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ABSTRACT Aims: To conduct a review of the literature concerning existing methods to detect alkaline phosphatase (ALP) in human serum and to examine the dietary factors that modulate ALP-intestinal isoenzyme (IAP) activity, in light of new findings about its additional functions. Method: Alkaline phosphatase (ALP) testing was used to detecting liver diseases and bone disorders. When the liver is impaired, damaged hepatocytes release increased amounts of ALP into the blood. Results: If the results of other liver tests, such as for bilirubin, aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), are high, usually the ALP is usually coming from the liver. If it is not clear from the patient’s signs and symptoms or from the results of other routine tests whether the high ALP originates from is due to liver or bone, then a test for ALP isoenzymes, produced by different types of tissue, may be necessary to distinguish the sources of APL. There are 4 gene ALP families: 1), intestinal (found on chromosome 2); placental (2); germ cell (3) and non–tissue-specific (4). The tissue nonspecific isoenzyme includes the common serum forms of ALP from bone and liver. Discussion of Testing Methods: The total ALP activity is typically measured colorimetrically using the p-nitrophenol method. ALP isoenzyme levels can be measured via a method described by the Japanese Society of Clinical Chemistry, in which the ALP isoenzymes are separated electrophoretically with Titan III supporting media. A mouse monoclonal antibody specific to the bone alkaline phosphatase (BAP) is available and, has been adapted to an immunoassay to detection this enzyme. Conclusion: Isoenzyme testing is crucial before an accurate diagnosis can be made; this option should be considered when the signs and symptoms of certain diseases fail to provide a clear answer that explains clinical or laboratory features in acute or chronic diseases. Keywords: alkaline phosphatase, bone alkaline phosphatase, neutrophil alkaline phosphatase, tissue-nonspecific alkaline phosphatase, intestinal alkaline phosphatase.

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Why is it important?

ALP is found in all human tissues, and is particularly is concentrated in liver, bone, kidney, intestines, placenta, and in mature or immature leukocytes, as neutrophil ALP (NAP). This enzyme exists in multiple forms; some are coded on specific genetic loci, whereas others (such as isoforms enzymes) differ only by post-translational modification (primary glycosylation) [1]. Measurement of ALP isoenzymes may be helpful in determining which organ and tissues contain elevated ALP [2]. Based on the results of studies of hypophosphatasia, a systemic skeletal disorder resulting from a tissue-nonspecific ALP (TNAP) deficiency, TNAP has been suggested to be indispensable for bone mineralization [3]. Results suggest that variation in TNAP may be an important determinant of age-related bone loss in humans and that the phosphate metabolism pathway may provide a novel target for the prevention and treatment of osteoporosis. Four isoenzymes can be distinguished in the human body: the placental-specific ALP (PLAP), germ cell–specific ALP, ALP-intestinal isoenzyme (IAP) and TNAP. The production of TNAP is strongest in the liver, kidney, and bones [4]. Alternately, it has been suggested that TNAP could be a plasma membrane transporter for inorganic phosphate; also, TNAP is known to be a marker of osteoblast differentiation. However, there have been no previous reports, to our knowledge, of cell-surface expression of TNAP by immature cells

Perspectives

Clinical Relevance/Interpretation of the Results Derived from the Semi-quantitative NAP Method NAP is not easily detected in the human serum of healthy persons; however its activity increases in cases of bacterial infection. A leukemoid reaction is an excessive reactive outpouring of leukocytes that involves the appearance of immature forms (eg, blast cells, myelocytes, and metamyelocytes); however, this reaction is distinct from leukemia. The leukemoid reaction appears in response to infection, as well as to toxic, inflammatory, and neoplastic disorders. It may also appear in acute or chronic form with numerous granulocytes; it rarely appears with numerous lymphocytes, [6]. The major pathologic manifestations associated with leukemoid reaction are acute or chronic infections, especially in children; severe hemolysis and various solid tumors (especially of the breast, kidney, and lung, as well as metastatic cancers) and other illnesses borne on arrival at the point-of-care department. In leukemoid reaction the total leukocyte count is increased, typically in values of 50 000 to 100 000 per/ mm³, and the granulocytes, observed via optic microscopy using May-Grüunwald/Giemsa staining, display predominant toxic granulation (eg, Döohle bodies). Absence of the Philadelphia chromosome, or an extremely, low score NAP, in chronic myeloid leukemia (CML), is usually sufficient to distinguish that this malignant disease to be distinguished from a leukemoid reaction, which involves with very high NAP activity. Increased NAP activity is in some myeloproliferative diseases, such as Hodgkins`s lyimphoma and polycythemia vera (PV). NAP is substantially decreased in hematopoietic stem cell disorders such as CML, acute myelocytic leukemia (AML), and paroxysmal nocturnal hemoglobinuria (PNH) [27]. In myelopoiesis, NAP production in neutrophils is induced by GCS-F, and NAP is released into the bloodstream, perhaps through leakage of ALP from damaged or dead neutrophils. Fossa et al. [28]. reported leukocytosis and increased serum ALP in response to GCS-F treatment. They suggested that increased serum ALP activity was related to release of the enzyme resulting from the increased leukocyte count. In experiments in which GCS-F was administered to rats, reported by Tsuruta et al [29], increased serum ALP activity was traced to neutrophils. Also NAP activity allows the health care professional to distinguish between among) the following types of acute leukemia (in the absence of cortisol medications): acute myeloblastic leukemia (AML), in which NAP has low activity or is absent in mature neutrophils;, acute lymphoblastic leukemia (ALL), in which NAP activity is decreased in mature neutrophils;, hairy cell leukemia (HCL) with severe neutropenia, in which NAP activity is very high; and non-Hodgkin lymphoma (NHL), in which NAP activity is decreased. In children diagnosed with the diagnosis of trisomy 21 (eg. Down syndrome), NAP activity is increased due to surplus chromosomesal. NAP values are useful in distinguishing between PV (increased NAP activity) and secondary polycythemia (decreased NAP activity). CONCLUSION Laboratory results that quantify ALP activity, which are obtainable via different methods, help clinician doctors, to make the correct decisions concerning treatment of hospitalized patients with benign or malignant diseases. Interpretation of ALP results, using appropriate references of populations, is particularly important in children. Isoenzymes testis is crucially before an accurate diagnosis can be made; and this should be considered when the signs and symptoms of certain diseases fail to provide a clear answer that explains clinical and laboratory features in acute or chronic diseases.

Professor Aurelian Udristioiu
Hematology and Oncology Specialists LLC

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This page is a summary of: Alkaline Phosphatase Isoenzymes and Leukocyte Alkaline Phosphatase Score in Patients with Acute and Chronic Disease: A Brief Review, British Journal of Medicine and Medical Research, January 2014, Sciencedomain International,
DOI: 10.9734/bjmmr/2014/3309.
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