The fate of intravenously administered calcium. Effect on urinary calcium and phosphorus, fecal calcium and calcium-phosphorus balance


Baylor, C.H.; Van, A.stine, Helene.; Keutmann, E.Henry; Bassett, S.H.

Journal of Clinical Investigation 29(9): 1167-1176

1950


Intraven. admd. Ca gluconate (550 mg. daily) was used to supplement the dietary intakes of 3 human subjects on metabolic balance. These included an essentially normal woman of 37 yrs., a woman of 57 yrs. with post-menopausal osteoporosis and a man aged 44 yrs. recovering from a long period of self-imposed partial starvation. In all subjects 50-75% of the Ca supplement was excreted in the urine within 24 hrs. Little if any of the parenteral Ca was transferred to the feces, since a consistent effect on fecal Ca could not be demonstrated. In control periods following Ca admn., both female patients excreted less Ca than in preliminary control periods. It is suggested that this effect may have been caused by parenteral Ca acting to depress temporarily the function of the parathyroid glands. Retention of supplemental Ca was accompanied by a retention of P which resulted from a decreased excretion of urinary P. While injns. of both testosterone propionate and alpha-estradiol benzoate caused the normal subject to retain more dietary Ca, neither appeared to influence the retention of intraven. Ca. A small N sparing effect was noted in the man and in the normal woman during periods when Ca gluconate was injd.

THE
FATE
OF
INTRAVENOUSLY
ADMINISTERED
CALCIUM.
EFFECT
ON
URINARY
CALCIUM
AND
PHOSPHORUS,
FECAL
CALCIUM
AND
CALCIUM—PHOSPHORUS
BALANCE
1
BY
CURTIS
H.
BAYLOR,
2,
3
HELEN
E.
VAN
ALSTINE,
4,
5
E.
HENRY
KEUTMANN,
AND
SAMUEL
H.
BASSETT
6
(From
the
Department
of
Medicine,
University
of
Rochester
School
of
Medicine
and
Dentistry
and
the
Medical
Clinics
of
the
Strong
Memorial
and
Rochester
Municipal
Hospitals)
(Submitted
for
publication
January
31,
1950;
accepted,
June
5,
1950)
The
fate
of
parenteral
calcium
when
given
to
man
in
amounts
which
contribute
an
appreciable
fraction
of
the
total
intake
has
not
been
exten-
sively
investigated.
While
it
is
generally
agreed
that
intravenous
calcium
salts
disappear
rapidly
from
the
blood
stream
(1)
,
there
have
been
differ-
ences
in
opinion
as
to
whether
the
calcium
was
ex-
creted
mainly
in
the
urine,
partitioned
between
urine
and
feces
or
retained
in
the
bones
and
other
tissues.
The
apparently
conflicting
results
of
balance
studies
may
be
reconciled
to
a
considerable
degree
if
one
considers
the
manner
and
quantity
in
which
the
supplementary
calcium
has
been
given
as
well
as
the
condition
of
the
recipient.
Some
experi-
ments
pertinent
to
the
present
discussion
may
be
cited
briefly.
Grosser
(2)
followed
the
intake
and
output
of
rachitic
infants
treated
with
subcutaneous
in
of
calcium
glycerophosphate
and
calcium
chloride.
A
large
part
of
the
injected
calcium
must
have
been
absorbed
and
retained
since
little
evi-
dence
of
increased
excretion
in
urine
or
feces
can
be
found
on
perusal
of
his
work.
Albright
and
Sulkowitch
(3)
gave
a
patient
with
idiopathic
hy-
poparathyroidism
daily
intravenous
injections
of
calcium
gluconate
equivalent
to
550
mg.
of
calcium
1
This
study
was
supported
by
a
grant
from
the
Ameri-
can
Cancer
Society
on
recommendation
of
the
Committee
on
Growth
of
the
National
Research
Council
and
the
Fluid
Research
Fund
of
the
University
of
Rochester.
2
Professor
of
Medicine
(on
leave)
from
the
University
of
Beirut,
Lebanon.
3
Present
adress
:
The
Texas
Company,
135
East
42nd
Street,
New
York
17,
New
York.
4
Hochstetter
Fellow
in
Medicine.
5
Present
adress
:
Vassar
College,
Poughkeepsie,
New
York.
6
Present
address
:
Veterans
Administration
Center,
Los
Angeles
25,
California.
for
six
days.
The
initial
very
low
level
of
serum
calcium
rose
transiently,
but
there
was
no
signifi-
cant
increase
in
the
excretion
of
calcium
in
the
urine
or
stools.
The
retention
of
the
parenteral
calcium
was
almost
complete.
The
question
of
provoking
intestinal
excretion
of
calcium
by
intravenous
calcium
has
been
in-
vestigated
in
six
normal
subjects
by
McCance
and
Widdowson
(4).
They
gave
daily
injections
of
the
gluconates
of
calcium
and
magnesium
equivalent
to
186
mg.
Ca
and
219
mg.
Mg
for
14
days.
A
careful
balance
was
conducted
during
this
interval.
Most
of
the
supplementary
calcium
was
recovered
promptly
in
the
urine
and
the
ratios
of
fecal
calcium
to
food
calcium
did
not
change.
In
their
opinion,
the
gastro-intestinal
tract
did
not
partici-
pate
actively
in
the
excretion
of
calcium.
It
is
clear
that
there
was
very
little
retention
of
the
in-
jected
calcium
;
however,
the
possible
effect
of
the
simultaneous
administration
of
magnesium
on
the
excretion
of
calcium
does
not
seem
to
have
been
considered.
Duncan,
Mirick
and
Howard
(5)
found
variable
but
usually
small
amounts
of
cal-
cium
in
the
fecal
excretions
of
patients
receiving
total
intravenous
alimentation.
From
their
data
one
gains
the
impression
that
the
parenteral
ad-
ministration
of
as
much
as
330
mg.
of
Ca
per
1.73
square
meters
of
body
surface
per
day
had
little
effect
on
the
amount
recoverable
in
the
feces.
On
the
other
hand,
Armstrong
and
Lienke
(6)
on
injection
of
labeled
calcium
(Ca
45
)
in
the
rat
found
that
from
six
to
ten
times
as
much
appeared
in
the
feces
as
in
the
urine.
In
general,
the
human
studies
are
confirmatory
of
the
experiments
of
Nicolaysen
(7)
on
the
dog.
Subcutaneous
injections
of
calcium
gluconate
in
this
animal
cause
increased
excretion
of
calcium
in
the
urine,
but
no
increase
in
fecal
excretion.
1167
1168
C.
H.
BAYLOR,
H.
E.
VAN
ALSTINE,
E.
H.
KEUTMANN,
AND
S.
H.
BASSETT
The
difference
between
the
amount
injected
and
excreted
in
the
urine
is
presumably
retained
in
the
bones.
Since
retention
of
phosphorus
is
obliga-
tory
in
the
formation
of
bone
salts,
it
is
to
be
ex-
pected
that
the
retention
of
parenteral
calcium
would
affect
the
phosphorus
balance.
This
was
found
to
be
the
case
in
Albright's
(3)
experiment
where
the
urinary
excretion
of
P
decreased
mark-
edly
and
the
retention
of
phosphorus
increased.
Numerous
gradations
must
exist
between
the
extremes
of
complete
retention
and
almost
com-
plete
excretion
of
parenterally
administered
cal-
cium.
It
is
probable
also
that
greater
urinary
losses
will
be
incurred
when
calcium
salts
are
given
intravenously
rather
than
subcutaneously.
Whether
the
responses
encountered
can
be
shown
to
fall
into
definite
patterns,
related
to
age,
growth,
disease,
etc.,
will
require
the
amassing
of
a
much
larger
body
of
evidence
than
is
available
at
pres-
ent.
Further
confirmation
of
the
findings
of
ear-
lier
investigators
is
desirable
especially
with
re-
gard
to
those
factors
which
influence
the
retention
of
calcium
and
its
excretion
in
the
urine.
The
experiments
detailed
in
subsequent
sections
of
this
report
were
done
in
the
course
of
other
stud-
ies
so
that
there
is
considerable
variability
in
the
programs
to
which
patients
were
subjected.
All
individuals,
however,
had
been
on
adequate
diets
for
some
time
prior
to
starting
the
investigation
and
were
continued
on
them
during
the
study.
They
were
either
in
nitrogen
equilibrium
or
posi-
tive
nitrogen
balance.
In
the
periods
of
parenteral
calcium
administration,
each
received
the
same
daily
dose
of
3
per
cent
calcium
gluconate
given
as
nearly
as
possible
at
identical
hours.
There
were
no
untoward
reactions.
Except
in
one
in-
stance,
which
may
have
been
due
to
failure
of
a
patient
to
cooperate
fully,
no
evidence
was
adduced
to
suggest
transfer
of
appreciable
amounts
of
cal-
TABLE
I
Daily
intakes
Fat
CHO
Ca
P
N
gm.
gm.
mg.
mg.
gm.
104
262
1111
1400
12.15
59
199
1465
1688
17.88
192
350
2373
2331
15.63
Values
for
Ca,
P,
and
N
were
determined
by
the
analysis
of
sample
diets.
Protein
=
Diet
N
X
6.25.
Fat
and
carbohydrate
have
been
estimated
from
tables.
cium
to
feces.
Other
findings
of
interest
were
that
1)
the
administration
of
large
doses
of
calcium
de-
pressed
the
urinary
excretion
of
calcium
in
post-
control
periods
;
2)
large
oral
doses
of
a
soluble
phosphate
decreased
the
excretion
of
calcium
in
the
urine
;
3)
the
injection
of
calcium
decreased
the
excretion
of
phosphorus
in
the
urine
and,
4)
cal-
cium
gluconate
appeared
to
have
a
small
nitrogen
sparing
effect
in
two
subjects.
MATERIALS
AND
METHODS
Experimental
subjects.
The
three
subjects
of
this
study
remained
continuously
on
the
Metabolism
Division
during
the
investigation.
Each
individual
received
the
same
diet
from
day
to
day,
but
the
diets
differed
some-
what
from
individual
to
individual.
All
of
the
diets
were
relatively
high
in
calcium.
(See
Table
I)
M.
G.
and
C.
R.
were
women
aged
37
and
57,
respectively.
M.
G.
was
essentially
normal,
while
C.
R.
had
severe
post-
menopausal
osteoporosis.
In
the
case
of
the
two
women
who
were
in
a
good
state
of
nutrition,
the
caloric
intake
was
adjusted
to
prevent
insofar
as
possible
either
gain
or
loss
of
weight.
A.
H.,
on
the
other
hand,
a
male,
pre-
sented
findings
typical
of
anorexia
nervosa
and
was
stud-
ied
during
a
phase
of
repletion
in
which
he
was
in
mark-
edly
positive
nitrogen
balance
and
gaining
in
weight.
Analysis
of
food
and
excreta.
The
intakes
of
calcium,
phosphorus
and
nitrogen
were
determined
by
analysis
of
a
series
of
sample
diets
prepared
in
the
same
manner
as
the
food
eaten
by
the
patients.
Average
values
were
used.
Urine
was
collected
in
periods
of
24
hours.
Nitrogen
de-
terminations
were
done
by
macro-Kjeldahl.
Aliquots
of
the
daily
urine
were
pooled
in
periods
of
four,
five
or
six
days
and
the
pools
paralleled
the
collection
of
feces.
Cal-
cium
and
phosphorus
of
the
urine,
feces
and
diet
were
de-
termined
gravimetrically,
using
the
procedure
of
Wash-
burn
and
Shear
(8).
In
certain
instances,
calcium
and
phosphorus
analyses
were
done
daily
or
even
at
shorter
intervals
on
urine.
At
such
times
calcium
was
deter-
mined
by
the
method
of
Kochakian
and
Fox
(9),
and
phosphorus
by
the
procedure
of
Fiske
and
Subbarow
(10).
Calcium
gluconate
solution
was
prepared
as
a
sterile
3
per
cent
solution.
One
hundred
ml.
aliquots
were
inj
ected
intravenously
twice
daily
at
a
rate
not
in
ex-
cess
of
80
to
90
drops
per
minute.
If
the
subject
complained
of
burning
or
flushing,
the
flow
was
decreased
until
the
symptoms
disappeared.
RESULTS
Diet.
The
analytical
data
on
the
diets
appear
in
Table
I.
It
is
to
be
recalled
that
the
values
for
fat
and
carbohydrate
were
obtained
from
standard
dietary
tables
;
those
for
nitrogen,
calcium,
and
phosphorus
are
from
the
analysis
of
sample
diets.
Protein
in
diet
=
nitrogen
x
6.25.
Calories
are
approximate.
Subject
Calories
Protein
gm.
M.
G.
2288
76
C.
R.
1775
112
A.
H.
3520
98
mg./day
+
32
+221
+
82
+127
+173
+
45
FATE
OF
INTRAVENOUSLY
ADMINISTERED
CALCIUM
1169
TABLE
II
Effect
of
intravenous
calcium
on
urinary
and
fecal
calcium
and
calcium
balance
Subject
M.
G.
Female
Age
37
Normal
Period
No.
days
5-9
25
10
&
11
10
12
5
14,
16,
17
15
18
&
19
10
20
5
Intake
Urine
Stool
mg./day
mg./day
mg./day
1111
238
841
1661
538
882
1111
147
882
1111
178
806
1661
519
969
1111
87
969
Balance
Medication
Control
I.V.
calcium
550
mg./day
Control
T.P.*
25
mg./day
I.M.
I.V.
calcium
550
mg./day
and
T.P.
25
mg./day
I.
M.
T.
P.
25
mg.
/day
I.M.
21
&
22
10
1111
78
820
+213
Control
790
683
683
112
469
102
23-26
20
27
5
28
5
1111
1605
1111
C.
R.
Female
Age
57
Osteoporosis
1-5
30
6
&
7
12
8
6
1465
229
2003
641
1465 195
1350
1250
1250
35
&
36
8
2008
600
1369
30-33
16
1465
101
1365
41
&
42
8
1999
452
1389
+209
+453
+326
Alpha
estradiol
benzoate
1.66
mg.
I.M.
every
other
day
I.V.
calcium
494
mg./day
and
alpha
es-
tradiol
benzoate
Alpha
estradiol
benzoate
114
+112
+
20
Control
I.V.
calcium
538
mg./day
Control
+
39
I.V.
calcium
543
mg./day
1
65
ml.
molar
solution
NaH2PO4
daily
by
mouth
+158
Phosphate
as
in
periods
30-33
plus
534
mg.
calcium
I.V.
daily
2375
2295
—186
+208
A.
H.
Male
Age
44
Anorexia
nervosa
7-9
12
11-13
12
2373
184
2924
421
Control
I.V.
calcium
551
mg./day
*
Refers
to
intramuscular
testosterone
propionate.
Effect
of
intravenous
calcium
on
urinary
and
fecal
calcium
and
calcium
balance.
(Table
II)
M.
G.,
who
was
an
essentially
normal
woman,
re-
ceived
calcium
on
three
separate
occasions.
The
first
series
of
injections
were
given
after
an
in-
terval
of
30
days
on
the
standard
diet.
A
very
steady
preliminary
value
for
urinary
calcium
was
obtained
with
an
average
of
238
mg.
a
day
(see
also
Figure
1)
and
she
was
found
to
be
in
approxi-
mate
calcium
equilibrium.
If
one
assumes
that
the
same
amount
of
calcium
in
the
urine
was
attribut-
able
to
the
basal
diet
during
both
the
pre-glu-
conate
periods
and
during
the
course
of
injection,
then
only
58
per
cent
of
the
intravenous
dose
was
excreted.
An
interesting
phenomenon
was
ob-
served
in
the
post-gluconate
control
periods
of
this
patient
and
it
appears
also,
but
to
a
lesser
de-
gree,
in
the
data
obtained
on
C.
R.
(Table
II).
In
the
interval
immediately
following
the
administra-
tion
of
calcium,
less
calcium
was
excreted
in
the
urine
than
in
the
preliminary
periods
of
observa-
tion.
The
persistence
of
this
lower
rate
of
excre-
tion
through
periods
13
to
17
may
have
been
due
to
therapy
with
testosterone
propionate.
However,
when
the
injections
of
calcium
were
repeated
while
the
patient
was
definitely
under
the
influence
of
androgen
(periods
18
and
19)
there
was
a
further
decrease
in
the
average
daily
urinary
calcium
of
the
after
periods
(periods
20
through
22)
.
Since
androgen
has
been
found
to
cause
a
reduction
in
the
excretion
of
calcium
in
the
urine
(11,
12)
,
one
must
concede
that
the
effect
may
have
been
due
to
testosterone
propionate.
On
the
other
hand
it
is
equally
probable
that
the
two
actions
were
super-
imposed.
There
was
no
evidence
that
androgen
increased
the
retention
of
calcium.
The
effect
of
estrogen
on
the
excretion
of
calcium
was
less
cer-
tain
for
there
was only
one
five-day
period
during
which
the
injections
were
given.
Nevertheless
the
full
action
of
the
alpha
estradiol
benzoate
should
have
been
attained
since
it
had
been
given.
for
20
preceding
days.
After
the
smaller
excre-
19
21
23
25
2?
V
3
§
590
NO
MEDICATION
TESTOSTERONE
PROPIONATE
g
I
fi
z
ESTRAOIOL
BENZOATE
DALY
CALCIUM
INTAKE
1111
MG.
DALY
PHOSPHORUS
INTAKE
1400
MG.
4406
2410*.
240
.
200,
3
120,
40,
0,
PERIOD
S
7
9
II
13
15
1?
1170
C.
H.
BAYLOR,
H.
E.
VAN
ALSTINE,
E.
H.
KEUTMANN,
AND
S.
H.
BASSETT
EFFECT
OF
INTRAVENOUS
CALCIUM
GLUCONATE,
ANDROGEN
AND
ESTROGEN
ON
DALY
EXCRETION
OF
URINARY
CALCIUM
(PERIOD
AVERAGES).
SUBJECT
M.G.
FEMALE
AGE
37
*
37944
FIG.
1.
THE
HEIGHT
OF
EACH
COLUMN
REPRESENTS
THE
AVER-
AGE
DAILY
EXCRETION
OF
CALCIUM
IN
THE
URINE
PER
PERIOD
OF
FIVE
DAYS
Periods
12
and
13
reveal
the
decrease
in
urinary
calcium
that
fol-
lowed
the
first
series
of
inj
ections
of
calcium
gluconate.
Androgen
and
calcium
gluconate
seem
to
have
produced
an
additive
effect
in
periods
20
through
22.
tion
of
calcium
in
urine,
which
had
resulted
from
previous
medication,
had
been
taken
into
account
there
was
likewise
no
indication
of
an
effect
of
this
steroid
on
retention
of
parenteral
calcium.
C.
R.,
who
had
osteoporosis,
excreted
about
75
per
cent
of
the
injected
calcium
during
two
widely
spaced
trials.
Later,
when
she
was
given
large
oral
doses
of
sodium
acid
phosphate,
the
antici-
pated
reduction
in
urinary
calcium
occurred
(13--
15).
When
the
ingestion
of
phosphate
was
con-
tinued
through
the
periods
in
which
supplementary
calcium
was
given
intravenously,
more
of
the
cal-
cium
was
retained
and
the
per
cent
excreted
de-
creased
from
75
to
66.
Sufficient
retention
took
place
to
produce
an
appreciably
positive
calcium
balance
(Table
II).
It
is
apparent
that
saturating
this
patient
with
phosphate
reduced
the
excretion
of
intravenously
administered
calcium
in
the
urine
just
as
it
did
calcium
derived
from
food
or
endoge-
nous
sources.
A.
H.,
who
had
lost
a
great
deal
of
weight
by
voluntarily
limiting
his
diet,
was
in
a
phase
of
re-
pletion
when
the
studies
were
made.
He
was
on
a
high
caloric,
high
calcium-phosphorus
intake
and
had
been
in
strongly
positive
nitrogen
balance
for
16
days
prior
to
the
experiment.
In
spite
of
this,
he
was
in
negative
calcium
balance
and
consecutive
four-day
metabolic
periods
revealed
no
evidence
of
a
change
in
excretion
of
either
urinary
or
fecal
calcium.
With
the
administration
of
calcium
glu-
conate
there
was
definite
retention
of
calcium
(Table
II)
.
The
percentage
of
intravenous
cal-
cium
escaping
in
the
urine
(Figure
2)
was
lower
than
in
either
of
the
women.
There
was
no
de-
crease
in
the
urinary
calcium
in
the
post-injection
period.
Unfortunately,
the
observations
had
to
be
terminated
at
this
point.
Rate
of
elimination
of
intravenous
calcium
in
the
urine.
Two
experiments
were
performed
on
the
rate
at
which
calcium
escaped
in
the
urine.
Subject
C.
R.
received
calcium
gluconate
in
the
usual
divided
doses
on
each
of
four
consecutive
M.G.
URINE
CALCIUM
111
CALCIUM
URINE
CALCIUM
FECAL
CALCIUM
01411
illlu
01$11
FATE
OF
INTRAVENOUSLY
ADMINISTERED
CALCIUM
1171
A.H.
I.V.
CA.
GLUCONATE
411
-
g11-9
CONTROL.
EV
CA.
GLUCONATE
TOTAL
INTAKE
CALCIUM
RETAINED
i
cA
LV
e
.
ium
CONTROL
CALCIUM
.
1
1
-11.1
RETAINED_
URINE
CALCIUM
FECAL__,
CALCIUM
DIET
"EAT.CIUM
10
0
EL
`CAL
C
IUM
FECAL
CALCIUM
FECAL
CALCIUM
FIG.
2.
EFFECT
OF
AN
INTRAVENOUS
SUPPLEMENT
ON
CALCIUM
BALANCE
Fecal
excretion
of
calcium
appears
to
be
independent
of
calcium
adminis-
tered
intravenously
hence
the
balance
in
the
experimental
period
is
effected
only
by
the
difference
between
the
intravenous
dose
and
the
calcium
excreted
in
the
urine.
TABLE
III
Rate
of
excretion
of
cakium
in
urine
after
intravenous
cakium
M.
G.
Normal
Day
1.
2.
3.
4.
5.
6.
7.
8.
9.
112.
113.
114.
115.
116.
117.
118.
119.
120.
Calcium,
I.V.
mg.
none
A.M.
271
P.M.
271
8
A.M.
271
5
P.M.
271
A.M.
271
P.M.
271
A.M.
271
P.M.
271
none
none
none
none
none
A.M.
275
P.M.
275
A.M.
275
P.M.
275
A.M.
275
P.M.
275
P.M.
275
A.M.
275
P.M.
275
none
none
none
Collection
periods
24
hrs.
24
hrs.
8
A.M.-11
A.M.
11
A.M.—
2
P.M.
2
P.M.—
5
P.M.
5
P.M.—
8
P.M.
8
P.M.-11
P.M.
11
P.M.—
8
A.-M.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
24
hrs.
Calcium
excreted
per
hour
Calcium
in
24
hrs.
Remarks
mg.
38
35
17
33
23
10
mg.
162
504
527
506
469
215
161
165
124
113
500
482
500
328
500
121
101
106
Alpha
estradiol
ben-
zoate
1.66
mg.
I.M.
every
other
day.
Subject
C.
R.
Osteoporosis
Subject
C.
R.
Subject
A.
H.
Subject
M.
G.
Phos-
phorus
in
urine
Day*
Calcium
I.V.
Calcium
in
urine
Calcium
I.V.
Medica-
tion
Calcium
in
urine
Phos-
phorus
in
urine
Period
6
days
Calcium
Calcium
I.V.
in
urine
Period
4
days
Phos-
phorus
in
urine
mg./day
mg./day
mg./day
252
923
231
936
538
655
898
538
626
848
195
963
4
5
6
7
8
mg./day
mg./day
122
108
113
500
482
500
328
500
121
101
106
mg./day
994
923
1044
795
785
842
758
761
931
946
981
mg./day
mg./day
195
185
305
429
433
400
183
mg./day
1012
1017
1030
881
895
902
1120
110
111
112
113
114
115
116
117
118
119
120
550
550
550
275
550
8
9
10t
11
12
13
14
550
550
550
550
1172
c.
H.
BAYLOR,
H.
E.
VAN
ALSTINE,
E.
H.
KEUTMANN,
AND
S.
H.
BASSETT
days
with
the
customary
prompt
rise
in
urinary
Ca,
in
this
case
from
162
to
504
mg.
in
24
hours.
(Table
III.)
On
the
second
day
of
the
period
the
urine
was
collected
at
intervals
of
three
hours
from
8
:00
a.m.
until
11:00
p.m.
The
maximum
rates
of
excretion
occurred
in
the
first
three
hours
after
the
morning
and
evening
doses
and
remained
high
during
the
second
three-hour
period.
There
was
some
delay
in
excretion
after
injections
were
stopped,
as
may
be
noted
in
the
first
post-control
day.
Thereafter,
the
amount
of
calcium
in
urine
had
fallen
to
that
of
the
fore-period
or
below.
M.
G.,
on
the
other
hand,
did
not
exhibit
any
carry-
over
of
parenterally
administered
calcium
into
the
post-control
period
while
under
the
influence
of
tions
in
a
completely
satisfactory
manner.
Both
tended
to
be
constipated
and
were
somewhat
ir-
regular
in
bowel
habits,
and
it
was
rarely
possible
to
separate
the
stools
precisely
at
the
carmine
markers.
For
this
reason,
it
has
seemed
preferable
to
include
the
first
post-control
period
following
the
injection
of
calcium
in
order
to
obtain
any
calcium
which
might
have
been
held
back
because
of
admixture
of
experimental
and
control
feces
in
the
colon.
M.
G.
showed
a
small
increase
in
fecal
calcium
during
the
first
periods
of
calcium administration
and
a
much
larger
increase
when
the
experiment
was
repeated
during
the
course
of
testosterone
propionate
injections
(Table
II).
The
rise
in
pe-
TABLE
IV
Effect
of
intravenous
calcium
on
urinary
phosphorus
(Average
Values
Expressed
as
mg./day)
*
The
excretion
of
Calcium
and
Phosphorus
was
determined
daily.
t
Injections
of
Calcium
Gluconate
on
last
two
days
of
period
only.
estrogen.
This
may
have
been
because
she
was
in
a
fairly
strongly
positive
calcium
balance
at
the
time.
Fecal
excretion
of
calcium.
It
is
more
difficult
to
determine
whether
any
of
the
intravenous
cal-
cium
escaped
in
the
feces.
Precise
demarcation
of
feces
into
periods
is
often
impossible
(5),
and
av-
erage
values
must
be
depended
upon
to
establish
the
level
of
excretion
on
any
particular
program.
It
is
certain
that
the
length
of
time
required
to
ob-
tain
a
base
line
will
vary
from
individual
to
indi-
vidual.
In
our
experience,
to
obtain
good
separa-
tion,
regular
bowel
habits
are
important
and
the
fecal
matter
should
be
formed.
Neither
of
our
fe-
male
patients
fulfilled
the
first
of
these
qualifica-
riods
10
to
12
is
unquestionably
well
within
the
limits
of
error
imposed
by
the
difficulties
in
the
separation
of
the
fecal
pool.
The
higher
level
of
fecal
calcium
in
periods
18
to
20,
while
the
subject
was
receiving
testosterone
propionate,
is
the
re-
sult
of
an
exceptionally
high
value
for
calcium
in
period
19.
On
the
fourth
day
of
this
period,
M.
G.
passed
a
large
loose
stool
which
obviously
con-
tained
undigested
food.
It
is
our
opinion
that
this
analysis
must
be
discounted
since
it
is
probable
that
the
appearance
of
undigested
food
represented
vomitus
which
the
patient
allowed
to
become
mixed
with
the
feces
and
failed
to
report.
If
the
fecal
calcium
of
the
first
gluconate
period
(period
18)
and
that
of
the
first
after
period
(period
20)
Diet
gm.
9.492
9.492
9.492
9.492
9.492
9.492
9.492
9.492
Supple-
ment
gm.
1.100
2.200
2.204
2.208
Periods
4
days
each
Calcium
Phosphorus
Urine
Stool
Balance
Urine
Stool
Balance
Medication
Urine
Nitrogen
Stool
Balance
gm.
6.75
+14.59
5.38
+14.89
8.43
+14.00
6.24
+17.37
6.86
+17.83
5.99
+18.27
5.73
+19.58
5.24
+14.78
gm.
gm.
gm.
gm.
gtn.
gm.
0.683
9.520
-0.711
3.890
4.920
+0.514
0.781
7.540
+1.171
4.050
3.955
+1.319
0.739
11.450
-2.697
4.070
5.720
-0.466
1.219
8.735
+0.638
4.120
4.045
+1.159
1.716
9.365
+0.611
3.525
4.595
+1.204
1.734
9.095
+0.867
3.580
4.425
+1.319
1.598
9.085
+1.017
3.610
4.550
+1.164
0.734
8.370
+0.388
4.480
4.235
+0.609
7
Control
8
Control
9
Control
10
Calcium
gluconate*
6
gm.
daily
I.
V.
11
Calcium
gluconate
6
gm.
daily
I.
V.
12
Calcium
gluconate
6
gm.
daily
I.
V.
13
Calcium
gluconate
6
gm.
daily
I.
V.
14
Control
gm.
41.18
42.25
40.09
38.91
37.83
38.26
37.21
42.50
FATE
OF
INTRAVENOUSLY
ADMINISTERED
CALCIUM
1173
TABLE
V
Balance
data-subject
M.
G.
Nitrogen
Calcium
Phosphorus
Periods
5
days
each
Medication
Urine
Stool
Balance
Urine
Stool
Balance
Urine
Stool
Balance
5-9
10-11
12
13, 14,
16,
17
20
21-22
23-26
27
18-19
28
Control
Calcium
gluconate,
I.V.
Control
Testosterone
propionate
25
mg.
daily,
I. M.
Testosterone
propionate
and
calcium
gluconate
Testosterone
propionate
Control
Alpha
estradiol
benzoate
1.66
mg.
every
other
day
Alpha
estradiol
benzoate,
I.
M.
and
calcium
gluconate,
I.
V.
Alpha
estradiol
benzoate
gm.
gm.
gm.
gm.
gm.
gm.
gm.
gm.
gm.
53.40
5.84
+1.43
1.191
4.200
+0.158
4.640
2.200
+0.161
51.41
5.16
+4.10
2.789
3.979
+1.540
4.138
1.979
+0.885
53.64
7.91
-0.88
0.734
5.270
-0.449
4.632
2.528
-0.158
36.83
5.91
+17.68
0.835
3.973
+0.744
3.512
1.957
+1.533
33.84
6.85
+19.98
2.593
5.336
+0.379
3.331
2.399
+1.272
37.94
5.14
+17.59
0.438
3.870
+1.247
3.900
1.750
+1.352
50.88
5.57
+
4.22
0.398
4.108
+1.050
5.190
1.826
+0.491
54.89
5.84
+
0.02
0.561
3.949
+1.045
4.827
1.919
+0.257
53.74
3.85
+
3.07
2.310
3.060
+2.937
4.210
1.423
+1.369
55.30
5.38
+
0.07
0.511
3.771
+1.243
4.890
1.738
+0.374
Averages
for
groups
of
similar
periods.
are
averaged,
the
result,
792
mg.
per
day,
is
the
same
as
the
average
of
the
preliminary
control
pe-
riods
on
androgen.
The
lower
fecal
calcium
of
this
subject
in
the
final
estrogen-calcium
gluconate
periods
may
well
reflect
the
decrease
in
fecal
calcium
induced
by
the
steroid
(12)
rather
than
a
specific
effect
of
intra-
venous
calcium.
Neither
C.
R.
nor
A.
H.
showed
any
clear-cut
evidence
of
fecal
excretion
of
the
parenteral
calcium.
All
subjects
were
in
positive
calcium
balance
during
the
periods
of
supple-
mentary
calcium
administration.
The
least
effect,
as
was
perhaps
to
be
expected,
was
on
C.
R.,
the
woman
with
osteoporosis.
Urinary
phosphorus
and
phosphorus
balance.
Intravenous
injections
of
calcium
were
attended
by
a
reduction
in
urinary
phosphorus
without
in-
creased
fecal
excretion,
which
suggests
the
forma-
tion
and
retention
in
the
body
of
some
compound
of
calcium
and
phosphorus,
probably
bone
salt.
The
effect
is
demonstrated
well
in
M.
G.,
period
27,
when
daily
determinations
of
calcium
and
phos-
phorus
in
urine
were
made
(Table
IV).
Supple-
mentary
calcium
was
responsible
for
increasing
the
retention
of
calcium
740
mg.,
and
decreasing
the
excretion
of
urinary
phosphorus
1,037
mg.
be-
low
that
of
period
26.
As
there
was
no
evidence
of
transfer
of
P
to
the
feces
or
its
subsequent
ex-
TABLE
VI
Balance
data-subject
A.
H.
*
Given
on
the
last
two
days
only
of
this
period.
1174
C.
H.
BAYLOR,
H.
E.
VAN
ALSTINE,
E.
H.
KEUTMANN,
AND
S.
H.
BASSETT
cretion
in
the
post-control
period,
the
reduction
in
urinary
P
must
be
regarded
as
an
addition
of
P
to
the
body.
It
is
clear
that
the
extra
amount
retained
was
in
excess
of
that
required
to
combine
with
cal-
cium
retained
from
calcium
gluconate
;
however
it
very
nearly
met
the
requirement
for
bone
salt
if
deposited
in
combination
with
the
total
retention
of
calcium
in
the
period.
Similar
changes
in
urinary
phosphorus
were
demonstrable
in
the
other
subjects
without
espe-
cially
good
correlation
between
"theoretical"
(16)
and
actual
phosphorus
balances.
In
fact,
the
data
for
A.
H.
reveal
that
even
with
the
increase
of
1,180
mg.
in
P
retention
induced
by
calcium
injec-
tions,
an
additional
1,500
mg.
of
P
would
have
been
required
to
combine
with
the
total
of
the
positive
Ca
and
N
balances
of
these
periods
(Pe-
riods
10-13,
Table
VI)
.
Whether
this
discrepancy
was
due
to
deposition
of
protein
of
less
than
aver-
age
phosphorus
content
or
to
errors
inherent
in
balance
experiments
is
not
known.
Effect
of
I.
V.
calcium
on
urinary
nitrogen.
In
two
patients,
M.
G.
and
A..
H.,
the
injection
of
cal-
cium
gluconate
was
associated
with a
decrease
in
urinary
nitrogen.
This
effect
was
not
very
striking
in
the
case
of
M.
G.
and
might
have
been
discounted
had
it
not
occurred
regularly
each
time
the
calcium
gluconate
was
given
(see
summary,
and
Table
V)
.
In
the
case
of
A.
H.,
however
(Table
VI)
there
was
a
definite
reduction
in
urinary
nitrogen.
DISCUSSION
Tolerance.
Mates
(17)
has
injected
as
much.
as
182
mg.
of
calcium
as
the
gluconate
into
pa-
tients
with
a
variety
of
diseases
in
a
matter
of
60
to
90
seconds
without
harmful
effects.
From
the
data
presented
here
it
is
evident
that
much
larger
amounts
(550
mg.
=-
1
-
-
)
are
well
tolerated
if
given
at
a
slow
rate
intravenously
and
in
divided
daily
doses.
None
of
our
three
subjects
experienced
any
appreciable
discomfort
or
apparent
injury
over
periods
of
10
to
12
days
and
the
injections
could
undoubtedly
have
been
continued
much
longer.
The
wisdom
of
giving
parenteral
calcium
over
extended
periods,
however,
may
be
questioned,
especially
in
view
of
the
tendency
for
the
metal
to
be
excreted
in
the
urine.
In
our
patients,
the
amount
eliminated
in
24
hours
was
of
the
order
of
that
observed
in
moderately
severe
hyperpara-
thyroidism.
The
injurious
renal
effects
of
the
latter
disease
are
too
well
known
to
require
fur-
ther
comment
(18).
Apparently
similar
damage
has
been
produced
in
the
kidneys
of
animals
by
the
injection
of
calcium
salts
(19)
and
very
large
amounts
of
parenteral
calcium
may
give
rise
to
pathological
calcification
in
various
tissues
(20)
.
The
abrupt
increase
in
urinary
calcium
after
intra-
venous
injections
suggests
that
a
considerable
part
of
the
calcium
is
excreted
before
utilization
can
occur.
Possibly
much
slower
rates
of
injection
would
avoid
flooding
the
circulation
with
calcium,
the
attendant
rise
in
serum
calcium
and
its
rapid
renal
excretion.
Effect
on
urinary
phosphorus.
The
effect
of
intravenous
calcium
on
urinary
phosphorus
is
to
depress
the
excretion
of
the
latter
(3)
,
just
as
large
oral
doses
of
a
soluble
phosphate
decrease
the
excretion
of
calcium
in
urine
(13-15)
.
The
re-
semblance
between
the
action
of
soluble
phosphate
on
the
urinary
calcium
of
patients
with
hyperpara-
thyroidism
(14,
15),
and
on
the
calciuria.
of
C.
R.
when
she
was
given
phosphate,
both
during
con-
trol
periods
and
when
she
received
calcium
glu-
conate
intravenously,
is
clear-cut.
A
significant
reduction
in
excretion
of
calcium
in
the
urine
oc-
curred
in
each
instance.
Temporary
decrease
in
solubility
of
bone
salts
when
the
system
is
flooded
with
POI
would
seem
to
be
the
explanation
of
this
effect.
In
an
acute
experiment
an
excess
of
Ca++
may
likewise
favor
deposition
of
calcium
phosphate
in
bone
and
thereby
decrease
excretion
of
urinary
phosphorus.
Does
intravenous
calcium
decrease
the
secretion
of
parathormone?
The
reason
for
the
decreased
excretion
of
calcium
in
the
urine
of
the
post-injec-
tion
periods
when
intravenous
calcium
was
given
to
M.
G.,
and
to
a
lesser
degree
in
the
case
of
C.
R.
is
mainly
a
matter
for
conjecture.
Possibly
we
have
the
converse
of
the
experiment
by
Drake,
Albright
and
Castleman
(21)
,
who
produced
para-
thyroid
hyperplasia
in
rabbits
by
the
injection
of
a
buffered
phosphate
solution.
In
the
dog,
on
the
other
hand,
it
is
claimed
that
injections
of
calcium
gluconate
bring
about
a
reduction
in
the
weight
of
the
parathyroids
(22)
.
The
mechanism
of
the
post-calcium
gluconate
depression
of
excretion
of
calcium
in
the
urine
of
M.
G.
would
then
be
ex-
plainable
as
a
temporary
decrease
in
the
secretion
of
parathormone.
Effect
on
nitrogen.
In
the
two
subjects
in
FATE
OF
INTRAVENOUSLY
ADMINISTERED
CALCIUM
1175
which
increased
retention
of
nitrogen
appeared
to
be
associated
with
the
calcium
gluconate
injections,
it
is
important
to
know
whether
the
extra
retention.
of
N
represented
merely
an
accumulation
of
non-
protein
nitrogen
in
the
body water
or
whether
it
actually
was
retained
as
protein.
The
evidence
in
A.
H.,
who
showed
the
greater
effect,
is
that
it
was
retained
as
protein,
for
the
serum
N.P.N.
did
not
increase
during
the
experiment,
and
gain
in
weight
was
only
2.1
Kg.
which
could
account
for
retention
of
but
0.69
gm.
of
N
as
N.P.N.,
while
the
observed
increase
in
nitrogen
retention
was
15.16
gm.
It
does
not
seem
probable
that
N
retention
was
the
result
of
a
nitrogen-sparing
effect
of
the
ex-
tra
calories
derived
from
gluconic
acid
since
the
amount
of
the
latter
injected
was
not
more
than
5.5
gm.
a
day.
Either
the
increased
retention
of
N
in
these
two
patients
is
purely
a
matter
of
coin-
cidence
or
intravenous
calcium
gluconate
stimu-
lates
some
mechanism
which
requires
N
retention,
such
as
the
formation
of
new
osteoid
tissue.
SUM
MARY
1.
Intravenously
administered
calcium
gluco-
nate
(550
mg.
Ca
daily)
was
used
to
supplement
the
dietary intakes
of
three
human
subjects.
These
included
an
essentially
normal
woman,
a
woman
with
postmenopausal
osteoporosis,
and
a
man
who
was
recovering
from
a
period
of
partial
starvation.
2.
A
considerable
part
of
the
calcium
was
ex-
creted
in
the
urine
within
24
hours.
3.
No
consistent
effect
on
fecal
calcium
could
be
demonstrated.
4.
Some
of
the
calcium
was
retained
in
each
case.
If
one
considers
the
urinary
calcium
alone,
the
retention
was
greatest
in
the
male
subject
dur-
ing
repletion
and
least
in
the
woman
with
osteo-
porosis.
5.
Intravenous
calcium
was
followed
by
a
de-
crease
in
urinary
calcium
excretion
in
both
female
patients.
It
is
suggested
that
this
may
have
been
caused
by
depression
of
the
activity
of
the
para-
thyroid
glands.
6.
Calcium
decreased
the
excretion
of
phos-
phorus
in
the
urine
of
all
patients
without
increas-
ing
its
fecal
excretion.
This
effect
is
the
converse
of
that
observed
when
large
doses
of
a
soluble
phosphate
are
given
orally.
7.
In
the
normal
woman,
steroid
therapy
(tes-
tosterone
propionate
and
alpha
estradiol
benzoate)
increased
the
retention
of
both
the
Ca
and
P
ab-
sorbed
from
the
food,
but
did
not
seem
to
increase
the
retention
of
the
calcium
supplement.
8.
A
small
nitrogen-sparing
effect
was
noted
in
the
male
subject
and
in
the
normal
woman
during
periods
when
calcium
gluconate
was
injected.
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