The liver is, in a way, the filter of our body. Everything that goes in, or must go out, is first metabolized by it. But how do you know if it works properly or not?
Medical professionals use different tools. Among these, the routine examination of “liver enzymes” . These are enzymes produced by our liver, whose blood values reflect valuable information about this organ.
Alkaline phosphatase is one of them, but you will discover that it is not exclusive to the liver and can be elevated in many other cases. Next, we will explain everything you need to know about it.
What is high alkaline phosphatase?
Generally, when doctors or a health professional suspect that the patient suffers from a disease related to the liver, they usually prescribe a blood test to measure the levels of the so-called “liver enzymes” .
These are used to analyze the functioning of the liver and the intrahepatic bile ducts , since the elevation or decrease of these can reflect certain diseases (as we will see later).
Among these enzymes, we have alkaline phosphatase (AP). It is an enzyme bound to the membrane of the hepatocyte (the specialized cells that make up the liver). But, despite the fact that it is generally associated with the liver, it is not produced exclusively in this organ.
There are actually two types of alkaline phosphatase: tissue-specific enzymes and non-tissue-specific alkaline phosphatase isoforms. The latter, as its name indicates, is specific and is produced in specific organs, such as the placenta or the mucosa of the small intestine.
The non-specific represents the majority of the circulating alkaline phosphatase in the blood plasma. 80% of FA in the blood comes from the liver, bone and kidneys. Under special circumstances, the specific FA rises and also contributes to its concentration in the blood.
Therefore, it is the non-specific alkaline phosphatase that has clinical value and helps clinicians to target a specific pathology.
Note: It is important to make it clear that an elevation of AF does not necessarily indicate a disease, it is also normal in physiological processes (as we will mention later).
Causes of High Alkaline Phosphatase in the Blood
There are many causes behind this phenomenon. Therefore, its elevation by itself is not indicative of a specific pathology .
It is something similar to fever. By itself, it is nonspecific. But, when it is accompanied by other signs and symptoms, it is more specific to something. Next, we will mention the most frequent causes.
They represent the most common cause of elevated alkaline phosphatase. Its elevation is due to damage at the level of the hepatocytes , which causes them to produce a greater amount of this enzyme.
Another cause could be biliary obstruction, also known as cholestasis . In hepatocytes, bile is produced, which is carried through ducts from the liver to the small intestine.
When the flow of bile is impeded (for whatever reason), cholestasis occurs . Under this context, alkaline phosphatase is elevated in almost 100% of patients.
Note: A disease responsible for the elevation of alkaline phosphatase due to injury to hepatocytes is viral hepatitis. Unlike biliary obstruction, however, viral hepatitis may not raise alkaline phosphatase.
A certain number of diseases that alter the metabolism of bone cells directly or indirectly elevate alkaline phosphatase. A common example of this is bone fractures .
When these cracks occur in the integrity of the bone, the cells seek to repair it. By accelerating their activity, they also increase the production of the enzyme inside, until it is released to the outside, which eventually ends up in the torrent.
On the other hand, acromegaly , caused by abnormal bone growth, is also responsible for its elevation. Other examples include Paget’s disease and various types of tumors (as we will see below).
Those tumors that involve, either the bone itself or the bone marrow, are also caused by an alteration in the replication of cells , of the bone, in which they reproduce uncontrollably.
This metabolic frenzy of the osteoblasts (bone cells) also generates the rise of the enzyme. Some examples are: sarcomas, osteosarcomas, osteochondroma, bone metastases, leukemia, myelofibrosis, and myeloma.
Important: Some studies have sought to establish the utility of ALP as a serum marker for detection tests and monitoring of this type of tumors, particularly for sarcomas. Its sensitivity is similar to that of other markers, such as carcinoembryonic antigen (used to detect lung tumors). (1)
Understanding the association between alkaline phosphatase and cardiovascular diseases first requires explaining atherosclerosis , one of the most common cardiovascular diseases today.
Atherosclerosis is the hardening of the arteries over time. The process by which it occurs is long and complex, but it consists of a prolonged inflammation where fat, calcium crystals and dead cell debris are deposited in the thickness of the artery walls.
It has also been observed that there is a relationship between serum AP and levels of C-reactive protein, a marker used to determine the levels of inflammation in the body of the person and, therefore, their proclivity to cardiovascular or metabolic diseases.
Note: Studies have shown a relationship between AF and the risk of mortality in patients with chronic kidney disease (CKD) on hemodialysis. (two)
CKD can cause or are caused by cardiovascular diseases, so its relationship with the serum levels of this enzyme is worth mentioning here, possibly due to an increase in the production of the different types of FA.
We had previously mentioned that alkaline phosphatase can be produced in bone and also that in certain cases, the elevation of this enzyme corresponds to a physiological event.
During the first two decades of life, bone growth and development leads to elevated levels of this enzyme. From the age of 15, its levels in the blood begin to decrease.
Why is this happening? Because alkaline phosphatase is involved in bone mineralization , that is, the solidification process of the materials that bone is made of.
Certain medications are capable of inducing a transient increase in liver enzymes, such as gamma glutamyl transferase, alanine transferase, aspartate aminotransferase and, of course, alkaline phosphatase.
This is due to a process called induction of hepatic enzymes , which is a physiological response of the liver against the entry of substances, such as drugs, to achieve their metabolization . Some examples are antibiotics, statins and antiepileptics.
Important: Certain drugs can also cause an adverse reaction in the liver, which is known as hepatotoxicity . When this occurs, there is an elevation of liver enzymes plus the appearance of other related symptoms.
The placenta is another tissue where a specific isoform of the enzyme is produced. Therefore, the pregnant woman will have elevated levels of the enzyme, even at levels where they are abnormal in a non-pregnant woman.
In this sense, the elevation becomes more noticeable in the last trimester of pregnancy . In addition to placental FA elevation, bone FA elevation also occurs, even up to 6 weeks postpartum.
Note: The routine tests that a doctor should do on his pregnant patient should also include evaluation of liver enzymes.
vitamin D deficiency
As we mentioned, the measurement of alkaline phosphatase is a very useful parameter for clinicians if a disease or disorder involving the bones is suspected.
Rickets and osteomalacia , in children and adults respectively, can present with very high levels of bone ALP and hypophosphatemia ( low blood phosphate levels).
In rickets, inadequate bone formation occurs, and in osteomalacia, a weakening of the bone occurs, making it soft and therefore susceptible to fractures and injury.
But why? Let us remember that FA is involved in the process that converts immature bone tissue (osteoid tissue) into robust and solid bone , by incorporating calcium crystals.
There are several factors that determine blood calcium levels, but one of the main ones is vitamin D. When it is decreased (generally due to a lack of it in the diet), circulating calcium levels are reduced.
Important: If there is not enough calcium, the body is unable to incorporate enough into the bones to keep them strong and healthy. As a secondary response, elevation of bone FA also occurs.
Chronic alcoholism can lead to alcoholic hepatitis , which in turn continues to be one of the leading causes of cirrhosis worldwide. Statistics show that acute alcoholic hepatitis can have a 50% mortality. (two)
Alcohol is toxic to our liver, particularly due to a specific component: ethanol . Ethanol is completely metabolized by the liver. In low or moderate concentrations, its damage is negligible.
But, its exaggerated and prolonged consumption over the years produces irreparable damage that, even with the regenerative capacities of the liver, can have deadly effects.
The injured liver compensates for this by increasing its function. Which, in turn, implies the elevation of multiple liver enzymes, such as alanine aminotransferase or FA.
Symptoms of high alkaline phosphatase
An elevated ALP does not always correspond to the appearance of a disease and, therefore, there are no symptoms (as occurs in growing children or pregnant women). On the other hand, when its values increase and there are symptoms, it is indicative of a pathology.
Next, we will mention some of the most frequent symptoms that accompany its increase in blood.
tiredness and weakness
Many illnesses generate a state of general malaise , characterized by weakness and prolonged fatigue , regardless of whether the person has been physically active or not.
An example of this is alcoholic hepatitis , where tiredness is one of its non-specific symptoms. Malignant bone tumors can also cause tiredness, weight loss, and much more.
nausea and vomiting
Due to the diversity of organs housed inside our abdomen, gastrointestinal symptoms , such as nausea, are not specific to anything.
In the context of elevated AF, it may be due to one of its main causes: biliary obstruction . It is usually accompanied by upper left abdominal pain, jaundice, fever, dark urine, and other symptoms.
Diseases that affect bone, directly or indirectly, are closely related to circulating bone FA levels . For example, in rickets, the epiphysis (the ends of the bone) do not relate properly, nor is there longitudinal growth of these.
In the adult, osteomalacia presents with bone pain and excessive brittleness. Bone pain is also common in bone tumors.
Dark urine and light stools
The color changes of urine and feces have nothing to do with FA levels. On the contrary, they have to do with the initial cause of AF, which is liver damage, because this organ is responsible for the conjugation of bilirubin .
Bilirubin is the waste resulting from red blood cells , which have completed their life time. This waste is transported to the liver, where it is metabolized. It is then transported to the intestine, where it passes in the feces or urine.
The metabolites derived from bilirubin are the ones that give the urine that yellowish hue, respectively. When liver damage occurs , there is an increase in a type of bilirubin and, consequently, a darkening of the urine.
Conversely, in liver damage, a lightening of the color of the stool occurs, because the metabolite derived from bilirubin that goes to the stool is reduced.
loss of appetite
It is common not to be hungry at all when we are sick. Even a slight cold is capable of robbing most people of their appetite.
Therefore, viral and alcoholic hepatitis, biliary obstruction and other liver diseases are capable of reducing the person’s appetite. If prolonged, the person may lose weight as a direct consequence.
Joint pain is common in infections, it can also occur in bone diseases, such as Paget’s disease (also causing high FA) or bone tumors, or weakening of these (as occurs in rickets).
Elevated body temperature is a common response to many conditions, whether due to direct or indirect causes, which is why it is considered a non-specific symptom.
Note: A good number of diseases can cause fever: infections of all kinds, biliary obstruction, acute alcoholic hepatitis, tumors, mononucleosis and much more.
Jaundice is the yellow coloration of different parts of the body, such as the sclera, skin, and other mucous membranes. It is produced by increased bilirubin levels , because they are generally associated with liver or biliary diseases, although it is not limited to these.
How to lower high alkaline phosphatase levels?
Treating alkaline phosphatase on its own is not a very effective solution, as this is usually a response to something and not the problem itself (same goes for fever).
Therefore, we recommend going to a health professional to provide you with an accurate diagnosis and effective solutions, such as some that we will mention just ahead.
If the patient requires medications to treat the underlying cause, these may reduce ALP levels. For example, patients with biliary obstruction from stones in the bile duct generally require surgery, but some opt for drugs to dissolve the stones.
Examples of these drugs are cholestyramine (trade name, Questran) or colestipol, who seek to reduce blood cholesterol levels to reduce obstruction.
Vitamin D supplements
In the event that the elevated ALP is due to bone diseases, derived from a dietary deficiency of vitamin D, the intake of supplements is recommended or a greater consumption of foods with this vitamin D.
Note: Vitamin D will help increase serum calcium levels, which in turn lowers AF and will strengthen bones.
Diet is the cornerstone of a healthy life. Without a proper diet, everything else will eventually fall apart. Consuming minerals, vitamins , antioxidants, and the right amount of calories is one of the keys to that.
Note: It is recommended to consume fresh vegetables, legumes, healthy fats, reduce the consumption of highly processed foods and ingest more fluids.
Your body needs to move, not only to burn those calories, but also to speed up your metabolism , stabilize your heart rate and blood pressure, ease digestion, and keep your mood up.
Even a light walk can reduce the risk of cardiovascular and metabolic diseases, it also strengthens bones and reduces the chances of suffering from mental conditions, such as depression.
If you suffer from a vitamin D deficiency , food is not an exclusive source of it. Your body is actually capable of making vitamin D on its own, but it is metabolically inactive. It needs the help of the sun’s UV rays .
Yes, UV rays are absorbed in our skin, triggering a series of biochemical reactions that transform vitamin D3 , or cholecalciferol, into another metabolite that travels to the kidneys, where it finally becomes calcitriol, the functional form of vitamin D. .
Reduced use of drugs that raise levels
Any drug consumption can cause a temporary elevation of liver enzymes , without generating any or persistent adverse effect. Once the person stops treatment (as in the case of antibiotics), these values decrease.
However, if the drug produces other symptoms (such as abdominal pain, fever or jaundice), immediately after it has been administered, we recommend going to a professional doctor , since he or she will tell you if you should stop taking the drug or replace it. with another.
- Alkaline phosphatase (AP) is an enzyme of the cells that make up the liver, but it can be produced in other organs.
- Increased levels may be due to liver or bone diseases, heart conditions, tumors, pregnancy, or drugs.
- Symptoms include tiredness, weakness, fever, bone problems, joint pain, and jaundice.
- The specialist doctor will make the appropriate diagnosis and treatment, which may include medications, vitamin D and healthy habits.