b o u r and the
r i s e o f plasm a u r i c a c i d and u r e a i s n o t ,
su rp risin g fin d in g .
in r e tr o s p e c t, a
The r i s e o c c u r s to th e same e x t e n t i n
normal a s i n toxa em ic p a t i e n t s and may be c o n s id e r e d a lm ost
p h y sio lo g ic a l;
but i n th o s e c a s e s w ith la b o u r over 48 hours
th e n i t r o g e n r e t e n t i o n i s so marked t h a t th e p o s s i b i l i t y o f
a c t u a l k id n e y damage a s a r e s u l t o f the o b s t r u c t i o n cannot
be e x clu d ed .
In a few c a s e s th e r e tu r n to normal v a lu e s
h a s been slo w and i t may be t h a t t h e s e p a t i e n t s have s u f f e r e d
some permanent r e n a l damage.
These f i n d i n g s a r e t h e r e f o r e
a n o th e r i n d i c a t i o n o f th e d an gers o f a p r o t r a c t e d la b o u r .
The r i s e o f plasm a u r i c a c i d and u r e a , due to lab o u r i s a l s o
o f im p o rta n ce, how ever, i n t h a t i t can produce such g r e a t
changes i n b lo o d c h e m is tr y a s to i n v a l i d a t e any work which
21.
d oes n o t ta k e i t i n t o a c c o u n t.
Summary.
The changes i n the plasm a u r i c a c i d and u rea
o c c u r r in g du rin g la b o u r and th e e a r l y puerperium have been
s t u d i e d i n d e t a i l i n a s e r i e s o f normal and toxaem ic women.
A r i s e o f plasm a u r i c a c i d and u rea i s found to occu r
i n v a r i a b l y d u rin g la b o u r , th e h e i g h t o f th e r i s e b e in g
dependent on th e l e n g t h o f the la b o u r .
The r i s e i s
in d ep en d en t o f toxaem ia and o t h e r f a c t o r s .
There i s a
c o r r e sp o n d in g f a l l i n th e e a r l y puerperium so t h a t normal
v a lu e s a r e u s u a l l y r e a c h e d by th e t h i r d day a f t e r d e l i v e r y .
22.
S E C T I O N
III.
CHANGES IN PLASMA URIC ACID AND UREA
IN ECLAMPSIA.
In th e p r e v io u s c h a p te r i t was i n d i c a t e d t h a t
w ide v a r i a t i o n s o f o p i n io n e x i s t e d ,
between i n v e s t i g a t o r s ,
on th e q u e s t i o n o f n o n - p r o t e i n n i t r o g e n r e t e n t i o n i n c a s e s
o f h y p e r t e n s i v e toxa.emia o f pregnancy.
I t was shown t h a t
t h e s e v a r ie d o p i n io n s were f r e q u e n t l y due to the f a c t
t h a t th e d a ta were o b t a in e d from d i f f e r e n t p a t i e n t s a t
d i f f e r e n t s t a g e s o f preg n an cy and t h a t no a cco u n t m s ta k en
o f th e i n f l u e n c e o f la b o u r on the blood n o n - p r o t e i n n i t r o g e n
fr a c tio n s.
In e c la m p s ia m ost workers a g r e e i n f i n d i n g r a i s e d
u r i c a c i d v a l u e s but e x c e p t i o n s have been n o te d and th e
h e i g h t o f th e v a l u e s r e c o r d e d v a r i e s g r e a t l y .
W illia m s (1 9 2 1 ) m s one o f the e a r l i e s t workers
to f i n d h ig h u r ic a c i d v a l u e s i n e c la m p tic p a t i e n t s w h ile
th e b lo o d u rea v a l u e s i n th e same p a t i e n t s were w i t h in normal
lim its.
He examined th e blood o f 5 e c la m p t ic s during the
a c u t e s t a g e o f th e d i s e a s e ;
the avera ge u r ic a c i d v a lu e from
t h e s e c a s e s was 7 -8 mg. p e r 100 c . c .
From t h i s s e r i e s he
was un able t o f i n d a r e l a t i o n betw een u r ic a c i d v a lu e s and
c l i n i c a l symptoms, la b o u r or s t a g e i n pregnancy.
C ald w ell
and Lye (1 9 2 1 ) found a n o n - p r o t e i n n i t r o g e n r e t e n t i o n , o f
v a r y in g d e g r e e , i n th e b lo o d o f n o n - c o n v u ls iv e toxaem ic and
e c la m p tic p a t i e n t s .
They c o n c lu d e d th a t i n c a s e s w ith a
s e v e r e r e t e n t i o n , th e p r o g n o s i s was bad.
K i l l i a n and Sherwin
( 1 9 2 1 ) found t o t a l n o n - p r o t e in n i t r o g e n o f the blood a t th e
upper l i m i t o f normal i n e c la m p tic c a s e s - the urea p e r c e n ta g e
was lo w , w h ile th e u r ic a c i d was markedly in c r e a s e d .
Each
p a t i e n t was examined once o n ly and t h e r e was wide v a r i a t i o n
from c a s e t o c a s e (ra n g e o f u r i c a c i d v a lu e s was 3 t o 11 mg.
p e r 100 c . c . ) .
The i n c r e a s e i n v a lu e s was th o u gh t t o be due
t o r e n a l im pairm ent.
Hellmuth ( 1 9 2 3 ) i n a l a r g e r s e r i e s o f
e c la m p tic c a s e s a l s o found h ig h blood u r i c a c i d v a lu e s w h ile
th e b lo o d u rea was normal or o n l y s l i g h t l y r a i s e d .
He
c o n c lu d e d from h i s s e r i e s t h a t th e h e i g h t o f the u r ic a c i d
v a lu e i n an e c la m p t ic c a s e was o f no v a lu e i n p r o g n o s is
and t h a t a h ig h v a lu e i n a p r e - e e l a m p t i c c a s e d id not
n e c e s s a r i l y i n d i c a t e impending f i t s .
Frey ( 1 9 2 3 ) , on t h e o t h e r
hand, found u r i c a c i d v a lu e s w i t h i n normal l i m i t s i n e c la m p tic
c a s e s w h ile b lood n o n - p r o t e in n i t r o g e n was o f t e n c o n s id e r a b ly
r a ise d .
H is u r i c a c i d f i n d i n g s in h i s d i f f e r e n t groups o f
p a t i e n t s , how ever, appear to be unusual - i n the normal non­
p reg n a n t group th e range i s g i v e n a s 12 to 15 mg. p er 100 c . c .
and i t must be a c c e p te d t h a t the method employed was not i n
any way a s r e l i a b l e a s th e modern methods.
P la s s ( 1924), as
m entioned i n the p r e v io u s c h a p te r , i n v e s t i g a t e d n o n - p r o t e i n
n it r o g e n f r a c t i o n s i n 7 e c la m p tic p a t i e n t s .
a c id r a is e d ,
He found u r ic
e s p e c i a l l y i n th e f i r s t two days o f the puerperium ,
w h ile u r e a v a l u e s were w i t h i n normal l i m i t s .
Stander ( 1 9 2 4 );
S tan d er, Duncan and S i s s o n ( 1 9 2 5 ); Bokelmann and Rother (1 9 2 5 ) ;
Stander and R a d e le t ( 1 9 2 6 ); C ruickshanks, H ew itt and
Couper ( 1 9 2 7 ); have a l l compared average u r i c a c i d f i n d i n g s
o f d i f f e r e n t groups o f p re g n a n t women and found high v a lu e s
i n e c la m p t ic c a s e s .
More r e c e n t l y , Stander and Oadden ( 1934b ),
and l a t e l y Cadden and Stan der ( 1 9 3 9 ) , made much more d e t a i l e d
s t u d i e s o f th e b io c h e m ic a l changes i n the plasma i n c a s e s o f
e c la m p s ia .
In the form er o f t h e s e pap ers th e y record ed th e
b io c h e m ic a l f i n d i n g s from 108 e c la m p tic and 40 p r e -e c la m p tic
c a s e s and i n the l a t t e r ,
e c la m p t ic c a s e s .
c o m p o site c h a r ts were made from 132
Blood n o n - p r o t e i n n it r o g e n and urea were
found to be low i n most c a s e s , a lth o u g h i n some c a s e s a r i s e
was found to o ccu r l a t e i n the d i s e a s e .
The blood u r i c a c id
c o n t e n t was found to be r a i s e d i n both p r e -e c la m p sia and
e c la m p s ia and was r eg a r d e d a s a c r i t e r i o n o f the s e v e r i t y o f
the d i s e a s e .
In s p i t e o f th e g r e a t volume o f l i t e r a t u r e which
h a s been w r i t t e n on the s u b j e c t o f the b io c h e m ic a l f i n d i n g s
i n e c la m p s ia , i t h a s a g a in been found th a t l i t t l e a ttem p t h as
been made to f o l l o w i n d e t a i l the changes which occur in
in d iv id u a l p a t ie n t s .
In th e p r e s e n t stu d y the changes
o c c u r r in g i n th e plasm a u r i c a c i d and u rea were f o llo w e d
i n a s e r i e s o f 42 e c la m p t ic p a t i e n t s throughout the cou rse o f
th e d i s e a s e , and an a tte m p t h a s been made to d i s e n t a n g l e th e
v a r io u s f a c t o r s i n f l u e n c i n g t h e s e n o n - p r o t e in n it r o g e n
fr a c tio n s.
In a l l c a s e s the b lo o d v/as examined d a i l y or
o f t e n e r , and i n many c a s e s d e t e r m in a t io n s were made a t h o u r ly
i n t e r v a l s d u rin g the a c u t e s t a g e .
The r e s u l t s from the
p r e v io u s s tu d y o f 25 normal p r e g n a n t and 56 p r e -e c la m p tic
p a t i e n t s a r e q u oted h e r e f o r com parison w ith the p r e se n t
fin d in g s.
I t i s to be s p e c i f i c a l l y n o te d th a t e v er y p a t i e n t
25.
who d e v e lo p e d e c la m p tic f i t s i s c l a s s e d h e r e under th e term
''eclampsia*1, even i n the s t a g e b e fo r e th e o n s e t o f f i t s ;
the
term " p r e -e c la m p tic " a g a in r e f e r s o n ly to p a t i e n t s w ith
to x a e m ia , c h a r a c t e r i s e d by h y p e r t e n s io n , a lb u m in u ria
and th e
o th e r s ta n d a r d s i g n s , who d id not d e v e lo p e c la m p t ic c o n v u ls io n s .
The e c la m p t ic p a t i e n t s have been d i v id e d i n t o 3 g r o u p s : (a )
18 A nte-oartum e c l a m n t i c s (G ases 104 to 121) - p a t i e n t s
who h a d , f i t s b e f o r e the o n s e t o f la b o u r , but not d u rin g
la b o u r or th e puerperium .
(b )
16 In tr a -o a r tu m e c l a m n t i c s (C ases 122 to I T ! ) - p a t i e n t s
who had f i t s d u rin g la b o u r ; t h i s group i n c lu d e s c a s e s
i n which f i t s began b e f o r e la b o u r but c o n tin u e d a f t e r
th e o n s e t o f p a i n s , and a l s o c a s e s w ith f i t s d u rin g
la b o u r which c o n tin u e d a f t e r d e l i v e r y .
(c)
8 P ost-p a rtu m e c l a m p t i c s (C a ses 138 to 1 4 5 ) - p a t i e n t s
who had f i t s which began o n ly a f t e r d e l i v e r y .
Two o f th e a n te-p a rtu m and one o f th e p ost-p artu m c a s e s
d i e d d u rin g th e a c u t e s t a g e o f th e d i s e a s e .
U r ic A cid F in d in g s .
In the p r e v io u s s e c t i o n i t was shown th a t d u rin g
la b o u r t h e r e i s a r i s e i n plasm a u r i c a c i d and u r e a , both i n
normal and i n n o n - c o n v u l s i v e toxaem ic p a t i e n t s ; a s w i l l be
shown h e r e , p r e c i s e l y th e same changes occu r i n e c la m p tic
p a t i e n t s d u rin g la b o u r .
In a d d i t i o n , i n p r e - e c la m p s ia and
i n e c la m p s ia th e r e a r e changes i n plasm a u r i c a c i d l e v e l
r e s u l t i n g from tox aem ia; and a ls o , i n e c la m p tic p a t i e n t s
th e r e a r e changes r e l a t e d to th e o n s e t o f f i t s .
The u r i c
a c i d f i n d i n g s i n v a r io u s t y p e s o f e c la m p t ic p a t i e n t s can be
u n d e r sto o d o n l y when t h e s e t h r e e f a c t o r s have been d is e n ta n g le d .
For t h i s pu rp ose th e c a s e s s t u d i e d h e r e a r e c o n s id e r e d under
t h r e e h e a d in g s .
(1)
The f i n d i n g s b e f o r e th e o n s e t o f f i t s or o f la b o u r .
T h is group i n v o l v e s o n l y the e f f e c t o f the p r e c e d in g
h y p e r t e n s i v e to x a em ia , th e o th e r two f a c t o r s b e in g
a u t o m a t i c a l l y e x c lu d e d .
(2 )
The changes which d e v e lo p i n r e l a t i o n to the f i t s .
To e x c lu d e the changes which had d e v e lo p e d p r e v i o u s l y
a s a r e s u l t o f th e to x a em ia the b a s ic l e v e l i s taken
a s t h a t which had been found i n each i n d i v i d u a l p a t i e n t
b e f o r e the o n s e t o f f i t s ;
th e r i s e due to th e f i t s i s
c a l c u l a t e d from t h a t l e v e l .
To e x c lu d e the changes
due t o la b o u r , a c o r r e c t i o n has been in tr o d u c e d i n t h o s e
c a s e s where th e f i t s c o i n c i d e d w ith or f o llo w e d the
tim e o f la b o u r .
T h is c o r r e c t i o n i s c a l c u l a t e d from th e
d a ta which have been g i v e n i n the p r e v io u s s e c t i o n
w ith r eg a r d to the i n f l u e n c e o f la b o u r i n p a t i e n t s
w ith o u t f i t s ;
th e mean f i g u r e a p p r o p r ia te to the a c t u a l
d u r a t io n o f la b o u r i s u sed in each c a s e .
o f t h i s c o r r e c tio n ,
The v a l i d i t y
i n the p r e s e n t c o n n e c tio n , i s shown
by th e c l o s e agreem ent o f the a c t u a l f i g u r e s from
e c la m p t ic p a t i e n t s n o t i n lab ou r w ith the c o r r e c t e d
f i g u r e s from e c la m p t ic p a t i e n t s i n la b o u r .
(3)
The i n f l u e n c e o f la b o u r .
When the s p e c i f i c e f f e c t s
o f the p r e v io u s toxa em ia and o f th e f i t s have been
27.
a n a l y s e d i t i s th e n p o s s i b l e to c o n s id e r th e a c t u a l
f i n d i n g s i n t h e s e p a t i e n t s w ith r e g a r d to la b o u r .
F in d in g s B e fo re th e Onset o f F i t s .
For com p arison w ith th e e c la m p t ic c a s e s , n o te may
be made o f t h e ch a n g es i n plasm a u r i c a c i d fo r a few weeks
b e fo r e th e o n s e t o f la b o u r , record ed i n the e a r l i e r s e r i e s
o f 25 normal and 5 6 p r e - e c l a m p t i c p a t i e n t s , who d id n o t
d e v e lo p e c la m p s ia .
The b lo o d was examined a t i n t e r v a l s o f
1 t o 2 days i n each c a s e .
I t wa>s found t h a t the u r ic a c i d
v a l u e s v a r ie d g r e a t l y from c a s e to c a s e .
In the m ild p r e ­
e c la m p t ic c a s e s th e v a lu e was r a r e l y much above normal l i m i t s .
C ases w ith h ig h v a l u e s were u s u a l l y o f s e v e r e c l i n i c a l ty p e ,
but th e r e v e r s e d id not h o ld ; th e c a s e s w ith s e v e r e symptoms
d id n o t a l l have h ig h u r i c a c i d v a l u e s .
Ten c a s e s from the p r e s e n t e c la m p tic s e r i e s were
examined b e f o r e the o n s e t o f f i t s .
125, 1 2 6 , 1 2 7 , 1 42, 143, 1 4 4 ).
(C a ses 104, 122 , 1 2 3 , 124,
In each c a s e the l a s t
e x a m in a tio n i n t h i s p r e - c o n v u l s i v e s t a g e was made s h o r t l y
b e f o r e o r du rin g th e f i r s t f i t .
Contrary to what i s g e n e r a l l y
s t a t e d i n the l i t e r a t u r e (S ta n d e r and Cadden, 1934b; Cadden
and S ta n d e r, 1939) fh e u r i c a c i d v a l u e s a t t h i s tim e were
found to be o n l y m o d e r a te ly r a i s e d .
In p a t i e n t s who d e v e lo p e d
e c la m p s ia su d d en ly w ith o u t any p r e c e d in g s t a g e o f s e v e r e
to x a em ia , th e u r i c a c i d v a lu e b e fo r e the f i r s t f i t was u s u a l l y
w i t h i n normal l i m i t s ( 3*0 t o 4*4 mS* Per 100 c . c . ) w h ile i n
c a s e s w ith e v id e n c e o f s e v e r e p r e c e d in g toxaem ia the u r ic
a c i d v a l u e s were s l i g h t l y h i g h e r ( 5*2 to 6 .5 mg. per 100 c . c . ) .
The mean v a lu e o f th e 10 c a s e s was 5*5 mg. p er 100 c . c .
When
t h e s e f i g u r e s a r e compared w ith th o s e from the n o n - c o n v u ls iv e
p r e - e c l a m p t i c c a s e s , i t w i l l be s e e n t h a t much h ig h e r v a lu e s
a r e o b t a in e d among p a t i e n t s w ith s e v e r e p r e - e c la m p s ia who
a r e n ot g o in g t o d e v e lo p c o n v u l s i o n s , a s i s shown i n Table I I I .
T able
III.
U r ic A cid V a lu es i n Normal and N on-C onvulsive
Toxaemic Oases n ear Term and i n E clam p tic Cases
b e f o r e th e Development o f F i t s .
Number
of
O ases.
Plasma U ric Acid: mg. per 100 c . c .
Normal P regnan t.
25
Mean.
3 .9
l l i l d P r e - e c la m p t ic .
29
4 .4
3 .0 t o 5 . 4
S ev ere P r e - e c la m p t ic .
27
6. 4
4 - 8 to 9 . 7
E clam p tic b e f o r e F i t s .
10
5 .5
3 . 0 t o 6 .5
Range.
2 . 5 to 5 .2
I t i s t h e r e f o r e c l e a r t h a t a v e r y h ig h u r i c a c i d v a lu e i n
a p r e - e c l a m p t i c p a t i e n t , w h ile o f im portance i n i n d i c a t i n g
a s e v e r e m e t a b o lic d is t u r b a n c e , i s n o t i n any way an in d ex
o f im pending e c la m p s ia .
From th e p r e s e n t f i n d i n g s i t appears
t h a t e c la m p s ia i s a c t u a l l y more l i k e l y to supervene i n a
p a t i e n t w ith o n l y m o d e r a te ly r a i s e d u r i c a c i d (under 6 mg.
p er 100 c . c . )
than i n one w ith a h ig h e r u r ic a c i d v a lu e .
This l a c k o f r e l a t i o n betw een the s e v e r i t y o f the p r e v io u s
b io c h e m ic a l f i n d i n g s and th e developm ent o f f i t s has a
c lin ic a l p a r a lle l;
the s e v e r i t y o f th e p r e c e d in g toxaem ic
s i g n s and symptoms i n the p r e s e n t s e r i e s d id n o t have any
r e l a t i o n to the s e v e r i t y o f th e e c la m p s ia .
CHART VI
G-ranh. siiowinf; R is e i n P la s m a U r i e A c id a f t e r P i t s .
V A L U E rv-r
ONSET O F
F IT5
HOU^S
l»F;TEJ\ O N S 6 T OF F l T J .
The E f f e c t o f F i t s ,
In e v e r y one o f t h e s e e c la m p tic p a t i e n t s a v e ry
r a p id r i s e o f plasm a u r i c a c i d was found t o o c cu r im m ed ia tely
a f t e r th e o n s e t o f f i t s .
The 10 c a s e s , i n which b io c h e m ic a l
s t u d i e s had been made b e f o r e t h e f i r s t f i t ,
were examined
f r e q u e n t l y - some a t h o u r ly i n t e r v a l s - a f t e r the f i r s t f i t .
A s t e a d y r i s e o f plasm a u r i c a c i d o f about 2 to 5 mg. p e r
100 c . c . o c c u r r e d d u rin g the few hours a f t e r the f i r s t f i t ;
th e a v e r a g e r i s e was about 1 mg. per hour.
The r i s e c o n tin u e d
f o r 4 t o 6 h o u r s , even i n p a t i e n t s w ith o u t any su bseq uent
fits,
fits.
but a g r e a t e r r i s e was found i n th o s e who had s e v e r a l
In Chart VI. th e mean u r ic a c i d v a lu e s from t h e s e
10 c a s e s and from 8 o t h e r s have been p l o t t e d to show t h e changes
du rin g the 24 hours f o l l o w i n g the f i r s t f i t .
The c a s e s have
been d i v i d e d i n t o groups a c c o r d in g to the number o f f i t s .
The b a se l i n e o f t h e graph r e p r e s e n t s the u r i c a c i d v a lu e
b e fo r e th e f i r s t f i t i n each c a s e , w h ile the c u r v e s i n d i c a t e
th e mean r i s e i n u r i c a c i d above the o r i g i n a l v a lu e .
The 8
a d d i t i o n a l c a s e s t h a t have been i n c lu d e d were p a t i e n t s who
had n o t been examined a c t u a l l y b e fo r e t h e i r f i r s t e c la m p tic
fit,
fit
t h e o r i g i n a l e s t i m a t i o n b e in g made soon a f t e r the f i r s t
; th e l o n g e s t tim e b e in g 3 h o u rs.
In t h e s e c a s e s an
a llo w a n c e h a s been made f o r th e i n i t i a l r i s e b e fo r e th e f i r s t
e s t i m a t i o n , based on th e tim e which had e la p s e d a f t e r the f i r s t
f i t and th e mean r i s e du rin g t h a t tim e i n comparable c a s e s o f
th e main s e r i e s .
In any o f th e c a s e s i n which la b o u r
c o i n c i d e d w ith th e f i t s ,
th e a p p r o p r ia te c o r r e c t i o n h a s
30.
been made, a s e x p la in e d e a r l i e r .
This c h a r t shows th e r a p id r i s e i n u r i c a c i d which
o c c u r s i n a l l c a s e s a f t e r th e commencement o f the f i t s and
d e m o n str a te s a c l e a r r e l a t i o n betw een the e x t e n t o f th e r i s e
and th e number o f th e f i t s .
This r a p id r i s e f o r 4 to 6 hours
a f t e r t h e f i r s t f i t was a c o n s t a n t f i n d i n g i n e v e r y c a s e , but
su bseq uent changes i n th e u r i c a c i d v a lu e s v a r ie d g r e a t l y from
c a s e t o c a s e depending on the c o u r se o f th e d i s e a s e .
High
v a l u e s were a lw ay s m a in ta in e d u n t i l th e f i t s c e a s e d , but t h e r e
was no r e l a t i o n between th e number o f f i t s and t h e d u r a tio n
o f tim e t h a t t h e h ig h v a l u e s were m a in ta in e d ; t h i s i s p r o b a b ly
b ecause th e tim e e l a p s i n g betw een f i t s v a r ie d g r e a t l y i n
d iffe re n t p a tie n ts.
A f t e r th e f i t s had c e a s e d , the f i n d i n g s
were o f two main t y p e s .
In some c a s e s the u r i c a c i d v a lu e s
began t o f a l l a few h ou rs a f t e r th e l a s t f i t ,
but i n o t h e r
c a s e s t h e v a l u e s were m a in ta in e d or even i n c r e a s e d f o r a
f u r t h e r 24 t o 48 h o u rs.
The p e r s i s t e n c e o f h ig h v a lu e s was
o f t e n r e l a t e d t o a p e r io d o f o l i g u r i a .
(O a ses 12 0 , 121 and 145)
In th e 3 f a t a l c a s e s
u r i c a c id v a lu e r o s e s t e a d i l y
t i l l d ea th even i n th e ab sen ce o f f i t s ;
th e v a lu e s a t death
were 1 1 . 0 m g., 1 4 . 2 mg. and 1 6 . 4 ^g. Per 100 c *c *
In c a s e 121, an a n te-p artu m e c la m p t ic , the f i r s t f i t
o c c u r r e d a t 4*30 a.m.
2 h ou rs l a t e r - a f t e r 4 f i t s - th e
b^ood ex a m in a tio n showed - u r ic a c id 1 1 .8 mg. per 100 c . c . ,
u r e a 40 mg. p e r 100 c . c . ; th e plasm a was v e r y red i n c o lo u r
and gave a n e g a t i v e r e a c t i o n t o th e i n d i r e c t van den Bergh
test.
The p a t i e n t had no more f i t s , but remained com atose.
6 hou rs a f t e r the f i r s t f i t th e plasma u r ic a c i d was 1 6 . 4
mg. p e r 100 c . c . , u rea 6l mg. p e r 100 c . c . , the plasm a was
dark orange i n c o lo u r and gave a p o s i t i v e r e a c t i o n to th e i n d i r : e c t van den Bergh t e s t - b i l i r u b i n 1 2 . 6 u n i t s .
The p a t i e n t
d ie d 2 h ou rs l a t e r .
At th e a u to p sy perform ed h a l f - a n - h o u r
PLATE
I.
Liver showing g r o s s eclamptic
haemorrhages.
( Oase
121 )
Low power vie?/.
S
II.
Liver showing patchy necrosis
and p e r i p o r t a l ec lam ptic
haem orrhages.
a&egg
$Sffe3l
H S ile
( Oase
145 )
«x w t *£*;S
Low power view.
PLATS
III.
» e :>aflg » w ^ S S i
Liver showing small periportal
4»%s«Mra&£HK
e c lam p tic haemorrhages.
HHKi
itai
fcfv#<*w T'UVS
( case
120 )
Low power view.
a f t e r d e a t h t h e l i v e r showed v e r y e x t e n s i v e a r e a s o f
haemorrhage.
(S e e p l a t e I . ) .
There were a l s o o e t e c h i a l
h a e m o r r h a g e s i n t h e c erebral c o r t e x and i n t h e i n t e r n a l
c a p s u l e t h e r e was a l a r g e h a e m o r r h a g e which h a d b u r s t i n t o
the t h i r d v e n t r i c l e .
I n c a s e 145? a post-parturn e c la m p tic w ith 3 f i t s b e fo r e
a d m issio n t o h o s p i t a l , th e plasm a u r i c a c i d v a lu e 12 h ou rs
a f t e r t h e f i r s t f i t was 8 . 3 mg. p er 100 c . c . , urea 57 mg. p e r
100 c . c .
The p a t i e n t d ie d 36 hours a f t e r the f i r s t f i t and
th e plasm a u r i c a c i d a t death was 1 4 .2 mg. per 100 c . c . a lth o u g h
she had no f i t s a f t e r a d m iss io n . B. urea 112mg. per 100 c . c .
At th e a u to p s y the l i v e r was y e l l o w i s h and th e r e were s e v e r a l
l a r g e deep red a r e a s o f haemorrhage. M i c r o s c o p i c a l l y th e r e
were numerous p e r i p o r t a l haemorrhages and a fev/ a r e a s o f
c o a g u l a t i v e n e c r o s i s a f f e c t i n g s e v e r a l l o b u l e s . (S e e p l a t e I I . ) .
In th e t h i r d f a t a l c a s e , c a s e 120, th e plasma u r i c acid,
v a lu e 2-g- h o u rs a f t e r th e f i r s t f i t and a f t e r 4 f i t s was 6 .2
mg. p er 100 c . c . , B. u rea 31 mS* Per TOO c *c * This p a t i e n t
had 6 f i t s during th e n e x t few hours but did not d ie u n t i l
21 hou rs a f t e r th e f i r s t f i t .
The plasma u r ic a c id v a lu e
a t d eath was 11 mg. per 100 c . c . ,
u r e a 69 mg. per 100 c . c .
The l i v e r a t th e post-m ortem e x a m in a tio n i n t h i s c a s e showed
numerous t i n y haem orrhages throughout i t s s u b s ta n c e , and
m i c r o s c o p i c a l l y o n l y sm a ll p e r i p o r t a l haem orrhages.w ere found.
( See p l a t e I I I . ).
In t h e s e th r e e f a t a l c a s e s th e plasma u r i c a c i d v a lu e s
a t d eath were p r o p o r t i o n a l to the e x t e n t o f the l i v e r damage.
The b lo o d u r e a v a l u e s r o s e s t e a d i l y a f t e r the f i t s had c e a se d .
The f a l l o f the plasm a u r i c a c i d towards normal
v a l u e s , a f t e r th e l a s t f i t ,
began e a r l i e s t i n p o st-partum
e c l a m p t i c s and l a t e s t i n ante-parturn c a s e s .
a c id v a lu e s fo r a l l c a se s ,
The mean u r i c
grouped a s p o st-p a r tu m , i n t r a ­
partum and a n te -p a r tu m , a r e p l o t t e d i n Chart V I I . to show
th e changes o c c u r r in g a f t e r the l a s t f i t .
As b e fo r e a
c o r r e c t i o n h a s been made f o r the changes due t o the d u r a t io n
o f la b o u r .
The base l i n e o f th e graph r e p r e s e n t s th e u r i c
a c id v a lu e im m e d ia te ly a f t e r th e l a s t f i t i n each c a s e .
I t w i l l be s e e n t h a t a mean r i s e o f 0 . 5
100 c . c .
u r ic a c id per
o c c u r s i n each group a f t e r th e l a s t f i t ,
and t h a t
QUART 7IJA
G-raph show ing Changes i n P la sm a U r i c A c id a f t e r l a s t
ttOtlRS
ft- FT E A L-AST
F*-»"
IN
P * 4 Td r \
f i t i n A n te ra r tu rn , I n t r a p a r t u m and P o s t u a r t u m C a s e s ,
'V wv*
“5-3 oO I V 3 J ‘bu> *. (LI ofc; V V n v w o t d
w I s-3 bhi-u-M o
i n p o st-p a r tu m c a s e s t h e f a l l b e g in s 4 h o u r s , i n i n t r a ­
partum c a s e s 12 h o u rs and i n t h e ante-partum c a s e s 24 h ou rs
a f t e r th e l a s t f i t .
There a r e c o r r e sp o n d in g d i f f e r e n c e s in
the r a t e o f th e su b seq u en t f a l l , p r o b a b ly r e l a t e d to t h e
grea ter ease o f e x c r e tio n o f u r ic a c id a f t e r d e liv e r y .
The E f f e c t o f Labour.
The e f f e c t o f la b o u r , a p a r t from f i t s ,
i s most
c l e a r l y d em on stra ted i n th e p a t i e n t s who r e c o v e r e d from
ante-partum e c la m p s ia and d id not go i n t o la b o u r u n t i l
some days l a t e r .
Most o f th e ante-partum c a s e s i n t h i s
s e r i e s were n o t a d m itte d to h o s p i t a l u n t i l s e v e r a l hours
a f t e r th e o n s e t o f f i t s and, i n t h e s e c a s e s , the u r ic a c i d
v a lu e s o b t a in e d on a d m iss io n were t h e r e f o r e v e r y h ig h .
The mean u r i c a c i d v a lu e fo r th e 16 ante-partum c a s e s
measured a f t e r th e f i t s had s to p p e d , but b e fo r e the o n s e t
o f la b o u r , was 8 . 4 mg* Pe r 100 c . c . ,
w ith a range o f 6 .2
to 1 1 . 5 mg* p e r 100 c . c . S e v e r a l o f t h e s e p a t i e n t s improved
c l i n i c a l l y a f t e r the f i t s and th e p regnancy was a llo w e d to
c o n tin u e f o r a few d a y s.
P a r a l l e l to t h i s c l i n i c a l
improvement t h e r e was a s t e a d y f a l l i n u r ic a c i d v a lu e s
u n t i l th e o n s e t o f la b o u r .
During la b o u r the f a l l i n u r i c
a c i d was a r r e s t e d and i n many c a s e s th e r e was an a b s o l u t e
r ise .
Chart V I I I .
shows th e changes o c c u r r in g i n th e
plasma u r i c a c i d f o r a few days b e fo r e and a f t e r the tim e o f
d e l i v e r y i n 10 o f t h e s e an te-partum e c la m p t ic c a s e s .
The
p o i n t s p l o t t e d r e p r e s e n t th e mean o f th e a c t u a l u r ic a c i d
v a lu es.
The c h a r t shows th e r a p id f a l l i n u r i c a c id a f t e r
CHART V I I I
u f tic
f l c i y ; tAc
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G-raph slio v d n g C h an ges i n P I assma U r ic A c id d u r in g L abour
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l j HoyA. S
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th e f i t s ,
i n t e r r u p t e d by a s h o r t r i s e due to la b o u r.
r i s e o c c u r s on a f a l l i n g c u r v e.
This
The r e a l e x t e n t o f t h e r i s e
i s o f c o u r s e t o be c a l c u l a t e d from the c o n t i n u a t i o n o f th e
p r e c e d in g p a r t o f th e c u rv e on through the tim e when la b o u r ,
d e l i v e r y and the f i r s t t h r e e days o f the puerperium a c t u a l l y
o c cu rr ed .
The r i s e i s then found to be a lm o st i d e n t i c a l
w ith t h a t which o c c u r s i n normal p a t i e n t s who have th e same
d u r a tio n o f l a b o u r , a s i s shown a t th e bottom o f Chart V III.
C o n s id e r a t io n o f th e i n d i v i d u a l c a s e s g i v e s th e same c o n c lu s io n ;
i n each c a s e t h e e x t e n t o f th e r i s e i n u r i c a c id d u rin g la b o u r
i s p r o p o r t i o n a l to th e l e n g t h o f la b o u r and eq u al to t h a t
which o c c u r s i n normal c a s e s w ith th e same l e n g t h o f la b o u r.
In th e in tr a -p a r tu m c a s e s the e f f e c t s o f la b o u r and
f i t s on th e plasm a u r i c a c i d a r e superim posed.
In Chart V III.
t h e mean u r i c a c i d v a l u e s f o r 6 in tr a -p a r tu m e c la m p tic c a s e s
a r e p l o t t e d to show th e changes o c c u r r in g b e fo r e and a f t e r
d e l i v e r y ; t h e o n l y c a s e s u sed a r e th o s e i n which v a lu e s were
o b t a in e d b e f o r e t h e o n s e t o f th e f i t s and o f la b o u r.
The
o r i g i n a l v a lu e i n t h e s e c a s e s was o n ly m o d e ra te ly r a i s e d
(mean 5 . 4 mg. p e r 100 c . c . ) ,
but th e u su a l ra p id r i s e o c cu rr ed
in r e l a t i o n to th e o n s e t o f f i t s .
When the c a s e s a r e arranged
a c c o r d in g t o th e l e n g t h o f la b o u r th e u r ic a c id r i s e d u rin g
la b o u r i s found to be much g r e a t e r than t h a t o f normal p a t i e n t s
w ith th e same l e n g t h o f la b o u r ; th e d i f f e r e n c e b ein g the r i s e
due to th e f i t s .
P ost-p a rtu m e c la m p t ic s show s i m i l a r u r ic a c i d
changes r e l a t e d t o la b o u r and f i t s .
The r i s e du rin g la b o u r
34.
i s s i m i l a r t o t h a t i n normal p a t i e n t s w ith th e same l e n g t h
o f la b o u r b u t, a f t e r d e l i v e r y , th e u s u a l r a p id r i s e b e g in s
a f t e r th e f i r s t f i t .
I t may t h e r e f o r e be con olu d ed t h a t la b o u r c a u s e s
th e same r i s e i n plasm a u r i c a c i d i n e c la m p t ic c a s e s a s i n
normal and n o n - c o n v u l s i v e toxaem ic c a s e s .
Urea F in d in g s .
The plasm a u rea f i n d i n g s i n t h e s e e c la m p tic p a t i e n t s
were much l e s s s t r i k i n g and l e s s c o n s i s t e n t than th e u r i c
a c id f i n d i n g s .
In i n d i v i d u a l c a s e s changes i n plasma u rea
d id n ot c o i n c i d e w ith ch a n g es i n plasma u r ic a c i d , and a
c o n s t a n t p r o p o r t i o n betw een th e v a lu e s o f t h e s e two n i t r o g e n
f r a c t i o n s was n ot found.
F in d in g s B efo re Onset o f F i t s .
Table IV.
shows th e plasma urea f i n d i n g s b e f o r e
t h e o n s e t o f f i t s and la b o u r .
These are tak en from th e
same s e r i e s o f c a s e s a s i n Table I I I . , though th e number
o f p a t i e n t s i n whom u r e a was e s t im a t e d i s r a t h e r l e s s .
Table IV.
Plasma Urea V a lu es i n Normal and N on-C onvulsive Toxaemic
P a t i e n t s a t Term and i n E clam p tic P a t i e n t s b e fo r e th e
Development o f F i t s .
Number o f
C ases.
Plasma Urea. Mg. p e r 100 c . c .
Mean.
Normal P regn an t.
M ild P r e - e c la m p t ic .
Severe P r e - e c la m p t ic .
E clam p tic b e fo r e F i t s .
12
18
20
9
18
21
30
32
h-
Range.
16
8
15
21
to
to
to
to
21
32
55
47
CHART IPC.
Graph sho w ing Gh.ono*e s i n P I asima u r e a a f ’t e r th e F i r s t
(P la sm a u r i c a c i d c hang es ; from th e same c a s e s
a r e shown f o r com p ariso n L . )
«
« ;
UK I C ftC I
* ...... -^. WAf«.
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35.
In c o n t r a s t to th e u r ic a c i d f i n d i n g s ,
urea v a lu e i n t h e s e e c la m p t ic c a s e s ,
onset o f f i t s i s ,
the plasma
im m ed ia tely b e fo r e th e
i f a n y t h in g , s l i g h t l y h ig h e r than th e
mean plasm a u rea i n th e s e v e r e n o n - c o n v u ls iv e p r e - e c la m p t ic
c a s e s a t t h e same s t a g e i n t h e i r pregnancy.
The E f f e c t o f F i t s .
A fter the on set of f i t s ,
w h ile th e plasma u r i c
a c i d was mounting r a p i d l y , the plasma urea was found to
change v e r y l i t t l e .
I n a few c a s e s th e u r e a va lu e f e l l
s l i g h t l y f o r 1 t o 2 h ou rs a f t e r the o n s e t o f f i t s w h ile
i n o t h e r s i t rem ained more or l e s s c o n s t a n t .
S e v e r a l hours
a f t e r th e f i r s t f i t i t began t o r i s e i n most c a s e s ; t h i s
occu rr ed s l o w l y and c o n t in u e d f o r v a r y in g l e n g t h s o f tim e.
N e ith e r th e h e i g h t o f the r i s e nor i t s d u r a tio n appeared
to have any r e l a t i o n to the number o f f i t s ;
a few p a t i e n t s
w ith numerous f i t s did not show any i n c r e a s e i n plasma urea
v a lu e a t a l l ,
w h ile s e v e r a l w ith o n ly one or two f i t s showed
a d e f i n i t e i n c r e a s e l a s t i n g fo r 2 to 4 days.
The mean plasm a urea changes i n 8 o f the c a s e s
examined b e f o r e and a f t e r th e o n s e t o f f i t s a r e shown i n
Chart IX. ; t h e mean plasm a u r i c a c id f i n d i n g s from t h e same
c a s e s a r e i n c lu d e d f o r com parison.
The r i s e i n u rea l a g g e d
behind th e r i s e i n u r i c a c id ; i n many c a s e s the maximum
blood u rea v a lu e was rea c h e d about 24 hours a f t e r th e l a s t
fit.
Very h ig h u r e a v a l u e s w ith a much d e la y e d r e tu r n to
normal o c c u r r e d i n th e same c a s e s i n which the h ig h u r i c
a c i d v a l u e s p e r s i s t e d f o r s e v e r a l days and were r e l a t e d to
a p e r io d o f o l i g u r i a .
The E f f e c t o f Labour.
I t h as been found to be i m p o s s ib le to dem onstrate
c l e a r l y t h a t la b o u r c a u s e s changes i n plasm a u r e a s i m i l a r
t o t h o s e a lr e a d y shown to o c cu r i n t h e plasm a u r ic a c i d .
The r e a s o n s f o r t h i s a r e , t h a t th e changes o f plasma u r e a
f o l l o w i n g c o n v u l s io n s a r e i r r e g u l a r and ten d to be p r o lo n g e d ,
th u s f r e q u e n t l y o b s c u r in g the e f f e c t o f la b o u r; and a l s o ,
th a t any r i s e i n plasm a u r e a which i s caused by la b o u r o c c u r s
l a t e r th a n th e u r i c a c i d r i s e and i s sm all i f the la b o u r i s
sh ort.
In a few o f th e c a s e s o f th e p r e s e n t s e r i e s , however,
i n which a week o r more e la p s e d between th e f i t s and la b o u r ,
th e f i n d i n g s i n d i c a t e t h a t changes o f plasm a u r e a , due t o
la b o u r , o c c u r a s i n normal c a s e s .
37.
The E f f e c t o f C o n v u lsio n s on Plasma U r ic A cid
and Urea i n Non-Pregnant P a t i e n t s , and i n A n im als.
The o c c u r r e n c e o f th e u r ic a c i d r i s e im m ed ia tely
a f t e r th e f i r s t e c la m p t ic f i t ,
and th e p r o p o r tio n between
th e h e i g h t o f th e r i s e and th e number o f f i t s ,
su ggests th at
the r i s e i s a d i r e c t con seq u en ce o f th e f i t s .
In ord er to
in v e s tig a te t h i s p o in t,
th e u r i c a c i d f i n d i n g s i n a s e r i e s
o f 10 p a t i e n t s (C a s e s 146 to 155) r e c e i v i n g “c o n v u ls io n
th e r a p y *1 f o r m en tal d i s o r d e r s , were s t u d ie d .
Most o f th e
p a t i e n t s were women betw een t h e a g e s o f 20 and 40 y e a r s , who
were s u f f e r i n g from s c h iz o p h r e n ia or m a n ic -d e p r e s s iv e p s y c h o s i s
but were p h y s i c a l l y h e a l t h y .
The c o n v u ls a n t drug used was
Azoman, a p r o p r i e t a r y p r e p a r a t i o n s i m i la r to C a r d ia z o l.
It
i s g i v e n i n t r a v e n o u s l y ; t h e l a t e n t p e r io d between the i n j e c t i o n
and th e c o n v u l s i o n i s v e ry sh o r t (5 secon d s to 10 m in u te s ).
For th e p r e s e n t stu d y 4 blood sam ples were ta k en
f o r ex a m in a tio n ; one im m e d ia te ly b e fo r e th e i n j e c t i o n o f
Azoman and t h e o t h e r s a t h a l f - a n - h o u r , fo u r h o u rs, and tw en ty
fou r h o u rs a f t e r t h e f i t .
Plasma u r i c a c i d and urea were
e s t im a t e d i n a l l sam p les.
Two o f th e p a t i e n t s (C a ses 154 a*nd
1 5 5 ) d id not c o n v u ls e a f t e r th e i n j e c t i o n ,
due t o i n s u f f i c i e n t
dosage o r a c q u ir e d t o l e r a n c e to th e drug; t h e s e two s e r v e a s
c o n t r o l s f o r th e a c t i o n o f t h e drug i t s e l f .
shown i n Table V.
The r e s u l t s a r e
f l CTUHU
A lS E
in
UfttC.
rt-Cl7> :
J. f t *
II?OC_<.
T i_ A S M fl.
Graph showing Changes i:i P la s m a U r i c A c id a f t e r as on on
C o n v u lsio n s.
o
fits
P i UST Fi-r
H otM 5
AFTER.
FiM T
FiT.
Table V.
Mean U r ic Acid and Urea Changes a f t e r Azoman C o n v u lsio n s in
Uon-Pregnant P a t i e n t s .
U r ic A cid.
Mg. p e r 100 c . c
Number
of
Fits.
Before
F its.
Urea.
Mg. p e r 100 c . c .
A fter F its .
B efore
^ hr.
4 h r s . 24 h r s F i t s .
i h r.
A fter F its .
4 hrs.
24 h r s .
0
3 .8
3 -5
3 .8
-
28
24
25
1
3*2
4 -3
5 -3
4 .1
22
22
23
27
2
3 .3
4 .9
8 .7
6. 4
25
26
25
37
‘
-
In Chart X. t h e changes i n th e plasm a u r ic a c i d f o l l o w i n g
th e f i t a r e p l o t t e d a s i n Chart VI.
In every c a s e a f t e r
t h e c o n v u l s io n t h e r e was an im mediate r i s e i n plasma u r i c
a c id .
The r i s e c o n t in u e d f o r 3 t o 4 h o u rs, a f t e r which
tim e th e v a l u e s s l o w l y r etu r n e d to normal, b u t, a t 24 hours
a f t e r th e f i t
a ll cases.
t h e y were s t i l l above th e o r i g i n a l v a lu e i n
In one c a s e (C ase
s e v e r e c o n v u l s io n s ;
146) th e p a tie n t
had two
i t w i l l be seen from th e t a b l e and
Chart t h a t th e r e s u l t a n t r i s e i n u r i c a c i d was much g r e a t e r
than i n t h e c a s e s w ith o n l y one c o n v u ls io n .
This, i s i n
agreement w ith t h e f i n d i n g s i n ecla m p sia ; but i t w i l l be
n o t i c e d t h a t th e r i s e i n plasm a u r i c a c i d i n t h e Azoman
c a s e s i s even
g r e a t e r th a n i n th e e c la m p t ic s . In the two
c a s e s w ith o u t
c o n v u l s io n s th e plasma u r ic a c id
d id n o t show
any change, i n d i c a t i n g t h a t the r i s e i n u r ic a c i d i n t h e
39.
o th e r c a s e s was due to th e c o n v u l s io n and not to th e drug
itse lf.
In a l l c a s e s th e plasm a u rea v a l u e s remained
p r a c t i c a l l y c o n s t a n t f o r a lo n g time a f t e r th e f i t s ,
b u t,
sometimes th e v a l u e s o b t a in e d 24 hours a f t e r th e c o n v u ls io n
showed a s l i g h t r i s e .
This f i n d i n g i s very s i m i l a r t o th e
changes i n e c la m p t ic p a t i e n t s .
The change i n plasm a u r ic a c i d a f t e r t h e s e
a r t i f i c i a l l y produced c o n v u l s io n s was a l s o s t u d i e d i n 14
r a b b i t s ; an i n j e c t i o n o f th e a p p r o p r ia te dose o f Azoman
was g i v e n i n t r a v e n o u s l y and a t y p i c a l c o n v u ls io n w ith t o n i c
and e l o n i c p h a s e s o c c u r r e d w i t h i n a few se c o n d s .
In e v e r y
c a s e t h e r e was a r i s e i n plasm a u r ic a c i d soon a f t e r t h e
c o n v u l s io n .
The mean r e s u l t s a r e shown i n Table VI.
Table VI.
R ise i n Plasma U ric A cid due to
Azoman C o n v u lsio n s i n R a b b its.
B e fo r e I n j e c t i o n .
Plasma U ric Acid: Mr . p er 100 c . c .
0 .5
i hour a f t e r f i t .
2.7'
2 h ou rs a f t e r f i t .
3 .1
4 h o u rs a f t e r f i t .
1 .7
I t was found t h a t i f th e p ro ced u re was r e p e a te d on one
r a b b it on s u c c e s s i v e d a y s, th e u r i c a c id r i s e f o l l o w i n g a
c o n v u l s io n became l e s s .
The p a t i e n t s r e c e i v i n g “c o n v u ls io n
therapy" were made to c o n v u ls e ev er y t h i r d d ay, but a
40.
r e d u c tio n i n t h e u r i c a c i d r i s e was not n o te d i n t h e s e
p a t i e n t s , even a f t e r s e v e r a l weeks o f t h i s tre a tm e n t.
The r e s u l t s from t h i s s e r i e s o f c a s e s i n d i c a t e
th a t n o n -e c la m p tic c o n v u l s io n s c a u se a r a p id and marked
r i s e i n plasm a u r i c a c i d though th e y c a u se l i t t l e
change i n th e plasm a u rea l e v e l .
immediate
This g i v e s f u r t h e r su pp ort
to th e v iew t h a t th e h ig h u r i c a c i d v a l u e s , found i n
e c la m p t ic p a t i e n t s some hours a f t e r th e o n s e t o f f i t s ,
have been c a u se d i n g r e a t p a r t by th e b o n v u ls io n s p e r s e .
Wuth ( 1 9 2 6 ) s t u d i e d the b lo o d changes i n e p i l e p t i c c a s e s
a f t e r c o n v u l s io n s ; h i s e s t i m a t i o n s were made once or t w ic e
on each p a t i e n t but o n l y a t i n t e r v a l s o f 24 hours or more.
H is f i n d i n g s show a r i s e in th e n o n - p r o t e i n n i t r o g e n , u r i c
a c i d and c r e a t i n i n e v a l u e s f o l l o w i n g e p i l e p t i c c o n v u l s io n s .
This i s presum ab ly a s i m i l a r e f f e c t to th a t i n e c la m p s ia
or i n Azoman c o n v u l s i o n s .
D isc u ssio n .
The plasm a u r i c a c i d i n e c la m p tic p a t i e n t s i s
i n f l u e n c e d by t h r e e f a c t o r s - la b o u r , p r e c e d in g h y p e r t e n s i v e
toxa em ia and c o n v u l s i o n s .
Labour c a u s e s th e same changes
i n plasm a u r i c a c i d i n t h e s e c a s e s a s i n normal c a ses, though
the r i s e due to t h i s c a u se
i n e c la m p tic c a s e s ,
sm a ll b e c a u se th e la b o u r i s u s u a l l y s h o r t .
is often
The u r ic a c i d
v a lu e b e fo r e th e o n s e t o f f i t s and la b o u r may show a s l i g h t
r e l a t i o n t o th e c l i n i c a l s e v e r i t y o f the tox aem ia , but i t
i s o f t e n s u r p r i s i n g l y low .
By f a r the most im portant f a c t o r
i n c a u s in g a h ig h u r i c a c i d v a lu e i n e c la m p tic c a s e s i s th e
-i'Ll »
A verage U r i c A c id Yaln.es i n 110 E c l a m p tic and S3 l-'ree c la m p tic C ases.
( S t s n d e r and Cadden, 1.934 1 . )
!
ECL<*r*TS <ft
^RE-ECLAfVPSt i*t
UR. 1C
rtcip
v a u ts
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60
op
r t o ^ w * t,
(j r i c , R c » ; p
v » L .u e s,
JftyS AntCPfldT uiA.
y fly S
' P O S T T> a r t u r v .
very r a p id i n c r e a s e which i s caused by th e a c t u a l c o n v u ls io n s ;
the e x t e n t o f t h i s i n c r e a s e i s r e l a t e d to the number o f
c o n v u ls io n s .
High v a l u e s f o r u r i c a c i d i n e c la m p sia have been
rep orted by v a r io u s workers (W illia m s , 1 9 2 1 ; C a ld w ell and Lye,
1921; K i l l i a n and Sherw in, 1921; H ellmuth, 1923; Heynemann,
1924; P l a s s , 1924;
S ta n d er, 1924; Stan der, Duncan and S i s s o n ,
1925; Bokelmann and R oth er, 1925; Stander and R a d e le t, 1 9 2 6 ;
Cruickshank, H ew itt and Couper, 192J; Stander and Cadden, 1 9 3 4 ).
In most c a s e s t h e s e can be s u f f i c i e n t l y e x p la in e d by th e f a c t
th a t th e d e t e r m in a t io n s were alw a ys made some tim e a f t e r th e
onset o f f i t s .
S tan der and Oadden ( 1 9 3 4 b ), s t a t e t h a t , th e h ig h u r i c
a c id v a l u e s i n e c la m p tic p a t i e n t s ar e out o f a l l p r o p o r t io n to
the s l i g h t ch an ges i n th e o t h e r n i t r o g e n o u s c o n s t i t u e n t s o f th e
blood and a r e p r e s e n t b e fo r e t h e outb reak o f c o n v u ls io n s ; t h e y
g iv e f i g u r e s to su pp ort t h i s s t a t e m e n t , however, not from
e c la m p tic p a t i e n t s b e f o r e c o n v u ls io n s but from p r e - e c la m p tic
p a t i e n t s who did not d e v e lo p c o n v u l s io n s .
They show a c h a r t
o f th e "average u r i c a c i d v a lu e s i n 110 e c la m p tic and 38 p r e ­
ecla m p tic c a se s" ( s e e Chart X I .) and s t a t e t h a t th e y a r e un able
to e x p l a i n th e d e p r e s s i o n i n the c u r v es s h o r t l y b e fo r e d e l i v e r y ,
but t h a t t h i s may prove o f s i g n i f i c a n c e when more i s known about
purine m eta b o lism .
I t seems o b v io u s from th e p r e s e n t r e s u l t s
th at t h i s d e p r e s s i o n i s an a n t e f a c t due to th e i n c l u s i o n o f both
ant e -p a r turn and i n t r a - p a r turn e c la m p tic c a s e s ; th e u r i c a c i d
va lu e s i n an te-p a rtu m e c l a m p t i c s , r e c o v e r in g from f i t s ,
fa ll
42.
f a l l b e f o r e t h e o n s e t o f la b o u r and th e v a lu e s i n i n t r a ­
partum e c l a m p t i c s b e f o r e la b o u r a r e low .
The g r e a t i n c r e a s e
in u r i c a c i d v a l u e s s e e n d u rin g la b o u r i s due to th e normal
r i s e due t o la b o u r i n both ant e -p a r turn and in tr a -p a r tu m c a s e s ,
t o g e t h e r w ith th e r i s e due to f i t s i n th e in tra-p a rtu m c a s e s .
Cadden and S ta n d er ( 1939 )> i n & f u r t h e r i n v e s t i g a t i o n
o f the b io c h e m ic a l f i n d i n g s i n e c la m p s ia , g iv e t a b l e s showing
the f i n d i n g ’’b e f o r e , d u rin g and a f t e r c o n v u ls io n s . ”
Their
f i g u r e s show h i g h e s t u r i c a c i d v a l u e s during c o n v u ls io n s but
th e e s t i m a t i o n s were n o t made f r e q u e n t l y enough to show th e
d e f i n i t e r e l a t i o n betw een the u r i c a c i d v a l u e s and th e
c o n v u l s io n s .
They found no impairment o f u r i c a c id e x c r e t i o n
i n t h e i r c a s e s and c o n c lu d e d t h a t th e h ig h v a lu e s were not due
to r e n a l i n s u f f i e n c y but were p ro b a b ly th e r e s u l t o f d im in ish e d
u r ic a c i d d e s t r u c t i o n i n th e l i v e r .
In the p r e s e n t s e r i e s th e
g r e a t r a p i d i t y o f th e r i s e i n plasm a u r i c a c i d i n a l l c a s e s ,
w ithout any c o n c o m ita n t r a p id r i s e in the b lo o d u rea, s u g g e s t s
a sim ila r c o n c lu sio n , i . e .
t h a t the r i s e i s due t o some i n c r e a s e
in u r i c a c i d p r o d u c t io n or d im in ish e d u r i c a c i d d e s t r u c t i o n
r a th e r th a n t o a r e n a l r e t e n t i o n .
Some e c la m p tic p a t i e n t s do
show e v id e n c e o f im p a ired r e n a l f u n c t i o n ( o l i g u r i a , r i s i n g
blood u r e a and p e r s i s t e n c e o f h ig h u r i c a c id v a lu e s ) a f t e r th e
c o n v u ls iv e p e r i o d ( o f t e n f o r 24 to 43 hours a f t e r th e l a s t f i t ) ,
and t h i s e v id e n c e p e r s i s t s u n t i l a good u r in a r y outp ut i s
e sta b lish e d .
This r e n a l impairment appears l a t e i n th e d i s e a s e
end o n ly i n some o f th e c a s e s .
Stander and Cadden ( 1934 b) and
43.
Frey ( 1 9 2 3 ) , r e c o r d s i m i l a r f i n d i n g s .
I t i s o f i n t e r e s t to
note t h a t Dunn and P o is o n (1 9 2 6 ) o b ta in e d a marked r i s e i n
blood u r e a i n r a b b i t s a f t e r th e in tr a v e n o u s i n j e c t i o n o f v e r y
la r g e amounts o f u r i c a c i d .
This was, however, due to a
s p e c i f i c damage to t h e k id n ey ; t h e r e i s l i t t l e
e v id e n c e t h a t
the r e l a t i v e l y low u r i c a c i d l e v e l s i n e cla m p sia have any
comparable e f f e c t on th e human k id n e y .
The p r e s e n t work d oes not in c lu d e any d i r e c t attem p t
to a s c e r t a i n th e c a u se o f th e u r i c a c i d r i s e a f t e r c o n v u l s io n s .
I t h as been shown by v a r io u s workers t h a t , a f t e r c o n v u l s io n s ,
t h e r e i s an i n c r e a s e i n b lo o d su g a r, (M aclean, 1936; T it u s ,
W i l l e t t s and L ig h tb o d y , 193 °)> b lo od l a c t i c a c i d (S ta n d e r and
R a d e le t, 1 9 2 6 ) , and in o r g a n ic p h o sp h ate (S ta n d e r , Duncan and
S is s o n , 1 9 2 5 ); t h e s e b lo o d f r a c t i o n s are a l l p r o d u c ts o f m uscle
m etabolism and a r e produ ced, presum ably, by th e m uscular e f f o r t
o f th e c o n v u l s io n .
B urian and Schnur ( 1910 ) have shown t h a t
u r ic a c i d i s formed by th e b rea k d cm o f m uscle h yp oxa n th in e
and i t i s presum ably a l s o produced by the a c tu a l m uscular e x e r t i a i
during a c o n v u l s io n .
In a h e a l t h y s u b j e c t , however, F o l i n ,
Berglund and D e r r ic k ( 1924 ) have shewn t h a t any e x c e s s o f u r i c
a c id i s e i t h e r e x c r e t e d or r a p i d l y d e str o y e d i n th e body.
The
s i t e o f u r i c a c i d d e s t r u c t i o n i n th e dog has been shown to be
the l i v e r (B ollm an, Mann and Magath, 1925 ; Gremels and Bodo, 1 9 2 6 ),
and i t i s p o s s i b l e t h a t some u r i c a c i d may be d e s tr o y e d n orm a lly
by th e human l i v e r .
I t may, t h e r e f o r e , be assumed t e n t a t i v e l y
th at th e r i s e o f plasm a u r i c a c i d a f t e r e c la m p tic c o n v u l s io n s
i s due t o one o r both o f t h e s e f a c t o r s : i n c r e a s e d u r i c a c i d
p r o d u ctio n by t h e m uscular e x e r t i o n , and d im in ish e d d e s t r u c t i o n
o f u r ic a c i d by t h e l i v e r .
Summary.
The ch an ges i n plasm a u r i c a c i d and urea o c c u r r in g
b e fo r e , d u r in g and a f t e r c o n v u l s io n s i n la b o u r have been s t u d i e d
i n a s e r i e s o f e c la m p t ic p a t i e n t s .
A r i s e o f plasma u r i c a c i d
was found to o c c u r i n e v e r y c a s e im m ed ia tely a f t e r th e o n s e t
of f i t s ,
of f it s .
t h e h e i g h t o f the r i s e b e in g dependent on th e number
Plasma u r e a v a l u e s showed l i t t l e
immediate change
a f t e r f i t s but a r i s e was o f t e n noted 24 or more hours l a t e r .
S im ila r f i n d i n g s were o b t a in e d a f t e r a r t i f i c i a l l y produced
c o n v u l s io n s i n non -pregn ant p a t i e n t s and r a b b i t s .
In e c la m p t ic p a t i e n t s la b o u r c a u se s t h e same changes
i n plasm a u r i c a c i d a s i n normal c a s e s .
45 .
S E C T I O N
IV.
CHANGES IN BLOOD CONCENTRATION IN NORMAL AND
!
TQXAEMIC PREGNANCY*
The o c c u r r e n c e o f hydraernia during pregnancy
has been known f o r many y e a r s , and has been shown by many
workers u s i n g a v a r i e t y o f methods (N a s se , 1876; Meyer,
1887 ; R e g n a u lt, 1904 ; Z a n g em e ister , 1904 ; Zunst, 1911 ;
M i l l e r , K e ith and Rowntree, 1915 ; Mahnert, 1921 ; P la s s
and B o g e r t, 1924 ; P l a s s and M atthews, 1926; Schoenh olz,
1929 ; S k aja a, 1929 ; Dieckmann and Wegner, 1934 a; Oberst
and P l a s s , 1935 and 1936; and Thomson, H irsh eim er, Gibson
and Evans, '1 938 ).
More r e c e n t l y i t h a s been shown t h a t ,
i n the h y p e r t e n s i v e to x a em ia s o f l a t e pregnancy, the normal
hydraernia i s o f t e n a b s e n t and the b lood may be abnorm ally
c o n c e n tr a t e d .
Rapid changes i n the c o n c e n t r a t i o n o f th e
blood have been shown to occu r i n t h e s e p a t i e n t s e s p e c i a l l y
about th e tim e o f d e l i v e r y .
These r a p id changes i n
c o n c e n t r a t i o n cannot be measured by d i r e c t e s t i m a t i o n s o f
blood volume, a s t h e s e methods in v o l v e i n j e c t i o n s o f dyes
and cannot be r e p e a t e d a t s h o r t i n t e r v a l s o f time i n th e
same p a t i e n t .
Most a u th o r s a r e ag reed t h a t , ov e r sh o r t
p e r io d s o f tim e , ch an ges i n the p r o p o r t io n o f c e l l s to
plasma, a s shown by r i s e and f a l l i n b lo od -h a em o glob in ,
r ed -b lo o d c e l l count and h a e m a to c r it r e a d in g , may, i n t h e
absence o f haemorrhage, be ta k e n a s a f a i r l y a c c u r a te in d ex
o f v a r i a t i o n i n t o t a l b lo o d or plasma volum es, produced by
changes i n t h e w a ter c o n t e n t o f th e plasm a.
Of t h e s e m ethods,
the h a e m a to c r it h a s been u sed most f r e q u e n t l y i n th e stu d y o f
t h e s e to x a em ic p a t i e n t s .
Skajaa ( 1 9 2 9 ) ,
Schwartz and Dieckmann ( 1 9 2 9 ) , and
Dieckmann (1 9 3 3 ) i n v e s t i g a t e d h aem oglobin and h a e m a to c r it
at v a r io u s i n t e r v a l s b e f o r e and a f t e r d e l i v e r y i n p r e -e c la r a p tic
p a tie n ts.
They found r a i s e d v a l u e s b e fo r e d e l i v e r y i n d i c a t i n g
a r e d u c t io n o f b lo o d volume due to c o n c e n t r a t io n o f b lo od , and
a g r e a t f a l l i n v a l u e s d u rin g the f i r s t few days o f th e
puerperium , i n d i c a t i n g an i n c r e a s e in blood volume due to
d i l u t i o n o f b lo o d a t t h a t tim e.
Skajaa ( 1 9 2 9 ) , and Schwartz and Dieckmann (192 9)
emphasized th e r e l a t i o n between the blood c o n c e n tr a t io n and
the to xaem ia and. c o n c lu d e d th a t the marked post-partum
d i l u t i o n was due to th e abatem ent o f the toxaem ia.
In a
more d e t a i l e d s tu d y , Dieckmann ( 1933 ) found th a t th e p o s t ­
partum d i l u t i o n o f th e b lo o d o c c u r r e d i n p r e - e c la m p t ic
c a s e s but n ot i n c h r o n ic toxaem ic c a s e s and s u g g e s t e d t h a t
t h i s f a c t m ight be u s e d i n d i f f e r e n t i a t i n g the two ty p e s o f
cases.
Sk ajaa ( 1929 ) and Dieckmann ( 1933 ) were unable to
fin d any c o r r e l a t i o n betw een post-p a rtu m blood d i l u t i o n and
the amount o f oedema p r e s e n t .
On the o th e r hand, P l a s s and
Bogert (1 9 2 4 ) i n an i n v e s t i g a t i o n o f plasma p r o t e i n v a r i a t i o n s
in normal and tox aem ic p a t i e n t s found plasma d i l u t i o n a f t e r
47 .
d e l i v e r y i n both t y p e s o f p a t i e n t s but more marked i n th e
toxaemic o n e s .
They n o te d t h a t the d i l u t i o n c o in c id e d w ith
the d is a p p e a r a n c e o f oedema, and con clu d ed th a t th e d i l u t i o n
was due t o th e oedema f l u i d e n t e r i n g the b lo o d -str e a m .
They
su g g e ste d t h a t t h e e x t e n t o f th e d i l u t i o n v a r ie d w ith th e e x t e n t
o f the oedema but t h e y d id n o t attem p t to prove t h i s .
A d e t a i l e d s tu d y d oes n o t appear to have been made
o f the changes i n b lo o d c o n c e n t r a t i o n i n normal c a s e s about
the tim e o f d e l i v e r y .
i n 1924,
Denecke, from a r ev iew o f the l i t e r a t u r e
s t a t e d t h a t a r e d u c t i o n o f b lood volume may be found
during la b o u r i n normal c a s e s .
Payer ( 1 9 0 4 ) , Carton ( 1 9 2 4 ) ,
and Horvath (1 9 2 4 ) have shown t h a t i n c a p i l l a r y blood an i n c r e a s e
o f a h a l f to one m i l l i o n i n the r e d -b lo o d c e l l count may occur
during la b o u r w ith a r e t u r n to normal i n the puerperium;
E c k e lt ( 1 9 1 9 ) n o te d s i m i l a r changes i n the plasma p r o t e i n s i n
normal c a s e s .
This i n c r e a s e was thou ght to be due to th e
muscular e f f o r t and i n c r e a s e d abdominal p r e s s u r e du rin g la b o u r
c a u s in g more b lo o d to be d r iv e n i n t o the p e r ip h e r a l c i r c u l a t i o n .
The changes a f t e r d e l i v e r y were a t t r i b u t e d to b lood l o s s and
the f i l l i n g up o f t h e s p la n c h n ic c i r c u l a t i o n .
Dieckmann and
Wegnel (1 9 3 4 a ) s t u d i e d changes i n blood and plasma volumes i n
a la r g e s e r i e s o f normal p a t i e n t s , but o n ly fo u r p a t i e n t s were
examined f r e q u e n t l y d u rin g la b o u r and the e a r l y puerperium .
In t h e s e fou r p a t i e n t s ,
changes i n h a e m a to c r it v a lu e s were
found i n d i c a t i n g c o n c e n t r a t i o n o f the blood during la b o u r and
d ilu tio n afterw ard s.
O berst and P la s s ( 193 ^) found in c r e a s e d
c o n c e n tr a t io n o f plasm a and c e l l s e a r l y i n la b o u r and a
fu r th e r i n c r e a s e i n c o n c e n t r a t i o n a t d e l i v e r y .
however, found l i t t l e
Skajaa ( 1 9 2 9 ) ,
or no change i n h a e m a to c r it v a l u e s i n
h i s normal c a s e s ; t h e y were, however, not examined a t fr e q u e n t
r e g u la r i n t e r v a l s .
The p r e s e n t pap er i s a d e t a i l e d stu d y o f the changes
which o c c u r in th e r e d - c e l l volume, e s tim a te d by th e h a e m a t o c r it,
i n normal and toxa em ic p a t i e n t s about th e time o f d e l i v e r y and
i n the puerperium .
th e o r e tic a lly ,
Rapid v a r i a t i o n s i n h a e m a to c r it may,
be due to a l t e r a t i o n s i n the t o t a l number o f
red c e l l s i n th e body, a s a f t e r haemorrhage or t r a n s f u s i o n ;
or to ch an ges i n s i z e o f the i n d i v i d u a l red c e l l s ,
due to
osm otic changes i n blood ; or to changes i n the number o f red
c e l l s p er c u b ic c e n t im e tr e o f b lo o d , due to an i n c r e a s e or
d e c r e a se i n th e a b s o l u t e amount o f w ater i n the plasma.
In a s m a ll p r e li m in a r y s e r i e s , a c c u r a te haem oglobin
e s t i m a t i o n s were made a lo n g w ith the h a e m a to c r it d e te r m in a tio n s
and i t was found t h a t ch an ges were a b s o l u t e l y p a r a l l e l i n
in d iv id u a l p a t i e n t s ,
i.e .
th e r e l a t i o n between b lood -h aem oglob in
and the t o t a l c e l l volume was c o n s ta n t e x c e p t f o r i n s i g n i f i c a n t
v a r i a t i o n s w i t h i n th e range o f e x p e rim en ta l e r r o r .
This
c o n sta n c y o f th e volume in d e x i n d i c a t e s th a t th e changes i n
h a e m a to c r it v a lu e s a r e not due to s w e l l i n g or sh rin k a ge o f
red c e l l s .
The a c t u a l s i z e o f r e d c e l l s i n pregnancy h a s been
shown by Dieckmann and Wegner ( 1934 b)
be s l i g h t l y l a r g e r
than norm al, but t h i s does not a f f e c t th e p o in t a t i s s u e .
Changes i n th e h a e m a to c r it v a lu e s due to changes i n
CHART
Changes i n H a e m a t o c r i t , H aem oglobin and f l a s m a H r o r e i n s
a b o u t t h e tim e o f D e l i v e r y .
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the t o t a l number o f r e d c e l l s i n th e body do occu r i n c e r t a i n
c a s e s , but t h e s e c a s e s can be e a s i l y r e c o g n is e d because t h e y
are due t o e a s i l y a s c e r t a i n e d f a c t o r s .
A l o s s o f red c e l l s
may be due to haemorrhage which i s n o ted c l i n i c a l l y or t o
h a e m o ly sis which i s shown by b i l i r u b i n e s t i m a t i o n s ,
A r a p id
in c r e a s e i n r e d c e l l s may be due t o b lo od t r a n s f u s i o n , and th e
volume o f t h i s i s known.
R e g e n e r a tio n o f red c e l l s i s a slo w e r
p r o c e s s and o n l y p l a y s a p a r t i n g radual changes i n h a e m a to c r it.
P a t i e n t s i n whom th e t o t a l number o f red c e l l s i n the body i s
a l t e r e d su d d e n ly can , t h e r e f o r e ,
be c o n s id e r e d s e p a r a t e l y from
the o t h e r s .
The c a u se o f th e ch an ges i n the h a e m a to c r it i s th e
d i l u t i o n or c o n c e n t r a t i o n o f th e bloo d due to th e p a ssa g e o f
water from the t i s s u e s t o plasm a or v i c e - v e r s a .
This w ater
n a t u r a l l y c a r r i e s w it h i t d i f f u s a b l e e l e c t r o l y t e s and a c e r t a i n
amount o f p r o t e i n .
In the p r e s e n t s e r i e s plasma p r o t e i n
e s t i m a t i o n s were made d a i l y fo r s e v e r a l days b e fo r e and a f t e r
d e l i v e r y i n 10 p a t i e n t s (C ases 24 , 25 , 47 , 51 , 79 , 81 , 9 3 , 9 4 ,
95 and 1 1 5 ) .
The mean r e s u l t s f o r plasma p r o t e i n , haem oglobin,
and h a e m a to c r it from t h e s e p a t i e n t s a r e p l o t t e d i n Chart X II.
to show th e changes about the tim e o f d e l i v e r y .
The haem oglobin
and h a e m a to c r it c u r v e s run a b s o l u t e l y p a r a l l e l a s has been
n oted e a r l i e r .
The plasm a p r o t e i n changes a r e s i m i l a r to th e
h a e m a to c r it c h a n g e s, but th e r i s e and f a l l o f the curve i s
l e s s i n th e c a s e o f th e p r o t e i n s because the f l u i d e n t e r i n g
and l e a v i n g th e b lo o d -str e a m c a r r i e s a c e r t a i n amount o f
50.
p r o t e i n w ith i t .
The c o n c l u s i o n th a t the changes o f th e
h a e m a to c r it a r e due to th e t r a n s f e r o f f l u i d from th e blood
to the t i s s u e s and v i c e - v e r s a i s i n agreement w ith th e
f i n d i n g s o f O berst and P l a s s (1935 and 1936) who e s tim a te d
changes i n c e l l volume, s p e c i f i c g r a v i t y , and w ater c o n te n t o f
the b lo o d , h aem og lo b in and plasm a p r o t e i n s i n pregnant women
a t term, d u rin g d e l i v e r y , and i n th e puerperium., and found
c o r r e sp o n d in g changes i n a l l f r a c t i o n s .
P r e s e n t Technique.
In th e p r e s e n t i n v e s t i g a t i o n venous blood was
drawn from th e arm w ith o u t any o b s t r u c t i o n t o the blood flo w .
H aem atocrit r e a d in g s were made u s in g a sta n d ard te c h n iq u e ,
and c a r e was ta k e n t h a t a l l d e t a i l s were th e same i n e v e r y
case.
The h a e m a to c r it v a l u e s a r e record ed a s th e p e r c e n ta g e
o f th e volume o f th e whole b lo o d which c o n s i s t s o f c e l l s .
The normal h a e m a to c r it f i n d i n g s with t h i s te c h n iq u e
were a s f o l l o w s ;
Normal n o n -p reg n a n t fe m a le , 42 ; corr esp o n d in g to
h aem o glo b in o f 84 Pe ^ c e n t.
Normal p r e g n a n t fem a le a t 39 weeks, 33 ; c o r r e sp o n d in g to
h aem oglob in o f 68 per c e n t.
The s e r i e s s t u d ie d throughout d e l i v e r y c o n s i s t e d o f
96 c a s e s which have been c l a s s i f i e d a s f o l lo w s ;
20 normal c a s e s ; 56 p r e - e c la m p t ic c a s e s ;
20 c h r o n ic to x a em ic c a s e s .
P a t i e n t s w ith any c o n v u l s io n s , e c la m p t ic ,
e p ile p tic
or h y s t e r i c a l have been e x c lu d e d from the p r e s e n t s e r i e s .
H aem a tocrit r e a d in g s were made about 7 days a n t e -
partum, n ear th e o n s e t o f la b o u r and l a t e i n la b o u r , and
d a ily d u rin g th e f i r s t 3 to 5 days o f the puerperium , a f t e r
which r e a d in g s were made a t i n t e r v a l s o f 2 to 3 days t i l l
the p a t i e n t * s d i s m i s s a l .
In many o f the toxaem ic c a s e s
r ea d in g s were made a t 1 -d a y or 2-d ay i n t e r v a l s du rin g t h e
l a s t few weeks a n t e - p a r turn, and i n many o f the normal and
toxaemic c a s e s th e b lo o d was examined a t i n t e r v a l s o f a few
hours d u rin g la b o u r and the f i r s t day a f t e r d e l i v e r y .
Only
the mean f i g u r e s are g i v e n i n t h i s s e c t i o n ; the i n d i v i d u a l
c a s e s showed t h e u s u a l s c a t t e r ,
but the v a r i a t i o n s i n each
i n d iv i d u a l c a s e f o l l o w q u i t e c o n s i s t e n t l y the mean f i g u r e s
fo r the group.
Ante-Parturn F in d in g s .
The mean h a e m a to c r it v a lu e s fo r a l l c a s e s i n each
group a r e shown i n th e f o l l o w i n g t a b l e :
Table VII.
P r e - e c la m p t ic .
Normal.
Range.
Mean.
Range.
Mean.
Chronic
to x a em ic .
Range.
Mean.
7 days an te-p a rtu m . 29 t o 37 . 33
24 to 42 .
35
20 t o 44 *
33
36
25 to 43 -
36
22 to 45 -
34
At o n s e t o f la b o u r .
29 t o 39.
Seven days a n t e —parturn t h e mean v a lu e f o r p r e —e c la m p tic c a s e s
i s s l i g h t l y h i g h e r th a n t h a t o f th e normal, w h ile the mean
52.
value f o r th e c h r o n ic toxaem ic c a s e s i s about normal.
The
range o f th e v a l u e s i n both the p r e - e c la m p t ic and ch r o n ic
toxaemic groups i s c o n s i d e r a b l y g r e a t e r than i n the normal
group.
The s i g n i f i c a n c e o f t h e s e f i n d i n g s w i l l be d i s c u s s e d
l a t e r w ith th e f i n d i n g s d u rin g lab ou r and p o s t - p a r turn.
It
w i l l be n o t i c e d t h a t the mean v a l u e s for each group show th a t
the b lo o d becomes r a th e r more c o n c e n tr a t e d during the week
b efo re th e o n s e t o f la b o u r .
In th e p r e -e c la m p t ic c a s e s s t u d ie d
during t h e l a s t few weeks ante-partum i t was found th a t th e
h a e m a to c r it v a l u e s v a r ie d from day to day.
With v e r y few
e x c e p t io n s a r i s e i n h a e m a to c r it was found to accompany i n c r e a s e d
s e v e r i t y o f th e toxaem ic s i g n s w h ile a f a l l i n h a e m a to cr it
accompanied c l i n i c a l improvement.
(T h is i s i n agreement w ith
the work o f Skajaa ( 1929 ) , Dieckmann ( 1933 )> and Schwartz and
Dieckmann ( 1 9 2 9 ) .
S im ila r e x a m in a tio n s were made i n o n ly a
few normal c a s e s but i n t h e s e the va lu e was more c o n s t a n t ,
showing o n l y a g rad u a l r i s e b e f o r e the o n s e t o f la b o u r.
Changes d u rin g Labour and th e Puerperium.
In a l l c a s e s , normal and tox aem ic, the h a e m a to c r it
f i g u r e s showed a r i s e d u rin g la b o u r f o llo w e d by a f a l l d u rin g
the f i r s t
3 days o f th e puerperium .
The r i s e and f a l l v a r ie d
in e x te n t from c a s e to c a s e but were i n v a r i a b l y p r e s e n t .
most p a t i e n t s th e v a l u e s i n c r e a s e d s t e a d i l y d u rin g la b o u r ,
reaching a maximum a t d e l i v e r y or a few hours p o st-p a r tu m ,
a f t e r which th e y began t o f a l l .
In a few c a s e s th e v a lu e s
In
CHART X I I I .
I
L ea n H a e m a t o c r i t Changes b e f o r e and d a r i n g L a b o u r , and
t h r o u g h o u t th e P u e r p e r i u m ., i n n o rm a l cases;,
J>nyS
flw TiT «^Tw n
'T>o*T"Fft f t - r u r v
0~
ro
5 3 / n w
j.iV 3 0 iy
U 3U H
53 .
remained h ig h or even i n c r e a s e d 6 to 12 hours a f t e r d e l i v e r y ,
and th e n f e l l ,
w h il e i n o t h e r c a s e s the h a e m a to c r it v a lu e
reached a maximum e a r l y i n la b o u r , and showed a s l i g h t d e c r e a s e
before d e l i v e r y , a f t e r which th e d e f i n i t e post-partum f a l l
began.
I t w i l l be shown l a t e r , i n S e c t io n V I I . , t h a t a d e la y e d
f a l l i n h a e m a to c r it v a l u e s a f t e r d e l i v e r y o f t e n accom panies
sig n s o f s l i g h t p o st-p a r tu m c o l l a p s e .
In p a r t i c u l a r t h e
exten t o f th e r i s e d u rin g la b o u r was found to be u n r e la te d
to th e l e n g t h o r s e v e r i t y o f t h e la b o u r .
c h a r ts ,
In the f o l l o w i n g
th e maximal v a lu e o b t a in e d on the day o f d e l i v e r y
has been u s e d a s th e f i g u r e f o r d e l i v e r y .
The mean h a e m a to c r it
v a lu e s o f 10 normal c a s e s ( p a t i e n t s who were d e l iv e r e d by
fo r c e p s o r who had had haemorrhage or were i n f e c t e d b e in g
exclu d ed ) from 7 days ante-partum t i l l 10 days post-partum
are shown i n Chart X I I I .
The cu rve shows a r i s e i n v a lu e s
from 7 days an te-p a rtu m and r e a c h e s a maximum a t d e l i v e r y .
The h a e m a to c r it v a l u e s d e c r e a s e r a p id ly during th e 1 s t day
post-partum and the f a l l c o n t in u e s more s lo w ly t i l l the Jxd
day p o st-p a r tu m when th e v a lu e s ar e d e f i n i t e l y below th e
o r i g i n a l a n te-p artu m l e v e l .
A fte r the Jxd day p o st-p a rtu m ,
the curve b e g in s to r i s e s t e a d i l y , approaching normal non­
pregnant l e v e l s by th e 10 th day p ost-p a rtu m .
The p ost-p artu m
d i l u t i o n i s d e f i n i t e l y not due to b lood l o s s ;
i t appears to
be an o v e r —com p en satiob fo r the i n c r e a s e i n blood c o n c e n t r a t i o n
which o c c u r r e d b e f o r e d e l i v e r y .
S e v e r a l f a c t o r s were found to i n f l u e n c e th e e x te n t
of th e p o st-p a r tu m d i l u t i o n , and t h e s e w i l l be d e a l t w ith
before a com p arison i s made between the d i f f e r e n t ty p e s o f
cases*
F a c t o r s I n f l u e n c i n g P ost-Fartum D i l u t i o n ,
A g r e a t e r p o st-p a rtu m f a l l i n th e h a e m a to cr it v a lu e s
was found to be produced by t h r e e f a c t o r s : haemorrhage,
d e l i v e r y by f o r c e p s , and i n f e c t i o n .
Normal and toxaem ic c a s e s
were a f f e c t e d a l i k e , and i n o r d e r to dem onstrate t h e s e changes
a l l the c a s e s from th e s e r i e s have been d iv id e d i n t o fo u r
groups.
(a )
57 p a t i e n t s d e l i v e r e d sp o n ta n e o u s ly w ithou t haemorrhage
or w ith o n l y i n s i g n i f i c a n t b le e d in g and w ith o u t any
su b seq u en t i n f e c t i o n .
(b)
7 p a t i e n t s w ith moderate or s e v e r e haemorrhage a t
d e liv e r y .
No e x a c t measurements o f haemorrhage were
made; th e amount i n e v e r y c a se was e s tim a t e d c l i n i c a l l y
a s none, s l i g h t (a b o u t 200 c . c . ) , m oderate, or s e v e r e .
Haemorrhage l e s s than 200 c . c . was c o n s id e r e d
in s ig n ific a n t.
(c )
21 p a t i e n t s d e l i v e r e d by f o r c e p s w ith ou t haemorrhage or
in fe c tio n .
(d)
A l l th e p a t i e n t s , 11 i n number, i n whom t h e r e was any
e l e v a t i o n o f tem p eratu re during the puerperium,
e x c lu d in g s l i g h t r e a c t i o n a r y tem p eratu res on t h e f i r s t
day p o s t-p a r tu m .
.e n a t o e r it \Talues in 3;pontaneou.c
an cl I n f e c t e d G ases.
S
J.I V ^ O i t l W
3«ri
HaemorrliaW
°i
The mean h a e m a to c r it v a lu e s f o r t h e s e fou r groups
have been p l o t t e d i n Chart XIV.
without haemorrhage or i n f e c t i o n ,
f a l l in h a e m a to c r it v a l u e s .
P a t i e n t s d e l i v e r e d sp o n ta n e o u sly ,
show the s m a l l e s t p ost-partum
I t i s o b v io u s th a t much haemorrhage
at d e l i v e r y w i l l c a u se a marked post-partum f a l l a s a r e s u l t
o f a c t u a l l o s s o f c e l l s and th e compensatory blood d i l u t i o n
which f o l l o w s any l o s s o f b lo o d .
The graph shows a much s t e e p e r
post-partum f a l l i n t h e s e haem orrhagic c a s e s , c h i e f l y w i t h i n
the f i r s t 24 h ou rs;
day p o st-p a r tu m .
th e minimal v a lu e b ein g reached on th e 3rd
A d e f i n i t e r i s e i n the h a e m a to cr it v a lu e s
b e g in s a f t e r th e ^th day, but the mean valu e i s s t i l l w e l l
below normal a t 10 days p o st-p a r tu m .
c a s e s i s between 500 c . c . and 600 c . c .
The average l o s s i n t h e s e
In th e o r y , ta k in g th e
blood volume a s 5 l i t r e s and assum ing th a t the volume i s
m ain tain ed by d i l u t i o n a f t e r a haemorrhage, the l o s s o f 550 c . c .
would red u ce th e h a e m a to c r it by o n e - n in th , i . e .
from 36 to J>2.
This i s superim posed on the f a l l o f 7 which o c cu rs i n sp ontan eou s
d e l i v e r i e s w ith o u t haemorrhage.
As a r e s u l t o f t h i s co m b in ation
o f 4 + 7, th e e x p e c te d f a l l i n t h e s e c a s e s would be from 36 to
25, which i s th e a c t u a l drop s e e n i n Chart XIV.
The curve from p a t i e n t s who were d e l i v e r e d by f o r c e p s
shows a p o st-p a r tu m f a l l r e se m b lin g th a t o f th e haemorrhage
ca ses e x c e p t t h a t i t i s o f l e s s e r e x t e n t .
In d e l i v e r y by fo r c e p s ,
s l i g h t haemorrhage, a s from an e p isio to m y , i s o f t e n regarded
as normal and l e f t unnoted i n the c l i n i c a l r e c o r d s .
Though
every p a t i e n t i n whom even m oderate haemorrhage was n oted h as
been e x c lu d e d , i t seems p r o b a b le t h a t the s l i g h t and unnoted
haemorrhage o c c u r r in g i n p a t i e n t s d e l i v e r e d by f o r c e p s a c c o u n ts
for the g r e a t e r f a l l i n h a e m a to c r it f i g u r e s i n t h e s e c a s e s , a s
compared w ith sp on tan eou s d e l i v e r i e s .
In order to e x c lu d e t h e
p o s s i b i l i t y t h a t th e g r e a t e r f a l l was due to the a n a e s t h e t i c
a t d e l i v e r y , a stu d y was made o f a s e r i e s o f p a t i e n t s i n which
an a n a e s t h e t i c was g i v e n fo r v a r io u s p u rp o ses 2 or 3 weeks
b efore d e l i v e r y .
The o n l y change found was a r i s e o f about 1
i n th e h a e m a to c r it v a l u e s f o r 24 t o 48 hours a f t e r th e a n a e s t h e t i c .
The a n a e s t h e t i c a t d e l i v e r y th u s p la y e d no p a r t i n the g r e a t e r
f a l l o f h a e m a to c r it r e a d in g s i n the p a t i e n t s d e l i v e r e d by f o r c e p s .
The f i n d i n g s i n the group o f c a s e s l a b e l l e d i n f e c t i o n
are v e ry s t r i k i n g .
Of th e c h r o n ic toxaem ic c a s e s , none o f th e
p a t i e n t s became i n f e c t e d ; a l l th e i n f e c t e d c a s e s are from th e
p r e - e c la m p t ic and normal grou p s.
In 10 o f the 11 c a s e s the
i n f e c t i o n o f the p a t i e n t was m ild , shown by s l i g h t i r r e g u l a r
f e v e r and o f f e n s i v e l o c h i a ; c e r v i c a l swabs were n e g a t i v e f o r
h a e m o ly tic s t r e p t o c o c c i and t h e r e was n ot any e v id en ce o f
h a e m o ly sis a s shown by the van den Bergh r e a c t i o n on th e plasm a.
In the rem a in in g c a s e (C ase 53 )
i n f e c t i o n was due to
h a e m o ly tic s t r e p t o c o c c i and a p o s i t i v e van den Bergh r e a c t i o n
in the plasm a a f f o r d e d d e f i n i t e e v id e n c e th a t h a e m o ly sis was
o c c u r r in g .
The most im portant f i n d i n g i n t h e s e c a s e s was th e
very low a n te-p artu m h a e m a to c r it r e a d in g s; in d e e d , t h r e e q u arters o f th e p a t i e n t s from th e normal and p r e - e c la m p t io
groups, who had an te-p artu m v a lu e s be].ow JQ, f e l l i n t o t h i s
group, i . e .
became i n f e c t e d i n the puerperium .
The graph
fo r t h e s e c a s e s shows a v e r y marked post-p a rtu m f a l l and th e
f a l l c o n t i n u e s l o n g e r th a n th a t o f the haemorrhagic c a s e s ;
the h a e m a t o c r it r e a d in g s do n o t rea ch t h e i r minimum u n t i l
the $th day post-parturn.
This a s s o c i a t i o n between ante-partum
anaemia and p o st-p a r tu m i n f e c t i o n appears to be o f im portance.
D e t a il e d b a c t e r i o l o g i c a l ex a m in a tio n , e x c e p t f o r the e x c l u s i o n
o f s t r e p t o c o c c u s h a e m o ly t ic u s , was not made i n t h e s e c a s e s ;
the i n f e c t i o n may be due to organism s which are norm ally h e ld
in c h eck , but which become p a t h o g e n ic to the p a t i e n t a f t e r
d e l i v e r y b ecau se h e r r e s i s t a n c e i s low ered as a r e s u l t o f the
p r e v io u s anaemia.
I t i s o f i n t e r e s t to n o te t h a t the o n ly
c a se o f the group t h a t had a normal ante-partum h a e m a to c r it
va lu e was t h e p a t i e n t who was i n f e c t e d by h a e m o ly tic s t r e p t o c o c c i
presum ably an exogenous i n f e c t i o n .
A lthough the i n f e c t i o n i n
most c a s e s was m ild , i t was u s u a l l y p r o lo n g e d , and i t can be
se en from th e graph t h a t the curve shows very l i t t l e r i s e
compared w ith t h a t i n the o th e r groups o f c a s e s .
was r e s o r t e d to i n s e v e r a l o f th e p a t i e n t s ,
r e c o v e r y was slo w .
T r a n sfu sio n
bu t, d e s p i t e t h i s ,
F urther i n v e s t i g a t i o n i s n e c e s s a r y t c
a s c e r t a i n w hether a b lo o d t r a n s f u s i o n g iv e n ante-partum to
t h e s e anaem ic p a t i e n t s would red uce the l i a b i l i t y to p o s t ­
partum i n f e c t i o n .
Changes i n Normal and Toxaemic O ases.
In view o f the e f f e c t o f d e l i v e r y by f o r c e p s ,
CHART XV. .
it
Me ail H a e m a t o c r i t V a lu e s i n 11o r m a l, P r e - e c l a m p t i c and
Chr o n i c Toxaemi c C a s e s .
o
'P A '/S
flN T E T flftT U rV
- J>Ry S
'P O S T ff lR T O M .
I
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haemorrhage and i n f e c t i o n on th e p o st-partum blood d i l u t i o n ,
a l l p a t i e n t s w ith t h e s e c o m p lic a t io n s have been exclu d ed
from th e su b seq u e n t d i s c u s s i o n .
Only p a t i e n t s d e l i v e r e d
sp o n ta n e o u s ly , w ith o u t haemorrhage, or any p u er p e r a l i n f e c t i o n
are c o n s id e r e d .
In Chart XV. th e mean h a e m a to c r it v a lu e s
fo r a l l t h e s e u n c o m p lic a te d c a s e s have been su b d iv id ed in t o
normal, p r e - e c l a m p t i c , and c h r o n ic toxaem ic groups to show
the changes o c c u r r in g from 7 days ante-partum t i l l 10 days
p o st-p a r tu m .
The normal curve h as a lr e a d y been d e sc r ib e d .
The mean graph f o r the p r e - e c l a m p t i c c a s e s ,
Jl i n number,
shows v a l u e s 7 days a nte-partum c o n s id e r a b ly h ig h e r than th e
normal c a s e s ,
but the p o st-p a rtu m f a l l i s ra th er g r e a t e r ,
so
th a t th e cu rve f a l l s w e l l below the normal and remains low.
The mean curve f o r the c h r o n ic toxaem ic c a s e s , 18 i n number,
shows a r a t h e r l e s s e r r i s e and f a l l than the normal.
This
ch a r t h a s been i n c lu d e d o n ly foJT comparison w ith the r e s u l t s
o f o t h e r w orkers.
The p r e s e n t f i n d i n g s fo r the toxaem ic
c a s e s a r e e s s e n t i a l l y s i m i l a r t o th o s e r e s u l t s - p r e -e c la m p t ic
p a t i e n t s h a v in g
a c o n c e n tr a t e d blood fo r s e v e r a l days b e f o r e
d e l i v e r y w ith a f u r t h e r i n c r e a s e i n c o n c e n t r a t io n on the day
b e fo r e d e l i v e r y and a d e f i n i t e post-partum d i l u t i o n ; c h r o n ic
toxaem ic c a s e s showing l e s s marked changes.
The e x t e n t o f
the changes i n c o n c e n t r a t i o n i n the normal c a s e s i s o b v i o u s l y
o f g r e a t s i g n i f i c a n c e i n t h i s co n n exion but i t s im portance
does n o t appear to have been s u f f i c i e n t l y a p p r e c ia t e d .
When th e i n d i v i d u a l c a s e s are a n a ly s e d , the
8.
3 IV?011IW3«H
QUART XVII .
Lie an H a e m a t o c r i t C hanges i n M ild P r e - e c l a m p t i c s
c h a r a c t e r i s t i c s o f th e p r e - e c l a m p t i c curve a r e found to
depend on two f a c t o r s ;
th e s e v e r i t y o f the toxaem ia, and th e
p r e s e n c e or a b se n c e o f oedema.
These p r e -e c la m p tic c a s e s
have been s u b - d iv i d e d from a c l i n i c a l p o in t o f view i n t o 20
se v e r e and 11 m ild c a s e s .
In the m ild c a s e s the p a t i e n t s had
o n ly s l i g h t h y p e r t e n s i o n , a lb u m in u ria or oedema and corresp o n d
to the low r e s e r v e k id n e y c a s e s o f American w r i t e r s ; th e s e v e r e
c l a s s i n c l u d e s a l l th e p a t i e n t s w ith more s e r i o u s symptoms.
The r e s u l t s from th e s e v e r e and m ild p r e - e c la m p t ic c a s e s are
p l o t t e d i n C harts XVI. and XVII. r e s p e c t i v e l y .
In each graph, th e p a t i e n t s w ith c l i n i c a l l y
r e c o g n i z a b le oedema have been se p a r a te d from the o th e r s ;
accou n t h as n o t been ta k e n o f o c c u l t oedema.
Oedema ivas
p r e s e n t i n 12 p a t i e n t s i n the s e v e r e group and in 6 p a t i e n t s
i n th e m ild group.
I t w i l l be n o t i c e d from each graph th a t
the mean an te-p a rtu m v a l u e s o f the oedematous c a s e s a r e lo w er
than t h o s e o f the non-oedem atous c a s e s ; the l e s s marked
d i f f e r e n c e aneng th e m ild c a s e s i s probably because t h e s e
p a t i e n t s had o n l y s l i g h t oedema,
in a l l c a s e s .
A r i s e during lab ou r o c cu rs
The p o st-p artu m d i l u t i o n i s g r e a t e r i n th e
oedematous p a t i e n t s ,
e s p e c i a l l y i n the s e v e r e p r e - e c l a m p t i c ,
and t h e s e l a t t e r do n o t r e tu r n to normal h a e m a to c r it l e v e l s
by th e end o f th e puerperium .
I t would appear th a t i n th o s e
p a t i e n t s w ith oedema th e r e i s a r e l a t i v e hydraemia or an
a s s o c i a t e d anaem ia.
This becomes more apparent a f t e r d e l i v e r y ;
th e v e r y g r e a t p o st-p a r tu m f a l l i s p ro b ab ly due to d i l u t i o n
o f the b lo o d by oedema f l u i d .
To e x c lu d e th e i n f l u e n c e o f t h i s f a c t o r ,
c o n s i d e r a t i o n may be l i m i t e d to t h o s e p a t i e n t s w ithou t
oedema.
The mean v a lu e f o r th e m ild c a s e s i s alm ost th e
same a s t h a t f o r th e normal.
Those p a t i e n t s w ith s e v e r e
p r e - e c l a m p t i c symptoms have v e ry h ig h v a lu e s 7 days a n t e ­
partum, but th e r i s e i n v a lu e b e fo r e d e l i v e r y i s l e s s than
in normal c a s e s and b e g in s o n l y 48 hours ante-partum .
The
post-p artu m f a l l i n th e s e v e r e c a s e s i s a lm ost th e same a s
t h a t i n normal c a s e s a lth o u g h a l l v a lu e s a r e a t a h ig h e r
le v e l.
This a n a l y s i s shows, t h e r e f o r e , t h a t , apart from th e
e f f e c t produ ced by oedema, the p r e - e c la m p t ic f i n d in g s d i f f e r
from th o s e o f the normal c a s e s o n ly i n showing h ig h e r
h a e m a to c r it v a lu e s d u rin g th e week or more b e fo r e d e l i v e r y .
The i n c r e a s e d p o st-p a r tu m d i l u t i o n o f the blood i n th e e n t i r e
group o f p r e - e c l a m p t i c c a s e s , which was shown i n Chart XV. ,
i s t h e r e f o r e r e a l l y due to the i n c l u s i o n o f oedematous c a s e s .
The wide a n te-p artu m range o f v a lu e s i n the p r e -e c la m p tic
cases,
shown i n page 5 1 , i s caused by the subnormal v a lu e s
o f th e oedematous m ild c a s e s and the high v a lu e s o f th e nonoedematous s e v e r e c a s e s .
Vi/hen an a n a l y s i s o f the ch ron ic toxaem ic c a s e s i s
made, the same i n f l u e n c e o f oedema i s found, but th e r e i s
an oth er f a c t o r o f im p ortan ce.
From a study o f the a n t e ­
partum h a e m a to c r it v a l u e s , th e ch ro n ic toxaem ia c a s e s ar e
found to f a l l i n t o two w e l l d e f i n e d groups - 5 anaemic
p a t i e n t s w ith h a e m a to c r it v a lu e s between 20 and JO, and 11
can H a e m a t o o r i t V a lu e s i n
-
C-ftiES
c
iuiaemi c
xivtoj.wvaI3 «h
oxaem ic
non-anaemic p a t i e n t s w ith h a e m a to c r it v a lu e s between 3 L
and 44.
The term s "anaemic" and "non-anaemic" a r e used f o r
c o n v e n ien ce ; th e term ‘'anaem ic 11 i n the p r e s e n t c o n t e x t i s
not in te n d e d to s i g n i f y a r e d u c tio n i n the t o t a l haem oglobin
in th e body but m e r e ly a r e d u c tio n i n the amount per c . c . o f
blood.
I t i s h i g h l y p r o b a b le th a t the low h a e m a to cr it
v a lu e s i n t h i s ‘'anaemic" group were a c t u a l l y the r e s u l t o f
hydraem ia.
A l l th e anaemic p a t i e n t s had marked oedema but
o n ly 3 o f th e non-anaem ic p a t i e n t s had oedema.
The r e s u l t s from t h e s e two groups are shown i n
Chart XVIII.
The curve from th e non-anaemic c a s e s c l o s e l y
r e se m b le s t h a t o f the non-oedem atous se v e r e p r e -e c la m p tic
cases,
showing h ig h ante-partum v a l u e s , w ith s l i g h t p r e ­
d e l i v e r y r i s e and a normal p ost-p artu m f a l l .
The f i n d i n g s
i n th e anaemic c a s e s are d i f f e r e n t from a l l the o t h e r s .
C o n c e n tr a tio n and d i l u t i o n o ccu r a s i n o th e r groups but are
o f e q u a l e x t e n t and t h e r e i s no post-partum r i s e towards
normal v a l u e s ; a p a r t from the r i s e and f a l l i n v a lu e s d u rin g
the 2 days b e f o r e and a f t e r d e l i v e r y , the h a e m a to cr it appears
to rem ain unchanged i n t h e s e c a s e s .
D iscu ssio n .
The p r e s e n t r e s u l t s a r e i n accordance w ith th e
f i n d i n g s o f e a r l y workers who showed th a t during la b o u r i n
normal c a s e s ,
t h e r e was a r i s e i n b lood -h aem oglob in and r ed
b l o o d - c o r p u s c l e s f o l lo w e d by a f a l l i n v a lu e s i n th e
puerperium.
In p r e - e c l a m p t i c to x a em ia s, Skajaa ( 1 9 2 9 ) ,
Schwartz and Dieckmann ( 1 9 2 9 ) , and Dieckmann (19,33) n o ted
the h ig h a n te-p artu m h a e m a to c r it v a l u e s , the r i s e during
lab ou r and th e p o st-p a r tu m f a l l .
The p r e s e n t s e r i e s o f
r e s u l t s c o r r o b o r a t e s t h e s e f i n d i n g s but shows t h a t th e seme
ch an ges, b e f o r e , d u rin g and a f t e r la b o u r , occu r i n a l l p a t i e n t s
toxaem ic or o t h e r w is e .
When the e f f e c t o f v a r io u s i n t e r f e r i n g
f a c t o r s such a s haem orrhage, s e p s i s or oedema i s e x clu d ed ,
th e p o st-p a r tu m d i l u t i o n o f the b lood i s found to be
a p p ro x im a te ly e q u a l i n a l l c a s e s .
Dieckmann1s c o n c lu s io n
th a t c h r o n ic toxaem ic c a s e s do n o t show the p r e - p a r t u r i t i o n a l
and p o s t - p a r t u r i t i o n a l changes i s not i n accordan ce w ith th e
p resen t fin d in g s.
The p r e s e n t r e s u l t s show, i n c o n t r a s t to
the f i n d i n g s o f c e r t a i n o th e r w orkers, t h a t the p r e sen ce o f
oedema d o e s i n c r e a s e t h e p ost-p artu m d i l u t i o n .
I f th e t o t a l plasm a volume i s c a l c u l a t e d from th e
h a e m a to c r it r e s u l t s i t i s found t h a t the changes d e s c r ib e d
in v o l v e th e t r a n s f e r e n c e o f c o n s id e r a b le volumes o f f l u i d
from th e t i s s u e s to th e b lo o d stream and v i c e v e r s a .
During
the l a s t 7 days a n te-p a rtu m , the mean h a e m a to c r it v a lu e f o r
normal c a s e s r i s e s from 33*5
33 *2 ; i f the t o t a l blo od
volume i n an i n d i v i d u a l c a s e were 5 l i t r e s , o f which 3i+ l i t r e s
were p lasm a, t h i s r i s e would be e q u iv a le n t to the removal o f
590 c . c . o f f l u i d from th e plasm a.
The p ost-p a rtu m f a l l i n
the h a e m a to c r it v a lu e i n t h e s e c a s e s would d en ote an i n c r e a s e
o f plasm a f l u i d o f 74-5 c . c .
In the non—oedematous toxaem ic
c a s e s t h e p o st-p a r tu m i n c r e a s e i n plasma volume i s
ap p ro x im a tely th e same; a mean o f 782 c . c .
in severe p re­
e c la m p tic c a s e s and o f 747 c *c, i n c h r o n ic toxaem ic c a s e s .
In the c h r o n ic anaemic c a s e s a lth o u g h th e h a em a to crit changes
appear s l i g h t ,
t h e y s i g n i f y the t r a n s f e r e n c e o f alm ost th e
same q u a n t i t i e s o f f l u i d a s i n normal c a s e s , plasma d e c r e a s in g
by 533 c . c .
partum.
a n te -p a r tu m , and i n c r e a s i n g by 678 c . c . p o s t ­
In th e oedematous p r e - e c l a m p t i c c a s e s , however, th e
changes a r e c o n s i d e r a b l e ; th e mean plasma volume i s i n c r e a s e d
by 1487 c . c .
i n th e f i r s t 2 days p ost-p artu m .
The p r o b a b le cau se o f the changes i n blood
c o n c e n t r a t i o n i n normal c a s e s i s u n c e r ta in .
The e f f e c t o f
m uscular work, in c r e a s e d abdominal p r e s s u r e and l o s s o f
w ater by p e r s p i r a t i o n during la b o u r ( a s su g g e s te d by Denecke
( 1 9 2 4 ) , P ayer (1 9 0 4 ) and o t h e r s ) may undoubtedly cause an
i n c r e a s e i n b lo o d c o n c e n t r a t i o n during lab ou r but th e y do
not s a t i s f a c t o r i l y e x p l a i n the t o t a l i n c r e a s e i n c o n c e n t r a t io n
b e fo r e d e l i v e r y ;
( a ) more than h a l f o f the r i s e i n h a e m a to c r it
v a lu e s o c c u r s b e fo r e th e o n s e t o f la b o u r, and ( b) i n s e v e r a l
c a s e s th e h a e m a to c r it v a l u e s b e g in to f a l l during th e l a s t
few h o u rs o f la b o u r when t h e s e f a c t o r s are most marked.
The p o st-p a r tu m d i l u t i o n o f th e blood i s much g r e a t e r than
the i n c r e a s e i n c o n c e n t r a t i o n which o c cu rs during la b o u r ,
but i t i s a lm o st eq u al to the t o t a l i n c r e a s e i n c o n c e n t r a t i o n
during th e l a s t 7 days ante-parturn.
When the e f f e c t o f a l l i n t e r f e r i n g f a c t o r s i s
64.
exclud ed i t i s c l e a r t h a t th e r e s u l t s from th e p r e - e c la m p t ic
and c h r o n ic non-anaem ic toxaem ic c a s e s are v e ry s i m i la r ; th e y
d i f f e r from th e normal o n l y i n h av in g h ig h e r h a e m a to c r it
v a lu e s a t 7 days a n te-p artu m and a s m a lle r r i s e i n v a lu e s
b efore d e l i v e r y .
This v a r i a t i o n from the normal appears to
be th e d i r e c t r e s u l t o f the tox aem ia s in c e the blood i n t h e s e
p a t i e n t s becomes more c o n c e n tr a t e d th an normal w ith the o n s e t
o f the to x a em ia .
The p o st-p a r tu m d i l u t i o n o f the b loo d i n
both t y p e s o f c a s e i s eq u a l t o the post-partum d i l u t i o n i n
normal c a s e s , and i s presum ably equal to the t o t a l i n c r e a s e
i n c o n c e n t r a t i o n which o c cu rr ed ante-partum .
I t seems l i k e l y
th a t th e same an te-partum c o n c e n t r a t i o n o c cu rs i n t h e s e
c a s e s a s i n normal o n e s , but t h a t i t o ccu rs e a r l i e r .
So f a r
as t h e s e f i n d i n g s a r e con c er n e d , th e r e does not appear to be
any d i f f e r e n c e between th e toxaem ia o f th e p r e -e c la m p tic and
th a t o f th e c h r o n ic non-anaem ic toxaem ic p a t i e n t s .
The c h r o n ic anaemic toxaem ic p a t i e n t s , however,
appear t o be q u i t e u n r e l a t e d to the oth er toxaem ic p a t i e n t s
both c l i n i c a l l y and i n t h e i r h a em a to crit f i n d i n g s .
They are
d e b i l i t a t e d , p a l e and v e r y oedem atous, and do not show any
improvement a f t e r d e l i v e r y a p a rt from the d isap p eara n ce o f
oedema.
Without d i r e c t e s t i m a t i o n s o f blo od volume i t i s
im p o s s ib le to d e c id e w hether the low h a e m a to cr it v a lu e s i n
t h e s e -p a t ie n t s a r e due to hydraemia or tru e anaemia.
The
same l a c k o f improvement i n s e v e r e anaemia i s se e n i n m u l t i :parous p a t i e n t s w ith a c c i d e n t a l haemorrhage though none o f
p r e se n t s e r i e s had a c c id e n t a l haem orrhage.
Summary.
D e f i n i t e i n c r e a s e i n b lood c o n c e n t r a t io n , a s
i n d i c a t e d by changes i n the h a e m a to c r it v a l u e s , o c cu rs i n
normal p a t i e n t s d u rin g the l a s t 7 days, and p a r t i c u l a r l y
during th e l a s t 2 d a y s, ante-partum ; t h i s i s fo llo w e d by a
r a p id b lo o d d i l u t i o n du rin g th e f i r s t 3 days p ost-p artu m .
A fte r t h i s ,
th e b lo o d g r a d u a l l y r e tu r n s to normal.
The
changes i n v o l v e th e t r a n s f e r o f 20 t o 25 per c e n t o f th e
f l u i d o f th e plasm a from th e b lo o d i n t o the t i s s u e s and
back a g a in .
S im ila r changes o ccu r i n p a t i e n t s s u f f e r i n g from
p r e - e c l a m p t i c to x a em ia , but t h e s e p a t i e n t s have i n a d d i t i o n
a d e f i n i t e i n c r e a s e i n blood c o n c e n t r a t i o n for one or more
weeks b e fo r e d e l i v e r y .
P a t i e n t s w ith symptoms o f ch r o n ic
toxaem ia f a l l i n t o two grou p s, a s e r i e s w ith anaemia ( c r
hydraeraia) which show th e normal h a e m a to c r it changes about
the tim e o f d e l i v e r y but do n ot show any r i s e i n v a lu e s
during th e puerperium , and a s e r i e s w ithou t anaemia which
c l o s e l y r e se m b le s th e p r e -e c la m p t ic c a s e s i n t h e i r h a e m a to c r it
ch an ges.
The p o st-p a r tu m d i l u t i o n o f the b lood i s in c r e a s e d
i n p a t i e n t s i n whom t h e r e i s oedema b e fo re d e l i v e r y , haemorrhage
a t d e l i v e r y or i n f e c t i o n i n th e puerperium.
66.
S E C T I O N
V.
VOMITING IN PREGNANCY.
In many d i f f e r e n t c o n d i t i o n s i n pregnancy s e v e r e
v o m itin g i s th e main f e a t u r e ; i n some the v om itin g appears
to be th e prim ary f a c t o r i n c a u s in g the a b n o r m a litie s
c h a r a c t e r i s t i c o f th e d i s e a s e , w h ile i n o t h e r s , th e v o m itin g
i s se c o n d a r y to some o t h e r f a c t o r .
At any time during
pregnancy s e v e r e v o m itin g may be caused by an i l l n e s s
u n r e la t e d to th e pregnancy,
e . g . a p p e n d i c i t i s , b rain tumour
e t c . , but t h e p r e s e n t s e c t i o n d e a l s o n ly w ith c a s e s i n which
th e v o m itin g was r e l a t e d to th e pregnancy.
The c a s e s are
d e a l t w ith under th e f o l l o w i n g h e a d in g s:
A)
V om iting o f e a r l y pregnancy, or Hyperemesis Gravidarum.
B)
V om iting o f l a t e pregnancy.
H yperem esis Gravidarum.
This term , h v p e r e m e sis gravidarum, i s a p p lie d to th e
c o n d i t i o n i n which p a t i e n t s i n the e a r l y months o f pregnancy
s u f f e r from p e r s i s t e n t and e x c e s s i v e v o m itin g.
The v o m itin g
i s , i n some way, caused by th e pregnancy i t s e l f but th e
actu a l e t io lo g y i s ,
a t p r e s e n t , ob scu re.
B io c h e m ic a l i n v e s t i g a t i o n s o f the blo od i n c a s e s
o f h y p e r e m e sis have r e v e a le d c e r t a i n a b n o r m a lit ie s to be
c o n sta n tly p r e se n t in sev ere c a se s.
Anhydraemia, r e s u l t i n g
from th e l o s s o f w ater and s a l t s , h as been shown by
Dieckmann and C ro ssen (1 9 2 ? ) to be an im portant f e a t u r e o f
the d i s e a s e and t h e s e workers have emphasized th e g r e a t
va lu e o f in t r a v e n o u s s a l i n e and g lu c o s e t r a n s f u s i o n s i n
tr e a tm e n t.
R a ised b lo o d n o n -p r o t e in n it r o g e n , urea and
u r ic a c i d v a l u e s a r e found by many workers (W illia m s, 1921;
K i l l i a n and Sherwin, 1921; S ta n d er, 1924; Dieckmann and
C rossen, 1927; Peckham, 1929; Glassman, 1933; H erald, 1 9 3 9 ).
Jaun dice i s u s u a l l y m entioned a s a p o s s i b l e symptom i n
e x tr e m e ly s e v e r e c a s e s and in c r e a s e d plasma b i l i r u b i n has
been f r e q u e n t l y r e p o r te d (Heynemann, 1928; Herold, 1939;
F ik e n t s c h e r , 1 9 3 9 ).
B lood c h l o r i d e s a r e u s u a l l y d e c re a sed
(Dieckmann and C rossen , 1927; Peckham. 1929) and th e r e may
be an a c c u m u la tio n o f amino and l a c t i c a c i d s and a c e to n e
b o d ie s i n th e b lo o d .
Most r e c e n t i n v e s t i g a t o r s are agreed
th a t a l l t h e s e ch an ges are due to the d e h y d ra tio n and
undernourishm ent produced by the v om itin g.
B io c h e m ic a l s t u d i e s have been made on s e v e r a l
h y p er e m e sis p a t i e n t s i n th e p r e s e n t i n v e s t i g a t i o n w ith
regard to anhydraem ia, n o n - p r o t e in n it r o g e n r e t e n t i o n and
h y p e r b ilir u b in a e m ia and th e f i n d i n g s are i n agreement w ith
th o s e o f p r e v io u s w orkers.
The c a s e s have been su b d iv id e d
c l i n i c a l l y a c c o r d in g to th e s e v e r i t y o f t h e i r c o n d i t i o n a s ,
very s e v e r e ,
s e v e r e and m o d e ra te ly s e v e r e .
are i n c lu d e d i n t h i s stu d y .
No m ild c a s e s
The r e s u l t s from 12 c a s e s
(156 t o 1 67 ) a r e shown i n T a b l e V I I I ,
Table
V III,
Mean R e s u l t s from 12 H yperem esis C ases.
H aem atocrit $
Mean.
Very Severe.
Severe.
4 8 . 5#
Range.
45# to 52#
. . i l l . ..-I I I t o 5 0 £
Hoderately S e v e r e .
40%
3.8# to 44#
U ric A cid
mg. p e r 100 c . c .
Mean
Range.
Urea mg.
per :.00 c . c .
Mean
Range.
1 3 .6 1 0 .9 to 1 6 . 4
6 .4
4 .0 t o
8 .9
3 .x
2 .3 t o
4. 3
164 136 t o 191.
3
1 to 6
12 t o
76
2
1 to 4
16 to
27
1
22
B lood c o n c e n t r a t i o n , a s measured by t h e
h a e m a to c r it, was a t th e upper l i m i t o f normal i n th e
m o d e r a te ly s e v e r e c a s e s and g r e a t l y i n c r e a s e d i n th e
very s e v e r e c a s e s .
H itr o g e n r e t e n t i o n appeared t o vary
d i r e c t l y w ith th e bloo d c o n c e n t r a t i o n i n i n d i v i d u a l p a t i e n t s
but t h e r e were v a r i a t i o n s betw een th e h a e m a to c r it v a l u e s
and t h e d e g r ee o f n i t r o g e n r e t e n t i o n from p a t i e n t to p a t i e n t .
In one p a t i e n t , c a s e 1 6 4 , th e h a e m a to c r it v a l u e was 37$
w h ile t h e plasm a u r i c a c i d was 8 .9 mg. p e r 100 c . c .
th e b lo o d u rea 40 mg. p e r 100 c . c . ;
and
i n a n o th er p a t i e n t ,
c a se 1 5 9 , th e h a e m a to c r it was 44$> u r i c a c i d 4 .0 mg. p e r
100 c . c .
and u r e a 12 mg. p e r 100 c . c .
B ilir u b in
u n its.
Mean.
Range.
These f i n d i n g s a r e
presumably p a r t l y due t o th e d i f f e r e n c e s i n th e c a p a c i t y
o f th e k id n e y s to d e a l w ith th e abnormal s i t u a t i o n i n each
CHART XIX.
Com posite Graph o f Changes d u r i n g T re a tm e n t
- 5r-=rv= s =1=™
«------- • 2 HAc<ni%rotA\f
i n C ases 1 5 6 , I d /,& 1 5 8 0
“
T t R . (O O c .c - .f L f lS r lr t .
*____ , - UaE* «n
„
•
jjo 10 So9/,
O o o sol
Otf&LT OF
TRtflr^E^r
/
3
A
. - ur/n aAy ooipu-'.
* - »n ftuwor:
case; anaemia may a cco u n t f o r th e low h a e m a to cr it v a l u e s
o b ta in ed from some p a t i e n t s w ith a n itr o g e n r e t e n t i o n and
i n such c a s e s th e plasm a p r o t e i n v a lu e would be a b e t t e r
guid e to th e d e g r ee o f b lo o d c o n c e n t r a t io n than th e h a e m a to c r it
v a lu e .
In c a s e s w ith n i t r o g e n r e t e n t i o n th e u r ic a c i d and
urea were u s u a l l y r e t a i n e d r o u g h ly t o the same degree and
the p r o p o r t i o n betw een t h e i r v a lu e s in mg. p e r 100 c . c . was
a p p r o x im a te ly 1 to 1 0 .
One v e r y s e v e r e (15&) and 2 s e v e r e (157 and 1 5 8 )
c a s e s o f h y p e r e m e sis were f o l lo w e d during th e f i r s t few
days o f tre a tm en t and s e r v e t o show th e r a p id improvement,
i n a l l th e b io c h e m ic a l f i n d i n g s , which u s u a l l y accompanies
blood d i l u t i o n .
Two o f the c a s e s , 156 and 1 5 8 , were g iv e n
c o n tin u o u s in tr a v e n o u s g l u c o s e s a l i n e during t h e i r f i r s t 48
hours i n h o s p i t a l ;
flu id .
the t h i r d c a s e , 1 5 7 , had no in tr a v e n o u s
A c o m p o site graph o f th e changes i n the h a e m a to c r it,
plasma u r i c a c i d and b lo o d urea v a lu e s i n t h e s e 3 c a s e s i s
g iv e n i n Chart XIX. ; th e d a i l y u r in a r y output i n ounces i s
a l s o c h a r te d .
I t w i l l be n o t i c e d t h a t the h a e m a to c r it, u r i c
a c id and u r e a c u r v e s a r e p r a c t i c a l l y p a r a l l e l and th a t t h e r e
i s an i n v e r s e p r o p o r t io n between the v a lu e s o f the b lood
n o n - p r o t e in n i t r o g e n f r a c t i o n s and the volume o f u r in e
e x c r e t e d i n d i c a t i n g t h a t the n it r o g e n r e t e n t i o n was th e
d i r e c t r e s u l t o f th e anhydraemia..
In 4 of the 12 c a s e s
( c a s e s 1 5 7 , 1 5 8 , 159 and 1 6 5 ) i n th e p r e s e n t s e r i e s th e
plasma gave a p o s i t i v e d e la y e d d i r e c t r e a c tio n to th e
7o.
van den Bergh t e s t end th e plasm a b i l i r u b i n ranged from
2*5 t o 6 u n i t s p e r 100 c . c . plasma.
The h y p e r b ilir u b in a e m ia
was a p p a r e n t ly u n r e l a t e d to th e anhydraemia and a zotaem ia
a lth o u g h i t was p r e s e n t i n most o f th e c a s e s i n which th e
v o m itin g had l a s t e d f o r many weeks.
S e v e r a l p r e v io u s workers
(H ero ld , 1939; F ik e n t s c h e r , 1939) have concluded t h a t th e
serum b i l i r u b i n may be ta k e n a s an ind ex o f the s e v e r i t y o f
th e m e t a b o lic u p s e t i n each c a s e ; th e p r e se n t f i n d i n g s ,
however, do n o t su pp ort t h i s v iew - c a s e s w ith h y p e r b i l i r u b i n raemia were a lw ay s o f th e s e v e r e ty p e but s e v e r a l o f th e
most s e v e r e c a s e s had normal plasm a b i l i r u b i n v a lu e s .
There i s a f a c t o r i n t h e s e hyp erem esis c a s e s which
ten d s t o c a u se d i s c r e p e n c y between th e s e v e r i t y o f the
c l i n i c a l c o n d i t i o n and th e b io c h e m ic a l f i n d i n g s .
th e developm ent o f W ern ick e's encep halopath y.
This i s ,
Campbell and
B ig g a r t (1 9 3 9 ) f i r s t drew a t t e n t i o n to t h i s syndrome i n c a s e s
dying a f t e r a p e r io d o f s e v e r e v om itin g e . g .
in cases of
g a s t r i c carcinom a, and t h e y found changes i n the c a p i l l a r y
endoth elium t o g e t h e r w ith sm a ll haemorrhages, a t c e r t a i n
s i t e s i n th e b r a in .
Sheehan (1939b) found s i m i la r l e s i o n s
i n th e b r a in s o f h y p e r e m e sis p a t i e n t s who d ev e lo p ed th e
te r m in a l c e r e b r a l syndrome.
The f e a t u r e s o f t h i s syndrome
are a p a th y , d r o w s in e s s and p a r a l y s i s o f v a r io u s p a r t s e . g .
so ft p a la te ,
eye m u s c le s e t c ;
s q u in t , d i p l o p i a , and p a r t i a l
or c o m p lete b l i n d n e s s f r e q u e n t l y occu r and b e fo r e death
th e r e may be a p h a se o f g r e a t lo q u a cy or mental c o n f u s io n
ending i n coma.
The p a t i e n t u s u a l l y l i v e s o n ly a few days
a f t e r t h i s syndrome i s f u l l y d e v e lo p ed but e a r l y s i g n s may
be found i n many c a s e s o f s e v e r e h y p er e m e sis.
These e a r l y
s ig n s a r e nystagm us, a p a th y , t e n d e r n e s s o f l e g m u scles end
a r a p id p u l s e .
B e fo re th e p a t h o l o g i c a l l e s i o n s i n the b r a in
r e s p o n s i b l e f o r t h i s c e r e b r a l syndrome were r e c o g n is e d and
f u l l y d e s c r i b e d , a l l t h e s e m en tal and nervous symptoms and
s i g n s u s e d t o be c o n s id e r e d to be the r e s u l t o f some s e v e r e
in to x ic a tio n .
Dieckmann and C rossen ( 19 2 7 ) , F i t z g e r a l d and
Webater ( 1 9 3 8 ) , H erold (1939)?
o t h e r s , d e s c r ib e c a s e s
w ith t y p i c a l s i g n s and symptoms o f W ernicke's en cep h alop ath y
but t h e y d id not r e c o g n i s e th e p a t h o l o g i c a l b a s i s o f th e
c o n d itio n .
I t i s now s u g g e s t e d t h a t th e c e r e b r a l l e s i o n s
are th e r e s u l t o f a v it a m in d e f i c i e n c y - p a r t i c u l a r l y a
d e f i c i e n c y o f the v ita m in B complex.
p o i n t e d o u t by Sheehan (1939b ) i s ,
A most important f a c t ,
th a t t h i s syndrome does
not n e c e s s a r i l y d e v e lo p i n the c a s e s w ith J;he most se v e r e
v o m itin g and i s l i a b l e to occu r i n p a t i e n t s a f t e r th e v o m itin g
has been c o n t r o l l e d by tr e a tm e n t.
When i t d e v e lo p s i n such
c a s e s th e s e v e r i t y o f the c l i n i c a l c o n d i t i o n becomes much
g r e a te r than th e accompanying anhydraemia and a zotaem ia would
su ggest.
In h y p e r e m e s is , t h e r e f o r e , t h e r e are two q u it e
d i s t i n c t p r o c e s s e s which may be p r e s e n t in any c a s e and e i t h e r
o f them may be th e ca u se o f d eath .
I)
These are
D e h y d ra tio n and anhydraemia w ith r e s u l t i n g a zo ta em ia , i n
some c a s e s a s s o c i a t e d w ith h y p e r b ilir u b in a e m ia or a c i d o s i s .
II)
W e r n ic k e 's e n c ep h a lo p a th y .
These f a c t o r s a r e o f c o u rse c l o s e l y r e l a t e d ,
th a t t h e y a r e both t h e r e s u l t o f the v om itin g .
in
In the g r e a t
m a j o r it y o f s e v e r e c a s e s both f a c t o r s are p r e s e n t but t h e i r
r e l a t i v e im portance v a r i e s from c a se to c a s e .
Death, i n
h y p e r e m e sis, i s som etim es due to o th e r f a c t o r s - namely shock, r e s u l t i n g from o p e r a t i v e i n t e r f e r e n c e , or d e la y e d
c h loroform p o i s o n i n g f o l l o w i n g o p e r a tio n .
The p a t i e n t s are
g r e a t l y p r e d i s p o s e d to t h e s e c o n d i t i o n s by th e p r e v io u s
e f f e c t s o f th e v o m itin g .
The f i n d i n g s i n fou r f a t a l c a s e s i l l u s t r a t e the
r e la tiv e s ig n ific a n c e of th ese fa cto rs.
Case 168.
T his p a t i e n t had vom ited f o r 12 weeks and
then d e v e lo p e d a " p e c u l i a r m en tal s t a t e " .
She r e f u s e d food
and d r in k and became v e r y l e t h a r g i c .
U rinary output was good
and t h e r e was no v o m itin g .
L a ter b l in d n e s s develop ed and
h y ste r o to m y was perform ed.
The tem perature r o se to 102° and
th e p u l s e r a t e was 160.
She remained u n co n sciou s a f t e r th e
o p e r a t i o n and had t w i t c h i n g s o f her fa c e and arms. Death
o c cu rr ed about 24 hours a f t e r th e o p e r a tio n .
The blood urea
a t d ea th was 57 mg. p e r 100 c . c .
At the autop sy p e t e c h i a l
haemorrhages were found i n th e corpora mam m illaria, mid b r a in
and f l o o r o f th e f o u r th v e n t r i c l e .
There was no e v id e n c e
t h a t th e d eath was due to shock.
In t h i s c a s e th e r e was a
moderate n i t r o g e n r e t e n t i o n but W ernicke's encep halopath y
was a p p a r e n t ly th e more im portant f a c t o r i n c a u sin g d ea th .
Case 1 6 9 . T h is p a t i e n t had vom ited fo r 7 weeks and had
e v id e n c e o f s e v e r e a c i d o s i s .
She improved g r e a t l y and was
ab le t o t a k e l i g h t d i e t but th e p u ls e r a te began to r i s e .
S l i g h t v o m itin g c o n tin u e d and th e u rin a ry output was good.
Her v o i c e became v e ry husky.
Temperature 101^. P u ls e 145*
She became d e e p ly com atose a f t e r o n ly l / 3 §>r « omnopon had
been g iv e n .
H ysterotom y was performed and p r a c t i c a l l y no
a n a e s t h e t i c was n e c e s s a r y because th e coma was so deep.
She d ie d 4 h ou rs a f t e r th e o p e r a tio n .
Blood u r e a a t death
was 69 mg. o e r 100 c . c .
Plasma b i l i r u b i n 2. p u n i t s .
At th e
a u to p sy t h e r e were few s i g n s o f W ernicke's encep halopath y'
o n ly a few p e t e c h i a l haemorrhages were found i n th e f l o o r ’
o f th e f o u r t h v e n t r i c l e and a l l o th e r p a r t s o f th e b r a in
appeared t o be norma. .
There were s e v e r a l m od erately l a r g e
su b e n d o c a r d ia l haem orrhages on the l e f t s i d e o f the
i n t e r v e n t r i c u l a r septum; t h e s e have been shown to be a
fr e q u e n t post-m ortem f i n d i n g i n c a s e s o f shock (Sheehan, 1959a ) ,
and i t may be assumed i n t h i s c a s e , where death occu rred a
few h o u rs a f t e r o p e r a t i o n , t h a t the u lt i m a t e cause o f death
was sh ock .
Case 1 70.
This c a s e o c c u r r e d b e fo re th e p a t h o l o g i c a l
b a s i s f o r W e rn ic k e 's e n c ep h a lo p a th y was r e c o g n is e d but the
h i s t o r y d u rin g th e l a s t few days o f l i f e i s very t y p i c a l .
The p a t i e n t had been v o m itin g fo r 5 weeks and then became very
drowsy and t h e p u l s e r a t e r o s e .
In tra ven ou s g lu c o s e s a l i n e
was g i v e n and th e v o m itin g become l e s s ; th e d row sin ess
i n c r e a s e d and p a r a l y s i s o f the s o f t p a l a t e was n oted.
H ysterotom y was perform ed.
The p a t i e n t r ec o v er ed c o n s c io u s n e s s
but l a t e r became com atose and d ie d 14 hours a f t e r th e
o p e ra tio n .
At d eath plasm a u r i c a c i d was 2 .4 rag* p er 100 c . c .
and u rea was 42 mg.
There was, t h e r e f o r e , o n ly s l i g h t
a z o ta e m ia i n t h i s c a s e end i t may be presumed th a t W ern icke's
e n c e p h a lo p a th y was th e more im portant f a c t o r in c a u sin g death.
Case 1 7 1 . This c a s e a l s o o ccu rred b e fo r e the
p a t h o l o g i c a l b a s i s f o r W ern ick e's encep halopath y was r e c o g n is e d .
In t h i s c a s e , how ever, th e r e were no s i g n s o f c e r e b r a l
d is tu r b a n c e u n t i l th e day b e f o r e death when the p a t i e n t
became e x tr e m e ly n o i s y and r e s t l e s s .
The tem perature r o se
g r a d u a l l y to reach 1 0 7 ° a t death and the p u ls e r a te was 170
t o 180.
E xam ination o f t h e b lo o d a t death r e v e a le d g r o s s
non—p r o t e i n n i t r o g e n r e t e n t i o n ; th e plasma u r i c a c i d was
20.9^ mg. p e r 100 c . c . and th e b lo od urea was 220 gms.
I t may
be presumed t h a t a z o ta e m ia and anhydraemia were more
im portant f a c t o r s i n c a u s in g death i n t h i s c a s e than W ern ick e's
e n c e p h a lo p a th y .
The b io c h e m ic a l f i n d i n g s i n s e v e r e h y p erem esis
c a s e s may be summarised a s f o l l o w s .
I)
II)
III)
High h a e m a t o c r it v a l u e s .
High plasm a u r i c a c i d and urea.
A p o s i t i v e d e la y e d d i r e c t r e a c t i o n to th e van den
Bergiafand s l i g h t l y in c r e a s e d plasma b i l i r u b i n i n some c a s e s .
These ch an ges a r e th e d i r e c t r e s u l t o f th e
d e h y d r a tio n produced by th e v o m itin g .
W ern ick e's e n c e p h a lo p a th y , d e v e lo p s
A c e r e b r a l syndrome,
i n some c a s e s , p ro b a b ly
the r e s u l t o f v it a m |n d e f i c i e n c y ; t h i s c a u s e s th e s e v e r i t y
o f th e c l i n i c a l s i g n s to be in c r e a s e d out o f p r o p o r tio n to
the b io c h e m ic a l f i n d i n g s and i s f r e q u e n t l y the cause o f d eath.
V om iting o f L ate Pregnancy.
S e v ere v o m itin g i n th e second h a l f o f pregnancy
may be due to s e v e r a l d i f f e r e n t c o n d i t i o n s - in some c a s e s
th e c a u se o f th e v o m itin g i s e a s i l y found but i n o t h e r s th e
v o m itin g may be th e o n ly o b v io u s s ig n and such c a s e s are
f r e q u e n t l y l a b e l l e d - " p e r n ic io u s vom itin g o f pregnancy" or
" t o x ic vom iting" o r " l a t e v o m itin g o f pregnancy".
Such
l a b e l s , however, o n l y ten d to obscu re the a c t u a l cau se o f
th e v o m itin g which can f r e q u e n t l y be determ ined by b io c h e m ic a l
i n v e s t i g a t i o n o f th e b lo o d .
I n the p r e s e n t stu dy many such
c a s e s were i n v e s t i g a t e d and i t has been p o s s i b l e to d i v i d e
them both from a c l i n i c a l and b io c h e m ic a l sta n d p o in t i n t o
s e v e r a l d e f i n i t e groups.
1.
P r o lo n g e d H yperem esis.
Three o f the p r e s e n t c a s e s belong to t h i s group,
c a s e s 1 72, 175 and 1 7 4 .
Each p a t i e n t was a d m itted to
h o s p i t a l a s a c a s e o f " l a t e v om itin g " , but on c a r e f u l
i n t e r r o g a t i o n i t was found t h a t th e v o m itin g , a lth o u g h more
s e v e r e im m e d ia te ly b e fo r e a d m issio n , had been p r e s e n t throughout
th e e a r l y months.
C ases 172 and 173 were both e x tr e m e ly i l l
CiiART XX*
Com posite Graph o f Changes d u r i n g T r e a tm e n t
•------- f"
*
i n C ases 172 & 17o.
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on a d m iss io n and th e b loo d i n v e s t i g a t i o n r e v e a le d g r o s s
changes; i n c a s e 1 7 4 , th e v o m itin g was not so se v e r e and
the b io c h e m ic a l ch an ges were l e s s .
The f i n d i n g s i n th e
th ree c a s e s a r e g i v e n i n th e appendix and a com p osite graph
o f th e ch a n g es o c c u r r in g du rin g treatm en t i n c a s e s 172 and
173 i s g iv e n o p p o s i t e - Chart XX.
c o n c e n tr a t e d ( h a e m a t o c r it 4
The blood was very
44$ r e s p e c t i v e l y ) and
th e re was v e ry marked a z o ta e m ia i n each c a se; th e plasma
u r i c a c i d and u rea v a l u e s were in c r e a s e d p r o p o r t i o n a l l y the r a t i o between t h e i r v a l u e s i n mg. per 100 c . c . b e in g
1 to 10 a p p r o x im a te ly - a s i n th e h yp erem esis c a s e s p r e v i o u s l
d e s c r ib e d .
C ases 172 and 174 were s l i g h t l y jau n d iced ; th e
plasma gave a p o s i t i v e d e la y e d d i r e c t r e a c t i o n to the
van den Bergh t e s t and th e plasm a b i l i r u b i n was 1 2 .2 and
5. 6 u n i t s r e s p e c t i v e l y :
was n e g a t i v e .
i n c a s e 173
van &en Bergh t e s t
The u r in a r y outp ut i n each c a se was very
sm all b e f o r e tr e a tm e n t was g iv e n but, a s can be se en from
Chart XX., im m e d ia te ly th e anhydraemia was r e l i e v e d by
in t r a v e n o u s g l u c o s e s a l i n e , th e u r in a r y output in c r e a s e d
and t h e n i t r o g e n r e t e n t i o n i n the blood d im in ish ed .
The
u r ic a c i d and urea v a l u e s d e c re a sed more or l e s s w ith th e
h a e m a to c r it v a lu e s and m a in ta in e d t h e i r mutual p r o p o r tio n .
These b lo o d changes a r e a l l s i m i l a r to th o s e found i n th e
very s e v e r e h y p e r e m e sis c a s e s and i t seems l i k e l y t h a t t h e y
are th e d i r e c t r e s u l t o f t h e u n u s u a lly p r o lo n g e d v o m itin g .
In c a s e s 172 and 173 th e r e were e a r l y s i g n s o f W ernicke's
76.
e n cep h alop ath y .
Case 172 was very drowsy and had nystagm us,
muscular t e n d e r n e s s and p a i n over the s c i a t i c n e r v e s.
Case
173 had nystagmus and te n d e r n e s s over s e v e r a l n e r v e s.
A ll
th e s e s i g n s c l e a r e d up r a p i d l y w ith the in tr a v en o u s g l u c o s e
th erap y and l a r g e d o s e s o f Vitamen
in tr a m u s c u la r ly .
In t h i s group o f c a s e s the c h a r a c t e r i s t i c f i n d i n g s
which d i f f e r e n t i a t e them from th e c a s e s o f the o th e r groups are
a)
The h i s t o r y o f t h e p r o lo n g e d v o m itin g .
b)
n e g a t i v e c l i n i c a l f i n d i n g s a p a r t from the v o m itin g .
c)
B lood changes - a l l seco n d a ry to th e v om itin g a s i n the
e a r l y h y p e r e m e sis group.
d)
S tead y improvement a s the anhydraemia i s r e l i e v e d .
II.
P y e l i t i s o f Pregnancy.
P y e l i t i s i s a fr e q u e n t cause o f very s e v e r e and
p r o lo n g e d v o m itin g .
About the f i f t h month o f pregnancy i s
the commonest time fo r symptoms o f p y e l i t i s to occur but th e y
may b e g in or become very s e v e r e a t any time i n the second
h a l f o f p reg n a n cy .
In most c a s e s the d i a g n o s i s i s e a s i l y
made from th e h i s t o r y o f lumbar p a in , r i g o r s e t c . and. from th e
u r in a r y f i n d i n g s , but q u i t e f r e q u e n t l y c a s e s p r e s e n t t h e m se lv e s
w ith v o m itin g a s th e o n ly symptom and s i g n , and i t i s not
u n t i l s e v e r a l days have e la p s e d th a t the vom itin g i s found
to be due to th e u r in a r y t r a c t i n f e c t i o n .
In such a. c a s e
the v o m itin g i s presum ably due to com plete b lockage o f th e
u r e t e r r e s u l t i n g i n a tem porary p y o n ep h r o sis on th e a f f e c t e d
s id e ;
i f the u r in a r y t r a c t on the oth e r s i d e i s u n i n f e c t e d
the u r in a r y f i n d i n g s a r e normal.
In th e g r e a t m a j o r it y o f c a s e s o f p y e l i t i s o f
pregnancy no a b n o r m a lity o f th e blo od can be found.
In a
few s e v e r e c a s e s , how ever, n i t r o g e n r e t e n t i o n d e v e lo p s and
t h e r e i s som etim es s l i g h t ja u n d ic e .
p y e litis,
stu d y.
S ix c a s e s o f s e v e r e
c a s e s 175 to 1 8 0 , were i n v e s t i g a t e d i n th e p r e s e n t
The b io c h e m ic a l f i n d i n g s during the c o u rse o f th e
d ise a se ,
i n each c a s e , a r e g i v e n i n th e appendix.
The
h a e m a to c r it v a l u e s were low i n each c a s e ; th e mean h a e m a to c r it
v a lu e from th e 6 c a s e s was 29*5$ r i t h a range o f 27- 5$ to
J l fo.
The v a l u e s showed v e ry l i t t l e change throughout t h e
cou rse o f th e d i s e a s e .
The ab sen ce o f blood c o n c e n t r a t io n i n
t h e s e c a s e s i s r a th e r s u r p r i s i n g s i n c e th e r e had been s e v e r e
and p r o lo n g e d v o m itin g i n each c a s e .
The low h a e m a to cr it
va lu e a p p ea r s to be a c o n s ta n t f i n d i n g i n c a s e s o f p y e l i t i s
o f p regn an cy and i t may be o f h e l p i n th e d i f f e r e n t i a l
d i a g n o s i s o f t h e s e c a s e s o f s e v e r e v om itin g w ithout o b v io u s
c a u se .
For exam ple, c a s e 178 was ad m itted to h o s p i t a l a s a
c a s e o f " l a t e vom itin g" near term; blood p r e s s u r e was normal,
th e r e was no p y u r ia but th e u r in a r y output was s m a ll.
V om iting
was v e r y s e v e r e but t h e h a e m a to cr it v a lu e was o n ly 2 7 *5$ .
The
p a t i e n t went i n t o la b o u r soon a f t e r a d m issio n and was d e l i v e r e d
the same day; th e maximum h a e m a to cr it v a lu e during la b o u r was
32$.
On t h e n e x t day she p a s s e d u r in e h e a v i l y la d e n w ith
pus and h er g e n e r a l c o n d i t i o n improved g r e a t l y ; plasma u r i c
a c id and u r e a d e c r e a se d r a p i d l y to normal.
The d i a g n o s i s o f
78.
p y e l i t i s was s u g g e s t e d i n t h i s c a s e on a d m issio n from th e
h i s t o r y o f s e v e r e v o m itin g , d im in ish ed u r in a r y o u tp u t, and
because t h e h a e m a to c r it v a lu e was low i n s p i t e o f th e v o m itin g .
The sudden e x c r e t i o n o f l a r g e q u a n t i t i e s o f pus a f t e r
d e l i v e r y co n firm e d th e d i a g n o s i s .
Anaemia r e s u l t i n g from th e
i n f e c t i o n i s a p o s s i b l e c a u se o f th e sm all c e l l volume.
The o r i g i n a l u r i c a c i d and urea v a lu e s i n 5 o f th e
c a s e s were p r a c t i c a l l y w i t h i n normal l i m i t s alth ou gh th e
p a t i e n t s were s h a r p ly i l l a t th e tim e .
The u r ic a c id and
urea v a l u e s r o se v e r y l a t e i n t h e d i s e a s e - i n th e two f a t a l
c a s e s , 176 and 1 7 7 , th e r i s e began o n ly a few days b e fo r e
death.
In c a s e 179 th e u r i c a c i d and urea v a lu e s were alw ays
w i t h i n normal l i m i t s a lth o u g h t h i s p a t i e n t appeared to be
a c u t e l y i l l w ith v o m itin g and p y u r ia .
Case 180 was o n ly
a d m itted to h o s p i t a l l a t e i n t h e d i s e a s e and t h e r e f o r e th e
o r i g i n a l u r e a v a lu e o b t a in e d was h ig h .
Labour appeared to a g g r a v a te th e c o n d it io n o f t h e s e
p a t i e n t s g r e a t l y - presum ably due to fu r th e r o b s t r u c t i o n o f
the u r e t e r s c a u s in g i n c r e a s e d sp read o f th e i n f e c t i o n i n t o
th e k id n e y t i s s u e .
I t w i l l be n o t i c e d th a t i n c a s e s 175 an(^
176 t h e n i t r o g e n r e t e n t i o n mounted r a p id ly b efore and a f t e r
d e liv e r y .
In c a s e s 175, 176 and 177 where a rap id i n c r e a s e
in t h e n i t r o g e n r e t e n t i o n o c cu rr ed , th e blood, urea r i s e was
g r e a t e r th a n th e c o r r e sp o n d in g r i s e i n plasma u r i c a c id .
In 4 o f th e 6 c a s e s , 175, 177, 178 and 180, s t u d ie d
in d e t a i l th e plasm a gave a p o s i t i v e immediate d i r e c t r e a c t i o n
79 .
to th e van den Bergh t e s t and th e plasma b i l i r u b i n was r a is e d :
the mean v a lu e f o r th e fo u r c a s e s was 4 .5 u n i t s with a range
of 3 to 7 u n its .
. In th e t h r e e f a t a l c a s e s , 1 7 6 , 177 and 180, p o s t ­
mortem e x a m in a tio n r e v e a l e d g r o s s p y e l o n e p h r i t i s .
In c a s e 177 t h e r e was g r e a t d e s t r u c t i o n o f th e k id n ey
t i s s u e on both s i d e s .
The r i g h t k id n ey weighed l8 0 gms. and
th e l e f t 90 gms.
The l e f t k id n e y was sm all and m isshapen and
had g r o s s h y d r o n e p h r o sis; o n ly one or two sm all a r e a s o f kid ney
t i s s u e rem ained.
The s u r f a c e o f th e r ig h t kidney was i r r e g u l a r
and showed l a r g e d e e p ly c o n g e s t e d a r e a s; a g a in th e r e was g r o s s
d i s t e n s i o n o f the c a l y c e s and th e k id n ey t i s s u e showed d i f f u s e
and s e v e r e p y e l o n e p h r i t i s w ith sm all a b s c e s s e s i n the o u te r
cortex.
In s p i t e o f t h i s g r o s s r e n a l damage which must have
been p r e s e n t f o r s e v e r a l weeks b e fo r e death, th e re was no
r e t e n t i o n o f plasm a u r i c a c i d and urea i n the blood u n t i l th e
day b e fo r e d eath .
In c a s e s 176 and 180 t h e r e was l e s s d e s t r u c t i o n o f th e
k id n e y s but p y e l o n e p h r i t i s was d i f f u s e and s e v e r e ; t h e r e were
numerous sm a ll c o r t i c a l a b s c e s s e s w ith p u ru len t tr a c k s l e a d in g
through th e c o r t e x and m ed u lla to th e p e l v i s .
In t h e s e c a s e s
a n i t r o g e n r e t e n t i o n was p r e s e n t for s e v e r a l days b e fo r e d ea th .
The c h a r a c t e r i s t i c b io c h e m ic a l f i n d in g s in th e bloo d
i n c a s e s o f p y e l i t i s o f pregnancy are:
a)
A lo w h a e m a to c r it v a lu e .
b)
A r e t e n t i o n o f n o n - p r o t e i n n i t r o g e n f r a c t i o n s , the r i s e i n
blood u r e a b e in g r e l a t i v e l y g r e a t e r than the r i s e i n plasma
u r ic a c i d .
In some c a s e s w ith g r o ss r en a l damage, however,
th e r e may be no r e t e n t i o n o f t h e s e f r a c t i o n s u n t i l v e r y l a t e
i n th e d i s e a s e .
c)
A p o s i t i v e im m ediate d i r e c t r e a c t i o n to th e van den Bergh
t e s t and a s l i g h t i n c r e a s e i n plasma b i l i r u b i n i n some c a s e s .
III.
“E r y t h r o b l a s t o s i s F o e t a l i s 11.
In fo u r o f th e c a s e s ( l 8l , 182, 183 and 1 8 4 ) o f
8o.
s e v e r e v o m itin g i n l a t e pregnancy i n th e p r e s e n t s e r i e s an
a b n o rm a lity o f th e ovum was found to be p r e s e n t .
The v o m itin g i n t h e s e c a s e s commenced about th e
28th t o t h e 32nd week o f pregnancy and was e x c e e d in g ly s e v e r e .
The p a t i e n t s r a p i d l y became a c u t e l y i l l and were d e l i v e r e d
p r e m a tu re ly o f p t i l l - b o r n c h i ld r e n .
In each c a s e th e u t e r i n e
c o n t e n t s were n o te d to be l a r g e and oedematous: i n c a s e 1 8 1 ,
the 7 month f o e t u s was h y d r o c e p h a lic , weighed 7 l b s . and th e
p l a c e n t a w eighed 5 l b s .
6 o z . ; i n c a s e 1 8 2 , th e f o e t u s a t 71-
months was v e r y oedematous and w eighed 7 l b s . , th e p la c e n t a
was n o te d to be l a r g e ;
in c a s e 1 8 3 ? th e 6 month f o e t u s had
g e n e r a l i s e d oedema but w eighed o n l y 4h l b s . w h ile th e p la c e n t a
w eighed ltj* l b s . ; and i n c a s e 1 8 4 ? th e f o e t u s a t 7if months
weighed 8-|- l b s .
In 3 o f th e c a s e s th e l iq u o r amnii was noted
to be a v e r y deep y e llo w c o lo u r .
These c h i ld r e n and p l a c e n t a e
were n ot examined f u r t h e r but th e y presumably belong to th e
e r y t h r o b l a s t o s i s group o f a b n o r m a lit ie s .
During th e a c u t e s t a g e o f th e i l l n e s s each o f t h e s e
p a t i e n t s was v e r y r e s t l e s s and e x h i b i t e d s l i g h t mental
c o n f u s io n .
There was s l i g h t i c t e r u s in th r e e o f th e c a s e s ,
1 8 1 , 1 8 3 , and 1 8 4 , w h ile c a s e 182 became d e e p ly ja u n d ic ed
a fte r d e liv e r y .
The plasm a gave a p o s i t i v e d e la y e d d i r e c t
r e a c t i o n t o th e van den Bergh t e s t i n each c a s e on a d m issio n .
The b lo o d p r e s s u r e was r a i s e d i n one c a s e but was normal i n
th e o t h e r t h r e e .
The u r in e co n ta in e d some albumen and a
t r a c e o f b i l e i n each c a s e .
81.
E xam ination o f th e b lood showed s l i g h t l y in c r e a s e d
h a e m a to cr it v a l u e s i n a l l c a s e s , but i n c a s e s a f t e r d e l i v e r y
or a f t e r in t r a v e n o u s g l u c o s e had been g iv e n the i n c r e a s e was
not an a b s o l u t e on e.
Plasma u r i c a c i d , u rea and b i l i r u b i n
were r a i s e d i n each c a s e .
In t h r e e o f the c a s e s , l 8l ,
183
and 1 8 4 , th e u r i c a c i d v a lu e was r e l a t i v e l y much h ig h e r than,
th e u r e a v a lu e and i n one c a s e th e blood urea was normal.
The a b n o r m a l i t ie s c l e a r e d up g r a d u a lly a f t e r d e l i v e r y .
In
th r e e o f th e c a s e s , 1 8 2 , 183 and 1 8 4 , continu ous in tr a v e n o u s
g lu c o s e was g i v e n and appeared to a i d r eco v ery .
The plasma
b i l i r u b i n ranged from 2 .9 u n i t s i n c a s e 181 to 22 u n i t s i n
c a s e 18 2 .
( I n d i v i d u a l f i n d i n g s g i v e n i n app en dix).
In t h e s e p a t i e n t s th e b lood changes were not m erely
the r e s u l t o f s e v e r e v o m itin g ; t h e r e was no obviou s r e l a t i o n
between anhydraemia and a z o ta e m ia .
There i s presumably a
r e l a t i o n s h i p betw een th e m o th e r 's i l l n e s s and th e abn orm ality
o f th e p r o d u c t s o f c o n c e p t io n but i t i s im p o s s ib le to say
which i s prim ary.
A lthough the term " e r y t h r o b la s t o s i s f o e t a l i s "
has been u s e d to d e s c r i b e t h i s group o f p a t i e n t s , i t i s not
s u g g e s t e d t h a t a l l p a t i e n t s d e l i v e r e d o f c h i ld r e n w ith
e r y t h r o b l a s t o s i s , s u f f e r from t h i s c o n d it io n .
The c o n d i t i o n
appears to be ■unrelated to h y p e r t e n s iv e toxaem ia - th e p a t i e n t s
were a l l e x tr e m e ly i l l w ith ou t any marked r i s e i n bloo d
p r e s s u r e o r s i g n o f impending e clam p sia and th e bloo d u rea
v a lu e s were h ig h i n c o n t r a s t t o th o s e in th e p r e -e c la m p tic
cases.
The e a r l y appearance o f ja u n d ic e , p o s i t i v e d e la y e d
82.
d i r e c t r e a c t i o n t o th e van den Bergh t e s t , and the r a i s e d
plasma b i l i r u b i n i n each c a s e s u g g e s t th a t l i v e r damage may
be a p rim ary f a c t o r but th e e t i o l o g y o f the c o n d i t i o n i s
o b scu re .
The main c h a r a c t e r i s t i c s o f t h i s s e v e r e v o m itin g
group a re:
a)
The f o e t a l and p l a c e n t a l a b n o r m a lit ie s .
b)
S l i g h t j a u n d ic e and r a i s e d plasma b i l i r u b i n w ith a p o s i t i v e
d e la y e d d i r e c t r e a c t i o n t o the van den Bergh t e s t .
c)
Very h ig h plasm a u r i c a c i d and m o d era tely h ig h b lood urea
v a lu e s.
XV.
M is c e ll a n e o u s Group.
This group i n c l u d e s c a s e s o f vom itin g due to
h y p e r t e n s i v e to x a em ia , a c u t e y e ll o w atrop hy and i d i o p a t h i c
v o m itin g o f l a t e pregnancy.
H y p e r te n s iv e to xaem ia must be in c lu d e d a s a cause o f
v o m itin g i n l a t e pregn an cy but i t i s seldom th e cause o f
p r o lo n g e d and s e v e r e v o m itin g .
Severe p r e -e c la m p tic and
e c la m p tic c a s e s o f t e n have a moderate amount o f s i c k n e s s
but v o m itin g i s r a r e l y th e main f e a t u r e o f the d i s e a s e .
Such c a s e s can , t h e r e f o r e , be e a s i l y d i f f e r e n t i a t e d from th e
o th e r groups d e s c r ib e d h e r e , by th e p r e se n c e o f th e c h a r a c t e r ­
istic
s i g n s o f h y p e r t e n s i v e toxaem ia.
In th e s e r i e s o f 56
p r e - e c l a m p t i c and 4 2 e c la m p tic c a s e s s t u d ie d i n s e c t i o n s I I .
anri h i . , no p a t i e n t had s u f f i c i e n t vom itin g to warrant h e r
i n c l u s i o n i n a group o f l a t e v o m itin g c a s e s .
Acute y e ll o w a tro p h y i s c e r t a i n l y a cause o f very
se v er e v o m itin g end t h i s c o n d i t i o n w i l l be d i s c u s s e d i n
the n e x t s e c t i o n on ja u n d ic e i n pregnancy.
With r e g a r d to i d i o p a t h i c vo m itin g o f l a t e pregnancy
i t seems v e r y u n l i k e l y t h a t such a c o n d it io n e x i s t s .
D e t a il e d
exam in ation o f each c a s e u s u a l l y r e v e a l s the cau se or natu re
o f the v o m itin g b u t, a t p r e s e n t , t h i s term may be g iv e n to any
c a s e , i n th e secon d h a l f o f pregnancy, w ith se v er e and p r o lo n g e d
v o m itin g which cannot be in c lu d e d i n any o f the groups
d e s c r ib e d h e r e .
I t w i l l be n o te d t h a t th e terms “t o x i c
v o m itin g 11, and “p e r n i c i o u s v o m it in g 11 o f pregnancy a r e not
used i n th e p r e s e n t work.
These term s have been a p p lie d to
alm ost any c a s e o f v o m itin g w ith s i g n s o f a gen eral m e ta b o lic
d is tu r b a n c e - f o r example, c a s e s o f se v e r e p y e l o n e p h r i t i s w ith
r a is e d tem p era tu re and a z o ta e m ia , c a s e s o f s e v e r e h y p erem esis
w ith a z o ta e m ia , a c i d o s i s or W ernickefs encephalopathy, and
c a s e s o f h y p e r t e n s i v e to x a em ia w ith some v o m itin g .
In some o f
t h e s e c a s e s t h e m e t a b o lic u p se t i s th e r e s u l t o f the v o m itin g
w h ile i n o t h e r s i t r e s u l t s from th e cause o f th e vom itin g; th e
use o f term s such a s “t o x i c vom iting" or “p e r n i c i o u s vomiting"
o f p regn an cy o n l y te n d to ob scu re the natu re o f th e i l l n e s s
p resen t.
Summary.
C ases o f s e v e r e v o m itin g , r e l a t e d t o , and o c c u r r in g
during p regn an cy, a r e s t u d i e d .
f o l lo w s :
They are c l a s s i f i e d a s
8*
A.
V om iting o f E a r ly Pregnancy. - Hyperemesis Gravidarum.
B.
V om iting o f L ate Pregnancy.
I.
P ro lo n g e d H yperem esis.
II.
P y e l i t i s o f Pregnancy.
III.
IV.
" E r y th r o b la sto sis F o e t a l i s . H
M is c e ll a n e o u s Group - i n c lu d in g h y p e r t e n s iv e
toxaem ic c a s e s , a c u t e y e llo w atrophy c a s e s and
id io p a th ic c a ses.
The b io c h e m ic a l f i n d i n g s from c a s e s i n each group
are g i v e n and th e p o i n t s o f d i f f e r e n t i a t i o n are d is c u s s e d .
S E C T I Q H
VI.
JAUNDICE IN PREGNANCY.
In t h e p r e c e d in g s e c t i o n s many p a t i e n t s s u f f e r i n g
from v a r io u s c o n d i t i o n s have been n o te d t o have s l i g h t
ja u n d ic e w ith r a i s e d plasm a b i l i r u b i n v a lu e s and to g i v e
p o s i t i v e r e a c t i o n s to th e van den Bergh t e s t .
In some c a s e s
th e p a t h o l o g i c a l b a s i s f o r t h e s e f i n d i n g s can be t r a c e d , but
in o t h e r s th e a c t u a l cau se i s o b scu re .
In E clam p sia, h a e m o ly s is may g iv e r i s e to a p o s i t i v e
i n d i r e c t r e a c t i o n to th e van den Bergh t e s t and in c r e a s e d
plasma b i l i r u b i n - e . g .
i n c a s e 121 d e s c r ib e d i n S e c t i o n I I I . ,
or th e l i v e r haem orrhages may cau se a p o s i t i v e d e la y ed d i r e c t
r e a c t i o n to th e van den Bergh t e s t and in c r e a s e d plasma
b iliru b in .
*n H y p e re m esis, however, t h e cau se o f the r a i s e d
plasma b i l i r u b i n and p o s i t i v e van den Bergh t e s t i n some
p a tie n ts,
i s not c l e a r .
H erold (1 9 3 9 ) , o b ta in e d no e v id e n c e
o f i n c r e a s e d d e s t r u c t i o n o f red blood c e l l s i n h y p erem esis
p a t i e n t s and he c o n c lu d e d t h a t th e r a is e d serum b i l i r u b i n and
in c r e a s e d p o r p h y r in e x c r e t i o n , which he found i n t h e s e c a s e s ,
were due t o d e p r e s s e d l i v e r f u n c t i o n .
P a t h o l o g ic a l f i n d i n g s
in th e l i v e r s o f f a t a l c a s e s do not g iv e much i n d i c a t i o n a s
to th e c a u se o f th e ja u n d ic e ; i t can not be a s c r ib e d i n any
way t o t h e c e n t r a l f a t t y change found i n some f a t a l c a s e s .
S l i g h t ja u n d ic e i n c a s e s o f P y e l o n e p h r i t i s mav
p o s s i b l y be due t o an e a r l y i n f e c t i v e c h o l a n g i t i s .
In f a t a l
c a s e s o f p y e l o n e p h r i t i s w ith ja u n d ic e , polymorph i n f i l t r a t i o n
i s found around th e p o r t a l t r a c t s ; and, i n fo u r o f th e
p y e l i t i s c a s e s o f th e p r e s e n t stu d y th e plasma gave a p o s i t i v e
immediate d i r e c t r e a c t i o n to th e van den Bergh t e s t ,
th a t t h e j a u n d ic e was o f th e o b s t r u c t i v e ty p e .
su g g e stin g
S l i g h t j a u n d ic e ,
r a i s e d plasm a b i l i r u b i n and a p o s i t i v e d e la y ed d i r e c t r e a c t i o n
to th e van den Bergh t e s t a r e a l s o f e a t u r e s o f the c a s e s o f
l a t e v o m itin g w ith f o e t a l a b n o r m a l i t ie s .
The p o s s i b l e l i v e r
le s io n s in th ese c a ses are d iscu sse d la t e r .
In a l l t h e s e
c o n d i t i o n s j u s t m en tio n ed , w ith th e e x c e p tio n o f the l a s t ,
the ja u n d ic e i s v e r y much a secon d ary f e a t u r e o f the d i s e a s e i t a p p ea r s l a t e i n th e d i s e a s e and i s s l i g h t .
The p r e s e n t s e c t i o n d e a l s w ith c a s e s i n which
ja u n d ic e i s one o f th e main f e a t u r e s .
Oases o f o b s t r u c t i v e
ja u n d ic e due to g a l l s t o n e s e t c . are not in c lu d e d .
Three
d i f f e r e n t c o n d i t i o n s have been found to cause such ja u n d ic e ;
th ese a re,
1.
O b s t e t r i c a c u t e y e ll o w atrop h y,
2,.
True a c u t e y e ll o w a tro p h y , and
3-
D elayed ch lo roform p o i s o n i n g .
Sheehan ( 1 9 4 0 ) , h a s shown t h a t the p a th o lo g y o f th e c o n d i t i o n
f r e q u e n t l y d e s c r i b e d a s a c u te y e llo w atrop hy o f pregnancy i s
q u ite d i f f e r e n t from t h a t o f th e a c u te y e llo w atrop h y met w ith
in n on -p regn an t p a t i e n t s .
He r e f e r s to the former a s
o b s t e t r i c a c u t e y e ll o w a tro p h y and th e l a t t e r a s tr u e a c u te
y e llo w a tr o p h y and t h i s t e r m in o lo g y w i l l be used h e r e .
In
each c o n d i t i o n ja u n d ic e i s th e main f e a t u r e o f the d i s e a s e
and c l i n i c a l l y th e two c o n d i t i o n s are very a l i k e a lth o u g h t h e i r
p a th o lo g y i s q u i t e d i s t i n c t .
One c a s e o f each ty p e o f l i v e r
damage h as been s t u d i e d i n the p r e s e n t s e r i e s and i t w i l l be
shown t h a t t h e b io c h e m ic a l changes d i f f e r w id e ly i n th e two
co n d itio n s.
O b s t e t r i c A cute Y ellow Atrophy.
The p a t i e n t , c a s e 1 8 5 , s u f f e r i n g from t h i s c o n d i t i o n
was a d m itte d to h o s p i t a l i n the 32nd week o f her pregnancy a s
a c a s e o f l a t e v o m itin g .
She had been w e ll u n t i l 2 weeks
b e fo r e a d m is s io n when she began to have s e v e r e vom itin g and
com p lete a n o r e x ia .
A tta c k s o f v o m itin g were preceded by some
p a in i n th e e p ig a s tr iu m and between the sh o u ld er b la d e s .
At
t h i s tim e th e b lo o d p r e s s u r e was s a id to be normal and th e
u r in e c l e a r .
26.
27.
3 .4 0 . The p a t i e n t was ad m itted to h o s p i t a l .
The b lood
p r e s s u r e was 1 7 6 /1 2 0 and the u r in e c o n ta in e d
albumen - .5 p a r t s Esbach - but no a c e to n e .
She
was w e l l- n o u r is h e d ; h e r l i p s were red and g la z e d
and t h e r e was s l i g h t i c t e r u s o f th e c o n j u n c t iv a e .
She was v e ry c o n s t i p a t e d .
There was no abdominal
t e n d e r n e s s and no oedema.
3 . 4 0 . She had o n l y o c c a s i o n a l vom itin g and was a b l e to
ta k e o r d in a r y d i e t .
Blood p r e s s u r e 140/ l l Q , u r in e
c o n t a in e d albumen . 5 p a r t s E . , no a c e to n e and no
b ile .
T. 9 7 .6 ; P. 100; R. 20.
CHART XXI.
*-----------* H*«*i * T » cA ( T*
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incj. ?e«, (ooc.c. 'PLfliMq
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28. 3*40.
B lig h t g e n e r a l i c t e r u s was n oted but th e r e was
no b i l e i n th e u r in e .
S t o o l s were normal and th e
u r in a r y o u tp u t was good.
She com plained o f backache
and e p i g a s t r i c p a in and had 22 oz. s i c k n e s s .
T. 97;
120; R. 20.
The ja u n d ic e deepened
du rin g th e n ext few days and she was r a th e r drowsy v o m itin g o c c a s i o n a l l y .
The u r in a r y output was good
(4 2 t o 62 oz. p er day) and th e u r in e c o n ta in e d
• 5 p a r t s E . , no a c e to n e and no b i l e .
30 .
3*40 * 600 c . c . 25$ g lu c o s e s a l i n e was g iv e n in t r a v e n o u s ly
and t h i s was f o l lo w e d by a d e f i n i t e improvement i n
her gen era l c o n d itio n .
Ho fu r th e r in tr a v e n o u s f l u i d
was g i v e n .
1. 4 . 4 0 .
The p a t i e n t had no v o m itin g and the ja u n d ic e was
unchanged.
2.
4. 4 0 . Labour p a i n s began a t 8 a.m.
The jau n d ice appeared
t o be d ee p e r and mucosae were r a th e r cyanosed.
The
p a t i e n t was e x tr e m e ly drowsy but her m ental c o n d i t i o n
was o t h e r w is e normal.
10 a.m.
T. 99; P. 112; R. 20.
Blood p r e s s u r e 1 7 0 /1 1 5
3 p.m.
She was d e l i v e r e d sp o n ta n eo u sly o f a l i v i n g ,
prem ature, fem a le c h i l d w eigh in g 4f l b s . ; th e
p l a c e n t a was not w eighed.
She became very s i c k and
had s e v e r e r e t c h i n g soon a f t e r d e l i v e r y . Her sk in
f e l t e x tr e m e ly h o t .
Blood p r e s s u r e 140/125*
4 . 3O p.m.
The p a t i e n t became very c o l l a p s e d b lo o d p r e s s u r e 1 4 0 / 1 3 0 . She was very a p a t h e t i c and
th e v o m itin g became s e v e r e .
Continuous in tra ven o iis
g l u c o s e s a l i n e was g i v e n but the p a t i e n t did not
improve.
9 p.m.
She became very r e s t l e s s and l a t e r comatose.
Death o c c u r r e d a t 1 1 .1 0 p.m.
The b io c h e m ic a l f i n d i n g s are g iv e n below and are shown
o p p o s i t e i n graph form - Chart XXI. - plasma sodium and whole
blood c h l o r i d e a r e not in c lu d e d i n t h i s graph.
*9.
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The b lo o d was e x tr e m e ly c o n c e n tr a t e d throughout the i l l n e s s .
The plasm a u r e a v a l u e s r o s e r a p i d l y during the f i r s t day o f
the i n v e s t i g a t i o n and th e n remained a lm o st unchanged; th e
plasma u r i c a c i d v a l u e s were g r e a t l y in c r e a s e d and were
r e l a t i v e l y much h ig h e r than the u rea v a lu e s .
The plasma gave
a p o s i t i v e d e la y e d d i r e c t r e a c t i o n to the van den Bergh t e s t
and th e plasm a b i l i r u b i n r a s h ig h .
Blood d i l u t i o n , accompanied
by a f a l l i n plasm a u r i c a c i d and u r e a , fo llo w e d in tr a v e n o u s
g lu c o s e t r a n s f u s i o n and the improvement l a s t e d fo r more than
24 h o u r s .
Whole b lo o d c h l o r i d e s were abnorm ally low u n t i l
a few h ou rs b e fo r e death when t h e y r o s e to 628 mg. p er 100 c . c .
plasma sodium v a lu e s ranged around the upper l i m i t o f normal
u n t i l a few hours b e fo r e death when th e y r o se to 3^9
100 c . c .
p er
Some o f the u r in a r y f i n d i n g s were r a th e r u n ex p ected .
During the p e r io d o f o b s e r v a t i o n th e p a t i e n t fs u r in a r y output
was v e r y good - 37 t o 79 oz. p e r day, i n s p i t e o f the f a c t
th a t her b lo o d was v e r y c o n c e n tr a t e d .
U n fo r tu n a te ly no r e n a l
f u n c t i o n t e s t s were perform ed but i t may be presumed t h a t th e
c o n c e n t r a t i n g power o f th e k id n ey was poor.
B ile was never
p r e s e n t i n th e u r in e a lth o u g h the plasma b i l i r u b i n was r a i s e d
and t h e r e was o b v io u s ja u n d ic e .
U rinary albumen remained
c o n s ta n t a t .3 p a r t s Esbach throughout the p e r io d o f
exa m in a tio n .
At th e a u to p s y , perform ed th r e e hours a f t e r d eath ,
the l i v e r w eighed 1 ,1 0 0 gms. and was very s o f t .
I t was l i g h t
y e llo w i n c o lo u r w ith a f i n e m o t t li n g o f p i n - p o i n t red d o t s .
PLATE
U .
L iver in O b s t e t r i c Acute Yellow Atrophy.
High power view showing cytoplasmic change in c e n t r o l o o u l a r cells
and absence of n e c r o s i s .
( Case
135 }
91.
On h i s t o l o g i c a l e x a m in a tio n th e c e n tr o lo b u la r c e l l s were
found to be s w o ll e n and f i l l e d w ith a f i n e foam o f sm a ll
fa tt y g lo b u le s.
were u n a f f e c t e d .
c e lls .
The c e l l s o f th e o u te r h a l v e s o f th e l o b u l e s
There was no t r a c e o f n e c r o s i s o f l i v e r
A m icroph otograp h o f th e c e n tr o lo b u ia r c e l l s i s shown
in P l a t e IV.
The changes a r e t y p i c a l o f o b s t e t r i c a c u te
y e llo w a tr o p h y , a s d e s c r ib e d by Sheehan ( 1 9 4 0 ) , a lth o u g h th e
zone o f f a t t y change i s l e s s e x t e n s i v e i n the p r e se n t c a se
than i n t h o s e o r i g i n a l l y d e s c r ib e d .
and v e r y fir m .
The kid neys were sm all
The c o r t e x was v e r y w h ite , the normal s t r i a t i o n
was d i s t o r t e d and th e c a p s u le was a d h eren t.
M ic r o s c o p ic a lly
th e r e was a v e r y f i n e e a r l y i n t e r s t i t i a l f i b r o s i s .
The
g lo m e r u li appeared to be normal but t h e r e was evid en ce o f
t u b u la r damage - th e e p it h e liu m o f the c o n v o lu te d tu b u le s
was v ery low; some o f the c e l l s were n ec ro se d and i n p a r t s
th e r e was r e g e n e r a t i o n o f tu b u la r c e l l s .
A s o f t , lo b u la t e d
tumour m ass, about 4 “ * 3" x 2" was found l y i n g on th e
p o s t e r i o r abdominal w a ll behind th e pan creas on the l e f t s i d e ,
with no a ttach m en t to any organ.
On s e c t i o n , the tumour
c o n s i s t e d o f y e l l o w i s h t i s s u e , o b v io u s ly f a s c i c u l a t e d , w ith
s e v e r a l haem orrhages i n t o i t s su b sta n c e and some c y s t i c change.
From m ic r o s c o p ic e x a m in a tio n a d i a g n o s is o f benign ch ro m affin
c e l l tumour (p a raga n g liom a ) was made.
The remaining p o s t ­
mortem f i n d i n g s r e v e a le d no a b n o r m a lit ie s e x ce p t fo r two
sm all p e d u n c u la te d s u b p e r ito n e a l u t e r in e f i b r o i d s , one o f
which showed marked red d e g e n e r a tio n and c o n ta in e d q u it e a
la r g e p a t c h o f n e c r o s i s .
In t h i s c a s e ( 1 8 5 ) the d e g e n e r a tiv e changes i n th e
l i v e r were t y p i c a l 0 f o b s t e t r i c a c u te y e llo w atrophy; th e y
were c o n f i n e d to th e c e n t r e h a lv e s o f the l o b u l e s , however,
and t h e y do n ot seem a s u f f i c i e n t cause o f d eath.
The p a r t
p la y e d by th e a d r e n a l i n - s e c r e t i n g paragangliom a which was
found a t th e post-m ortem e x a m in a tio n i n t h i s c a s e must be
e s t im a te d .
A h i s t o r y was not o b ta in e d o f paroxysmal
h y p e r t e n s io n or o t h e r c l i n i c a l m a n i f e s t a t io n s which have
been r e p o r t e d i n th e l i t e r a t u r e a s a s s o c i a t e d w ith t h e s e
benign c h r o m a ffin c e l l tumours (E ise n b e r g and Wall e r s t e in ,
1932; B e lt and P o w e ll, 1934; W ells and Boman, 1937; Howard
and Barker, 1937; H e g g lin and Nabholz, 1 9 3 8 ; and H o ls t , 1 9 3 8 ).
D e t a il e d b lo o d p r e s s u r e r e a d in g s were n ot a v a i l a b l e i n th e
present c a se,
but a f t e r a d m is s io n to h o s p i t a l , th e s e v a r ie d
between 1 7 6 /1 2 6 and 140 /H O .
A g r e a t l y in c r e a s e d s u s c e p t i b i l i t y
to sh ock , how ever, i s one o f th e o u ts ta n d in g f e a t u r e s o f the
benign c h r o m a ffin c e l l tumour syndrome and O berling and Jung,
( 1 9 2 7 ) , r e p o r t an example o f t h i s syndrome i n a pregnant
woman who d ie d o f shock s i x hours a f t e r a normal d e l i v e r y .
I t seems v e r y l i k e l y t h a t , i n the p r e s e n t c a s e , t h e u l t im a t e
cau se o f d e a th was shock.
This c o n c lu s io n i s supported by
the c l i n i c a l f i n d i n g s - the sudden d e t e r i o r a t i o n i n the
p a t i e n t * s c o n d i t i o n during la b o u r , th e g r e a t l y d im in ish ed
p u lse p r e s s u r e a f t e r d e l i v e r y and f i n a l c o l l a p s e .
This c a s e
may, t h e r e f o r e , be regarded a s one o f m ild o b s t e t r i c a c u te
y e llo w a tr o p h y i n which death occu rred from an i n c i d e n t a l
cause.
Stander and Cadden ( 1934a) d e s c r i b e a c a s e o f
"acute y e l l o w a tr o p h y o f the l i v e r " i n pregnancy w ith f i n d i n g s
very s i m i l a r to t h o s e o f the c a s e j u s t d e s c r ib e d .
The
d i s e a s e a p p ea rs t o have been more a c u te i n t h e i r c a se - death
o c c u r r in g 6 days a f t e r the o n s e t o f symptoms.
They found
r a i s e d b lo o d n o n - p r o t e i n n i t r o g e n , u r i c a c id , a m in o -a c id s
and c r e a t i n i n e w ith low blood c h l o r i d e s and d im in ish ed COg
volumes p e r c e n t; th e o n l y d i f f e r e n c e between t h e i r f i n d i n g s
and t h o s e o f the p r e s e n t c a s e i s i n the blood urea v a lu e
which was w i t h i n normal l i m i t s i n t h e i r c a s e .
The p a t h o l o g i c a l
l i v e r ch an ges i n th e two c a s e s appear to be i d e n t i c a l .
Sheehan (1 9 4 0 ) d e s c r i b e s s i x c a s e s w ith s i m i l a r p a t h o l o g i c a l
f i n d i n g s and h a s p o in t e d out t h a t t h i s ty p e o f l i v e r l e s i o n
i s n o t , a s s u g g e s t e d by Stander and Cadden (I934t>)> a s t a g e
p r e c e d in g the n e c r o s i s o f t r u e a c u te y e llo w atrop hy but i s
a d e fin ite e n tity .
There a r e s e v e r a l p o i n t s o f resem blance between
the b io c h e m ic a l f i n d i n g s i n c a s e 185 and th o se i n c a s e s l 8l
to I 8 4 , th e t h i r d group o f l a t e vom itin g c a s e s a s s o c i a t e d
with e r y t h r o b l a s t o s i s f o e t a l i s .
Severe vom itin g and v a r y in g
d e g rees o f j a u n d ic e a r e th e main f e a t u r e s o f each c a s e and
the tim e o f o n s e t o f symptoms i s a p p ro xim ately the same i n
a ll cases.
I n c r e a s e d blood c o n c e n t r a t io n , very h ig h plasma
u r ic a c i d , r a i s e d blo od u r e a , p o s i t i v e d ela y ed d i r e c t r e a c t i o n
H .
to th e van den Bergh t e s t and r a i s e d plasma b i l i r u b i n are
found i n both t y p e s o f c a s e .
The q u e s t io n a r i s e s whether
th e s e l a t e v o m itin g c a s e s a r e n o n - f a t a l examples o f o b s t e t r i c
acute y e ll o w a tro p h y .
Duncan and MacLachlan ( 1 9 3 3 ) , r e p o r te d
a c a s e o f “y e ll o w a tr o p h y o f th e L iv e r i n Pregnancy” i n which
the b io c h e m ic a l f i n d i n g s resem bled th o se o f the p r e se n t s e r i e s .
The b lo o d urea r ea ch ed 168 mg. per 100 c . c .
not e s t i m a t e d .
but u r ic a c id was
Their p a t i e n t r e c o v e r e d a f t e r the d e l i v e r y
o f a m acera ted f o e t u s .
Sheehan ( 1 9 4 0 ) , p o in te d out t h a t th e
appearance o f the l i v e r l e s i o n s i n t h i s c o n d i t i o n su g g e s te d
th a t t h e y were o f a r e v e r s i b l e n a tu re and th a t th e y were
p o s s i b l y o n l y the r e s u l t o f a p a r t i c u l a r type o f m eta b o lic
d is tu r b a n c e ; he m en tio n s th a t i n h i s c a s e s a l l the c h i ld r e n
were s t i l l - b o r n .
In c a s e 1 8 5 , the c h i l d was born a l i v e but,
as has been m en tion ed , th e l i v e r l e s i o n s were not very fa r
advanced and t h i s c a s e was presum ably o n ly a m ild example o f
o b s t e t r i c a c u t e y e ll o w atrop h y; th e r e was the a d d i t io n a l
f a c t o r o f th e a d r e n a l i r e s e c r e t i n g tumour.
One can o n ly
s p e c u l a t e w ith r e g a r d to th e r e l a t i o n o f the l i v e r changes
and t h i s tumour but h yp erad ren al i n i sm r e s u l t i n g i n a d e p l e t io n
o f l i v e r g ly c o g e n may have been a f a c t o r i n c a u sin g the
l i v e r damage.
D i f f e r e n t f a c t o r s c a u sin g g ly c o g e n d e p l e t i o n
o f the l i v e r may be o p e r a t i v e i n other c a s e s o f o b s t e t r i c a c u te
y e llo w a tro p h y .
From the b io c h e m ic a l f i n d i n g s i n t h i s c a s e and th e
few p r e v i o u s l y d e s c r i b e d i n the l i t e r a t u r e the c h a r a c t e r i s t i c
changes i n th e b loo d i n o b s t e t r i c a c u te y e llo w atrophy may
be summarised a s f o l l o w s .
I)
II)
I n c r e a s e d b lo o d c o n c e n t r a t io n .
Very h ig h plasm a u r i c a c i d and m o d era tely r a i s e d blood
urea v a lu e s.
Ill)
IV)
Low whole b lo o d c h l o r i d e s .
P o s i t i v e d e la y e d d i r e c t van den Bergh t e s t and r a i s e d
plasm a b i l i r u b i n .
These changes a r e , o f c o u r s e , by no means d i a g n o s t i c o f
o b s t e t r i c a c u t e y e ll o w a tr o p h y but t h e y may be h e l p f u l when
tak en i n c o n j u n c t i o n w ith o th e r f i n d i n g s .
True A cute Y ellow Atrophy.
One c a s e o f tr u e a c u t e y e llo w atrop h y o f the l i v e r
has been e n c o u n te r e d i n a pregnant woman during the p r e s e n t
stu d y (C ase 186) and an accou nt o f the c l i n i c a l , b io c h e m ic a l
and p a t h o l o g i c a l f i n d i n g s i s in c lu d e d h ere f o r comparison
with t h o s e o f the p r e v io u s c a s e ( 1 8 5 ).
The p a t i e n t , a g i r l o f 17 y e a r s , was 7 weeks pregn an t
when a d m itte d to h o s p i t a l .
A week b e fo re a d m issio n she had
n o t i c e d s l i g h t y e llo w n e s s o f her c o n ju n c tiv a e and had had
s l i g h t v o m itin g and d ia r r h o e a w ith l i g h t y e llo w s t o o l s .
Jaun dice deepened but she had no more s i c k n e s s .
25. 6. 4O.
Adm itted to h o s p i t a l .
She wr.s d e e p ly ja u n d ic e d ,
the u r in e c o n ta in e d albumen +, and a t r a c e o f b i l e
p ig m en t, but no o th e r ab n orm ality was made out on
g e n e r a l e x a m in a tio n .
T. 9 7 .6 ; P. 92; R. 2 0 .
B. P. 1 2 0 /6 5 .
-LATE
V.
Liver in True Acute Yellow Atrophy.
Naked eye view showing red and yellow p atch es
( dase
135
j
PLATE
71.
Liver in True Acute Yellow
L\i*r'A
Atrophy.
( Case- 136 )
Low power view from red area
showing absence of liver cells
and numerous newly formed bile
ducts.
PLATE
711
L iver in True Acute Yellow
Atrophy.
*fc.v.* - S A j r p ' + j : - ' * • i : £ v f . n^.*
*•'/’■*•f1'i* . - / fM•.' :^','A1±'.•» 4
;<* •
? •• b
•
V f ^ X i V . •: v -;t . v - g r * * > £ -/
'*'‘r,.1. r i.* *i v . v ■*'J W
( b ase
186
Low power view from yellow
a r e a showing small groups of
■,
s u r v i v i n g l i v e r c e l l s with
s t r o n g l y b a s o p h il staining
reaction
26. 6 .4 0 .
29. 6 .4 0
30. 6. 4 0 .
1 . 7-40.
2. 7*40.
She appeared w e ll and her mental c o n d it io n v/as
normal. Her s t o o l s were l i g h t c l a y c o lo u re d .
She had no s i c k n e s s during the n ext few days.
The ja u n d ic e was s t i l l very deep,
a t 2 p.m.
The p a t i e n t suddenly became very
i r r i t a b l e and screamed lo u d ly when touched or
d is t u r b e d .
1 1 .3 0 p.m.
She had become stu p e r o s e and would not
speak but when ro u sed she was m aniacal.
She had
no v o m itin g .
300 c . c . 50$ g lu c o s e s a l i n e + 10 u n it s
o f i n s u l i n were g iv e n in tr a v e n o u s ly .
10 a.m.
She was somewhat improved and was now
c o n s c io u s and a b le to speak. Her s t o o l was o f
normal c o lo u r and the u rin e d e e p ly b i l e - s t a i n e d .
L ater i n the morning she began to vomit and
g r a d u a lly r e l a p s e d i n t o a se m i-c o n s c io u s s t a t e
becoming m aniacal when roused.
The p u ls e r a t e rco e
to 130 per m inute but the tem perature remained
normal.
30$ g lu c o s e was g iv e n in tr a v e n o u s ly .
T. 9 8 . 2 ; P. 140; R. 24 . She remained d e e p ly
com atose throughout the day and e x h i b i t e d Cheyne
S to k es r e s p i r a t i o n .
Jaundice appeared to be
d eep er.
Continuous in tr a v e n o u s 3
g lu c o s e was
g iv e n w ith no e f f e c t .
The u r in a r y volume p a sse d
was l a r g e and the u r in e c o n ta in e d a la r g e amount
o f b i l e pigm ent. At 9 P*m* s’ne
tw itch in g s of
h e r f a c e and s e v e r e r i g h t - s i d e d c l o n i c spasms o f
the body and lim b s.
T. 1 0 2 .4 ; R* 144; R- 24*
The p a t i e n t d ie d a t 1 .4 9
At t h e a u to p s y , performed l j hours a f t e r d eath , the
l i v e r w eighed o n ly 700 grns.
su r fa c e was w r in k le d .
I t was shrunken and the p e r i t o n e a l
The c u t su r fa c e was dark red i n c o lo u r
w ith a m o t t l i n g o f i r r e g u l a r y e llo w p a tc h e s - s e e P l a t e V.
M i c r o s c o p i c a l l y th e r e was w idespread n e c r o s i s o f l i v e r c e l l s .
In the red a r e a s o n ly shadows o f the columns remained - se e
P l a t e V I . , end i n the y e llo w a r e a s th ere were sm all groups o f
su rv iv in g l i v e r c e l l s j
t h e s e c e l l s showed a s t r o n g l y b a s o p h il
sta in in g r e a c tio n -
s e e P l a t e VII.
Over l a r g e a r e a s t h e
n e c r o t i c d e b r i s had
been s/osorbed, i t s p la c e being o c c u p ie d
by d i l a t e d s i n u s o i d s packed w ith blood.
There was some
CHAKT XXlI.
*—
-----------* -
# . U f \ I C A C I ”®
Graph, o f f i n d i n g s i n Ge.se 186,
___ ^
loot.c.TLrtsnfl.
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in
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.
1N
n*?. ? e f \
,~
NOf t Mf l U
cwniNuo^s
300cx.2S^<j<-ocosE
XV. I
^wc.st ?lE:p
/ N T A A V E (Wo <JU-.y
j
i
s
y ( \ y s . R p r t ft
A -'p f^ ^ S lo i^
S'
i n f i l t r a t i o n o f s m a ll round c o l l s and. polymorphs from the
p ortal t r a c t s .
Large numbers o f new-formed b i l e d u cts
surrounded th e p o r t a l t r a c t s i n many p l a c e s - se e P l a t e V I .,
and t h e r e was some i n c r e a s e i n the p e r i p o r t a l fib r o u s t i s s u e .
Sudan s t a i n i n g r e v e a le d th e p r e se n c e o f d r o p le t s o f f a t i n
many o f the s u r v i v i n g l i v e r c e l l s .
a b n o rm a lity .
In th e lu n g s th e r e was a very haemorrhagic
broncho-pneum onia.
in fla m e d .
The k id n ey s showed no
The mucosa o f the duodenum was s w o lle n and
The u t e r u s c o n t a in e d an e a r l y g e s t a t i o n sac about
2 cm. d ia m e te r .
I t w i l l be seen th a t the post-mortem f i n d in g s are
t y p i c a l o f tru e a c u t e y e llo w a tro p h y , such a s o ccu rs e i t h e r
i d i o p a t h i c a l l y or a s th e r e s u l t o f o o is o n in g by v a r io u s
s u b s ta n c e s - e . g .
dope, T .N .T ., cin cop h en e t c . ; and i n t h i s
c a se t h e r e were grounds f o r s u s p e c t in g th a t some chem ical
or drug had been tak en a lth o u g h no h i s t o r y o f t h i s c o u ld be
o b t a in e d from th e r e l a t i v e s .
The b io c h e m ic a l f i n d i n g s are g iv e n below and are
shown i n graph form o p p o s i t e - s e e Chart XXII.
B io ch em ica l F in d in g s i n Case 18 6 .
27. 6. 1 0 .
H aem atocrit.
Uric A cid .
U rine.
•54#
2. 6
Urea.
Urine.
1 4 .3
B ilir u b in .
22
3756
3 a.m. P.M.
.. 2,7.,..4P.f................ .
12 m. d.
1 .7 .4 0 .
10 p.m.
30. 6 .4 0 .
_ .... J 3 k
3 . 6 ....
0 .0 3
16.
0 .4 6
29
In tra v e n o u s
g l u c o s e , 30*6. 40>
a t 8 p.m.
4.4___
23,,
.
8 .0
0 .0 5 6
35 .
----- 32-----
98.
On 27. 6 .4 0 , t e n days a f t e r the o n s e t o f ja u n d ic e and o th e r
symptoms, the blood i n v e s t i g a t i o n r e v e a le d no ab n o rm a lity,
apart from a d i r e c t p o s i t i v e r e a c t i o n to the van den Bergh
t e s t w ith o n ly a £ m inute d e la y , and a very h igh plasma
b i l i r u b i n (2 2 u n i t s ) ; th e h a em a to crit rea d in g was normal and
the plasm a u r i c a c i d and urea were w i t h in normal l i m i t s
a lth o u g h th e urea v a lu e was r a th e r low.
The s t o o l s c o n ta in e d
no b i l e pigm ent and a t t h i s s t a g e a d ia g n o s is o f c a ta r r h a l
ja u n d ic e was made.
A fte r the p a t i e n t had become a c u t e l y i l l ,
blood i n v e s t i g a t i o n showed a r i s e i n h a e m a to cr it value from
34$ to 37$ (p r o b a b ly l e s s th an th e a c t u a l r i s e because th e
specim en o f blood was withdrawn 2 hours a f t e r 300 e . c . o f
30$ g l u c o s e had been g iv e n i n t r a v e n o u s l y ) .
The blood
s e d im e n ta tio n r a t e o f t h i s specim en was n i l . a t 1 hour,
s u g g e s t in g a g r e a t i n c r e a s e i n f ib r in o g e n .
Plasma u r ic a c id
and urea were s t i l l w i t h i n normal l i m i t s w h ile the plasma
b i l i r u b i n had i n c r e a s e d .
J u s t b e fo re death th e re was a
marked i n c r e a s e i n b lood c o n c e n t r a t io n , the plasma u r i c a c id
showed a rap id i n c r e a s e to 8 . 0 mg. per 100 c . c .
urea r o s e t o 35 mg. per 100 c . c .
and th e plasma
U ric a c id and urea p e r c e n ta g e s
in th e u r i n e were low.
The s t r i k i n g f e a t u r e . i n both the c l i n i c a l and
b io c h e m ic a l f i n d i n g s i n t h i s c a s e was the absen ce o f s i g n s o f
se v e r e l i v e r damage u n t i l 48 hours b efore death.
It i s q u ite
c l e a r , how ever, from the h i s t o l o g i c a l appearance o f the l i v e r
th a t th e m a ssiv e n e c r o s i s did not ta k e p la c e during the l a s t
few days o f l i f e ;
th e e x te n t o f the b i l e duct p r o l i f e r a t i o n
and th e com p lete d isa p p ea r a n c e o f the l i v e r c e l l remnants a t
most a r e a s i n d i c a t e th a t th e l e s i o n was p rob ab ly o f 10 t o 14
d a y s 1 d u r a t io n , i . e .
o n s e t o f symptoms.
i t had occu rred about th e tim e o f th e
A low blood urea va lu e was to be e x p e c te d
i n such a c a s e b ecause i t h as been shown t h a t urea i s formed
by th e l i v e r (Mann and Magath, 1 9 2 1 ).
Numerous r e p o r t s o f c a s e s o f a c u te y e llo w atrop h y
have been g i v e n i n the l i t e r a t u r e but o n ly two hav e been
found which in c lu d e b io c h e m ic a l f i n d i n g s i n such c a s e s .
S ta d ie and Van Slyk e (1 9 2 0 ) r e p o r t th e c a se o f a woman aged
29 y e a r s who d ie d a f t e r 7 d a y s ’ i l l n e s s ;
the l i v e r a t p o s t ­
mortem e xa m in ation w eighed 1 ,0 0 0 gms. and th e r e was e x t e n s i v e
n e c r o s i s o f l i v e r c e l l s a lth o u g h some o f the p e r i p o r t a l c e l l s
appeared h e a l t h y .
The b lo od urea n it r o g e n v a lu e s during th e
l a s t 3 days o f l i f e were 1 2 , 9 and 16 mg. per 100 c . c. respective!
and th e u r in a r y u rea n i t r o g e n p e r ce n ta g e was very low.
Blood
a m in o -a c id n i t r o g e n v a l u e s during the l a s t 3 days o f l i f e
were 1 4 , 1 7 , and 26 mg. per 100 c . c . r e s p e c t i v e l y w h ile
u r in a r y a m in o -a c id n i t r o g e n and ammonia r a t i o were g r e a t l y
in c r e a s e d .
U ric a c i d was not e stim a te d .
The a u th o rs regarded
t h e s e f i n d i n g s e s e v id e n c e o f p a r t i a l l o s s o f th e d e a m in isin g
power o f the l i v e r .
Rabinowitch ( 1 9 2 9 )» r e p o r t s a c a s e o f a
woman aged. 28 y e a r s , who died a f t e r 3 days* i l l n e s s .
The
l i v e r a t post-m ortem ex a m in a tio n weighed 650 gms. and showed
n e c r o s i s o f alm o st a l l c e l l s .
No blood urea was found i n t h i s
100.
oa.se and. th e b lo o d a m in o -a c id n it r o g e n v a lu e was 216 mg. per
100 c . c .
The bloo d u r i c a c id was 1 * 9 6 mg. per 100 c . c .
The
case o f S t a d ie and Van Slyke and th a t o f Rabinowitch were
both a p p a r e n t ly more a c u te than the p r e s e n t c a s e .
U n fo r tu n a te ly
blood ami n o - a c i d s were not determ ined i n th e p r e s e n t c a s e but
the b lo o d and u r in a r y u rea f i n d i n g s are s im ila r to th o s e o f
the c a s e s j u s t m entioned and ten d to support th e c o n c lu s io n
o f p r e v io u s workers w ith rega rd to th e p a r t p la y ed by th e
l i v e r i n u rea m eta b olism .
The u r i c a c i d f i n d i n g s were v ery un exp ected .
The
work o f Bollman, Mann and Magath ( 1 9 2 5 ), and Gremels and Bodo
(1926),
liv e r ;
i n d i c a t e s t h a t i n dogs u r ic a c id i s d e str o y e d in the
and i n man i t i s g e n e r a l l y a c c e p te d th a t l i v e r damage
r e s u l t s i n an i n c r e a s e i n blo od u r ic a c id .
The p r e s e n t
f i n d i n g s do n ot su pp ort such a h y p o t h e s i s .
I t i s p o ssib le
t h a t , i n th e p r e s e n t c a s e , r e g e n e r a t i o n o f l i v e r c e l l s was
s u f f i c i e n t to d e a l w ith th e endogenous u r ic a c i d and to form
a c e r t a i n amount o f urea; c e r t a i n l y the s u r v iv in g l i v e r c e l l s ,
i
se e n m i c r o s c o p i c a l l y , appear to be young and were presumably
a c tiv e .
The low u r i c a c i d v a lu e found i n Rabinowitch 's c a s e ,
however, s u g g e s t s t h a t another e x p la n a tio n i s n e c e s s a r y s i n c e
th e l i v e r damage was g r o s s and th e r e was no s i g n o f any c e l l
r e g e n e r a t io n .
In c o n t r a s t to the non—p r o t e i n n i t r o g e n f i n d i n g s ,
the plasm a b i l i r u b i n v a l u e s , i n the p r e sen t c a s e , were d i r e c t l y
p r o p o r t io n a l to th e s e v e r i t y o f the d i s e a s e .
During the
101
p e r io d o f ex a m in a tio n th e plasm a b i l i r u b i n r o se s t e a d i l y from
22 u n i t s to J>2 u n i t s a t d eath .
The plasma gave a p o s i t i v e
d i r e c t r e a c t i o n t o the van den Bergh t e s t w ith o n ly \ m inute
d e la y on 2 7 . 6. 4 0 , about 10 days a f t e r the o n s e t o f symptoms,
and t h i s f i n d i n g , a lo n g w ith the absence o f pigment i n th e
s t o o l s l e d t o th e erro n eo u s d i a g n o s i s o f c a ta r r h a l ja u n d ic e .
In the t e r m in a l s t a g e o f the d i s e a s e the plasma gave a p o s i t i v e
d i r e c t r e a c t i o n to the van den Bergh t e s t w ith 1-J- minute
d e la y and the s t o o l s c o n t a in e d b i l e pigm ent.
The main p o i n t s o f i n t e r e s t i n t h i s c a s e o f tr u e
a c u te y e ll o w a tro p h y may be summarised a s f o llo w s :
I)
The a b se n c e o f c l i n i c a l s i g n s and symptoms, a p a rt from
th e ja u n d ic e , fo r about 12 days a f t e r the o n s e t o f th e
l i v e r damage.
II)
No i n c r e a s e d b lood c o n c e n t r a t io n u n t i l about 48 hours
b e f o r e d e a th .
Ill)
Normal plasm a u r i c a c i d and low blo od urea v a lu e s u n t i l
j u s t b e fo r e death; a r e t e n t i o n o f both plasma u r i c a c id
and u r e a follow ed, the i n c r e a s e i n bloo d c o n c e n t r a t io n .
IV)
A s t e a d i l y r i s i n g plasma b i l i r u b i n c o n te n t throughout
the i l l n e s s and a p o s i t i v e d e la y ed d i r e c t r e a c t i o n
to the van den Bergh t e s t .
D elayed Chloroform P o iso n in g .
P o is o n in g due to chloroform c a u se s y e t a n o th er
type o f l i v e r l e s i o n and c a s e s o f d ela y ed chloroform p o i s o n i n g
PLATE
VIII.
o.
' 3 - •*,
L iver in Delayed
Ohloroform P o iso n in g^ showing
t/
CJ m id-zonal necrosis,
a ,
S u rv iv in g c e n t r o l o b u l a r c e l l s ,
o ,
Band of n e c r o s i s ,
c ,
S u rv iv i n g p e r i p o r t a l c e l l s .
I
Oase
117 )
Low power vi e w
10 Z
are o c c a s io n a lly met with in the puerperium.
Sheehan ( 1 9 4 0 ) ,
has p o in ted out that the a c id o sis and dehydration r e s u ltin g
from a long labour, make p erturient women s p e c ia lly su sc e p tib le
to the i l l e f f e c t s o f t h is drug..
He has found that the l i v e r
le s io n in th e se d y sto cia cases i s a mid-zonal n ecrosis which
spreads c e n t r a l ly in severe cases.
A f a t a l case, case 1 8 7 , of delayed chloroform
poisoning was examined during the present study but no
biochemical fin d in g s were obtained from i t .
The p a tie n t had
been g iv en chloroform for 20 minutes on two occasions.
She
had had moderately severe vomiting for 48 hours before the
f i r s t a d m in istration of chloroform and t h is sickness continued
during the next day when labour began.
and the p a tie n t was very a c id o t ic .
Vomiting was severe
Chloroform was again given
for the d e liv e r y a f te r a 4 hour labour.
The p a t ie n t 's
co n d itio n a f t e r d e liv e r y was very poor.
She died 6 hours
a f te r the d e liv e r y and about 72 hours a fte r
ad m in istration of chloroform.
weighed 1 ,2 2 0 gms.
the f i r s t
At the autopsy, the l i v e r
M icroscopically there was very d e f in it e
mid-zonal n e c r o sis with f a t t y degeneration of the centrolobular
c e l l s ; a microphotograph o f t h is i s shown in P late VIII. for
comparison with the li v e r le s io n s in cases 185 &nd 1 8 6 .
Three very severe but non—fa ta l ca ses, (1 8 8 , 189 and
1 9 0 ) , and two milder ca ses, (135
^91) >
delayed
chloroform poisoning have been in v estig a ted during the present
study and i t i s in te r e s tin g to compare the biochemical
193 chenges found i n t h e s e c a s e s w ith th o se found i n the c a s e s
o f the two o th e r t y p e s o f l i v e r damage, p r e v i o u s l y d e s c r ib e d .
In each o f th e s e v e r e c a s e s chloroform was g iv e n fo r th e d e l i v e r y
a f t e r a lo n g la b o u r; th e mean le n g t h o f labou r for the 3 c a s e s
was 52 h o u r s .
A l l th e p a t i e n t s vom ited f r e q u e n t ly d u rin g
labour and were, t h e r e f o r e , dehydrated and a c i d o t i c b e fo r e
d e liv e r y .
In c a s e s 189 and 190 chloroform was g iv en on two
d i f f e r e n t o c c a s i o n s du rin g lab ou r and a g a in at d e l i v e r y .
Case 189 was d e l i v e r e d by f o r c e p s a f t e r a 52 hour la b o u r
and was under chloroform a n a e s t h e s ia for 5° m inutes; 200 c . c .
50$ g l u c o s e were g iv e n i n t r a v e n o u s l y a t the d e l i v e r y .
One o f
the m ild c a s e s ( 19^) r e c e i v e d chloroform fo r 25 m inu tes a f t e r
a 51 hour la b o u r; 200 c . c .
50 $ g lu c o s e had been g iv e n h a l f - a n -
hour b e f o r e th e a n a e s t h e t i c was s t a r t e d .
The oth er m ild c a s e
(13 5) was an e c la m p tic t r e a t e d by the S tr o g a n o ff method.
Chloroform was g i v e n fo r a few m inutes on four d i f f e r e n t
o c c a s i o n s du rin g and a f t e r la b o u r.
and th e d e l i v e r y was sp ontan eou s.
Labour l a s t e d 24 hours
This was the o n ly e c la m p tic
p a t i e n t o u t o f a v e r y la r g e s e r i e s t r e a t e d by the S tr o g a n o ff
method, who showed d e f i n i t e s i g n s o f chloroform p o is o n in g .
A l l t h e s e p a t i e n t s , c a s e s 188, 1 8 9 , 190, 191> SSL,
33=3 and 1 3 5 , vom ited a l i t t l e
during the f i r s t two days o f
the puerperium and on the t h i r d day they were n o t i c e d to be
ja u n d ic ed ; tem perature and p u ls e r a te were e l e v a t e d Temperature 9 9 ° ~ 1 0 1 °, p u l s e r a t e about 1 2 0 .
The s e v e r e
c a s e s became r e s t l e s s and l a t e r d e l i r i o u s ; two o f them, c a s e s
chart
xxm .
Composite G-raph o f f i n d i n g s i n t h r e e e a s e s o f
s e v e r e D e l a y e d C h lo r o f o r m P o i s o n i n g .
( C a s e s 1 8 8 ,1 8 9 & 1 90.
A verage
*
*'
#
*
-
l e n g t h o f l a b o u r : 52 h o u r s . )
J
________________________________________________________________________ __ __________
3o uo
to «ro
0
JO if0
C0HTINUOU.S
VENOWS
qLUCOSE.
?Eu\zeHy
7>fi.ys
' “- ' I
IN
io v m m
H
s>
J
T ’ os T ' T a r r u r v ,
„
,
OI i-l n 0 ft>i N ( N .
Pt K IQOcc AftSMB
lP3 and 1.39, were c o m p le te ly comatose by the fo u r th day p o s t
partum.
The tem p erature ranged from 103° to 105° and th e
p u ls e was v e r y weak and r a p id - o f t e n over 160 per m inute.
Continuous in tr a v e n o u s g lu c o s e was s t a r t e d on th e t h i r d day
p o s t partum: s l i g h t improvement ( f a l l i n tem perature and
p u lse r a t e and s i g n s o f r e tu r n in g c o n s c io u s n e s s ) began on th e
f i f t h day p o s t partum and p e r s i s t e d .
In the m iM c a s e s th e
ja u n d ic e l a s t e d o n ly a few days and th e r e were no m ental symptone;
i n the s e v e r e c a s e s th e ja u n d ic e became very deep and l a s t e d
fo r abou t 2 weeks.
and f a e c e s .
B i l e pigm ents were p r e s e n t i n both u r in e
The b io c h e m ic a l f i n d in g s throughout the c o u r se
o f the d i s e a s e i n each c a se a r e g iv e n i n the appendix.
A
com p o site c h a r t o f the changes i n the v a r io u s blood f r a c t i o n s
in th e t h r e e s e v e r e o a s e s i s g iv e n in Chart XXIII.
In v e stig a tio n
o f t h e s e c a s e s was not s t a r t e d u n t i l th e jTd. day p o s t partum
and t h e r e f o r e the changes o c c u r r in g i n the blood f r a c t i o n s
im m ed ia te ly a f t e r d e l i v e r y a r e not known.
In the graph,
however, th e e x p e c te d changes i n haem atocrit, plasma u r ic
a c id and u r e a i n a normal c a s e w ith a 52 hour labour, during
th e f i r s t 3 days p o s t partum, are in d ic a t e d w ith d o t t e d l i n e s ,
f o r com parison w ith the f i n d i n g s i n the p r e s e n t c a s e s ; th e
v a lu e s have been c a l c u l a t e d from the data recorded i n S e c t i o n s
I I . and IV.
I t w i l l be n o t i c e d th a t the h a em atocrit v a lu e s
during th e a c u t e s t a g e o f th e i l l n e s s were r e l a t i v e l y h ig h
and t h a t improvement c o in c id e d w ith a d e c r e a se ..n th e
h a e m a to c r it v a l u e s .
In each c a s e the plasma gave a p o s i t i v e
d elayed d i r e c t van den Bergh r e a c t i o n and the plasma bi. i r u b i n
was v e r y h ig h (2 4 to 32 u n i t s i n s e v e r e o a s e s ) ; the plasma
b i l i r u b i n appeared to vary w ith the s e v e r i t y o f th e c l i n i c a l
co n d itio n .
Plasma u r i c a c id and urea were r a is e d i n each c as
The plasm a u r i c a c i d v a lu e s were r e l a t i v e l y h ig h e r than th e
urea v a l u e s i n i n d i v i d u a l c a s e s and the maximum urea v a lu e
was u s u a l l y rea c h e d a day l a t e r than the maximum u r ic a c id
v a lu e .
A f a l l i n th e plasma u r i c a c id l e v e l o ccu rred i n each
c a se a t l e a s t 24 hours b e fo r e th e r e was any o th e r b io c h e m ic a l
or c l i n i c a l s i g n o f improvement; a p art from t h i s , however,
th e plasm a u r i c a c i d and urea v a lu e s f o llo w e d th e h a e m a to c r it
changes.
In each c a se trea tm en t with in tr a v en o u s g lu c o s e
was i n s t i t u t e d a s soon a s the d i a g n o s i s was made: i n th r e e o f
the c a s e s th e d i a g n o s i s was s u g g e s te d from the b io c h e m ic a l
f i n d i n g s b e fo r e t h e r e was any ja u n d ic e c l i n i c a l l y .
In th e
s e v e r e c a s e s c o n tin u o u s d r ip t r a n s f u s i o n s were g iv e n .
A ll
th e p a t i e n t s r e c o v e r e d i n s p i t e o f the f a c t th a t two o f them,
c a s e s 188 and 1 8 9 , were moribund fo r more than 24 h o u rs.
The
fa v o u r a b le r e s u l t s i n t h e s e c a s e s appeared to be due t o th e
e a r l y and c o n t in u e d in tr a v e n o u s g lu c o s e therap y and t h e y
support th e view e x p r e ss e d by Sheehan (1940) and Townsend
( 1 9 3 9 ) t h a t th e p r o g n o s is i n c a s e s o f d e la y ed chloroform
p o i s o n i n g , even w ith much l i v e r d e s t r u c t io n , sh o u ld n o t be
unduly p e s s i m i s t i c .
The main b io c h e m ic a l f i n d in g s i n th e b lo o d i n
t h e s e c a s e s o f d e la y ed chloroform p o is o n in g are
106.
I)
II)
An i n c r e a s e i n h a e m a to c r it v a lu e .
High plasm a u r i c a c i d and m o d e r a te ly r a i s e d
urea v a lu e s.
b lo o d
A f a l l i n plasm a u r i c a c i d v a lu e was
found to be the f i r s t s i g n o f improvement; i t occurred
w h ile th e u rea v a lu e was s t i l l r i s i n g .
Ill)
A p o s i t i v e d e la y e d d i r e c t r e a c t i o n t o the van den Bergh
t e s t and v e r y h i g h plasm a b i l i r u b i n v a l u e s . The plasm a
b i l i r u b i n v a l u e s were d i r e c t l y p r o p o r t i o n a l to the
s e v e r i t y o f the c l i n i c a l c o n d i t i o n .
D iscu ssio n .
The main f i n d i n g s i n t h e s e t h r e e t y p e s o f l i v e r
damage, a s shown by the p r e s e n t c a s e s , a r e summarised i n
I
f .h f l
* P n l 1 m w l -no*
“h a h i
«=»
TY.
1
Table
IX.
O b s t e t r i c A cute
Y e llo w Atrophy.
True A cute
Y e llo w Atrophy.
D ela yed Chloroform P o ison in g .
per Lesion.
C e n tr o lo b u la r
c y■
t oplasm i c c h a n g e .
Ho n e c r o s i s .
Widespread a z o n a l
n e c r o sis.
M id -zo n a l n e c r o s i s
w ith f a t t y change in
su rv iv in g c e l l s .
lociated
pal changes.
D e g e n e r a tio n o f
t u b u la r e p it h e liu m and
ea rly i n t e r s t i t i a l
fib r o sis.
K idney a p p a r e n t ly
normal.
Marked f a t t y change i n the
e p it h e liu m o f th e 1s t
c o n v o lu t e d tu b u le s .
fed c o n c e n tr a t io n . M arkedly i n c r e a s e d .
Unchanged.
Increased.
tea u r ic a c i d .
Very h ig h .
No rrnal.
High.
t e Urea.
High.
S l i g h t l y subnormal.
M o d e ra tely h ig h .
^ den Bergh
8&ction.
P o s i t i v e d i r e c t w ith
2 m inutes d e la y .
p o s itiv e d ir ec t
w ith 1^ m in u te s
d e la y .
P o s i t i v e d i r e c t w ith
-J- m inu te d e la y .
HiRh-
High.
H ig h .........................
—
tea B i l i r u b i n .
, ......................
.............................
In each o f t h e s e c o n d i t i o n s th e r e are d e f i n i t e p a t h o l o g i c a l
changes i n th e l i v e r a lth o u g h i n o b s t e t r i c a c u te y e llo w
atrophy t h e r e i s no n e c r o s i s o f l i v e r c e l l s .
The o n ly
b io c h e m ic a l a b n o r m a lity common to the th r e e c o n d i t i o n s i s th e
r a i s e d plasm a b i l i r u b i n and i n each c a s e the h e i g h t o f th e
plasm a b i l i r u b i n was a good in d e x o f the s e v e r i t y o f th e
d isea se .
The ch an ges i n the b lo o d n o n - p r o t e in n i t r o g e n
f r a c t i o n s , how ever, appear to have no d i r e c t r e l a t i o n to th e
e x t e n t o f th e l i v e r damage.
In each c o n d i t i o n th e r e a r e a t
l e a s t t h r e e f a c t o r s which m ight i n f l u e n c e the b lo od n o n - p r o t e i n
f r a c t i o n s and t h e s e a r e , - l i v e r damage, k id n ey damage and
anhydraem ia.
In th e c a s e o f tru e a c u te y e llo w a tr o p h y o f th e
p r e s e n t s e r i e s th e o n l y one o f t h e s e f a c t o r s p r e s e n t , i n th e
e a r l y s t a g e s o f the d i s e a s e , was the l i v e r damage and a t t h i s
time the b lo o d urea v a lu e was normal.
Im m ediately b e f o r e
d e a th , h ow ever, a marked i n c r e a s e i n blood c o n c e n t r a t i o n
d e v e lo p e d and t h e r e was a sim u lta n eo u s r i s e i n both the plasm a
u r ic a c i d and urea - presum ably the r e s u l t o f th e anhydraem ia.
The u r i c a c i d f i n d i n g s i n t h i s c a s e are s p e c i a l l y i n t e r e s t i n g ;
th e y i n d i c a t e t h a t g r o s s l i v e r damage does not c a u se an
in c r e a s e i n plasm a u r i c a c i d but t h a t a r i s e i n plasm a u r i c
a c id may d e v e lo p , i n such a c a s e , as a r e s u l t o f anhydraem ia.
The f a c t t h a t an a c t u a l r i s e i n blood urea occu rr ed t e r m i n a l l y
i n d i c a t e s t h a t l i v e r damage - a s w idespread a s i n th e p r e s e n t
c a s e - i s i n s u f f i c i e n t to ca u se much r e d u c tio n i n urea
fo r m a tio n .
I t may t h e r e f o r e be concluded th a t even g r o s s
l i v e r damage has l i t t l e
d i r e c t e f f e c t on the plasma u r i c a c i d
and u r e a l e v e l s i n th e b lo o d .
In o b s t e t r i c a c u te y e llo w atrop h y and d e la y e d
c h lo ro fo r m p o i s o n i n g t h e r e i s a d e f i n i t e r e t e n t i o n o f non­
p r o t e i n n i t r o g e n f r a c t i o n s i n the b lo o d .
The changes i n
plasm a u r i c a c i d and u rea a g a in appear to have a d e f i n i t e
r e l a t i o n t o th e ch an ges i n b lo o d c o n c e n t r a t i o n but i n t h e s e
c a s e s t h e r e i s a s s o c i a t e d r e n a l damage which i s presum ably
th e p rim ary ca u se o f the r e t e n t i o n .
No i n v e s t i g a t i o n o f a c i d - b a s e b a la n ce h a s been
made i n the p r e s e n t c a s e s a lth o u g h th e p o s s i b i l i t y t h a t
some o f the changes may have r e s u l t e d from an u p se t o f t h i s
b a la n c e h a s n o t been o v e r lo o k e d .
The i n c r e a s e i n b lo o d
c o n c e n t r a t i o n , found i n many o f t h e s e c a s e s , d id not r e s u l t
from p r o lo n g e d v o m itin g or d e h y d ra tio n ; i t was presum ably
due t o some a c i d b a se im b alan ce.
Summary.
The b io c h e m ic a l f i n d i n g s i n a f a t a l c a s e o f
o b s t e t r i c a c u t e y e ll o w a tr o p h y and i n one o f tr u e a c u t e
y e ll o w a tr o p h y and i n f i v e n o n - f a t a l c a s e s o f d e la y e d
ch lo ro fo r m p o i s o n i n g a r e reco rd ed ; p a t h o l o g i c a l f i n d i n g s i n
th e two former c a s e s and i n one f a t a l c a se o f d e la y e d
ch lo ro fo rm p o i s o n i n g a r e a l s o g iv e n .
The h e i g h t o f t h e
plasm a b i l i r u b i n i s found to be the b e s t in d ex o f th e
s e v e r i t y o f th e l i v e r dnmege.
In each c o n d i t i o n th e r e was
i n c r e a s e d b lo o d c o n c e n t r a t i o n a t some tim e d u rin g th e i l l n e
lo ^ .
and c h a n g e s i n th e n o n - p r o t e i n n i t r o g e n f r a c t i o n s o f th e
b lo o d a p p eared to depend d i r e c t l y on changes i n blood
c o n c e n t r a t i o n r a th e r th a n on th e e x t e n t o f the l i v e r damage.
A h ig h plasm a u r i c a c i d was n o t found to be t h e i n v a r i a b l e
r e s u l t o f l i v e r damage.
CHANGES IN BLOOD BIOCHEMISTRY ABOUT THE
TIME OF DELIVERY WITH SPECIAL REFERENCE
TO OBSTETRIC SHOOK.
During r e c e n t y e a r s a t t e n t i o n has been drawn to
t h e s i m i l a r i t y o f th e syndrome o f a d r e n a l c o r t e x i n s u f f i c i e n c y
t o s e c o n d a r y shock and i t has been s u g g e s t e d t h a t th e
symptoms and s i g n s o f se con d ary shock a r e due to tem porary
e x h a u s t io n o f th e a d r e n a l c o r t e x .
In 1933 S w in g le, P f i f f n e r , Vars, B ott and P a r k in s
i n v e s t i g a t e d th e f u n c t i o n o f th e a d r e n a l c o r t i c a l hormone
and th e e u a s e o f d eath from a d r e n a l i n s u f f i c i e n c y , u s in g
a d r e n a le c t o m is e d dogs which had been kept a l i v e and normal
f o r s e v e r a l y e a r s w ith i n j e c t i o n s o f c o r t i c a l e x t r a c t .
W ithdrawal o f t h e hormone cau sed a p r o g r e s s i v e d e c r e a s e i n
b lo o d volume and a f a l l i n b lo o d p r e s s u r e u n t i l death o c c u r r e d
8 t o 12 days l a t e r .
H aem oconcentration and i n c r e a s e d b lo o d
v i s c o s i t y were marked, depending on the d e c r e a s e i n plasm a
volume.
The h e a r t r a t e v a r ie d in verss?.y w ith the b lo o d
p r e s s u r e a s d id b lo o d n o n - p r o t e in n i t r o g e n and u rea v a l u e s .
The d ogs i n t h i s s h o c k - l i k e c o n d i t i o n were found to be u n ab le
to d i l u t e t h e i r b lo o d a t a l l .
I f a sm all haemorrhage
o c c u r r e d t h e i r c o n d i t i o n became r a p i d l y worse and d e a th
o c c u r r e d i n a sh o r t t i m e 5 even when f l u i d was g i v e n i n t r a -
111.
j p e r i t o n e a l l y no b lo o d d i l u t i o n o ccu rred .
When c o r t i c a l
hormone was i n j e c t e d , however, the f l u i d was absorb ed , blood
d i l u t i o n o c c u r r e d and the anim al r e c o v e r e d .
One f u n c t i o n o f
th e a d r e n a l c o r t i c a l hormone t h e r e f o r e appeared t o be t h e
r e g u l a t i o n and m aintenance o f a normal c i r c u l a t i n g volume.
The a u th o r s em phasize th e s i m i l a r i t y between the symptoms
and s i g n s o f a d r e n a l i n s u f f i c i e n c y and t h o s e o f seco n d a ry
sh ock .
Lock (1 9 3 2 ) drew a t t e n t i o n to the s i m i l a r i t y o f the
c l i n i c a l p i c t u r e o f a d r e n a l i n s u f f i c i e n c y to th a t o f d i s e a s e d
c o n d i t i o n s i n which a l o s s o f in o r g a n ic base p la y e d an
im p o rta n t p a r t , e . g . h ig h i n t e s t i n a l o b s t r u c t i o n , c h o l e r a ,
and d i a b e t i c a c i d o s i s - such p a t h o l o g i c a l s t a t e s b e in g
c h a r a c t e r i s e d by p r o s t r a t i o n ,
d e h y d r a tio n , n i t r o g e n r e t e n t i o n ,
low plasm a b ic a r b o n a t e and s e v e r e 11sh ock 1*.
He found low
b lo o d sodium and h ig h b lo o d p o ta ssiu m in 3 c a s e s o f A d dison *s
d isea se .
Loeb, A t c h le y , B e n e d ic t and L eland (1 9 3 3 ) made
e l e c t r o l y t e b a la n ce s t u d i e s on dogs b e fo r e and a f t e r
a d r e n a le c to m y and found a f a l l i n blood sodium, c h l o r i d e
and b ic a r b o n a te w ith an i n c r e a s e i n b lo o d p o ta ssiu m and
n o n - p r o t e i n n i t r o g e n to occu r a f t e r ad ren a lectom y .
The f a l l
i n b lo o d sodium was shown to r e s u l t from an e x c e s s i v e l o s s
o f sodium i n the u r in e and i t was s u g g e s t e d th a t th e a d r e n a l
g la n d s must have a r e g u la t o r y e f f e c t on sodium m eta b olism
and r e n a l f u n c t i o n .
The r e l a t i o n o f the a d r e n a l c o r t e x to
th e sodium m etab o lism h a s been f u r t h e r i n v e s t i g a t e d by many
o th e r w orkers (Loeb, A t c h le y , Gutman&Jillson, 1933; Swemer,
1934; Zwemer and S u l l i v a n , 1 9 3 4 ; Loeb, 1 9 3 5 ; Hartman, Lewis
and Toby, 1 0 38 .
High s a l t d i e t s have been used w ith some
s u c c e s s i n th e tr e a tm e n t o f A d d iso n 's d i s e a s e and o t h e r t y p e s of
a d r e n a l c o r t i c a l i n s u f f i c i e n c y (R o g o ff and S te w a r t, 1 9 2 8 ;
Loeb, 1 9 3 2 ; Harrop, W e in ste in , S o f f e r and T r esch er , 1933;
Swemer, 1 9 3 4 )-
More r e c e n t l y a c t i v e a d ren a l c o r t i c a l e x t r a c t s
have beer, p rep ared and a r e now used i n the tre a tm en t o f a l l
t y p e s o f a d r e n a l c o r t i c a l i n s u f f i c i e n c y (Harrop and W e in s te in ,
1932; Harrop, W e in s te in ,
1935; S w in g le , P a r k in s,
S o f f e r and T r esch er , 1933; K e n d a ll,
Taylor and Hays, 1 9 3 8 ).
The marked
s i m i l a r i t y o f th e symptoms and s i g n s o f t h e a d r e n a l d e f i c i e n c y
syndrome to t h o s e o f s u r g i c a l shock h as s u g g e s t e d t h a t
a d r e n a l e x h a u s t io n may be a f a c t o r i n the e t i o l o g y o f
tr a u m a tic and s u r g i c a l sh ock .
Many ex p e rim en ta l s t u d i e s i n
dogs i n which a d r e n a l c o r t i c a l hormone was used i n t h e
tr e a tm e n t o f sh ock , in d u c ed by trauma and by a d r e n a l in e
i n j e c t i o n s , have been perform ed w ith s u c c e s s f u l r e s u l t s
( S w in g l e , P a r k in s ,
T aylor and Hays, 1937 s & b; P a r k in s ,
S w in g le , T ay lo r and Hays, 1938)*
Recent work by S w in g le ,
P a r k in s , T aylor and Hays (1 937 a & b, and 193&) b as t e n d e d
to i n d i c a t e t h a t a d r e n a l c o r t i c a l hormone has a d i r e c t
a c t i o n i n th e low blo od p r e s s u r e o f shocked dogs a p a r t from
any c o n t r o l i t
e x e r t s on f l u i d and e l e c t r o l y t e b a la n c e .
The b io c h e m ic a l changes i n the b lo o d r e s u l t i n g
from a d r e n a l c o r t e x i n s u f f i c i e n c y are summarised by Loeb
( 1 935) as fo llo w s
I)
D e cr ea se i n serum sodium.
113.
II)
Ill)
IV)
I n c r e a s e d b lo o d c o n c e n t r a t i o n .
R e t e n t io n o f n o n - p r o t e i n n i t r o g e n f r a c t i o n s .
I n c r e a s e i n b lo o d p o ta ssiu m .
At p r e s e n t very l i t t l e
in fo r m a tio n h as been
p u b l i s h e d w ith r eg a r d to the e f f e c t o f a d r e n a l c o r t i c a l
hormone i n c a s e s o f shock i n human b e in g s .
Reed ( 1 9 3 8 ) ,
used a d r e n a l c o r t i c a l e x t r a c t i n 50 s u r g i c a l c a s e s - some
a f t e r shock had d e v e lo p ed and some p r o p h y l a c t i c a l l y .
The
t r e a t e d c a s e s were found to improve q u i c k ly a f t e r o p e r a t i o n p u l s e r a t e and h e a r t a c t i o n w ere s t a b i l i s e d .
In one or two
c a s e s b io c h e m ic a l f i n d i n g s were noted: i n u n t r e a t e d shock
c a s e s b lo o d sodium and c h l o r i d e f e l l markedly but n o n - p r o t e i n
n i t r o g e n d id n ot r i s e :
i n t r e a t e d shock c a s e s b lo o d sodium
and c h l o r i d e rem ained unchanged.
W ilson, Rowley and Gray,
(1 9 3 6 ) , W ilso n , MacGregor and Stewart (1937)> and W ilson and
S tew a rt (1 9 3 9 ) s t u d i e d changes i n blood c h e m is tr y i n c a s e s o f
shock due t o burns and found a d e f i n i t e f a l l i n serum sodium
w h ile serum p o ta s s iu m , b lo o d c h l o r i d e , n o n - p r o t e in n i t r o g e n
and u r e a i n c r e a s e d .
They r e p o r t t h a t i n f e c t i o n s o f d e s o x y -
: c o r t ic o s te r o n e , a s y n th e tic adrenal c o r t i c a l p rep a ra tio n ,
ca u se d r a p id r e s t o r a t i o n to normal o f the serum sodium l e v e l
and o t h e r b lo o d a b n o r m a l i t ie s but t h a t t h i s drug had o n ly an
o c c a s i o n a l b e n e f i c i a l e f f e c t on the c i r c u l a t o r y f a i l u r e i n
t h e s e shock c a s e s .
A stu d y o f c a s e s o f o b s t e t r i c shock r e v e a l s
s e v e r a l f a c t o r s which s u g g e s t t h a t a d ren a l c o r t i c a l e x h a u s t io n
may p o s s i b l y p l a y a p a r t i n t h i s syndrome.
There i s a c l o s e
resem b lan ce betw een the c l i n i c a l c o n d i t i o n o f shocked p a t i e n t s
and t h a t o f a n im a ls s u f f e r i n g from a d r e n a l c o r t e x i n s u f f i c i e n c y ;
b lo o d p r e s s u r e f a l l s v e r y low and even v e r y s l i g h t haemorrhage
r a p i d l y c a u s e s d e a th .
Freeman ( 1 9 3 3 ) , working w ith c a t s
found t h a t p r o lo n g e d h y p e r a c t i v i t y o f the sym p a th e tic nervous
sy stem brought about a d e c r e a s e i n b lood volume and what he
c a l l s a **pre~shock s t a t e 1*; i f the animal l o s t a v e ry sm a ll
amount o f b lo o d , when i n t h i s c o n d i t i o n , a p r e c i p i t a t e f a l l
i n b lo o d p r e s s u r e r e s u l t e d and death occu rr ed i n a v e r y s h o r t
tim e.
In c e r t a i n o b s t e t r i c p a t i e n t s t h e r e i s p r o lo n g e d
s y m p a th e tic o v e r a c t i v i t y ,
due t o th e a n x i e t y and fo r e b o d in g
o f th e days b e fo r e th e o n s e t o f la b o u r , which makes them l e s s
a b le t o sta n d th e e x e r t i o n and trauma o f d e l i v e r y ; such v e r y
nervous p a t i e n t s a r e e s p e c i a l l y l i a b l e to d e v e lo p o b s t e t r i c
sh o ck .
I n c r e a s e d a d r e n a l in ou tp u t i s presum ably a f a c t o r i n
c a u s in g t h i s ty p e o f s h o c k ; , P a r k in s, S w in g le, Taylor and Hays
( 1 9 3 8 ) produced shock i n dogs by g i v i n g l a r g e d o s e s o f
a d r e n a l i n and t h e y found th a t t h i s type o f shock resp ond ed
w e l l t o tr e a tm e n t w ith a d r e n a l c o r t i c a l hormone.
I n the p r e s e n t i n v e s t i g a t i o n a c l i n i c a l and
b io c h e m ic a l s t u d y o f some p a t i e n t s s u f f e r i n g from v a r y in g
d e g r e e s o f o b s t e t r i c shock ha,s been made in an a ttem p t to
d e t e c t any e v id e n c e o f a d r e n a l e x h a u s t io n i n t h i s c o n d i t i o n .
The ch an ges o c c u r r in g i n h a e m a to c r it v a l u e s , plasm a sodium,
whole b lo o d c h l o r i d e s and b lo od urea have been d eterm in ed i n
t so
D t L . v tft.y
U
S
i a,
i fc>
do
a^
'.eon B lo o d P r e s s u r e Changes
' «M JO
^bwidvi'i)
ij-w
-KII
a v o s s 9 i i i c l < Co oi y
Ilf.
a s e r i e s o f 2 6 p reg n an t women about th e tim e o f d e l i v e r y .
A c a r e f u l watch was kept on the c l i n i c a l c o n d i t i o n o f each
p a tie n t for sig n s o f c o lla p s e ,
e s p e c i a l l y du rin g th e f i r s t
few h o u r s a f t e r d e l i v e r y ; blood p r e s s u r e r e a d in g s and p u l s e
r a t e were ta k e n a t h a l f h o u r ly i n t e r v a l s i n most c a s e s .
The p a t i e n t s have been d i v i d e d , from a c l i n i c a l s t a n d p o in t ,
in to 3 groups: a)
12 O ases (1 9 2 to 203) w ith no p ost-p artu m c o l l a p s e .
b)
8 O ases (2 0 4 to 211) w ith s l i g h t p ost-p a rtu m c o l l a p s e .
c)
6 O ases (2 1 2 t o 217) w ith marked p ost-p artu m c o l l a p s e .
Each group i n c l u d e s p a t i e n t s d e l i v e r e d sp o n ta n e o u s ly and by
f o r c e p s , p a t i e n t s w ith sh o r t and lo n g la b o u r s and to xaem ic
and n o n -to x a em ic p a t i e n t s .
In group c . t h e r e a r e 2 c a s e s o f
r e ta in e d p la c en ta .
Blood sp ecim en s were ta k e n o f f during la b o u r ,
u s u a l l y i n th e secon d s t a g e and a t a p p ro x im a te ly 1 , 2 , 4
and 24 h o u rs a f t e r d e l i v e r y .
In group c. c a s e s however,
i t was found to be im p o s s ib le t o o b t a i n sp ecim en s o f b lo o d
a t r e g u la r i n t e r v a l s o f time b eca u se the p a t i e n t s were so
c o l l a p s e d and b e c a u se i n most c a s e s b lo o d t r a n s f u s i o n s were
b e in g g i v e n .
O c c a s io n a l specim ens were o b ta in e d , how ever,
and i f each c a s e i s c o n s id e r e d s e p a r a t e l y the changes
o c c u r r in g can be f o l lo w e d .
Mean s y s t o l i c and d i a s t o l i c b loo d p r e s s u r e r e a d in g s
from th e p a t i e n t s o f groups a . and b. are c h a r te d i n Chart
XXIY. to show th e ch an ges o c c u r r in g during the p e r io d o f
116.
in v e stig a tio n .
The a b s o l u t e v a l u e s c h a r te d ar e not o f
im p o rta n ce a s both groups i n c lu d e d s e v e r a l p a t i e n t s s u f f e r i n g
from h y p e r t e n s i v e to x a em ia , c a u s in g a wide range o f v a l u e s .
As m ight be e x p e c t e d t h e r e was a s l i g h t and gradual p o s t ­
partum f a l l i n s y s t o l i c b lood p r e s s u r e i n the normal c a s e s
and a sudden p o st-p a r tu m f a l l w ith su bseq uent r i s e i n th e
s y s t o l i c b lo o d p r e s s u r e s o f the c a s e s w ith s l i g h t p o st-p a r tu m
c o lla p se .
The w ide v a r i a t i o n between the two s y s t o l i c c u r v e s
i n Chart XXIV. i s s i g n i f i c a n t ,
but the d i a s t o l i c c u r v e s do
n ot show th e same d i f f e r e n c e .
As a r u l e p u l s e r a t e v a r i e d
i n v e r s e l y w ith the b lo o d p r e s s u r e r e a d in g s .
The mean h a e m a to c r it changes i n the same p a t i e n t s
d u rin g th e f i r s t fo u r hou rs p ost-p artu m are shown i n T able X.
Table
X,
Mean H aem a tocrit v a l u e s from Groups a. and b. b e f o r e and
No. o f
C a ses.
Jroup a.
11
Iroup b.
6
Antepartum.
Im m ed iately b e f o r e
d e liv e r y .
Postpartum .
1 h r.
2 h r.
4 hr.
24 h r s .
Mean.
38#
Range.
31 to 43
37$
36#
35. 5#
31#
42 #
34 to 50
41$
41#
39. 5#
33#
The mean v a l u e s from the group a.
c a s e s show t h e normal
p o s t —partum d e c r e a s e d e s c r i b e d i n S e c t i o n I V . ; i n t h e group b.
c a s e s h ig h v a l u e s a r e m a in ta in e d f o r s e v e r a l h o u rs a f t e r
d e liv e r y .
The range o f ante-parturn v a l u e s i n each group i s
wide but h ig h v a lu e s p redom inate i n group b . ; t h e y a r e
Mean P la sm a Sodium Chanae
-t o o o )
't/ad- ‘bio
;vjni<tos
rorn C a se s o f Grorro
w
11J.
*■;
presum ab ly due t o d im in ish e d blo od volume.
!:
l a t e r t h a t c o r r e s p o n d in g ante-partum changes i n th e plasm a
|
It w ill
be shown
sodium o c c u r i n many o f t h e s e c a s e s .
ijj
J
The plasm a sodium e s t i m a t i o n s were made bv Rourke*s
m o d i f i c a t i o n o f Kramer and G ittle m a n 'e p yroan tim on ate method
■;jj
'ii
(1928 ).
In t h e p r e s e n t i n v e s t i g a t i o n the mean plasma sodium
I
v a lu e from 30 p regn an t women, near term or v e r y e a r l y i n
jj
la b o u r was 332 mg. p er 100 c . c .
-j
347
Per 100 c . o .
w ith a range o f 321 mg. to
The mean plasma sodium f i n d i n g s i n
p a t i e n t s o f groups a. and b. du rin g the f i r s t 4 hours p o s t
•
partum,
a r e shown i n Chart XXV. and Table XI,
Table
XI.
Mean Plasm a Sodium and Whole B lood C h loride changes i n
Groups a. and b.
I
Plasma Sodium
i n mg. p e r
100 a . c .
Mean.
Range.
jW
ore
. liverv. 325
1tour
r
ito.
7 tour8
jut
fetuin.
pours
1st
ten.
fi hours
| 8t
'ten*
i
Group b.
Group a.
■j
Whole Blood
C h lo r id e
i n mg. p e r
100 c . c .
Range.
Mean,
Plarna Sodium
in mg. p er
LOO c . c .
Range.
/lean.
Whole Blood
C h lo r id e
i n mg. p e r
100 c . c .
Mean.
Range.
311 t o 344 u s
481 t o 656 321 301 to 337
514 428 to 601
325
317 to 339 571
475 to 63? 291 266 to 101
528 480 to 612
129
119 to 148 178
510 to 632 305 £85 to 130
537 441 to 612
111
119 t o 112 7 M
542 to 648 320 101 t o 3 3 1
538 p5 1 6 J o„Z82.
332
319 to 350 611
565 t o 664
333
120 to 146. 575 498 t o 610
_
>m I n d i v i d u a l
ox G-roup a.
3X0
Hoon.S '?o$'T'^rt-R-r v f\
" T3 rn
a ) \ -L
lj - —xi.i.1
.VII
F i n d i n g s fro m I n d i v i d u a l C a se s o f Grout) 1.
V
u
O
Q 300
14ooA.s ■po5TrPft^rt>
11?.
I t w i l l be n o te d t h a t t h e r e i s a s i g n i f i c a n t drop i n t h e
plasm a sodium v a l u e s a f t e r d e l i v e r y i n th e c a s e s o f group b . ,
w ith r e t u r n t o normal a t 4 hours p o s t partum.
The mean plasm a
sodium v a l u e s f o r th e 12 normal c a s e s show p r a c t i c a l l y no
change d u r in g th e same p e r io d .
In Charts XXVI. and XXVII.
th e v a l u e s from th e i n d i v i d u a l p a t i e n t s o f groups a. and b.
r e s p e c t i v e l y have been p l o t t e d s e p a r a t e l y i n order to
d em o n stra te th e c o n s i s t e n c y o f the r e s u l t s and the tim in g
o f th e f a l l i n plasm a sodium v a l u e s .
In most c a s e s th e
l o w e s t v a l u e s o ccu r a t 1 hour p o s t partum w ith a r a p id r e tu r n
t o normal l e v e l s a t 2 hours p o s t partum.
In a few c a s e s
th e f a l l c o n t in u e s t i l l 2 hours p o s t partum and th e v a l u e s
r e t u r n more s l o w l y to normal.
l i m i t s a t 24 hours p o s t partum.
A l l v a lu e s are w i t h i n normal
I t i s o f i n t e r e s t to n o te
t h a t i n both groups a. and b. t h e r e a r e a few c a s e s w ith low
plasm a sodium v a l u e s b e fo r e d e l i v e r y ;
i n Chart XXVI. (from
group a . ) th e v a lu e s from such c a s e s show a r i s e towards
normal l e v e l s im m e d ia te ly a f t e r d e l i v e r y w h ile i n Chart XXVII.
( from group b . ) th e c u r v e s from a l l c a s e s f a l l im m ed ia tely
p o s t partum.
These c a s e s w ith low ante-partum plasma sodium
v a l u e s a l l had h ig h ante-partum h a e m a to c r it v a l u e s .
sig n ific a n c e ,
The
L ln i'B fm a, o f t h i s f i n d i n g w i l l be d i s c u s s e d
la te r .
Whole b lo o d c h l o r i d e d e te r m in a tio n s c a r r i e d out a t
th e same t im e s a s th e plasma sodium d e t e r m in a t io n s and on th e
same p a t i e n t s do not r e v e a l s i m i l a r c h a n g es.
I t was not
found p o s s i b l e ,
i n th e p r e s e n t c ir c u m s ta n c e s , to e s t im a t e
plasm a c h l o r i d e s b ecau se o f the d i f f i c u l t y i n m a in ta in in g
a n a e r o b ic c o n d i t i o n s .
The e s t i m a t i o n s o f whole b lo o d c h l o r i d e
were made by W hitehornf s m o d i f i c a t i o n o f V o lh a r d 's method
(1 9 2 1 ).
The mean r e s u l t s from p a t i e n t s o f both groups a . and
b. show a s t e a d y r i s e i n whole b lo od c h l o r i d e from b e f o r e
d e l i v e r y t o 24 h o u rs p o s t partum.
Table XI.
The r e s u l t s a r e g i v e n i n
There a r e wide v a r i a t i o n s i n the whole b loo d
c h l o r i d e v a l u e s o b t a in e d from i n d i v i d u a l p a t i e n t s o f both
grou p s due to f a c t o r s not under c o n s i d e r a t i o n a t p r e s e n t ,
so t h a t th e d i f f e r e n c e between the mean v a l u e s o f th e two
groups i s n ot o f s i g n i f i c a n c e .
The blo od urea f i n d i n g s were
v e r y v a r i a b l e and i n most c a s e s th e changes c o u ld be regard ed
a s a r e s u l t o f t h e l e n g t h o f the la b o u r .
In 4 o f the s e v e r e l y
shocked p a t i e n t s ( c a s e s 21 3 , 2 1 4 , 216 and 2 1 7 ) , however,
t h e r e was a g r e a t e r r i s e during the p e r io d o f shock th an c o u ld
be a c c o u n te d f o r by th e la b o u r .
In such c a s e s t h e i n c r e a s e
i n th e b lo o d u r e a i s presum ably the r e s u l t o f the shocked
co n d itio n .
The v a l u e s fo r h a e m a t o c r it, plasma sodium and
b lo o d p r e s s u r e from th e i n d i v i d u a l p a t i e n t s o f group a . ,
which have been u s e d to c o n s t r u c t th e v a r io u s graphs, a r e
shown t o g e t h e r i n th e c o m p o site t a b l e , Table X I I . ,
in order
t h a t t h e r e l a t i o n between th e v a r io u s changes i n each
i n d i v i d u a l p a t i e n t may be compared.
A sim ila r t a b le ,
i s g iv e n f o r th e f in d in g s from group b. c a s e s .
T able X I II
I t w i l l be
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122.
n o t i c e d from t h e s e t a b l e s th a t i n i n d i v i d u a l c a s e s t h e r e i s
n e i t h e r a c o n s t a n t p r o p o r t io n between the d e c r e a s e i n plasm a
sodium and th e f a l l i n blood p r e s s u r e , nor d oes th e minimum
plasm a sodium v a lu e c o i n c i d e w ith th e l o w e s t b lo od p r e s s u r e
r e a d in g .
In a l l c a s e s w ith s l i g h t c o l l a p s e , however, a f a l l
i n b lo o d p r e s s u r e , a r i s e i n p u l s e r a t e , and a lo w e r in g o f
plasm a sodium l e v e l o ccu r im m ed ia te ly p o s t partum.
I t h as n o t been found p o s s i b l e to arrange th e r e s u l t s
from th e c a s e s o f group c . , th o s e w ith s e v e r e p o st-p a rtu m
c o l l a p s e , i n t a b l e s or graphs.
itse lf.
Each c a s e must be s t u d i e d by
As one would e x p e c t , du rin g the p e r io d o f s e v e r e
shock th e b lo o d p r e s s u r e was alw ays e x tr e m e ly low e . g . ,
r e a d in g s o f 4 0 /3 0 * 5 5 /5 0 were o f t e n rec o rd ed and o c c a s i o n a l l y
no r e a d in g a t a l l c o u ld be o b t a in e d .
I t was n o t i c e d i n t h i s
group o f o e s e s t h a t a sm all p u l s e p r e s s u r e was an im p o rtan t
s i g n o f commencing or e s t a b l i s h e d shock and th a t a d e c r e a s e
i n p u l s e p r e s s u r e was more s i g n i f i c a n t th an a f a l l i n
s y s t o l i c b lo o d p r e s s u r e .
As i n group b. c a s e s th e r e was no
a b s o l u t e p r o p o r t i o n betw een the blood p r e s s u r e and th e plasm a
sodium l e v e l .
In 6 p a t i e n t s during s e v e r e shock th e plasm a
sodium ranged from 289 t o 300 mg. p er 100 c . c . w ith a mean
v a lu e o f 297 mg. p er 100 c . c .
These v a lu e s a r e subnormal but
th e r e was no d e f i n i t e r e l a t i o n between the d eg ree o f sh ock
and t h e plasm a sodium v a lu e ; s e v e r a l p a t i e n t s from group b.
had lo w e r plasm a sodium v a lu e s during t h e i r s l i g h t c o l l a p s e
than had any o f the p a t i e n t s o f group c.
In th e l a t t e r group,
CHART XTVTII.
Graph o f P l a s m a Sodium F i n d i n g s i n 6 c a s e s o f s e v e r e
|OOc.c,
postpartum c o lla p s e
5 oj> i v r\
:
520
310
U
HOORS
~ P 0 S T - P f t f t T U (v \.
V
123
how ever, a l o n g e r tim e e la p s e d b e fo r e the plasm a sodium
r e g a in e d normal l e v e l s .
The plasma sodium changes about the tim e o f d e l i v e r y
i n th e 6 c a s e s o f group c . a r e shown i n Chart XXVIII. and th e
o t h e r f i n d i n g s a r e g iv e n i n the appendix.
I t w i l l be n o t i c e d
th a t t h e plasm a sodium v a lu e s were v e r y low a f t e r d e l i v e r i n
a l l cases.
Three o f the c a s e s (2 1 2 , 213 and 214) were o n ly
a d m itte d t o h o s p i t a l a f t e r d e l i v e r y .
They were s e v e r e l y
sh ock ed and i n each t h e r e had been s e v e r e haemorrhage; th e
h a e m a to c r it v a l u e s i n t h e s e c a s e s were t h e r e f o r e low.
In c a se 212 th e plasma sodium remained low and t h e
p a t i e n t d ie d i n a few hours i n s p i t e o f b lo o d t r a n s f u s i o n
b e in g g iv e n .
Post-m ortem e x a m in a tio n r e v e a le d an a d h eren t
p l a c e n t a and s i g n s o f o b s t e t r i c shock.
Case 213 remained s e v e r e l y shocked fo r s e v e r a l h o u rs and
d u rin g t h i s tim e t h e plasm a sodium va lu e was subnormal.
The
n e x t day th e p a t i e n t was improved and the plasms, sodium
v a lu e was normal.
In c a s e 214 normal plasma sodium v a l u e s were r e g a in e d
16 h o u rs a f t e r d e l i v e r y and the s i g n s o f shock had d is a p p e a r e d .
Case 215? a p r e - e c l a m p t i c , showed marked s i g n s o f
e x h a u s t io n d u rin g la b o u r .
She was e x tr e m e ly a n x io u s , c r i e d
w ith o u t c a u se and com plained o f com plete e x h a u s tio n .
The
p u l s e r a t e was r a p id throughout la b o u r and b e fo r e d e l i v e r y
t h e p u l s e p r e s s u r e became v e r y sm a ll.
The a c t u a l h a e m a to c r it
r e a d in g s were not g r e a t l y r a i s e d but th e y were r e l a t i v e l y
v e r y h ig h a s compared w ith th e v a lu e o b ta in e d on the day a f t e r
d e l i v e r y : t h a t i s , th e post-p a rtu m d e c r e a s e i n v a l u e s was
e x c e s s i v e c o n s i d e r i n g t h a t t h e r e was no l o s s o f b loo d a t
d e liv e r y .
The plasma sodium v a lu e s i n t h i s c a s e f e l l d u rin g
la b o u r and became v ery low a t th e tim e o f d e l i v e r y .
The
p a t i e n t became c o l l a p s e d about 1-J- hours a f t e r an e a s y f o r c e p s
d e l i v e r y but r e c o v e r e d w ith tr e a tm e n t.
Case 216
plasm a sodium
l e a s t 2 h o u rs
plasma sodium
became c o l l a p s e d 1 hour a f t e r a e l i v e r y b u t th e
v a lu e s remained w i t h i n normal l i m i t s t i l l a t
a fte r d e liv e r y .
At 4 l o u r s p o s t partum t h e
v a lu e had f a l l e n c o n s id e r a b ly but r e g a in e d
12^
normal l e v e l s by th e n ext day.
Case 217 became e x tr em e ly shocked 3 h ou rs a f t e r
d e liv e r y .
She improved s l i g h t l y w ith tre a tm en t but c o l l a p s e d
s e v e r a l tim e s l a t e r .
Her g e n e r a l c o n d i t i o n remained
e x tr e m e ly poor and she d ie d 2 days l a t e r .
Post-mortem
e x a m in a tio n r e v e a l e d g e n e r a l i s e d p e r i t o n i t i s , - a p p a r e n tly
due t o d i r e c t sp read from u t e r u s and th e broad lig a m e n t , and p a tc h y l i v e r n e c r o s i s . Plasma sodium v a lu e s showed a
marked f a l l i n t h i s c a s e , im m ed ia tely p o s t partum i n s p i t e o f
t h e a d m i n i s t r a t i o n o f in tr a v e n o u s s a l i n e ( t h e r e i s u s u a l l y
a r i s e i n plasm a sodium f o r 1 to 2 hours a f t e r in tr a v e n o u s
s a l i n e ) , and th e v a l u e s remained low during th e l o n g p e r io d
o f c o lla p se .
D isc u ssio n .
The r e s u l t s record ed h er e i n d i c a t e t h a t , i n women
who show s i g n s o f s l i g h t or s e v e r e p ost-p artu m c o l l a p s e ,
th e
marked f a l l i n b lo o d p r e s s u r e i s accompanied by a f a l l i n
t h e plasm a sodium l e v e l .
The f a l l i n blood p r e s s u r e i s
a p p r o x im a te ly p r o p o r t i o n a l to th e d eg ree o f c o l l a p s e , a s one
m ight e x p e c t , but th e d e c r e a s e i n plasma sodium i s not so
r e la te d .
I t i s v e r y d i f f i c u l t to a s s e s s th e s i g n i f i c a n c e
o f t h e t r a n s i t o r y lo w e r in g o f th e plasma sodium i n t h e s e
cases.
This f i n d i n g , however, ten d s to support t h e s u g g e s t i o n
o f p r e v io u s w ork ers, t h a t shock r e s u l t s from an a c u t e
a d r e n a l c o r t e x i n s u f f i c i e n c y ; th e h a e m a to c r it and b lo o d
u r e a ch a n g es i n th e p r e s e n t c a s e s , a lth o u g h not v e ry s t r i k i n g ,
a r e a t l e a s t c o n s i s t e n t w ith such a th e o r y .
In A ddison*s
d i s e a s e th e b loo d sodium o f t e n rem ains f a i r l y normal u n t i l
j u s t b e f o r e death but i n such c a s e s the d e s t r u c t i o n o f th e
a d r e n a l g la n d s i s very slo w and the e x c e s s i v e sodium
11$.
e x c r e tio n i s compensated.
I t was not found p o s s ib le , in
the p resen t study to determine the sodium ex c r e tio n in the
urine with any accuracy because of the d i f f i c u l t y in c o l l e c t i n g
a l l the urine passed about the time of d e liv e r y .
The present
r e s u l t s , however, are sim ila r to those recorded by Reed (1938),
in ca se s o f s u r g ic a l shock, and those of Wilson and Stewart
(1939)?
ca ses o f burn shock, and i t i s p o s s ib le that both
the blood p ressure and the plasma sodium changes are the
r e s u lt o f adrenal cortex in s u f f ic ie n c y .
On t h is theory, the high ante-parturn haematocrit
values and the low ante-partum plasma sodium values found in
some c a s e s, might, perhaps, be regarded as an in d ic a t io n o f
a pre-shock s t a t e , r e s u ltin g from prolonged sympathetic
o v e r a c t iv it y before, and exhaustion during labour ( on an
anology with Freeman^ experiments mentioned above).
The
development o f d e f i n i t e post-partum c o lla p s e or shock, in
th e se c a se s, would then depend on the amount o f trauma or
haemorrhage su stain ed a t d e liv e r y .
High ante-partum
haem atocrit values and low plasma sodium values are not, o f
course, an in v a r ia b le fin d in g in cases which l a t e r develop
o b s t e t r ic shock; fo r example, in anaemic women, the haem atocrit
values would be low even i f some reduction in blood volume had
taken p la c e , and a ls o , in many cases the trauma and haemorrhage
su sta in e d at d e liv e r y are s u f f i c i e n t to cause shock in the
absence o f p red isp osin g f a c t o r s .
The conception of a p re-
shock s t a t e i s suggested only to explain the post-parturn
B l o o d p r e s s u r e a nd p u l s e r a t e f l u c t u a t i o n s i n f o u r c a s e s o f
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CASE
218.
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126.
c o l l a p s e which o c c u r s i n c e r t a i n c a s e s a f t e r r e l a t i v e l y
easy d e l iv e r i e s ;
c a s e 21 5 , a lr e a d y d e s c r ib e d , i s an example
of th is.
In s e v e r a l o f t h e s e c a s e s o f o b s t e t r i c shock
tr e a tm e n t w ith " e s c h a t i n 11, an a d r e n a l c o r t i c a l e x t r a c t , was
tr ie d .
The r e s u l t s were not dram atic but i n a few c a s e s
t h e y were e n c o u r a g in g .
The changes i n s y s t o l i c and d i a s t o l i c
b lo od p r e s s u r e and p u l s e r a te i n fo u r o f the c a s e s , b e f o r e
and d u rin g th e p e r io d o f shock and tr e a tm e n t, are g i v e n i n
Chart XXIX.
Case 213, was ad m itted to h o s p i t a l very shocked; blo od
t r a n s f u s i o n was g i v e n on a d m is s io n but the p a t i e n t c o l l a p s e d
a g a in so o n a f t e r .
8 c .c .
e s c h a t i n were g iv e n in t r a v e n o u s l y
when no b lo o d p r e s s u r e r e a d in g c o u ld be o b ta in e d and th e
p a t i e n t was p u l s e l e s s ; an hour l a t e r the blood p r e s s u r e was
35/ 3O and th e p u l s e was v e ry f a i n t and i r r e g u l a r .
Manual
removal o f th e p l a c e n t a was c a r r ie d out a t t h i s s t a g e ; no
a n a e s t h e t i c was r e q u ir e d a s th e p a t i e n t was u n c o n s c io u s .
Blood t r a n s f u s i o n was a g a in s t a r t e d but o n ly 200 c . c . had
run i n when th e n e e d le b lock ed .
Two hours a f t e r th e e s c h a t i n
i n j e c t i o n th e b lo o d p r e s s u r e was 5 0 /^ 8 &nd p u l s e r a t e 1 7 6 .
5 c .c .
e s c h a t i n were th e n g iv e n and the b lo o d p r e s s u r e
c o n tin u e d t o r i s e s l o w l y throughout the e v en in g and t h e
p a t ie n t g ra d u a lly recovered .
In c a s e s 215 and 216 th e e s c h a t i n was g i v e n soon a f t e r
th e o n s e t o f c o l l a p s e and i t can be se e n , from Chart XXIX. ,
th a t a r i s e i n b lo o d p r e s s u r e fo llo w e d :
th e g e n e r a l c o n d i t i o n
showed g r a d u a l improvement.
In c a s e 216 no tre a tm en t a p a rt from the e s c h a t i n was
g iv e n ;
the b lo o d p r e s s u r e r o se g r a d u a lly f o r 4 hou rs a f t e r
t h e e s c h a t i n i n j e c t i o n but l a t e r f e l l s l i g h t l y ; a secon d
i n j e c t i o n o f e s c h a t i n was g i v e n and w i t h i n h a l f an hour t h e
b lo o d p r e s s u r e had begun to r i s e .
In c a s e 218, a s i m i l a r m s u i t was o b ta in e d - s e e Chart XXIX.
but no b io c h e m ic a l i n v e s t i g a t i o n was c a r r ie d o u t.
In c a s e 217, the e s c h a t i n appeared to have l i t t l e
e f f e c t on the b lo o d p r e s s u r e or g e n e r a l c o n d i t i o n but i t
was found l a t e r t h a t the s i g n s of c o l l a p s e were due to
p e r ito n itis.
In s e v e r a l o t h e r c a s e s g e n e r a l improvement f o l lo w e d
tr e a tm e n t w ith e s c h a t i n a lth o u g h i t was d i f f i c u l t to e s t i m a t e
t h e p a r t p la y e d by the e s c h a t i n a s o th e r forms o f tr e a tm e n t
were a l s o g i v e n .
I t i s very d i f f i c u l t to a s s e s s th e v a lu e o f a
new t r e a t m e n t , e s p e c i a l l y o f a c o n d i t i o n such a s o b s t e t r i c
shock i n which one can never e s t im a t e th e sp o n ta n eou s powers
o f r e c o v e r y o f th e i n d i v i d u a l .
The p r e s e n t c a s e s s u g g e s t
t h a t a d r e n a l c o r t i c a l e x t r a c t may be o f v a lu e but much
f u r t h e r i n v e s t i g a t i o n i s n e c e s s a r y b e fo r e any c o n c l u s i o n s
can be drawn.
I t would appear t h a t r e sp o n se t o th e i n j e c t i o n
o f e x t r a c t d oes n o t b egin f o r i to 2 hours a f t e r th e i n j e c t i o n
and th e n improvement i s v e ry g ra d u a l.
This means th a t u n l e s s
th e e x t r a c t i s a d m in is t e r e d e a r l y , death may o c cu r b e f o r e
ns.
th e a c t i o n t a k e s p l a c e .
P r o p h y la c t ic trea tm en t w ith a d r e n a l
c o r t i c a l e x t r a c t w i l l r e q u ir e to be i n v e s t i g a t e d .
Summary.
A c l i n i c a l and b io c h e m ic a l stu d y h a s been made,
about th e tim e o f d e l i v e r y , on a s e r i e s o f p a t i e n t s i n c l u d i n g
c a s e s w ith no p o st-p a rtu m c o l l a p s e , c a s e s w ith s l i g h t p o s t ­
partum c o l l a p s e and c a s e s w ith s e v e r e post-p artu m c o l l a p s e .
A d e c r e a s e i n plasm a sodium i s found in ' e v e r y c a s e w ith
c l i n i c a l sig n s of c o lla p s e .
A s t e a d y r i s e i n whole b lo o d
c h l o r i d e o c c u r s i n a l l c a s e s from b e fo r e d e l i v e r y to 24
h ou rs p o s t partum.
Changes i n whole blood c h l o r i d e a r e n o t
found r e l a t e d to shock.
Blood p r e s s u r e , p u l s e , h a e m a t o c r it ,
plasm a sodium and u rea f i n d i n g s i n c o l l a p s e d c a s e s a r e
c o n s i s t e n t w ith th e th e o r y t h a t temporary e x h a u s t io n o f th e
a d r e n a l c o r t e x i s a f a c t o r i n o b s t e t r i c sh ock .
Treatment
w ith a d r e n a l c o r t i c a l e x t r a c t may be o f v a lu e i n some c a s e s .
SECTI ON
GENERAL
SUMMARY AND
VIII.
CONCLUSIONS.
I n d i v i d u a l summaries a r e appended to each o f
th e p r i n c i p a l s e c t i o n s o f t h i s t h e s i s and t h e r e f o r e o n l y
a v e r y s h o r t a c co u n t o f th e c o n t e n t s o f th e work i s g i v e n
here.
I n th e i n t r o d u c t o r y s e c t i o n t h e v a r io u s t h e o r i e s
r e l a t i n g to th e e t i o l o g y o f e c la m p s ia ar e m en tion ed , and th e
d iv e r g e n c e o f o p i n io n o f i n v e s t i g a t o r s w ith r eg a r d t o th e
q u e s t i o n o f r e t e n t i o n o f n o n - p r o t e in n i t r o g e n f r a c t i o n s i n
t h e h y p e r t e n s i v e to x a e m ia s o f p regnancy i s n o te d .
The l a c k
o f d e t a i l e d i n v e s t i g a t i o n o f the changes o c c u r r in g i n th e
b lo o d o f i n d i v i d u a l p a t i e n t s throughout the c o u r se o f th e
d isea se i s str e sse d .
In S e c t i o n I I .
th e changes i n the plasm a u r i c a c i d
and u r e a d u rin g th e l a s t few weeks o f p regn an cy, d u rin g
la b o u r and through out t h e puerperium are s t u d i e d i n normal
and n o n - c o n v u l s i v e toxaem ic p a t i e n t s .
A r i s e i n t h e s e non­
p r o t e i n n i t r o g e n f r a c t i o n s i s found to occu r alw ay s d u r in g
la b o u r and the h e i g h t o f the r i s e i s dependent on t h e l e n g t h
o f t h e la b o u r i n each c a s e .
The v a lu e s r e t u r n t o normal
l e v e l s d u rin g th e f i r s t few days o f th e puerperium .
These
ch a n g es i n plasm a u r i c a c i d and u rea a r e q u i t e u n r e l a t e d t o
tox a em ia or o th e r f a c t o r s .
The im portance o f t h e s e r e s u l t s
130 .
i s t h a t any i n t e r p r e t a t i o n o f b io c h e m ic a l f i n d i n g s about th e
tim e o f d e l i v e r y which d oes n o t take i n t o c o n s i d e r a t i o n t h e
ch an ges which have been shown t o r e s u l t from la b o u r i t s e l f ,
i s l i a b l e to be f a l l a c i o u s .
A s i m i l a r d e t a i l e d i n v e s t i g a t i o n o f e c la m p tic
p a t ie n t s i s recorded in S e c tio n I I I .
A s e r i e s o f e c la m p tic
c a s e s i s s t u d i e d b e fo r e the o n s e t o f f i t s and i t i s shown
t h a t , c o n t r a r y to the s t a t e m e n t s o f p r e v io u s a u t h o r s , a h ig h
plasm a u r i c a c i d v a lu e i n a p r e - e c l a m p t i c c a s e i s not an
in d e x o f impending e c la m p s ia .
A marked and r a p id i n c r e a s e
i n plasm a u r i c a c i d l e v e l i s shown to o c c u r , i n e v e r y c a s e ,
im m e d ia te ly a f t e r th e o n s e t o f f i t s and the e x t e n t o f th e
r i s e i s d i r e c t l y p r o p o r t i o n a l to th e number o f the f i t s .
The plasm a u r e a f i n d i n g s do not show any such d e f i n i t e changes;
i n some c a s e s , how ever, the u rea l e v e l r i s e s c o n s i d e r a b l y
l a t e i n the d i s e a s e and t h i s r i s e i s r e l a t e d t o a p e r io d o f
o lig u r ia ;
i n such p a t i e n t s the h ig h plasma u r i c a c i d v a lu e s
a r e m a in ta in e d or even i n c r e a s e a f t e r the f i t s have c e a s e d
u n t i l th e u r in a r y o u tp u t i s in c r e a s e d .
Labour i s found to
c a u se th e same changes i n plasm a u r ic a c i d and u r e a in
e c la m p t ic p a t i e n t s a s i s shown to occu r i n normal and nonc o n v u l s i v e to x a em ic c a s e s .
C o n v u lsio n s i n n on -p regn an t c a s e s
and i n a n im a ls a r e f o l lo w e d by changes i n th e plasm a u r i c
a c i d s i m i l a r to th o s e found i n th e e c la m p tic c a s e s ; i t i s
t h e r e f o r e co n c lu d e d t h a t c o n v u l s io n s , p er s e , r e s u l t i n a
r a p id and marked r i s e i n plasm a u r i c a c i d and the c a u se o f
1)1
t h i s r i s e i s d iscu sse d .
In S e c t i o n I ? , v a r i a t i o n s i n b lood c o n c e n t r a t i o n ,
d u rin g th e l a s t few days o f pregnancy, du rin g la b o u r and
th ro u g h o u t t h e puerperium , a s measured by changes i n t h e
h a e m a to c r it v a l u e , a r e s t u d i e d i n a s e r i e s o f normal p reg n a n t
women, p r e - e c l a m p t i c and c h r o n ic toxaem ic p a t i e n t s .
In th e
normal c a s e s , a d e f i n i t e in c r e a s e i n b lo od c o n c e n t r a t i o n i s
shown to o c cu r d u rin g th e l a s t few days b e fo r e d e l i v e r y ,
r e a c h in g a maximum v a lu e about the time o f d e l i v e r y .
There
i s r a p id b lo o d d i l u t i o n d u rin g the f i r s t 3 days p o s t partum
and a f t e r t h i s ,
th e b lo o d g r a d u a l l y r e t u r n s t o normal.
The
ch a n g es i n v o l v e th e t r a n s f e r o f 20 to 25$ o f the f l u i d o f
th e plasm a from the b lo o d i n t o the t i s s u e s and back a g a in .
P r e - e c la m p t ic c a s e s show s i m i l a r changes and i n a d d i t i o n ,
t h e r e i s an i n c r e a s e i n b lo o d c o n c e n t r a t i o n ante-partum
r e l a t e d to the s e v e r i t y o f the toxaem ia i n each c a s e ;
oedem atous c a s e s have r e l a t i v e l y low er h a e m a to c r it v a l u e s .
The c h r o n ic to x a em ic c a s e s a r e found to be o f 2 t y p e s t h o s e w ith o u t anaemia and t h o s e w ith s e v e r e anaemia or
hydraem ia.
Those w ith o u t anaemia c l o s e l y resem b le t h e p r e ­
e c la m p t ic c a s e s i n t h e i r h a e m a to c r it changes w h ile t h e
anaemic c a s e s show th e normal h a e m a to c r it changes about th e
tim e o f d e l i v e r y but do not show any r i s e i n v a l u e s d u r in g
th e puerperium .
The p o st-p a rtu m d i l u t i o n o f the b lo od i s
i n c r e a s e d i n p a t i e n t s i n whom th e r e i s oedema b e fo r e d e l i v e r y ,
haemorrhage a t d e l i v e r y or i n f e c t i o n i n th e puerperium .
S e c t i o n V. c o n s i s t s o f some b io c h e m ic a l s t u d i e s i n s e v e r a l
d i f f e r e n t c o n d i t i o n s c h a r a c t e r i s e d by s e v e r e v o m itin g .
In
e a r l y p reg n an cy t h e most im portant c a u se o f s e v e r e v o m itin g
i s h y p e r e m e sis gravidarum.
High h a e m a to c r it v a l u e s , r a i s e d
plasm a u r i c a c i d and urea v a l u e s a r e found i n a group o f
p a t i e n t s s u f f e r i n g from s e v e r e h y p er e m e sis; i n c r e a s e d plasm a
b i l i r u b i n o c c u r s i n a few c a s e s .
This n it r o g e n r e t e n t i o n
d is a p p e a r s r a p i d l y a s th e anhydraemia i s r e l i e v e d .
The
s e v e r i t y o f the c l i n i c a l s i g n s i n any i n d i v i d u a l c a se i s
found t o depend on th e d egree o f anhydraemia and t h e
developm ent o f W ern ickefs en c ep h a lo p a th y .
Several f a t a l
c a s e s a r e d e s c r i b e d to i l l u s t r a t e the r e l a t i v e im portance
o f t h e s e two f a c t o r s .
In l a t e pregnancy, c a s e s w ith s e v e r e v o m itin g a s
t h e i r main symptom a r e found to be o f s e v e r a l d i f f e r e n t ty p e s
t h e y a r e c l a s s i f i e d i n fo u r groups.
I)
P ro lo n g e d H y p e r e m e s is :-
In t h i s group o f c a s e s th e
b io c h e m ic a l f i n d i n g s a r e th e same a s t h o s e i n th e s e v e r e
h y p e r e m e s is c a s e s and appear to be th e d i r e c t r e s u l t o f t h e
v o m itin g .
The changes d isa p p e a r r a p i d l y when in tr a v e n o u s
g l u c o s e i s a d m in is te r e d .
I t i s con clu d ed t h a t t h e s e p a t i e n t s
a r e s u f f e r i n g from h y p erem esis gravidarum which has c o n tin u e d
i n t o th e l a t e months.
II)
P y e l i t i s o f P r e g n a n c y :-
In t h i s group o f c a s e s th e
c h a r a c t e r i s t i c b io c h e m ic a l f i n d i n g s a r e , a v e r y low haem atocr
v a lu e i n s p i t e o f s e v e r e v o m itin g , normal plasm a u r i c a c i d
I}?and u r e a v a l u e s e x c e p t l a t e i n th e d i s e a s e i n s e v e r e c a s e s
when a r e t e n t i o n o f both n o n - p r o t e in n i t r o g e n f r a c t i o n s i s
found, and, i n some c a s e s , a p o s i t i v e immediate d i r e c t
r e a c t i o n to th e van den Bergh t e s t and a s l i g h t i n c r e a s e i n
plasm a b i l i r u b i n .
A v e r y marked i n c r e a s e i n th e n o n - p r o t e i n
n i t r o g e n f r a c t i o n s o f the b lo o d i s found to occu r d u rin g
la b o u r i n t h e s e c a s e s .
Ill)
nE r * y th r o b la s to s is f o e t a l i s ”
Severe v o m itin g i s
found to o c c u r i n a group o f p a t i e n t s a s s o c i a t e d w ith f o e t a l
and p l a c e n t a l a b n o r m a l i t i e s .
Plasma u r i c a c i d v a lu e s a r e
v e r y h ig h and plasm a urea m o d e r a te ly r a i s e d i n each c a s e .
S l i g h t ja u n d ic e and r a i s e d plasma b i l i r u b i n a r e found e a r l y
i n th e d i s e a s e .
IV)
The e t i o l o g y o f the c o n d i t i o n i s not known.
A m i s c e l l a n e o u s g r o u p :-
in c lu d i n g c a s e s o f h y p e r t e n s i v e
to x a e m ia , a c u t e y e ll o w a tr o p h y o f pregnancy and i d i o p a t h i c
ones.
No b io c h e m ic a l f i n d i n g s are g i v e n fo r c a s e s o f t h i s
group.
In S e c t i o n VI. c o n d i t i o n s w ith ja u n d ic e a s a
prom inent f e a t u r e a r e d e a l t w ith .
The e t i o l o g y o f th e
s l i g h t i c t e r u s , p o s i t i v e van den Bergh and r a i s e d plasm a
b iliru b in ,
found i n some c a s e s o f e c la m p s ia , h y p e r e m e sis,
and p y e l i t i s i s d i s c u s s e d .
A f a t a l c a s e o f o b s t e t r i c a c u te y e ll o w a tro p h y i s
d e s c r i b e d w ith th e b io c h e m ic a l and p a t h o l o g i c a l f i n d i n g s ;
dea th i n t h i s c a se was due to shock and a la.rge p a ragan gliom a
was found a t th e a u to p sy .
I t i s s u g g e s t e d t h a t th e
m
“e r y th r o b la s t o s is f o e t a l i s 11 group o f l a t e vomit'ing c a s e s may
be n o n -fa ta l examples o f o b s t e t r ic acute yellow atrophy.
A f a t a l case of true acute yellow atrophy o f the
l i v e r occurring during pregnancy i s next described and the
biochemical and p a th o lo g ic a l fin d in g s are given in d e t a i l .
The biochemical fin d in g s in se v era l n o n -fa ta l
ca ses o f delayed chloroform p oison ing are recorded and the
changes during treatment are follow ed.
The rapid improvement
which occurs in such ca ses fo llo w in g the ad m in istration of
continuous intravenous glu cose i s emphasized.
A comparison i s then made between the biochemical
and p a th o lo g ic a l fin d in g s in th ese three typ es o f l i v e r damage
o b s t e t r ic acute yellow atrophy, true acute yellow atrophy
and delayed chloroform p oison ing.
The h eigh t o f the plasma
b ilir u b in i s found to be the best index o f the s e v e r it y o f
the d is e a s e .
I t i s shown that gross l i v e r damage does not
n e c e s s a r ily r e s u lt in a high plasma uric acid .
S ection VII. in clu d es a short resume o f the
experimental and c l i n i c a l research which has in d ica ted a
r e la t io n s h ip between su rg ic a l or secondary shock and adrenal
co rtex in s u f f ic i e n c y .
The biochemical changes in the blood
which have been shown to r e su lt from adrenalectomy are given.
It i s noted that there i s a c lo s e resemblance between the
c l i n i c a l con d itio n o f p a tie n t s s u ffe r in g from o b s t e t r ic
shock and that of animals with adrenal in s u f f ic i e n c y .
Changes
in blood p ressu re, p ulse ra te , haem atocrit, whole blood
135c h l o r i d e , plasm a sodium and u rea are s t u d i e d i n p a t i e n t s
about t h e tim e o f d e l i v e r y and i n the e a r l y puerperium .
In c a s e s w ith s l i g h t or s e v e r e c o l l a p s e b io c h e m ic a l ch an ges
s u g g e s t i v e o f a tem porary a d r e n a l c o r t i c a l i n s u f f i c i e n c y
a r e found to o c c u r ; th e most im p ortan t f i n d i n g i s a f a l l in
plasm a sodium i n shocked c a s e s .
The e x i s t e n c e o f a “p r e -
sh ock *1 s t a t e i n some p a t i e n t s i s s u g g e s t e d .
Improvement
r e s u l t e d i n a few c a s e s o f o b s t e t r i c shock a f t e r tr e a tm e n t
w ith a d r e n a l c o r t i c a l e x t r a c t s .
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l 6l
A P P E N D IX .
151-
A P P E N D I X
The biochemical findings from all the cases quoted throughout
the -work are given in detail in this section. They are grouped as
follows:25 Normal cases, Nos.l to 25.
27 Mild Pre-eclamptic cases, Nos.26 to 52.
29 Severe Pre-eclamptic cases, Nos.53 to 82.
20 Chronic Toxaemic cases, Nos.83 to 103.
42 Eclamptic cases, Nos.104 to 145.
10 Azoman cases, Nos.146 to 155.
16 Eyperemesis cases, Nos.156 to 171.
4 Late hyperemesis cases, Nos.172 to 174.
6 Pyelitis cases, Nos.175 to 180.
4 1Erythroblastosis foetalis1 cases, Nos.181 to 184.
1 Case of Obstetric Acute Yellow Atrophy, No.185.
1 Case of True Acute Yellow Atrophy, No.186.
5 Delayed Chloroform Poisoning cases, Nos.187 to 191.
26 Obstetric Shock cases, Nos.192 to 217.
The results are given in tabular form.
Plasma uric acid, urea
and sodium and whole blood chlorides are expressed in mg. per 100 c.c.;
Plasma bilirubin is expressed in units per 100 c.c.
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