A 25-year-old man with very high alkaline phosphatase

Cleveland Clinic Journal of Medicine. 2011 December;78(12):793-800 | 10.3949/ccjm.78a.10166

December 1, 2011|Cleveland Clinic Journal of Medicine

Jamak Modaresi Esfeh, MD;Ibrahim A. Hanouneh, MD;Nizar N. Zein, MD, FAASLD

A 25-year-old man presented to his primary care physician with generalized malaise. His symptoms started around 2 months earlier with progressive fatigue, nausea, decreased appetite, and weight loss (15 lb in 2 months). He denied having fever, chills, night sweats, abdominal pain, diarrhea, melena, or hematochezia.

His medical history was remarkable only for depression, well controlled with sertraline (Zoloft), which he started taking 3 years ago. He was not taking any other prescribed, over-the-counter, or herbal medications.

He had no family history of cancer or liver disease. He did not smoke and rarely drank alcohol. He had never used recreational drugs. He was sexually active with one female partner, used condoms for protection, and had never been diagnosed with a sexually transmitted disease. He had not traveled recently and had not been exposed to any pet.

On physical examination, the patient was alert and oriented. He was afebrile, his heart rate was 90 beats per minute and regular, his respiratory rate was 18 breaths per minute, and his blood pressure was 125/77 mm Hg. Auscultation of the chest was clear. His heart sounds were normal, and there was no murmur, gallop, or rub. His right upper quadrant was mildly tender, and his liver was palpably enlarged. He had no peripheral edema, clubbing, rash, telangiectasia, or other skin changes. Examination of the joints revealed no warmth, swelling, or erythema.

The patient’s laboratory values on admission are shown in Table 1. Of note, his serum alkaline phosphatase level was 1,307 U/L (reference range 40–150 U/L).

LIVER TESTS CAN NARROW THE DIAGNOSIS

The most commonly used laboratory tests of the liver can be classified into those that measure either:

Liver synthetic function (eg, the serum albumin and bilirubin concentrations and the prothrombin time) or
Liver damage, as reflected by the serum concentrations of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and gamma-glutamyltransferase (GGT).^1,2

ALT and AST are normally concentrated in the hepatocytes and thus, when present in the serum in elevated concentrations, are markers of liver cell injury. The serum levels of these enzymes start to increase within a few hours of liver cell injury as they leak out of the cells via the damaged cell membrane. AST is less liver-specific than ALT, since AST levels can be elevated not only in liver injury but also in muscle, cardiac, and red blood cell injury.^3,4

Alkaline phosphatase is actually a heterogeneous group of enzymes found mainly in liver and bone cells. Hepatic alkaline phosphatase is concentrated near the biliary canalicular membrane of the hepatocyte. Accordingly, increased levels of hepatic alkaline phosphatase are mainly seen in liver diseases that predominantly affect the biliary system.³

GGT is also concentrated in hepatic biliary epithelial cells, and thus GGT elevation is another marker of hepatobiliary disease. In fact, measuring the GGT level can help to determine whether an isolated elevation of alkaline phosphatase is due to liver injury.^2,3

Accordingly, liver diseases can be classified into two broad categories:

Hepatocellular injury, in which the primary injury occurs to the hepatocytes
Cholestatic injury, in which the primary injury is to the bile ducts.

In the former, elevated levels of ALT and AST predominate, while in the latter, elevated alkaline phosphatase is the main finding.³

References

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