ALKALINE
PHOSPHATASE
Alkaline
Phosphatases are a group of enzymes found primarily the liver (isoenzyme ALP-1)
and bone (isoenzyme ALP-2). There are also small amounts produced by cells
lining the intestines (isoenzyme ALP-3), the placenta, and the kidney (in the
proximal convoluted tubules). What is measured in the blood is the total amount
of alkaline phosphatases released from these tissues into the blood. As the
name implies, this enzyme works best at an alkaline pH (a pH of 10), and thus
the enzyme itself is inactive in the blood. Alkaline phosphatases act by
splitting off phosphorus (an acidic mineral) creating an alkaline pH.
The
primary importance of measuring alkaline phosphatase is to check the
possibility of bone disease or liver disease. Since the mucosal cells that line
the bile system of the liver are the source of alkaline phosphatase, the free
flow of bile through the liver and down into the biliary tract and gallbladder
are responsible for maintaining the proper level of this enzyme in the blood.
When the liver, bile ducts or gallbladder system are not functioning properly
or are blocked, this enzyme is not excreted through the bile and alkaline
phosphatase is released into the blood stream. Thus the serum alkaline
phosphatase is a measure of the integrity of the hepatobiliary system and the
flow of bile into the small intestine.
In
addition to liver, bile duct, or gallbladder dysfunction, an elevated serum
alkaline phosphatase can be due to rapid growth of bone since it is produced by
bone-forming cells called osteoblasts. One would expect that growing children
have higher levels than full-grown adults. The relationship of alkalinity to
bone development warrants further discussion because it plays a major role in
the prevention and reversal of osteoporosis. Just as calcium builds up around
faucets, so is calcium laid down into bone. The reason the calcium deposits on
your faucet is because the water is alkaline and calcium comes out of solution
and crystallizes in an alkaline environment. The reverse is also true,
"Lime -Away", vinegar, or any other acidic solution dissolve the
calcium deposits because they are acidic. It makes sense that osteoblasts by
creating a local environment of alkalinity via alkaline phosphatase helps build
bone. It also implies that in order to slow bone loss, one can not be in an
acidic state. Studies have shown that giving bicarbonate of potassium is just
as effective as calcium in correcting osteoporosis! One would expect then that
in an acidic state, the body will compensate for this by increasing the bone
alkaline phosphatase levels…
Because
acid-alkaline is influenced by many other glands, the implications of serum
alkaline phosphatase levels must consider more than just bone and liver
function. Associated organs/glands include adrenals, uterus, prostate, and
intestine.
The
consequences of impaired bile flow are pervasive since bile is critical to your
body's ability to process fats. As a result, fats remain undigested in the
digestive tract and can cause bloating, cramps, light colored stools,
gaseousness, etc. especially after a rich food. Many patients report pressure
or pain in the right upper area of their abdomen where the liver and
gallbladder are located. You may have discomfort in the right shoulder or
between your shoulder blades anywhere from your mid-back to the base of your
neck. Many people say they "carry my stress in the upper back and
neck." This may due to gallbladder dysfunction. Unfortunately, a normal
alkaline phosphatase does not exclude hepatobiliary dysfunction. In many cases,
even the ultrasound shows no gallstones, etc. Rather the problem is that the
bile does not flow freely throughout the system, which may result in
insufficient bile action.
The
consequences of impaired bile function involve the endocrine system in a major
way because all of the steroid hormones are metabolized in part by the liver.
These include the sex hormones (androgens and estrogens). As a result the
menstrual cycle, sexual functions and sex characteristics can be affected.
The
optimal range for alkaline phosphatase depends on your age. A growing
adolescent will have a much higher alkaline phosphatase than a full grown adult
because his/her osteoblasts are laying down bone very rapidly. For an adult,
50-75 mg/dl is considered a reasonable optimal range.
An increased
serum Alkaline Phosphatase may be due to:
Congestion
or obstruction of the biliary tract, which may occur within the liver, the
ducts leading from the liver to the gallbladder, or the duct leading from the
gallbladder through the pancreas that empty into the duodenum (small
intestine). Any of these organs (liver, gallbladder, pancreas, or duodenum) may
be involved.
Liver
congestion/cholestasis
- Oral contraceptives
- Obstructive pancreatitis
- Hepatitis/Mononucleosis/CMV
- Congestive heart failure
- Parasites
- Malignancy involving liver
*See
the lab section on liver enzyme tests for more about causes of liver
dysfunction.
Osteoblastic/Bone Conditions
- Paget's Disease
- Herpes Zoster (Shingles)
- Hyperthyroidism
- Over-activity of the Parathyroid glands (Primary
Hyperparathyroidism, Secondary Hyperparathyroidism from kidney disease,
osteomalacia, malabsorption)
- Rickets - Vitamin D deficiency
- Healing fractures, rapid bone growth Rapid bone
growth such as after a fracture, bone cancers like osteogenic sarcoma,
Osteomalacia, and Paget's Disease.
- Osteoporosis treatment
- Adrenal cortical hyperfunction
Non-Bone/Non-Liver Conditions
- As a normal part of late pregnancy since the placenta
produces alkaline phosphatase (placenta - ~2x normal)
- Amyloidosis
- Granulation tissue
- Gastrointestinal inflammation (Inflammatory Bowel
Disease: Ulcerative colitis, Crohn’s; ulcers)
- Systemic infections (sepsis)
- Sarcoidosis.
- Rheumatoid arthritis.
- Certain cancers such as Hodgkin's Lymphoma,
gynecologic malignancies.
- Acute tissue damage in the heart or lungs (myocardial
or pulmonary infarctions).
An elevated alkaline phosphatase almost always requires
other tests to determine the origin of the condition. For example, liver enzyme
tests to check the integrity of the liver, x-rays or other bone images if a
bone abnormality is evident. Although not used often, the isoenzyme profile of
alkaline phosphatases can be determined to see if the elevation of alkaline
phosphatase came primarily from liver (ALP-1), bone (ALP-2), or elsewhere. Most
often, however there is a modest elevation from ideal but the actual value is
within the laboratories reference range and the origin is inferred from the
symptoms, exam, or existing lab results.
A decreased serum
alkaline phosphatase may be due to:
- Zinc deficiency.
- Hypothyroidism.
- Vitamin C deficiency/Scurvy.
- Folic acid deficiency.
- Excess Vitamin D intake.
- Low phosphorus levels (hypophosphatasia)
- Celiac disease.
- Malnutrition with low protein assimilation (including
low stomach acid production/hypochlorhydria).
- Insufficient Parathyroid gland function.
- Pernicious anemia
- Vitamin B6 insufficiency
