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Physicochemical Changes in Intestinal Obstruction
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION EUGENE
M.
SCHLOSS,
M.D.*
IT is only within the past thirty-five years, beginning with the experimental work of Hartwell and Hoguet,1 that the importance of the physical and chemical factors in intestinal obstruction has been recognized. During this period a great volume of data has been accumulated by inquiry into the various component fields-detailed studies at representative levels of the alimentary tube and investigation of changes in the experimental animal or clinical case as a whole. For several years now the major changes have been described and rational therapy directed toward their correction or control. While many basic problems remain to be clarified and while contemporary or future findings may change concepts now widely held, it seems worth while to present an integrated view of the subject in its present status. BASIS OF THE PHYSICOCHEMICAL CHANGES
The basis of the physicochemical changes in gastrointestinal obstruction lies in the distention of all or parts of the alimentary tube proximal to the point of obstruction and in the chemical changes incident upon the loss of fluids and electrolytes due to vomiting, lavage or suction drainage before or after surgery. The cause of the morbidity and mortality in obstruction is probably a combination of these factors-distention and loss of fluids and electrolytes-but, in addition, there may be still others, as yet undiscovered, unconfirmed or even presently uninterpreted. Whipple 2 and his fellow workers found many years ago that if incisions are made across the gut of the dog at two places to create an isolated segment a few inches long with its ends closed off and the continuity of the main portion of the alimentary tract is then restored, death occurs more rapidly than if a simple obstruction is created by ligation at the same level of the gut. Now, undoubtedly, there is a combination of distention and fluid secretion into this isolated segment, but it remains to be demonstrated conclusively whether this explanation of the subsequent morbidity and mortality is adequate or whether there are further factors such as toxic proteoses formed in the intestinal mucosa (as Whipple has From the Jewish Hospital, Philadelphia. in Medicine, Temple University Medical School; Associate in Medicine, Jewish Hospital; Gastroenterologist, Doctors Hospital.
* Associate
1717
1718
EUGENE M. SCHLOSS
suggested), serIOUS reflex neurological or enzymatic phenomena, or others. It is certain that simple distention of the bowel can ultimately lead to death, even without a significant loss of fluids or electrolytes. Yet the mechanism here is not fully understood. Taylor 3 and his associates placed a balloon in the duodenum of the dog, distended the segment to a pressure of 100 mm. of mercury but had an open rubber tube so placed that there was no disturbance of the continuity of the digestive canal; thus therc was no appreciable loss of their contents yet these animals exhibited all the phenomena of acute obstruction including exitus. That there may have been a neurological element in this demonstration is indicated by the fact that animals in which the selected duodenal segment was denervated prior to the distention procedure survived much longer. Carrying this over into the field of human medicine we can find the occasional instance of Richter's hernia in which only a portion of the intestinal lumen is cut off from the direct continuity of the canal; this is not a true occlusion yet the clinical picture is one of acute intestinal obstruction. It must also be borne i~ mind that distention, per se, is a strong stimulus to glandular secretion so that in long-continued obstruction the distended portion of bowel is apt to pour out large quantities of fluid and salts which may be vomited or retained; if retained the secretion is excluded from the normal interchange of fluids and electrolytes and is just as effective a mechanism in producing the train of dehydration and electrolyte imbalance as if it had been vomited. The quantities of fluid so lost may be of unexpected magnitude. In the rabbit, which cannot vomit, intestinal obstruction may lead to the accumulation of as much as thirteen per cent of the animal's body weight in fluids found in the stomach and intestine postmortem. In the human being, during the course of untreated obstruction, analogous volumes of fluids and quantities of electrolytes are lost by the vomiting of gastric juice plus hepatic, pancreatic and intestinal secretions, depending upon the level at which obstruction has occurred. The distention factor is, of course, well recognized today and the use of t,he Wangensteen apparatus or the Miller-Abbott tube has become a routine procedure in effecting decompression and evacuation of retained secretory products before or after appropriate surgical treatment. The relief of distention is thus accomplished efficiently but the very procedure leads to a great loss of fluids, salts and enzymes. In pyloric obstruction suction drainage of gastric contents may amount to over 6 liters a day 4 and in itself provides a basis for the development of dehydration and dechlorination.
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
1719
CHARACTERISTIC ALTERATIONS
In the majority of instances, these two factors--dechlorination and dehydration-are responsible for the chemical changes in intestinal obstruction. The characteristic alterations which result include: 1. Hemoconcentration, with shrinkage of plasma volume. 2. Reduction in the fixed base of the serum. 3. Diminution in plasma chlorides. 4. Increase in blood urea and nonprotein nitrogen. 5. Increasing carbon dioxide combining power of the plasma. 6. Urine, often highly acid, which may contain ketone bodies, and shows a marked reduction in chloride content. Originally it was thought that the dehydration was simply the result of vomiting of quantities of digestive fluids, but according to Gamble and ROSS5 the train of events begins with the loss of chlorides in the vomited material. As compared with blood plasma, gastric juice contains about 140 per cent of chloride, pancreatic secretion about 40 per cent, liver bile about 100 per cent and jejunal and ileal secretions about 125 per cent. Hence when large volumes of such fluids are lost, the withdrawal of chloride from the plasma and ultimately the tissues becomes a matter of great importance. In order to compensate for the hypochloremia, carbon dioxide is retained and bicarbonate increased so that the remaining chloride and the increased bicarbonate together may maintain a workable concentration of cations. However, if sufficient such retention of carbon dioxide and bicarbonate occurs, alkalosis develops and a renal mechanism comes into play by which increased quantities of sodium arc excreted in the urine in an attempt to counter the alkalosis. This depletion of base, for which the body cannot compensate as it does for chloride, is accompanied by a proportionate water loss. The loss of electrolytes from the blood and tissues leads to dehydration of the tissues and hemoconcentration with reduction of the blood plasma volume. Thus we arrive at the chemical factors of the most critical significance-dehydration and reduction of fixed base. The diminution of blood chlorides is probably due largely to their loss in gastric juice which is vomited or retained, but there may be additional factors such as a shift from blood to tissues or from plasma to corpuscles. Since the loss from vomiting is an obvious one, it has been widely held that the degree of hypocltloremia largely depends upon the quantity of chloride secreted into the stomach. Under such circumstances it would be expected that in stenosing duodenal ulcer, when the gastric juice contains normal or excessive amounts of free hydrochloric acid, the extent of hypochloremia would greatly exceed that found in carcinomatous obstruction, where hypochlorhydria or achlorhydria most often exists. However, this does
1720
EUGENE M. SCHLOSS
not universally hold true and McVicar and Weir6 have stated that the concentration of free hydrochloric acid in the gastric juice cannot be correlated with the degree of hypochloremia present, citing instances in which it occurred in the presence of anacidity. Furthermore, it is difficult to correlate the levels of blood chloride with the clinical status of the patient in many instances. It is certain that the extent of plasma chloride diminution may be masked by the concomitant hemoconcentration so that it may not be a true index of chloride depletion. In 1944 Coller 7 and his associates concluded that the clinical status offered the best index for the administration of corrective measures. This impression has been borne out in the experience of the author with cases in which laboratory studies available at the time of need would have been misleading if not weighed against the observable clinical condition. In the case of a 36 year old male seen in 1945, vomiting from pyloric obstruction due to stenosing duodenal ulcer had led to moderately severe dehydration and prostration. Blood alkali studies were not then available-plasma chloride level was 590 mg. per 100 cc. (as NaCl), yet mild convulsive seizures, constant headache and dulled perception indicated the probability of alkalosis. Despite the administration of normal saline solution according to the simple rules of Power, Pederson and Maddock,8 the syndrome persisted while blood chloride levels remained within normal limits and hematocrit readings dropped from 61 to 47. In this instance, a quantity of saline solution approximately two and a half times the volume of fluid lost by vomiting per twenty-four hours was required for restoration of the clinically normal acid-base equilibrium. In 1946, Sanchez-Vegas and Collins,9 investigating the electrolyte status of patients with pyloric obstruction due to duodenal ulcer, found marked diminution in urinary chlorides. This progressed to a point significantly below the normal 5 to 10 gm. in twenty-four hours, as in the case cited above, even in the presence of normal plasma chlorides, but with marked alteration in the acid-base balance of the blood. In their opinion the decrease in urinary chlorides was due to depletion of the tissues in an attempt to maintain blood chloride content at or near a normal level. Whether we use the blood chloride level or the twenty-four hour excretion of urinary chloride as our measure of chloride loss, we must recognize that the organism attempts to compensate for its depletion by the retention of bicarbonate and may do so to the extent of developing alkalosis. It would be thought that the administration of normal saline solution with its replacement of water, sodium and chloride would invariably correct such an alkalosis; that is, if the patient were supplied with sufficient normal saline solution, and if ketosis were prevented, the electrolyte pattern of the plasma would be satisfactorily
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
1721
adjusted by the kidneys. However, in some instances, the excess sodium is not wholly excreted and the chloride administered may be incapable of displacing enough bicarbonate to nullify the alkalosis. Zintel, Rhoads and Ravdin 4 suggested in 1943 that ammonium chloride be used intravenously in a 2 per cent solution to supplement the other measure, and reported its successful use in seven patients. The solution is readily made up and sterilized by autoclaving for twenty minutes at 15 pounds pressure. The dosage is based on the patient's requirements; to reduce the carbon dioxide combining power by 1 per cent, ammonium chloride is given in the proportion of 16 mg. per kilogram of body weight. No unfavorable reactions were encountered in this series. Since then this procedure has had fairly wide usage and very recently Grace and Barr10 described its application in nine cases of alkalosis, including two due to intestinal obstruction. Grace and Barr also stressed two points of interest: first, the danger of inducing alkalosis by the administration of sodium lactate without the simultaneous use of normal saline while gastric suction is in operation, and second, the persistence of renal damage after continued alkalosis, at times to a point at which it appears to be permanent. On the other hand, in cases in which there is a greater loss of sodium than that of chloride, a status of acidosis may develop. This is particularly true when the loss of pancreatic, jejunal and ileal secretions is greater than that of gastric juice with its higher chloride content, and may be heightened by impairment of renal function. It is important to note at this point that where the acid-base equilibrium is disturbed in either direction, this disturbance occurs simultaneously with dehydration and the primary corrective measure remains the same~the administration of water, sodium and chloride. A state of ketosis may develop in the presence of either alkalosis or acidosis. We are accustomed to associating ketosis with acidosis due to starvation, as may well occur in intestinal obstruction. Abbott and Mellorsll have demonstrated that in experimental low intestinal obstruction the late development of vomiting may permit evidence of starvation and malnutrition to long precede severe dehydration. At intermediate points of obstruction there may well be mixed states in which the development of starvation and the loss of chloride by vomiting occur at parallel rates. There it is possible that the excess of ketone acids due to starvation may yet be insufficient to balance the preponderance of accumulated bicarbonate which has resulted from chloride depletion. Again, however, regardless of the state of acidosis or alkalosis, correction of the ketosis lies in the administration of sufficient glucose to prevent the further incomplete breakdown of the even-numbered fatty acids.
1722
EUGENE M. SCHLOSS
In addition to the foregoing, an increase in nonprotein nitrogen, first observed by Tileston and Comfort'2 in 1941, appears whenever complete gastrointestinal obstruction occurs at any level from the esophagus to the rectum. In comparison with most other types of azotemic retention, there is less effect on the urea nitrogen than on the remaining fractions, but both are increased. An increased destruction of protein due to the effects of starvation and dehydration upon tissue cells throughout the body has been repeatedly observed. Because of hemoconcentration and reduced blood pressure, the filtration pressure in the kidney is lowered and while the renal system may be able to concentrate well, it is usually unable to excrete the increased nitrogenous load so liberated, and hyperazotemia appears. As in the case of ketosis, the use of isotonic glucose solution tends to prevent the element of starvation in the destruction of protein and the administration of normal saline solution tends to restore the electrolytes, the loss of which is the major factor in the dehydration. SUMMARY
To summarize, the physicochemical factors in gastrointestinal obstruction are based on the effects of distention and loss of fluid and electrolytes which lead to dechlorination, loss of fixed base and dehydration. This is evidenced in studies which show: 1. Hemoconcentration. 2. Reduction in the fixed base of the serum. 3. Diminution in plasma chlorides. 4. Increase in urea and nonprotein nitrogen. 5. Change in acid-base equilibrium, more often to alkalosis, not infrequently in the direction of acidosis. 6. Hypochloremia and hypochloruria. 7. Frequent ketosis and high acidity of the urine. These phenomena are readily countered in the majority of instances by the parenteral administration of adequatc amounts of glucose and saline solutions. However, in some cases, ample quantities of these substances have been given to a point where the total serum base has been brought above the normal accepted range without controlling alkalosis. In these cases the intravenous use of 2 per cent ammonium chloride has been highly effective in treating or preventing the tetany, convulsions and possibly permanent renal damage which may result from alkalosis. The estimation of the quantities of fluids and electrolytes necessary to restore equilibrium is at present best made from serial studies of blood chlorides, carbon dioxide combining power, twenty-four hour urinary study for ketone bodies, urinary chloride excretion, intake and output records,
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
17~3
blood nonprotein nitrogen, all as adjuncts to the clinical observation of the patient. REFERENCES 1. Hartwell, J. A. and Hoguet, J. P.: Experimental Intestinal Obstruction in Dogs, with
Especial Reference to the Cause of Death and the Treatment by ],arge Amounts of Normal Saline Solution. J.A.M.A. 59:8'2, 191'2. '2. Whipple, G. H., Stone, H. B. and Bernheim, B. M.: Intestinal Obstruction. I. A Study of a Toxic Substance Produced in Closed Duodenal Loops. J. Exper. Med. 17:'286, ]9]3.
3. Taylor, N. B., Weld, C. B. and Harrison, K.: Experimental Intestinal Obstruction. Canad. M. A. J. 2f!:'2'27, ]933. 4. Zintel, H. A., Rhoads, J. E. and Ravdin, I. S.: The Use of Intravenous Ammonium Chloride in the Treatment of Alkalosis. Surgery 14:7'2'1'., ] 943. 5. Gamble, J. 1.. and Ross, S. G.: The Factors in the Dehydration Following Pyloric Obstruction. J. (,lin. Investigation 1:403, 19'24. 6. McVicar, C. S. and Weir, J. F.: Toxemia of Intestinal Obstruction and Ileus; Clinical Deductions Regarding Its Nature and Treatment. Proc. Staff Meet., Mayo Clin. 8:193, 19'2'1'.. 7. Caller, F. A., Campbell, K. N., Vaughan, H. H., lob, L. V. and Moyer, C. A.: Postoperative Salt Intolerance. Ann. Surg. 119:533, ]944. 8. Power, F. H., l'ederson, S. and Maddock, W. G.: Clinical Experience with Sodium Chloride Replacement. Surgery 12:43'1'., 194'2. 9. Sanchez-Vegas, J., and Collins, E. N.: Importance of Urinary Chloride Determinations in Treatment of Patients with Pyloric Obstruction. Am. J. M. Sc. 211:4'28, 1946.
10. Grace, W. J. and Barr, D. P.: Complications of Alkalosis. Am. J. Med. 4:33], ]948. ] 1. Abbott, W. E. and Mellors, It. C.: Body Fluid Studies in Experimental Obstruction at Various Levels of the Gastrointestinal Tract. Surgery 12:445,1942. ]'2. Tileston, ·W. and Comfort, C. W.: The Total Non-protein Nitrogen and the Urea of the mood in Health and in Disease, as Estimated by Folin's Methods. Arch. Int. Med. 14:620, 1914.
M.
SCHLOSS,
M.D.*
IT is only within the past thirty-five years, beginning with the experimental work of Hartwell and Hoguet,1 that the importance of the physical and chemical factors in intestinal obstruction has been recognized. During this period a great volume of data has been accumulated by inquiry into the various component fields-detailed studies at representative levels of the alimentary tube and investigation of changes in the experimental animal or clinical case as a whole. For several years now the major changes have been described and rational therapy directed toward their correction or control. While many basic problems remain to be clarified and while contemporary or future findings may change concepts now widely held, it seems worth while to present an integrated view of the subject in its present status. BASIS OF THE PHYSICOCHEMICAL CHANGES
The basis of the physicochemical changes in gastrointestinal obstruction lies in the distention of all or parts of the alimentary tube proximal to the point of obstruction and in the chemical changes incident upon the loss of fluids and electrolytes due to vomiting, lavage or suction drainage before or after surgery. The cause of the morbidity and mortality in obstruction is probably a combination of these factors-distention and loss of fluids and electrolytes-but, in addition, there may be still others, as yet undiscovered, unconfirmed or even presently uninterpreted. Whipple 2 and his fellow workers found many years ago that if incisions are made across the gut of the dog at two places to create an isolated segment a few inches long with its ends closed off and the continuity of the main portion of the alimentary tract is then restored, death occurs more rapidly than if a simple obstruction is created by ligation at the same level of the gut. Now, undoubtedly, there is a combination of distention and fluid secretion into this isolated segment, but it remains to be demonstrated conclusively whether this explanation of the subsequent morbidity and mortality is adequate or whether there are further factors such as toxic proteoses formed in the intestinal mucosa (as Whipple has From the Jewish Hospital, Philadelphia. in Medicine, Temple University Medical School; Associate in Medicine, Jewish Hospital; Gastroenterologist, Doctors Hospital.
* Associate
1717
1718
EUGENE M. SCHLOSS
suggested), serIOUS reflex neurological or enzymatic phenomena, or others. It is certain that simple distention of the bowel can ultimately lead to death, even without a significant loss of fluids or electrolytes. Yet the mechanism here is not fully understood. Taylor 3 and his associates placed a balloon in the duodenum of the dog, distended the segment to a pressure of 100 mm. of mercury but had an open rubber tube so placed that there was no disturbance of the continuity of the digestive canal; thus therc was no appreciable loss of their contents yet these animals exhibited all the phenomena of acute obstruction including exitus. That there may have been a neurological element in this demonstration is indicated by the fact that animals in which the selected duodenal segment was denervated prior to the distention procedure survived much longer. Carrying this over into the field of human medicine we can find the occasional instance of Richter's hernia in which only a portion of the intestinal lumen is cut off from the direct continuity of the canal; this is not a true occlusion yet the clinical picture is one of acute intestinal obstruction. It must also be borne i~ mind that distention, per se, is a strong stimulus to glandular secretion so that in long-continued obstruction the distended portion of bowel is apt to pour out large quantities of fluid and salts which may be vomited or retained; if retained the secretion is excluded from the normal interchange of fluids and electrolytes and is just as effective a mechanism in producing the train of dehydration and electrolyte imbalance as if it had been vomited. The quantities of fluid so lost may be of unexpected magnitude. In the rabbit, which cannot vomit, intestinal obstruction may lead to the accumulation of as much as thirteen per cent of the animal's body weight in fluids found in the stomach and intestine postmortem. In the human being, during the course of untreated obstruction, analogous volumes of fluids and quantities of electrolytes are lost by the vomiting of gastric juice plus hepatic, pancreatic and intestinal secretions, depending upon the level at which obstruction has occurred. The distention factor is, of course, well recognized today and the use of t,he Wangensteen apparatus or the Miller-Abbott tube has become a routine procedure in effecting decompression and evacuation of retained secretory products before or after appropriate surgical treatment. The relief of distention is thus accomplished efficiently but the very procedure leads to a great loss of fluids, salts and enzymes. In pyloric obstruction suction drainage of gastric contents may amount to over 6 liters a day 4 and in itself provides a basis for the development of dehydration and dechlorination.
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
1719
CHARACTERISTIC ALTERATIONS
In the majority of instances, these two factors--dechlorination and dehydration-are responsible for the chemical changes in intestinal obstruction. The characteristic alterations which result include: 1. Hemoconcentration, with shrinkage of plasma volume. 2. Reduction in the fixed base of the serum. 3. Diminution in plasma chlorides. 4. Increase in blood urea and nonprotein nitrogen. 5. Increasing carbon dioxide combining power of the plasma. 6. Urine, often highly acid, which may contain ketone bodies, and shows a marked reduction in chloride content. Originally it was thought that the dehydration was simply the result of vomiting of quantities of digestive fluids, but according to Gamble and ROSS5 the train of events begins with the loss of chlorides in the vomited material. As compared with blood plasma, gastric juice contains about 140 per cent of chloride, pancreatic secretion about 40 per cent, liver bile about 100 per cent and jejunal and ileal secretions about 125 per cent. Hence when large volumes of such fluids are lost, the withdrawal of chloride from the plasma and ultimately the tissues becomes a matter of great importance. In order to compensate for the hypochloremia, carbon dioxide is retained and bicarbonate increased so that the remaining chloride and the increased bicarbonate together may maintain a workable concentration of cations. However, if sufficient such retention of carbon dioxide and bicarbonate occurs, alkalosis develops and a renal mechanism comes into play by which increased quantities of sodium arc excreted in the urine in an attempt to counter the alkalosis. This depletion of base, for which the body cannot compensate as it does for chloride, is accompanied by a proportionate water loss. The loss of electrolytes from the blood and tissues leads to dehydration of the tissues and hemoconcentration with reduction of the blood plasma volume. Thus we arrive at the chemical factors of the most critical significance-dehydration and reduction of fixed base. The diminution of blood chlorides is probably due largely to their loss in gastric juice which is vomited or retained, but there may be additional factors such as a shift from blood to tissues or from plasma to corpuscles. Since the loss from vomiting is an obvious one, it has been widely held that the degree of hypocltloremia largely depends upon the quantity of chloride secreted into the stomach. Under such circumstances it would be expected that in stenosing duodenal ulcer, when the gastric juice contains normal or excessive amounts of free hydrochloric acid, the extent of hypochloremia would greatly exceed that found in carcinomatous obstruction, where hypochlorhydria or achlorhydria most often exists. However, this does
1720
EUGENE M. SCHLOSS
not universally hold true and McVicar and Weir6 have stated that the concentration of free hydrochloric acid in the gastric juice cannot be correlated with the degree of hypochloremia present, citing instances in which it occurred in the presence of anacidity. Furthermore, it is difficult to correlate the levels of blood chloride with the clinical status of the patient in many instances. It is certain that the extent of plasma chloride diminution may be masked by the concomitant hemoconcentration so that it may not be a true index of chloride depletion. In 1944 Coller 7 and his associates concluded that the clinical status offered the best index for the administration of corrective measures. This impression has been borne out in the experience of the author with cases in which laboratory studies available at the time of need would have been misleading if not weighed against the observable clinical condition. In the case of a 36 year old male seen in 1945, vomiting from pyloric obstruction due to stenosing duodenal ulcer had led to moderately severe dehydration and prostration. Blood alkali studies were not then available-plasma chloride level was 590 mg. per 100 cc. (as NaCl), yet mild convulsive seizures, constant headache and dulled perception indicated the probability of alkalosis. Despite the administration of normal saline solution according to the simple rules of Power, Pederson and Maddock,8 the syndrome persisted while blood chloride levels remained within normal limits and hematocrit readings dropped from 61 to 47. In this instance, a quantity of saline solution approximately two and a half times the volume of fluid lost by vomiting per twenty-four hours was required for restoration of the clinically normal acid-base equilibrium. In 1946, Sanchez-Vegas and Collins,9 investigating the electrolyte status of patients with pyloric obstruction due to duodenal ulcer, found marked diminution in urinary chlorides. This progressed to a point significantly below the normal 5 to 10 gm. in twenty-four hours, as in the case cited above, even in the presence of normal plasma chlorides, but with marked alteration in the acid-base balance of the blood. In their opinion the decrease in urinary chlorides was due to depletion of the tissues in an attempt to maintain blood chloride content at or near a normal level. Whether we use the blood chloride level or the twenty-four hour excretion of urinary chloride as our measure of chloride loss, we must recognize that the organism attempts to compensate for its depletion by the retention of bicarbonate and may do so to the extent of developing alkalosis. It would be thought that the administration of normal saline solution with its replacement of water, sodium and chloride would invariably correct such an alkalosis; that is, if the patient were supplied with sufficient normal saline solution, and if ketosis were prevented, the electrolyte pattern of the plasma would be satisfactorily
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
1721
adjusted by the kidneys. However, in some instances, the excess sodium is not wholly excreted and the chloride administered may be incapable of displacing enough bicarbonate to nullify the alkalosis. Zintel, Rhoads and Ravdin 4 suggested in 1943 that ammonium chloride be used intravenously in a 2 per cent solution to supplement the other measure, and reported its successful use in seven patients. The solution is readily made up and sterilized by autoclaving for twenty minutes at 15 pounds pressure. The dosage is based on the patient's requirements; to reduce the carbon dioxide combining power by 1 per cent, ammonium chloride is given in the proportion of 16 mg. per kilogram of body weight. No unfavorable reactions were encountered in this series. Since then this procedure has had fairly wide usage and very recently Grace and Barr10 described its application in nine cases of alkalosis, including two due to intestinal obstruction. Grace and Barr also stressed two points of interest: first, the danger of inducing alkalosis by the administration of sodium lactate without the simultaneous use of normal saline while gastric suction is in operation, and second, the persistence of renal damage after continued alkalosis, at times to a point at which it appears to be permanent. On the other hand, in cases in which there is a greater loss of sodium than that of chloride, a status of acidosis may develop. This is particularly true when the loss of pancreatic, jejunal and ileal secretions is greater than that of gastric juice with its higher chloride content, and may be heightened by impairment of renal function. It is important to note at this point that where the acid-base equilibrium is disturbed in either direction, this disturbance occurs simultaneously with dehydration and the primary corrective measure remains the same~the administration of water, sodium and chloride. A state of ketosis may develop in the presence of either alkalosis or acidosis. We are accustomed to associating ketosis with acidosis due to starvation, as may well occur in intestinal obstruction. Abbott and Mellorsll have demonstrated that in experimental low intestinal obstruction the late development of vomiting may permit evidence of starvation and malnutrition to long precede severe dehydration. At intermediate points of obstruction there may well be mixed states in which the development of starvation and the loss of chloride by vomiting occur at parallel rates. There it is possible that the excess of ketone acids due to starvation may yet be insufficient to balance the preponderance of accumulated bicarbonate which has resulted from chloride depletion. Again, however, regardless of the state of acidosis or alkalosis, correction of the ketosis lies in the administration of sufficient glucose to prevent the further incomplete breakdown of the even-numbered fatty acids.
1722
EUGENE M. SCHLOSS
In addition to the foregoing, an increase in nonprotein nitrogen, first observed by Tileston and Comfort'2 in 1941, appears whenever complete gastrointestinal obstruction occurs at any level from the esophagus to the rectum. In comparison with most other types of azotemic retention, there is less effect on the urea nitrogen than on the remaining fractions, but both are increased. An increased destruction of protein due to the effects of starvation and dehydration upon tissue cells throughout the body has been repeatedly observed. Because of hemoconcentration and reduced blood pressure, the filtration pressure in the kidney is lowered and while the renal system may be able to concentrate well, it is usually unable to excrete the increased nitrogenous load so liberated, and hyperazotemia appears. As in the case of ketosis, the use of isotonic glucose solution tends to prevent the element of starvation in the destruction of protein and the administration of normal saline solution tends to restore the electrolytes, the loss of which is the major factor in the dehydration. SUMMARY
To summarize, the physicochemical factors in gastrointestinal obstruction are based on the effects of distention and loss of fluid and electrolytes which lead to dechlorination, loss of fixed base and dehydration. This is evidenced in studies which show: 1. Hemoconcentration. 2. Reduction in the fixed base of the serum. 3. Diminution in plasma chlorides. 4. Increase in urea and nonprotein nitrogen. 5. Change in acid-base equilibrium, more often to alkalosis, not infrequently in the direction of acidosis. 6. Hypochloremia and hypochloruria. 7. Frequent ketosis and high acidity of the urine. These phenomena are readily countered in the majority of instances by the parenteral administration of adequatc amounts of glucose and saline solutions. However, in some cases, ample quantities of these substances have been given to a point where the total serum base has been brought above the normal accepted range without controlling alkalosis. In these cases the intravenous use of 2 per cent ammonium chloride has been highly effective in treating or preventing the tetany, convulsions and possibly permanent renal damage which may result from alkalosis. The estimation of the quantities of fluids and electrolytes necessary to restore equilibrium is at present best made from serial studies of blood chlorides, carbon dioxide combining power, twenty-four hour urinary study for ketone bodies, urinary chloride excretion, intake and output records,
PHYSICOCHEMICAL CHANGES IN INTESTINAL OBSTRUCTION
17~3
blood nonprotein nitrogen, all as adjuncts to the clinical observation of the patient. REFERENCES 1. Hartwell, J. A. and Hoguet, J. P.: Experimental Intestinal Obstruction in Dogs, with
Especial Reference to the Cause of Death and the Treatment by ],arge Amounts of Normal Saline Solution. J.A.M.A. 59:8'2, 191'2. '2. Whipple, G. H., Stone, H. B. and Bernheim, B. M.: Intestinal Obstruction. I. A Study of a Toxic Substance Produced in Closed Duodenal Loops. J. Exper. Med. 17:'286, ]9]3.
3. Taylor, N. B., Weld, C. B. and Harrison, K.: Experimental Intestinal Obstruction. Canad. M. A. J. 2f!:'2'27, ]933. 4. Zintel, H. A., Rhoads, J. E. and Ravdin, I. S.: The Use of Intravenous Ammonium Chloride in the Treatment of Alkalosis. Surgery 14:7'2'1'., ] 943. 5. Gamble, J. 1.. and Ross, S. G.: The Factors in the Dehydration Following Pyloric Obstruction. J. (,lin. Investigation 1:403, 19'24. 6. McVicar, C. S. and Weir, J. F.: Toxemia of Intestinal Obstruction and Ileus; Clinical Deductions Regarding Its Nature and Treatment. Proc. Staff Meet., Mayo Clin. 8:193, 19'2'1'.. 7. Caller, F. A., Campbell, K. N., Vaughan, H. H., lob, L. V. and Moyer, C. A.: Postoperative Salt Intolerance. Ann. Surg. 119:533, ]944. 8. Power, F. H., l'ederson, S. and Maddock, W. G.: Clinical Experience with Sodium Chloride Replacement. Surgery 12:43'1'., 194'2. 9. Sanchez-Vegas, J., and Collins, E. N.: Importance of Urinary Chloride Determinations in Treatment of Patients with Pyloric Obstruction. Am. J. M. Sc. 211:4'28, 1946.
10. Grace, W. J. and Barr, D. P.: Complications of Alkalosis. Am. J. Med. 4:33], ]948. ] 1. Abbott, W. E. and Mellors, It. C.: Body Fluid Studies in Experimental Obstruction at Various Levels of the Gastrointestinal Tract. Surgery 12:445,1942. ]'2. Tileston, ·W. and Comfort, C. W.: The Total Non-protein Nitrogen and the Urea of the mood in Health and in Disease, as Estimated by Folin's Methods. Arch. Int. Med. 14:620, 1914.