Alkaline phosphatase (ALP) is an enzyme found throughout the body and is routinely measured as part of a common blood test panel. A significantly elevated level of this enzyme in the blood can point toward various underlying health issues, most often related to the liver or bones. This article explores the biological role of ALP, defines the thresholds for concern, and outlines the conditions that can lead to a dangerously high result.
Understanding Alkaline Phosphatase (ALP)
Alkaline phosphatase plays a role in numerous bodily functions, primarily by breaking down phosphate molecules. This process is important for cellular metabolism and the mineralization of bone. Since the enzyme is made in several different organs, a high reading on a standard blood test is not immediately diagnostic on its own.
The enzyme exists in different forms, known as isoenzymes, which originate from specific tissues. The liver and bones are the two largest contributors of ALP to the bloodstream. Smaller amounts are also produced in the intestines and, temporarily, in the placenta during pregnancy. This multi-source nature means that an elevated level requires further investigation to pinpoint the exact tissue responsible for its production.
Defining Elevated and Dangerously High Levels
The normal range for alkaline phosphatase in adults typically falls between 44 and 147 International Units per Liter (IU/L), though this range varies slightly by laboratory. Any result exceeding the upper limit is considered elevated, but it is not immediately alarming unless the increase is substantial. A “dangerously high” level is generally considered three to four times the upper limit of normal, potentially exceeding 500 U/L, and may indicate a serious underlying disease. Levels can sometimes reach 10 times the upper limit, especially in cases of complete bile duct blockage.
Not every elevated ALP result signifies a serious medical condition. Children and adolescents naturally have much higher ALP levels due to rapid bone growth during puberty, as the enzyme is involved in bone formation. ALP levels also rise significantly during the third trimester of pregnancy due to placental production, sometimes reaching three times the normal adult limit. Even a fatty meal consumed before the blood draw can cause a temporary, mild increase from the intestinal source.
Primary Causes of Pathological Elevation
Pathological causes of a sustained, significantly elevated ALP level are typically categorized by the organ system involved. These causes most commonly relate to issues in the liver or the skeleton.
Liver and Biliary System Issues
A high ALP level from the liver source often indicates a problem with the bile ducts, which is a condition known as cholestasis. Bile duct obstruction, caused by gallstones, scar tissue, or tumors, is a common reason for a dramatic rise in ALP. When the flow of bile is blocked, the pressure causes the liver cells lining the ducts to produce and release large amounts of ALP into the bloodstream.
Diffuse liver diseases, such as advanced cirrhosis (scarring of the liver) and various forms of hepatitis, can also lead to increased ALP, but the highest elevations are usually seen with obstructive issues. Drug-induced liver injury, caused by certain medications or supplements, can similarly disrupt bile flow and elevate the enzyme.
Bone Disorders
The second major source of pathologically elevated ALP is the bone, where the enzyme is made by osteoblasts, the cells responsible for building new bone tissue. Any condition that causes an abnormal or accelerated rate of bone turnover will lead to a rise in the bone-specific ALP isoenzyme. Paget’s disease of bone, a chronic disorder of excessive bone breakdown and regrowth, is a classic cause of very high ALP levels.
Other skeletal conditions that cause significant elevation include bone cancers, both primary and metastatic (cancer that has spread to the bones from another site). Disorders that affect bone mineralization, such as osteomalacia and hyperparathyroidism, which affects calcium regulation, can increase ALP as the body attempts to repair or rebuild bone tissue. ALP levels may also be temporarily elevated during the healing process of a recent bone fracture.
Next Steps in Diagnosis and Investigation
When a dangerously high ALP level is detected, the immediate medical priority is to determine the source of the enzyme elevation. A simultaneous measurement of another liver enzyme, Gamma-Glutamyl Transferase (GGT), is the initial step in this process. Both ALP and GGT are typically elevated in liver and biliary diseases, particularly those involving bile duct blockage.
If the ALP level is high but the GGT level is within the normal range, the source of the elevation is highly likely to be the bone or a non-hepatic source, effectively ruling out a primary liver problem. If both ALP and GGT are elevated, the next step involves imaging studies, such as an abdominal ultrasound or CT scan, to visualize the liver and bile ducts for signs of obstruction. If the cause remains unclear, a test called ALP isoenzyme analysis can be performed to directly measure the amount of enzyme coming from the liver versus the bone. The treatment for a high ALP level is not to lower the enzyme itself, but to treat the underlying condition that is causing the abnormal enzyme production.