Metabolic bone disease – Biochemistry Flashcards
what makes bone strong?
mass
material properties (collagen, cross-linking, woven vs lamellar, mineralization etc)
microarchitecture (trebecular thickness and connectivity, cortical porosity)
macroarchitecture (hip axis length, diameter)
what happens to bone when you get older
gets more mineralised and brittle
bone mass decreases
why do men have bigger bones?
in bone remodelling bone is pushed out further under the influence of testosterone
describe the process of bone remodelling
Activation occurs
A microcrack crosses canaliculi, so severing osteocyte processes causing osteocytic apoptosis. This is thought to act as a signal to the connected surface lining cells (which are osteoblast lineage), which along with the osteocytes release local factors that attract cells from blood and marrow into the remodeling compartment. For the resorption phase to start osteoclasts are generated locally and resorb matrix and the offending microcrack, then successive teams of osteoblasts deposit new lamellar bone. Osteoblasts that are trapped in the matrix become osteocytes; others die or form new, flattened osteoblast lining cells.
ACTIVATION
RESORPTION
REVERSAL
FORMATION
how long do the osteoclast and blasts live?
CLAST- FEW WEEKS
BLAST - SEVERAL MONTHS
what is blood calcium regulated by?
parathyroid hormone
inc PTH= inc blood Ca levels
what are the actions of PTH?
BONE- increase bone resorption
KIDNEY- increase calcium reabsorption and phosphate secretion
increases production of active vitamin D
where exactly does PTH work in the kidney?
drives active Ca absorption in the distal convoluted tubule.
how does PTH stimulate bone resorption
PTH activates osteoblasts which activate osteoclasts through the RANK system. which then go on the break down bone
how is primary hyperparathyroidism diagnosed?
an elevated total/ionised calcium with PTH levels elevated
or in the upper half of the normal range’
what are the clinical features of primary HPT?
due to high calcium:
thirst/polyuria
tiredness, fatigue, muscle weakness
calcium stones
GIT problems
physchological problems (depression, impaired concentration, coma)
outline the formation of active Vit D
7-dehydrocholesterol + UV + diet --> cholecalciferol --> liver 25- cholecalciferol --> kidney + PTH calcitriol (1,25(OH)2 Vit D
what are the symptoms of rickets?
Bone pain and tenderness (axial)
Muscle weakness (proximal)
Lack of play
what are the signs of rickets?
Age dependent deformity Myopathy Hypotonia Short stature Tenderness on percussion
what are the causes of rickets?
insufficient Ca in diet
small bowel malabsorption
pancreatic insufficiency
liver/billary disturbance
drugs- phenytoin, phenobarbitone
chronic renal failure
rare hereditary -Vitamin D dependent rickets:
type I deficiency of 1 α hydroxylase
type II defective VDR for calcitriol
