Liver Function Tests on Normal and Adrenalectomized Dogs

141 Pages·8.591 MB·English

by  Martin, Constance R

II?SR FUNCTION TESTS ON NORMAL AND /J)R3»ALBCT01II2J5D DOGS
by
Constance Bigler Martin
A dissertation submitted in partial fulfillment of th© requirments
for the degree of Doctor of Philosophy, in the Department of
Physiology, in the Graduate College of the State
University of Iowa
February, 1951
ProQuest Number: 10991986
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ACKNOWLEDGMENTS
The author is deeply indebted to Dr# W* D# Colllngs of
the Department of Physiology and Pharmacology, Michigan State
College, for suggestion of the problem and for constant encourage­
ment and assistance throughout its completion, and to Dr# S. B#
Barker of the Department of Physiology of the State University of
Iowa for guidance in preparation of the manuscript*
The author also wishes to express appreciation to Dr#
J* J« Pfiffner of the Hesearch Laboratories of Parke, Davis and
Company for generous quantities of Eschatin, and to Dr# B*
Oppenheimer of Ciba Pharmaceutical Products, Inc* for the supply
of Percorten#
TABLE OF CONTENTS
Chapter Page
X Introduction, 1
XX Methods ......... . , . . . h
III Evaluation of the Degree of Adrenal Cortical
Insufficiency » • • • « » » • < > • • • • * « • • 11
IV The Bromsulphalein Test............ 1*0
V Galactose Tolerance * . . . . . . . 59
VI The Senm Alkaline Phosphatase Test.......... 75
VII Hemoglobin Content of the Blood . .......... 85
VIII The Albumin-Globulin Ratio 9h
IX Suamary and Conclusions 106
Bibliography............. 110
iii
TABLE OF TABLES
Table Page
I Detailed Protocol for Dog Gus . . * * « « * * * * * » • lb
II Detailed Protocol for Dog Goofy . » • « « • • » » » » » 16
III Detailed Protocol for Dog Curly • » » • • • • « * « » • 18
IV Detailed Protocol for Dog Bushy.......... 20
V Detailed Protocol for Dog George « » * * * » • * * « • 22
VI Effect of Unilateral Adrenalectomy upon BSP Retention • bb
VII BSP Retention Seven to Ten Days Following Bilateral
Adrenalectomy with Animals on Replacement Therapy « . * bS
VIII Effect of Progressive Reduction of AGE Dosages upon
BSP Retention * » « • « * • * » • b?
II Effect of Alternate Administration and Withdrawal of
BGA on BSP Retention of Dog George * b8
I Relative Effectiveness of Adequate Dosages of ACE as
Compared with DCA for Maintenance of Ability to Remove
BSP ...................................... SO
XI Relative Effectiveness of ACE Compared with DCA for
Maintenance of Ability to Remove BSP « « * * ........... Si
H I Effect of Severe Adrenal Insufficiency on BSP Retention S3
XIII Pre-Operative Urinary Excretion of Galactose • • » * • 6b
XIV Comparison of Galactose Data Obtained Several Days
Po3t-Operat i vely with Pre—Operative Average Values* * . 66
XV Urinary Excretion of Galactose Following Intravenous
Administration .......... 70
iv
TABUS OF TABLES (COHTU).)
Table Pag®
XVI Summary of Results of the Serum Alkaline Phosphatase
Test * . * . . * SO
XVII Effect of Adrenalectomy and Administration of ACE and
BOA upon Hemoglobin Concentration of the Blood » « « « 87
OTIX Effect of Adrenalectomy and Administration of ACE and
DCA Upon Hemoglobin Concentration of the Blood -
Bog George . « • * « • * • * » * • * • ........ * • * 83
XIX Effect of Adrenalectomy and of Administration of ACE
and DCA Upon the Albumins Globulin Ratio » , « « « • 96
XX Effect of Adrenalectomy and of Administration of ACE
and DCA Upon the Albumins Globulin Ratio} Bog Georg© » 91
TABLE OF FIGUBES
Figure Fag©
1 Pr©’*Op©rattv© Galactose Tolerance
Curves • * , * » » * * * « « » « 63
2 Average Blood Galactose Values of
Four Bof;s Under Four Experimental
Conditions • .......... • » « 69
vi
1
Chapter X
INTRODUCTION
Although numerous investigations (116) have demonstrated the
influence of adrenal cortical hormones upon hepatic enzyme system© both
in vivo and in vitro, comparatively little attention has been directed
towards the role of these hormones in maintaining the function of the
liver a® a whole in the intact animal* The presence of adrenal cortical
insufficiency in the experimental animal is established without the us©
of liver function tests* while pathologic values on these tests in
patients with Addison1® disease are considered to be indicative of co­
existing hepatic disorder not necessarily related in etiology to the
glandular deficiency*
It is the purpose of this study to determine (1) whether
impairment of hepatic function to & degree detectable by the more
commonly used liver function tests occurs following bilateral
adrenaleetoigy in the dog, (2) what effect, if any, the administration
of either an aqueous extract of whole adrenal glands or an oily solution
of desoxycorticosterone in appropriate dosage will have upon the course
of such impairment, and (3) whether liver function tests will yield
abnormal values when adrenalectomized animals are well maintained
according to the standard© which hav© been adopted for measuring the
adequacy of replacement therapy*
2
Evaluation of the functional status of the liver presents
many problems* Since the various phases of hepatic activity may b©
independently altered to different degrees or even in different
4
directions following an experimental procedure, a large number of tests
of different types must be employed if a complete picture is to be
obtained* Kapid and extensive hepatic regeneration necessitates
repetition of the tests at frequent intervals to point up transient
changes* Moreover, under the most carefully controlled conditions,
minor degrees of dysfunction may escape detection because of the
tremendous reserve capacity of the liver*
The adrenal cortex also perforins numerous apparently
independent functions. Her® again, several procedures are required in
order to obtain a reliable measurement of activity. Changes are
difficult to quantitate because there is marked variation in response
among individual animals subjected to identical external conditions and
in the same animal when an attempt is made to duplicate experiments.
The investigation is further restricted because there is a limit to the
number of procedures to which an adrenal©etomized animal can be
repeatedly subjected if it Is to survive for completion of the study.
In the present investigation, the decision was made to perform
as many different test© for each function on each of th® animals as
could reasonably be expected to be compatible with survival. Th® tests
are used with the realisation that "normal** values do not necessarily
rule out th© presence of dysfunction, and that a specified treatment
regime will not necessarily produce th© same degree of adrenal cortical
3
insufficiency in on© animal aa in another.
Intensive work of this nature makes impractical, from the
standpoint® of both time and coat of material, the use of large
numbers of animals* A total of ten dogs was studied during the course
of the investigation. Of these, only five survived for completion of
the experiments. It was impossible to treat even these five in
exactly th© same manner, partly because of th® well-known physiological
capriciousness of adrenalectomized dogs, and partly because of
occasional delays in obtaining materials. For these reasons, no attempt
was made to group the data for the purpose of a formal statistical
analysis•
This necessarily limits the accuracy of predictions concerning
th® liver-adrenal cortex relationship in the dog population as a whole.
/
Th© data are useful, however, because they point up unmistakable
trends, and because they form a background against which more restricted
investigations may b® patterned.