Hypophosphatemia

What is Hypophosphatemia?

Phosphate is a vital element in our bodies, involved in basic cell functions. One of its key roles is in the creation of DNA and RNA, our bodies’ essential molecules. Furthermore, it’s an energy source in a specific molecule called adenosine triphosphate (ATP) that fuels bodily functions. It forms a part of cell membranes, contributes to the modification of proteins, and works as a switch controlling various molecular activities. Therefore, changes in phosphate levels in the body can significantly impact these essential processes.

Hypophosphatemia means that an adult’s phosphate level in their blood is less than 2.5 mg/dL. In children, the normal level of phosphate is quite higher, between 4.0 to 7.0 mg/dL. Hypophosphatemia is fairly common and is often discovered by chance during tests for other issues. Roughly 85% of the body’s phosphorus, the chemical phosphate comes from, can be found in bones and teeth, with 14% inside cells, and only 1% found in blood or body fluids. Most of the phosphate in the body is stored inside our cells.

In broad terms, our bodies increase phosphate levels through the absorption in our intestines and lower them through excretion from the kidneys. Any surplus phosphate is stored in our bones for later use, helping maintain a stable amount in the body. A balanced diet provides around 1000 to 2000 mg of phosphate each day, with 600 to 1200 mg getting absorbed in the intestines. The absorbed phosphate goes chiefly to the bones, where its level remains relatively stable. Except in diseased conditions, the amount of bone phosphate remains the same with approximately 3 mg/kg added and removed each day.

Mainly, the parathyroid hormone, vitamin D, and sex hormones keep the phosphate level in balance. About 70% to 80% of phosphate in the blood is absorbed in a part of the kidneys known as the proximal convoluted tubule. Quite a few of the processes that regulate phosphate levels take place here, under the influence of certain proteins called Sodium-dependent phosphate type 2 (NaPi II) cotransporters.

Three key hormones, the parathyroid hormone (PTH), 1,25 dihydroxy vitamin D3 (1,25D), and FGF23 (Fibroblast growth factor 23), play important roles in regulating phosphate. The full understanding of these hormones’ influences on phosphate metabolism is complex and remains incomplete. However, it’s clear that these hormones and the regulation of phosphate and calcium in the body are all closely interconnected.

What Causes Hypophosphatemia?

Hypophosphatemia is a condition where there is a very low level of phosphate in your blood. This can happen for three main reasons:

1. Not enough phosphate is absorbed from the food you eat.
2. Too much phosphate is being removed from your body.
3. Phosphate moves from the fluid part of your blood into your cells or into your bones.

Now, let’s talk about what can cause each of these situations.

Too much phosphate can be removed from your body because of several factors. One way this can happen is when the parathyroid hormone or PTH, a hormone that helps regulate calcium and phosphate levels in your body, isn’t working right. This can be due to either primary hyperparathyroidism or secondary hyperparathyroidism. It can also be caused by a lack of vitamin D.

There are also several genetic disorders that could cause high phosphate excretion, including X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR). Certain types of tumors, fibrous dysplasia (a bone disorder), and neurofibromatosis (a genetic disorder that causes tumors to form on nerve tissue) can also lead to this.

Other factors that can cause hypophosphatemia are certain kidney conditions or the use of specific medications such as diuretics, corticosteroids and estrogen.

Not enough phosphate absorption can occur because of things like not eating correctly, alcoholism, or diseases that affect the digestion of food such as Crohn’s disease or after having bariatric surgery. Certain drugs that bind phosphate can also reduce the amount of phosphate your body absorbs from food.

Sometimes, phosphate can move from the fluid part of your blood into your cells or bones. This may happen during alkalosis (when there’s too much base and not enough acid in your body fluids), after eating a lot of food after a period of not eating enough (refeeding syndrome), or when there’s too much insulin in your body. Other causes can include the consumption of alcohol, certain medications, or the use of intravenous iron.

Lastly, other conditions such as poorly controlled diabetes, renal replacement therapy, prolonged fasting, or having a portion of the liver removed (partial hepatectomy) can also result in low phosphate levels.

Risk Factors and Frequency for Hypophosphatemia

Hypophosphatemia is a condition that often doesn’t show symptoms, so it’s hard to determine how many people in the general population have it. However, we know that it occurs in 2.2% – 3.1% of patients in hospitals and 29% – 34% of patients in intensive care units. This condition is particularly common in people with alcoholism, diabetic ketoacidosis, or sepsis, showing up in as many as 80% of these individuals. If hypophosphatemia is severe, it can greatly increase the risk of death. How dangerous hypophosphatemia is can greatly depend on what caused it and how severe it is.

Signs and Symptoms of Hypophosphatemia

Hypophosphatemia is a health condition that usually doesn’t show symptoms. However, some individuals may experience mild to general weakness. There are several factors that could suggest a person might be at risk for hypophosphatemia. These include poor nutrition, trouble absorbing nutrients from food, frequent or recurring bone pain, history of bone fractures, suspicion of a certain type of cancer called multiple myeloma, needing nutrient supplements via injections, having a form of diabetes that presents with high acid levels in the blood, and the use of certain medications like chronic glucocorticoids, antacids, cisplatin, or pamidronate.

When the condition becomes more severe, patients might start to show symptoms. These can include changes in mental state, difficulty with speech, loss of stability leading to seizures, and specific neurological signs such as numbness or increased reaction to reflex tests. In severe cases, the condition can cause the heart and lungs to stop working properly. Muscle weakness and pain can also occur, which may be a sign of a condition called rhabdomyolysis that’s related to hypophosphatemia.

Testing for Hypophosphatemia

Hypophosphatemia, or low phosphate levels in your blood, is usually diagnosed by a simple blood test. It’s important to understand that this test only shows a small fraction of your body’s total phosphate levels, so even small changes could mean your body is running low on phosphate.

Doctors usually can find out the cause of hypophosphatemia from your medical history. But if the cause is not clear, they will want to check how much phosphate your kidneys are getting rid of. They can do this by collecting all of your pee for 24 hours or by testing a sample of your pee to calculate the fractional excretion of filtered phosphate (FEPO4). FEPO4 is a percentage calculated using levels of phosphate and creatinine (a waste product) in your pee and blood:

FEPO4 = (Urine phosphate level x Blood creatinine x 100) / (Blood phosphate level x Urine creatinine)

If the 24-hour urine phosphate test is less than 100 mg, or the FEPO4 is less than 5%, it means your kidneys are not excreting enough phosphate. In this case, the low phosphate levels in your blood could be due to a shift in phosphate within your body or a problem with your intestines not absorbing phosphate properly. But if the 24-hour urine phosphate is more than 100 mg or the FEPO4 is more than 5%, it means your kidneys are getting rid of too much phosphate. This could be due to overactivity of your parathyroid glands or a lack of vitamin D.

Treatment Options for Hypophosphatemia

Hypophosphatemia, a deficiency of phosphorus in the blood, can affect virtually every system in the body. Symptoms of this deficiency usually occur when levels fall below 1 mg/dL (or 0.32 mmol/L). While mild to moderate cases often show no clear symptoms, it’s crucial to address and monitor any phosphorus abnormalities and replenish levels as necessary. The method for replenishing phosphorus will depend on the individual’s symptoms.

Oral replenishment of phosphorus might be used to treat cases of hypophosphatemia, where someone takes specified amounts of phosphate supplements orally based on their phosphorus levels and symptoms.

Severe cases of hypophosphatemia can be treated with intravenous phosphate, particularly when the phosphorous level in the blood dips below 1 mg/dL (or 0.32 mmol/L). Once the blood phosphorous level goes above 2 mg/dL (or 0.48 mmol/L), the patient can switch from intravenous to oral replacement.

Intravenous replacement is also a viable option for those who can’t take oral medications or find it hard to tolerate oral replacement. Sodium phosphate and potassium phosphate are commonly used for intravenous replacement. The dosages to used follow standard medical procedures and vary depending on the patient’s phosphorous levels and other health factors, including kidney health and the person’s weight.

Physicians adjust these dosages of phosphorus supplements for people with kidney problems and those who have a weight that exceeds their advised body weight. This calculated approach ensures the best result for the patient’s health.

What else can Hypophosphatemia be?

The most common sign of having low phosphorus in the body is feeling generally weak. Apart from this, you might also have low potassium, calcium, or magnesium levels.

There are also certain conditions that might seem like you have low phosphorus levels such as:

• Benzodiazepine toxicity (an overdose of anti-anxiety medications)
• Delirium tremens (severe alcohol withdrawal)
• Guillain-Barre syndrome (a rare neurological disorder)
• Hypothyroidism (underactive thyroid)
• Hyperparathyroidism (overactive parathyroid glands)
• Insulin overdose
• Myopathies (muscle diseases)
• Primary muscle disorders
• Rhabdomyolysis (a serious syndrome due to muscle injury)
• Multiple myeloma (cancer of plasma cells)
• Uremic encephalopathy (a brain disorder due to kidney failure)

What to expect with Hypophosphatemia

Most patients with low phosphate levels in their blood, known as hypophosphatemia, generally have a mild to moderate form of this condition and will recover without any complications. Even those people with severe hypophosphatemia can escape serious complications if their condition is identified early and treatment to replace their phosphate levels is quickly started.

It’s important to note that severe hypophosphatemia has been linked to a significantly higher death rate in seriously ill patients who have either sepsis or septic shock. Sepsis is a potentially life-threatening condition caused by the body’s response to an infection while septic shock is a severe form of sepsis that can cause organ failure and low blood pressure. However, it’s not yet clear whether these risks come from the low phosphate levels alone or in connection with other factors.

Possible Complications When Diagnosed with Hypophosphatemia

Severe low levels of phosphate in the blood (hypophosphatemia) can lead to a multitude of negative health effects, particularly if it lasts a long time and is not treated quickly. The most dramatic effects are seen in the bones, but many other parts of the body are affected as well.

These effects can include:

• Bone Issues: Long-term hypophosphatemia can cause osteopenia, osteoporosis, rickets, or osteomalacia. These conditions all lead to a decrease in bone mineralization, which can result in more bone fractures. Dental problems such as gum disease (periodontitis) are also common.
• Muscle Issues: This disorder can cause generalized muscle weakness. On a cellular level, it can deplete the ATP in cells and impair the functionality of mitochondria, leading to muscle breakdown that can damage the kidneys and increase creatine phosphokinase levels. This is particularly pronounced in individuals with a chronic drinking problem.
• Central Nervous System Issues: The nervous system can also be affected, leading to metabolic encephalopathy due to ATP depletion. Symptoms can include changes in mental status, increased irritability, tingling sensations, numbness, seizures, or even coma.
• Cardiac Issues: Hypophosphatemia can also affect the heart. The heart cells become less stable, and heart rhythm problems become more likely. Some studies show a significantly increased risk of heart failure, possibly due to lower levels of a compound called 2,3 DPG in red blood cells and depleted ATP causing cardiomyopathy, a disease of the heart muscle.
• Respiratory Issues: Breathing problems are associated with hypophosphatemia. There can be decreased function of the diaphragm, affecting the lungs and leading to underbreathing. Patients who are dependent on a ventilator have been shown to have longer hospital stays and worse outcomes when hypophosphatemia is present.
• Gastrointestinal Issues: ATP deficiency causes dysfunction in the digestive system, which could result in difficulty swallowing, ileus (a type of bowel obstruction), or constipation.
• Hematologic Issues: Hypophosphatemia can reduce ATP within red blood cells, which impairs the ability of these cells to carry oxygen, and may cause a certain type of anemia called hemolytic anemia. Also, phosphorus is necessary for the formation of 2,3-diphosphoglycerate, a compound that helps oxygen release from hemoglobin.

Preventing Hypophosphatemia

Doctors should advise patients to monitor what they eat and drink. Eating foods high in phosphate like dairy products, meat, chicken, and peanuts, is good for them. They should visit the doctor as recommended or if they notice any of the following issues:

* Feeling confused
* Acting irritable
* Experiencing muscle pain
* Feeling nauseous, vomiting, or having diarrhea
* Being constipated for more than two days