Hyperphosphatemia

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Hyperphosphatemia

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Hyperphosphatemia

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Hyperphosphatemia is associated with (primary/secondary) hyperparathyroidism.

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An 86-year-old woman is brought to the emergency department, by her cleaner, because of an inability to walk, and a sore left hip for 2 days. She states that she was washing the dishes 2 days ago when she slipped and fell. She lives alone and was unable to reach the phone to call for help. She has also been unable to reach any food or fluids since she fell. In addition to her excruciating hip pain, she feels nauseated and fatigued. Her medical history includes essential hypertension. Her temperature is 36.8°C (98°F), pulse is 110/min, respirations are 18/min, and blood pressure is 115/80 mm Hg. Examination shows a thin appearing woman with dry lips, and a shortened, externally rotated left lower limb. Laboratory results show elevated serum creatinine. Which of the following is the most likely electrolyte disturbance?

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Content Reviewers:

Rishi Desai, MD, MPH

Contributors:

Tanner Marshall, MS

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.

So this means that phosphate is left in the lumen and eventually gets sent out in the urine.

Now, that calcium’s still in the lumen, but parathyroid hormone also affects the distal convoluted tubule and increases calcium reabsorption.

So when the dust settles, as a result of parathyroid hormone, phosphate is lost in the urine while ionized calcium is kept in the blood, so ionized calcium levels rise and phosphate levels fall!

With all that in mind, hyperphosphatemia can develop a few different ways. The first possibility is as a result of acute or chronic kidney disease, and for this we’ll use some numbersss.

So, let’s say normally the glomerular filtration rate, or GFR, which is the fluid filtered into the kidney per unit time, is 180 L / day, and the phosphate concentration of that blood is 0.04 g / L, that means that 7.2 g of phosphate get filtered per day, and let’s say 90% of that gets reabsorbed, or 6.48 g, that leaves 10%, or 0.72 grams to get excreted per day.

Now with kidney disease, the GFR falls to 28.8 L/day, which means only 1.2 g gets filtered, and only 0.12 g get excreted in a day, and so where there was 0.72 grams being excreted per day, now there’s only 0.12 g, and that means that the difference stays in the blood every day, and this contributes to hyperphosphatemia!

This number, 28.8 L/day, or 20 mL/min, is the point at which it’s thought excretion can’t keep up with intake.

In addition, the kidneys may be unable to reabsorb calcium and so more gets excreted.

Remember that in response to low calcium, the parathyroid glands release parathyroid hormone...but since calcium just gets wasted, it keeps releasing parathyroid hormone - this is called secondary hyperparathyroidism because the primary problem is with the kidneys.

This causes a continuous release of calcium and phosphate from the bones like an open tap, and while calcium is excreted due to impaired reabsorption, phosphate is reabsorbed due to impaired excretion, so phosphate ends up building up in the blood.

To make matters worse, all this loss from the bones makes them thin and weak, which is part of a process called renal osteodystrophy, which describes the overall bone changes that happen in people with chronic kidney disease.

Related to this is pseudohyporparathyroidism, which is where the kidneys simply don’t respond to parathyroid hormone because of a genetic defect in the parathyroid hormone receptor.