Biology of Bone and Extracellular Calcium Flashcards
intracellular calcium concentration is
low (< 1 micro mole/L)
extracellular calcium concentration is
higher (~1 mmol./L)
extracellular calcium allows for
bone mineralisation
acitivity of excitable tissue
intracellular calcium allows
calcium protein binding
extracellular calcium is measured
in liquid (serum or plasma) albumin and total calcium both measured
calcium is made of how many components?
2
ionised - active
albumin-bound - non-active
aging usually marked by
slow phase of negative calcium balance (leads to loss of bone density –> osteoporosis)
What are the functions of bone?
support, protection, leverage, RBC production, enocrine function, mineral homeostasis
What is the morphology of bone?
trabecular - mesh
cortical - dense edges
What do osteoblasts do?
make bone by mineralising osteoid collagen fibres with hydroxyapatite crystals
What does mineralisation of osteoids achieve?
rigidity, compression resistance
What happens if there is calcitriol deficiency?
failed mineralisation - Rickets, osteomalacia
What is the role of ALP in mineralisation?
expressed on differentiated osteoblast surface and released into ECF
promotes mineralisation of hydroxyapatite by increasing local phosphate and hydrolysing pyrophosphate (mineralisation inhibitor)
What are osteoclasts?
multinucleate, motile, bone-resorbing cells
What does the ‘ruffled border’ of osteoclasts secrete?
H+ and enzymes
What is the role of RANK and RANKL?
RANK on osteoclast precursor binds RANKL on bone marrow stromal cell to activate NFkB in the precursor which leads to maturation
how do osteoclasts resorb bone?
degrade the matrix
What do osteocytes do?
mechanosensory
What is Paget’s disease?
overactive osteoclasts lead to bone loss, increased bone resorption –> osteoporosis
Which 2 hormones regulate plasma calcium?
parathyroid hormone (peptide) and calcitriol (steroid)
How does PTH regulate calcium?
falling calcium leads to PTH secretion, stimulate efflux, renal absorption of calcium, formation of calcitriol by intestinal absorption of calcium, loss of phosphate and bicarbonate from the kidney
What is the source of calcitriol?
vitamin D (fat-soluble)
How is calcitriol produced?
UV light action on 7-dehydroxycholesterol
in liver 25-hydroxylase converts to 25(OH) vitamin D
in kidney 1alpha-hydroxylase converts to 1,25(OH)2 vitamin D or calcitriol
What is calcitriol?
active form of vitamin D, hormone made at kidney and is required for long-term calcium (and phosphate) maintenance, bone growth and mineralisation
How is vitamin D produced?
UV light action on precursor 7-DHC in skin
What is the mechanism of action of calcitriol?
binds vitamin D receptor
new protein synthesis stimulated - intestine makes calbindin-D9k (promotes absorption)
stimulates osteoblast differention - RANKL formation (stimulates osteoclast activation)
How does PTH cooperate with calcitriol?
promotes 1alpha-hydroxylase activity (promotes calcitriol formation)
What are the limitations of action between PTH and calcitriol?
switch off PTH gene transcription - limits PTH action
What is the key difference between PTH and calcitriol calcium regulation?
PTH - short term (min-by-min)
calcitriol - long term
