Flashcards in Calcium Metabolism Deck (75):
What regulate calcium balance?
Gut, Kidneys, Bone
What is the importance of calcium?
In plays a critical role in many cellular processes
Give 6 roles of calcium
- Hormone secretion
- Muscle contraction
- Nerve conduction
- Activation of many enzymes
- Intracellular second messenger
How does Ca 2+ serve as an intracellular second messenger?
By carrying information from the cell membrane to the interior of the cel
What is it important that the body regulates very tightly?
The plasma concentration of free ionised calcium ([Ca 2+ ])
Why is free ionised calcium concentration controlled?
Because this is the physiologically active form of the metal
At what level is free plasma [Ca 2+ ] maintained?
Within the narrow range of 1.0-1.3mmol/L
Where does phosphate play a critical role?
In cellular energy metabolism
Why does phosphate play a critical role in cellular energy metabolism?
Because it’s part of the adenosine triphosphate molecule
Other than in ATP, where else does phosphate play a crucial role?
In activation and deactivation of enzymes
How does regulation of plasma phosphate differ from calcium?
It is less tightly regulated, and the levels fluctuate throughout the day, particularly after means
Why are calcium homeostasis and phosphate homeostasis intimately linked?
- Because calcium and phosphate are the principal components of hydroxyapatite crystals
- They are regulated by the same hormones
What is the formula for hydroxyapatite crystals?
Ca 10 (PO 4 ) 6 (OH) 2
What do hydroxyapatite crystals constitute?
The major portion of the mineral phase of bone
What hormones regulate calcium and phosphate?
Primarily parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitrol), and, to a lesser extent, calcitonin
Where do PTH, calcitriol and calcitonin act?
The organ systems of bone, kidney and GI tract
What is the purpose of PTH, calcitriol and calcitonin?
To control the levels of calcium and phosphate ions in the plasma
Why are the actions PTH, calcitriol and calcitonin on calcium and phosphate typically said to be opposed?
A particular hormone may elevate the level of one ion while lowering the other
Where is calcium location?
How much calcium is in the bone?
What is the total amount of calcium in the extracellular pool?
Only a fraction of the amount in bone, about 1g
What is the typical daily dietary intake of calcium?
~800 to 1200mg
What are the major dietary sources of calcium?
What do the intestines do regarding calcium?
- Absorb ~half of the dietary calcium (~500mg/day)
- Secrete calcium for removal from body (~325mg/day)
What is the net intestinal uptake of calcium?
What happens to bone in a steady state?
Calcium deposition in bone of about 280mg/day is matched by an equal amount of calcium reabsorption
How much calcium to the kidneys filter a day?
10 times the total extracellular pool of calcium, about 10,000mg/day
What happens to 98% of the pool that is filtered by the kidneys?
What is the net renal excretion of Ca 2+ ?
Less than 2% of the filtered load
What happens regarding kidney filtering in a person in calcium balance?
Urinary excretion (~175mg/day) is the same as net absorption by the GI tract
How does calcium exist in plasma?
- As free ionised species
- Associated with anionic sites on serum proteins, especially albumin
- Complexed with a low-molecular-weight organic anion
Give 2 examples of low-molecular-weight organic anions calcium may be complexed with?
What is the total concentration of all three physiochemical forms of calcium in the plasma?
How much calcium is free in healthy individuals?
How much calcium is bound to proteins in healthy individuals?
How much calcium is bound to small organic anions in healthy individuals?
What form of calcium is most important with regard to regulating the secretion of PTH?
What is the ionised form of calcium involved in?
Most of the biological actions of calcium
What do common laboratory tests measuring calcium usually measure?
Total calcium, including not only physiologically active free ionised calcium, but calcium bound to albumin and other proteins
How is it determined if free calcium is in the correct range or not?
The levels are corrected depending on the level of albumin
What is hypocalcaemia?
When calcium levels are too low
What is the consequence of hypocalcaemia?
Hyper-excitablity of the nervous system, including the neuromuscular junction, leading to parasthesia
What does paraesthesia lead to?
Tetany, paralysis and convulsions
What is hypercalcaemia?
Calcium too high
What are the consequences of hypercalcaemia?
Formation of kidney stones, constipation, dehydration, kidney damage, tiredness and depression
What is it clear from the consequences of dysregulation of serum calcium?
That it’s very important that levels are maintained within set limits
What are the two key hormones in calcium regulation?
What do PTH and calcitriol both act to do?
Raise serum calcium concentrations
How do PTH and calcitriol differ?
They act by different mechanisms, and over different time scales
What is the short term regulation of serum calcium under control of?
What is long term regulation of serum calcium under control of?
What is vitamin D?
A collective term for a group of prohormones
What are the 2 major forms of vitamin D?
- D2 (ergocalciferol)
- D3 (cholecalciferol)
Where is vitamin D obtained from?
Is vitamin D reactive?
No, it’s biologically inert
What must happen for vitamin D to be activated in the body?
Two hydroxylation reactions
What is calcitriol?
An active form of vitamin D found in the body, involved in calcium regulation
Other than the prohormones, what else is the term vitamin D used to refer to?
The metabolites of vitamin D, and other analogues of these substances
What is parathyroid hormone related peptide (PTHrP)?
What produces PTHrP produced by?
What may production of PTHrP lead to?
Where can the measurement of PTHrP be useful?
In determining the cause of an otherwise unexplained hypercalcaemia
What does the secretion of PTHrP from cancer cells lead to?
Humeral hypercalcaemia of malignancy (HHM)
Where is PTHrP commonly produced?
In patients with breast or prostate cancer, and occasionally in patients wiht myeloma
What does PTHrP share with PTH
What does the similarities in action of PTH and PTHrP lead to?
- Increased calcium release from bone
- Reduced renal calcium excretion
- Reduced renal phosphate reabsorption
What activity does PTHrP not increase?
What is the result of PTHrP not increasing renal C-1 hydroxylase activity?
It doesn’t increase calcitrol concentration, unlike PTH
What does calcitonin do?
In an animal, lowers serum calcium levels
What does calcitonin do in humans?
What suggests that calcitonin has little function in humans?
It appears to lack pathology associated with either hypo or hyper secretion
Where is calcitonin secreted from?
What happens if the thyroid gland is removed or destroyed, regarding calcitonin?
The lack of secretion appears to have no effect on calcium homeostasis
Where might calcitonin be important?