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Xerox University Microfilms
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£qZq Gaudino, Nicolas Mario Horacio, 1918-
Xo Influence of the adrenal cortex on
0 * body water distribution and renal
- function,, New York, l9l|-9«
39 typewritten leaves* diagrs.
29cm.
Thesis (PhoD.) - New York Univer
sity , Graduate School, 19!?0*
Bibliography: p .31-39•
C50718
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• ,
Shell List
Xerox University Microfilms, Ann Arbor, Michigan 48106
THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED.
LIBRAR2 Of
m TORK UfllYERSlTT
m n ® in heiohis
I N F L U E N C E OF THE A D R E N A L C O R T E X
ON BODY WAT E R D I S T R I B U T I O N
AND
R ENAL F U N C T I O N
«»*
N. MAR I O H. G A U D I N O
A dissertation in
the department of Physiology submitted
to the faculty of the Graduate School
of Arts and Science of New York Uni
versity in partial fulfillment of
the requirements for the degree of
Doctor of Philosophy.
* * r
f " " ^
ftflKWnWT .EDGMKHT
I wish to express my indebtedness to Dr. Homer
W. Smith for providing facilities and guidance for the
prosecution of this vork, to Dr. Domingo Gamez for his
valuable advice and criticism, to Dr. Marvin F. Levitt
for his help and companionship in accomplishing the
actual vork, and to all those that one vay or another
had an influence in its final completion.
2 o \ o ^
INFLUENCE OF THE ADRENAL CORTEX ON BODY EATER AND RENAL FUNCTION
TABLE OF CONTENTS
Page
INTRODUCTION ....................................................................... . . . . . 1
REVIEW OF THE LITERATURE................................................... 3
Influence of the Adrenal Cortex on
the Body Water Distribution• • • • • « » • • • . • . 3
Influence of the Adrenal Cortex on.
Renal Function 5
METHODS ....................................................................................................... 7
RESULTS ......................................................................................................... 9
Aotion of PesQgycortiooBteroneA cetate . . . . . . . . 9
Action of Adrenal Cortical E x tra c t.......................... 15
Effect of Total Adrenalectomy ............................ • . 15
DISCUSSION ....................................................................... . . . . . . . 25
SUMMARY .............................................................................. 29
BIBLIOGRAPHY............................................................................ 31
UfTRQDUCTIOH
A relation between the adrenal oortex and the distribution
of body water has been recognised since the first demonstration
that adrenal insufficiency was associated with a marked degree
of haaoconoentration. The suggestion that this hemoccncantraticn
night be attributed to a deerease in plasma volune was later
confirmed by direct measurement and by the circumstance that nomal
plasma volume was restored with adequate desoxycorticosterone
therapy*
The administration of cortical extract to animals in adrenal
insufficiency was followed by hemodilutian and diuresis even though
no water was ingested. Swingle and his collaborators suggested
that adrenaleotoaised animals were unable to mobilize fluids from
the interstitial and oell spaces, and that the hormone ef footed
the redistribution of. fluids in the organism. According to Harrop
fluid entered eells during insufficiency and was released by therapy.
The extracellular spaoe, as judged by the volume of distribution
of ohloride and thiocyanate, was decreased after adrenalectomy and
restored by hormone therapy. Moreover, the picture of adrenal
insufficiency was simulated by peritoneal dialyBis, a prooedure
whioh reduoes extracellular fluid volume.
As a consequence of the changes noted in serum eleetrolyte
pattern during adrenal insufficiency, attention was focused on the
simultaneous electrolyte and water changes in the tissues. Calcula
tions of the tissue water compartments, based upon the assumption
that ehloride is limited to extraoellular distribution, revealed a
shift of water from the interstitial into the intraoellular space*
Marshall and Davis, by measuring the excretion of phenol -
sulfaaephthalein, urea and creatinine, demonstrated a decrease in
renal function following oomplete adrenalectomy* The subsequent
use of more precise measures of renal activity confirmed the
latter observation* Inulin, creatinine, urea and diodrast clearances
as well as diodrast Tm were found to be reduced after adrenalectomy
and restored after adequate hormone therapy.
In view of the above evidence, it seemed desirable to measure
ohanges in all the body water compartments and to correlate them with
modifications in renal function observed simultaneously in animals
subject to alterations of adrenal function. Previous methods for
the estimation of the extracellular space used either thiocyanate
or chloride, both of which substances are now known to enter cells
in a variable proportion. To overcome this objeotion a more accurate
method (inulin spaoe ) for the determination of the extraoellular
volume was devised. Coupled with the use of heavy wqter (DgO) as a
measure of the total body water, accurate estimates of intracellular
24
volume were feasible. The use of radioactive sodium (9a ) or
potassium (X42 ), afforded means for determining the intraoellular
distribution of these ions.
"3"
REVIEW OP THE LITERATURE
Influence of the adrenal oortex on the body water
distribution. Since the first observations of adrenal
insufficiency in animals and in man. the existence of a
marked degree of hemoooncentration and a high hematocrit
count were recognized as an outstanding manifestation of
the disease (3*24*33,35*57,62). These changes were consi
dered to be an indication of a diminished plasma volume*
a concept that was later confirmed by direct measurement
with various methods (total exsanguination* vital red*
T-1824). The plasma volume was decreased 50 per cent or
more from the control values (6*53*57*60,62). After desoxy-
corticosterone therapy* the blood volume of patients with
Addison's disease revealed a marked increase (62). The same
effeot was observed in adrenalectomized dogs up to values
above preoperative controls (6*53). m the dog* the maximum
action of desoxycorticosterone was reached about the seventh
day and tended to disappear under prolonged treatment (53).
Cortin was less effective in the restoration of the plasma
volume and required the addition of sodium ohloride for com
plete normalisation. (6).
The withdrawal of the oortioal hormone in adrenalectomised
dogs was followed by a negative water balance* but the loss of fluid
was not enough to account for the deeline in blood volume (59). Re
establishment of the treatment determined an immediate blood di
lution and a significant diuresis* although no water was ingested
(20*58).
The suggestion was made by Swingle and collaborators that animals
in adrenal insufficiency are unable to mobilise fluids from the
interstitial and oell spaces (68). According to Barrop (20)* the
interstitial fluid entered the oells during insufficiency and was
released by the hormone therapy* The improvement of the hemocon-
centration as a consequence of the hormone treatment was indepen
dent of the plasma levels of sodium and chloride and led Swingle
and collaborators (55) to postulate that the hormone effected the
redistribution of fluids in the organism.
Harrop (20) and Winkler* Ekinton and Eisenman (65) studying
one dog respectively* found that the extraoellular space* as measured
by the volumes of distribution of thiocyanate and radioaotive chloride*
was deoreased after adrenalectomy and restored with hormone therapy.
The effect of desoxycorticosterone was more intense when used alone
than when combined with cortin (65). Cortin normalises the thio-
oyanate space but the ooupling with desoxyoorticosterane results in
an increase of that space above normal values (6). In patients with
Addison's disease* the volume of distribution of thiooyanate is also
enlarged after desoxycorticosterone therapy (35).
The intraperitoaeal injection of gluoose* a prooedure that
is considered to reduce extracellular fluid volume (9)* reproduces
the picture of adrenal insufficiency* including the hemoconoentration
and the decrease in the thiooyanate space (14*20*42*54).
The characteristic changes observed in the plasma eleotro-
lyte pattern during adrenal insufficiency (5*4*55) direoted the
attention to the simultaneous eleotrolyte and water modifications
in the tissues. The total water o on tent of the liver* musole and
other tissues inoreased after adrenalectomy (50*51)* By assuming
that all the ehloride is extraoellular* the tissue water ocmpart-
ments were calculated during adrenal insufficiency* revealing a
shift of water from the interstitial into the intraoellular space
(8«17*26»43). According to Harrison and Darrow (8*17)* the con
centration of the extracellular electrolyte is the prineipal factor
in the control of water exchange in adrenal insufficiency* the inw
crease in the intraoellular water being the consequence of the de
crease in the plasma and interstitial fluid concentrations of
sodium and chloride* When Upjohn* s oortioal extract was given the
total water decreased*the extraoellular fluid being further reduced
with a simultaneous further expansion of the intracellular volume
(42)* Conversely* desoxycorticosterone in normal animals produoed
a shift of water from the intraoellular into the interstitial space
(41).
The above evidence supporting the eonoept that during
adrenal insufficiency there is a decreased volume of extra
cellular fluid with a probable increase in the intracellular water
is based on the estimation of the extraoellular spaoe with thio
cyanate or ohloride. Both of these substances are known to enter
the cells in a variable proportion (1*2*7*36*37)* especially in
certain pathological conditions (44*45*46)* Thus* there is no
certainty that calculations based an the assumption that these sub-
stanoes measure extraoellular space are actually presenting the true
picture of the events concerned*
Influence of the adrenal oortex on renal functions Marshall
and Davis (39)* in 1916* mentioned an inorease in the urea content
