Locomotor: PBL 2 (Rickets) Flashcards
Outline the 4 stages of intramembranous ossification
1) Within mesenchyme, mesenchymal cells –> osteoblasts and form numerous centres of ossification
2) Osteoblasts –> osteoid at centres –> mineralisation of osteoid –> spicules of bone
3) Ossification centres grow (due to osteoblast differentiation) –> grow around foetal blood vessels in mesenchymal membrane until centres meet –> fuse –> spongy bone –> mesenchyme condenses on outer surface –> vascularised periosteum
4) Further fusion of outer trabeculae and periosteum formation –> outermost bone –> continuous sheet of woven bone –> remodelling –> outer woven to lamellar compact –> inner bone –> lamellar trabecular, mesenchymal cells within spaces of spongy bone –> haemopoietic marrow cells
What is endochondral ossification?
Formation of bone from a cartilage model (typified by long bone development)
What is intramembranous ossification?
Formation of bone from within a membrane of primitive mesenchymal tissue (occurs in flat bones)
Define ‘hypotonia’
Loss of muscle tone often involving reduced muscle strength
What is ‘rachitic rosary chest’?
Knob-like deformities across the costochondral junctions (like rosary beads)
What is ‘Harrison’s sulcus’?
Horizontal groove along the lower border of the thorax corresponding to the costal insertion of the diaphragm (usually caused by chronic asthma or obstructive respiratory disease)
How does the body respond to low levels of serum calcium?
Stimulates parathyroid hormone release from the parathyroid glands
Describe the effect of parathyroid hormone on the body (to increase serum calcium)
1) Increases calcium reabsorption and phosphate excretion at the kidneys
2) Increases the number and activity of osteoclasts
3) Synthesis of 1,25-dihydroxyvitamin D to increase calcium reabsorption from the gut
Explain how parathyroid hormone can increase the number of osteoclasts
PTH binds to receptor on osteoblast which expressed RANKL, and osteoclast precursors have a receptor RANK and this can bind to the ligand (L) and this facilitates the differentiation into osteoclasts
Describe the role of oestrogen in bone metabolism
Decreases calcium absorption in the gut, and also inhibits osteoclasts (bone resorption)
Describe the role of glucocorticoids in bone metabolism
Decrease calcium absorption in the gut and increase bone degradation (bone desorption)
Describe the role of calcitonin in bone metabolism
Rising serum calcium levels stimulate the thyroid gland to release calcitonin which stimulate bone deposition and inhibits osteoclasts, and also reduce the calcium uptake in the kidneys
What is the active metabolite of vitamin D3?
Calcitriol/1,25-dihydroxyvitamin D3
Outline how calcitriol/1,25-dixhydroxyvitamin D is produced in the body
Provitamin D3 to vitamin D3: cholesterol derivate under UVB light –> cholecalciferol (SKIN)
1st hydroxylation: cholecalciferol –> calcidiol/5-hydroxycholecalciferol (LIVER)
2nd hydroxylation: calcidiol –> calcitriol (1,25-dihydroxyvitamin D3) (KIDNEYS)
Describe the role of calcitriol/1,25-hydroxyvitamin D3
1) Promotes absorption of calcium and phophates in the intestines (potent ligand of the vitamin-D receptor and can cause changes in gene expression due to transcription factors to increase numbers, and increase intestinal absorption)
2) Increases phosphate reabsorption in the kidney
3) Encourages bone resorption to release phosphate and calcium
Why may an individual with rickets have a low serum calcium level?
May be unable to absorb a sufficient amount of calcium from the gut due to vitamin D deficiency for example (aids in calcium uptake in the gut)
Why may an individual with rickets have a very high alkaline phosphatase level?
Alkaline phosphatase is a by-product of osteoblast activity in bone deposition and therefore in an individual with rickets, therefore, this is indicative of the body’s response to desperately try and reform the bone that is being lost through the action of osteoclasts
Why may someone with rickets have a low Vitamin D level?
The lack of vitamin D could be the cause of their rickets; vitamin D is produced on exposure to sunlight, and therefore in it’s absence a defiency may cultivate
Why may someone with rickets have a normal-low phosphate level?
There may be just enough vitamin D for the phosphate to be sufficiently absorbed in the intestine, and if serum calcium levels drop, this also increases the quantity of serum phosphate
Why may someone with darker skin be more susceptible to rickets?
Have a higher quantity of melanin which blocks the UV-B light from penetrating the skin in areas of low-sunlight levels, and therefore are more likely to be unable to produce sufficient vitamin-D in such climates
Describe how vitamin-D deficiency affects bone metabolism
Hypocalcaemia (insufficient amount absorbed) –> excess secretion of PTH to compensate –> increased renal phosphate loss –> reduced calcium deposition in bone –> abnormal mineralisation of any newly formed bone (osteoid) due to low calcium and phosphate availability –> reduces/inhibits osteoblast function further
Describe the role of alkaline phosphatase in bone metabolism
Osteoblasts secrete alkaline phosphatase in vesicles –> ALP cleaves phosphate groups (dephosphorylation) and acts as a focal point for calcium and phosphate deposition –> vesicle ruptures and acts as a centre for crystals/ECM to grow on
Outline the causes of rickets
Lack of vitamin D or calcium
Outline the symptoms of rickets
Pain in movement (affected bones may be sore), skeletal deformities e.g. thickening of joints or bowed legs, poor growth and development (shorter height than average if untreated), fragile bones (more likely to fracture) and Harrison’s sulcus (due to softened bones diaphragm can pull the bone inward so there may be an indentation of the lower ribs at point of diaphragmatic attachment)
How is rickets diagnosed?
Blood test: low serum calcium, low serum phosphate (sometimes), high ALP
Outline the treatment for rickets
Eat more foods rich in calcium and vitamin D, take daily supplements, have vitamin D injection each year (only if can’t take oral supplements or has intestinal/liver disease) and seek sunlight exposure where possible
What vitamin D supplement is recommended?
Cholecalciferol (active vitamin D3 prior to hydroxylation in the liver and/or kidney)
Name the 5 layers of chondrocytes at an epiphyseal growth plate
1) resting/reserve cartilage
2) proliferation
3) transitional
4) maturation and hypertrophy
5) degeneration and calcification
