Regulation Of Ca+ And PO4 Flashcards
What is calcium?
Most abundant metal in our bodies
How is the body’s calcium requirement met?
Diet meets all requirements
What is the recommended calcium intake for an adult?
1000 mg/day
Why is calcium important?
- Neuromuscular excitability
- Muscle contraction
- Bone strength
- Intracellular 2nd messenger
- Intracellular co-enzyme
- Hormone/neurotransmitter stimulus-secretion coupling
- Blood coagulation (factor IV)
How is Calcium approximately distributed in the body?
Skeleton (99%)
Intracellular (1%)
Extracellular (0.1%)
How is extracellular calcium distributed?
Ionised (45%)
Bound (the rest)
→ to plasma proteins (45%)
→ as anions
How is calcium stored in bones + teeth?
As calcium hydroxyapatite crystals
What part of total body calcium is biologically active?
Extracellular, unbound + ionised calcium
approx 50% of serum calcium
Why is phosphate important?
Essential component of:
• High energy compounds e.g. ATP
• 2nd messengers
• Fundamental molecules eg DNA, RNA, phospholipids
Why are phosphates + calcium regulated by the same hormones?
Extracellular phosphate is inversely proportional to extracellular calcium
What hormones regulate + increase calcium?
Parathyroid Hormone + Vitamin D (mainly act on gut, bone + kidney)
What hormone regulates + decreases calcium?
Calcitonin
What are the 2 sources + types of Vitamin D?
Diet = vitamin d2 (ergocalciferol)
Sun + skin = vitamin d3 (cholecalciferol)
How is Vitamin D3 synthesized?
When UVB meets skin:
7-dehydrocholesterol → pre-vitamin D3 → vitamin d3
How is vitamin D2 + D3 used to synthesize the active form of vitamin D?
Vitamin d2 + d3 → 25(OH)cholecalciferol
Enzyme: 25-hydroxylase, in liver
25(OH)cholecalciferol → 1,25(OH)cholecalciferol
Enzyme: 1-alpha hydroxylase, in kidney
Why is serum 25(OH)cholecalciferol useful?
Can be measured as a good indicator of vitamin D levels
What is calcitriol?
Active form of Vitamin D, 1,25(OH)calciferol
How does Vitamin D regulate its own synthesis?
Decreases transcription of 1-alpha hydroxylase
How does calcitriol regulate calcium in the bones?
Increases calcium in bloodstream by increasing osteoclasts activity indirectly
How does calcitriol regulate calcium + phosphates in the kidneys?
Increases reabsorption of calcium + phosphate
How does calcitriol regulate calcium + phosphates in the gut?
Increases reabsorption of calcium + phosphate
What is PTH?
parathyroid hormone
Where is PTH produced + secreted?
chief cells in the parathyroid glands (embedded behind the thyroid gland)
How is PTH secretion regulated?
G-protein coupled receptors on chief cells detect changes in circulating calcium concentration
What happens to PTH secretion when serum calcium conc. is high?
PTH secretion is inhibited
What happens to PTH secretion when serum calcium conc. is low?
PTH is secreted
What is the relationship between PTH secretion and serum calcium?
both are inversely proportional
How does PTH regulate calcium in bones?
Increases calcium in bloodstream by increasing osteoclasts activity indirectly
How does PTH regulate calcium + phosphates in the gut?
increases absorption from gut
How does PTH regulate calcium + phosphates in the kidneys?
increases calcium reabsorption from distal tubules + renal collecting ducts, BUT decreases phosphate reabsorption + plasma conc.
How does PTH effect Vitamin D synthesis?
stimulates conversion of 25-hydroxy vitamin D → 1,25-dihydroxy vitamin D (calcitriol),
up-regulates 1-alpha hydroxylase
How does Vitamin D effect PTH synthesis?
25(OH) vitamin D inhibits PTH secretion
What is the difference between osteoblast and osteoclast?
Osteoblast = BUILD bone Osteoclast = CONSUME bone
Why do PTH and Calcitriol INDIRECTLY increase osteoclast activity?
osteoclasts don’t have receptors; osteoblasts do - so hormones bind to osteoblasts + cause osteoclast precursors to form, creating new osteoclasts
What is calcitonin?
hormone that reduces serum calcium (mechanism still unknown)
Where is calcitonin produced + secreted?
parafollicular (C) cells of thyroid gland (however, removal of thyroid gland don’t affect serum calcium)
How is calcitonin secretion regulated?
increase in serum calcium is detected by parafollicular cells + calcitonin release is triggered
What does calcitonin regulate calcium?
decreases osteoclast activity (by increasing osteoblast activity) + increasing calcium excretion in kidneys
What is FGF23?
fibroblast growth factor 23, protein that regulates phosphates + vitamin D
How does FGF23 regulate phosphate reabsorption in kidneys?
decreases the expression of NPT2 (sodium-phosphate co-transporter) in the proximal tubule, decreasing phosphate reabsorption
Where is FGF23 secreted from?
osteocytes when serum calcium levels are elevated
What is hypocalcaemia?
low serum calcium levels
What are the consequences of hypocalcaemia?
enables greater sodium influx → more membrane excitability → sensitises excitable tissues
What are some general symptoms of hypocalcaemia?
Paraesthesia (tingling, prickling, pins + needles) Convulsions Arrhythmias Tetany Muscle Cramps
What are two specific signs of hypocalcaemia?
Chvostek’s Sign + Trousseau’s sign
What is Chvostek’s Sign?
Tap facial nerve just below zygomatic arch; Positive response = twitching of facial muscles → Indicates neuromuscular irritability
What is Trousseau’s sign?
Carpopedal spasm due to inflation of blood pressure cuff for several minutes = neuromuscular irritability
What are causes of hypocalcaemia?
- Low PTH levels = Hypoparathyroidism
- Neck surgery
- Auto-immune
- Magnesium deficiency
- Congenital (agenesis, rare) - Vitamin D deficiency
What are causes of Vitamin D deficiency?
- Malabsorption or dietary insufficiency
- Inadequate sun exposure - - Liver disease
- Renal disease
- Vitamin D receptor defects
What are consequences of Vitamin D deficiency?
- Lack of bone mineralisation = ‘soft’ bones
- In children – rickets (bowing of bones)
- In adults – osteomalacia (fractures, proximal myopathy)
What is hypercalcaemia?
high serum calcium
What are the consequences of hypercalcaemia?
Ca2+ BLOCKS Na+ influx, so LESS membrane excitability
What are signs + symptoms of hypercalcaemia?
- Atonal muscles
- Renal effects: Nephrocalcinosis – kidney stones, renal colic
- GI effects:
Anorexia, nausea, dyspepsia, constipation, pancreatitis - CNS effects:
Fatigue, depression, impaired concentration, altered mentation, coma
What are causes of hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy
How does primary hyperparathyroidism cause hypercalcaemia?
too much PTH, usually due to a parathyroid gland adenoma, no negative feedback - high PTH, but high calcium
How does malignancy cause hypercalcaemia?
Bony metastases produce local factors to activate osteoclasts, certain cancers (e.g. squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors, vitamin D excess
