Locomotor: PBL 2 (Rickets)

Question 1

Outline the 4 stages of intramembranous ossification

Answer 1

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

Question 2

What is endochondral ossification?

Answer 2

Formation of bone from a cartilage model (typified by long bone development)

Question 3

What is intramembranous ossification?

Answer 3

Formation of bone from within a membrane of primitive mesenchymal tissue (occurs in flat bones)

Question 4

Define ‘hypotonia’

Answer 4

Loss of muscle tone often involving reduced muscle strength

Question 5

What is ‘rachitic rosary chest’?

Answer 5

Knob-like deformities across the costochondral junctions (like rosary beads)

Question 6

What is ‘Harrison’s sulcus’?

Answer 6

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)

Question 7

How does the body respond to low levels of serum calcium?

Answer 7

Stimulates parathyroid hormone release from the parathyroid glands

Question 8

Describe the effect of parathyroid hormone on the body (to increase serum calcium)

Answer 8

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

Question 9

Explain how parathyroid hormone can increase the number of osteoclasts

Answer 9

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

Question 10

Describe the role of oestrogen in bone metabolism

Answer 10

Decreases calcium absorption in the gut, and also inhibits osteoclasts (bone resorption)

Question 11

Describe the role of glucocorticoids in bone metabolism

Answer 11

Decrease calcium absorption in the gut and increase bone degradation (bone desorption)

Question 12

Describe the role of calcitonin in bone metabolism

Answer 12

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

Question 13

What is the active metabolite of vitamin D3?

Answer 13

Calcitriol/1,25-dihydroxyvitamin D3

Question 14

Outline how calcitriol/1,25-dixhydroxyvitamin D is produced in the body

Answer 14

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)

Question 15

Describe the role of calcitriol/1,25-hydroxyvitamin D3

Answer 15

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

Question 16

Why may an individual with rickets have a low serum calcium level?

Answer 16

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)

Question 17

Why may an individual with rickets have a very high alkaline phosphatase level?

Answer 17

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

Question 18

Why may someone with rickets have a low Vitamin D level?

Answer 18

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

Question 19

Why may someone with rickets have a normal-low phosphate level?

Answer 19

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

Question 20

Why may someone with darker skin be more susceptible to rickets?

Answer 20

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

Question 21

Describe how vitamin-D deficiency affects bone metabolism

Answer 21

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

Question 22

Describe the role of alkaline phosphatase in bone metabolism

Answer 22

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

Question 23

Outline the causes of rickets

Answer 23

Lack of vitamin D or calcium

Question 24

Outline the symptoms of rickets

Answer 24

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)

Question 25

How is rickets diagnosed?

Answer 25

Blood test: low serum calcium, low serum phosphate (sometimes), high ALP

Question 26

Outline the treatment for rickets

Answer 26

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

Question 27

What vitamin D supplement is recommended?

Answer 27

Cholecalciferol (active vitamin D3 prior to hydroxylation in the liver and/or kidney)

Question 28

Name the 5 layers of chondrocytes at an epiphyseal growth plate

Answer 28

1) resting/reserve cartilage
2) proliferation
3) transitional
4) maturation and hypertrophy
5) degeneration and calcification