Flashcards in Phosphate Physio and Disorders Deck (35)
Normal plasma phosphate?
2.5 - 4.5 mg/dL
It's really hard to have a low-phosphate diet, but how might a person develop hypophosphatemia from low intake?
Starvation will cause hypophosphatemia (because it will still be lost via feces).
Main 2 ways the body gets rid of phosphate?
Urine and feces.
But renal excretion is the part that gets turned up when extra phosphate is present.
Effects of phosphate levels on bone?
High levels suppress bone resorption.
Low levels stimulate bone resorption.
2 renal things that phosphate levels affect?
Vit D activation: High phosphate suppresses it, low levels stimulate it.
Calcium excretion: Low phosphate increases Ca++ excretion.
Phosphate absorption in the proximal tubule is very similar to the absorption of what? How so?
Very similar to glucose, in that if the filtered load is beneath the maximum transport rate, it will be completely reabsorbed.
If the phosphate filtered load exceeds transport capacity, phosphate will start to appear in the urine. The excess is not absorbed at all.
(and like glucose, it's cotransported with Na+)
What are 3 major factors that regulate phosphate transport?
Dietary PO4 intake
What's the transporter for phosphate reabsorption?
How does PTH affect phosphate?
How does phosphate affect PTH release?
PTH decreases phosphate absorption (lowers the maximum transport rate), causing phosphaturia amd reduced serum PO4.
High plasma phosphate stimulates PTH release
But wait, doesn't PTH cause PO4 to be liberated from bone? Why does PTH lower PO4?
You're right, PTH does PO4 liberation from bone. But the decreased absorption produces net decreased serum phosphate.
If hypophosphatemia is caused by low intake, how will urine phosphate levels be?
They'll be really low.
If they're not, the kidney is participating in phosphate wasting.
How will decreased PO4 intake promote its own intake?
Low PO4 promotes Vitamin D activation, which will lead to increased intestinal and renal reabsorption.
Other than PTH, what's a particularly important hormone that promotes PO4 excretion (i.e. inhibits renal PO4 absorption)?
What's the receptor (or cofactor?) for FGF23?
(Trivia: Klotho knockout -> premature aging)
What affect does a carbohydrate load (e.g. glucose infusion) have on serum PO4? Is this a problem?
Serum PO4 will fall, but intracellular stores will buffer this drop unless phosphate is severely depleted.
5 effects of chronic low phosphate on hormones / ions, etc.? (they've all been mentioned already, and make sense)
Reduced PTH and FGF23.
Reduced urine phosphate.
Increased Vit D activation.
Increased bone resorption.
Increased Ca++ excrettion.
(chronic high phosphate does the exact opposite)
6 systems affected by chronic severe hypophosphatemia?
Musculoskeletal (muscle problems, osteomalacia).
Cardiovascular (myopathy, arrhythmia).
Pulmonary (resp. failure, can't wean from vent.).
Hemotologic (impair O2 release, hemolysis).
Metabolic (metabolic acidosis, glucose intolerance).
Why does prolonged severe hypophosphatemia cause metabolic acidosis?
Lack of the buffering done by PO4.
Why does prolonged severe hypophosphatemia cause glucose intolerance?
Without PO4 to add to glucose (by hexokinase), glucose can't be trapped within cells.
How does prolonged severe hypophosphatemia impair O2 release?
RBCs need PO4 to synthesize 2,3-bisphosphoglycerate (2,3-BPG), which is important for O2 release from hemoglobin.
Not being able to make ATP is really bad.
3 broad causes of hypophosphatemeia (3 different locations)?
Decreased absorption in GI.
Increased renal excretion.
4 things that can drive hypophosphatemia due to intracellular shifts?
Hormones (catecholamines and insulin... just like K+).
Rapid cellular proliferation.
2 examples of rapid cellular proliferation that can drive hypophosphatemia?
Leukemic blast crisis.
Hungry bone syndrome (post-parathyroidectomy sudden reduction from hyperPTH causes bone to rapidly take up PO4)
Malabsorption and Vitamin D deficiency do reduce phosphate absorption in the GI tract, but what's the more important reason why they cause hypophosphatemia?
Low Ca++ will stimulate PTH.
PTH will cause PO4 to be excreted renally.
What OTC drug can cause impaired GI phosphate absorption?
Antacids containing aluminum.
It's not common, but if one really goes at it, the aluminum can chelate away the phosphate.
How was FGF23 discovered to be important?
Tumors secreting FGF23 -> osteomalacia.
Genetic defects in breakdown of FGF23 -> Rickets.
What enzyme breaks down FGF23?
If it's defective, too much FGF23 -> PO4 wasting.
How does hyperPTH cause CHF?
Decreased phosphate -> decreased 2,3-BPG -> decreased O2 delivery to cardiac muscle -> CHF