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Liver Function Tests: Alkaline Phosphatase (Alk Phos)

As I mentioned in my previous post on " Liver Function Tests: An Overview", here I will discuss how the results of Alk Phos testing can be used to evaluate liver (dys)function. Some details may not be mentioned; more detailed posts will be coming soon.

The Basics

  • Alkaline phosphatase (aka "Alk Phos") has optimal activity when the pH is alkaline (9)

  • Alk phos is present in most tissues; Most concentrated in bone, liver, intestine and placenta

  • Alk Phos Elevations usually = Bone or Liver problem

  • In regards to liver, Alk phos is a sensitive marker for metastatic liver disease

Causes of a Falsely Elevated Alk Phos:

  • States of Normal growth: in childhood & Pregnancy (also hyperthyroidism)

  • Non-fasting individuals (due to elevations in intestinal Alk Phos; can be elevated for 2-12 hrs)

  • Patients with Lewis positive group B or O secretors

  • Some medications (especially Oral Contraceptives)

When to worry about/do further workup of a high Alk Phos level?

  • When greater than 1.5 x the upper limit of normal on 2 separate occasions, >6 months apart

Causes of MILD ELEVATIONS in Alk Phos:

  • Liver disease (especially cholestatic or infiltrative metastases)

  • Pregnancy (unrecognized)

  • Bone disease (Paget's disease, Osteomalacia, Rickets)

  • Congestive Heart Failure

  • Hyperthyroidism

  • Drugs (Ibuprofen, Acetaminophen)

Causes of MAJOR ELEVATIONS (>3X ULN) in Alk Phos:

  • Extra-hepatic biliary obstruction (i.e. gall stones, tumor in pancreas, duodenum or stomach)

  • Primary biliary cholangitis (formerly called primary biliary cirrhosis)

  • Severe drug-induced hepatocellular cholestasis

  • Paget disease of bone

What could cause a LOW Alk Phos Level?

  • Hypophosphatasia (inborn deficiency)

  • Malnutrition

  • Hemolysis (falsely low)

  • Wilson disease

  • Theophylline therapy

  • Estrogen therapy in post-menopausal women


A Quick Word on How to Perform the Test

Testing for Alkaline phosphatase isoenzyme:

Historically (aka not often performed today as there are much better tests), alkaline phosphatase enzyme could be separated via electrophoresis to determine whether the source was bone, liver, intestine or placenta. This was based on inhibition of the enzyme from application of heat, incubation with urea, or via addition of L-phenylalanine.

I won't pretend to know all the details here... for the boards, just remember that in the presence of HEAT...

  • "Bone Burns"= Heat (or urea) inactivates nearly all of the Alk Phos

  • "Biliary Blisters/Blotched"= Heat (or urea) inactivates ~50% Alk Phos

  • "Placenta Persists"= Heat (or urea) does NOT affect Alk Phos. However, Placenta & Intestinal Alk Phos are nearly entirely inhibited by L-Phe

As I mentioned, this is not routinely performed today as GGT or 5' nucleotidase tests are much better for detecting liver damage. If the results of these tests are normal, then an elevated alk phos is likely secondary to a problem in the bone instead of liver.


Additional studies may be helpful in the correct clinical setting

  • Imaging studies: Rule out mass lesions & assess biliary tree anatomy/status

  • Serologic studies: Anti-mitochondrial Ab (PBC)

  • Bone scan (indicator of osteoblast activation such as in Paget dz, osteomalacia, or hyperparathyroidism- Consider testing PTH/Ca/PO4 levels)


As always, be aware of pre-analytic, analytic, and post-analytic errors when interpreting any test result. Be on the lookout for the upcoming post on Acid Phosphatase and its use as a marker for prostate cancer (PSA) or for hairy cell leukemia (TRAP).

Disclaimer: this is NOT medical advice... consult your physician, medical literature etc before making any assumptions from this article

Reference: Daniel D. Mais, MD. "Practical Clinical Pathology". pg 2. Amer Soc for Clin Path. 2014.


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