Episode Details

Episode 94: Elevated Alk Phos. 

Akhil explains what to do when the alkaline phosphatase is elevated, including labs, imaging and other studies. 

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Elevated Alk Phos. 
By Akhil Patel, MS4, American University of the Caribbean. Comments by Hector Arreaza, MD.

Serum alkaline phosphatase: When you find elevated serum alkaline phosphatase, you must consider the two most common sources: the liver and bones. Other sources to consider include the third-trimester placenta, intestine, and kidneys. To determine if the abnormal elevation of alkaline phosphatase has clinical significance, you need to consider if it is a physiological or pathological elevation first. 

Ruling out physiological concerns: Typically, you should rule out physiological causes first as they are fewer and easier to determine via patient history. This can be even quicker to determine but also sometimes bypassed if a patient’s history and labs present with more concerning etiologies of pathological elevation.

Common causes of physiological elevations in alkaline phosphatase include pregnancy, patients with blood type O and B after eating a fatty meal, and younger children. 

Pregnancy: During pregnancy women in their third trimester will have elevated serum alk phos from the placenta. 

Blood type: During digestion, alk phos is released from the intestines in patients of blood type O and B. A postprandial increase can be 1.5 to 2 times the upper limit of normal in these patients, however, there is no clinical significance. 

Children: Younger children tend to have higher alk phos due to increased bone turnover. You can find a reference range chart online for different age groups. It is possible for alk phos to be up to three times higher in infancy and adolescence reflecting the ages with the highest bone growth velocity. 

Fun fact: Alkaline Phosphatase (also known as ALP) is a natural enzyme present in raw milk. Complete pasteurization will inactivate the enzyme in milk, therefore, presence of alkaline phosphatase in milk is an indicator of failed pasteurization. This is because the most heat-stable bacteria found in milk, Mycobacterium paratuberculosis, is destroyed by temperatures lower than those required to denature ALP.

Evaluation of pathological alkaline phosphatase: 

Degree of elevation: Another consideration is the level of alk phos elevation. If alk phos is at least four times the upper limit of normal, then cholestasis is the likely cause with many specific etiologies to consider. If alk phos is not markedly elevated (four times the upper limit) then the cause is likely not as specific and many different etiologies should be considered whether hepatic or non-hepatic.  

Liver source: 

Common symptoms: Jaundice, abdominal pain, ascites, easy bruising, nausea and/or vomiting, choluria, acholia or hypocholia, unexplained weight loss, fatigue, or anasarca.

If alk phos is elevated along with liver function testing and bilirubin, it is easier to determine the liver etiology (hepatitis, cirrhosis). However, if it is an isolated elevation in alkaline phosphatase, then other sources must be considered more carefully. 

A helpful test at this point is to look at is GGT or serum 5’-Nucleotidase for elevation. Typically, these will be elevated with alk phos if it is of liver origin. If they are not increased, you should consider bone-related etiologies.

-If a hepatic cause