Calcium, Phosphate Metabolism And Homeostasis Flashcards
What is the total amount of calcium normally found in the body?
25,000 mmol or 1 kg
How is calcium distributed throughout the body?
- 99% contained in mineral phase of bone as a component of hydroxyapatite
- remaining 1% split between extracellular ionised Ca and intracellular cytosolic Ca
List some of the biological roles of calcium. (5)
- muscle contraction
- intracellular messenger
- nerve excitability
- blood coagulation
- cofactor for enzymes of intermediary metabolism
How is calcium distributed in serum?
- approx 47% is free/unbound/ionised
- approx 47% is bound to proteins, mainly albumin
- approx 6% complexed to anions e.g. to phosphate
Why is the free fraction of calcium in serum physiologically important?
The free fraction regulates many feedback mechanisms
How can calcium be measured?
Either by free calcium or total calcium (free + bound)
What is the adjusted calcium level?
What the serum total calcium would have been in the albumin had been normal.
What is the equation for the adjusted calcium level?
Ca (adj) = Ca (total) + [0.02(45-alb)]
What is the normal range for serum calcium?
2.2 - 2.6 mmol/l
Define a serum calcium level above 2.6 mmol/l
Hypercalcaemia
Define a serum calcium level below 2.2 mmol/l
Hypocalcaemia
List the main organs involved in calcium homeostasis.
- kidney
- gut
- bone
- parathyroid glands (calcium sensing receptors)
What are the two hormones involved in calcium homeostasis?
Parathyroid hormone and calcitriol.
What is calcitriol also known as?
Vitamin D3 / 1,25 dihydroxyvitamin D / dihydroxycholecalciferol / 1.25DHCC
What is the daily dietary intake of calcium?
25 mmol per day
List some dietary sources of calcium.
- milk, cheese and other dairy foods
- curly kale
- soya drinks with added calcium
- bread and anything made with fortified flour
- fish where you eat the bones e.g. sardines and pilchards
Where does calcium absorption mainly occur?
In the duodenum and jejunum.
How is calcium absorbed in the duodenum and jejunum?
- via a cell mediated active transport pathway which is controlled by 1.25 DHCC
- via passive diffusion which depends on luminal Ca concentration and is unaffected by 1.25 DHCC
How much calcium is filtered through the kidneys each day?
Approx 240 mmol
How much calcium is excreted in urine each day?
Approx 6 mmol
How much calcium is released and laid down in bone each day?
Approx 8 mmol released and then 8 mmol laid down again.
The proportion of ingested calcium that is absorbed can vary from…
20% to 60%
How much calcium that filters through the kidney is reabsorbed in the proximal tubule?
65%
When calcium is reabsorbed in the proximal tubule what it is coupled to?
Bulk transport of solutes such as Na and water.
How much of the calcium that filters through the kidneys is reabsorbed by the cortical thick ascending loop of Henle?
20%
How much of the calcium that filters through the kidney is reabsorbed in the distal convoluted tubule?
15%
In which areas of the kidney does parathyroid hormone increase re absorption of calcium?
Cortical thick ascending loop of Henle and distal convoluted tubule.
What is parathyroid hormone and where is it produced?
An 84 amino acid polypeptide that is produced by the parathyroid glands.
How is secretion of PTH regulated?
By free calcium levels which are detected by the calcium sensing receptors.
Where are calcium sensing receptors found?
In parathyroid cells and renal tubules.
What type of receptor are the calcium sensing receptors?
G protein coupled receptors.
What is the function of the calcium sensing receptors on parathyroid cells?
To mediate the effect of extracellular ionised Ca on PTH release.
What is the function of the calcium sensing receptors in the renal tubules?
To mediate the effect of high peritubular ionised Ca to inhibit Ca reabsorption.
Name a drug which is used clinically to reduce PTH secretion in patients with conditions such as hyperparathyroidism and parathyroid cancer.
Cinacalcet
What abnormalities may occur due to disorders of the calcium sensing receptors?
Abnormalities in serum calcium concentrations
Describe the curve which demonstrates the relationship between ionised calcium and PTH.
- Ca along x axis
- PTH along y axis
- steep, inverse sigmoid also curve
- PTH falls as Ca increases
Which point of the PTH/Ca curve gives the sensitivity of the parathyroid gland (calcium sensing receptors) to iCa?
The midpoint
Summarise the actions of PTH in regards to calcium levels.
- Stimulates renal tubular calcium reabsorption
- Promotes bone resorption
- Stimulates formation of 1,25 DHCC in kidney which then enhances calcium absorption from the gut.
Will a fall in ionised calcium levels lead to an increase or decrease of PTH secretion?
Increase
Where can vitamin D be obtained?
Through diet (e.g. oily fish like salmon, mackerel) and from sunlight
Where is vitamin D initially synthesised?
In the skin as cholecalciferol.
What happens to vitamin D3/cholecalciferol in the liver?
It is converted to 25OH cholecalciferol
What happens to 25OH cholecalciferol in the kidney?
It is converted to 1,25 DHCC (the active form of vitamin D)
What is hypoparathyroidism?
A rare condition where the parathyroid glands produce too little PTH which leads to a decrease in calcium levels.
List 3 causes of hypoparathyroidism.
- Neck surgery
- Idiopathic
- Magnesium deficiency
What can cause hypocalcaemia?
- Issues with PTH
- Vitamin D issues
List 2 ways in which an issue with vitamin D production may arise.
- Deficiency from malabsorption or little exposure to sunlight
- Renal disease where the kidneys cannot make the active form of vitamin D
List 3 causes of hypercalcaemia.
- Too much PTH due to hyperparathyroidism e.g. adenoma of parathyroid gland
- Too much vitamin D due to over dosage
- Malignancy e.g. lung cancer, breast cancer, multiple myeloma
What happens to calcium and PTH levels in hyperparathyroidism?
Calcium levels rise, PTH levels rise
What happens to calcium and PTH levels when hypercalcaemia occurs due to malignancy?
Calcium levels rise and PTH levels are suppressed
Why is phosphate important for the body?
- Important in bone mineralisation and skeleton development
- Component of cell membranes, nucleotides and involved in cell signalling
What percentage of phosphate is found in the mineralised matrix of bone?
85%
Approximately how much phosphate is found intracellularly?
14% found as part of cell membranes, nucleic acids, enzyme cofactors, glycolytic intermediates and ATP
Approx how much phosphate is found extra cellularly?
1%
How much extracellular phosphate is inorganic?
30%
Why is serum phosphate not an accurate depiction of true phosphate stores?
Because phosphate shifts between organic/inorganic pools and in and out of cells.
State one way in which phosphate enters cells.
Via insulin mediated entry of glucose in to cells after meals.
List the main organs involved in phosphate homeostasis.
Kidney, gut and bone
List the main hormones involved in phosphate homeostasis.
PTH, FGF23 and 1,25 DHCC
How much phosphate is ingested on a daily basis?
Approx 45 mmol
How much phosphate is filtered through the kidney each day?
160 mmol
How much phosphate is reabsorbed through the kidney each day?
135 mmol
How much phosphate is excreted via urine each day?
25 mmol
Where, in the small intestine, does reabsorption of phosphate occur?
Throughout the entire small intestine
What increased absorption of phosphate in the small intestine?
1,25 DHCC
How much phosphate is protein bound?
15-20%
How much of filtered phosphate is reabsorbed in the proximal tubule?
75%
How much of filtered phosphate is reabsorbed in the distal tubule?
5-20%
What inhibits the reabsorption of phosphate by the renal tubules?
PTH and FGF23
Will PTH and FGF23 increase or decrease in response to increased phosphate levels?
Increase
State some factors which influence serum phosphate values.
- Marker diurnal variation rhythm - low before noon, highest after midnight
- Dietary effects - will fall due to rise in insulin
- Age related changes - highest levels in infancy due to growth velocity being high
