Hyperphosphatemia

With hyperphosphatemia, hyper- means over, -phosphat- refers to phosphate, and -emia refers to the blood, so hyperphosphatemia means having a high phosphate level in the blood, typically above 4.5 mg/dL.

Now, phosphate is made up of one central phosphorus atom surrounded by four oxygen atoms in a tetrahedral arrangement, kind of like a mini pyramid, and has a charge of minus 3 and is written PO43-.

In the body, about 85% of the phosphate is stored in the bones, where it combines with calcium to make a tough compound called hydroxyapatite which is the stuff that makes bones hard.

Of the remaining phosphate, a tiny amount is extracellular, or outside the cells like in the blood, so this is the bit that gets measured, and the majority is intracellular, or inside cells, where it does all sorts of things.

It’s responsible for phosphorylation, where it binds to fats and proteins.

It forms the high energy bonds of adenosine triphosphate or ATP, which is the most common energy currency in the cell.

It’s part of the DNA and RNA backbone that links individual nucleotides together, and it’s also part of cellular signaling molecules like cyclic-adenosine monophosphate or cAMP. Bottom line is that phosphate is really important.

Now, because most of phosphate is locked up with calcium in the bones, the levels of phosphate are heavily tied with the levels of ionized calcium in the body.

If calcium levels fall, the four parathyroid glands buried within the thyroid gland release parathyroid hormone which frees up both calcium and phosphate ions from the bones.

It does this by stimulating osteoclasts, the cells that break bone down, to release hydrogen ions which dissolves the hard, mineralized hydroxyapatite.

As soon as the positively-charged calcium and negatively-charged phosphate are released from the bones, they grab onto each other again, meaning that the ionized calcium level doesn’t really go up very much at all.

These two make their way to the nephron of the kidney, and at this point in the proximal convoluted tubule, phosphate usually gets reabsorbed back into the blood via sodium-phosphate cotransporters. It turns out, though, that parathyroid hormone also shuts this down.