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N METABOLISM IN THE PUERPERIUM.*
BY VICTOR JOHN HARDING AND RICHARD CLIFTON MONTGOMERY.
(From the Department of Pathological Chemistry, University of Toronto, and the Metabolism Ward, Burnside Maternity thing, Toronto
General Hospital, Toronto, Canada.)
(Received for publication, February 7, 1927.)
It is usual to regard the puerperal period as marked by a N loss. The early experiments of Grammatikati (l), Zacher- jewski (2), etc., and the more recent ones of Slemons (3), Murlin (4), and Wilson (5), have made it evident that a diet which, under ordinary circumstances, would be adequate in calories and protein, and which in fact produces large N gains in the latter half of pregnancy, proves itself inadequate to maintain a N balance in the puerperium. It is usual to ascribe this N loss to the involution of the uterus. The atrophic changes which this organ undergoes, changing from roughly 1000 gm. to 50 to 100 gm. in the space of a fortnight are striking, and it cannot be doubted that amino acids set free by autolysis in this process will find their way into the urine as urea during a period of N loss. Zacherjewski appears to have been the first to particularize the involution of the uterus as responsible for the N loss, but it was emphasized vigor- ously by Slemons, who compared the N loss in a case of simple cesarean section with that in which the uterus was removed. The case of simple cesarean section lost 2 to 3 gm. more N than the other, an amount comparable with that expected, were the extra loss due to the involution of the uterus. Grammatikati alone appears to
have offered another explanation of the N loss, ascribing it to the process of lactation. Under the conditions of his experiments he
* The authors wish to thank the Medical Research Committee of the University of Toronto for a grant enabling them to carry out this work. They also wish to thank Miss H. Murphy for her care of patients and Miss J. Porter and Miss M. J. Ketchem for supervision of diets. To Dr. B. A. Eagles they are indebted for the determinations of crestinine and creatine.
27
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28 IT Metabolism in Puerperium
observed a maximum output of urea coincident with the appear- ance in the breast of a heavy milk flow, and a low urea output in those cases nursing irregularly. He explained his results as due to the conversion of protein to the fat of the milk with the liberation of the N into the urine. In our opinion the inadequacy of his explanation has obscured the accuracy of his observations.
The origin of the N loss is also of interest in its bearing on the problem of postpartum creatinuria. Shaffer (6) first observed this phenomenon in women, and Murlin (7) in dogs. Here again the involuting uterus would appear to offer a simple solution of the origin of the urinary creatine at this time. The amount of crea- tine excreted however is often in excess of that expected were the creatine to arise solely from the autolyzing uterus. Thus Shaffer observed as high as 1.5 gm. of creatine a day. Beker’s (8) calcu- lations, based on a creatine content of uterine muscle of 89 mg. per 100 gm., make only 0.73 gm. of total creatine. This amount is probably too low judging by the experience of Harding and Eagles (9) who found the creatine content of brain to be 100 to 116 mg. per 100 gm. compared with the figure of 51 to 63 mg. per 100 gm. of Beker; but even making every allowance for error, 1.5 gm. repre- sents a maximum amount of uterine creatine. Mellanby (lo), assuming the ut.erus, as a plain muscle, contained little or no creatine, advanced the view that lactation should be regarded as responsible for the creatinuria. He observed a parallel between t,he creatine-creatinine ratio and the rate of growth of the breast- fed babies; delayed lactation corresponded to a delayed creati- nuria; early lactation and early creatinuria were also associated. One must observe here, however, that creatinuria is often found in late pregnancy. Morse’s (11) experiments on the creatinuria of simple cesarean section and cesarean section accompanied by hysterectomy, convinced him that the origin of postpartum creatinuria was not in the uterus, though he refused to accept Mellanby’s explanation. The histories of the N balance and of the creatinuria of the puerperium thus offer an interesting parallel.
Is the N loss of the puerperal period inevitable? Previous experiment,s have simply observed the change of N balance on diets, which should have been adequate under ordinary condi- tions. Can diets, containing a sufficient amount of N and an excess of calories, cause N gains? Gains such as these could, of
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V. J. Harding and R. C. Montgomery
course, be att’ained, either by checking the involution of the uterus, or masking the N losses consequent on its involution by N gains in other parts of the body. Experiments involving a similar problem have been common in the field of N losses in febrile conditions. The feeding of high calory diets at a sufficiently high level of N intake has resulted in N gains in typhoid fever (12) and tuber- culosis (13) without deciding how such gains are actually attained. Experiments on N balance during the involution of the uterus have the advantage that the organ can be measured by a pelvime- ter and thus a rough idea of the atrophy obtained by independent means. The results also are not complicated by fluctuating temperature. It is true that the involution of the uterus repre- sents a localized occurrence, and that its contraction after labor is sharp and rapid, thus cutting off some of its blood supply before dietary influences have time to come into play; nevertheless the acute at’rophic processes continue some 14 days, giving ample opport’unity for observation. The course of the N balance under these conditions might also be expected to supply further evi- dence on the creatinuria.
With such ideas in mind we have carried out experiments on four selected cases, placing each subject on a diet ample in calories and N intake immediately after labor. All subjects were normal, had been under observation some 3 or 4 months previous, passed through a normal labor and returned from the delivery room in excellent condition. Immediately, 2000 cc. of 10 per cent glucose in normal saline were given intravenously and food was urged in the first 24 hours. There was thus no period of starvation. The subjects remained in bed during the whole of the observation period. Three diets were used, 2500, 3000, and 4000 calories respectively and containing 25, 23, and 34 gm. of protein. The 4000 calory diet was used for two subjects (D-k-n and W-r). The subjects received 38, 52, 54, and 74 calories, and 0.079, 0.092, 0.094, 0.14 gm. of N per kilo of body weight respectively. The amount of N is rather low according to ordinary standards except in the last case, but should have been sufficient to cover the ordinary wear and tear N in view of the calories supplied; 6 gm. of salt were given daily. The food was constant throughout the experiment. The details of the diets are to be found in Table I.
Urine was collected daily, preserved under toluene, and analyzed
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TABLE I.
Food.
Breakfast. Stewed figs ........................................ Rolled oats (dry weight) .......................... Marmalade ......................................... Bread ............................................. Butter ............................................. Cream,32 per cent ................................ Sugar .............................................
Dinner. Grape juice with 10 gm. sugar ...................... Chicken ........................................... potato ............................................ Vegetable (I, 10 per cent) (II, 15 per cent). ........
“ salad (5 per cent). ....................... Corn .............................................. Lettuce with 50 gm. banana (edible portion). ...... Bread .............................................. Butter ............................................. Cream,32 per cent ................................ Sugar .............................................. Rice ............................................. Raisins ...........................................
2.30 p.m. 100 gm. orange juice wit,h 10 gm. sugar.. S upper.
Baked potato ...................................... Vegetable, 10 per cent ..............................
“ 5 “ “ ........................... Lettuce .......................................... Orange ............................................ Parsnips .......................................... Bread ............................................ Butter ............................................ Cream, 32 per cent. ............................... Honey. ........................................... Sugar ............................................ Baked apple ......................................
8 p.m. Grape juice ................................. Sugar .......................................
Carbohydrate ..................................... Fat, .............................................. Protein ........................................... Calories ..........................................
I -
-
-
80 20 30 40 20 60 30
100 100
75
30 12 80 30
100 30
2oa 1oc
75
200 100
40 50
3( 4c 1: 10
6( 60 3( 4:
2f 3c
37: 9! 2.
249
Diets.
vm.
130 30 30 40 20 60 30
120 100 100
40 15 80 30
120 40
2oc
-
501 lC(
2: 300(
- [II - Irn.
150 30 40 60 25 80 30
210 40
130
120 90 50 25
100 30
100 40
110
200
40 60
100 50 18
100
19 150 200
10
628 150
34 4001
30
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TABL
E II
N Ba
lanc
e.
Case
M
-l-r.
Grav
ida
1;
age
19
yrs.,
he
ight
5 ft.
4;
in
., we
ight
1444
lb
s.
Labo
r, Fe
b. 21
, 19
26.
Loi?
?ir
7-
- I - _
1
. - _
I Bl
ood
analy
sis
Pelvi
m&r
re
ading
s. M
ilk.
---__
Vol-
N um
e.
-__ cc
. lm
.
134.
9 0.
34
227.
2 0.
58
340.
8 0.
92
397.
6 0.
81
397.
6 0.
81
333.
7 0.
72
333.
7 0.
71
269.
8 0.
69
333.
7 0.
56
298.
2 0.
60
291.
1 0.
61
446.
2 0.
91
426.
0 0.
94
390.
5 0.
84
383.
4 0.
80
-- 1998
.411
0.84
Urine
.
W:fh
t ba
by.
I I
Vol-
N “Il
Ie.
“Y-Y
“i?
.” 3d
MlC
C’
___
N.
Date
.
gm.
5.08
5.29
5.14
I
.- _ -
- 82
.72
Date
. N0
n-
prP m
u.
25.1
20
.2
20.5
22
.4
21.6
20
.2
20.4
20
.8
Uroa
N
per
100
cc.
nw.
1.65
0.
42
8.15
7.
45
8.85
5.
35
5.12
6.
52
Feru
m
pro-
te
in.
er
ten
5.25
5.
25
5.70
5.
68
6.12
5.
47
5.47
6.
55
Date
.
--- ur
n.
CC.
am.
3742
.0
3700
17
.09
3628
.8
2150
9.
93
3642
.9
2420
10
.09
3664
.1
1260
5.
36
3727
.7
1550
8.
85
3756
.0
1930
6.
05
1520
4.
70
3713
.7
1200
5.
30
1400
5.
94
3727
.7
(150
) 37
98.6
14
50
5.35
38
26.9
13
50
4.76
38
26.9
76
0 4.
37
870
3.80
38
26.9
10
70
2.74
38
26.9
15
00
3.46
---
97
.79
- - 4 -
am.
0.22
0.
21
0.36
0.
16
0.15
0.
31
0.37
0.
32
0.30
r7m
.
2.23
0.
69
2.70
1.
88
0.98
2.57
0.
27
3.08
1.27
1.
39
1.57
1.
70
0.64
1.
74
um.
18.9
4 12
.11
12.6
6 8.
07
11.4
4 8.
80
7.42
7.
96
8.56
7.58
7.
00
6.91
6.
37
5.21
5.
89
cm. 9 11
10
10
10 9 8 5
s.
P.
$wc.
-13.
77
Feb.
23
-6.9
4 “
25
-7.5
0 “
27
-2.9
0 Ma
r. 1
-6.2
7 ”
3 -3
.63
“ 5
-2.2
6 “
8 -2
.78
“ 10
-3
.40
-2.4
1 -1
.83
-1.7
4 -1
.20
-0.0
4 -0
.72
-57.
39
Feb.
22
“ 23
“
24
“ 25
“
26
“ 27
“
28
Mar.
1 ‘I
2
Feb.
22
“ 23
“
24
“ 25
“
26
“ z
27
“ 28
Ma
r. 1
“ 2
“ 3t
(’
4 “
5 “
6 “
7 “
8 “
9
Tota
ls.
. .
2.40
!2
.70
* In
ca
lcula
ting
the
N ba
lance
th
e av
erag
t ?f
i
134.
9:
igure
s of
1.
63
gm.
of
feca
l N
and
5.17
gm
. of
fo
od
N ar
e us
ed.
t Te
mpe
ratu
re
102-
103”
; co
nges
tion
of
mam
mar
y gla
nd.
No
urine
co
llect
ions
. S.
P.
= At
lev
el of
sy
mph
ysis
pubi
s.
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TABL
E III
.
N Ba
lanc
e.
Case
B-
l-n.
Grav
ida2;
age
20
yrs.,
he
ight
5 ft.
34
in
., we
ight
127
Ibs.
La
bor,
Mar.
20,1
926.
- I
Milk
. I
Bloo
d an
alysis
.
Date
.
-- cm
.
Mar.
22
8 “
23
8 ”
24
7 “
25
6 “
26
5.5
“ 27
5
“ 28
4
“ 29
3.
5 “
30
3 “
31
s.
P.
--
--
Urine
.
“:Pt
baby
. Vo
l-
- -
umc.
N
--
gm.
cc.
2664
.2
1360
26
78.3
14
50
2664
.2
1050
27
10.6
12
00
2806
.5
1460
95
0 28
41.8
87
0 28
84.2
95
0 29
33.8
10
20
2962
.1
1040
14
20
3132
.9
(700
12
50
3089
.5
1060
31
53.1
95
0 --
(Im.
7.17
5.
68
5.93
4.
70
6.17
5.
15
4.81
5.
22
4.41
4.
16
3.67
3.
22
3.29
3.
47
3.16
‘0.21
>och
ia N.
V0
l- “II
W.
N
CJm
.
0.41
0.
43
0.71
0.
53
0.52
0.
47
0.00
0.
27
0.24
0.
13
0.16
0.
09
um.
cc.
Urn.
*m.
1.42
14
0 0.
41
9.53
1.
03
318
0.93
8.
58
1.04
31
8 0.
93
9.11
1.
29
279
0.88
7.
65
2.71
49
7 1.
27
9.50
2.
03
294
0.91
8.
07
1.46
36
5 1.
15
7.50
1.
88
211
0.66
7.
69
1.75
34
9 1.
09
7.28
1.
05
451
1.42
7.
24
1.80
41
4 1.
30
6.66
1.
03
367
1.16
6.
01
0.88
36
8 1.
16
6.00
1.
03
433
1.33
6.
34
2.78
50
9 1.
60
6.30
3.96
!3
.18
i223
6.20
Food
N.
om.
5.46
5.03
5.25
gm
-4.3
0 Ma
r. 23
-3
.34
“ 25
-3
.87
“ 27
-2
.41
“ 29
-4
.26
“ 31
-2
.83
Apr.
2 -2
.26
“ 6
-2.4
5 “
9 -2
.04
“ 12
-2
.01
“ 14
-1
.43
-0.7
7 -0
.75
-1.1
0 -1
.06
13.4
1 78
.6(
-34.
881
Dat
e.
I , / _
-
T NO
W
Uri?a
hr
um
mot
ein
N.
N pe
r pro
- 10
0 co
. te
in.
Date
. I
_-
_-
-
ml.
mc7.
ler
cenl
18.8
8.
15
5.68
19
.6
7.68
6.
12
20.8
9.
46
6.12
19
.7
9.32
6.
55
21.2
8.
12
8.49
19
.8
7.45
8.
25
19.1
6.
83
7.89
29
.8
16.4
6 7.
42
30.6
to
.50
8.49
26
.9
18.1
7 7.
73
Mar.
23
“ 24
“
25
“ 26
3
“ 27
“
28
‘( 29
“
30
“ 31
Ap
r. 1
“ 2
“ 3
“ 4
“ 5
“ 6
_ 1 To
tals.
. . .
* In
ca
lcula
ting
the
N ba
lance
th
e av
erag
e fig
ures
of
1.
54
gm.
of
feca
l N
and
5.24
gm
. of
fo
od
N ar
e us
ed.
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TABL
E IV
.
N Ba
lanc
e.
Case
D-
k-n.
Grav
ida
2;
age
23
yrs.,
he
ight
5 ft.
43
in.
, we
ight
1651
lb
s.
Labo
r, Ap
r. 24
, 19
26.
Apr.
25
“ 26
“
27
“ 28
“
29
22
“ 30
Ma
y 1
CL
2 “
3 “
4 “
5 “
6 I‘
7 “
8 9 “
10
“ 11
Tota
ls..
.
Urine
.
Vol-
ume.
cc.
1340
12
50
1200
10
40
1750
14
20
1420
10
00
1420
11
90
1480
19
00
1950
15
00
1550
15
80
1730
- _ 7
N l7m.
6.96
4.
02
4.27
5.
02
4.46
3.
67
4.19
3.
74
3.96
3.
57
4.45
4.
17
4.17
3.
82
3.25
3.
51
3.65
0.88
om.
0.40
0.
17
0.16
0.
42
0.20
0.
28
0.24
0.
23
0.16
0.
04
0.03
0.
12
0.14
2.59
“m.
2.24
1.
35
2.32
2.
21
2.45
1.
76
2.24
2.
93
2.28
2.
17
2.21
1.
97
2.06
2.
38
3.24
1.
88
2.61
8.30
Milk
.
Vol-
ume.
cc.
Tota
l lal
sncc
* N.
“i?
” N.
D&o.
vn.
gm.
gm.
9.61
6.
38
-2.6
1 Ap
r. 27
6.
44
7.20
+0
.56
“ 29
6.
68
7.53
+0
.32
May
1 7.
69
-0.6
9 “
4 6.
91
f0.0
9 “
6 6.
20
$0.8
0 “
7 6.
68
t-O.32
“
10
6.22
+0
.78
6.37
6.
86
f0.6
3 5.
86
6.94
+1
.14
6.73
f0
.27
6.54
7.
11
+0.4
6 6.
42
7.36
+0
.58
6.21
+0
.79
5.50
f1
.50
5.76
+1
.24
5.90
+1
.10
11.7
2119
.0
-10.
58
I Bl
ood
analy
sis.
-
I
.- -
NOW
m
otcil
N.
mg.
VW
.
12.8
1 5.
86
14.8
( 5.
98
18.6
1 6.
76
17.9
t 7.
78
10.6
l 4.
66
16.8
1 4.
66
16.2
( 6.
99
UreZ
i N
per
100
cc.
pro-
te
in.
‘W
em
6.34
6.
44
6.98
6.
98
7.20
7.
42
6.98
Pclvi
met
cr
read
ings.
Date
.
Apr.
24
“ 25
“
26
“ 27
“
28
“ 29
“
30
May
1 ic
2
“ 3
“ 4
cm.
11 9 10 9 8 8 8 7 5
s.
I’ “
* In
ca
lcula
ting
the
N ba
lance
th
e av
erag
e fig
ures
of
2.
25
gm.
of
feca
l N
and
7.0
gm.
of
food
N
are
used
.
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TABL
E V.
N Ba
lanc
e.
Case
W
-r.
Grav
ida
1;
age
19
yrs.,
he
ight
5 ft.
2;
in
., we
ight
118
lbs.
La
bor,
May
22,1
926.
- Lo
chia N.
N
D&3.
Weo
ifht
baby
. um
e.
-- gm
. cc
.
May
23
1850
“
24
1920
“
25
3075
.3
1180
“
26
3131
.9
1000
“
27
3153
.1
1000
“
%
“ 28
31
53.1
10
50
29
3097
.8
1031
“
30
1000
“
31
3198
.3
1000
Ju
ne
1 32
71.1
10
00
” 2
3271
.1
1000
”
3 34
01.6
10
00
“ 4
3462
.6
1000
“
5 35
28.9
10
00
“ 6
1000
“
7 35
43.1
10
00
” 8
3599
.7
1000
“
9 36
42.8
10
00
-~
Tota
ls..
. . .
-__
*??I.
gm
.
8.44
0.
76
8.04
0.
42
5.81
0.
57
5.74
0.
83
6.49
0.
95
7.73
0.
56
5.91
0.
25
4.57
0.
13
4.53
0.
19
4.91
0.
19
4.90
0.
15
5.01
0.
13
4.32
0.
08
4.59
0.
16
6.02
0.
14
5.19
5.
20
4.55
-
__
91.9
5 5.
51
Fece
s N.
fJm
.
0.21
0.63
1.
37
3.94
3.
73
1.85
0.
99
2.37
1.
97
1.59
2.
10
1.30
12.0
5
Milk
.
--.-
- cc
. gm
.
105
0.25
67
0 1.
62
925
1.76
97
5 1.
55
855
1.67
81
5 1.
56
690
1.29
90
5 1.
59
865
1.52
71
2 1.
18
615
1.08
57
5 1.
11
715
1.34
53
0 0.
96
670
1.23
51
0 0.
94
690
1.32
~_
_
1,82
2,21
.97
I I
I Blo
od
analy
sis.
Tota
l N.
Da
te.
~ ~-
- -
gm.
gm.
c?m
. 11
.00
7.44
-3
.32
May2
4 10
.52
-2.8
3 “
27
9.81
-2
.12
“ 31
10
.14
-2.4
5 10
.80
-3.1
0 11
.77
7.86
-4
.08
9.53
-1
.84
7.80
-0
.11
8.12
-0
.44
8.43
-0
.74
8.04
-0
.35
8.03
7.
78
-0.3
4 7.
32
to.3
7 7.
90
-0.2
0 8.
94
-0.2
0 8.
23
-1.2
4 7.
95
-0.5
4 7.
68
-0.2
6 ~_
_--~
62.0
1 13
7.42
-2
4.15
I
-
NOW
xo
tei.
N.
-r n : 1
_ -
-
UWl
N pe
r 00
cc.
mg.
L
11.2
10
.3
10.3
-
brum
pr
o-
tein
.
MT
een
5.47
7.
25
6.34
Pelvi
mete
r rea
dings
.
I -- !I -- -
Date.
May
23
“ 24
“
25
“ 26
“
27
“ 28
“
29
“ 30
cm.
13
12
11 8 8 7 6
s.
P
* In
ca
lcula
ting
the
N ba
lance
th
e av
erag
e fig
ures
of
1.
81
gm.
of
feca
l N
and
7.69
gm
. of
fo
od
N ar
e us
ed.
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V. J. Harding and R. C. Montgomery 35
for N by the Kjeldahl-Gunning method. Lochia was collected on N-free pads; the pads collected daily and allowed to hydrolyze in warm 20 per cent sulfuric acid. The hydrolysate was made up to a definite volume and an aliquot portion used for N determina- tion. Feces were obtained by a daily enema, placed in a jar, emulsified with warm 20 per cent sulfuric acid made up to 2000 cc., and 50 cc., were used for N determinations. The food N was determined by obtaining on three separate occasions, for each subject, a series of duplicate trays of the day’s supply from the diet kitchen. The contents were well mixed, heated from 12 to 24 hours on a water bath with 20 per cent sulfuric acid until thoroughly disintegrated and emulsified, made up to 2000 cc., and 25 cc. sample used for N determination. A specially calibrated wide tipped pipette was used in obtaining this sample. Milk N was determined on 5 cc. by the Kjeldahl-Gunning method. The details of the N balance of each case are to be found in Tables II to V. Creatine and creatinine were determined by the method of Folin (14). Routine blood analyses were made from time to time throughout the experiment as shown in the Tables.
RESULTS AND DISCUSSION.
In no case were we able to affect measurably the rate of involu- tion of the uterus. Even in the case of W-r, with an intake of 74 calories per kilo of body weight and 7.69 gm. of N, the involution of t’he uterus was complete in the usual time.
In only one case (D-k-n, Table IV) were we able to observe N gains. Marked losses of N occurred in the other three cases. The N gains of D-k-n occurred with an intake of 54 calories per kilo of body weight and 7.6 gm. of N. Normal involution meas- urements showed the autolytic processes in the uterus evidently continued at their usual rate, and one may calculate from an approximate weight of the uterus (1000 gm.) that at least 40 gm. of N in the form of tissue were broken down. Yet this was en- tirely masked by the influence of the diet which brought about a tot,al gain of 2.45 gm. of N in 17 days. With the exception of 3 days, N gains were made steadily throughout the period of the active involution of the uterus, and as two of these losses were immediately following parturition it is reasonable to suppose that the diet had not had time to exert its masimum protein-sparing
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36 N IMetabolism in Puerperium
effect. Some objection perhaps may be raised that the N of the uterus was retained in some form other than synthetic. If so, this form at least was not urea as judged by the concentration of that substance in the blood. The serum proteins rose but this is usual during a normal puerperium and similar rises can be found in the other cases.
The other three cases all show continuous N losses. The case of M-l-r (Table II) may perhaps be discarded as in comparison with D-k-n she was on a lower plane of intake both of calories and N, though bot,h calories (38 per kilo) and N (5.17 gm.) would be judged amply sufficient under ordinary conditions. We do not believe this to be the explanation of the N loss, but no such criticism can be advanced against cases B-l-n and W-r (Tables III and V). In the former the calory value and N content of the diet were the same per kilo of body weight as for D-k-n. In the latter both values were markedly higher. The conditions were such that the N set free from the involuting uterus should either have been utilized or its loss compensated by a new N gain. The difference in result can be attributed only, we think, to lactation. In D-k-n the baby was born dead through an accident, and lactation was suppressed by bandaging. The comparison forces us to con- clude that the initiation of the process of lactation is attended by a N loss. Part of the loss is due to the actual milk N itself, but even if this is allowed for, as shown in Table VI, negative balances are still obtained. M-l-r and B-l-n do not show positive balances until the 15th and 14th day after delivery respectively. W-r, on the very high calory diet, with increased N intake, shows a positive balance on the 8th day if we exclude the milk N. It is possible that under the conditions of lactation a positive N balance may never be attained, for increases in protein intake or increases in calories will only result in an increased flow of milk, if one may judge by the experimental evidence on dairy cows. Meigs (15) in his excellent review of this subject has cited the literature lead- ing to such a conclusion, though we find the N content of the milk of W-r to ‘be 0.185 per cent in contrast with M-l-r and B-l-n with a milk N percentage of 0.217 and 0.310 respectively (cf. volumes of milk in Tables II, III, Vj. On the other hand, it would appear that a positive balance might be attained with a higher intake of N throughout the puerperium were we to
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V. J. Harding and R. C. Montgomery 37
exclude the milk N from our calculations as an excretory product. Such a postulate is not usual, yet the formation of milk proteins represents a series of reactions differing totally from those leading to the formation of such nitrogenous excretory products as urea and properly classed as catabolites. The calculation of the N balance of the mother under such conditions would, however, be justified if we took into account the metabolic relation to the baby. Milk merely represents an intermediate in the nutritional
TABLE VI.
Daily N Balances Excluding Milk.
Days after labor.
1 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16 17 18
M-l-r. B-l-n N s
Urn.
-13.77 -6.60 -7.92 -1.98 -5.46 -2.82 -1.54 -2.07 -2.71
-1.81 -1.22 -0 83 -0.26 +o 80 +O.OS
“VL.
-3.89 -2.41 -2.94 -1.53 -3.99 -1.92 -1.11 -1.79 -0.95 -0.50 -0.13 +0.39 f0.41 +0.23 $0.54
um. -3.32 -1.78 -0.50 -0.69 -1.55 -2.41 -0.28 +1.18 +1.15 +0.78 +O. 83 +0.74 $0.74 +1.14 +0.76 -0.01 +0.40 +1.06
relation of the mother and child, and a determination of the N balance of the puerperium should include a study of this aspect. Otherwise, we must conclude that the process of lactation repre- sents a synthesis on the part of the group of cells of the maternal organism, attended usually by a N loss even under conditions where the N of the uterus would appear to be available.
Later in the lactation the maternal organism goes into N equilib- rium on an adequate diet, and one may well question the mechan- ism which forces a N loss on the body as a whole when one group
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38 N Metabolism in Puerperium
of cells commences a synthetic process. The N of the uterus may take part in the synthesis of milk proteins. The N stored in the latter half of pregnancy in excess of the needs of the fetus, hyper- trophy of the uterus, mamma!, etc., may also be utilized for syn- thesis at the commencement of lactation. Hoffstrom (16) first suggested in a general way that this N might be utilized for milk
TABLE VII.
Postpartum Creatinuria. -- l
om.
1 1.34 2 0.72 3 1.12 4 1.16 5 1.31 6 1.39 7 0.98 8 1.20 9 1.03
10 1.15 11 1.18 12 1.13 13 1.23 14 1.37 15 1.11 16 1.15 17 1.25 18
Creatine -t creatmine
&B ereatinine
Creatinine
-
--
Creatim as
creatinine.
gm.
1.09 0.59 0.98 1.05 1.10 1.14 0.98 1.04 1.00 1.18 1 .I1 1.06 1.10 1.20 1.02 1.11 1.13
cz5 0.13 0.14 0.11 0.22 0.25
-0.01 0.16 0.03
-0.03 0.06 0.08 0.13 0.20 0.08 0.05 0.12
Totals. . . . 2 01
D-k-n.
-
- ,
--
-
Creatine + creatinine
88 crestinine.
Creatine. Creatine
&8 creatinine.
gm. gm. inn.
1.72 1.32 0.40 1.87 1.12 0.74 1.49 1.04 0.45 1.06 0.86 0.21 1.14 0.77 0.36 1.73 1.25 0.48 1.63 1.00 0.63 1.51 0.90 0.61 1.63 0.97 0.66 1.50 0.92 0.58 1.50 1.07 0.41 1.47 1.06 0.41 1.44 1.00 0.45 1.31 0.99 0.33 1.35 1.10 0.28 1.48 1.20 0.30 1.26 1.10 0.16 1.04 1.06 -0.01
W-r.
7.46
product,ion, but its more particular use may be to act as a reserve store of N, anticipating the N loss inevitable under ordinary con- ditions of diet at the commencement of lactation. Our experi- ments justify to some extent the conclusion drawn by Gram- mat,ikati on a relationship between the N losses of the puerperium and lactation
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V. J. Harding and Ii;. C. Montgomery
If the origin of the N loss is to be ascribed to the process of lactation rather than to the involution of the uterus, a similar reason would account for the phenomenon of postpartum creat- inuria, and Mellanby’s general conclusion would be upheld. Our measurements of the creatinuria were confined to two cases- D-k-n and W-r. The results are shown in Table VII. Both cases showed creatinuria; D-k-n on a positive N balance excreted slightly over 2 gm. during the 17 days of observation. This amount’s to an average of 0.118 gm. per day. The excretion, however, is irregular, especially after the 6th day, minus quan- tities hcing found on the 7th and 10th days, and one cannot help but suspect that some of the analytical figures do not represent creat’ine. Such being the case the amount of creatine escreted puerperally might be no more than could reasonably be expected to arise from the involuting uterus.’ In any event one must con- clude that creatine set free by the breakdown of tissue is not immediately utilizable, though the subject may be in positive N balance. The case of W-r presents a complete contrast: the total creatine excretion amounts to nearly 7.5 gm. The excretion is sustained throughout the observation period until the 18th day. The amounts are so large that one can hardly doubt the presence of a sustained creatinuria. Here the difference between the lactat- ing and non-lactating puerperium makes itself evident again. JVhat is the origin of this extreme outpouring of creatine’! It cannot all have arisen from the uterus. Has it arisen from the breakdown of the nitrogenous tissue occurring at the commence- ment of lact.ation? If so, such a breakdown must have continued for 16 t,o 17 days though the N balance (excluding milk S) indi- cated storage after the 8th day. Such an interpretation involves the masking of a N breakdown by greater X gains, and again the non-utilization of the liberated creatine by the new tissue. In this connection Shaffer (6) observed the excretion of creatine in exophthalmic goiter which was improving rapidly and Fost.er (17) has noted the persistence of creatinuria in typhoid convalescence accompanied by K gains.
* The suppression of lactation by bandaging is never complete. There is always a small production of milk even though it may never he expressed from the breasts. The small amount of creatine may thus have arisen as a sequel to the processes initiating lactation as in the case of W-r.
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40 N Metabolism in Puerperium
SUMMARY.
High calory, high carbohydrate diets do not check the normal involution of the human uterus. The IV loss and creatinuria of the puerperium are referable to the processes attending the onset of lactation rather than to the involution of the uterus, though the latter factor is not necessarily excluded.
BIBLIOGRAPHY.
1. Grammatikati, T., Cents. Gynec., 1884, viii, 353. 2. Zacherjewski, A. U., 2. Biol., 1894, xii, 368. 3. Slemons, J. M., Johns Hopkins Hosp. Rep., 1904, xii, 111; Bull. Johns
Hopkins Hosp., 1914, xxv, 195. 4. Murlin, J. R., Am. J. Physiol., 1910, xxvii, 177; Swg., Gynec. and Obst.,
1913, xvi, 43. 5. Wilson, K. M., Bull. Johns Hopkins Hosp., 1916, xxvii, 121. 6. Shaffer, P. A., Am. J. Physiol., 1908-09, xxiii, 1. 7. Murlin, J. R., Am. J. Physiol., 1911, xxviii, 422. 8. Beker, T. C., Z. physiol. Chem., 1913, lxxxvii, 21. 9. Harding, V. J., and Eagles, B. A., J. Biol. Chem., 1924, lx, 301.
10. Mellanhy, E., Proc. Roy. Sot. London, Series B, 1912-13, lxxxvi, 88. 11. Morse, A., J. Am. Med. Assn., 1915, lxv, 613. 12. Shaffer, P. A., and Coleman, W., Arch. Int. Med., 1909, iv, 538. 13. McCann, W. S., Arch. Int. Med., 1922, xxix, 33. 14. Folin, O., J. Biol. Chem., 1914, xvii, 469. (Cf. also Folin, O., and
Doisy, E. A., J. Biol. Chem., 191617, xxviii, 349.) 15. Meigs, E. B., Physiol. Rev., 1922, ii, 204. 16. Hoffstrom, K. A., Skand. Arch. Physiol., 1910, xxxii, 326. 17. Foster, N., Proc. Sot. Exp. Biol. and Med., 1910, viii, 30.
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MontgomeryVictor John Harding and Richard Clifton
N METABOLISM IN THE PUERPERIUM
1927, 73:27-40.J. Biol. Chem.
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