General
=========================================================================

• Membrane bound glycoprotein with hepatic, osseous, renal and placental isoenzymes
• See also PLAP-placental alkaline phosphatase
• Tissue-nonspecific alkaline phosphatase (TNAP) plays a key role in bone mineralization by degrading inorganic pyrophosphate and providing free inorganic phosphate
• TNAP gene defect causes hypophosphatasia, characteristic of systemic skeletal hypomineralization
• Surgical pathology applications discussed below

Clinical features-serum levels
=========================================================================

• May be affected by ABO loci and obesity (BMC Genomics 2013;14:684)
• Elevated alkaline phosphatase screens for Vitamin D deficiency, although rarely alkaline phosphatase is normal (Clin Pediatr Endocrinol 2013;22:73)
• Bone alkaline phosphatase is associated with acute myocardial infarction in a population with high prevalence of hypovitaminosis D (Clin Chim Acta 2013;425:192)
• May predict outcome in alcoholic hepatitis (Biomed Res Int 2013;2013:614081)
• Higher serum levels in patients with chronic kidney disease stages 3-4 are associated with higher mortality and end stage renal disease (Am J Kidney Dis 2013;62:703)

Uses by pathologists
=========================================================================

• Component of an alternative method in immunohistochemistry, click here
• Muscle biopsies uses an enzymatic technique
  • Use frozen tissue (protocol from IHC World)
  • In inflammatory myopathies, appears to “spill out” from capillaries into interstitium due to increased vascular permeability
  • Also a marker for regenerating myofibers
• Osteoblasts (active)
  • Often labeled using naphthol phosphate and the diazonium dye fast blue to demonstrate alkaline phosphatase enzyme activity directly, present on apical (secretory) cell membrane
  • Confirms diagnosis of giant cell tumor of bone (Virchows Arch A Pathol Anat Histol 1978;378:287)

Micro images
=========================================================================

Muscle: regenerating fibers and proliferative connective tissues

Muscle: various images

Muscle: immature small fibers have cytoplasmic staining

Positive staining - normal
=========================================================================

• Cardiac muscle, smooth muscle
• Endothelial cells: sites of alkaline phophatase activity appear red, nuclei stain blue
• Osteoblasts

Positive staining - disease
=========================================================================

• Giant cell tumor of bone and soft tissue, mononuclear stromal cells (Hum Pathol 2005;36:945)
• Muscle: regenerating fibers, immature muscle fibers, proliferative connective tissues

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).