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UBC Theses and Dissertations

Changes in the function and ionic composition of the alimentary tract in response to dietary cation deficiences,… Bass, Paul 1955

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CHANGES IN THE FUNCTION AND IONIC COMPOSITION OF THE ALIMENTARY TRACT IN RESPONSE TO DIETARY CATION DEFICIENCES, AND THE POSSIBLE ROLE OF ADRENAL MEDULLARY AND CORTICAL HORMONES IN MEDIATING THESE RESPONSES by Paul Bass  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF ARTS in the Department of Pharmacology  We accept this thesis as conforming to the standard required from candidates f o r the degree of Master of Arts  Members of the Department of Pharmacology The University of British Columbia October, 19!>5>  — V  —  Abstract The possibility that loss of intestinal motility occurs as a result of potassium or sodium depletion has been investigated* A new technique, based on the passage of a solution containing the dye, gentian violet, was developed for estimating upper bowel motility« Lower bowel motility was not objectively studied* The sodium and potassium content of various portions of the gut from rats on a low sodium, low potassium diet and on a high sodium, low potassium diet have been determined and compared with that of similar portions of the gut of animals on a control diet*  The possibility that excess adrenal cortical or medullary hormones  may cause or permit electrolyte and motility changes has been studied^ The response to dietary potassium restriction in the presence of a high sodium intake were also determined after adrenalectomy, both with and without medullory or cortical hormonal supplementation. The electrolyte pattern of plasma liver and of skeletal muscle from different portions of the body were analysed and compared in order to aid in understanding the overall electrolyte shifts*  Analyses of the selected tissues of the body  indicated that initial electrolyte concentrations and responses to diets and hormones vary within similar tissues as well as between different organs» It was not possible to correlate alterations in the gastro—intestinal tract content of sodium and/or potassium with changes in motility* Dietary potassium deprivation led to depletion of potassium only in plasma, skeletal muscle and certain portions of the gastro—intestinal tract in intact animals. This effect was prevented by adrenalectomy* Evidence i s presented that cortisone can influence the electrolytes of the body by acting in the cells of peripheral tissues as well as on  - vi the kidney and that the high dose administered (4 mgm/day) had direct dietary potassium deficiency actions i n addition to permitting depletion to occur in the presence of certain tissues* The hypothesis that excess adrenal cortical hormones cause intestinal iamotility through loss of potassium or a gain of sodium in this tissue was not confirmed by the data* Evidence is presented indicating that adrenalin can partially restore the ability to excrete potassium and the ability of tissues to undergo potassium depletion in adrenalectomized animals on a potassium deficient diet*  i t does not correct the electrolyte levels in adrenalectomiaed  animals on a control diets The possibility that adrenalin may play some role in maintaining electrolyte homeostatis is discussed*  •* i i •» TABLE OF CONTENTS! Page I.  A STUDY OF THE EFFECTS OF DIETARY ELECTROLYTE CHANGES ON THE ELECTROLYTE CONTENT OF SELECTED TISSUES IN THE RAT  1  Mm Introduction  1  B. Methods  3  C. Diet  7  D„  Limits and Sources of Errors  26  Results?  IL»  1, Effect of Diet on the Weight of the Animals  29,  2. Effect of Diet on Out Motility  29  3»  29  Electrolyte Analyses a)  Plasma Electrolytes  29  b)  Skeletal Muscle Electrolytes  30  e)  Gastro-«Inte8tinal Tract Electrolytes  32  d)  Liver Electrolytes  35  EFFECTS OF VARYING DIETARY ELECTROLYTE INTAKE, ADRENALIN AND CORTISONE ADMINISTRATION TO ADRENALECTOMIZED AND INTACT RATS 36 Results* 1 Effect of Diet and Hormone Treatment on the Weight of Animals 36 9  2, Effect of Diet and Hormone Treatment on Gut Motility 3» 4«  III.  37  Effect of Diet and Hormone Treatment on Mortality  37  Electrolyte Analyses  38  E,  Discussion  48  F*  Summary and Conclusions  61  BIBLIOGRAPHY  63  a  - ill -  L I S T OF T A B L E S  Table I  n H I IV V  VI  VII  VIII  K X  XI  XII  Page Composition of diets Motility data  9  10-11  Mortality  12  Analytical data on the electrolytes of the blood  13  Analytical and derived data on the electrolytes of the thigh muscle  lk  Analytical and derived data on the electrolytes of the abdominal muscle  15  Analytical and derived data on the electrolytes of the stomach  16  Analytical and derived data on the electrolytes of the duodenum  17  Analytical and derived data on the electrolytes of the ileum  18  Analytical and derived data on the electrolytes of the large intestine  19  Analytical and derived data on the electrolytes of the rectum  20  Analytical and derived data on the electrolytes of the liver  21  iv LIST OF FIGURES Figure 1  Page Weight changes i n intact animals on: i. ii. iii. iv.  2  Low sodium, low potassium diet High sodium, low potassium diet Low sodium, low potassium diet plus .1$% KC1 Control diet  22  Weight changes i n : i. ii.  Adrenalectomized animals plus control diet Adrenalectomized animals plus high sodium, low potassium diet plus adrenalin i i i . Adrenalectomized animals plus control diet plus adrenalin  3  23  Weight changes i n : i.  Animals plus high sodium, low potassium diet plus cortisone i i . Animal 3 plus control diet plus cortisone i i i . Adrenalectomized animals plus control diets plus cortisone i v . Adrenalectomized animals plus high sodium, low potassium diet plus cortisone k  Effect of the various diets and treatments on the gastro-intestinal tract motility  2k  2$  - vii • Acknowledgments  The writer wishes to thank Dr. E*E* Daniel of the Department of Pharmacology for advice and guidance throughout the period of research*  Thanks are due to Dr. J.G. Foulke of  this department for. his very helpful criticism*  He wishes to  express his appreciation to Mrs* Ruth Bass for the typing of this thesis and for her encouragement. He also wishes to express his gratitude to Miss Mho"  Powell for assistance with  the typing and to Mr* Jerry Kent for help with the figures and to Miss Shirley Driver and the other members of the Department of Pharmacology for assistance with the technical and l i t e r a r y aspects of this thesis*  The work presented herein was partly supported by the Canadian Foundation for the Advancement of Pharmacy*  I,  A STUDY OF THE EFFECTS OF DIETARY ELECTROLYTE CHANGES ON THE ELECTROLYTE CONTENT OF SELECTED TISSUES IN THE  RAT  A. Introduction The role of potassium i n the functioning of smooth muscle and the influence of various conditions and substances on the potassium content of tissues containing smooth muscle have not been extensively investigated. The effects of similar procedures on the electrolytes of skeletal muscle have been subjected to much study. This subject has been reviewed by Manery, $h, Overman, 'Si, and Danowski, "51. x  In general a loss of  potassium from skeletal muscle i s accompanied by an increase of muscle sodium. This exchange of ions does not impair the activity of the skeletal muscle (Heppel, '39)«  Previous investigators (Kornberg, '1.6,  Skinner,  'UJ>,  and Henrikson, '51) have reported that animals placed on low potassium diets became anorexic and constipated.  Upon post-mortem examination, the  gut was described as being hypomotile, and distended with gas and f l u i d . From these studies several basic questions arise,  why should the  gut become relatively- inactive following a lack of dietary potassium?  Are  the electrolyte changes produced i n the gut by potassium deficiency similar to the changes produced i n striated muscle?  Striated muscle retains i t s  a b i l i t y to contract, even after a loss of approximately $0 percent of i t s potassium (Fuhrman, *5l). Is the inactivity of the gat due to changes i n i t s electrolyte content?  Steiribach, '5b, postulated that an increase i n  the muscle sodium may be inhibitory to contraction. Is hypomotility i n the bowel the result of an increase i n sodium, a decrease of potassium, or  are both changes required? Does the gastro-intestinal tract respond as a whole to electrolyte imbalance or do i t s various portions differ i n the degree of their response? It seemed of interest to analyse the effects of potassium depletion, and of other procedures tending to impair motility on the electrolyte content of the gut wall.  Some of the animals on the potassium depleted  diet were subjected to decreased sodium intake as well, whereas others were placed on a diet of high sodium content. The tissues of potassium deficient animals were compared with those of animals on a normal diet. Liver, and several samples of skeletal muscle also were analysed to compare the degree of potassium depletion with that reported by other workers.  The effect of the various diets on gut motility was also i n -  vestigated. Chronic dietary electrolyte alterations would appear to constitute a "stress" which might well activate the adrenals. Extensive work has r e vealed the importance of the adrenal glands (Woodbury, '53, and Drury, f  53) i n the metabolism of electrolytes and water of the body. The present  experiments were designed to study what role the adrenals might play In producing or modifying the changes produced by potassium deficiency. An attempt was made to answer the following questions: 1.  Were the adrenals essential for the appearance of any or a l l of the  effects of potassium deficiency; i . e . did adrenalectomy slow or prevent the loss pf potassium from tissues caused by low potassium diets? 2.  Did cortical or medullary hormones have the greater tendency to return  the electrolyte pattern of tissues to that of intact rats on the various diets?  Did the hormones have any direct action on electrolyte patterns  unrelated to diet?  - 3 3.  Was the electrolyte pattern of these tissues related to motility? In order to investigate the effects of both cortical and medullary  hormones of the adrenal gland on the electrolytes of the gastro-intestinal tract, cortisone and adrenaline were individually administered to adrenalectomized animals, fed diets varying i n potassium content. The effects of these hormones on motility was also investigated. The a b i l i t y of i n d i v i dual hormones of the medulla and the cortex to maintain l i f e and affect growth of the animals i s also reported.  B. Methods Male albino Wistar rats were used throughout these experiments. The i n i t i a l weights of the animals were 175 to 200 gnu  Diets (Table 1) varying  in sodium and potassium content were used i n the experiments and were offered to the rats ad libitum.  The rats were divided into two major sec-  tions: Section I. Intact Animals Group A. Low potassium, low sodium diet Group B. Low potassium, high sodium diet Group C. Control diet. In each of the several runs of animals i n Section I, the animals were grouped as follows: 1. A group of animals subjected to the experimental diet (Table I ) . 2.  Two rats placed on the experimental diet plus added potassium.  3*  Two rats placed on the control diet (Table I ) .  Since no significant variation was seen between animals on Fox Chow (control diet), and the animals on the experimental diet plus added potassium, the data from these animals were combined.  - h Section II* Adrenalectomized Animals and Hormone Treated Animals Group D* Adrenalectomized rats on low potassium, high sodium intake (Table I) GroupE* Adrenalectomized rat on control diet Group F* Adrenalectomized rats on low potassium, high sodium intake plus adrenalin* Group Q. Adrenalectomized rats on control diet plus adrenalin Group H* Adrenalectomized rats on low potassium, high sodium intake plus cortisone Group I* Adrenalectomized rat on control diet plus cortisone Group J* Intact rats on low potassium, high sodium intake plus cortisone Group K. Intact rats on control diet plus cortisone Groups A, B, and C were maintained for an average of 35 days.  One  animal of group A was maintained for 81 days with no significant change i n the electrolyte pattern as compared with others i n the group.  The food,  but not water, was removed 2k hours before sacrificing the various animals. The gut motility of the animals was estimated by force-feeding the animals a one percent solution of gentian violet. one cc. of solution per 100 gm. body weight.  The animals were given  After 1$ minutes, they were  anaesthetized with ether and exsanguinated by heart, puncture with a heparinized syringe. The abdomen was opened and the sharp demarcation between that part of the small intestine containing gentian violet and the untraversed portion was clamped with a haemostat. The time from the forcefeeding of the gentian violet solution to the placing of the haemostat was noted.  The entire gut was then removed and the distance the dye had  * Adrenalin refers to the Adrenalin 1:1000 solution of Parke Davis & Co.  travelled from the pyloric sphincter to the point of demarcation was measured (Table I I ) .  The percent distance travelled (Table II, Figure 17)  was obtained by dividing the distance the dye travelled by the total length of gut measured from the pyloric sphincter to the ileo-caecal valve, multiplied by 100.  The tissues were divided, trimmed of a l l visible  fat and mesentric attachments, and the luminal contents were gentlydexpelled., The samples of skeletal muscle and l i v e r were removed immediately afterwards. A l l the tissues were gently blotted, placed i n tared beakers and weighed.  The entire procedure, from the time of heart puncture to  f i n a l weighing took approximately twenty minutes per animal. The following tissue samples were removed:  ;  1. Bight rectus abdominus muscle 2. Right thigh muscle 3. Right lobe of l i v e r k* Stomach muscle, stripped of mucosa 5. Duodenum 6. Ileum 7. Large intestine 8. Rectum  ,  „  The mucosa was stripped from the duodenum, ileum, large intestine and rectum of three of the rats i n Group A.  It i s d i f f i c u l t to be certain that  ftli the mucosa had been removed; no significant change between the tissue electrolytes with or without the mucosa was noted. The procedure was abandoned. However the easy and complete removal of the mucosa from the stomach was carried out on a l l stomach tissues.  After the wet weights of the t i s -  sues were obtained, the tissues were dried i n an oven (temperature 95 to 105° C.) for a minimum of five days. The tissues were then removed, and  the dry weights obtained*  The dried tissues were pulverized i n a mortar  and portions of the powder were used for analysis*  The portion for sodium  and potassium analyses were digested with n i t r i c acid, redissolved with a minimum amount of one N hydrochloric acid, diluted, and analysed i n duplicate on a Jahnke flame photometer using lithium as an internal standard* The tissue chlorides were analysed i n duplicate by the Wilson et a l , '28, modification of the Van Slyke method, '23* The exsanguinated blood was centrifuged, the plasma removed and placed i n a refrigerator for analysis which was completed vithing 2h hours*  The  sodium and potassium analyses were done on the Jahnke flame photometer using lithium as an internal standard; the chloride analyses were done by the Schales and Schales method* The rats i n Groups D to I were bilaterally adrenalectomized In a single stage operation by a dorso-lumbar approach*  Untreated, adrenalec-  tomized rats (Group D and E),. due to a high mortality rate, were sacrificed at the end of l l ; days*  Adrenalin and cortisone treated rats (Groups F to  K) were sacrificed at the end of 21 days*  The adrenalectomized animals  were maintained on their respective diets plus 0*9 percent sodium chloride and one percent glucose i n demineralized water* Two hormones were used i n order to investigate the individual roles of the medulla and the cortex since the sites of both adrenaline and c o r t i cal hormone production were removed* Of the cortical hormones available, cortisone was chosen because i t i s known to be one of the hormones produced by adrenal cortex.  It was given i n the form of cortisone acetate* i n a  dose of four mg. per day* Adrenalin was administered i n a 1:1000 solution; * Cortisone acetate — Cortone, Merck and Co*, was used.-  the dose being 1;0 micrograms per day per 100 gnu of body weight.  Both  drugs were injected subcutaneously at 2k hour intervals.  C. Diet Composition of the synthetic diet with respect to sodium and potassium i s shown i n Table I* The low potassium synthetic diet was made up as follows: (gnu per 1000 gnu diet). Starch (Canadian Corn Starch)  665 gm  Casein  270 gm  Fat (Mazola Oil* Crisco)  20 gm  Mineral Mix  12 gm  Calcium Carbonate  7 gm  Vitamins (Litrison)*  2 capsules  Mineral Mix was made up i n bulk, and aliquot portions were taken from the diet.  The mixture was made up as follows: 100 gm  Ferric citrate  13 gm  Copper sulphate (hydrated)  k gm  Manganese sulphate Magnesium sulphate (hydrated)  10 gm  Zinc sulphate  2 gm  Calcium chloride (hydrated)  1 gm 870 gm  Sucrose  Six gm. of sodium chloride per 1000 gnu of diet were added to the diets designated as high sodium low potassium diet (Table I ) .  3.4 gm. of  potassium mono acid ortho phosphate (K HP0| ) was added to the synthetic 2  i  diets when potassium supplement was required. * Litrison was kindly supplied by Hoffman La Roche Ltd.  . 8 The synthetic diet was analysed for phosphate content.  I t was  found to c ontain the equivalent amount as found i n the control diet*  Calculations The method of calculations was based on Manery, '39, Manery, '£lu  TABLE I Composition of Diets per 1000 gnu of Diet Diet  Sodium (mEq.)  Potassium (mEq.)  Low potassium, low sodium  .004  .005  High sodium, low potassium  .20  .005  Control diet  .14  .22  - 10 TABLE n Motility Treatment and Diet Low Na, Low E  Distance Dye Travelled (cm.)  Total Intestinal Length (cm.)  32 39 4o 38  80 88 90  High Na, Low E  35  37.3  86.3  Adrenalectomized + Low E Diet Average  b  07  20  38 21 15  20  34  43.2 1.2  19  40  58  61*0 81.3 75.7 63.5 73.6  61 64  96 87  96.2  20  33  67.0 9.2  81  53 90 58  109 97 109 109 80 115 83  21 22 20 22 19 20 19  41 20 25 10 50 42 44  62.4 71.1 66.1 74.3 66.3 78.3 69.9  70.4  100.3  20  58  69.8 1.9  55 48 h9  93 84 87  21 21 21  14 55 04  59.1 57.1 56.3  50.7  88  21  20  57.5 0.8  106  20  55  35.9  38  Adrenalectomized * Normal Diet  23 19 19  4o.o 44.3 44.4 40.9 47.6 42.1  22 19 20 20  68 69 72  Average  19 min. 26 sec. 38 19  100  68.2  Control  Time  Percent Distance Travelled  61 7U  81  Averages  93  84 83  ho Average  Data  91 107  18  51  •11Table U  (cont'd) Motility  Treatment and Diet  Distance Dye Travelled (cm.)  Total Intestinal Length (cm.)  24 2k 2k  98 10U 88  Adrenalectomized + Low K Diet • Adrenalin  26 18  13 10  li4.7 28.6  38  104  22  12  36.7  35 27 21 2k  112 92 97 103  21 22 21 20  26 30 55  31.3 29.3 21.7 23.3  26.8  101  20  53  26.4 2.3  22 33 21  106 117 109  23 22 19  2 51 54  20.8 28.2 19.3  25.3  110.7  22  6  22.8 2.6  29  111  19^'  2  26,1  27 2k  105 99  22 21  30 59  25.7 24.2  25.5  102  22  15  25.0 0.7  Average Adrenalectomized * Low E Diet • Cortisone  Intact + Low E Diet • Cortisone Intact * Normal Diet + Cortisone Average  24.5 23.1 27.3  103 105  46 30  .  2k min. Ii2 sec. 23 51 25 1*7  25.0 1.0  Adrenalectomized • Normal Diet + Adrenalin  Adrenalectomized + Normal Diet + Cortisone  Time  47  2k  Average  Percent Distance Travelled  2k  Average  Average  Data  96.7  ko  8.0  - 12 TABLE  HI  Mortality Data Treatment and Diet  Percent Survival  Duration of Experiment (days)  Low Na, Low K  100  35 (average)  High Na, Low E  100  35 (average)  Control  100  35 (average)  Adrenalectomized + Low K Diet  50  Adrenalectomized • Normal Diet Adremalectomized • Low K Diet + Adrenalin Adremalectomized • Normal Diet * Adrenalin  Hi .  5o  Ifc  21  50  21  Adrenalectomized + Low E Diet * Cortisone  67  21  Intact * Law K Diet + Cortisone  5o  21  Adrenalectomized + Normal Diet + Cortisone  75  21  100  21  Intact * Normal Diet + Cortisone  - 13 TABLE IV Blood Treatment and Diet Low Na, Low K High Na, Low K Control Adrenalectomized + Low K Diet  No# of Samples 10  Analyses mEq. per l i t r e Sodium  Potassium  Chloride  149.3 ±1.2  2.64 ±0.2  100.4  147.9 ±4.5  3.02 ±0.2  98.1 ±4.0  10  150.9 ±0.7  4.45 ±0.2  107.9 ±1.9  3  152.6 ±1.6  5.77 ±0.1  113.4  5-.  ±1.5  ±2.6  Adrenalectomized + Normal Diet  1  152.8  5.1  114.5  Adrenalectomized + Low K Diet + Adrenalin ,  3  157.4 ±0.7  1.84 ±0.4  84.5 ±2.6  Adrenalectomized + Normal Diet + Adrenalin  3  150.2 ±3.8  2.63 ±0.7  91.8 ±0.5  Adrenalectomized + Low K Diet + Cortisone  4  161.4 ±1.9  1.59 ±0.2  94.3 ±2.9  1  150.8  1.22  91.0  3  161.5 ±2.8  3.03 ±0.7  101.3 ±1.1  2  156.7  1.90  96.0  Intact + Low K Diet + Cortisone Adrenalectomized + Normal Diet + Cortisone Intact + Normal Diet + Cortisone  T A B L E THIGH  A N A L Y T I C A L Treatment and Diet  mEq./Kgm. WET WEIGHT  Ig,  of Tissues  87.8  136.7  186.7 ±8.4  45.9 . 80.7 ±1.8 ±2.1  126.6  23.7  117.8 ±2.0  141.5  ±2.5  28.9  108.3 ±2.5  1  41.4  Adrenalectomized + Low K Diet •i- Adrenalin  3  58.4 ±0.9  Adrenalectomized + Normal Diet + Adrenalin  3  29.5 ±0.7  High Na, Low K  5  Control  7  Adrenalectomized + Low K Diet Adrenalectomized + Normal Diet  3  4S.9 ±3.1  ±2.6  D E R I V E D  mEq./Kgm. DRY WEIGHT Na.  5  MUSCLE  DATA  Total  Low Na, Low K Diet  Na  V  Total mEq/Kgm Water Tissue No., of -Tissue i n CI Water . Tissues CI Space  Total  Water  335.5 ±2.6  522.2  738.2 ±8.4  185.2  5  185.6 ±4,6  326.4 ±4.2  512.0  752.7 ±5.7  168.2  85.2 ±4.3  447.5 ±7.1  532.7 753.3  137.2  .127.9 ±10.1  480.7 ±9.3  608,6  118.2  159.6  174.2  496.6  91.3 ±0.9  149.7  251.9 ±6.2  107.0 • 136.5 ±4.6  K  ±3.2  K  DATA mEq./Kgm. INTRACELLULAR WATER  Cellular Water  Na  K  Total  ±3.2 ±8.5  14.6  134.1  604.1 ±14.1  46.7 ±5.8  145.4 ±8.1  182.1  5•  11.7 ±0.8  107.6 ±8.1  644.6 ±7.0  46.2  ±3.3  124.7 ±3.4  170.9  187.8  7  14.2 ±1.1  118.4 ±7.7  634.9 ±9.4  8.4 ±3.5  184.9 ±4.6  193.3  774.7 ±2,8  177.1  3  19.7 ±2.1  157.3  617.4  ±13.1  71.3 ±3.7  174.1 ±7.0  245.4  ±14.1  670.8  761.9  209.5  1  13.4  106.4  655.5  36.2  179.4  215.6  393.9 ±7.0  645.8  764.2 ±4.2  195.9  3  15.9 ±1.7  166.1 ±20.9  602.2 ±22.7  52.2 ±5.2  151.1 ±4.0  203.3  139.1 ±1.9  503.5 ±4.5  642.6  787.6 ±8.3  173.3  3  17.6 ±2.3  ±23.6  174.6  612.9 ±15.5  4.2 ±6.8  173.6 ±3.5  177.8  19.0 ±1.9  183.0 ±17.1  569.0 ±16.6  33.7 ±6.6  167.7 ±6.8  201.4  ±3,4  49.1 ±2.0  95.5 ±3.4  144.6  197.9 ±8.6-  384.8 ±8.9  582.7  752.0 ±3.7  192.3  4  1  58.0  97.9  155.9  245.0  413.7  658.7  763.3  204.2  1  15.9  158.6  604.7  55.6  161.6  217.2  Adrenalectomized + Normal Diet + Cortisone  3  48.6 ±0.7  94*7 ±0.6  143.3  575.3  750.7 ±3.2  190.9  3  22.8  ±5.9  204.8 ±6.2  545.9 ±7.2  26.9 ±1.2  172.4 ±1.8  199.3  Intact  2  48.6  86.2  134.8  681.7  797.0  169.1  2  28.7  268.1  528.7  11.3  160.9  172.2  Adrenalectomized + Low K Diet + Cortisone Intact + Low K Diet + Cortisone  + Normal Diet + Cortisone  4  - 195.0 380.3 ±5.6 ±1.4 258.8  422.9  -15T A B L E ABDOMINAL  mEq./Kgm. WET WEIGHT  Diet No. of Tissues  Na  K  Total  MUSCLE  D ATA  A N A L Y T I C A L Treatment and  VI  DE RIVED  mEq./Kgm. DRY WEIGHT  -Na  *  -Total mEq/Kgm Tissue •No. of -Tissue W,ater Tissues CI  -K  -Total  Water  176.7 ±6.0  323.9  500.6  741.8 ±4.0  174.2  7  3  DA T A -mEq./Kgm. INTRACELLULAR WATER  Water i n CI Space  Cellular Water  Na  K  18.7 ±1.3  170.9 ±11.9  573.5 ±11.6  31.3 ±5.3  144.4 ±5.1  175.7  ±3.2  19.9  173.0 ±26.7  577.8 ±24.0  46.8 ±6.2  125.5  172.3  Total  45.6 ±1.2  83.6 ±1.8  129.2  5  50.7 ±2.3  71.0 ±2.2  121.7  219.9 ±9.1  289.2 ±4.2  509.1  754.8 ±4.5  161.2  10  34.8 ±2.2  106.1 ±3.4  140,9  143.5 ±9.8  436.0 ±11.4  579.5  755.7 ±3.3  186.4  10  18.4 ±1.5  155.4 ±12.0  600.3 ±10.6  17.8 ±3.7  175.8 ±5.2  193.6  Adrenalectomized + Low K Diet  3  37.5 ±2.0  101.1 ±2.3  138.6  170.7 ±9.7  460.3 ±5.2  631.0  783.7 ±7.7  176.9  3  19.3 ±2.5  153.8 ±18.2  629.8 ±22.4  21.3 ±1.5  159.6 ±7.8  180.9  Adrenalectomized + Normal Diet  1  38.7  110.4  149.1  167.8  478.2  646.0  731.0  204.0  1  21,9  174.0  557.0  20.8  196.6  217.4  Adrenalectomized + Low K Diet + Adrenalin  3  50.6 ±1.0  77.9 ±0.2  128.5  226.1 ±3.2  350.9 ±1.0  576.8  776.2 ±1.3  165.6  3  21.4 ±1.2  230.9 ±19.7  545.2 ±19.1  32.1 ±2.7  132.6  164.7  Adrenalectomized + Normal Diet + Adrenalin  3  45.6 • 110.6 ±2.1 ±2.4  156.2  212.8 ±4.6  517.5 ±4.7  730.3  786.2 ±6.7  198.7  3  19.4 ±1.8  191.7 ±18.5  594.3 ±15.1  27.3 ±6.5  185.2 ±4.8  212.5  Adrenalectomized + Low K Diet + Cortisone  4  50.5 ±2.0  80.0 ±2.7  130.5  199.0 ±10.3  313.7 ±5.7  513.4  745.4 ±4.4  175.1  4  23.1 ±2.1  229.3 ±4.6  ±24.2  25.6  153.5 ±11.4  179.1  ±9.4  1  53.6  78.1  131.7  230,8  336.3  567.1  767.9  171.5  1  26.3  262.7  505.2  26.1  154.0  180.1  Adrenalectomized + Normal Diet + Cortisone  3  . 45.7 ±2.5  80.2 ±2.8  125.9  182.5 ±6.2  321.1 ±4.8  503.6  750.1 ±5.4  167.8  3  21.8 ±1.2  195.6 ±11.4  554.5 ±10.5  24.2 ±5.4  143.7 ±5.1  167.9  Intact + Normal Diet + Cortisone  2  48.8  95.1  143.9  232.6  445.6  678.2  788.1  182.6  2  27.5  271.9  516.2  10.0  182.1  192.1  Low Na, Low K  High Na, Low K  Control  Intact + Low K Diet + Cortisone  11  ±5.1  •  522.4  ±5.8  ±5.4  - 1 6 T A B L E  V I I  S-T 0 M A C H  A N A L Y T I C A L Treatment and Diet  mEq./Kgm. WET WEIGHT No. of Tissues  DATA  D E R I V E D  mEq./Kgm. DRY WEIGHT  Total mEq/Kgm Tissue No. of Water Water Tissues  mEq./Kgm. INTRACELLULAR WATER Water Tissue i n CI Space CI  Cellular Water  Na  K  Total  491.4 ±20.3  281.5 ±26.5  -46.3 ±16.6  233.0 ±26.7  186.7  52.3 ±0,4  493.2 ±26.5  294.8 ±17.5  U.3 ±30.6  235.6 ±26.4  246.9  7  55.2 ±3.3  473.3 ±36.7  310.7 ±35.3  252*6 ±23.4  181.3  174.5  3  61.1 ±0.8  489.4 ±4.8  305.8 ±2.6  14.0 ±18.3  206.6 ±2.5  220.6  766,5  187.6  1  60.8  487.4  482.5  -40.1  272.9  232.8  694.7  789.0 ±10.7  185.6  3  62.1 ±2.7  667.7 ±25.3  121.3 ±31.4  -237.7 ±100.1  572.9 ±169.0  335.2  707.1  801.5 ±4.0  175.2  3  59.3 ±0.4  586.7 ±3.0  214.8 ±7.0  -60.3 ±6.0  290.8 ±19.4  230.5  364.2 ±3.2  302.4 666.6 ±9.8  763.3 ±1.5  206.9  4  60.9 ±0.6  588.6 ±23.1  174.7 ±22.3  -91.6 ±45.2  425.1 ±56.9  333.5  165.5  417.8  383.6  701.4  787.1  210.3  1  59.0  588.6  198.5  -33.8  407.6  373.8  74.3 ±0.7  148.6  298.9 ±0.8  313.4 ±8.3  612.3  762.6 ±4.5  194.9  3  61.5 ±1.4  561.4 ±10.2  201.2 ±13.9  -94.2 ±28.3  363.7 ±21.4  269.5  52.3  119.2  336.6  254.7  591.3  804.3  148.2  2  63.3  602.4  201.9  -154.5  384.4  229.9  Total  Na '  K  Total  66.2 ±1.7  •123.8  239.5 ± 8.5  285.9 ± 7.4  525.4  765.0 ± 6.0  161.8  4  52.6 ±1.8  74.6 ±3.6  65.8 ±5.9  140.4  366.6 ±7.2  316.3 ±14.1  682.9  795.1 ±6.9  176.6  3  10  53.6 ±1.1  69.5 ±1.3  123.4  247.3 ±5.9  316.9 ±5.5  564.2  773.6 ±7.3  159.5.  Adrenalectomized + Low K Dmet  3  72.0 ±0.9  66.8 ±0.7  138.8  351.4 ±4.5  326.0 ±5.5  677.4  795.2 ±2.4  Adrenalectomized + Normal Diet  1  63.8  80,0  143.8  273.8  342.4  615.6  Adrenalectomized + Low K Diet + Adrenalin  3  83.8 ±3.6  62.6 ±2.1  146.4  397.7 ±3.3  297.0 ±5.1  Adrenalectomizeii + Normal Diet + Adrenalin  3  76.6 ±0.9'  63.8 ±1.8  140.4  385.9 ±6.0  321.2 ±7.8  Arenalectomized + Low K Diet + Cortisone  4  86.2 +1.0  71.7 ±2.7  157.9  1  83.9  81.6  3  74.3 ±2.7  2  66.9  Low Na, Low K Diet  High Na, Low K  Control  Intact + Low K Diet + Cortisone Adrenalectomized + Normal Diet + Cortisone Intact + Normal Diet + Cortisone  •Na  K  57.6 ±2.4 .  5  10  DATA  71.3 ±10.4  -17TABLE  VIII  •DUODENUM  ANALYTICAL Treatment and Diet  MEq./Kgm. WET WEIGHT -No. of Tissues -Na  Low Na, Low K  11  DATA  DERIVED  mEq./Kgm. DRY WEIGHT Total  K  Total  54.7 93.7 ±1.8 :'±1.3  148.4  233.2 ±5.1  403.6 ±7.7  636.8 769.0 ±2.8  193.0  4  37.7 ±1.1  352.4 ±13.4  Na  K  Total mEq/Kgm Water Tissue No. of -Tissue in CI Cellular CI Space Bater -Water Water Tissues  DATA mEq./Kgm. INTRACELLULAR WATER Na  K  Total  413.9 ±14.8  8.4 ±10.9  221.9 ±9.1  230.3  5  51.9 ±2.2  80.1 ±1.4  132.0  250.4 ±3.5  395.9 ±4.4  646.3 788.9 ±2.7  167.3  3  27.3 ±2.0  244.7 ±12.1  534.4 ±11.5  36.9 ±0.4  154.4 ±0.5  191.3  10  52.3 ±1.5  92.4 ±2.3  144.7  232.0 ±6.1  409.6 ±7.8  641.6 774.2 ±4.6  186.9  5  41.2 ±0.7  348.6 ±18.4  425.9 ±16.0  8.5 ±8.8  216.7 ±15.2  225.2  Adrenalectomized + Low K Diet  3  57.4 ±2.2  94.2 ±8.6  151.6  281.8 ±3.4  461.7 ±8.6  743.5 796.2 ±3.2  190.4  3  41.0 ±1.8  328.3 ±7.9  467.9 ±10.7  13.7 ±3.5  197.6 ±11.3  211.3  Adrenalectomized + Normal Diet  1  40.7 115.6  156.3  189.2  537.7  726.9 785.0  199.1  1  35.5  281.9  503.1  -6.6  226.8  220.2  Adrenalectomized + Low K Diet + Adrenalin  3  64.5 91.8 ±1.6 ::±2.1  156.3  320.8 ±2.1  456.2 ±8.2  777.0 798.9 ±2.2  195.6  3  45.1 485.3 " ±5.8 ±66.4  313.6 ±20.3  -59.7 ±39.8  313.1 ±58.7  253.4  59.0 111.3 ±1.8 ±4.3  172.3  299.1 ±7.0  563.4 ±4.9  862.5 802.4 ±7.9  214.7  3  39.5 ±8.8  390.2 ±8.9  412.2 ±4.5  1.9 . 267.6 ±5.4 ±10.8  265.7  High Na, Low K  Control  Adrenalectomized + Normal Diet + Adrenalin  3  Adrenalectomized + Low K Diet + Cortisone  4  63.5 103.4 ±1.7 ±2,0  166.9  257.9 ±5.6  420.4 ±7.1  678.3 754.1 ±1.4  221.3  4  42.7 ±2.1  411.5 ±12.7  342.7 ±12.2  -7.4 ± 1.7  301.2 ±14.5  293.8  Intact + Low K Diet + Cortisone  1  57.7 103.4  161.1  281.1  503.7  784.8 794.8  202.7  1  36.4  362.7  432.1  4.4  238.1  242.5  Adrenalectomized + Normal Diet + Cortisone  3  62.7 113.6 ±2.9 ±3.1  176.3  252.7 ±6.8  458.1 ±4.0  710.8 763.8 ±2.1  230.8  3  44.6 ±3.7  409.1 ±24.5  354.6 ±24.0  19.7 ±6.3  318.4 ±29.9.  338.1  Intact + Normal Diet + Cortisone  2  69.4 104.1  173.5  376.5  548.5  82§.0 808.3,  214.6  2  44.7  421.4  386.8  7.5  267.7  275.2  -18 TABLE  IX  ILEUM  ANALYTICAL Treatment and Diet  DATA  DERIVED  mEq./Kgm. WET WEIGHT mEq.'/Kgm. DRY WEIGHT No. of Tissues  Na  K  -Total  Na  K  Total  DATA mlSq./Kgm.  Total aEq/Kgm Water No. of Tissue in CI Cellular Tissue .* CI Space Water Water Tissues Water  INTRACELLULA1* WATER Na  K  Total  Low Na, Low K  8  54.3 ±2.9  ;.'85.6 ±1.0  139.9  193.0 ±9.8  307.2 ±6.7  510.2  723.1 193.5 ±6.1  5  32.5 ±1.8  291.2 ±9.4  424.5 ±5.9  34.1 ±9.8  200.7 ±6.9  234.8  High Na, Low K  5  51.7 ±1.8  84.6 ±1.5  .136.3  311*4 ±9.8  334.8 ±7.0  546.2  754.7 180.6 ±7.5  4  32.6 ±2.4  293.3 ±13.8  460.5 ±21.5  15.0 ±4.5  181.8 ±9.6  196.8  Control  5  58.2 ±1.9  90.9 ±2.9  149.1  261*5 ±7.4  407.8 ±11.5  669.3  777.1 191.9 ±5.0  5  34.4 ±2.8  322.3 ±27.3  474.8 ±30.5  23.4 ±5.1  192.7 ±17.1  216.1  Adrenalectomized + Low K Diet  3  59.0 ±1.8  98.2 ±1.7  157.2.  284.6 ±1.6  474.6 ±9.2  759.2  792.8 198.3 ±5il  3  34.8 ±0.8  278.9 ±6.8  513.9 ±5.7  30.2 ±5.7  188.0 ±2.3  218.2  Adrenalectomized + Normal Diet  1  53.6  104.1  157.7  270.9  474.9  745.8  780.9 201.9  1  51.9  411.4  369.5  -26*8  276.0  249.2  Adrenalectomized * Sow K Diet + Adrenalin  3  69.1 ±0.1  89.4 ±4.1  158.5  354.1 ±9.3  457.5 ±7.7  811.6  804.9 196.9 ±3.9  3  46.3 ±1.1  482.5 ±3.9  322.4 ±1.6  -28.2 ±1.1  273.8 ±14.0  245.6  Adrenalectomized + Normal Diet + Adrenalin  3  65.0 ±2.0  102.8 ±1.8  167.8  312.7 ±8.9  494.8 ±4.7  807.5  792.4 211.8 ±2.6  3  37.1 ±4.1  366.8 ±41.1  425.6 ±42.1  14.3 ±6.5  '244.3 ±25.7  258.6  Adrenalectomized + Low K Diet + Cortisone  4  59.8 ±2.1  95.4 ±1.1  155.2  216.6 ±8.9  345.6 ±4.8  562.2  723.9 214.4 ±2.1  4  34.3 ±1.8  333.6 ±13.2  390.3 ±11.8  12.1 ±2.9  243.9 ±10.2  256.0  Intact + Low K Diet + Cortisone  1  58.9  99.2  158.1  249.6  420.1  669.7  763.9 207.0  1  34.9  348.7  415.2  12.5  238.0  250.5  Adrenalectomized + Normal Diet + Cortisone  3  60.2 ±0.8  108.3 ±0.9  168.5  225.0 ±3.1  404.6 ±7.9  629.6  732.3 230.8 ±6.1  3  35.1 ±1.3  314.8 ±10.9  417.4 ±13.2  19.7 ±6.4  257.4 ±7.4  277.1  2  62.9  96.2  159.1  288.1  429.1  717.2  773.0 205.8  2  40.9  386.6  386.4  4.1  248.9  253.0  Intact + Normal Diet + Cortisone  -19T A B L E LARGE  A N A L Y T I C A L Treatment and Diet  mEq./Kgm. WET WEIGHT No. of Tissues  Na  K  Total  X  I N T E S T I N E  DATA  DERIVED  mEq./Kgm. DRY WEIGHT  Na  K  Total  Total mEq/Kgm * Tissue No. of Tissue Tissues CI Water Water  DATA mEq./Kgm. INTRACELLULAR WATER  Water i n CI Space  Cellular Water  Na  K  Total  11  50*9 ±1.1  84.4 ±2.0  135.3  206.4 ±4.9  342.2 ±9.2  548.6  752.7 ±5.5  179.6  4  34.6 ±1.9  322.1 ±15.0  432.3 ±14.2  6.5 ±17.2  187.2 ±13.1  193.7  5  53.1 ±1.0  82.5 ±1.4  135.6  216.0 ±5.6  336.0 ±6.2  552.0  751.8 ±8.6  180.4  3  44.8 ±1.3  401.9 ±2.4  347.9 ±20.4  20.7 ±2.1  227.3 ±16.1  228.0  10  52.5 ±2.3  91.0 ±2.6  143.5  223.6 ±9.5  386.7 ±8.7  610.3  756.4 ±8.4  189.7  4  40.1 ±2.5  351.9 ±31.8  413.9 ±36.5  5.5 ±8.9  234.2 ±31.1  239.7  Adrenalectomized + Low K Diet  3  57.9 ±1.5  89.3 ±2.0  147.2  307.3 ,±1.4  474.5 ±7.9  781.8  811.7 ±5.3  181.3  3  37.1 ±1.0  297.3 ±5.2  514.5 ±3.6  22.7 ±5.3  170.1 ±1.2  192.8  Adrenalectomized + Normal Diet  1  45.2  102.6  147.8  235.7  535.0  770.7  808.2  182.9  1  36.0  285.2  523.0  1.3  193.3  194.6  Adrenalectomized + Low K Diet + Adrenalin  3  77.9 ±0.5  84.8 ±2.3  162.7  400.2 ±10.5  434.8 ±10.2  835.0  804.9 ±4.4  202.1  3  42.6 ±2.7  459.5 ±38.9  345.4 ±36.4  9.4 ±15.2  246.8 ±17.9  256.2  57.3 ±1.1  98.2 ±3.9  155.5  287.2 ±8.0  517.5 ±6.7  804.7  801.5 ±2.6  194.0  3  39.0 386,0 415.4 ±2.0 . ±21.3 ±23.7  -4.2 ±6.4  235.9 ±19.3  231.7  4  67.5 ±1.6  93.2 ±1.0  160.7  263.4 ±5.1  372.5 ±2.6  635.9  747.5 ±3.1  215.0  4  41.4 ±1.4  399.3 ±13.4  348.2 ±10.5  47.5 ±8.5  266.4 ±6.4  313.9  1  70.2  85.0  155.2  248.0  300.3  548.3  716.8  216.5  1  33.4  333.8  383.0  49.1  220.9  270.0  3  54.8 ±1.5  92.6 ±0.5  147.4  201.0 ±8.5  381.3 ±7.1  582.3  760.4 193.8 ±2.9  3  32.1 ±1.0  332.6 ±12.6  427.8 ±9.7  -14.2 ±4.5  213.6 ±5.6  199.4  2  60.5  90.3  150.8  284.8  426.7  711.5  787.8  2  39.9  378,4  409.4  -0.1  218.9  218.8  Low Na, Low K i i High Na, Low K i •  Control  Adrenalectomized + Normal Diet + Adrenalin Adrenalectomized + Low K Diet + Cortisone Intact + Low K Diet + Cortisone Adrenaleo t omi zed + Normal Diet + Cortisone Intact + Normal Diet + Cortisone  3  191.4  - 2 0 T. A B L E  XI  RECTUM  -ANALYTICAL Treatment and Diet  mEq./Kgm. WET WEIGHT No. of Tissues  DATA  DERIVED  mEq./Kgm. DRY WEIGHT  Total mEq/Kgm Water Tissue No. of Tissue in CI Cellular CI Water Water Tissues ,Space i Water  K  Total  414.6 ±20.9  43.1 ±6.0  196.4 ±14.6  239.5  274.4 ±18.5  478.3 ±18.5  43.7 ±3.9  173.4 ±7.5  217.1  41.5 ±1.4  359.1 ±23.7  417.0 ±27.7  12.6 ±8.4  230.1 ±20.2  242.7  3  35.6 ±1.4  284.9 ±7.5  514.8 ±14.7  36.8 ±7.5  180.5 +8.4  217.3  801.4 195.0  1  26.2  207.4  594.0  49.8  157.1  206.9  444.6 806.9 ±5.0  807.7 192.0 ±4.5  3  ±1.6  44.4-  478.9 ±28.4  328.8 ±24.0  -23.4 ±15.3  259.1 ±12.7  235.7  346.1 ±10.8  499.6 845.7 ±6.7  816.4 190.0 ±6.9  3 • 40.8 ±1.7  403.1 ±16.8  413.3 ±13.8  -3.5 ±4.3  219.5 ±7.3  216.0  159.5  273.1 ± 8.0  347*8 620.9 ±5.8  742.7 214.8 ±9.5  3  36.2 . 303.1 ±6.8 ±18.4  439.6 ±26.8  46.8 ±0.6  204.2 ±16.5  251.0  117.2  196.6  325.9  481.5 807.4  756.5 259.9  3  28.1  280.7  475.8  76.1  245.5  321.6  108.6 ±2.5  171.6  252.2 ±4.0  434.0 686.2 ±3.5  749.8 228.9 ±7.6  3  39.0 ±1.3  349.8 ±13.9  399.9 ±10.5  13.4 269.2 ±4.7 • ±9.5  282.6  439.1 769.7  798.8 192.0  2  45.3  425.4  373.4  33.0  273.1  K  Total  K  Total  11  61.2 ±1.0  80.7 ±1.4  141.9  229.3 ±7.3  346.5 ±7.9  575.8  767.4 184.9 ±10.0  4  37.4 ±2.1  349.1 ±19.7  5  58.1 ±3.4  75.4 ±4.4  133.5  264.1 ±6.0  342.2 606.3 ±3.2  780.0 171.2 ±11.6  3  31.2 ±2.2  10 •  56.1 ±1.9  91.5 ±2.4  147.6  245.8 ±8.8  395.5 ±7.3  641.3  773.6 190.8 ±4.5  4  Adrenalectomized + Low K Diet  3  63.3 +2.1  93.8 ±2.3  157.1  334.1 ±6.8  498.6 832.7 ±7.1  799.7. 196.4 ±16.5  Adrenalectomized + Normal Diet  1  61.9  94.4  156.3  311.8  475.3 381.4  Adrenalectomized * Low K Diet + Adrenalin  3  69.6 +1.0  85.5 ±2.8  155.1  362.3 ±8.9  Adrenalectomized + Normal Diet + Adrenalin  3  63.4 +0.1  91.7 ±3.0  155.1  Adrenalectomized + Low K Diet + Cortisone  3  70.1 ±1.3  89.4 ±1.9  Intact + Low K Diet + Cortisone  1  79.4  Adrenalectomized + Normal Diet + Cortisone  3  63.0 ±1.5  High Na, Low K  Control  Intact + Normal Diet + Cortisone  MEq./Kgm. INTRACELLULAR WATER  Na  Na  LowNa, Low K  DATA  Na  -  2  65.3  88.1  153.4 a  330.6  235.1  - T A B L E  X I I  L I V E R  A N A L Y T I C A L Treatment Diet  and  mEq./Kgm. WET No. o f Tissues  Low  High  Na, Low K  Na, Low K  Na  •K  WEIGHT  -Total  D A T A mEq./Kgm. DRY  Na  K  D E R I V E D WEIGHT  -Total  *  -Water  Total mEq/Kgm Tissue Water  No. o f Tissue CI Tissues  Water, in C I Space  D A T A mEq./Kgm. INTRACELLULAR WATER  Eellular Water  Na  K  Total  10  36.5 ±1.6  100.5 ±4.4  137.0  122.7 ±5.4  325.0 ±7.5  #47.Ti 702.3 ±7.7  195.1  6  29.1 258.9 ±1.0 ±10.6  441.2 ±11.7  -6.4 ±5.9  241.1 ±15.5  234.7  5  36.5 ±2.3  88.9 ±2.8  125.4  128.3 ±5.2  310.0 ±7.9  438,3 713.8 ±3.5  175.7  3  27.6 ±0.1  263.1 ±22.3  445.3 ±24.0  -7.7 ±0.8  207.9 ±1.3  200.2  *  34.9 ±1.0  80.8 ±2.9  115.7  122.8 ±3.7  288.7 ±8.0  411.5 715.2 ±3.6  161.8  8  2925i ±1.2  352.6 ±8.1  463.3 ±8.1  -10.1 ±2.1  176.2  166.1  99.2 ±0.7  138.0  152.3 ±4.2  391.1 ±12.8  543.4 745.8 ±9.7  185.0  3  23.1 ±1.4  185.0 ±711  560.1 ±16.9  18.0 ±3.0  175.5 ±6.1  193.5  3  38.8 ±2.5  Adrenalectomized + Normal Diet  1  52.6  100.4  153.0  196.4  374.8  571.2 769.1  198.9  1  25.0  198.2  570.9  38.0  173.6  211.6  Adrenalectomized + L o w K Diet + Adrenalin  3  46.1 ±0.6  101.1 ±3.4  147.2  185.3 ±6.8  406.1 ±7.0  591.4 750.8 ±9.2  196.1  3  22.4 ±3.0  241.2 ±32.1  509.6 ±30.5  13.4 ±13.2  198.7 ±10.2  212.1  Adrenalectomized + Normal Diet + Adrenalin  3  47.4 ±0.8  110.5 ±5.2  157.9  194.3 ±5.1  452.0 ±1.2  646.3 755.5 ±11.1  209.0  3  25.4 ±3.2  251.0 ±32.8  504.6 ±30.9  17.3 ±8.0  219.5 ±16.9  236.8  Adrenalectomized + L o w K Diet + Cortisone  4  51.6 ±3.1  106.5 ±1.3  158.1  156.4 ±8.0  326.4 ±9.9  482.8 669.7 ±15.1  236.1  4  28.6 ±3.2  274.1 ±27.0  398.6 ±34.0  13.9 ±4,6  272.3 ±23.9  286.2  1  36.6  102.1  138.7  133.4  371.9  505.3 725.5  191.2  1  20.4  203.5  522.0  10.2  195.0  205.2  3  50.6 ±0.2  98.6 ±1.6  149.2  159.2 ±6.2  309.4 ±6.1  468.6 680.8 ±11.2  219.2  3  24.5 ±0.8  223.3 ±2.0  457.6 ±10.3  30.3 ±2.4  214.4 ±8.3  244.7  2  47.2  111.0  157.2  179.2  429.6  608.8 736.7  213.4  2  20.2  189.1  547.6  31.2  201.9  233.1  Control  Adrenalectomized. + L o w K Diet  Intact + L o w K Diet + Cortisone Adrenalectomized + Normal Diet + Cortisone Intact + Normal Diet + Cortisone  10  T Fl ,c 90it  .  80it  . •  <  ire f )N *M•  6  )F  !  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C A S T M - l r j n T S T l N i ^ L T R A C T  70  CHIUTX  Figure: I  60  50  -d •5 40  3  i  ro vn i  « 30  -*rl  •2 20  Oej-ici +i  ^drewilect  Adrermled.  COMIfflL  10  Diet  20-36  20-33  20-58  ! Diet  21-20 20-55  TIME  +K Defic Gjrusatje Adrwalect —jtonoa^ Diet Cortisboe iCortuioae  24-41 22-1220-53  (MmuCes - Seconds)  226  19 • £  ZZ-15  - 26 D.  Limits and Sources of Errors  The magnitude of changes observed i n the tissue sodium and potassium content greatly exceeded the possible sources of errors i n chemical determination, or i n procurement of specimens*  In the case of the chloride  determination, there vas less agreement i n duplicate samples, but this error was random and probably would not significantly alter the results. The use of the chloride ions for the determination of extracellular space i s questionable (Amberson et a l , '38, Manery and Hastings, '39, Crismon et a l , k3 1  and Conway, h£)* %  9  As yet there i s no ideal chemical  available for determining extracellular space.  The boundaries and nature  of the extracellular space are s t i l l poorly defined. The mechanism of movements of electrolytes from extracellular space into the cells are based on hypothesis rather than unequivocal proof. The influences of hormonal imbalance and alteration of water retention on the extracellular f l u i d i s even less clearly understood.  Recently White et a l , 'J>S>> have studied the  influence of adrenalectomy on extracellular f l u i d .  These workers concluded  that current methods for determining extracellular f l u i d i n vivo are not sufficiently accurate to permit comparison of total intra- and extracellular electrolytes before and after adrenalectomy.  Although the derived  data of Section I and II were recorded, no attempt was made to interpret these results.  As a result of the i n a b i l i t y to derive any secure informa-  tion concerning the intracellular concentration of electrolytes, one i s faced with the task of obtaining alterations i n the total tissue electrolytes that are significantly different i n order to give some demonstration of the effects of various experimental procedures*  Oroil man,  'f?U, has per-  formed chronic experiments on adrenalectomized dogs and obtained significant changes i n the total tissue electrolytes*  These changes were not  - 27 dependent on any assumption regarding the coincidental changes i n the relative volumes of the extracellular and cellular compartments based on chloride determinations. Another possible source of error is.the variable fat content of the tissues. However, even after several extractions with ether and other "fat" solvents, some l i p i d residue remains. This i s because the i n d i v i dual members of the l i p i d group show large individual variations i n their solubility (Hawk et a l , '1*8). Substances like cholesterol, and compound l i p i d s , like the phospholipids, glycolipids, would be extracted as well as neutral fats. These substances form an intricate part of the tissue structure*  Removal of these substances may introduce a greater error i n elec-  trolyte determination than i s present by including the small amount of neutral fat that may remain with the tissue after the macroscopically visible fat, i f any, has been.removed*  Cotlive et a l , '51}  have done fat  determinations on skeletal tissues of potassium deficient and control animals and found the total fat extract to be less than one percent*  Thus  the fat content of the tissues analysed was not considered to be an important factor i n causing an error i n the results. The blood content of the tissues may be a source of incorrect estimation of the electrolyte values. However, there i s no simple accurate technique available for carrying out tissue blood determinations. Manery et a l , '38, and Gardner et a l , '50, have reported that i n animals which were decapitated, or as i n the present study, bled by heart puncture, many tissues do not contain a measureable amount of blood*  Blood determinations  were not carried out on the tissues i n the present investigation* The question arises as to whether the low potassium diets may be so poorly palatable as to lead to starvation*  Evidence against this possibility  - 28 i s seen i n the weight charts. The control animals on the diet with added potassium had normal weight gains. While the animals on low potassium diets did not gain weight,none of the animals involved showed a marked loss of weight. The weights of the diets consumed were recorded at regul a r intervals, but due to loss of diet from the cages, the recordings were not accurate. Though the animals on the low potassium diet became anorexic towards the latter portion of the experiments, there was a continued consumption of the diet.  - 29 -  Section  I  EFFECT OF DIETARY CATION CHANGES ON THE ELECTROLYTES OF SELECTED TISSUES OF THE BODY  Results 1, Effect of Diet on the Weight of the Animals The animals were studied at a stage of development normally accompanied by active growth (Controls, Figure I ) . This weight gain was completely prevented by placing the animal s on a low potassium diet, whether the sodium content of the diet was restricted or increased (Figure I).  Addition of 0*15 percent potassium chloride to the low potassium diet  resulted i n restoration of the growth curve to a normal pattern*  2. Effect of Diet on Gut Motility Animals on a low sodium, low potassium diet showed a highly s i g n i ficant decrease (ii3«2 percent) i n their gut motility as compared with the controls (69,8 percent) (Table II and Figure 17)*  The animals on a high  sodium, low potassium diet showed no significant difference i n the motility (67*0 percent) compared with the controls*  There was a significant  difference between the gut motility of the animals on a low sodium, low potassium diet and the animals on a high sodium, low potassium diet*  3. Electrolyte Analyses a) Plasma Electrolytes From Table 17, i t can be seen that alterations i n the electrolyte content of the diet had no effect on the sodium levels of the plasma* The potassium and chloride levels were significantly lowered i n the rats fed  low sodium low potassium, and high sodium low potassium diets as compared with the controls.  There was no significant difference between the potas-  sium and chloride levels of either group of rats on the low potassium diets*  The plasma electrolytes of the controls and the potassium deficient  animals are i n agreement with the results reported by Schwartz, *53> and others*  Therefore altering sodium Intake had no significant effect on the  sodium, potassium or chloride levels of plasma, b) Skeletal Muscle Electrolytes Skeletal Muscle of the Control Animals Significant differences were observed i n the content of the various electrolytes when skeletal muscle from the thigh was compared to that of the abdomen (Table 7 and VI).  The  abdominal muscle contained more sodium (3b.8 mEq. per Eg. wet weight) and less potassium (107.1 mEq. per Eg. wet weight) than the thigh muscle (23.7 mEq. per Eg. sodium wet weight and 117.8 mEq. per Eg.,potassium wet weight). The abdominal muscle also contained a significantly higher level of chloride ions.  This may be due to a higher content of chloride-rich tissue i n the  abdominal muscle. The ionic pattern of the control thigh muscle was i n general agreement with that reported by Lovry et a l , 'li2, Darrow, '2(6, and Muntwyler et al,'50. The difference between our data and that of other workers was no greater than has been shown to exist between controls of different strains of animals of different ages (Lowry et a l , U2). !  Effect of Altering Sodium and Potassium Intake on Skeletal Muscle In addition to their i n i t i a l differences i n ionic patterns, the electrolyte content of thigh and abdominal muscle differed i n the degree of alteration produced by changes i n electrolyte intake.  On decreasing the  potassium intake of the rats, approximately 30 percent of the i n i t i a l potassium content of the tissues was lost and was only partially replaced  by sodium i n both the abdominal and thigh muscle as has been reported by several workers (Heppel, '39, Conway et a l , '1*8). The shift was quantitatively different for the two muscle samples*  The thigh muscle exchange  was 25*2 mEq* per Kg. sodium increase for a 30 mEq. per Kg. potassium decrease.  In the abdominal muscle, the content of sodium uptake i n exchange  for potassium loss was even less complete (10.8 for 22*5).  As shown by  Holiiday, '55* an increase i n sodium ingestion accentuated the muscle changes produced by potassium deficiency. However, the increase i n sodium intake did not affect skeletal muscle uniformly. The exchange of sodium for potassium i n the thigh muscle was 22.2 for 37.1, values which are not significantly different from those found with a low sodium intake. The abdominal muscle sodium:potassium exchange-ratio was 15»9:22.E>«  For the  same degree of potassium loss, the sodium uptake was significantly i n creased. The voluntary muscle of the body did respond to a potassium deficiency regardless of the amount of sodium intake. However, the electrolytes of skeletal muscle from different parts of the body responded differently when the electrolyte intake was altered.  The thigh muscle, which had more  potassium i n i t i a l l y , experienced a greater potassium depletion i n response to a potassium deficiency, than did abdominal muscle, and also a correspondingly greater sodium intake. However, when the dietary sodium was increased, an altered degree of sodium - potassium exchange was found i n the abdominal muscle, rather than the thigh muscle. These differences between muscle of thigh and abdominan were largely^ due to differences i n the proportion of extracellular material which they contained since shifts i n c a l culated cellular electrolytes were more nearly identical i n the two muscles than shifts i n tissue electrolytes.  - 32 c) Qastro-Intestinal Tract Electrolytes Electrolytes of Hats on Control Diet  The data presented i n Tables  VII to XI indicate that the electrolyte and the water content of the various segments of the gastro-intestinal tract responded differently to the dietary regimes and were also different from striated muscle. The total electrolyte content, per kilogram of wet weight of various segments of the gut i n the control animals with the exception of the stomach, i s approximately the same* The concentration of cations i n the stomach was lower than the rest of the gut, possibly as a result of removal of the mucosa* With the exception of the stomach, the various sections of the intestinal tract contained a higher total concentration of electrolytes than striated muscle; the ileum showing the highest concentration*  This  high tissue electrolyte concentration i s due to the low content of nonelectrolyte -containing solids, since calculated i n terms of mEq* per kilogram tissue water no differences between striated muscle and gut are observed*  The sodium concentration per kilogram wet weight of gastro-  intestinal tract was approximately the same ($2.3 - 58.2 mEq. per k i l o gram) throughout the gut, with the duodenum containing the highest concentration.  In contrast, striated muscle had a lower and more variable  sodium concentration, (thigh muscle, 23*7 mEq*, abdominal muscle 3U.8 mEq. per kilogram wet weight).  The potassium levels per kilogram wet weight of  various portions of intestinal tract were quite uniform (90.5 - 92.U) except for stomach which contained a markedly lower content of potassium (69.5).  From these data i t i s not possible to decide whether stomach  smooth muscle actually contains less potassium than other intestinal muscle or i f the mucosa generally possesses a high potassium content. The striated muscle had a higher and more variable potassium content (117.8  - 33 mEq* per kilogram i n thigh muscle and 106.1 mEq. per kilogram i n abdominal muscle)* Effects of Low Potassium, Low Sodium Diet Alterations i n Sodium  On placing idle animals on a low sodium, low  potassium diet, there was no significant change i n the sodium content (59*0 - 61.2 mEq* per kilogram wet weight) of the stomach, duodenum, large intestine or rectum, but there was a significant decrease of sodium,in the ileum*  This response i s i n marked contrast to the striated muscle which  showed a highly significant increase i n sodium content i n the presence of potassium deprivation. Alterations In Chloride  Tissue chloride was significantly decreased  i n the duodenum and large intestine, but unaffected i n other regions of the bowel* Alterations i n Potassium.  The potassium levels i n the gut.of the  animals on a low sodium, low potassium diet did not change i n stomach muscle or duodenum* There was a significant decrease of potassium i n the ileum, large intestine and rectum; the ileum having the greatest decrease* The decrease i n potassium content of i l e a l tissue, unlike that of large intestine and rectum, was not accompanied by a decrease i n cellular potassium levels since there was a marked cellular dehydration. The de- , crease i n potassium i n these tissues was significantly smaller (approximately eight percent of the i n i t i a l value) than was shown to occur.in the striated muscle (approximately 30 percent)* . Thus the various segments of the gastro-intestlnal tract responded differently when the diet was low i n both sodium and potassium*  The elec-  trolyte pattern of the upper portion of the intestinal tract (stomach muscle and duodenum) was not affected despite changes i n motility* The  lower portions of the bowel had potassium loss, but i n contrast to skeletal muscle, there was no corresponding sodium uptake.  The ileum was unique i n  that although i t lost both sodium, potassium and water, these changes i n tissue electrolyte concentrations were not accompanied by similar changes i n calculated cellular electrolyte concentrations. Effects of-High Sodium, Low Potassium Diet Alterations in, Sodium  On placing the rats on a high sodium, low  potassium diet there was a highly significant increase i n the sodium content of the stomach (366.6 mEq. per kilogram) compared to the controls (21*7.3 mEq. per kilogram), and to the animals on low sodium, low potassium diet (239.5 mEq. per kilogram). The duodenum showed some increase of sodium content i n terms of tissue dry weight (250.1i mEq. per kilogram) as compared to the controls (232.0 mEq. per kilogram) and the animals on the low sodium, low potassium diet (233*2 mEq* per kilogram). The high sodium, low potassium intake had no significant effect on the sodium level of the large intestine or rectum as compared to the controls. However, the sodium content did tend to be higher per kilogram dry weight than i n animal a with dietary, restrictions of both sodium and potassium.  There was  a decrease i n the sodium content of the ileum, indicating that increasing the dietary sodium content did not prevent the decrease i n sodium which potassium depletion had produced.  Thus the ileum was unable to retain i t s  sodium content i n the presence of a potassium deficiency regardless of the level of sodium intake. Alterations i n Potassium  The potassium levels i n the duodenum of the  rats on a high sodium, low potassium diet decreased so that now the duodenum as well as more anal regions became deficient. i n the stomach muscle.  Again there was no change  It should be recalled that these tissues were as  - 35 motile as controls i n spite of their potassium loss* In summary, i n rats subjected to dietary potassium deficiency, the stomach and duodenum showed no change i n ionic pattern when the sodium intake was also restricted*  Ileum, large intestine and rectum lost  significant quantities of potassium on both diets, but showed no increase i n sodium content* The ileum actually lost sodium on both diets*  No  relation between these changes and motility was apparent* d) Liver Electrolytes Gardner et a l , *J>0, and Heppel, *39, have shown that placing rats on a low potassium diet does not cause the l i v e r to lose potassium*  The  results i n Table XII shows that l i v e r potassium was actually increased i n our rats on a low potassium diet, even when the sodium content of the diet was high, and that a dietary decrease of both sodium and potassium caused a highly significant increase of potassium concentration (325*0 mEq* per kilogram dry weight) compared to the.controls (288*7 mEq* per kilogram dry weight)* Gardner et a l , '£0, reported a significant increase i n l i v e r sodium i n their potassium deficient rats*  Our results showed no significant  alteration i n the l i v e r sodium* Since the sodium levels did not alter, and the potassium levels were increased without an accompanying increase i n cellular water, the animals on the low potassium diet showed increases i n the total electrolyte content of the l i v e r per kilogram wet weight*  Thus placing an animal on a low  potassium diet caused a paradoxical increase In l i v e r potassium*  Section I I EFFECTS OF VARYING DIETARY ELECTROLYTE INTAKE, ADRENALIN AND CORTISONE ADMINISTRATION TO ADRENALECTOMIZED AND INTACT RATS  Results 1. Effect of Diet and Hormone Treatment on the Weight of Anlmal.B (Figure I to H I ) A l l adrenalectomized, hormone-treated animals were maintained on a high sodium intake, both from the diet (Table I) and from 0.9 percent 8odium chloride as the sole source of f l u i d intake* the maintenance of animals after adrenalectomy*  This was done to aid  Further, as was indicated  i n the intact animals, the high sodium intake can cause a greater alteration i n the tissue electrolytes during dietary potassium deprivation* The untreated adrenalectomized rats lost weight on a high sodium, low potassium diet, as well as on a control diet (Figure I I ) .  The adrenalin-  treated adrenalectomized rats on the control diet (Figure II) experienced a gain i n weight (+33.1 gm.) almost equal to the weight gain (approximately 37 gm.) of the intact control animals for the same period of time. A similar, though more variable effect was obtained i n adrenalin treated animals on low potassium intake.  Thus adrenalin was capable of producing  a weight gain i n the animals. Whether this weight gain i s due to normal growth or water retention w i l l be discussed (page  ). Both the intact and  adrenalectomized rats lost weight when treated with cortisone.  Among the  cortisone treated animals, the adrenalectomized animals on the low potassium diet, lost the least weight (-8.5 gm.), as compared with the intact animals on the control diet (-18.0 gnu), intact animals on low potassium diet (-20.0 gm.) and adrenalectomized rats on control diet («3L7*li gm.).  Therefore the results indicate that i n the dosages administered, adrenalin causes a gain i n weight whereas cortisone causes a weight loss*  2* Effect of Diet and Hormone Treatment on Gut Motility (Table II, Figure 17) Adrenalectomy  The gut motility of untreated, adrenalectomized  animals (57*5 percent) on a high sodium low potassium diet was not s i g n i f i cantly different from that of intact animals (67 percent) on the same diet. Thus the presence or absence of the adrenal glands had no significant effect on gut motility when a high sodium, low potassium diet was used. The decreased motility of the single, adrenalectomized animal on a normal diet may hare been due to i t s nearly moribund state. Adrenalin  Administration of adrenalin to adrenalectomized rats  reduced the gut motility as compared with other adrenalectomized rats not receiving hormonal treatment. Thus adrenalin, as might be expected from i t s inhibitory effects on intestinal muscle i n vitro, did not improve motility. Cortisone  Cortisone treatment decreased motility (26.1; - 22.8 per-  cent) i n both intact and adrenalectomized rats as compared with similar animals not receiving hormonal treatment. The decrease i n motility was the same for adrenalectomized and intact animals regardless of electrolyte content of diet.  Therefore i t appears that cortisone^ exerts a direct  action on the gastro-intestinal tract. 3. Effect of Diet and Hormone Treatment on Mortality (Table III) The adrenalectomized rats on a normal diet had the highest mortality*  - 38 The temperature of the animals' room was about 15° C. and this may have contributed to the limited survival of these rats.  Similarly the  adrenalectomized rats on a high sodium, low potassium intake had a tendency to die sooner and were therefore sacrificed earlier than the animals that were undergoing hormonal treatment.. The animals receiving adrenalin had a prolonged l i f e span compared to the untreated rats.  These animals also appeared to be more vicious and  vigorously resisted the subcutaneous injections of the adrenalin. The cortisone treated animals also had a prolonged l i f e span compared to the untreated rats.  These animals appeared quite docile and languid.  From the small series of rats used, i t i s not possible to say whether adrenalin or cortisone was capable of maintaining l i f e longer for adrenalectomized rats.  k*> Electrolyte Analyses a) Plasma Electrolytes (Table 17) A significant increase i n the plasma potassium and chloride levels occurred i n adrenalectomized animals i n spite of a high sodium, low potassium diet, but there was no change i n plasma sodium. Other workers (White et a l , '55) tomized rats.  have reported a drop i n plasma sodium i n adrenalec-  However, maintaining the animals on a high sodium diet and  on a 0.9 percent sodium chloride as drinking water, prevented the drop i n plasma sodium. Adrenalin i n adrenalectomized rats on a high sodium, low potassium diet caused an increase i n plasma sodium and a decrease i n plasma potassium and chloride compared with the plasma level of these ions i n the same diet. Exogenous adrenalin i n the adrenalectomized rats on a control diet had no  - 39 effect on sodium, but did cause a drop i n the potassium and chloride (Table IV) even below the levels found i n the intact rat. Therefore, adrenalin alone seemed to be capable of reversing the electrolyte changes of adrenalectomy (high potassium and chloride), and could stimulate the plasma electrolyte pattern of hypochloremic hypokalemic alkalosis* Cortisone i n the adrenalectomized rats caused a marked increase i n plasma sodium and a decrease i n potassium and chloride, compared with the corresponding values i n untreated adrenalectomized rats as well as intact rat8 on similar diets*  However, the reduction i n plasma potassium and  chloride with cortisone administration was much less marked i n animals fed adequate amounts of potassium. Cortisone i n the intact rats caused no increase i n plasma sodium, but reduced -the plasma potassium and chloride even more than i n the cortisone treated adrenalectomized rats.  Thus cortisone seemed to produce a greater  change i n the blood electrolytes i f -the adrenals were intact. In summary, both adrenalin and cortisone caused an increase i n plasma sodium and a decrease i n plasma potassium and chloride i n adrenalectomized rats on a high sodium, low potassium diet.  However, the sodium increase  was greater with cortisone and the chloride decrease was more significant when adrenalin was used, b) Skeletal Muscle Electrolytes The skeletal muscle was considered i n detail to provide a basis for comparison with the gastro-intestinal tract.  Also the effects of the  various procedures have been studied on skeletal muscle by other workers. Therefore these data permit a comparison of the status of these animals with those of other investigators who used similar conditions. Effects of Adrenalectomy Normal Diet  Due to the high degree of martality i n the group of  - ho adrenalectomized. animals on the control diet and the desire to avoid variation due to post-mortem changes, results from only one animal, are presented. The results are comparable to similar data for adrenalectomized rats reported by Darrow et a l , 'US. Adrenalectomy led to an increase of sodium and potassium content i n both abdominal and thigh muscle. The increase i n sodium (+89 mEq. sodium per kilogram dry weight) of thigh muscle was greater; than that of abdominal muscle (+2li.3 mEq. sodium per kilogram dry weight). The increase i n potassium i n the two muscles are not markedly different (thigh muscle U9.1 mEq. per kilogram dry weight potassium, abdominal muscle 1(2.2 mEq. per dry weight). Low Potassium Diet.  Since the untreated, adrenalectomized animals were  sacrificed only fourteen days after adrenalectomy, the question arose as to whether these animals had sufficient time for the potassium deficient diet to produce i t s effect.  In similarly-fed adrenalectomized rats, Darrow et  a l , '1(6, reported levels of 10.9 mM. sodium per 100 gm. and 1+7.0 potassium per 100 gm. of muscle tissue.  mM.  These workers sacrificed their  animals fourteen days after adrenalectomy, at which time the muscle of their intact animals did show the electrolyte pattern characteristic of potassium deficiency.  The results for thigh muscle shown i n Table V (12.8 mEq.  sodium per 100 gm. and h& mEq. potassium per 100 gm. dry weight of tissue) are similar to those of Darrow et a l . Thus adrenalectomy prevents the development of potassium deficiency i n muscle as well as i n plasma. The muscle and the plasma potassium of the adrenalectomized rats actually remained high instead, of the usual decrease seen on a potassium deficient diet.  The effects of adrenalectomy on plasma and muscle electrolytes were  not prevented by the diet.  The increase of muscle sodium was small compared  -ia with the concentrations found i n intact controls on a normal diet.  These  results are i n marked contrast to the intact animals on the low potassium diet where there was a highly significant increase of muscle sodium along with a marked decrease of potassium.  Thus both adrenalectomy and the high  sodium, low potassium diet tend to cause an increase i n muscle sodium. The failure of muscle sodium to be additively elevated, when these two experimental procedures are combined, remains unexplained. This situation contrasts with that of other tissues (gastro-intestinal tract, liver) where the anticipated additive effects were obtained. Effects of Replacement with Medullary and Cortical Hormones of the Adrenal Gland on Skeletal Muscle Adrenalin  A comparison of the muscle electrolyte levels i n adrenalin  treated adrenalectomized animals on a normal diet and on a low potassium diet, to those of intact animals on similar diets revealed that adrenalin was able to r estore the muscle electrolyte levels of adrenalectomized rats towards those of intact rats only i n the case of the rats on the potassium deficient diet.  In contrast, on a diet containing potassium there was no  marked correction of the abnormalities i n muscle electrolyte produced by adrenalectomy, with the exception of the sodium levels of the thigh muscle. In addition, adrenalin caused marked hydration of tissues i n the animals on a control diet.  Therefore adrenalin alone, without dietary alterations,  did not mobilize the excess potassium from tissues after adrenalectomy even though i t did produce hypokalemia.  It appears that adrenalin permits the  low potassium diet to exert i t s usual effeots on tissue potassium rather than i t s e l f directly altering tissue electrolyte levels. Cortisone  In the intact animals and the adrenalectomized animals,  regardless of diet, cortisone caused effects similar to the low potassium  - U2 diet i n untreated intact animals. In general, cortisone caused the skeletal muscle to have a smaller loss of potassium than was caused by the potassium deficient diet alone. The potassium depletion produced by c o r t i sone was not enhanced by the presence of a deficiency i n the diet and i s resumably a direct action of the hormone. There i s some indication that the presence of the adrenals interfered with potassium depletion by c o r t i sone. These experiments do not support the hypothesis that cortical hormones act simply by permitting the effects of a low potassium diet to be manifest. In summary, i t can be seem that both adrenalin and cortisone can alter the electrolytes of skeletal muscle.  Both hormones, i n the dosage  used, were incapable of correcting the water and electrolyte disturbances of adrenalectomy.  Cortisone, i n the dosage used, reduced the high plasma  and tissue levels of potassium seen after adrenalectomy to levels beneath those seen i n the intact control animals. Adrenalin reduced plasma potassium levels and enabled the low potassium diet to produce i t s usual depletion of tissue potassium. Cortisone duplicated these changes by a pharmacological action of i t s own independent of the diet, c) Qastro-Intestinal Tract Electrolytes (Table VII to XI) Effect of Adrenalectomy Control Diet  The data of the adrenalectomized animals on the control  diet are available for only one animal. This analysis i s presented i n the tables, but no attempt was made to evaluate the results. Low Potassium Diet  When compared with intact animals on the same  potassium deficient diet, adrenalectomy produced no further significant change i n the total electrolyte content or the tissue water levels of the stomach. Potassium deprivation after adrenalectomy caused a marked increase  i n the total electrolyte content per kilogram dry weight i n the remainder of the gastro-intestinal tract.  This effect i s similar to that seen i n  skeletal muscle under comparable circumstances. Actually there was a markedly greater increase i n total electrolytes i n the tissues aboral to the duodenum than i n the striated muscle. This increase i n total cations was quantitatively different i n the various portions of the intestines with the increase being lest i n the duodenum of the adrenalectomized rat (+97,2 mEq. per kilogram dry weight), as compared with the remainder of the intestines(213 - 229,8 mEq. per kilogram dry weight). In general, the tissue potassium content was relatively more elevated after adrenalectomy than was the sodium content, so that, i n spite of dietary restrictions, potassium depletion was prevented i n these tissues as i n striate muscle.  In summary, adrenalectomy showed no effect on the  stomach, prevented the depletion of tissue potassium by a deficient diet in those segments of the gastro-intestinal tract where i t had previously occurred, and elevated the sodium content of a l l segments except the stomach. Effects of Replacement with Medullary and Cortical Hormones of the Adrenal on Gastro-intestinal Tract Adrenalin Treated Adrenalectomized Rats  The adrenalectomized rats  treated with adrenalin, when compared with untreated adrenalectomized rats showed an increase of sodium i n the stomach, duodenu, ileum, large intestine and rectum, beyond that caused by adrenalectomy alone whether dietary potassium was restricted or not. As i n skeletal muscle, adrenalin treatment of adrenalectomized rats on a potassium deficient diet produced a decrease i n the potassium content throughout the entire gastro-intestinal tract, toward the levels seen i n intact rats on the same diet. The potassium depletion was not significant i n a l l cases and was not as great  - U i as that seen i n intact animals on the potassium deficient diet.  The  change i n potassium content was least i n the duodenum. Thus adrenalin caused a greater increase i n tissue sodium than was caused by adrenalectomy alone, and partially opposed the action of the potassium deficient diet, reducing the degree of tissue potassium depletion i n those portions of tiie gut where i t occurred. Thus, although adrenalin decreased the motility of the gastro-intestinal tract, i t did not produce a corresr ponding reduction i n potassium content. Cortisone Treated Intact Rats  When intact animals were treated  with cortisone, regardless of diet, there was an increase of sodium throughout the gastro-intestinal tract.  The potassium levels of a l l  portions of the gastro-intestinal tract (with the exception of the stomach) were increased to varying degrees.  This action of cortisone was not  accentuated by the low potassium diet (one animal). Thus i n the intact animal treated with cortisone, the gastro-intestinal tract (except f o r the stomach) was seen to have an opposite electrolyte shift to skeletal muscle, i n that cortisone decreased potassium content i n skeletal muscle but increased i t i n the gastro-intestinal tract.  Both skeletal muscle and  alimentary tract responded to cortisone i n characteristic responses regardless of dietary potassium intake. There was decreased gastrointestinal motility i n cortisone-treated animals even though the potassium content of the tissue was elevated. Cortisone Treated Adrenalectomized Animals  Cortisone administration  caused an alteration i n the electrolyte patterns of the gut, as compared with that of untreated adrenalectomized rats.  The sodium content of the  stomach increased, while the potassium levels In a l l tissues decreased toward normal values regardless of diet.  Though cortisone caused a  - k$ decreased i n i t s motility, the sodium and potassium content of the tissues of the gastro-intestinal treact was not reduced as compared with intact controls. In the cortisone treated adrenalectomized animals fed a potassium deficient diet, the gastro-intestinal tract contained less potassium than that of animals fed the control diet, hut not a l l the differences were significant.  In a l l segments, excpet duodenum and large intestine, the  reduction i n potassium content with cortisone treatment and deficient potassium intake was sufficient to lower the levels of that of intact control; animals on the same diet.  Similarly, i n a l l tissues except duo-  denum and rectum, tissue potassium after cortisone treatment and normal potassium intake was lowered to the levels observed i n intact control animals on the same diet.  Thus, i n the gastro-intestinal tract, c o r t i -  sone restored potassium levels of adrenalectomized rats to those found i n intact animals on comparable diets, except i n duodenum. On the potassium deficient diet, cortisone restored the sodium levels which had been elevated by adrenalectomy to those found i n intact controls i n this diet, except that the sodium level of the large intestine was not reduced to control values. On the control diets, sodium levels were reduced to normal by cortisone i n a l l tissues except stomach, i n which there was some residual elevation of sodium, and ileum, i n which the sodium concentration was depressed below control levels. The lack of relationship between potassium levels and motility was again indicated by the fact that cortisone produced extreme reductions i n motility irrespective of diet or the presence or absence of the adrenal gland, but did not correspondingly decrease the potassium levels of the gastro-intestinal tract. Furthermore, i n contrast to effects observed i n  -  16  *  skeletal muscle, the potassium deficient diet did have effects i n addition to those produced by cortisone alone*  In the gastro-intestinal tract of  adrenalectomized rats, cortisone partially restored the a b i l i t y of the various tissues to lose potassium when on a potassium deficient diet, i n addition to correcting most of the increases i n tissue potassium caused by adrenalectomy* d) Liver Electrolytes Effect of Adrenalectomy Adrenalectomy caused an increase of sodium and potassium i n the l i v e r as compared with intact animals on similar diets.  The greatest increase  occurred i n the animals on the control diet. Effect of Replacement with Individual Hormones of the Adrenal Gland Adrenalin Treated Adrenalectomized Rats  Adrenalin caused a s i g n i f i -  cant increase of l i v e r sodium and no change i n potassium content i n adrenalectomized animals on potassium deficient diets as compared with untreated adrenalectomized animals on the same diet.  Conversely, adrenalin  caused no increase i n sodium, but an increase of potassium i n the l i v e r of adrenalectomized animals on a control diet.  Adrenalin did not return  the liver cation levels to those of intact animals. further retention of cations.  In fact, i t caused a  It seems possible that adrenalin may reduce  potassium i n plasma i n animals on a control diet partially by depositing i t in liver.  Dury, »53» has previously shown that adrenalin i n proper amounts  can cause an increase i n l i v e r potassium. Cortisone Treated Intact Rats  When cortisone was administered to  animals with intact adrenals, there was a rise of both sodium and potassium in the l i v e r to levels above those seen i n untreated intact rats on ;t similar diets*  The interpretation of these electrolyte disturbances i s not  clear* Cortisone Treated Adrenalectomized Rats  Cortisone caused a dehydration  of the l i v e r i n adrenalectomized animals as compared with untreated adrenalectomized animals and intact animals on similar diets* effect on the dehydrating action of cortisone*  Thus diet had no  In relation to dry weight,  cortisone reduced the tissue potassium levels, which had been enhanced by adrenalectomy.  It did not reduce tissue sodium values*  Thus adrenalin alone intensified the l i v e r sodium and potassium retention caused by adrenalectomy.  In intact rats, cortisone caused a similar  increase of l i v e r sodium and potassium but caused a reduction of potassium and had no marked effect on sodium i n livers of adrenalectomized rats as compared with those of untreated adrenalectomized rats.  E * Discussion The basic problems initially proposed will be discussed in the light of the present results under the following headings t 1*  The role of the electrolytes in motility*  2m The comparison of the electrolyte changes in the gut with that of striated muscle and liver* 5o  The role of the hormones in the pattern of alterations of electrolytes seen in potassium and/or sodium deficiency* Bole of Electrolytes in Motility Limitations of the method of assessment of motility  The problem of  measuring the gastrointestinal motility of rats led to the investigation of various techniques of recording gat movement in vivo*  The balloon  recording devices (Gruber et a l , »35) and the intraluminal pressure devices (Qoigley et a l , '52) were found to give too great a variability in their results, i f results were obtainable* Other workers. (Chapman et a l , *50), have emphasised the great variation in results obtained with balloon techniques* Also the effect on motility of the introduction of a foreign object into toe fluid or semi-fluid contents of the small intestine is difficult to evaluate. The use of a mixture containing a high percentage of charcoal and acacia (Northup et a l , *52) also would introduce a large mass of foreign material into the alimentary tract* Furthermore, the absorptive properties of charcoal may have an adverse influence on the electrolyte levels of the gastro-intestinal tract* In our experiments a dilute solution of gentian violet was used to follow the movement of solutions through the gastro-intestinal tract* The gentian violet solution was analysed for sodium and potassium content and was found to be free of these ions*  Thus the results were not influenced by the introduction of exogenous  mm  ions in the test solution*  mm  The possibility exists that minor decreases  in the electrolyte content of the gut wall might be produced by uptake of water from or loss of ions into the dilute contents of the lumen. This effect would be restricted to those portions of the bowel which were transversed by the dye solution*  It i s not expected that the magnitude  of these changes would be appreciable* Since the same solution was used in test and control animals, the composition of this fluid cannot account for differences in these results*  In particular i t seems unlikely that  potassium depletion was responsible for impaired motility where this occurred but that this effect was masked by a greater loss of potassium into the test solution in control animals* If potassium depletion actually was responsible for impairment of motility* then dilution of the test "solution" should reduce the intestinal motility of a l l animals to the same level, since the final potassium content was the same in a l l animals both experimental and control*  The present procedure gave excellent repro-  ducible results and appeared to provide a valid estimate of upper intestinal motility in vivo (Tabla II)* It would seem likely that i f any segment of the upper intestinal tract showed significant decrease in motility this would be manifested as an overall decrease in transit of the dye solution* However* the technique did not permit a direct evaluation of variations in motility in different portions of the upper intestine and provided no indication of the activity of the lower bowel* The large intestine and rectum of the animals on a low sodium, low potassium diet were distended with a larger quantity of faeces than was present in the control animals* This suggests that the lower part of the gastro-intestinal tract may also have been in a state of hypomotility*  - 50 -  .  However, no objective method of noting the extent of this inactivity- was developed* s  he adrenalectomised animals and those that received the hormones  contained yellowish semi-fluid material throughout their gastro-dntestinal tracts* Again, the motility of the upper portions of the tracts were evaluated with the gentian violet solution*  The lower parts of the tracts  were assumed to be hypomotile due to their marked distensions* Changes in Electrolytes of Stomach Muscle in Relationship to Motility* There was no variation in the potassium level of the stomach, regardless of diet of treatment* Therefore the overall loss of motility could not be correlated with any potassium changes in the stomach. The tissue sodium level of the stomach was increased under certain conditions (intact animals on a high sodium, low potassium diet; adrenalin treated animals)*  Stein-  bach* '54 in a review article, suggests that sodium uptake decreases the force of a nvyiwai contraction of skeletal muscle* However, the stomach muscles of the animals on a high sodium, low potassium diet, though increased in sodium content, were apparently normal in motility*  At least* no overall  change in motility in the upper bowel could be detected* Therefore the possibility that increased sodium concentration may be inhibitory was not supported by these results in the case of smooth muscle* The stomach muscle, differed from the other samples of gastro-intestinal tract in that the mucosa was consistently stripped from i t *  This raises  the-possibility that the changes in potassium level seen in the rest of the gastro-intestinal tract may be due to alterations only in the mucosa rather than the smooth muscle, though this appears unlikely*  Our methods do not  differentiate between mucosa and smooth muscle of the gastro-intestinal  - 51 -  tract aboral to the stomach. Changes in Electrolytes In the Duodenum and Ileum In Relation to Activity The duodenum and ileum like the stomach, in general, showed very few instances in which potassium depletion occurred* Specifically, the duodenum had no loss of potassium or of sodium in any of the experimental procedures even in those groups that showed diminished intestinal activity* The possibility that a high tissue sodium may inhibit motility is not supported by this data, since the intact animals on a high sodium, low potassium diet did not have a loss of motility, even though the duodenum sodium content was increased* Similarly, the duodenum of the adrenalectomized animals on a low potassium diet contained a significant increase of sodium,and again, there was l i t t l e indication of inhibition of motility*  Finally,  there were elevations in potassium content in some groups of hormone-treated animals but their intestinal motility was not different from other such groups with normal potassium levels* Therefore, as in the stomach, the duodenum showed no correlation between electrolyte levels and motility* The ileum was unique in that in several procedures sodium and potassium were both decreased* The depletion of both cations did not invariably produce an alteration of motility* For instance, motility was decreased on the K deficient diet when sodium was also restricted, but not when the dietary sodium content was elevated, although the pattern of ionic change in the ileum was the same in both instances* Similarly, there is no indication that an increase in cation levels alters motility*  In fact  adrenalectomy alone causes an elevation in both sodium and potassium content of the ileum without causing an appreciable decrease of motility* In view of the possibility that the overall changes which were recorded  - 52 -  in motility might have been due to diminished activity and altered electrolyte content in but one segment, i t seems worthwhile to inquire i f such an explanation can be excluded by the data* These data taken together exclude the possibility that decreases in potassium or in sodium in any segment might be correlated with loss of motility since there was loss of motility without depletion of sodium or potassium in any segment except the ileum in the doubly deficient diet, but a similar alteration of ileum electrolyte content on the low K, high sodium diet did not cause loss of motility*  In  no instance where motility was impaired (intact animals on doubly deficient diet) was there an increase in tissue potassium in any segment of the bowel  0  The possible role of increased sodium can likewise be eliminated since i t occurred only in the stomach and duodenum and then on a high sodium diet where no loss of motility was recorded* Changes in Electrolytes of Large Intestine and Rectum in Relation to Motility  In no experimental procedure was the sodium level of the large  intestine or rectum significantly lower than the levels of the intact control animals which had normal motility*  Several procedures did cause  an increase of tissue sodium* However, there was no correlation between these increases in tissue sodium and the decreases in motility which were noted in toe upper intestine of some groups* Furthermore* although both increases and decreases in potassium content occur in the lower bowel, there is no correlation between either of these changes and motility changes elsewhere in the large intestine or rectum as indicated by i t s distension* The problem as to why the gut should become relatively inactive, whereas the striated muscle retains its ability to contract, whan the animals are  -53subjected to adrenalin or cortisone treatment or to low sodium., low potassium diets remains unanswered*  The casuistic theories of Vaughn Williams*  '54  Darrow, '50, and Henrlkson, »51, that paralytic ileus or gut distention i s due to the loss of potassium from the gastrointestinal tract sees to be i n correct*  The data indicate that, though both adrenalin and cortisone can  cause a marked reduction i n gut motility, they do not cause a drop i n the potassium levels of the tissue*  In fact, i n intact animals, cortisone  produces an increase i n the potassium content of the tract*  gastro-intestinal  While large doses of cortisone-like compounds can cause loss of  motility this i s not accomplished by depletion of potassium i n these tissues* The possibility that the increased sodium content of the alimentary tract might be inhibitory was definitely disproven for the upper portions of the gastro-intestinal tract*  Alterations i n the cation content of the  lower bowel can not be correlated with changes of motility, since objective measurement of activity i n this region was not achieved*  C l i n i c a l l y , the  infusion of potassium solution corrects the symptoms of paralytic ileus (Darrow, '45)*  It would be of interest to analyse the  gastro-intestinal  tissues after a potassium infusion i n various conditions associated with impaired intestinal mobility to determine whether or not the motility would be restored to normal and to observe any tissue electrolyte changes which might accompany this procedure* The Comparison of the Electrolyte changes i n the Gut with that of Striated Muscle and Liver  It i s commonly assumed that the electrolyte  content of one tissue and i t s responses to different treatments are representative of other tissues of the body*  In agreement with Woodbury's  results our data indicate that the responses to a given experimental  - 54 procedure of various tissues of the body are not uniform*  For example,  cortisone, i n our intact rats, decreases skeletal muscle potassium but increases intestinal potassium*  The results demonstrate that the  two  samples of skeletal muscle, five samples of gastro-intestinal tract, and l i v e r a l l contained different i n i t i a l levels of sodium, potassium and  the  chloride  ions, and these responded differently to the various experimental procedures* It i s possible that the various tissues may have contained differing amounts of extracellular material, especially connective tissue*  This could account  for differences i n the i n i t i a l levels of electrolytes i n the same type of tissue*  i f this were the sole source o f v a r i a t i o n , calculated cellular  cation contents should be similar i n a l l tissues.  This was not the case,  since a l l gastro-intestinal tissues had higher calculated cellular potassium values than did skeletal muscle*  Since the calculation of cellular content  i s based on the assumption that the chloride space i s a measure of extracellular space, conclusions must be tentative until this assumption i s verified or disproven*  However, the electrolyte changes i n the various  types of tissue produced by the various procedures differ far too much from one another to be explained by differences i n gross tissue structure* The interpretation of tissue electrolyte changes i n terms of underlying intracellular ionic alterations i s d i f f i c u l t *  The changes i n t o t a l  tissue electrolyte can result from changes i n water or electrolyte content of cells or from changes of the extracellular content of tissues*  From a  functional point of view intracellular changes are of primary interest* Unfortunately the available methods do not allow accurate assessment of these changes* Nevertheless dubious assumptions are commonly accepted i n an effort to arrive at an estimate of cellular ionic concentrations*  - 55 The results of such calculations must be evaluated with a great deal of reserve* Role of Hormones i n the Pattern of Alteration of Electrolytes seen i n Sodium and/or Potassium Deficiency. Effects of Adrenalectomy  In adrenalectomized animals, both sodium  and potassium content were increased i n a l l tissue examined with the exception of the stomach* After adrenalectomy dietary potassium reduction did not have i t s usual effect on the electrolyte pattern of the tissues. This suggests that some portion of the adrenal gland i s necessary for the depletion of plasma and muscle potassium during dietary potassium deficiency* Further, since the increases i n tissue potassium following adrenalectomy were general and occurred even i n the face of diminished potassium intake* The lack of tissue potassium depletion under these circumstances as a result of failure to excrete the potassium released by tissue catabolism seems to be an acceptable hypothesis* Response of Plasma and Tissues to Cortisone Cortisone caused a hypochloremic, hypokalemic state i n the animals regardless of diet*  However, on  investigating the individual tissues, a more complex picture appeared*  In  skeletal muscle, the electrolyte changes due to cortisone were independent of potassium  intake*  This suggests that cortisone can reduce muscle  potassium by direct action*  Thus the hypothesis that low potassium diets  exert their influences by causing an excessive release of adreno-c ortic a l hormones i s compatible with this evidence* Cortisone produced different changes i n the gastro-intestinal tract electrolytes of intact as compared with adrenalectomized animals*  The  gastro-intestinal electrolytes of the adrenalectomized animals were also different from those of striated muscle*  In cortisone treated adrenalectomized  rata the potassium free diet produced further potassiu^^^  in the  gat in addition to that caused by cortisone alone, and the levels recorded approximated to those found in intact animals on similar diets* whereas dietary potassium deficiency did not enhance the potassium depleting effect of cortisone in skeletal muscle of adrenalectomized animals* These results suggest that hypercorticism alone could account for the potassium depletion of skeletal muscle seen in dietary potassium deficiency but i s inadequate to explain the potassium depletion of the bowel produced by a deficient potassium intake* although cortisone i s necessary for dietary potassium restriction to produce i t s usual effect in adrenalectomiaed animals. Although the effects of cortisone on plasma and skeletal muscle electrolytes might be attributed to improved renal capacity toe xcrete potassium, and a decreased rate of sodium excretion, .thljamecnanism cannot explain the increased potassium content of gastro-intestinal tissues and liver in cortisone-treated intact animals* Here some direct alteration of the tissue distribution of electrolytes must be involved* This finding i s perhaps worthy of emphasis since i t further extends the evidence, presented by Woodbury, •SS, that cortical steroids-have direct extra-renal actions* In addition, some of the data suggest strongly that cortisone can act directly on the kidney to cause additional potassium excretion*  There  seems to be no other explanation for the cortisone induced potassium depletion in a l l tissues and the plasma of adrenalectomized animals on an adequate potassium intake. If cortisone simply enabled the kidney to make homeostatie adjustments more efficiently (in this case to a potassium load derived from tissue catabolisn) then i t would not lower tissue or  - 57 -  plasma levels below those in the intact animal* ihe needs of the body for cortical steroids vary widely depending upon the activity and the environment of the organism* The dose which would induce hypercorticism under optimal conditions, that is a dose which might be classified as pharmacological, may barely satisfy the needs of an organism vigorously engaged in a homeostatis response to stress or an organism lacking hormonal secretions* Therefore the electrolyte response to the same dose of hormones under the varying circumstances of hypercorticism, eucorticism, or hypocorticism, may be entirely different and the stress induced by dietary potassium deficiency might have been expected to increase the amount of cortisone required for controlling potassium metabolism*  However, some of the effects of the doses of cort-  isone used here (e*g* weight loss, lowering of plasma potassium) are usually considered to be evidence of pharmacological effects*  A pharmacological  dosage was not undesirable for the purpose of testing theories of motility because other workers claim that symptoms seen in gut distention and paralytic ileus are due to excessive activation of the adrenal cortex* However, high dosage makes interpretation of other effects uncertain in relation to normal physiology* For example, the difference in the response between intact and adrenalectomised animals might be attributed to the use of a fixed dose of cortisone* Furthermore, the direct action of cortisone on tissue electrolytes and on renal excretion demonstrated in this study may be the result of the high dosage used* In any case the data contradict the theory that excess adrenalcortical steroids are the cause of paralytic ileus following operative procedures*  - 58 S B a result of their effects on intestinal potassium.  In no case did a dose  of cortisone which was so large as to produce weight loss intestinal hypomotility and pronounced potassium loss from skeletal muscle, cause any depletion of gastro-intestinal potassium beneath levels i n intact animals* Why cortisone i n this dosage, antagonised the effects of adrenalectomy on gastro-intestinal potassium content but caused additional changes i n skeletal muscle potassium remains an enigma* Responses of Plasma and Tissue to Adrenalin  The animals were treated  with adrenalin simply to provide controls for complete replacement therapy* It was rather unexpected that adrenalin should cause adrenalectomized animals to gain weight and to prolong their lives*  The drop i n plasma potassium  produced by adrenalin has been reported by Rogoff et a l , *50.  Re concludes  that adrenalin can function as well as steroid components of the cortex i n maintaining normal blood plasma potassium levels*  I t would be of interest  to investigate further the effects of chronic pharmacological doses of adrenalin on intact animals, and on the prolonged maintenance of adrenalectomized rats*  The doses of adrenalin used i n the experiment were  pharmacological i n that they caused edema-formation, and a hypokalemia* In future experiments i t would also seem desirable to investigate the effects of physiological doses of'adrenalin on the maintenance of adrenalectomized rats* In adranalectomised animals, adrenalin i n the presence of a low potassium diet, lowered the electrolyte concentration of skeletal muscle to the values found i n intact animals, an effect which could not be accomplished by dietary potassium restriction alone. Adrenalin alone did not prevent the changes initiated by adrenalectomy*  Adrenalin permits the low potassium  diet to exert i t s usual effects on skeletal muscle potassium content despite  - 59 adrenalectomy. The possibility remains that the potassium deficient diet dees cause a depletion i n this tissue by a direct action provided that the adrenal medulla i s functional* without the effect being mediated v i a one of the adrenal hormones* The adrenal medulla may be essential for the renal excretion of potassium which accompanies potassium depletion during dietary potassium restriction* In the gastro-intestinal tract, adrenalin had a different effect than i n the skeletal muscle*  Here adrenalin i n the presence of the low potassium  diet could not completely correct the electrolyte changes caused by adrenalectomy* Furthermore, i t caused an even greater increase of the sodium content of the alimentary tract*  Thus the adrenalin combined wifch low  potassium diet could p a r t i a l l y but not completely correct the electrolyte changes caused by adrenalectomy i n the gastro-intestinal tract*  This suggests  that the presence of the adrenal medullary hormone alone i s not sufficient to permit potassium depletion to occur i n the lower bowel of intact animals deprived of dietary potassium*  This suggestion i s i n agreement with the  previously mentioned possibility that cortical steroids are essential for the development of potassium depletion i n the bowel*  However, these data  are inconsistent with the theory that potassium depletion from skeletal muscle during deficient dietary intake i s the result of hypercorticism, since adrenalin alone Is capable of permitting depletion to occur i n this tissue* One other conclusion can be drawn from the data concerning the effects of adrenalin on tissue and plasma electrolytes*  Most of the effects of  adrenalin on potassium levels could be explained i n terms of "improved" renal potassium excretion*  However, there Is a suggestion that there i s  actually an increase i n tissue potassium, especially i n l i v e r , when adrenalin  - 60 m> i s administered to adrenalectomized animals with an adequate potassium intake*- The simplest explanation of this observation would be a direct action of adrenalin on the tissues leading to potassium accumulations Anatomically, the site of production of adrenalin and cortisone are related, but chemically the two structures bear no relationship to one another*  This gives rise to an interesting problem as to how two  chemicals  so dissimilar i n structure, can exert certain similar reactions (e«g* hypokalemia, hypomotility) i n the body*  As yet, no metabolic pathway  has been identified for the synergistic action of these two hormones*  - 61 F. Summary and Conclusions 1*  The cation content of various portions of the gut from rats on a low  sodium, low potassium diet and on high sodium, low potassium diet, have been determined and compared with those of similar portions of the gut of animals on a control diet.  The responses to a high sodium,low potassium  diet after adrenalectomy both with and without medullary or cortical hormonal supplementation was also determined.  The electrolyte patterns of  l i v e r and of skeletal muscle from different portions of the body were similarly analysed and compared. 2.  A new technique based on the passage of a solution containing the dye,  gentian violet, was developed for estimating upper bowel motility, but the procedure did not permit evaluation of motility of the lower bowel. 3*  In none of the circumstances studied was i t possible to correlate  alterations i n the gastro-intestinal tract content of sodium and/or potassium with motility.  The problem as to why the gut should become relatively  inactive when subjected to various procedures remains unsolved. h»  Careful analyses of the selected tissues of the body indicate that  i n i t i a l electrolyte concentration and responses to diets and hormones vary within similar tissues and between different organs. Evidence i s presented to show that not a l l differences could be the result of i n i t i a l differences in extracellular material. J>. Adrenalectomy prevented dietary potassium deficiency from decreasing tissue potassium.  Evidence indicating that adrenalectomy results i n impaired  a b i l i t y to excrete potassium i s discussed. 6.  Although an excess of cortisone did cause diminished alimentary tract  motility, and loss of potassium from striated muscle, the hypothesis that adrenal cortical hormones cause immobility through a loss of potassium or  a gain of sodium was 7*  disproven.  Evidence i s presented that cortisone can influence the electrolytes of  the body by acting on the cells of peripheral tissues as well as on the kidney and that a high dose administered has direct as well as permissive effects* 8*  Evidence i s presented indicating that adrenal in can partially restore  the a b i l i t y to excrete potassium and the a b i l i t y of tissues to undergo potassium depletion i n adrenalectomized animals on a potassium deficient diet*  The possibility that adrenalin may play an important role i n main-  taining electrolyte homeostasis i s discussed* 9*  The possibility i s suggested that the cortex and medulla of the adrenal  gland may exert synergistic influences on the electrolytes of the body*  - 63 m .  BIBLIOGRAPHY  Amberson, W.R., T.P. Nash., A.G. Holder, and D. Binns, 1936, The Relationship Between Tissue Chloride and Plasma Chloride, Am. J . Physiol*, 122, pp. 22li235* Chapman, W.P., E.N. Rowland, A. Taylor, and C.H. Jones, 1950, MultlpleBaloon-Eymograph Recordings of Variations i n Motility of the Upper Small Intestine i n Man During Long Observation Periods Before and After Placebo Administration., 1950, Gastroenterology, lj>, pp. 3^1 - 355. Conway, E.J., 19U5, The Physiological Significance of Inorganic Levels i n the Internal Medium of Animals., B i o l . Rev, of the Cambridge P h i l . S o c , 20, pp. 56 - 72. Conway, E.J., and Hingerty, D., Relations between Potassium and Sodium Levels i n Mamalian Muscle and Blood Plasma., 19U8, Biochem. J.. 1+2, pp. 372 - 376. Cbtlive, E«, M.A. Holliday, R. Schwartz, and W.M. Wallace, 1951, Effeet of Electrolyte Depletion and Acid-Base Disturbances on Muscle Cations, Am. J . Physiol*, 167. pp. 665-675. Crismon, J.M., C.S. Crismon, M. Calabresi, and D.C. Darrow, 1913, Electrolyte Redistribution i n Cat Heart and Skeletal Muscle i n Potassium Poisoning. Am. J . Physiol.. 139. pp. 667 - 67l*» Dai owski, T.S., and J.R. EUdnton, 1951, Exchange of Potassium Related to Organs and Systems, Pharmacol. Rev. 3, pp. 1»2 - 58. Darrow, D.C., 19U5, Body-Fluid Physiology: Relation of Tissue Composition to Problems of Water and Electrolyte Balance, New Eng. J. Med., 233, pp. 91 - 97. Darrow, D.C, 19U6, Changes i n Muscle Composition i n Alkalosis, J. C l i n. Invest., 25, pp. 32lt - 330.  -61+ -  Darrow, D. C , 1 9 5 0 , Body-Fluid Physiology: The Role of Potassium i n C l i n i c a l Disturbances of Body Water and Electrolytes, New Eng. J.Med.. 22+2, pp.  978 -  983.  Darrow, D.C, R. Schwartz, J . Iannucci and F. Coville, 191(8, The Relation of Serum Bicarbonate Concentration to Muscle Composition, J, C l i n . Invest.. 2 J , pp. 198 - 2 0 8 , Duty, A., 1953, Mechanisms of Insulin and Epinephrine Effect on the Level of Plasma Potassium, Endocrinology. Jj3., pp. 5^U - 5 7 1 . Fuhnman, F.A., 1 9 5 1 , Glycogen, Glucose Tolerance and Tissue Metabolism i n Potassium Deficient Rats, Am. J.Physiol., 1 6 7 . pp. 311* - 3 2 0 . Gardner,L. I., N.3. Talbot, CD. Cook, and H. Berman, 1950, The Effect of Potassium Deficiency on Carbohydrate Metabolism, J . Lab, and C l i n . Med.. 3 i , pp. 592 - 6 0 2 .  Grollman, A., 1951+, Water and Electrolyte Content of Tissues of the Adrenalectomized and Adrenalectomized-flephrectomized Dog, Am.J. Physiol.. 1 7 9 . pp. 36 - 3 8 .  Gruber, CM.,  and A. Denote, 1935, iThe Effect of Different Sizes of Balloons  Inserted i n the Gut and Changes i n Pressure within them upon the Small Intestine. Am. J.Physiol., I l l , pp. 561+ - 570. Hawk, P.B., B. L.Oser, and W.H..Suraraerson, Practical Physiological Chemistry, Toronto, Blakiston Co., 191+8, p. 6 6 . Henrikson, H. W., 1 9 5 1 , Effect of Potassium Deficiency on Gastro-intestinal Motility i n Rats, Am. J , Physiol., 161+, pp. 263 - 2 7 3 . Heppel, L.A., 1 9 3 9 , The Electrolytes of Muscle and Liver i n Potassium Depleted Rats, Am. J.Physiol. 1 2 7 , pp. 385 - 3 9 2 . Holliday, M.A., 1955, Acute Metabolic Alkalosis: Its Effect on Potassium and Acid Excretion* J . Clin. Invest., 3 U , pp. 1+28 - 1+33.  - 65 Kornberg, A., and K. M. Endicott, 19^6, P tassium Deficiency i n the Rat, 0  Am. J. Physiol., 1U5. pp. 291 - 298* Lowry, OH., A.B. Hastings, T. Z. Hull, and A. N. Brown, 191*3, Histoohemical Changes associated with Aging.II. Skeletal and Cardiac Muscle i n the Rat, J . B i o l . Chem., 1U3, pp. 271 - 280. Manery, J.F., 195U, Water and Electrolyte Metabolism, Physiol. Rev., 3jj,pp. 33U - U 7 . Manery, J.F., I.S. Danlelson, A. B. Hastings, 1938, Connective Tissue Electrolytes, J . B i o l . Chem., 12U, pp. 359 - 375. Manery, J.F., and A.B. Hastings, 1939, The Distribution of Electrolytes i n Mammalian Tissues, J . B i o l . Chem. 127, pp. 657 - 676. Muntwyler, E., G. F. G r i f f i n , G. S. Samuelsen and I.G. G r i f f i t h , 1950, The Relation of the Electrolyte Composition of Plasma and Skeletal Muscle, J . B i o l . Chem., 185, pp. 525 - 536. Northup, D.W., J . C. Stecksey, and G. I. Van Liere,  Effect of Atropine,  Tetraethylaramonium, Banthine, and Bentyl on Motility of the Small Intestine. Am.J.Physiol., 171, pp. 513 - 515. Overman, R.R., 1951, Sodium, Potassium and Chloride Alterations i n Disease, Physiol. Rev., 31, pp. 285 - 311. Quigley, J . P., and D. A. Brody, 1952, A. Physiologic and C l i n i c a l Consideration of the Pressures Developed i n the Digestive Tract, Am. J . Med., 13, pp. 7 3 - 8 1 . Rogoff, J . M., JMm Quashnock, E.N. Nixon, and A. W.Rosenberg, 1950, Adrenal Functions and Blood Electrolytes, Proc. Soc. Exper. B i o l , and Med.., 73, pp. 163 - 169. Schales, 0., and S.S. .Schales, 19tiL, A Simple and Accurate Method for the Determination of Chloride i n Biological Fluids, J . B i o l , Chem& lijO, pp. 879 - 88lu  -66Sklnner, J, T., and J. S. McHargue, 19U5, Response of Rats to Boron Supplements when Fed Rations Low i n Potassium, Am. J. Physiol. ll|3, PP. 385 - 390. Steiribach, H. B«, "The Regulation of Sodium and Potassium i n Muscle Fibres i n Symposia of the Society for Experimental Biology, Cambridge n  University Press, 195U, Vol. 7, pp» 1*38 - U52. Schwartz, R., J, Cohen and W.M. Wallace, 1953, Tissue Electrolyte Changes of the Whole Body, Muscle, Erythrocyte and Plasma of Rats on a Potassium Deficient Diet. Am, J , Physiol. 172, pp. 1 - 5. t  Van Slyke, D.D., 1923, The Determination of Chloride i n Blood and Tissues, J, B i o l . Chem., 58, pp. 523 - 529. Vaughan Williams, G.M., 195b, The Mode of Action of Drugs upon Intestinal Motility, Pharmacol. Rev., 6, pp. 159 - 190. Wilson, W,, and E.G. Ball, 1928, A Study of the Estimation of Chloride i n Blood and Serum, J, Biol, Chem,, 79,.pp. 221 - 227. Woodbury, D.M., 1953, Extrarenal Effects of Desoxycorticosterone, Adrenocortical Extract and Adrenocorticotrophic Hormone on Plasma and Tissue Electrolytes i n Fed and Fasted Rats, Am. J. Physiol., 17k, pp. 1 - 19.  

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