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EVALUATION OF ANTEMORTEM ACID-BASE STATUS BY MEANS OF DETERMINING T H E P H OF POSTMORTEM BLOOD JON V. STRAUMFJORD, J R . , M.D., AND JAMES J. BUTLER, M.D. Departments of Surgery and Pathology, Stale University of Iowa, College of Medicine, Iowa City, Iowa The evaluation of the antemortem fluid and electrolyte status by means of analyzing postmortem material has long been somewhat of an enigma to the pathologist. Relevant anatomic findings in human beings have been limited (.1) to the extremes of hydration, as observed on gross examination, and (2) to rare, nonspecific microscopic findings in disturbances of electrolytes.1 In recent years, more information has accumulated from chemical studies on postmortem blood and cerebrospinal fluid, with the emphasis on determinations of urea nitrogen, creatinine, and glucose in blood.3' *•7 These studies have been of only limited use, however, in evaluating the fluid and electrolyte status. One of the more important considerations of fluid and electrolyte balance is the concentration of hydrogen ions and the regulation of the pH of body fluids. It is frequently of interest to ascertain postmortem the possible existence and the degree of antemortem acidosis or alkalosis. A study on the pH of postmortem blood was described previously,4 but the results were largely inconclusive. This paper deals with the question of whether or not the antemortem acidbase balance in several patients was reflected in the pH of blood that was collected postmortem. MATERIALS AND METHODS After the usual exposure of the mediastinum at autopsy, blood was collected anaerobically from the left ventricle of the heart, using a long 16-gauge needle and a 10-ml. syringe that was rinsed with heparin (10 mg. per ml.). Samples of blood were also collected, in some cases, from the right ventricle or from the cephalic or antecubital veins. Within 20 min. after the blood was drawn, the pH was determined in a Cambridge pH meter (model R) with a constant-temperature electrode that was maintained at 37.5 C. Owing to the fact that the pH of blood varies considerably with changes in temperature, 6 we decided to determine the pH at 37.5 C , in order to permit a better comparison with antemortem pH. Patients were randomly selected from those who were autopsied. A wellestablished routine at the University Hospitals minimized the differences in the manner in which cases were handled after death. The clinical record, postmortem findings, and antemortem studies of electrolytes were evaluated, and the patients were classified with regard to their acidbase status into 3 groups: "normal," acidotic, and equivocal. All of the following Received, January 31, 1957; accepted for publication April 1. Dr. Straumfjord is College of Medicine Post-Doctoral Fellow, and Dr. Butler is Instructor in Pathology. 165 166 STRAUMFJORD AND BUTLER Vol. 28 criteria were fulfilled if the patient was classified in the acidotic group: (1) a clinical diagnosis of acidosis, or mention in the record of the signs and symptoms of acidosis; (2) a pathologic process of sufficient severity to produce an acidosis; and (3) blood chemical values that were consistent with acidosis. The chemical determinations used for classification were the postmortem levels of urea nitrogen and creatinine in the blood, and the antemortem values for total carbon dioxide, sodium, potassium, chloride, urea nitrogen, and creatinine in the blood that was analyzed on the day of death or the day prior to death. The patients who were classified in the "normal" group had no condition— recognized clinically or at autopsy—which predisposed them to a metabolic or respiratory acidosis. Only cases with an excellent clinical description of the course of the disease were accepted for this group. Generally, these persons had died unexpectedly. In a relatively large number of instances, the clinical records and postmortem findings yielded insufficient information to justify the classification of the patient into either the acidotic or the "normal" group, and these were then included in the equivocal group. RESULTS A comparison of the values for pH of blood collected postmortem from "normal" and acidotic patients is illustrated in Figure 1. The differences between the 2 categories are 0.2 of a pH unit or greater. The sole exception was a patient who had severe pancytopenia and multiple myeloma that was accompanied by a great elevation of the globulin fraction of the serum proteins. The decreased cellular constituents of the blood and the increased serum proteins may have been the reason for the exception in this instance. The pH of blood decreases in proportion to the length of time after death. This is apparent in Figure 1, but it is more graphically illustrated in Figure 2. The latter illustration consists of curves derived from serial determinations of pH performed after death of 5 patients. Case 1 was classified as "normal"; cases 3, 4, and 5 were acidotic; case 2 was equivocal. Case 3 was the previously mentioned patient who had multiple myeloma. The postmortem pH varies, depending upon the source of the blood, as indicated by the data in Table 1. The pH of blood from the upper extremities was higher than that of blood from the left ventricle of the heart, and this, in turn, was higher than that of blood from the right ventricle. Inasmuch as the values for pH in the "normal" and acidotic groups approach each other at approximately 6, it is of value to analyze a specimen from the source where the blood has the highest pH. Collecting blood from the veins of the arm has some technical difficulties; because of this, the left ventricle of the heart is regarded as the best source for postmortem specimens of blood. Blood that was removed from the cadaver and stored anaerobically at 25 C. decreased in pH at a rate that was 10 to 30 per cent of that for blood left in the body. This rate of decrease was only slightly less than that for blood removed from living persons and stored anaerobically at 25 C. Aug. 1957 167 pH OF POSTMORTEM BLOOD Owing to the fact that we could not establish with certainty the acid-base status of the equivocal group prior to death, we classified them further into acidotic, normal, or intermediate, depending upon the relation of the pH of their postmortem blood to that in the known acidotic and "normal" patients described in the previous section. On this basis, 10 were included in the acidotic group, 10 7.00 • NORMAL o ACIDOTIC 6.80 6.60 6.40 6.20 6.00 5.80 4 5 6 HOURS POST MORTEM 10 F I G . 1. The p H of whole blood from the left ventricles of the hearts of " n o r m a l " and acidotic patients, a t the indicated intervals postmortem. 7.00 BL000 FROM 6.80 • - 6.60 - 6.40 - ^ - ^ ^ ~ A ^ ^ " ^ 2 ^ x\ _^__^ ----^^ 6.00 5.80 " " • • - - - . —3 ^^^!1 6.20 -- -LEFT VENTRICLE, ARM VEIN \J _- ^ I • ' ^ I 2 "5 "~-»^ ^ I I " _ HOURS POST MORTEM F I G . 2. T h e decrease in pH of whole blood in relation to the postmortem interval in 5 patients. T h e specimens of blood were collected from t h e left ventricle of the heart; in 2 of the 5 patients, specimens were also collected from the antecubital veins. 168 Vol. 28 STRAUMFJORD AND BUTLER TABLE 1 COMPARISON O F T H E P H O F B L O O D COLLECTED SIMULTANEOUSLY FROM T H E L E F T AND T H E R I G H T V E N T R I C L E S O F T H E H E A R T , AND FROM T H E L E F T V E N T R I C L E AND ANTECUBITAL V E I N Case 1 2 3 4 5 6 7 8 9 10 11 12 Left Ventricle Right Ventricle 6.27 6.74 6.25 6.27 6.42 6.41 6.21 6.30 6.57 6.75 6.55 6.47 6.02 6.45 6.16 6.09 6.39 6.37 Antecubital Vein 6.57 6.47 6.74 6.93 6.55 6.64 in the intermediate group, and 6 in the normal group. Their clinical records and postmortem findings were then studied in order to determine what factors contributed to the postmortem value for pH. All of the 10 patients in the acidotic group had 1 or several of the following: advanced respiratory disease, advanced renal disease, septicemia, or prolonged periods of shock prior to death. The patients with intermediate values for pH had mild to moderate degrees of respiratory or renal disease, or an elevated temperature prior to death. Several diabetics were in this group. Four of the 6 patients with normal postmortem values for pH had no significant autopsy findings that suggested the likelihood of an antemortem alteration of acid-base balance. One of the remaining 2 persons was polycythemic and had seemingly complete occlusion of the pulmonary arteries. On the other hand, there was no antemortem clinical evidence of an alteration of acid-base balance in this patient. The remaining person in this group suffered from a moderate degree of acute pyelonephritis, but the postmortem levels of urea nitrogen and creatinine in the blood were normal. I t is also of interest that only 3 of 19 patients with malignant neoplasms had postmortem values for pH in the "normal" range. Eleven of the remaining 16 had pH values that indicated acidosis, and 5 were in the intermediate range. DISCUSSION Several factors contribute to the decrease in the pH of blood postmortem, among them the continued production of acids after death, and the variable concentrations of buffers in the blood and tissues. Increases in carbon dioxide, lactic acid, and inorganic and organic phosphates in postmortem blood have been described,4 with the accumulation of carbon dioxide accounting for the initial, sharp decrease in the pH of blood after death. 2 Carbon dioxide continues to accumulate until available oxygen is exhausted. Thereafter, there is a gradual Aug. 1957 pH OF POSTMORTEM BLOOD 169 decrease in pH as a result of the production and accumulation of metabolic acids. Possible sources of these acids include (1) lactic acid that is produced by the blood cells and by other cells, (2) accumulation of inorganic and organic phosphates, (3) the release of di- and tricarboxylic acids by cells, and (4) the hydrolysis of organic phosphates. Lactic acid that is produced by anaerobic metabolism of glucose is the most likely major metabolic acid, as suggested by the postmortem decrease in blood glucose.3' *•7 The quantitative effect of the various factors requires further study. Available information is not sufficient for evaluating the effects of buffers in tissue and blood as they relate to the decrease of pH in postmortem blood. The effects of acid from erythrocytes and leukocytes after death account for only a small part of the decrease in the pH of postmortem blood, as suggested by the difference in the reduction of pH of blood stored outside the body and that left in the body. The greater portion of acid produced, therefore, comes from other cells or tissues. It is not known whether or not the clearly defined difference between the acidotic and "normal" persons is solely the result of the antemortem acidotic state, or if it is also a reflection of a decreased buffering capacity. Inasmuch as the values for pH of acidotic and normal persons begin to converge at approximately 6 hours postmortem, the production of acid by the acidotic patients must occur at a lower rate after death. Because cessation of respiration produces a respiratory acidosis, there is some question as to whether or not the postmortem determination of pH is as useful for detecting an antemortem respiratory acidosis as it is for detecting an antemortem metabolic acidosis. Clarification of this distinction is not feasible without further studies. .letter, McLean, and Nutter 4 determined the pH of postmortem blood and their reported values were much higher than ours. A detailed description of the method for determining pH was not included in their paper, and we may only speculate on the reasons for the difference. The most likely reason for the difference is the temperature of the electrode and the electrode system used. The use of an open, probe-type electrode system at room temperature would yield much higher values for pH than those we obtained with a constant-temperature, MacInnes-Belcher electrode maintained at 37.5 C. The determination of pH of postmortem blood seems to be a useful means of evaluating the acid-base status of a patient prior to death, provided the analysis is performed within 5 hours after death. Further studies may prove that this limitation of time may be prolonged. The determination of the pH of blood, together with other factors, may also be of value in determining the time of death. If postmortem values for the pH of blood are to have significant meaning, the blood must be drawn anaerobically; for comparative purposes, all of the determinations must be performed at one temperature, preferably 37.5 C , and with blood from the same site, preferably the left ventricle of the heart. The instrument used for the measurement of pH must be sensitive to small changes in pH. Not all pH meters are satisfactory for this purpose. 170 S T R A U M F J O R D AND B U T L E R Vol. 28 SUMMARY The pH of blood decreases in relation to the length of time after death. During the first 5 hours postmortem, it is useful in evaluating the antemortem acidbase status of a patient. The pH of postmortem blood collected from different sites varies. The left ventricle of the heart seems to be the most suitable source of blood for postmortem determinations of pH. SUMMARIO I N I N T E R L I N G U A Le pH de sanguine descende in proportion al tempore passate depost le morte. Durante le prime 5 horas post morte, determinationes del pH del sanguine es utile pro evalutar le stato acido-basic del patiente ante su morte. Le pH de sanguine colligite post morte ab varie sitos non es identic. Le ventriculo sinistra del corde es apparentemente le plus appropriate fonte de sanguine pro determinationes de pH post morte. Acknowledgment. The authors would like to express their appreciation to Paul A. Nielsen, L.E., for his assistance in this study. REFERENCES 1. GOODOF, I . I., AND MACBRYDB, C. M . : H e a r t failure in Addison's disease with myocardial changes of potassium deficiency. J . Clin. Endocrinol., 4: 30-34, 1944. 2. G R O D I N S , F . S., L E I N , A., AND A D L E R , H . F . : Changes in blood acid-base b a l a n c e d u r i n g asphyxia and resuscitation. Am. J . Physiol., 147: 433^45, 1946. 3. H A M I L T O N - P A T E R S O N , J . L., AND J O H N S O N , E . W. M . : P o s t m o r t e m glycolysis. J. P a t h . & Bact., 50: 473^182, 1940. 4. J E T T E R , W. W., M C L E A N , R., AND N U T T E R , M . K . : P o s t m o r t e m biochemical c h a n g e s . Am. J . P a t h . , 25: 789-790, 1949. 5. NAUMANN, H . N . : Studies on postmortem chemistry. J . Clin. P a t h . , 20: 314-324, 1950. 6. ROSENTHAL, T . B . : T h e effect of temperature on the p H of blood and plasma in vivo. J. Biol. Chem., 173: 25-30, 1948. 7. T O N G E , J . I., AND W A N N E N , J . S.: T h e postmortem blood sugar. M . J . Australia, 1: 439-447, 1949.