Hypophosphatemia

Excerpt

Phosphate is one of the most important molecular elements to normal cellular functions within the body. It acts as an integral component of nucleic acids and is used to replicate DNA and RNA. It is an energy source for molecular functions through its role in adenosine triphosphate (ATP). It incorporates into the phospholipids of cell membranes. It adds and deletes phosphate groups to or from proteins and functions as an on/off switch to regulate molecular activity. Given its widespread role in nearly every molecular and cellular function, aberrations in serum phosphate levels can be highly impactful.

Hypophosphatemia is defined as an adult serum phosphate level of less than 2.5 mg/dL. The normal serum phosphate level in children is considerably higher, between 4.0 to 7.0 mg/dL for children. Hypophosphatemia is a relatively common laboratory abnormality and is often found incidentally. About 85% of phosphorus is found in bones and teeth, 14% intracellularly, and 1% in the serum/extracellular fluid component. Free phosphate within the body is predominantly intracellular.

Phosphorus Homeostasis

In general, phosphate levels increase through upregulated absorption in the intestines and decrease through renal excretion. Excess is stored in the bones, which act as a buffer to maintain a relatively stable total body content. A typical, nutritious diet provides 1000 to 2000 mg of phosphate daily. Of this, 600 mg to 1200 mg is absorbed via the intestines. Phosphate exists primarily in the crystallized extracellular matrix of bones, where it is relatively stable and inert. In the absence of pathology, the homeostasis of bone phosphate is neutral, with resorption and deposition of approximately 3 mg/kg per day. Bone homeostasis of phosphate is regulated primarily by the parathyroid hormone, vitamin D, and sex hormones. The serum phosphate levels are predominantly maintained by absorption via the kidneys, of which 70% to 80% occurs in the proximal convoluted tubule. Sodium-dependent phosphate type 2 (NaPi II) cotransporters in the proximal tubule are a primary site of regulation. The three types of type II transporters are type IIa, type IIb, and type IIc. Type IIa and IIc transporters are expressed predominately in the kidney. Type IIb transporters are expressed in the small intestine and control the dietary uptake of phosphate.

Three important regulatory hormones central to phosphate regulation are:

1. Parathyroid hormone (PTH)

2. 1,25 dihydroxy vitamin D3 (1,25D)

3. FGF23 (Fibroblast growth factor 23)

The role of each of these hormones on phosphate metabolism is complex (Figure 1: Phosphate Homeostasis) and incompletely understood. Phosphate regulation is intricately connected to calcium metabolism through regulation by these three important hormones.