10: Regulation of Calcium, Magnesium, and Phosphate Flashcards
What percentage of total body calcium is stored in the bone?
99%
What are the three most important functions of Calcium?
- constituent of bone - 99% of Ca here
- second messanger in cells–> rapid signal transmission
- stabilizes the electrical sensitivity of voltage-gated membrane channels
What are the different forms of plasma Calcium?
- free and ionized (40%)
- protein-bound (40%)
- complexed (20%)
Name two examples of substances Ca may be complexed with in the plasma.
- phosphate
- citrate
How does hypocalcemia cause low-calcium tetany?
Low levels of Ca –> Na-channels sense more depolarization than actually exists –> spontaneous firing of motor neurons –> inappropriate muscle contractions
How can the acid/base status contribute to or worsen hypocalcemic tetany?
Acute alkalosis
hydrogen ions and Ca can both be bound to albumin anionic sites –> if there are less hydrogen ion/protons –> more Ca binds to albumin –> less free ionized Ca available –> hypocalcemic tetany worse
What are the 3 main clinical signs of hypercalcemia?
- CNS depression
- muscle weakness
- GI tract immobility
In what form is Ca stored in bones and what are its constituents?
hydroxylapatite - complex of: Ca, P, hydroxyl groups
Regarding Calcium absorption in the GI tract: How much of dietary Ca is absorbed, where are the two areas of Ca absorption, how is Ca absorbed there and in what proportion?
- less than half of ingested Ca is usually absorbed
- main areas of absorption: duodenum and lower small intestines
duodenum:
* active transport - most important when dietary Ca is limited (does not rely on the cc gradient)
* Ca-selective channels on luminal side (TRP familty) –> enters duodenal cells –> binds to mobile cytosolic Ca-binding proteins (calbindins) –> actively excreted on basolateral side via Ca-ATPase and some Na-Ca antiporter
lower small intestines
* paracellular diffusion - following cc gradient
* most absorbed here under normal conditions
What percentage of filtered Ca is reabsorbed and excreted in the kidneys?
98% reabsorbed
2% excreted
Regarding calcium reabsorption in the kidneys: What are the areas of reabsorption, what proportion of Ca is reabsorbed in each tubular region, and how is Ca reabsorbed there?
-
proximal tubule
* 65% of filtered Ca
* paracellular passive diffusion, following cc gradient, cc gradient achieved by water reabsorption (following the Na reabsorption) causing increased luminal Ca cc compared to interstitium -
thick ascending limb of Loop of Henle
* 20% of filtered Ca
* paracellular passive diffusion –> caused by lumen-positive potential -
distal convoluted tubule and connecting tubule
* ~15%
* active and transcellular
* luminal entrace via calcium specific TPR channels –> transport through cell via calbindins –> exit on basolateral side via Ca-ATPase and Na-Ca antiporter
Where in the kidneys does endocrine control affect Ca absorption?
- distal convoluted tubule and connecting tubule
What is calbindin and how many binding sites does it have?
cytosolic calcium-binding protein
4 binding sites for Ca
what percentage of total body calcium is intracellular?
0.01%
What cells of the bone lower Ca and P by inserting into bone and what cells increase Ca and P by deliberating it from bone?
Osteoclasts –> release Ca and P
Osteoblasts –> build Ca and P into bone
What are the different body compartments of phosphate storage and what are their proportions (%)?
- bone (as hydroxyapatite) 85%
- intracellular (as phosphorylated proteins and metabolic intermediates) 14%
- ECF 1%
What proportion of the ingested phosphate is typically absorbed?
65%
Where and how in the GI tract is phosphate absorbed?
throughout the small intestines
* transcellular active transport and paracellular diffusion
* active transport = Na-phosphate symporters on apical membrane - basolateral not known (presumed uniporters)
What proportion of phosphate in the blood is protein-bound?
5-10%
What percentage of filtered phosphate is actively reabsorbed under normal conditions?
75%
Where and how is phosphate reabsorbed in the kidneys?
- proximal tubule
- active transcellular - Na-phosphate symporters
Is phosphorous tubular-maximum or gradient-limited?
tubular-maximum limited system
under normal circumstances most transporters are saturated and there is no “spillage” paracellulary
What is the active form of vitamin D?
1,25-Dihydroxy-Vitamin-D [1,25-(OH)2-D]
syn. Calcitriol
What steps does ingested Vitamin D undergo to become active Vitamin D
Vitamin D3 = cholecalciferol
Vitamin D2 = ergocalciferol
ingested vitamin D –> travels to the liver –> liver hydroxylates it at the 25 position –> travels to the kidneys –> hydroxylated at the 1 position by proximal tubular cells –> 1,25-Dihydroxy-Vitamin-D
How do PTH and FGF23 affect Vitamin D?
PTH stimulates vitamin D hydroxylation in proximal tubules
FGF23 inhibits hydroxylation of vitamin D in the proximal tubules
How does vitamin affect Ca and P homeostasis?
increases transcellular and paracellular (effect on tight functions) Ca absorbtion in intestines –> P to lesser extend
stimulates renal-tubular reabsorption of both calcium and P
How does calcitriol affect PTH and FGF-23 levels?
–> inhibits PTH synthesis in the parathyroid gland
–> promotes FGF23 production
What is the half-life of PTH?
less than 10 min –> degradated fast by liver
How does ECF Ca cc affect PTH secretion?
ECF Ca cc –> binds to Ca receptor couple to G protein-linked signaling cascades –> inhibits PTH secretion
low Ca cc –> removes tonic inhibition –> increased PTH release
How does Phosphate affect PTH secretion?
High phosphate –> stimulates PTH secretion
What are the 5 actions of PTH
- increases movement of Ca and P from labile pool in bone into ECF
- stimulates bone remodeling (net effect on Ca if normal PTH levels, if high –> erosion of hydroxyapatite)
- sitmulates hydroxylation of vitamin D in proximal tubules
- increaes renal tubular Ca reabsorption in distal convoluted tubules
- reduces proximal tubular P reabsorption
Where is FGF-23 produced?
osteoblasts and ostercytes –> secretin increased in response to elevated P levels
here
What are the effects of FGF-23?
primarily regulator of P, but secondary effects on Ca (indirect)
- acts on FGF-23 receptors containing protein called “Klotho”
- decreases reabsorption of P by causing the internalization of Na-phosphate symporters
- decreases production of calcitriol
Describe the mechanisms behind secondary hyperparathyroidism from chronic kidney disease
Decreased GFR –> decreased P excretion –> hyperphosphatemia –> elevated PTH and FGF-23
decreased renal function + high FGF-23 –> decreased active Vitamin D
–> reduced calcium uptake from GI tract –> removal of inhibitory effect on PTH synthesis –> high PTH –> excessive bone resorption
high P –> calcification of vascular smooth muscles
What proportion of dietary Mg is absorbed?
about 50%
How is dietary Mg absorbed?
paracellular diffusion mostly through tight-junctions of small intestines + some transcellular uptake
What are the fractions of Mg in the blood?
60% free
30% albumin-bound
10% complexed
Regarding Mg reabsorption in the kidneys: where is it rabsorbed, in what proportion and how?
- 20% parcellular proximal tubule
- 70% paracellular loop of henle
- rest distal tubules - transcellular, active
