Common Causes
What Causes Elevated Alkaline Phosphatase?
- Pregnancy- The placenta, at the beginning of the third trimester, produces high levels of alkaline phosphatase enzymes. ...
- Liver Disease- Different forms of liver diseases can change and increase the levels of the alkaline phosphatase.
- Bone Disease- The bone disease is among the most common causes of elevated alkaline phosphatase. ...
Related Conditions
Your Alkaline phosphatase level of 132 is a High Alkaline phosphatase level. If your Alkaline phosphatase is in between 30 U/L and 120 U/L, then you need not worry as 30-120 U/L is the normal range for Alkaline phosphatase. But if your Alkaline phosphatase is lesser or greater than the above values, then there may be some problem in your body. Normal range of Alkaline phosphatase found among men : 30 - 120 U/L
What are the reasons for an elevated alkaline phosphatase?
High alkaline phosphatase symptoms include fatigue and weakness, nausea and vomiting, weight loss, fever, itching, yellow skin, dark urine, abdominal pain, and many more. In most cases, high levels of alkaline phosphatase are usually temporary and don’t pose a serious concern. However, to be safe, it’s important to talk to the doctor to ...
What are dangerous levels of alkaline phosphatase?
What is considered to be a high alkaline phosphatase level? Dr. Pietro Seni answered Orthopedic Surgery 48 years experience 20-100IU/L: Normal levels in adult are between 20 to 140iu/l.In children and pregnant women levels can be higher up to 350iu?L.Anything above 200iu/l should be in... Read More 4.9k views Answered >2 years ago Thank 20 thanks
What are the symptoms of high alkaline phosphatase?
What is considered a very high level of alkaline phosphatase?
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How does alkaline phosphatase affect bone?
Insulin-like growth factor and other osteoclastogenic cytokines are also implicated. Serum alkaline phosphatase (ALP) is associated with vascular calcification, while bone-specific alkaline phosphatase, or BAP, is a marker of bone formation and bone turnover and is used in the evaluation of skeletal status.
What is the function of alkaline phosphatase?
ALP is an enzyme found in your bloodstream. It helps break down proteins in the body and exists in different forms, depending on where it originates. Your liver is one of the main sources of ALP, but some is also made in your bones, intestines, pancreas, and kidneys.
How does alkaline phosphatase affect bone density?
Their findings, published March 11 in BJU International, show that a decrease in alkaline phosphatase is linked to an increase in bone mineral density — or alternatively, that the higher the level of alkaline phosphatase, the higher chance of having weak bones.
What does high alkaline phosphatase in bone mean?
Instead, it can indicate a bone disorder, such as Paget's Disease of Bone, a condition that causes your bones to become abnormally large, weak, and prone to fractures. Moderately high levels of alkaline phosphatase may indicate conditions such as Hodgkin lymphoma, heart failure, or a bacterial infection.
Is alkaline phosphatase a marker of bone formation?
Alkaline phosphatase activity, a hallmark of the osteoblast phenotype, is a widely accepted marker of new bone formation and early osteoblast activity.
What proteins does alkaline phosphatase break down?
3.1), or basic phosphatase, is a homodimeric protein enzyme of 86 kilodaltons. Each monomer contains five cysteine residues, two zinc atoms and one magnesium atom crucial to its catalytic function, and it is optimally active at alkaline pH environments....Alkaline phosphatase.Available protein structures:PDBsumstructure summary3 more rows
What is the level of alkaline phosphatase in osteoporosis?
The spinal bone mineral content has revealed significant correlations with serum total ALP. Recent study has also shown that the activity of serum total ALP >129 U/L is used as an indicator for osteoporosis in men [16].
What is alkaline phosphatase bone specific test?
The ALP bone isoenzyme test is a blood test that measures the levels of ALP-2 in your bones. The test can detect abnormal levels of bone growth that may indicate a bone disease or another serious condition such as leukemia or hyperparathyroidism.
What happens if alkaline phosphatase is too high?
While alkaline phosphatase may not necessarily cause harm to the body itself, elevated levels are associated with cancer, bone, liver, and kidney diseases [7]. Additionally, lifestyle factors, medication, and certain supplements can raise alkaline phosphatase levels.
Can a fracture cause elevated alkaline phosphatase?
The level of serum alkaline phosphatase is often valuable in the diagnosis of metabolic bone disease but rises after any uncomplicated fracture, and since such a rise may limit the diagnostic usefulness of this measurement in detecting osteomalacia its extent was assessed in 106 patients.
What is the reason for increase in alkaline phosphatase?
Causes of high ALP levels. ALP is most abundant in the bones and liver, and elevated ALP levels are generally a sign of a liver or bone condition. An obstruction of the liver or damage to it causes ALP levels to rise. Elevated levels can also result from an increase in bone cell activity.
What happens when alkaline phosphatase is high?
An alkaline phosphatase (ALP) test measures the amount of ALP in your blood. Although ALP exists throughout your body, the two main sources of ALP in your blood are your liver and bones. High levels of ALP may indicate liver disease or certain bone disorders, but an ALP test alone cannot diagnose a condition.
What does it mean if your alkaline phosphatase is low?
Low alkaline phosphatase is when your blood levels are under 30 U/L (lab dependent). Your body needs just the right amount of alkaline phosphatase to keep your gut, brain, and bones healthy. Low levels can suggest zinc, magnesium, or protein deficiency.
What are symptoms of low alkaline phosphatase?
Low ALP: Could it be HPP?Failure to thrive (in infants)Short stature.Bone and joint pain.Missed gross motor milestones (standing, sitting, crawling, turning over)Misshapen head, caused by craniosynostosis or chiari malformation.Brain fog.
Should I be worried if my alkaline phosphatase is high?
While alkaline phosphatase may not necessarily cause harm to the body itself, elevated levels are associated with cancer, bone, liver, and kidney diseases [7].
Overview
Alkaline phosphatase (ALP) is an enzyme that’s found throughout your body. An enzyme is a type of protein in a cell that acts as a catalyst and allows certain bodily processes to happen. There are thousands of enzymes throughout your body that have important functions.
Test Details
A healthcare provider called a phlebotomist usually performs blood draws, including those for an ALP blood test, but any healthcare provider who is trained in drawing blood can perform this task. The samples are sent to a lab where a medical laboratory scientist prepares the samples and performs the test on machines known as analyzers.
Results and Follow-Up
Blood test reports, including alkaline phosphatase (ALP) test reports, usually provide the following information:
What is the function of bone alkaline phosphatase?
Bone alkaline phosphatase (bone ALP) is an ectoenzyme on the outer surface of the cell membrane of osteoblasts. It is partly released into the circulation. Bone ALP and liver ALP constitute about 95% of the total ALP activity in human serum. They are isoforms of the tissue nonspecific ALP encoded on chromosome 1 and differ by posttranslational ...
What is bone ALP?
Bone ALP is a major regulator of bone mineralization. It hydrolyzes inorganic pyrophosphate which is a naturally occurring inhibitor of mineralization. Bone ALP also provides inorganic phosphate (from pyrophosphate and organic phosphomonoesters) for the synthesis of hydroxyapatite [7,8].
What is hypophosphatasia in dentistry?
Hypophosphatasia is a genetic disorder in which the enzyme bone alkaline phosphatase is deficient or defective. Phenotypes of hypophosphatasia can vary from premature loss of deciduous teeth to severe bone abnormalities leading to neonatal death. 21 In general, the earlier the presentation of symptoms, the more severe the disease. In mild forms the early loss of primary teeth may be the first and only clinical sign, as shown in Fig. 25.10. The early loss of teeth is the result of defective cementum formation, which affects attachment of tooth to bone. There currently is no treatment for the disease, but the dental prognosis for the permanent teeth is good. Typically, the primary incisors are exfoliated before the age of 4 years, the other primary teeth are affected to varying degrees, and the permanent dentition is normal. Hypophosphatasia can be diagnosed by a finding of low alkaline phosphatase levels in a serum sample.
What is the relationship between IGFs and ALPBi?
ALPBi is relationship to IGFs implies a relationship between serum ALPBi and all the activities in which the IGF family plays a role , such as energy production through the regulation of glucose entry into the cell, membrane permeability, free radical production, ATP production, inflammation, etc.
Where is ALP expressed?
Bone ALP is constitutively expressed in the osteoblast and has been localized to the plasma membrane by a variety of histological techniques [ 2, 88 ]. It is also found in ameloblasts and odontoblasts [ 89] and in cultured cells with the osteoblast phenotype [ 88, 90, 91 ].
Is ALP important for bone mineralization?
Since ALP was first identified in calcifying mammalian cartilage, it has been considered important in bone mineralization ( Table 2 ), but hypophosphatasia mutations are the most compelling evidence for its essential role in skeletal metabolism [ 4, 98 ]. Table 2. bTNAP properties relevant to bone mineralization. 1.
Is ALP released into the circulation?
It is partly released into the circulation. Bone ALP and liver ALP constitute about 95% of the total ALP activity in human serum. They are isoforms of tissue nonspecific alkaline phosphatase (TNAP) encoded by the gene on chromosome 1 and differ only by post-translational modifications (N- and O-glycosylation, sialic acid content).
What Is Alkaline Phosphatase?
Alkaline phosphatase is an enzyme. An enzyme is a type of protein that catalyzes (causes or accelerates) chemical reactions in the body. ALP is produced mainly by the liver and bones but is also synthesized in smaller quantities by the intestines and kidneys. ALP is also secreted from the placenta during pregnancy. 1
What is ALP in blood work?
Other Blood Tests. Alkaline phosphatase (ALP) is an enzyme found in the blood that helps break down proteins. ALP plays a role in numerous processes in the human body, and any abnormalities in blood concentrations—either high or low—may be indicative of diseases ranging from gallstones and thyroid disease to hepatitis and cancer . ...
What does high ALP mean in blood test?
If blood test results show a high level of alkaline phosphatase (ALP), it could indicate liver damage or a bone disorder. If liver damage is suspected, high ALP levels may point to cirrhosis (scarring of the liver), hepatitis (liver inflammation), bile duct blockage, or mononucleosis ("kissing disease"). 10
What is the enzyme that catalyzes chemical reactions?
Alkaline phosphatase is an enzyme. An enzyme is a type of protein that catalyzes (causes or accelerates) chemical reactions in the body. ALP is produced mainly by the liver and bones but is also synthesized in smaller quantities by the intestines and kidneys. ALP is also secreted from the placenta during pregnancy. 1 .
What is an ALP test?
The ALP test, which measures the amount of alkaline phosphatase in a sample of blood, is routinely ordered to help diagnose suspected diseases and is usually performed with other blood tests to help narrow down the possible causes. Common Blood Tests and What They Mean. David Silverman / Getty Images.
Why is ALP important?
ALP tests play an important role in the diagnosis of liver disease. Similar symptoms can occur with gallbladder diseases. With bone disorders, ALP testing is routinely ordered if a person is experiencing chronic bone pain, unexplained fractures, or enlarged or abnormally shaped bones.
What is the normal ALP level for a child?
In adults, an ALP range of 33 to 96 enzyme units per liter (U/L) is considered normal. For children, this range is under 350 U/L. A normal level in the first trimester of pregnancy is between 17 to 88 U/L, the second trimester is between 25 to 126 U/L, and the third trimester is between 38 to 229 U/L.
What is the role of alkaline phosphatase in mineralization?
The existing status of this critical enzyme should be reviewed periodically. ALP increases inorganic phosphate local rates and facilitates mineralization as well as reduces the extracellular pyrophosphate concentration, an inhibitor of mineral formation. Mineralization is the production, inside matrix vesicles, of hydroxyapatite crystals that bud from the outer membrane of hypertrophic osteoblasts and chondrocytes. The expansion of hydroxyapatite forms into the extracellular matrix and its accumulation between collagen fibrils is observed. Among various isoforms, the tissue-nonspecific isozyme of ALP (TNAP) is strongly expressed in bone, liver and kidney and plays a key function in the calcification of bones. TNAP hydrolyzes pyrophosphate and supplies inorganic phosphate to enhance mineralization. The biochemical substrates of TNAP are believed to be inorganic pyrophosphate and pyridoxal phosphate. These substrates concentrate in TNAP deficient condition which results in hypophosphatasia. The increased level of ALP expression and development in this environment would undoubtedly provide new and essential information about the fundamental molecular mechanisms of bone formation, offer therapeutic possibilities for the management of bone-related diseases.
What is the signaling mechanism involved in bone mineralization?
Fig. 7. Signaling mechanism involved in bone mineralization. Hydroxyapatite deposition in the matrix vesicles budding with hypertrophic osteoblasts/chondrocytes is the initial stage of the mineralization phase. Hydroxyapatite crystal is produced from Ca2+ absorbed by the annexin calcium channel and Pi given by type-IIINa/Pico transporter and PHOSPHO1, which hydrolyzes the membrane-derived phosphoethanolamine (PEA) and sphosphocholine (PCho). Then, the hydroxyapati te reaches matrix vesicle membrane and propagates with the TNAP impact, and is accumulated within fibrils of the collagen. TNAP hydrolyzes PPi which inhibits hydroxyapati te formation. NPP1 produced PPi and is transported with the help of ANKH into extra cellular space. The coordinated expression and interactions of TNAP, NPP1 and ANKH are essential for second stage of mineralization process.
What are the consequences of ALPL mutations?
ALPL mutations contribute to defects in TNAP function and, as such, extracellular aggregation of PPI, a normal TNAP substrate and a potent inhibitor of mineralization, are the consequence of hypophosphatasia. Hypophosphatasia also includes rickets, osteomalacia and tooth sludge. Enzyme substitution with minerally-target TNAP from birth avoided extreme hypophosphatasia disease in TNAP −/− knockout mice and then proved that babies and young children with life-threatening hypophosphatasia disease was saved and handled significantly. Clinical studies show features of hypophosphatasia, such as craniosynostosis and muscle fatigue in extreme hypophosphatasia, that have not been completely established ( Millán and Whyte, 2016 ). It is distinguished by rough tissue hypomineralization and is graded into 5 (1) perinatal, (2) baby, (3) infantile, (4) adult and (5) odontophosphatases by the extent of the disease and age of onset. (1) the most extreme perinatal type contributes to the death of the fetus affected. (2) the infantile type develops about six months following birth, and the principal cause of death is respiratory failure. (3) the childhood type includes milder signs, deformity of the limbs and precocious loss of the fevery teeth within 2 years after conception. (4) The adult type shows moderate symptoms in the young adulthood. (5) Dental signs but not skeletal abnormalities describe odontohypophosphatasia. 409 mutations in TNAP have so far been reported which cause exceptional clinical heterogeneity ( http://www.sesep.uvsq.fr/03_hypo_mutations.php ). The mutant protein's enzyme function and properties were studied. The kinetic behavior of secreted-type mutant proteins for PPi and PLP differ from the commonly utilized artificial substrate pnitrophenyl phosphate ( Di Mauro et al., 2002 ). Mediator of ErbB2‐driven cell Motility 1 (MEMO1) utilizes numerous extracellular signals and regulates the dimerisation and activity of ALP via the manipulation of the local redox state. ALP monomers are dimerized by disulfide bond, and divalent ions such as Zn++ or Mg++ are associated with ALP stabilisation. The active ALP dimer catalyzes iPP and releases Pi used to mineralize the bone. If Memo is absent, the cells' redox state is changed, and ALP cannot be integrated in a dimer or balanced by divalent ions resulting in diminished activity i.e hypophosphatasia ( Moor et al., 2018 ).
What is ALP in chemistry?
ALP is an echoenzyme hydrolyzing the ester of monophosphate at elevated pH (8–10) . Human ALP is categorized into four groups, depending on where they are predominantly expressed, as seen in Table 1. Tissue-nonspecific alkaline phosphatase (TNAP) is found in hypertrophic chondrocytes and osteoblasts cell membranes and often concentrates in those cells on the membranes of matrix vesicles. The biochemical substrates of TNAP shall be assumed to be pyridoxal 5′-phosphate (PLP) ( Whyte et al., 1995 ). During mineralization, TNAP hydrolyzes PPi. This reduces PPi, a hydroxyapatite-forming blocker, and supplies Pi for hydroxyapatite production. Additionally, it is reported that in serum and urine of TNAP knockout mice and TNAP-deficient patients, PPi and PLP phosphoethanolamin were increased ( Millán and Whyte, 2016) Retinoic acid regulates the expression of TNAP by interacting between the complex retinoic acid receptor and retinoic acid response factor in the TNAP gene promoter region ( Orimo and Shimada, 2005 ). The mineralization regulator by increasing TNAP activity is considered to be an active source of Vitamin D3. This event does not increase transcriptional activity, but through post-transcription regulation by increased stabilization of TNAP mRNA. ( Nam et al., 2017 ). Phosphates that lead to positive regulation of TNAP in bone cells and β-glycerophosphate enable activation of both TNAP and mineralization ( Vimalraj et al., 2016 ). TNAP deficient Mice cause extreme type of hypophosphatasia. This TNAP −/− mice are deficient in development, experience epileptic and apnea seizures, and die before they wean. A tissue analysis shows an irregular osteoblast mineralization and morphological changes, aberrant growth of the lumbar nerve core, abnormalities of intestinal morphology, decreased thymus apoptosis and irregular spleens ( Narisawa, 2015 ). The matrix around matrix vesicles of growth plate and bone in Akp2 −/− deficient mice inhibits the proliferation and growth of hydroxyapathy crystals, although mineral crystals are initiated within matrix vesicles ( Yamamoto et al., 2011 ). At least 4 isozymes are found in the mouse and the Akp2 gene is referring the human ALPL gene.
How does FGF23 affect bone?
FGF23 decreases the production of TNAP in bone cells through a FGF-3 regulated signaling axis Klotho-independent, which leads to an accumulation of pyrophosphate, an inhibitor of mineralization. Increased Fgf23 synthesis leads to an auto/paracrin inhibition of TNAP which results in aggregation of pyrophosphate in the patient with chronic kidney disease-mineral and bone disorder ( Andrukhova et al., 2018 ). There were no discrepancies observed between various bone types after six day cultivation for osteoblast replication time, proliferation and basal TNAP function. Osteoblasts were initially extracted from various bone types, subchondral, trabecular and canine cortical in dog model ( Meeson et al., 2019 ). The inhibition of the osteoblast matrix mineralization with unique targeting of TNAP is shown to significantly affect acute myeloid leukemia osteoblast-mediated defense ( Sterner et al., 2018 ). PTH is a potent down-regulator of osteoblasts Phosp1 and Smpd3, and is a co-operative mechanism for inducing mineralization in PHOSPHO1, nSMase2 and TNAP ( Houston et al., 2016 ).
Why is bone mineralization important?
Understanding of the underlying mineralization processes is important not only in physiological growth, but also to manage mineralization with deficiency. The recent problem in age related bone mineralization is an alert to the researchers to give more attention on development of prevention method in mineralization deficient and disease related to calcification.
Where is the ALP gene located?
3 ALP genes are located at chromosome 2 and the fourth one that is L/B/K ALP resides at chromosome 1 as shown in Fig. 1. The nomenclature of these genes is based on the tissue where they are highly expressed and the detail has been tabulated in Table 1. The gene L/B/K is longer than that of others due to increased introns length. The details of human ALP gene are obtained from http://atlasgeneticsoncology.org/Genes/GC_ALPL.html. The intron and exon numbers and length details are clearly described in self-explanatory images obtained from “Atlas of Genetics and Cytogenetics in Oncology and Haematology” website. Briefly, ALPL gene located in chromosome 1 starts at 21,509,358 and ends at 21578412 bp from pter (according to hg38-Dec_2013) and link to chromosome band 1p36.12. Three transcripts have shown with their NCBI reference numbers namely, (1) NM_000478 has 12 exons, (2) NM_001127501 has 11 exons and NM_001177520 has 10 exons.
What is an alkaline phosphatase test?
What’s an Alkaline phosphatase bone isoenzyme test? Alkaline phosphatase (ALP) is an enzyme that’s naturally present throughout your body. It comes in many variations called isoenzymes. Each isoenzyme of ALP is different, depending on where in your body it’s made. Your bones make an isoenzyme called ALP-2.
What enzyme increases when bones are growing?
Your bones make an isoenzyme called ALP-2. Levels of this enzyme increase when your bones are growing or bone cells are active.
What is the ALP test?
The ALP bone isoenzyme test is a blood test that measures the levels of ALP-2 in your bones. The test can detect abnormal levels of bone growth that may indicate a bone disease or another serious condition such as leukemia or hyperparathyroidism.
What is the condition of bone that causes elevated bone test results?
osteoblastic bone tumors. osteomalacia, or rickets. osteoporosis. Paget’s disease of bone. An elevated test result could also indicate serious conditions such as hyperparathyroidism or leukemia. Both diseases affect your bones as well as other parts of your body.
How to do ALP bone isoenzyme test?
They will tie a tourniquet around your upper arm and locate a vein inside your elbow for the blood draw. Next, they’ll clean the area around it. A needle will be inserted, and blood will be drawn into a small vial.
Why do doctors order ALP-2?
Your doctor may order an ALP-2 test if they’re concerned you may have a bone disease. The symptoms of bone disease include: chronic bone and joint pain. bones that are brittle or break easily. deformed bones. An ALP-2 test can also be used to monitor bone disease treatment.
Is ALP-2 normal for children?
Children have higher levels of ALP bone isoenzyme. ALP-2 is also elevated in people with broken bones. In both groups, bone growth is expected and normal.
What is the function of alkaline phosphatase?
Alkaline phosphatase is an enzyme found in all tissues in the human body. In balance, it protects your gut against harmful bacteria and aids digestion. However, high blood levels usually point to liver or bone problems. Read on to understand the symptoms and causes of high alkaline phosphatase and how to reduce it naturally.
What Does High Alkaline Phosphatase Mean?
Children and pregnant women can have significantly higher levels of the enzyme in their blood [ 1 ].
How to lower alkaline phosphatase?
To lower your alkaline phosphatase levels, you may stop smoking and get more omega-3s in your diet.
What does ALP do to your body?
Its major function is to protect your intestinal tract against bacteria, aid in digestion, breakdown fats and some B vitamins, and promote bone formation [ 1 ]. High levels of ALP in the blood may indicate bone, liver, or bile duct disease.
Which type of anemia is more likely to have high alkaline phosphatase levels?
People with sickle cell anemia and children with epilepsy are more likely to have high alkaline phosphatase levels.
Where is alkaline phosphatase found?
Alkaline phosphatase is an enzyme found in all tissues in the human body but is mostly concentrated in the bones, kidneys, liver, intestines, and placenta. It exists in different forms, depending on where it originates [ 1 ].
How long does it take for ALP to decrease?
In untrained male subjects, one single bout of resistance exercise can cause bone ALP activity to significantly decrease two and three days after the exercise [ 37 ].
Why is alkaline phosphatase important?
Although the primary importance for measuring alkaline phosphatase is to check for the possibility of bone disease or liver disease, forming a differential diagnosis should focus on the pathology (see below for causes of normal, physiologic elevations) found within each location where the enzymes are found.
Where are alkaline phosphatases found?
Alkaline phosphatases act by splitting off phosphorous, creating an alkaline environment. They are found predominantly in the liver and bone , with intestinal enzymes contributing up to 20% of total activity; other tissue beds include the kidney, placenta, adrenal cortex, lung.
Why is alkaline phosphatase elevated during pregnancy?
Use appropriate reference ranges for pregnant patients: Women in the third trimester of pregnancy have elevated alkaline phosphatase levels (increases up to 2-3 times normal) because of an influx of placental alkaline phosphatase. A separate reference range is required for pregnant patients.
How to determine if a phosphatase level is elevated?
Because of the diverse sources of the enzyme, the fist step in determining a non-physiologically elevated alkaline phosphatase level is to identify the source of the elevation . Electrophoretic separation into distinct isoenzymes on polyacrylamide gel or Sepharose is the most sensitive and specific way to do this; however, these tests are not widely available and not commonly used. Hepatic origin can, in these cases, be evaluated by obtaining a serum γ-glutamyltransferase or 5′-nucleotidase level.
What causes elevated alkaline phosphatase?
Non-hepatobiliary causes of elevated alkaline phosphatase can be further divided into osteoblastic/bone disease and non-bone, non-liver disease: Phsyiologic and pathologic bone growth (healing fracture, osteoblastic bone tumors, metastatic cancer to the bone, myeloma, osteomalacia) Non-bone, non-liver disease:
Why is the bone isoenzyme elevated?
The bone isoenzyme is elevated as a result of increased osteoblastic activity . The highest total values have been attributed to Paget’s disease and osteomalacia/rickets, with levels correlating with the extent of the disease on skeletal surveys and with parameters of bone resorption.
When a serum alkaline phosphatase elevation is detected, it must be interpreted in the clinical?
When a serum alkaline phosphatase elevation is detected, it must be interpreted in the clinical setting of the patient’s historical findings and physical examination. The enzymatic activity of alkaline phosphatase is stimulated in tissues during active metabolism, and as such there are both physiologic and pathologic causes of elevations in this enzyme. The first step in the diagnostic approach, therefore, should be to evaluate for physiologic causes of the elevation.
