Hyperphosphatemia – causes, symptoms, diagnosis, treatment, pathology

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. Since parathyroid hormone tells the kidneys
to save calcium and get rid of phosphate, calcium again gets lost and phosphate builds
up in the blood, following the same pattern as kidney disease, including the thinning
of the bones. All right, so since, again, parathyroid hormone
causes excretion of phosphate and reabsorption of calcium, then another cause of hyperphosphatemia
is hypoparathyroidism, when the parathyroid glands don’t produce enough parathyroid
hormone in the first place. This results in the same situation of increased
reabsorption of phosphate and decreased reabsorption of calcium. This can happen following a thyroid gland
removal surgery when the parathyroids are accidentally taken out too or radiation treatment
for cancer of the head or neck. Also, people with the genetic disease DiGeorge
syndrome, are often born with parathyroid glands that are too small and can’t produce
enough parathyroid hormone. Alternatively, phosphate levels can rapidly
increase in the blood from excessive intake and absorption through the gastrointestinal
tract or bloodstream via intravenous fluids. One cause is taking too much of a phosphate-based
laxative either orally or rectally as an enema. A final cause of hyperphosphatemia relates
to the fact that most phosphate in the body is within the cells. Any time a lot of cells die, that phosphate
gets spilled into the bloodstream, causing hyperphosphatemia. This includes things like crush injuries,
like when a piano falls on someone’s legs, or tumor lysis syndrome, which is cancer treatment
which causes lots of tumor cells to die all at once, or rhabdomyolysis, or rapid destruction
of skeletal muscle cells. Another situation is when living cells get
affected by respiratory acidosis, which is when the carbon dioxide levels rise because
a person isn’t breathing or ventilating it out of the lungs quickly enough. That carbon dioxide can diffuse into a cell
and react with water to form carbonic acid which quickly breaks into a proton and bicarbonate. The bicarbonate goes back into the blood in
exchange for a chloride ion, leaving behind a proton. And all this ends up lowering the cellular
pH. Now, normally glycolysis in the cell uses
up a lot of phosphate, but this lower pH tends to inhibit glycolysis. So as a result, the cells don’t pull as
much phosphate out of the blood, and this allows levels in the blood to rise. Somewhat similarly, in diabetic ketoacidosis,
there are low levels of insulin, and although the exact mechanism is unclear, it reduces
the amount of phosphate that cells extract from the blood, causing it again to build
up in the blood. In this case, though, it’s a slower process
since there’s also an osmotic diuresis or increased urination from the hyperglycemia,
or high blood sugar. Mild hyperphosphatemia doesn’t usually cause
symptoms, but severe hyperphosphatemia can make neurons more excitable. This can trigger the spontaneous firing of
neurons and tetany or the involuntary contraction of muscles. This can end up causing Chvostek’s sign, which
is when facial muscles twitch after the facial nerve is lightly finger tapped 1 cm below
the zygomatic process. It can also cause Trousseau’s sign, which
is where a blood pressure cuff occludes the brachial artery, and that pressure on the
nerve is enough to make it fire, resulting in a muscle spasm that makes the wrist and
metacarpophalangeal joints flex. It can also cause symptoms like tingling around
the mouth, seizures, and bone pain. The high levels of phosphate also cause it
to find and stick to calcium which forms bone-like crystals containing calcium and phosphate
in places that they shouldn’t be, like just beneath the skin, in the walls of blood vessels,
in the joints, or in the kidneys where they can form kidney stones. With long-term hyperphosphatemia, the whole
kidney can eventually turn into bone, which is called nephrocalcinosis. In other words, flesh literally turning to
bone. This widespread calcification of healthy tissues
is called metastatic calcification. In this case, metastatic means that the tissue
rapidly changes from one thing to another, rather than referring to cancer. Diagnosis of hyperphosphatemia is based on
the phosphate level being above 4.5 mg/dL, and treatment involves decreasing phosphate
intake. And this is accomplished by avoiding foods
that contain a lot of phosphate like dairy, meat, and soda – in other words, no more pepperoni
pizza with coke. To decrease the amount of phosphate that’s
absorbed from the gastrointestinal tract, people can given medications called phosphate
binders. Now, you can also try to increase excretion
of phosphate, and in people with healthy kidneys, a combination of intravenous saline and a
loop diuretic like furosemide can increase excretion. And this is called forced diuresis and it
essentially overwhelms the proximal convoluted tubule of the nephron with so much fluid that
it’s unable to effectively reabsorb solutes, including phosphate. Alright, as a quick recap, hyperphosphatemia
describes high phosphate levels in the blood, above 4.5 mg/dL, and this can result from
increased absorption and intake, decreased excretion, or a shift of phosphate from the
inside of cells to the bloodstream. High levels of phosphate ions in the blood
also like to bind with calcium forming bone like crystals which can slowly turn into bony structures.


  1. Sir i am in Bachelor Of Dental Surgery, 3rd year, i must admit you are doing a really great work, your Animated 7-8 mins video clears the topic what i've been trying to understand in books…
    thak you so much 🙂 ❤

  2. Hi , really helpfull videos! i have just done a 5 hours marathon in renal videos :D!! keep up the good work

  3. osmosis!!! lot of love from PAKISTAN…i am 4th year MBBS student…your lectures are truly helpful in fact it is my daily dose…i am also waiting for your lectures on HISTOLOGY and CLINICAL MEDICINE!!!!

  4. Hi , thank you very much for these amazing videos.
    Could you please make a video about the thyroid diseases ?

  5. this channel and it's videos are a life saver
    after going through so many videos I feel lucky I found this
    you guys are doing great work
    pls keep posting videos for all subjects of medicine 👌👌👌👍👍👍👍

  6. Awesome presentation team osmosis, really learned something new.

    Sir, may i ask for name of the video editing software you are using for the whiteboard presentation

    Hope to hear from you team osmosis?

  7. Really nice; clear and informative video. At the respiratory acidosis section, 7:54 , is the "less phosphate being pulled out from the blood" due to downregulation of phosphate-sodium-cotransporter (like phosphate is regulated in kidneys and intestine), or is it some other active mechanism? Or do you have answer for this question..? 😀 Thanks already

  8. I s tetany, chvotek sign, a sign of direct hyperphosphatemia, or indirect result of hypocalcemia? If we correct Ca2+, does it (tetany) still persist?

  9. hey i noticed you mention PTH stimulates to osteoclasts but in actuality it stimulates osteoblasts to make osteoclast stimulating factor and that causes it to break down the bone and release Ca and PO4-. I say this bc I have seen a question on this. Thank you for all your videos though ! They really are excellent

  10. i have a question..around 5:00 , about kidney failure + secondary hyperparathyroidism, why is the parathyroid hormone doesnt inhibit phosphate absorption?

  11. @4:40 If the kidney isn't filtering enough blood (as in acute/chronic kidney disease) then how is enough Ca2+ getting filtered for it not to get reabsorbed and cause hypocalcemia? Can there be "selective" kidney disease that only damages the glomeruli or only damages the collecting duct? I would have thought if it lost 50% of it's ability to filter blood at the glomerulus that it would likely also lose 50% of its ability to reabsorb throughout the tubule and vice versa. No?

  12. Fab video, although you said in CKD that "Phosphate is reabsorbed due to impaired excretion", don't you mean "less is filtered so stays in the blood"?

  13. You say a respiratory acidosis causes CO2 to enter the cells and thus form H+ -> lowering the pH.

    But in the hyper-kalemia video, you mentioned that a resp. acidosis does not lead to hyperkalemia (for that exact reason)?

  14. Great video thanks.. but metastatic does not mean that one tissue changes to another. The term to describe that may be metamorphosis or commonly used metaplasia. Metastasis is one thing stays where is not its actual place.

  15. Why do patients with secondary hyperparathyroidism develop hyperphosphatemia if PTH shuts down phosphate reabsorption?

Leave a Reply

(*) Required, Your email will not be published