physiology of calcium regulation Flashcards
where is the majority of the calcium stored
- within the bone as extracellular matrix
total calcium of blood consists of:
- 40% bound to plasma proteins
- 10% in compexes
- 50% in an ionized form
how is blood calcium levels maintained
- buffering (exchangebale clacium in bone salts and in mitochondria)
- hormonal control
what hormones control calcium
- parathyroid hormone (PTH)
- calcitonin
- active vitamin D3 (calcitriol)
where is PTH produced and by what
external and internal parathyroid glands by the principle cells (chief cells)
where is calcitonin produced
parafollicular cells of thyroid
where is calcitriol activated
kidney
how is calcium homeostasis maintained
- if hypocalcemic and need more calcium: increase PTH and produce more activated vitamin D3
- if hypercalcemic and need less clacium: decrease PTH
- in severe hypercalcemia: calcitonin
continuous secretion of PTH allows for increase or decrease depending on needs
what stimulates parathyroid hormone
hypocalcemia
- acts to raise blood calcium level
what kind of receptor mediates PTH
G-protein couple calcium sensing receptor
discuss PTH synthesis
- preprohormone
- prohormone (amino acids cleaved)
- into secretry vesicles as PTH (more amino acids cleaved)
where is PTH degraded
liver
discuss PTH secretion
- PTH secreted continuously but increases a extracellular fluid iCa level decreases
- direct negative feedback system
- membrane receptors on principal cells
- receptor coupled G protein which controls exocytosis of PTH containing vesicles
- PTH secreted at moderate rate at normal range of iCa
- PTH secretion increases when iCa falls and decreases when it increases
- very responsive system
what are the actions of PTH within the body
- bone (fast) gets calcium from bone fluid
- bone (slow) phase gets calcium from bone
- kidney: reabsorption within tubules recovers more calcium from urinary filtrate
- intestine: indirect effect through the actiation of vitamin D to get calcium from gut
what tissues does PTH interact with
- bone
- kidney
- intestine
describe the fast phase of calcium turnover from bone
- begins in minutes and progressively increases for hours
- PTH acts on existing osteocytes and osteoblasts
- cells connected by long filmy processes that extend through the bone called osteocytic-osteoblastic membrane system contain fluid within themselves and the bone = bone fluid
- increased calcium uptake from bone fluid
discuss how PTH interacts with bone fluid to increase calcium
- PTH interacts with membrane receptors on osteocytes and osteoblasts
- increases permeability to calcium on bone fluid side of membrane
- increased calcium uptake from bone fluid takes Ca out of bone via ATP powered pump
- bone fluid calcium level drops
- nearby calcium phosphate crystals replace calcium in the bone fluid (osteolysis)
discuss the slow phase of gaining calcium from bone
- activation of osteoclasts
- no receptors for PTH on osteoclasts so signal comes from activated osteocytes and osteoblasts
- existing osteoclasts are activated (stage 1)
- new osteoclasts are formed (stage 2)
- progressive depletion of bone mineral
- takes 48 hours to respon
- gets phosphate as well
discuss how bone resorption releases calcium
- multinucleated osteocasts attach to bone
- formation of reaction chamber at attachment = creation f resorption cavity
- bone resorption by release of organic acids and proteolytic enzymes
- released Ca and P transported across osteoclast to blood
discuss the interaction between PTH and the kidney
- increases calcium reabosrption in the late distal tubules and collecting tubules
- results in retention of Ca and Mg
- decreases phosphorus reabsorption in the renal proximal tubule
- results in rapid loss of phosphorus
- important as PTH gets Ca from bone but also P so needs to find a way to get rid of P as P will effect availibility of Ca
discuss the interaction between PTH and vitamin D
- get vitamin D from skin or diet
- first conversion from vitamin D to 25-hydroxyvitamin D in liver
- final conversion to active vitamin D (calcitriol) occurs in the renal tubules
- catalyzed by the enzyme 1 alpha hydroxylase (25 hydroxyvitamin D becomes 1,25 dihydroxyvitamin D
- enzyme is activated by PTH
- rise in PTH = increase in calcitriol
relate PTH to vitamin D activation
PTH activates vitamin D in the renal tubules through 1-alpha-hydroxylations when blood phosphorus levels are low
discuss the importance of calcitriol for calcium regulation
- increases calcium absorption from the intestine
- decreases calcium excretion by the kidneys
- needed for normal functioning of bone
- increases the active transport of calcium
- enters intestinal epithelial cells and increases the synthesis of calcium-transport proteins
- effects renal tubular epithelial cells to increase calcium reabsorption from urine
- essential for bone reabsorption in response to PTH and deposition of bone
how does active vitamin D work
- through calcium channel proteins in lumen of intestine
- calcium binding protein (calbindin)
- calcium ATPase pumps (basolateral)
is calcitonin clincially significant
usually no - has an overall weaker influence than PTH
what stimulates calcitonin
hypercalcemia
what secretes calcitonin
parafollicular cells
what are the effects of calcitonin
- fast phase bone response (inhibits osteoclast absorptive activities)
- slow phase bone response (reduce formation of new osteoclasts)
- slight (insignificant) effects on the kidney and intestinal tract
is magnesium hormonally controlled
no
