Effects of acute hypochloremia on glomerular filtration rate and electrolyte excretion in the dog


Toussaint, C.; Telerman, M.; Vereerstraeten, P.

Experientia 14(11): 417-419

1958


Hypochloremia was induced in dogs using an artificial kidney to remove Cl by dialysis and replacing it with carbonate or nitrate. Hypochloremia was accompanied by no change in glomerular filtration rate, an increased excretion of Na, K and Cl, and an elevation of the threshold of bicarbonate excretion.

[15.
XI.
1958]
Kurze
Mitteilungen
Brief
Reports
417
treten
lassen,
gingen
wir
zu
vergleichenden
Versuchen
fiber,
die
wir
in
Carrelschalen
mit
zusatzlicher
Begasungs-
einrichtung
vornahmen".
Als
malignes
Testmaterial
ver-
wendeten
wir
Jensen-Sarkom
der
Ratte,
das
11
Tage
nach
der
Beimpfung
exstirpiert
und
in
Form
von
diinnen
Gewebestiickchen
(etwa
1
mm
2
)
zunachst
5
Tage
lang
in
iiblicher
Weise
auf
festem
Plasmaboden
angeziichtet
wurde.
Vom
6.
bis
9.
Tag
wurde
dann
mit
Reinststick-
stoff,
dem
etwa
5%
0
2
-freies
CO
3
beigemischt
waren,
kon-
tinuierlich
begast.
Im
Verlauf
der
anaeroben
Versuchs-
periode
erfolgte
die
Fiitterung
(ebenfalls
streng
anaerob)
in
Versuchsreihe
I
weiterhin
mit
normalem
Nahrsubstrat
(2
Teile
Tyrodelosung,
2
Teile
Pferdeserum,
1
Teil
nerembryonalextrakt),
in
Versuchsreihe
II
dagegen
mit
Krebskochsaft-Nahrlosung,
die
sich
von
der
normalen
le-
diglich
dadurch
unterscheidet,
dass
die
Tyrodesalze
hier-
bei
nicht
in
Wasser,
sondern
in
der
gleichen
Menge
Krebs-
kochsaft
gelost
werden.
Am
9.
Versuchstag,
unmittelbar
nach
Abschluss
der
Begasung,
wurden
die
Kulturen
beider
Versuchsreihen
aus
den
Carrelschalen
herausgenommen.
Die
erste
Halite
der
Explantate
priiften
wir
auf
Lebensfahigkeit
mit
Try-
panblau
(Verdiinnung
1:5000),
die
andere
Halite
prapa-
rierten
wir
zwecks
Untersuchung
auf
Mitosen
(Fixierung
mit
Kaliumbichromat-Formalinlosung;
3wochige
Einbet-
tung
in
Celloidin-Paraffin).
Alsdann
wurden
die
angefer-
tigten
Gewebeschnitte
zur
Mitosen-Bestimmung
einmal
mit
Hamatoxylin-Eosin
15
angefarbt
und
zweitens
der
Feulgen-Reaktion
unterzogen.
Auf
Grund
der
Trypanblau-Farbung
und
des
Mitosen-
Nachweises
gelangten
wir
zu
folgendem
Untersuchungs-
ergebnis
:
Versuchsreihe
I:
intensive
Blaufarbung
der
peripheren
Zellen,
keine
Mitosen;
Versuchsreihe
II
:
keine
Farbung
der
peripheren
Zellen,
Mitosen
in
mehreren
Bezirken.
Der
Ausfall
obiger
Vergleichsversuche
gibt
eindeutig
zu
erkennen,
dass
unter
strikter
Fernhaltung
von
Sauer-
stoff
die
mit
Krebskochsaft
behandelten
Krebszellen
re-
sistenter
sind
als
die
unbehandelten.
Unter
dem
Einfluss
der
in
den
Krebsdekokten
von
uns
nachgewiesenen
ener-
giefreisetzenden
Cofaktoren
bleibt
offensichtlich
die
Le-
bensfahigkeit
der
Krebszellen
und
ihr
Vermogen
zur
Mi-
tosenbildung
'anger
erhalten
als
ohne
Eingreifen
dieser
Akzessorien.
Das
vorliegende
positive
Ergebnis
veran-
lasste
uns,
zu
Untersuchungen
an
Einzell-Kulturen
iiber-
zugehen
und
den
Transplantationstest
einzubeziehen.
F.
WINDISCH,
H.
KERNER
und
W.
SCHACHT
Institut
lily
Medizin
und
Biologie
der
Deutschen
Aka-
demie
der
Wissenschalten
zu
Berlin
und
Universitats-
Hautklinik
der
Charite,
Berlin,
17.
Mai
1958.
Summary
Cancer
cells
treated
in
anaerobic
tissue-culture
with
tumour-decocts
keep
their
vitality
and
their
ability
of
building
mitosis
longer
than
untreated
ones.
From
this
it
follows
that
electrontransferring
cofactors
found
in
tu-
mour-decocts
excite
an
anoxygenic
energy-effect
also
on
cancer
tissues.
oxygenen
Reaktivierung
im
Anabiosestadium
besteht
darin,
dass
sie
nur
bei
Garungszellen,
nicht
aber
bei
Atmungszellen
(Q0
2
:
1)
eintritt.
14
F.
WINDISCH
und
W.
HEUNIANN
SOWie
H.
KRIEGEL
und
A.
GRAFFI
(Gemeinschaftsarbeit),
Z.
Naturforsch.
8b,
673
(1953).
15
Hamatoxylinliisung
nach
DELAFIELD
und
ROMEIS,
Mikro-
skopische
Technik
(Leibniz-Verlag,Nliinchen
1918),
und
zwar
§
669.
Exper.
27
Effects
of
Acute
Hypochloremia
on
Glomerular
Filtration
Rate
and
Electrolyte
Excretion
in
the
Dog
Acute
hypochloremia
was
induced
in
dogs
by
the
use
of
an
artificial
kidney'.
During
a
priming
stage,
plasma
chloride
concentration
was
acutely
decreased
by
dialyzing
the
blood
against
an
isotonic
chloride-free
rinsing
fluid
where
NaCI
was
replaced
by
NaHCO
3
or
NaNO
3
(Table
I).
Subsequently,
a
steady
hypochloremic
state
was
main-
tained
by
a
second
bath
containing
electrolytes
in
con-
centrations
similar
to
those
of
the
dog
plasma
at
the
end
of
the
priming
stage.
With
this
method
it
was
possible
to
study
the
effects
of
hypochloremia
without
hyponatremia
and
with
or
without
alkalosis
on
the
glomerular
filtration
and
electrolyte
excretion
rates
(Fig.
1
and
2).
NO
3
GFR
m(/min
Cl
removed-5,13mfq1kg
65
60
55
50
Diuresis.
5.-
11
2
0
ml/min
4
3
-
-
7
2
-
-
UcIV
p
fqlmin
60
50
40
-
-
7
7
-
30-
20-
10
0
/
4
Na
-
-
-
7
7
088.V
600
pfq/l
500
400
300
200'
100
Uk
V
0
pfq/min
200
15
0
-
t.
K
7
/
750
///
7
50
77
o
/
.
1
,
r,/,
100
200
300
400
min
min
Fig.
1.—Glomerular
filtration
rate
and
electrolyte
excretion
changes
observed
in
same
experiments
as
in
Figure
2.
3
experiments
were
performed
with
NaNO,
and
6
with
NaHCO
3
.
The
following
results
were
obtained
during
12
standard
10
min-clearance
periods
for
each
experiment.
(1)
Glomerular
Filtration
Rate
2
.
Hypochloremia,
with
1
We
arc
much
indebted
to
Dr.
R.
P.
HERWICK,
from
Baxter
Laboratories,
Morton
Grove,
Ill.
(U.S.A.),
for
supplying
the
Kolff's
coil
kidney
units
used
in
these
experiments.
2
The
experiments
involving
a
drop
of
blood
pressure,
as
is
often
observed
during
hemodialysis
in
dogs,
have
been
omitted
from
our
results.
M
/
/I
/
,
100
200
300
400
11
2
0
1171
Na
Cl
11CO
3
Cl
removed-8,38
mfqlkq
GfR
7
/
ft
7
418
Breves
communications
-
Brevi
comunicazioni
[EXPERIENTIA
VOL.
XIVIli]
NO
3
Priming
Sustaining
pH
7-70
7-60
750
740
00
3
mM/i
40
HCO
3
35
30
25
20
15
No
3
mEq/1
30
25
Cl
MEV
120
115
110
105
100
95
90
85
Na
mf
q/I
160
155
150
K
mfg/I
3-5
3.0
2.5
0
pH
7-70
7.60
7
-
50
7-40
HCO
3
40
35
30
25
20
15
pCO
2
toffilig
35
30
No
3
25
Cf
mEgil
120
115
110
105
100
95
90
01
85
Na
Na
mEg/I
160
155
150
K
mfg/I
3.5
3.0
2.5
HCO
3
Priming
Sustaining
pH
HCO
3
pCo
z
CI
Na
pH
HCo
3
K
_
.
50
100
1
50
200
250
300
350
400min
0
50
100
750
200
250
300
min
Fig.
2.-Blood
changes
during
NO
3
(left)
and
HCO
3
(right)
induced
hypochloremia.
The
vertical
lines
indicate
the
beginning
of
each
type
of
bathes
used.
or
without
alkalosis,
does
not
lower
the
glomerular
filtra-
tion
rate
(Table
II).
(2)
Sodium
Excretion.
Although
there
was
no
significant
change
in
the
sodium
glomerular
filtered
load
during
these
experiments,
the
excretion
of
sodium
increased
markedly
in
both
types
of
hypochloremia.
The
ratio
of
excreted
Na/filtered
Na
rose
from
a
mean
control
value
of
0.2
up
to
4.5%
when
the
chloremia
was
decreased
from
117
to
84
mEq/1.
Table
I
Composition
of
Bathing
Fluids
Bathing
Fluids
Milliequivalents
per
1
Cl
NO
3
HCO
3
Na
K
Ca
Mg
Normal
. .
. .
120
-
30
142
4
2.5
1.5
NO
3
Priming
8
115
30
145
4
2.5
1.5
Sustaining
80
143
30
145
4
2.5
1.5
HCO
3
Priming
.
8
145
145
4
2.5
1.5
Sustaining
80
73
145
4
2.5
1.5
(3)
Potassium
Excretion.
Potassium
excretion
was
also
raised
during
both
types
of
experiments.
In
NO
3
-induced
hypochloremia,
the
ratio
excreted
K/filtered
K
rose
from
18
up
to
65%
as
the
plasma
chloride
concentration
fell
from
118
to
84
mEq/1.
Potassium
excretion
was
much
more
increased
in
hypochloremic
alkalosis
where
the
excreted
K/filtered
K
ratio
increased
proportionally
to
the
blood
pH
(Fig.
3),
as
has
been
previously
shown
by
FRANGLEN
et
a1.
3
.
3
G.
T.
FRANGLEN,
E.
MCGARRY,
and
A.
G.
SPENCER,
J.
Physiol.
121,
35
(1953).
(4)
Chloride
Excretion.
Despite
the
marked
reduction
of
the
chloride
glomerular
filtered
load,
chloride
excretion
was
usually
increased
in
both
types
of
hypochloremia.
The
ratio
of
excreted
Cl/filtered
Cl
rose
from
0.2
up
to
1.4%
in
the
nitrate
experiments
and
from
0.7
to
1.0%
in
hypochloremic
alkalosis.
(5)
Bicarbonate
Excretion.
Although
bicarbonate
excre-
tion
was
regularly
increased
in
hypochloremic
alkalosis,
it
never
reached
the
values
observed
during
4
control
experiments
where
a
6%
NaHCO
3
solution
was
infused
Table
II
Effect
of
Hypochloremia
on
Glomerular
Filtration
Rate
Experiment
No.
Plasma
chloride
mEiiil
Glomerular
Filtration
Rate
ml/min**
Control
7 1
11
10
7,1
-
ia
Control
Hyo-
chlore
p
mia
1*
118
89
5-4.6
55.5
2*
121
76
90.8
89.8
3*
115
87
71.2
68.8
4
136
92
76-2
75.5
5
116
92
53.1
60.4
6
118
76
64-1
68.0
7
118
80
43.4
59.0
8
115
85
69-9
79.0
9
116
79
81.3
95.0
Means
117
84
67.2
72.3
*
NO
3
-induced
hypochloremia.
**
Each
value
represents
the
mean
of
three
successive
creatinine
clearance
periods.
in
dogs
submitted
to
hemodialysis
against
a
normally
balanced
bathing
fluid.
In
these
latter
experiments,
not
involving
hypochloremia,
the
usual
threshold
value
for
bicarbonate
was
obtained:
from
26
to
28
niM
of
bicar-
o
Normochloremia
Hypochl
uremia
I
t
0 0
0
a
0
0
0
10
20
30
40
Plasma
bicarbonate
m11/1
419
[15.
XI.
1958]
Kurze
Mitteilungen
Brief
Reports
bonate
reabsorbed
per
liter
of
glomerular
filtrate'.
In
contrast
to
this,
our
dogs
in
hypochloremic
alkalosis
showed
bicarbonate
threshold
values
rising
parallel
to
the
0.5
-0.5
7-40
760
7-80
Blood
pH
Fig.
3.—The
ratio
of
excreted
K/filtered
K
in
relation
to
blood
pH
in
hypochloremic
alkalosis.
plasma
bicarbonate
concentration
(Fig.
4),
such
as
has
been
observed
by
RELMAN
et
al.
5
,
BRAZEAU
and
GILMAN
8
,
and
DORMAN
and
SULLIVAN
7
in
respiratory
acidosis
and
by
ROBERTS
et
al.°
in
potassium
depletion.
A
similar
in-
Re
a
bsor
be
d
b
ic
a
r
bona
te
m
M/100
0m
tg
lom
eru
la
r
f
iltr
a
te
50
40
30
20
10
Fig.
4.—Bicarbonate
reabsorption
during
hypochloremic
alkalosis
(black
circles)
and
during
6%
NaHCO
3
infusion
(open
circles).
The
values
under
25
mEq/1
represent
data
obtained
during
the
control
periods.
R.
F.
PITTS
and
%V.
D.
LOTSPEICI1,
Amer.
J.
Physiol.
147,
481
(1946).
1
A.
S.
RELMAN,
B.
ETSTEN,
and
W.
B.
SCHWARTZ,
J.
din.
Invest.
31,
972
(1953).
6
P.
BRAZEAU
and
A.
GILMAN,
Fed.
Proc.
12,
19
(1953).
P.
J.
DORMAN
and
W.
J.
SULLIVAN,
Fed.
Proc.
12,
34
(1953).
8
K.
E.
ROBERTS,
H.
T.
RANDALL,
U.
L.
SANDERS,
and
M.
HOOD,
J.
din.
Invest.
34,
666
(1955).
27o
crease
in
bicarbonate
reabsorption
was
observed
when
a
6%
NaHCO
3
solution
was
infused
during
NO
3
-induced
hypochioremia.
These
findings
demonstrate
a
definite
competition
be-
tween
bicarbonate
and
chloride
in
tubular
reabsorption.
This
phenonemon
was
first
described
by
PITTS
and
LOTSPEICH
4
and
more
recently
by
HILTON
et
al.°
who
studied
the
effect
of
increased
plasma
chloride
concen-
tration
on
bicarbonate
reabsorption.
CB.
TOUSSAINT,
M.
TELERMAN,
and
P.
ViomlinsTRAETEN
Laboratoire
de
Medecine
expdrimenlale,
Universitd
Libre
de
Bruxelles
el
Fondation
A9Erlicale
Reine
Elisabeth,
Bruxelles
(Belgium),
June
30,
1958.
ResionO
La
chloremie
du
chien
a
ate
abaissee
a
l'aide
d'un
rein
artificiel
en
utilisant
des
liquifies
de
dialyse
ou
une
cer-
taine
quantity
de
chlore
etait
remplacee
par
du
bicar-
bonate
ou
du
nitrate.
Dans
ces
conditions,
l'hypochlore-
mie
s'accompagne:
1
0
d'une
conservation
de
la
filtration
glomerulaire;
2
0
d'un
accroissement
de
l'excretion
du
sodium,
du
po-
tassium
et
du
chlore;
d'une
elevation
chi
seuil
d'excretion
du
bicarbonate.
9
J.
G.
HILTON,
N.
E.
CAPECI,
G.
T.
Kiss,
0.
R.
KRUICSI,
V.
V.
GLAVIANO,
and
K.
klif:catA,
J.
din.
Invest.
3.5,
.181
(1956).
On
the
Participation
of
the
Zona
Glomerulosa
on
the
Adrenal
Response
to
Stress
The
adrenal
glomerulosa
is
considered
to
be
the
site
of
mincralocorticoid
production,
as
was
recently
proved
by
HARTROFT
and
EISENSTEIN
I.
However,
the
physiological
mechanism
by
which
its
function
is
regulated
still
remains
obscure.
The
conception
of
the
high
independence
of
glo-
merulosa
on
pituitary
control°
disagrees
with
the
obser-
vation
of
glomerulosa
reaction
taking
place
only
in
the
presence
of
hypophysis
3
or
the
glomerulosa
reaction
on
ACTH
in
hypophysectomized
animals
4
.
The
experimen-
tal
results,
here
presented,
contribute
to
the
closer
eluci-
dation
of
this
problem.
White
Wistar
rats,
males
about
5
months
old
and
21)0
to
250
g
in
weight,
were
the
object.
The
rats
were
stressed
by
a
single
intramuscular
injection
of
4%
formaldehyde
in
the
quantity
of
0.3
m1/100
g,
and
were
killed
at
inter-
vals
of
1
h.
and
3
h
after
the
injection.
The
adrenals
were
fixed
by
4%
formaldehyde
with
1%
CaCl
2
.
The
lipids
of
P.
Al.
HARTROFT
and
A.
II.
EISEN:WEIN,
Rndocrigtology
60,
641
(1957).
2
H.
%V.
DEANE
and
R.
0.
GREEP,
Amer.
J.
Anat.
79,
117
(1016).
H.
W.
DEANE,
J.
H.
Slimy,
and
R.
0.
GEEEr,
Endocrinology
43,
133
(1948).—
E,
KNonii.,
A.
MonsE,
and
K.
O.
GEEEr,
Anat.
Rec.
121,
324
(1955).
K.
KovAcs,
Hoavkru,
B.
M.
KovAcs,
G.
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