Alkaline Phosphatase (ALP) is an enzyme found in tissues throughout the body and is frequently measured during routine blood work. The level of ALP circulating in the bloodstream serves as an important marker, providing physicians with valuable information about the health of specific organs and systems. Variations in this level can signal changes, particularly those related to the liver or bones, that may require further investigation.
Biological Function and Tissue Sources
The biological role of Alkaline Phosphatase is to catalyze the removal of phosphate groups from various molecules, a process known as dephosphorylation. This action occurs most efficiently in an alkaline environment. ALP is involved in transporting molecules across cell membranes and in regulating metabolic pathways.
ALP is not a single enzyme but rather a group of isoenzymes, which are structurally similar proteins produced by different tissues. The majority of the ALP found in the bloodstream, often over 80%, originates from just two major sites: the liver and the skeleton. Liver ALP is located on the bile canalicular membrane of hepatocytes and increases when bile flow is obstructed. Bone ALP, or bone-specific alkaline phosphatase, is produced by osteoblasts, the cells responsible for building new bone tissue.
Other tissues also contribute small amounts of ALP to the serum, including the intestines, kidneys, and the placenta during pregnancy. The intestinal isoenzyme can sometimes be transiently elevated, particularly after a fatty meal. The placental isoenzyme causes a significant, normal increase in ALP levels late in gestation, helping clinicians narrow down the origin of an abnormal result.
Understanding the Alkaline Phosphatase Blood Test
An Alkaline Phosphatase test is a simple blood draw, typically ordered as part of a larger diagnostic panel. The test measures the total amount of ALP enzyme circulating in the blood, expressed in units per liter (U/L). Because ALP is produced in multiple organs, this single test provides a broad screening tool for possible issues in the liver, bile ducts, or bones.
Test results are interpreted by comparing the measured number to a laboratory-specific reference range for healthy individuals. While these ranges vary between facilities, a common upper limit for adults is around 120 to 147 U/L. A result such as 138 U/L falls near the upper boundary of this typical adult range, but would still be considered normal by many labs. Age and gender significantly affect the reference range, as children and adolescents naturally have much higher levels due to active bone growth.
Interpreting a value like 138 U/L requires looking at the specific reference range provided on the lab report for the individual’s demographic. If the result slightly exceeds the upper limit, it is considered a mild elevation, which can sometimes be insignificant or related to non-disease factors. However, the result serves as a trigger for a physician to consider the patient’s symptoms and order additional tests to determine the source and significance of the level.
Primary Causes of Elevated ALP Levels
When the ALP level is significantly elevated, the cause is usually traced back to increased production or reduced clearance from either the hepatobiliary system or the skeletal system. The most common liver-related issues fall under the category of cholestasis, where the flow of bile from the liver is slowed or blocked. Conditions like gallstones, tumors, or strictures in the bile ducts cause a buildup of pressure, prompting the liver cells to release excess ALP into the bloodstream.
Inflammatory liver diseases, such as hepatitis or cirrhosis, can also cause a rise in ALP, though this is often accompanied by elevations in other liver enzymes like ALT and AST. Autoimmune conditions that affect the bile ducts, such as Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC), are known causes of marked ALP elevation. In these cases, the ALP level can be several times higher than the upper limit of the normal range.
Elevations due to bone activity are characterized by increased osteoblast function, the process of new bone formation. Paget’s disease, a chronic condition of abnormal bone remodeling, is a classic cause of highly elevated ALP. Healing bone fractures, osteomalacia, and hyperparathyroidism all stimulate osteoblasts and increase bone-specific ALP. In adolescents experiencing a growth spurt, the rapid formation of bone tissue physiologically raises the ALP level.
Interpreting a high total ALP level is difficult because the enzyme from the liver and the enzyme from the bone are measured together in the standard test. A physician must rely on the patient’s symptoms and co-existing blood tests to distinguish between a liver condition and a bone condition. For instance, if the enzyme Gamma-Glutamyl Transferase (GGT) is also high, the elevation is highly likely to be hepatic in origin.
Low ALP Results and Advanced Diagnostic Steps
While high ALP is more common, a result that falls below the established reference range is a less frequent but still important finding. The most recognized cause of a significantly low ALP level is a rare genetic disorder called hypophosphatasia. This condition affects bone mineralization, leading to soft and brittle bones and teeth due to a deficiency in the tissue-nonspecific ALP enzyme.
Other causes of low ALP are often related to nutritional deficiencies, such as a lack of zinc or magnesium. Severe malnutrition or conditions that cause malabsorption can also result in low circulating levels. An underactive thyroid gland, or hypothyroidism, is another condition associated with a reduced total ALP measurement.
When a total ALP result is abnormal, the next diagnostic step is often to order an advanced test known as isoenzyme testing or fractionation. This specialized test separates the total ALP into its component parts, identifying the exact proportion originating from the liver, the bone, or other sources. This resolves the diagnostic ambiguity of the initial total ALP result, allowing the physician to focus on the specific organ system responsible for the change in enzyme activity.