Calcium & Phosphorus Metabolism Flashcards
Where is calcium found in the body?
- 1% is in the cells and organelles
- .1% is in extracellular fluid
- 98.9% is in bone
50% of calcium in the body is found in what form?
Ionized Ca2+
Which form of calcium is biologically active?
Ionized Ca2+
41% of calcium in the body is found in what form?
Bound to proteins:
- Typically albumins
- Cannot diffuse through capillary walls
9% of calcium in the body is found in what form?
Combined with anions:
- Citrate, phosphate, bicarbonate
- NOT ionized
How much of calcium in the body is biologically active?
50% Ionized Ca2+
What is a normal level of calcium in the body?
9.4mg/dl (range 8.6-10.6)
Why is calcium mg/dl very tightly controlled?
Very small changes can have a drastic effect
What is the effect of hypercalcemia?
Depresses the nervous system:
- Excess calcium shuts down the sodium-calcium pumps in nerves
- Weakness, flaccid paralysis
- Anorexia, constipation
What is the effect of hypocalcemia?
Creates spontaneous nerve firing:
- Insufficient calcium increases sodium concentrations in nerves
- Spasm, tetany, seizures
Calcium is a major ___-ion in bone and teeth
cation
Phosphate is a major ___-ion in bone
anion
Which mineral is fundamentally important in:
- All glycolytic compounds
- ATP, ADP, AMP, creatine phosphate
Phosphate
Which mineral is fundamentally important in:
- Neurotransmission
- Skeletal/cardiac/smooth muscle contraction
Calcium
Which mineral is fundamentally important in:
- Enzymatic reactions
- Hormone secretion; mediates hormone events
- Blood clotting
Calcium
Which mineral is fundamentally important in:
- Cofactors - NAD, NADPH
- Lipids like phosphatidyl choline
- Covalent modifier of enzymes
Phosphate
The majority of calcium and phosphate is tied up together in ___
hydroxyapatite Ca10(PO4)6(OH)2
What is the normal level of phosphate in the body?
3-4.5 mg/dl
Why aren’t phosphate levels as tightly controlled as calcium?
Larger variations are needed before any symptoms
Where is phosphate found in the body?
- 85% is in bone
- 14% is in cells
- 1% is in extracellular fluid
How much dietary calcium should be consumed?
About 1000mg of calcium/day
How much dietary calcium should be excreted?
About 1000mg of calcium/day (900mg in feces, 100mg in urine)
Which vitamin is essential for the gut wall to absorb calcium?
Vitamin D
How much calcium is absorbed by the gut wall?
About 350mg/day
How much calcium is excreted by the gut wall?
About 250mg/day
90% of calcium in excreted urine is reabsorbed in ___
proximal filtrate
10% of calcium in excreted urine is reabsorbed in ___
distal filtrate (depending on serum calcium levels)
Dietary phosphorus is readily absorbed ___ due to ___
readily absorbed across the gut wall due to calcium binding
Phosphorus is excreted in urine via ___
overflow mechanism
When concentrations are below 1mmol/L, kidneys reabsorb all ___
phosphate
Above 1mmol/L, ___ excretes via overflow mechanism
phosphate
Excretion of phosphate above 1 mmol/L is equal to ___
excess phosphate
Parathyroid hormone can greatly increase ___ excretion
phosphate
Phosphate control is mainly via ___
urinary excretion
Ca2+ movement between bone, gut, and kidneys is regulated by:
- Parathyroid Hormone (PTH)
- Calcitriol or Vitamin D
- Calbindin
- Calcitonin
Secretion of PTH is inversely related to ___
plasma Ca2+ levels
Release of PTH is monitored by ___ on cell membrane of parathyroid gland cells
Ca2+ sensing receptor
PTH and ___ form a negative feedback pair
Ca2+
As Ca2+ levels increase, PTH secretion ___
decreases
As PTH secretion increases, Ca2+ levels ___
decrease
What form of calcium regulates PTH secretion (within minutes)?
Ionized Ca2+
What is the half life of PTH?
Less than 20 minutes
How does hypercalcemia affect the parathyroid gland?
PTH synthesis is shut down and stores are degraded (glandular atrophy)
How does hypocalcemia affect the parathyroid gland?
Gland hypertrophy
What are the short term effects of PTH on bone?
- Downregulate osteoblasts
- Release of calcium and phosphate by osteoblasts and osteocytes
(reminder: PTH has a 20 minute half life)
What are the long term effects of PTH on bone (persistent hypocalcemia)?
- Stimulate production of osteoclasts and activates resorption of bone
- Remove calcium phosphate salts from bone lying near these cells waiting to be mineralized
- All constituents of bone are liberated
Which constituents of bone are liberated by long term effects of PTH?
- Calcium
- Phosphate
- Bicarbonate
- Other minerals and proteins
How does PTH affect the proximal and distal tubules of kidneys?
- Increase Ca2+ resorption from distal tubule
- Proximal tubule is very consistent, barring renal disease
What is the most dramatic effect of PTH on the kidneys?
Inhibit resorption of phosphate; less phosphate to bind Ca2+, increasing serum calcium
PTH stimulates synthesis of ___ in the kidney
Calcitriol, a Vitamin D metabolite
What is the action of calcitriol in the kidneys?
Binds with cytosolic receptor and enters nucleus; stimulates protein synthesis of calbindin
What is the action of calbindin in the gut?
Facilitates Ca2+ absorption
Calcium absorption across the gut is facilitated by ___
calbindin
production stimulated by calcitriol
Phosphate absorption across the gut is stimulated by ___
vitamin D
What is the action of calcitriol in bone?
Stimulates bone resorption working with PTH
PTH stimulates synthesis of calcitriol
How does calcitriol affect osteoblasts?
How does calcitriol affect osteoclasts?
Osteoblast receptors for calcitriol are signaled to form osteoclasts
Osteoclast receptors for calcitriol are signaled to increase activity
The gut is affected by PTH indirectly via ___
calcitriol and calbindin production and release (from kidneys)
PTH makes these
___ facilitates active transport of Ca2+ across the gut wall
Calbindin
Calbindin facilitates active transport of ___ across the gut wall
Ca2+
PTH causes increase of ___ and decrease of ___ in plasma
increase of calcium and decrease of phosphate in plasma
How do the kidneys initially react to phosphate and calcium when prompted by PTH?
Kidney dumps phosphate and conserves calcium initially
As plasma calcium levels rise and PTH levels decrease, how does the kidney react?
Kidney excretes more calcium so urinary calcium levels maintain homeostasis
Actions of PTH on parathyroid, kidney, and gut increase ___ influx into blood
calcium
How does PTH affect the kidney when plasma phosphate levels rise?
PTH action on the kidney overwhelms phosphate levels causing elimination of phosphate in the urine
How is phosphate indirectly related to PTH?
Role of phosphate on PTH is indirect through mechanisms that lower calcium levels
With increased phosphate, ___ is excreted in urine
calcium
Increased phosphate leads to ___ dropping due to binding with phosphate, leading to ___ increasing and preventing ___
calcium dropping due to binding with phosphate, leading to PTH increasing and preventing metastatic calcification
___ modulates hyperphosphatemic situations by increasing renal excretion of phosphate
PTH
PTH modulates hyperphosphatemic situations by what effect on the kidney?
Increasing renal excretion of phosphate
Vitamin D has a potent effect of increasing ___ absorption from the gut
calcium
___ has a potent effect of increasing calcium absorption from the gut
Vitamin D
How is Vitamin D necessary to bone?
Needed to build bone, also important in bone resorption via its role in calcium metabolism
May play a role in bone remodeling as inflammatory mediator
What is a major storage site for Vitamin D?
Muscle
Profound muscle weakness is seen in ___ deficiency
Vitamin D
Vitamin D is converted to more metabolically active metabolites in the:
- Liver
- Kidney
Vitamin D is stored in the kidney as ___
calcitriol
What gland cells produce calcitonin?
Parafollicular cells of the thyroid gland
Calcitonin acts to lower plasma ___
calcium
What is the relationship between calcitonin and PTH?
Calcitonin is a PTH antagonist
Calcitonin binds to membrane receptors (in all cells of the body) causing ___ levels to increase
cAMP (cyclic adenosine monophosphate)
cAMP as second messenger initiates ___ action
calcitonin
Calcitonin sequesters calcium into ___, reducing serum levels
mitochondria
How does calcitonin lower plasma levels of calcium?
Lowers cytosolic calcium, pulling calcium into cells (mitochondria)
Which bone cells are inhibited by calcitonin?
Osteoclasts (because there’s less calcium available in the blood); this is the opposite effect of PTH
Calcitonin has the same results as PTH on ___
phosphate
How is calcitonin’s effect of phosphate different from PTH’s effect?
- Mechanism is different
- Calcitonin enhances phosphate uptake into bone
Basically, what is the effect of calcitriol on calcium?
Tries to conserve calcium; increases calcium in serum
Basically, what is the effect of calbindin on calcium?
Binds calcium in gut; increases calcium absorption
Basically, what is the effect of calcitonin on calcium?
Tones down levels of calcium; decreases calcium in serum