Calcium Metabolism Flashcards
_____ of calcium is located in bones and teeth`
99%
- hydroxyapatite
How much calcium is intracellular?
1%
How much calcium is extracellular?
- 1% in ECF and plasma
- 30-40% is protein-bound
- ionized (50-60%) (unbound) –> biologically active form, fraction dependent on pH
- complexed (10%) –> citrate, lactate, bicarb, phosphate
Ionized calcium makes up ____ of intracellular plasma
55%
3 functions of calcium
- nerve impulses via membrane stabilization
- muscle contraction via release of Ach and NMJ (affects skeletal, smooth, and cardiac)
- coagulation
Clinical signs of hypocalcemia in dogs
- due to stabilization of sodium channels
- anxiety
- tremors
- tetanic concentration
- seizures
- paw chewing
- facial rubbing
Phosphorus concentrations
- 85% in bone
- 15% intracellular (cell membrane, nucleotides)
- <1% extracellular fluid (buffer)
Site of calcium regulation
- GIT
- kidney
- bone
- parathyroid gland
Hormones of calcium metabolism
- PTH
- vitamin D (active form)
- calcitonin
How much calcium is excreted in the feces
90%
Bone is in constant _____
Equilibrium
- balance of calcium resorption and deposition
- calcium reservoir
______ of ingested Ca is absorbed thru the intestine
35%
- via activated calcitriol
Almost all dietary P is absorbed from the ___
Gut
Where does calcium reabsorption occur in the kidneys?
90% reabsorbed in the proximal tubules, loops of Henle and early distal tubules
- reabsorption of remaining 10% is selective!! –> dependent on blood ionized Ca concentration
Bone cells
Osteoclasts - monocyte derivatives - bone resorption Osteoblasts - bone deposition
Vitamin D inhibits ________
Release of Ca from bone
Parathyroid hormone
- chief cells of PT
- maintains plasma ionized calcium concentration
- regulates plasma phosphorous concentration
PTH and the set point
Set point is the calcium concentration required to produce half of the max inhibition of PTH secretion
- small change in [Ca] = large change in [PTH]
PTH effect on bone
Resorption, release of Ca, P from bone
- effect on blood levels
- increased blood calcium, increased phosphorous
- rapid phase of bone resorption (min-hrs)
- slow phase of bone resorption (days-weeks)
PTH effect on kidney
Reabsorption
- increased calcium
Excretion
- decreased phosphorous
PTH effect on small intestine
Indirectly increases active vitamin D
- increase Ca, increase P
Rapid phase of bone resorption
Osteocytic membrane system
- osteoblasts, osteocytes
- bone fluid between osteoblast membrane and bone containing Ca and P salts
Osteocytic pump
Pumps Ca from bone fluid to ECF
- activated by PTH
Slow phase of bone resorption
Osteoclasts
- requires activation and proliferation
- days to weeks
Net effect of PTH on bone
- increased serum Ca
- increased serum P
PTH stimulates calcium reabsorption from the ______ and _____ (fine tuning)
Distal tubules; collecting ducts
_______ stimulates P excretion
Proximal tubules
- has more of an impact that resorption of bone!!!!
= overall decrease in phosphorous concentration
Net effect of PTH on kidneys
- increase serum Ca
- decrease serum P
Proximal tubules stimulates synthesis of _____
Active form of vitamin D
- increases activity of 1-alpha hydroxylase to catalyze vitamin D reaction
What is the net effect of PTH in the blood?
- increase calcium
- decrease phosphorous
Hyperparathyroidism
- increase calcium
- decrease phosphorous
- use to differentiate causes of hypercalcemia*
What are the inactive and active forms of Vitamin D?
- inactive: cholecalciferol
- active: calcitriol
Animals mainly rely on _____ to get vitamin D
Diet; due to heavy fur content
- liver is responsible for synthesizing digested vitamin D
- proximal tubules of kidney is responsible for synthesizing it to active form
Calcitriol effect on the small intestine
- increase calcium
- increase phosphorous
Calcitriol target tissues
- small intestine
- bone
- parathyroid: decrease PTH via feedback inhibition
Nuclear transcription factor
- binds DNA
- increase formation of calcium binding protein (on brush border of intestinal epithelia)
- increases Ca
- increases P
- takes 2 days to take effect due to time it takes to get to the tip of the villi
Small quantities of calcitriol
- increases bone calcification
- increases calcium deposition in bone
Large quantities of calcitriol
- stimulates bone resorption
- increases Ca and P in blood
Ability of PTH to cause bone resorption is reduced/prevented _______ 1,25 vitamin D
Without!!
Calcipotriene toxicity
Derivative of calcitriol
- used for psoriasis
- dogs can eat it = max increase in Ca and P
PTH regulation
Feedback inhibition
- does not involve pituitary or hypothalamus
Secretion is decreased by
- hypercalcemia
- calcitriol
Secretion is increased by
- hypocalcemia
- hyperphosphatemia
Hepatic activation is decreased in response to
- 25-(OH)D (feedback inhibition)
- conserves vitamin D stores in liver
- prevents excessive activation of vitamin D
- 25a-hydroxylase*
Renal activation
Most important site of vitamin D regulation!!
- 1a hydroxylase
- increases in response to increased PTH and decreased P
- decreases in response to decrease P
PTH increases in response to
- decreased calcium
- increased phosphorous
PTH decreases in response to
- increased calcium
- increased calcitriol
Target tissues of PTH
Kidney - resoprtion: increased Ca - excretion: decreased P Small intestine - increased calcitriol - increased Ca and P Bone - resorption - increased Ca and P
Calcitriol regulation
- renal activation via 1a-hydroxylase
- increases in response to increase PTH, decrease P
- decreases in response to increased P
Calcitriol target tissues
Small intestine - CBP: increased Ca and P Bone - variable Parathyroid - decrease PTH
Parafollicular cells of thyroid ______ Ca concentrations
Decrease
Calcitonin
Opposite effects of PTH
- decreases osteocytic membrane activity and osteroclast formation
- less significant than PTH
