Calcium and Phosphate Homeostasis Flashcards
what is the biologically active form of calcium?
free, ionized Ca2+
What effect does aging have on calcium levels?
during aging, there are decreases in the amount of calcium absorbed from dietary intake and in dietary intake of calcium
What effect does the decreased calcium absorption/intake levels have in association with aging?
aging contributes to osteopenia or osteoporosis
what are the symptoms of hypocalcemia?
hyperreflexia, spontaneous twitching, muscle cramp, tingling and numbness
what two signs are associated with hypocalcium?
Chvostek sign and trousseau
what are the symptoms of hypercalcemia?
constipation, lack of appetite, polyuria, muscle weakness, hyporeflexia, lethargy
what effect does a low extracellular Ca2+ level have on the action potential?
it reduces the activation threshold for Na+–> so its easier to evoke an AP
what effect does a high extracellular Ca2+ level have on the acton potential?
it raises the activation threshold–> decreased the membrane excitability–> harder to evoke an action potential
the forms of Ca2+ in the blood can be altered by what?
changes in plasma protein concentration, changes in anion concentration, acid-base abnormalities
what is the ionized Ca2+ concentration going to look like in an acidemia situation?
free ionized Ca2+ concentration increases (because less Ca2+ is bound to albumin
what is the ionized Ca2+ concentration going to look like in an alkalemia situation?
free ionized Ca2+ concentration decreases (because less Ca2+ is bound to albumin)
To maintain Ca2+, what must the kidneys do?
they must excrete the same amount of Ca2+ that is absorbed by the GI tract
Ca2+ homeostasis involves the coordinated interaction of three organ systems. What are they?
Bone, kidney, intestine
Ca2+ homeostasis involves the coordinated interaction of 3 hormones. What are they?
PTH, calcitonin, and vitamin D
How is extracellular phosphate (Pi) related to extracellular free ionized Ca2+?
they are inversely related
what is the role of the Parathyroid glands?
they secrete PTH
what specific cell type in the parathyroid gland secretes PTH?
chief cells
What type of hormone is PTH?
peptide hormone
what is the stimulus for secretion of PTH?
low plasma Ca2+ levels
What senses the amount of extracellular Ca2+ levels?
Calcium-sensing receptor (CaSR)
when is the CaSR activated?
whenever there are high levels of extracellular Ca2+
what happens when the CaSR is activated?
there is going to be a downstream signaling pathway that either shuts down the production of PTH or it can also inhibit the PTH gene
What effect does vitamin D have on PTH production?
the active form of vitamin D is going to exert a negative feedback mechanism on the regulation of PTH
Chronic hypercalcemia causes what to PTH?
causes decreased synthesis and storage of PTH and increased breakdown of stored PTH
chronic hypocalcemia causes what to PTH?
causes increased synthesis and storage of PTH and hyperplasia of the parathyroid glands
what type of receptor is the PTH receptor?
it is a GPCR
what does recognition of PTH by the PTH GPCR lead to?
increased levels of cAMP through the activation of AC
where are PTH receptors mostly found?
in the bone and the kidney tubule
what is a byproduct of the activation of PTH?
cAMP
what is the significance of cAMP being a byproduct of activation of PTH?
you are going to see increased levels of cAMP in the urine, so therefore increased urine cAMP could indicate increased levels of PTH
what is the effect of PTH secretion on bone?
increased bone resorption
what is the effect of PTH secretion on the kidney?
decreased Pi reabsorption (phosphaturia), increased Ca2+ reabsorption, increased urinary cAMP
what is the effect of PTH secretion on the intestine?
increased Ca2+ absorption
What type of hormone is vitamin d?
steroid hormone
what is the stimulus for the production of the active form of vitamin D?
decreased levels of Ca2+, increased levels of PTH and decreased levels of Phosphate
what is the main circulating form of vitamin D?
25-OH-cholecalciferol but it is inactive
what converts 25-OH- cholecalciferol into its active form? and where does this occur?
CYP1 alpha (aka 1alpha-hydroxylase) and this occurs in the renal proximal tubule
how is kidney 1alpha-hydroxylase enxyme tightly regulated?
at the transcriptional level
where exactly on bones is the PTH receptor located?
on the osteoblasts
what are the short-term actions of PTH on bone?
bone formation (via direct action on osteoblast)
what are the long-term actions of PTH on bone?
increased bone resorption (due to indirect action on osteoclasts mediated cytokines released from osteoblasts)
What is M-CSF?
it induces stem cells to differentiate into osteoclast precursors
What is the primary mediator of osteoclast formation?
RANKL
Where is RANK found?
it is a cell surface protein receptor on osteoclasts and osteoclast precursors
What are the specific actions of PTH on bone formation and resorption?
increased RANKL and decreased OPG
what is OPG?
produced by osteoblasts- inhibits RANKL/RANK interaction
what are the specific actions of vitamin D on bone formation and resorption?
increased RANKL
how does PTH cause phosphaturia?
by inhibiting the Na+ Phosphate transporter
How does PTH stimulate the kidney?
it stimulates the 1alpha-hydroxylase activity
what is the effect of vitamin D on the intestines?
it is going to promote calcium absorption as well as Pi absorption
how does vitamin D promote calcium absorption in the intestines?
it promotes the protein synthesis of the TRPV6-Ca2+ channel
what is the stimulus for calcitonin release?
high levels of Ca2+ in plasma
where is calcitonin released from?
the parafollicular cell (c cells) in the thyroid gland
what are the effects of calcitonin on bone?
it inhibits bone resorption
where are calcitonin receptors found on bone?
osteoclasts
what is the main effect of calcitonin on bone?
it promotes bone formation
what would you expect the calcitonin levels to be after a thyroidectomy?
decreased, but no effect on Ca2+ levels
what would you expect the calcitonin levels to be with a thyroid tumor?
increased levels, but no effect on Ca2+ levels
what are the effects of Estradiol-17 B on the intestines and kidney?
it stimulates intestinal Ca2+ absorption and renal tubular Ca2+ reabsorption
what is the most potent regulator of osteoblast and osteoclast function?
estradiol-17B
what is the effect of estrogen on bone?
estrogen promotes the survival of osteoblasts and apoptosis of osteoclasts
what is the affect of the adrenal glucocorticoids (cortisol) on bone, kidney, and intestines?
they promote bone resorption, renal Ca2+ wasting, and inhibit intestinal Ca2+ absorption
patients treated with high levels of a glucocorticoid (aka a patient with addison disease) could develop what?
osteoporosis
what is primary hyperparathyroidism?
adenoma of the parathyroid gland- over secretion of PTH
what would expect to see with a patient with primary hyperparathyroidism?
stone, bones, and groans(constipation); hypercalciuria- leads to kidney stones; increased bone resorption
what levels would you expect to see with a patient with primary hyperparathyroidism?
increased PTH, increased Ca2+, decreased Pi, increased Vitamin D
what are some causes of low Ca2+ in the blood that could cause secondary hyperparathyroidism?
renal failure or vitamin d deficiency
what levels would you expect to see in a patient with renal failure?
increased PTH, decreased Ca2+, increased Pi, decreased vitamin D
what levels would you expect to see in a patient with vitamin d deficiency?
increased PTH, decreased Ca2+, decreased Pi, decreased vitamin D
what do the symptoms of hypoparathyroidism resemble?
hypocalcemia
What levels would you expect to see in a patient with hypoparathyroidism?
decreased PTH, decreased Ca2+, decreased vitamin D, increased Pi
what is the treatment of hypoparathyroidism?
oral Ca2+ supplement and active form of vitamin D
what is albright hereditary osteodystrophy?
an inherited autosomal dominant disorder where the Gs for the PTH receptor in the bones and kidneys is defective
what is the result of albright hereditary osteodystrophy?
hypocalcemia and hyperphosphatemia
what would you expect to the PTH levels to be in a patient with albright hereditary osteodystrophy?
high PTH levels (PTH resistance)
what would the treatment of albright hereditary osteodystrophy with PTH result in?
it would produce no response and no increase in urinary cAMP
what would you expect the levels to be in a patient with albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)
increased PTH levels, decreased Ca2+ levels, increased Pi levels, decreased vitamin D levels
what is the phenotype of pseduohypoparathyroidism?
short stature, short neck, obesity
some malignant tumors secrete what?
PTH-related peptide (PTH-rp)
what would you expect the levels of PTH and vitamin D to be in humoral hypercalcemia of malignancy?
low
what is familial hypocalciuric hypercalcemia (FHH)
a mutation that inactivates the CaSR in the parathyroid glands
what does familial hypocalciuric hypercalcemia
decrease in urinary Ca2+ excretion (hypocalciuria) and increased serum [Ca2+] levels
in children vitamin D deficiency causes what?
rickets
what is rickets?
there is an insufficient amount of Ca2+ and Pi available to mineralize growing bones
In adults vitamin D deficiency results in what?
osteomalacia
What is osteomalacia?
new bone fails to mineralize, resulting in bending and softening of the weight-bearing
what are two things you could use to treat osteoporosis?
estrogen and RANKL inhibitors (Denosumab)
