Physiology of Bone Calcium and Phosphate Homeostasis Flashcards
What is the most common calcium phosphate?
Hydroxyapatite
What are osteoblasts?
Modified fibroblasts involved in forming bone
How do osteoblasts build bone?
Produces enzymes and osteoid to which hydroxyapatite binds
What is osteoid?
Collagen and protein mix
Which proteins aid in deposition of bone?
Osteocalcin and osteonectin
What are chondrocytes and where in the developing bone are they found?
Collagen-producing cells of the cartilage located near the epiphysis
How are chondrocytes involved in lengthening bone?
Continuously dividing and laying down columns of collagen; as the collagen layer thickens, the old chondrocytes die and leave spaces for osteoblasts to lay down bone on the collagen base
What are osteocytes?
Less active osteoblasts
What are osteoclasts?
Large, mobile, multinucleate cells derived from haematopoietic stem cells involved in bone resorption
How do osteoclasts resorb bone?
Secrete acid and proteases to dissolve the calcified matrix and collagen support
What hormones are involved in Ca2+ metabolism?
PTH
Vitamin D3 (calcitriol)
Calcitonin
List 4 physiological roles of Ca2+
Intracellular signalling
Structural functions (e.g. bone matrix, tight junctions)
Cofactor in coagulation
Neuronal and muscle excitability
What are the 3 pools of Ca2+ in the body and in what form does Ca2+ exist in each? What % of total Ca2+ does each account for?
Bone matrix (99%)
Extracellular (ionised; 0.1%)
Intracellular (free; 0.9%)
Which of the 3 pools of Ca2+ in the body is carefully regulated?
ECF (moves freely in and out of plasma)
How does Ca2+ get in and out of cells?
In: down the electrochemical gradient (from ~2.5mM to 0.001mM)
Out: active transport
How and where is Ca2+ reabsorbed in the kidney?
Reabsorption occurs in the distal nephron via the following transporters:
ECaC
Na+-Ca2+ antiport
Ca2+-ATPase
What is the effect of PTH on serum Ca2+ and phosphate?
Increases Ca2+
Decreases phosphate
What are the actions of PTH on bone?
Increases Ca2+ and phosphate release into plasma
Favours bone resorption
What are the actions of PTH on the kidney distal tubule?
Increases Ca2+ reabsorption
Decreases phosphate reabsorption (and increases excretion)
What are the actions of PTH on the intestine?
No direct actions (actions mediated by vitamin D3)
What is the result of the absence of PTH?
Hypocalcaemic tetany leading to death
Where is calcitonin produced?
C cells of the thyroid (parafollicular cells)
What is the stimulus for calcitonin release?
Increased plasma Ca2+
What are the effects of calcitonin?
Decreased release of Ca2+ from bone
Decreased bone resorption
Increased renal Ca2+ excretion
When is calcitonin relevant?
Only in extreme hypercalcaemia (no role in normal homeostasis)
May play be protective for bone Ca2+ during pregnancy and lactation
What are calcitonin’s effects on the gut?
No effect
Describe the pathway of vitamin D activation
Precursor in skin (dehydrocholesterol) is converted by UV light to vitamin D3 (cholecalciferol), or D3 is ingested directly
Vitamin D3 is hydroxylated in the liver to produce 25-OH D3
25-OH D3 is further hydroxylated in the kidney to produce the active form, 1,25-(OH)2 D3
1,25-(OH)2 D3 acts mainly on the intestine
What factors affect the 2nd hydroxylation of vitamin D3 in the kidney?
PTH stimulates kidney enzymes to increase conversion to the activated form, as does decreased plasma phosphate
Prolactin also stimulates synthesis
Will kidney and gut dysfunction affect Ca2+ homeostasis?
Yes
Which of the 3 organ systems responsible for modulating Ca2+ homeostasis act quickest? Which takes longest?
Kidneys quickest
Intestine longer
Bone resorption longest
What hormone controls epiphyseal closure?
Oestrogen
What are the 3 main physiological roles of phosphate?
Energy transfer and storage (ATP, cAMP)
Control of enzymes, transporters, ion channels
Part of DNA and RNA backbone
What is a possible cause of hyperparathyroidism? What are the biochemical findings?
Tumour
Hypercalcaemia, hypophosphataemia (but effects variable)
What are some possible causes of hypoparathyroidism? What are the biochemical findings and what are some possible effects?
Autoimmune attack of glands or inadvertent parathyroidectomy during thyroid surgery
Hypocalcaemia, hyperphosphataemia
Causes neuromuscular excitability (hypocalcaemic tetany) and is ultimately fatal
What disorders result from a vitamin D deficiency in childhood and adulthood?
Childhood: rickets
Adulthood: osteomalacia
What are the effects of a vitamin D deficiency?
Impaired intestinal Ca2+ absorption
Plasma Ca2+ is maintained at the expense of bones
What causes osteoporosis?
Long term imbalance of bone resorption and bone formation (loss of protective role of oestrogen may influence)
In what population is osteoporosis most common?
Postmenopausal women >50
List some risk factors for osteoporosis
Inactivity (especially lack of weight-bearing exercise) Malnutrition Alcohol Smoking Endocrine disorders (e.g. Cushings) Low dietary Ca2+
What is the effect of cortisol on bone?
Causes increased bone resorption
Where is most phosphate reabsorbed?
Proximal tubule
What are the physiological effects of 1,25-(OH)2 D3?
Increases intestinal Ca2+ and phosphate absorption
Increases calbindin
Increases Ca2+-sensing receptors
Weakly increases phosphate resabsorption in the kidney)
