Lec 8 Ca Flashcards
What are the physiologic roles of Ca?
- maintain electronic gradient
- maintain skeletal structure
- intracellular messenger
What are symptoms of hypercalcemia?
- depression
- lethargy
- coma
- muscle wekaness
- constipation
What are symptoms of hypocalcemia?
- convulsions
- parasthesias
- muscle cramps
- tetany
- osteoporosis –> bone pain and pathologic fracture
What is state of normal extracellular Ca?
- half bound to serum proteins [albumin]
- small amount in complex with carbonate and phosphate
- rest is free ionized Ca
What is role of intestines in Ca hemostasis?
- Ca absorbed in jejunum
- amount of Ca absorbed is regulated by levels of 1,25 vit D
What is effect of vit D level on Ca absorption?
higher vit D = more Ca absorption
lower vit D = less Ca absorption
What are 3 disorders that cause high Vit D and thus high Ca?
- absorptive hypercalciuria
- primary hyperparathyroidism
- sarcoidosis
What are 3 disorders associated with low vit D leading to low Ca?
- hypoparathyroidism
- malignancy-associated hypercalcemia
- immobilization-induced hypercalcemia
Where is 1,25 vit D produced?
in kidney
How do you calculate the filtered load of Ca?
multiple GFR by ionized serum CA = 10,000 mg/day
What happens to Ca that is filtered at glomerulus?
90% is reabsorbed in proximal tubule
this is not regulated by Ca regulating hormones
10% goes to distal tubular sites where tightly regulated b PTH
What is effect of PTH level on kidney regulation of Ca?
- does not affect reabsorption in proximal tubule
- high PTH –> increase Ca reabsorption and reduce Ca excretion in distal tubule
What is the major means of moment-to-moment maintenance of normocalcemia?
PTH on distal tubule of kidney
What is role of skeleton in Ca hemostasis?
- osteoclasts resorb bone –> increase blood Ca leve
What happens to osteoblast and osteoclast activity in hyperparathyroidism?
both increase
What is only exception to rule that in disease states bone turnover does not contribute or remove significant net Ca?
- when osteoblast/clasts become uncoupled –> immobilization hypercalcemia and malignancy-associated hypercalcemia –> have more osteoclast and less osteoblast
- PTH levels acutely rise or fall –> osteoclast activation requires hrs; osteoblast activation requires days to weeks –> acute rise in PTH leads to acute increase in osteoclastic bone resorption with net skeletal Ca loss lasting a couple weeks until osteoblast catches up
What is normal serum Ca?
9.5 mg/dL
What are 2 sources of vit D?
- dietary vit D supplement
- photoconversion of vit D in skin from sunlight
How is vit D activated?
add two OH groups
- 1 in liver at 25 position
- 1 in prox tubule of kidney [regulated by PTH]
becomes 1,25 vit D = calcitrol
What happens to vit D level in hyperparathyroid?
more activation of vit D –> more vit D avialble
What is effect of phosphorous on vit D?
high serum phosphorous –> inhibits calcitrol synthesis
hypophosphatemia –> stimulates vit D synthesis
What are two effects of vit D on Ca level?
- directly cause uptake of Ca from jejunal enterocyte [1ary]
- stimulate osteoclast [2ndary]
What stimulates PTH secretion?
low Ca [sensed by calciusm sensing receptor [CaSR]]
What are effects of PTH on kidney?
- stimulate distal tubular Ca reasborption
- stimulate conversion 25 OH D to 1,25 OH vit D
- inhibit prox tubule phosphorous reabsorption
- stimulate prox tubule cAMP synthesis and excretion
What is TmP/GFR? What is effect of PTH on this?
TmP/GFR = renal tubule maximum for phosphorous
decreased wtih high PTH; increases with low PTH
What are effects of PTH on bone?
- stimulates osteoclastic bone resorption
- stimulates osteoblastic bone formation
What is mech of calcitonin?
high dose – >induce hypocalcemia through action of calcitonin
chronic high or low dose = no effect
What happens in hypocalcemia?
- have PTH burst –> inhibits renal Ca excretion; osteoclastic bone resorption
if persists –> PTH secretion continues and vit D levels rise –> more Ca intestinal absorption; eventually osteoblasts kick in to prevent skeletal mineral loss
How is acute vs chronic hypocalcemia corrected?
acute: renal Ca conservation + skeletal Ca loss
chronic: PTH induced renal Ca conservation + intestinal Ca hyperabsorption
What is acute response to hypercalcemia?
inhibit PTH –> rapidly lose Ca in urine
What is subacute/chronic response to hypercalcemia?
inhibit PTH –> lose Ca in urine; reduce vit D –> stop intestinal Ca absorption
