Regulation of calcium and phosphate metabolism Flashcards
What is the active form of Ca2+ in the body? Where is most calcium stored?
Free ionized Ca2+. Most is stored in bones and teeth
Why is extracellular calcium concentration important?
It affects the excitability of neurons
What is the effect of aging on Ca2+?
Decrease in dietary intake of calcium and how much calcium is absorbed from diet (osteopenia or osteoporosis)
What symptoms does hypocalcemia usually present as?
Low Ca2+ > lower threshold of neurons for AP > lots of random AP so hyperreflexia, twitching, cramping, tingling and numbness, aka excite the nervous system
What are Chovstek sign and trousseau signs? What do these indicate?
Chovstek: facial twitching triggered by tapping on CN VII
Trousseau: carpopedal spasm upon inflation of blood pressure cuff
-Indicative of hypocalcemia
What symptoms does hypercalcemia usually present with?
High Ca2+ > higher threshold of neurons for AP > less Aps > muscle weakness, hyporefelxia, lethargy, no appetite aka depress the nervous system
How can you alter Ca2+ concentration in blood?
- plasma protein concentration (directly proportional)
- Anion concentration (inversely proportional)
- change the fraction of Ca2+ bound to albumin (acid/base)
Acidemia does what to Ca2+ concentration? How?
If there’s lots of H+, they occupy most of the binding sites in albumin, leaving Ca2+ in the blood
Alkalemia does what to Ca2+ concentration? How?
If there’s less H+, Ca2+ can bind to albumin > less Ca2+ floating around in the blood
What are the roles of these molecules in Ca2+ homeostasis?
Vitamin D
PTH
Calcitonin
- absorb the Ca2+ from the intestines, bone resorption
- increase Ca2+ in the blood (resorption of bone)
- decrease Ca2+ in the blood (reabsorption by bone and excretion by kidney)
What is the relationship of extracellular phosphate concentration to Ca2+ concentration? What regulates phosphate and where is it found?
Inversely proportional, regulated by the same hormones that regulate Ca2+ and found mostly in bone
What produces PTH?
Chief cells of the parathyroid gland
Describe the synthesis of PTH
preproPTH > pro PTH > cleaved by Golgi to PTH > packaged to granules
Draw the pathway of regulation of PTH synthesis and secretion
Ok
What happens to PTH synthesis if you have chronic hypercalcemia? How about chronic hypocalcemia?
- decreases (since lots of Ca2+ feedback)
- increases (since no Ca2+ feedbacks)
How does magnesium affect PTH secretion?
Same as Ca2+. But severe hypomangesemia (alcoholics) can inhibit PTH altogether
Draw the mechanism of action of PTH
Ok
What is active Vitamin D? What is its main function in relation to Ca2+ and Pi?
1-25, dihydroxycholecalciferol. Increase Ca2+ and Pi blood concentration
What is the mechanism of action of Vitamin D?
It’s a steroid so it travels in the blood via binding protein > attaches to RXR nucleus receptor and ups/downs gene expression with end goal to increase ca
Draw the synthesis of Vitamin D
Ok
How is 1a hydroxylase regulated?
Comes from CYP1a gene. Activated by PTH binding to receptor in proximal tubule cell and deactivated by Ca binding to receptor in proximal tubule cell.
How exactly does PTH increase Ca2+ in blood?
Binds to osteoblasts first (short term - bone formation) > osteoblast releases cytokines > binds on osteoclasts which takes the Ca2+ out of the osteoblast
Draw the mechanism of bone resorption and formation
Ok
Roles of M-CSF, RANK L, RANK and OPG in bone formation and resorption
M-CSF: induces maturation of osteoclasts
RANK L: binds to RANK receptor on osteoclasts > allows them to osteoclast
RANK: RANK L receptor
OPG: decoy receptor for RANK L to prevent it from enabling osteoclasts
What are the actions of PTH and Vitamin D on RANKL and OPG?
PTH increases RANKL and decreases OPG
Vitamin D increases RANKL eceptor for RANK
What is the action of the PTH on the kidney cell?
PTH wants to keep Ca2+ and get rid of Phosphate. Inhibits the NPT2a phosphate receptor so it can’t travel to the bloodstream and stays in the urine filtrate
Draw how Vitamin D regulates the absorption of Ca2+ from the intestine into the bloodstream
OK
How does Vitamin D facilitate absorption of phosphate into bloodstream?
Activates NPT2a to let the phosphate in
What does calcitonin do?
Bone formation and lower Ca2+ and Pi levels by binding to receptors on osteoclasts and inhibiting them
What happens to calcitonin levels after a thyroidectomy? How about thyroid tumor?
Decreased calcitonin
Increased calcitonin
How does estradiol affect Ca2+ and Pi metabolism?
promote GI bsorption and kidney reabsorption. of Ca2+. Osteoblast survival and osteoclast apoptosis
How do glucocorticoids affect Ca2+ and Pi metabolism?
Promote resorption
Primary hyperparathyroidism
Cause
Clinical
Treatment
-Parathyroid problem (too much PTH, could be caused by adenoma)
-Groans: stones and constipation, plus lots of Ca, Pi and cAMP excretion
Bones: resorption
-Parathyroidectomy
Secondary hyperparathyroidism:
-Low blood Ca2+ (due to renal failure or vitamin D deficiency) causes increased PTH.
What happens to phosphate in 2ndary hyperparathyroidism?
Kidney failure: defective kidney, phosphate isn’t excreted and Ca2+ isn’t reabsorbed
Vitamin D deficiency: kidney is fine and getting rid of phosphate, but intestine doesn’t absorb the Ca2+
Hypoparathyroidism:
Cause
Clinical
Treatment
- Insufficient PTH due to problem with parathyroid causing low Ca2+. —-
- Hypocalcemia symptoms and hyperphophatemia
- Ca2+ and Vitamin D supplement
Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)
Cause
clinical
- Lots of PTH but cannot activate adenylate cyclase. No response to PTH
- hypocalcemia and hyperphosphatemia, lots of urinary cAMP. Short everything, obese, calcified skin
Humoral hypercalcemia of malignancy
Cause:
Tumor produces PTHrP which mimics PTH and binds the type 1 PTH receptor. Low PTH but lots of PTH effects cause of the impostor
Humoral Hypercalcemia of malignancy:
Clinical
Lots of PTHrP, blood Ca, urinary Ca, Pi and cAMP but low PTH
Familial hypocalciuric hypercalcemia (FHH)
CaSR not working (mutated). Can’t respond to Ca2+ so chief cell keeps making PTH
-High blood Ca2+ and low urinary Ca2+. Normal to high PTH
Vitamin D deficiency results in …
Rickets in kids and osteomalacia in adults
Rickets:
Weak bones in kids.
Type 1: lack of 1a hydroxylase
Type 2: lack of vitamin D receptor
Osteomalacia:
Cause
Clinical
- GI problems that it can’t absorb Vitamin D, no sun exposure
- bone pain, fractures, muscle cramps, positive Chvostek’s sign
Osteoporosis:
Cause
Treatment
- Loss of bone mass overtime. Lots of resorption with disproportionate formation
- anything that increases osteoblast formation or inhibits osteoclasts
