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  • The Utility of Lactate Dehydrogenase Isoenzyme Pattern: DISCUSSION

LDH is an enzyme in the glycolytic pathway and its released as the result of cell damage. LDH isoenzyme analysis, which requires small volume samples, is quick and easy to perform. LDH isoenzymes may be useful in differential diagnosis since tissue damage releases isoenzymes contained therein, leading to a change in their pattern. Previous studies of the diagnostic utility of serous fluid LDH isoenzyme pattern reported controversial results. Several studies describe relative values of LDH isoenzymes in different pathologic states, concluding that serous fluid LDH isoenzymes were not diagnostic. The commonly used criteria of Light et al. for the differentiation of serous effusion establish the exudative or transudative nature of the serous fluid but do not determine its specific etiology. LDH isoenzymes may be released from cells that have infiltrated the body fluids other than serum. For example, in viral and tuberculous meningitis causing lymphocytosis, it may create an elevation of LDH-1 through LDH-3.

All the hundreds of different enzymes present in the human body are synthesized intracellularly, and most of them carry out their functions within the cells in which they are formed. With a few exceptions, the clinical chemist is principally concerned with changes in the levels (i.e., activity or mass) in serum, plasma or ascites of enzymes that are predominantly intracellular and that are normally present in the body fluids in low levels only. By measuring changes in the levels of these enzymes in a disease, it is possible to infer the location and nature of pathological changes in the tissues of the body. Therefore, it is necessary to understand the factor that affects the rate of release of enzymes from their cells of origin and the rate at which they are cleared from the circulation, so that changes in levels in disease can be interpreted correctly. These are: leakage of enzymes from cells (viruses, organic chemicals, shock, hypoxemia) and altered enzyme production (enzyme induction, proliferation).

Patients with malignant diseases show increased LDH activity in serum and malignant effusions; the LDH pattern usually shows a nonspecific increase in LDH-4 and LDH-5. LDH and its isoenzyme LDH-5 have been successfully used as prognostic markers for melanoma, various types of leukemia, testicular and some solid tumors. Schneider and colleagues reported that peritoneal fluid and serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumor or other gynecological malignancies. Interestingly, peritoneal fluid LDH demonstrated higher diagnostic sensitivity (87%) and greater diagnostic accuracy (90%) than serum LDH (60% and 77%, respectively) or serum CA-125 (73% and 83%, respectively). Vergnon et al. reported a high LDH-5 activity in 60% of patients with malignant effusion. It has also been shown that malignant lymphomas and small-cell lung carcinoma differ from other malignancies by a low LDH-5 isoenzyme secretion. Alternatively, the extent of the serosal inflammatory response to malignancy and the variable degree of serosal polymorphonuclear leukocytosis may determine the relative levels of LDH-4 and LDH-5 isoenzymes.

The LDH isoenzymes are unable to discriminate between hepatocellular carcinoma and cirrhosis or between abdominal neoplasia with and without liver metastases. In Lossos et al.’s study, there was more than one LDH isoenzyme pattern in the malignancy-associated effusions. In our study, elevated LDH level and LDH-4 and LDH-5 activities were also found to be in malignant ascites than nonmalignant ascites. A marked heterogeneity of malignant etiologies and a relatively small number of the malignant group in the present study precluded separation between two LDH isoenzyme patterns according to the cytopathological diagnosis. Moreover, we detected low LDH-1 activity in malignant ascites group than nonmalignant ascites group. This could be due to the various neoplastic tissues that secrete different LDH isoenzymes. Cobben et al. reported that the malignant pleural effusion group showed a low percentage of LDH-1, whereas the percentages of LDH-4 and LDH-5 were higher compared to transudative pleural effusion group, supporting our view. buy female viagra

Elevations of LDH activity are especially high in toxic hepatitis with jaundice; slightly lower values are observed in viral hepatitis which are often associated with elevations of LDH-3. Serum LDH-5 is often markedly elevated in patients with either primary liver disease, viral hepatitis or liver anoxia secondary to decreased oxygen perfusion. Rotenberg et al. reported, in patients with acute liver disorders, both the serum LDH and LDH-5 proportions were sensitive for liver injury. On the other hand, LDH-5 proportion was much less sensitive than LDH in patients with chronic liver disorders. In our study, we did not evaluate serum LDH isoenzymes, as we could not detect ascitic fluid LDH-5 activity in those patient groups. Interestingly, we had also found elevated ascitic fluid LDH-1 activity in patients with cirrhotic ascites. Ascitic fluid LDH-1 was found to be higher in the sterile cirrhotic group when compared with other groups. Moreover, LDH-3, LDH-4 and LDH-5 activities were higher in other groups when compared with sterile cirrhotic ascites. Therefore, ascitic fluid LDH isoenzyme activity may be more helpful in the diagnosis of sterile cirrhotic ascites.

LDH-5 values may be moderately elevated in congestive cardiac failure with hepatic congestion as a result of hepatic anoxia. Prabhakaran and Henderson reported two cases of congestive cardiac failure with unusually high activities of serum LDH and LDH-5. The LDH-5 component was 87% of the total serum activity. We had also found the highest ascitic fluid LDH-5 activity in the group of congestive heart failure supporting this view. You can afford your medication buy your Cialis Jelly online

In patients with suspected tuberculous peritonitis, the elevated ascitic fluid LDH levels have high sensitivity for the disease. In viral and tuberculous meningitis with lymphocytosis, an elevation of LDH-3 was detected. Zhang reported that both LDH level and isoenzymes in pleural fluid between the tuberculous and malignant groups did not correlate significantly. Contrary to these findings, we detected highest ascitic fluid LDH levels and LDH-3 activity in patients with tuberculosis. In addition, we found high ascitic fluid LDH-4 and LDH-5 activities in the tuberculous and malignant groups. However, these isoenzymes activities were similar in these groups.

Suzuki et al. studied the usefulness of fibrin degradation products (FDP) and lactic dehydrogenase isoenzyme patterns in assessing the clinical course of peritonitis. They concluded that the failure of normalization of FDP and LDH isoenzyme patterns suggests an incomplete recovery from peritonitis. They also proposed that FDP and LDH isoenzymes were useful in assessing the course of relapsing and persistent episodes of peritonitis. In our study, ascitic fluid LDH-2 and LDH-3 activities were found to be significantly elevated in the SBP group than in the sterile cirrhotic ascites group. Ascitic fluid LDH-2 and LDH-3 activities might be helpful in discriminating whether the ascitic fluid is infected or not.
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Paavonen et al. reported that the LDH concentration correlated somewhat with the pleural protein content. They concluded that the pleural LDH isoenzyme distribution, both in benign and malignant conditions, differed from that in serum, having shifted towards LDH-4 and LDH-5. These data possibly suggested that visceral or parietal pleural cells were rich in LDH isoenzymes 4 and 5. In our study, we also detected positive correlations between ascitic fluid LDH, LDH-2, LDH-3, LDH-4 and LDH-5 activities with ascitic fluid albumin, globulin and protein levels. However, there were negative correlations between ascitic fluid LDH-1 and ascitic fluid albumin, globulin and protein levels.

In conclusion, LDH and its isoenzyme activities in the ascitic fluid may contribute to the differential diagnosis of ascitic fluid etiology. In patients with malignant ascites, ascitic fluid LDH and LDH isoenzyme activities have high sensitivity and low specificity for the disease groups. However, owing to the relatively small study population, further studies are indicated to confirm the utility of LDH isoenzyme patterns in the diagnostic evaluation of ascites for malignant and nonmalignant etiologic categories.
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