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Why Does Lactic Acidosis Occur in Acute Lung Injury?
fluid than in plasma but albumin is relatively increased, owing to its lower molecular weight and ease of transmembrane transport. Electrolyte concentrations are as predicted for a plasma filtrate, yielding fluid osmolarity consistent with such an ultrafiltrate and therefore less than plasma osmolarity. 1 Ideally, normal pericardia! fluid is studied in thoracotomized patients without pericardia! disease. Abnormal pericardia! fluids (pericardia! effusions and hydropericardia) differ qualitatively and quantitatively and are obtained during therapeutic or diagnostic pericardiocentesis, or surgical pericardiotomy, which is a more satisfactory approach. 2 It is these abnormal fluids that somehow have escaped the intense investigation accorded to pleural and ascitic fluids. Now Meyers and colleagues (see page 1213) make a signal contribution to the understanding of many pericardia! diseases and the chronically vexing question of distinguishing between exudates and transudates. This is the first large series (175 patients), an investigation that overcomes many drawbacks of a retrospective design by utilizing strict definitions and diagnostic criteria. The authors demonstrate striking similarities between pericardia! and pleural fluids and use Light's pleural fluid criteria3 effectively. Indeed, they "were unable to improve" upon them. They also characterize pericardia! fluids in diseases like rheumatoid arthritis; systemic and drug-induced lupus erythematosus; bacterial pericarditis; tuberculous pericarditis; viral pericarditis; uremia, myxedema, radiation, postmyocardial and postpericardial injury syndromes; malignancies; and their own term, "parainfective pericardia! effusion," all of which are compared using the variably scant literature on each. Differentiation between exudates and transudates sometimes is quite difficult based on ordinary tests and may be confounded by treatment. For example, in patients with improving congestive heart failure, more rapid reabsorption of water than protein and lactic dehydrogenase (LDH) can convert the hydropericardium typical of uncomplicated heart failure to a pseudoexudate. 4 However, it is in primary pericardia! disease that differentiation can be most valuable. The authors confirmed the sensitivity of numerous commonly measured constituents, such as leukocytes, LDH, glucose, protein, fluid-to-serum protein ratio, and others that have been considered valuable for specific investigations. Moreover, they confirm what had long been suspected-none of these are specific.4 In contrast, determinations such as fluid cytology had very high specificity for malignancy, and other "nonroutine tests" could be specific for various disease states. The authors conclude that evaluation of pericardia! fluids should begin with an attempt to differentiate between exudate and tran-
sudate, the most efficient approach requiring only four tests; tests for disease with actual or potential severity included bacterial culture and fluid cytology. In all approaches erythrocyte counts were practically worthless, probably because of varying additions of erythrocytes by the drainage procedures themselves. 2 This important contribution should stimulate searches for improved methodology, including physical characterization of fluids. Magnetic resonance imaging, for example, shows signal intensity in exudative fluids comparable to or stronger than that of myocardium, while transudates typically have very low signal intensity. 4 However, MRI itself would be impractical and is not "routine." Meyers and colleagues' careful extraction of important data in a large series and meticulous statistical approach finally puts the study of pericardia! fluid on a par with that of pleural fluid. This confers the dual benefit of a better understanding of the many diseases that involve the pericardium. David H. Spodick, MD, DSc, FCCP ·w orcester, Massachusetts Professor of Medicine, Cardiology Division, St. Vincent Hospital, University of Massachusetts Meaical School. Reprint requests: Dr. Spodick, St. Vincent Hospital, 25 Winthrop Street, Worcester, MA 01604-4593
REFERENCES l Spodick DH. Physiology of the normal pericardium: functions of the pericardium. In: Spodick DH. The pericardium: a comprehensive textbook. New York: Marcel Dekker, 1997; 15-26 2 Spodick DH. The technique of peticardiocentesis. J Crit Illness 1995; 10:807-12 3 Light RW, McGregor MI, Luchsinger FC, et a!. The evaluation of pleural effusion: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77:507-13 4 Spodick DH. Pericardial effusion and hydropericardium\vithout tamponade. In: Spoclick DH. The pericardium: a comprehensive textbook. New York: Marcel Dekker, 1997; 126-52
Why Does Lactic Acidosis Occur in Acute Lung Injury?
L actic acidosis is characteristic of all forms of
shock, including that due to systemic infection. It has been generally assumed that accumulation of excess lactate in patients with the systemic inflammatory response syndrome (SIRS) is due to hypoxia or inadequate delivery of oxygen to the tissues because of local or generalized ischemia. In the absence of sufficient oxygen, there is a shift from oxidative to anaerobic metabolism. Although lactate production provides a temporary source for muchneeded energy to the tissues, it is extremely ineffiCHEST/111/5/MAY, 1997
1157
cient and is associated with the rapid development of a severe metabolic acidosis. Maintenance of adequate tissue perfusion and oxygenation remains a key objective in the treatment of these patients. In a provocative article in this issue of CHEST (see page 1301), Kellum and colleagues propose a very different scenario to explain the accumulation of lactic acid in patients who have acute lung injury associated with sepsis or pneumonia. The investigators found that lactate concentrations in the arterial blood slightly exceeded those in the mixed venous blood in each of nine patients with these abnormalities, but not in patients who had no evidence of lung injury. They cite literature that failed to show either tissue hypoxia or systemic lactate production in animal or clinical studies of sepsis, and suggest that lactate generation by the lungs is responsible for metabolic acidosis in these patients. It has long been recognized that approximately 50% of the glucose consumed by the lungs is converted to lactate and appears in the pulmonary venous outflow.I In contrast, less than 25% of glucose consumed in other tissues (eg, the heart) is converted to lactate. This level of lactate production by the lungs is puzzling since they are exposed to the highest oxygen tensions of any internal organ. Tierney2 suggested that high pulmonary lactate production can be attributed to the absence of mitochondria in the attenuated portions of the type I pneumocytes and there is little room for mitochondria in the adjacent endothelium. Extrapolating from animal studies, one can estimate that normal human lungs, weighing a total of 1000 g, produce 11 mmol of lactate each hour. 1 It is certainly conceivable that injured lungs containing large numbers of leukocytes, which also produce lactate, may release significantly more lactate into the circulation. Whether they can generate as much as 200 mmollh remains to be confirmed. Even if the lungs can produce this much lactate, it cannot be concluded that they are the principal culprits responsible for lactate accumulation, because other organs that metabolize lactate should be able to accommodate this additional metabolic load. It can be estimated that a normal liver can consume a maximum of 140 mmol of lactate each hour and even more can be metabolized by other tissues, particularly skeletal muscle. 3 Liver abnormalities are common in septic patients, 4 and decreased extrapulmonary lactate consumption may play a more important role in the development of lactic acidosis than abnormal pulmonary metabolism. Detection of excessive pulmonary lactate production theoretically could help grade the severity of lung disease, but these measurements are fraught with technical difficulties. Because the entire cardiac output traverses the lungs, arteriovenous differences 1158
tend to be very small. Lactate derived from the heart and entering the left ventricular cavity through thebesian veins may increase arterial lactate levels. It would be difficult to attribute the differences in hemoglobin concentrations reported by Kellum and colleagues to shifts of fluid in the lungs. (An increase in hemoglobin from 14.9 to 15 gldL at a cardiac output of 5 Umin would require the movement of 33 mUmin between the plasma and lung tissues and could not be sustained for very long.) The collected samples may contain some residual saline from the catheters, which could also dilute lactate. Unless lactate concentrations are measured in whole blood, the relationship between red cell and plasma lactate concentrations must be determined. 5 Much remains to be learned about both pulmonary and extrapulmonary lactate metabolism in patients with SIRS. Further research in this area should address the question of whether injury to the lungs can alter extrapulmonary lactate metabolism, or whether abnormalities in extrapulmonary lactate metabolism are due to the direct effects of hemodynamic or other disturbances associated with sepsis. Richard M. Effros, MD, FCCP Randolph]. Lipchik, MD, FCCP Milwaukee Dr. Effros is Professor and Chief, and Dr. Lipchik is Associate Professor, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Medical College of Wisconsin . Reprint requests: Dr. Richard Ef(ros, Division of Pulmonary and Critical Care Medicine, Medicarcollege of Wisconsin, 9200 West Wisconsin Ave, Milwaukee WI 53226 REFERENCES 1 Fisher A. Intermediary metabolism. In: Crystal RG, West JB, Weibel ER, eds. The lung: scientific foundation. 2nd ed. Philadelphia: Lippincott-Raven Publishers, 1997; 1-7 2 Tierney DF. Intermediary metabolism of the lung. Fed Proc 1974; 33:2232-237 3 Naylor JM , Kronfeld DS, Freeman DE , et al. Hepatic and extrahepatic lactate metabolism in sheep: effects of lactate loading and pH. Am J Physiol 1984; 247:E747-E755 4 Parker MM, Fink MP. Septic shock. In: Rippe JM, Irwin RS , Fink MP, et al, eds. Intensive care medicine. 3rd ed. Boston: Little, Brown, and Co, 1995; 1886-99 5 McKelvie RS , Lindinger MI, Heigenhauser GJF, et al. Contribution of erythrocytes to the control of electrolyte changes of exercise. Can J Physiol Phannacol 1990; 69:684-93
Strategies for Treatment of Occult Carcinomas of the Endobronchus carcinomas of the lung are a subpopulation 0 ccult defined as carcinomas diagnosed by sputum
cytology, and bronchoscopy using brushings, wash-
sudate, the most efficient approach requiring only four tests; tests for disease with actual or potential severity included bacterial culture and fluid cytology. In all approaches erythrocyte counts were practically worthless, probably because of varying additions of erythrocytes by the drainage procedures themselves. 2 This important contribution should stimulate searches for improved methodology, including physical characterization of fluids. Magnetic resonance imaging, for example, shows signal intensity in exudative fluids comparable to or stronger than that of myocardium, while transudates typically have very low signal intensity. 4 However, MRI itself would be impractical and is not "routine." Meyers and colleagues' careful extraction of important data in a large series and meticulous statistical approach finally puts the study of pericardia! fluid on a par with that of pleural fluid. This confers the dual benefit of a better understanding of the many diseases that involve the pericardium. David H. Spodick, MD, DSc, FCCP ·w orcester, Massachusetts Professor of Medicine, Cardiology Division, St. Vincent Hospital, University of Massachusetts Meaical School. Reprint requests: Dr. Spodick, St. Vincent Hospital, 25 Winthrop Street, Worcester, MA 01604-4593
REFERENCES l Spodick DH. Physiology of the normal pericardium: functions of the pericardium. In: Spodick DH. The pericardium: a comprehensive textbook. New York: Marcel Dekker, 1997; 15-26 2 Spodick DH. The technique of peticardiocentesis. J Crit Illness 1995; 10:807-12 3 Light RW, McGregor MI, Luchsinger FC, et a!. The evaluation of pleural effusion: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77:507-13 4 Spodick DH. Pericardial effusion and hydropericardium\vithout tamponade. In: Spoclick DH. The pericardium: a comprehensive textbook. New York: Marcel Dekker, 1997; 126-52
Why Does Lactic Acidosis Occur in Acute Lung Injury?
L actic acidosis is characteristic of all forms of
shock, including that due to systemic infection. It has been generally assumed that accumulation of excess lactate in patients with the systemic inflammatory response syndrome (SIRS) is due to hypoxia or inadequate delivery of oxygen to the tissues because of local or generalized ischemia. In the absence of sufficient oxygen, there is a shift from oxidative to anaerobic metabolism. Although lactate production provides a temporary source for muchneeded energy to the tissues, it is extremely ineffiCHEST/111/5/MAY, 1997
1157
cient and is associated with the rapid development of a severe metabolic acidosis. Maintenance of adequate tissue perfusion and oxygenation remains a key objective in the treatment of these patients. In a provocative article in this issue of CHEST (see page 1301), Kellum and colleagues propose a very different scenario to explain the accumulation of lactic acid in patients who have acute lung injury associated with sepsis or pneumonia. The investigators found that lactate concentrations in the arterial blood slightly exceeded those in the mixed venous blood in each of nine patients with these abnormalities, but not in patients who had no evidence of lung injury. They cite literature that failed to show either tissue hypoxia or systemic lactate production in animal or clinical studies of sepsis, and suggest that lactate generation by the lungs is responsible for metabolic acidosis in these patients. It has long been recognized that approximately 50% of the glucose consumed by the lungs is converted to lactate and appears in the pulmonary venous outflow.I In contrast, less than 25% of glucose consumed in other tissues (eg, the heart) is converted to lactate. This level of lactate production by the lungs is puzzling since they are exposed to the highest oxygen tensions of any internal organ. Tierney2 suggested that high pulmonary lactate production can be attributed to the absence of mitochondria in the attenuated portions of the type I pneumocytes and there is little room for mitochondria in the adjacent endothelium. Extrapolating from animal studies, one can estimate that normal human lungs, weighing a total of 1000 g, produce 11 mmol of lactate each hour. 1 It is certainly conceivable that injured lungs containing large numbers of leukocytes, which also produce lactate, may release significantly more lactate into the circulation. Whether they can generate as much as 200 mmollh remains to be confirmed. Even if the lungs can produce this much lactate, it cannot be concluded that they are the principal culprits responsible for lactate accumulation, because other organs that metabolize lactate should be able to accommodate this additional metabolic load. It can be estimated that a normal liver can consume a maximum of 140 mmol of lactate each hour and even more can be metabolized by other tissues, particularly skeletal muscle. 3 Liver abnormalities are common in septic patients, 4 and decreased extrapulmonary lactate consumption may play a more important role in the development of lactic acidosis than abnormal pulmonary metabolism. Detection of excessive pulmonary lactate production theoretically could help grade the severity of lung disease, but these measurements are fraught with technical difficulties. Because the entire cardiac output traverses the lungs, arteriovenous differences 1158
tend to be very small. Lactate derived from the heart and entering the left ventricular cavity through thebesian veins may increase arterial lactate levels. It would be difficult to attribute the differences in hemoglobin concentrations reported by Kellum and colleagues to shifts of fluid in the lungs. (An increase in hemoglobin from 14.9 to 15 gldL at a cardiac output of 5 Umin would require the movement of 33 mUmin between the plasma and lung tissues and could not be sustained for very long.) The collected samples may contain some residual saline from the catheters, which could also dilute lactate. Unless lactate concentrations are measured in whole blood, the relationship between red cell and plasma lactate concentrations must be determined. 5 Much remains to be learned about both pulmonary and extrapulmonary lactate metabolism in patients with SIRS. Further research in this area should address the question of whether injury to the lungs can alter extrapulmonary lactate metabolism, or whether abnormalities in extrapulmonary lactate metabolism are due to the direct effects of hemodynamic or other disturbances associated with sepsis. Richard M. Effros, MD, FCCP Randolph]. Lipchik, MD, FCCP Milwaukee Dr. Effros is Professor and Chief, and Dr. Lipchik is Associate Professor, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Medical College of Wisconsin . Reprint requests: Dr. Richard Ef(ros, Division of Pulmonary and Critical Care Medicine, Medicarcollege of Wisconsin, 9200 West Wisconsin Ave, Milwaukee WI 53226 REFERENCES 1 Fisher A. Intermediary metabolism. In: Crystal RG, West JB, Weibel ER, eds. The lung: scientific foundation. 2nd ed. Philadelphia: Lippincott-Raven Publishers, 1997; 1-7 2 Tierney DF. Intermediary metabolism of the lung. Fed Proc 1974; 33:2232-237 3 Naylor JM , Kronfeld DS, Freeman DE , et al. Hepatic and extrahepatic lactate metabolism in sheep: effects of lactate loading and pH. Am J Physiol 1984; 247:E747-E755 4 Parker MM, Fink MP. Septic shock. In: Rippe JM, Irwin RS , Fink MP, et al, eds. Intensive care medicine. 3rd ed. Boston: Little, Brown, and Co, 1995; 1886-99 5 McKelvie RS , Lindinger MI, Heigenhauser GJF, et al. Contribution of erythrocytes to the control of electrolyte changes of exercise. Can J Physiol Phannacol 1990; 69:684-93
Strategies for Treatment of Occult Carcinomas of the Endobronchus carcinomas of the lung are a subpopulation 0 ccult defined as carcinomas diagnosed by sputum
cytology, and bronchoscopy using brushings, wash-