L&b - Week 1 (Pbl)

Front 1

How is the body (shaft) of a bone called?

Back 1

Diaphysis

Front 2

How is the extremety of a bone called?

Back 2

Epiphysis

Front 3

What is the region between the diaphysis and epiphyses called?

Back 3

Metaphysis

Front 4

What do metaphyses contain in growing individuals?

Back 4

Epiphyseal plate - a layer of hyaline catrilage that allows growth.

Front 5

What is the name of an ossified epiphyseal plate?

Back 5

Epiphyseal line

Front 6

What is the superficial layer of a bone's extremety?

Back 6

A layer of articular cartilage

Front 7

What is the significance of articular cartilage on bones?

Back 7

It reduces friction and absorbs shock at the articulation point between two bones.

Front 8

What is periosteum?

Back 8

A superficial layer of tough connective tissue together with its blood supply that covers bones where articular cartilage is absent

Front 9

What are the fucntions of periosteum?

Back 9

Protection

Osteogenic cell residence

Repair assisstance

Tendon attachments.

Front 10

What are the two bone tissue types?

Back 10

1) Cortical/compact bone

2) Spongy/trabecular/cancellous bone

Front 11

What are the structural features of compact bone?

Back 11

1) Consists of osteons between outer and inner circumferential lamellae.

2) Osteons are ring-like structures with central canal in the middle and osteocytes residing along lamellular lines.

3) The stronger of the two.

Front 12

Describe the structure of bones.

Back 12

Front 13

Whar are the 4 types of bone cells?

Back 13

Osteoblasts

Osteocytes

Osteoclasts

Osteoprogenitor cells

Front 14

What are the microscopic features of osteoblasts?

Back 14

1) Pale activated nucleus

2) Lots of rER and Golgi

3) Evidence of collagen production

Front 15

What are the microscopic features of osteocytes?

Back 15

1) Deactivated nucleus

2) Presence of canaliculi

Front 16

What are the microscopic features of osteclasts?

Back 16

1) Ruffled border

2) Several nuclei

Front 17

What is the bone matrix made of?

Back 17

1) Collagen type 1 - provides resilience and wholeness

2) Bone salts, e.g. Calcium Hydroxyapatite (Ca10(PO4)6(OH)2)

Front 18

How is blood supplied to bones and nutrients distributed?

Back 18

Blood is delivered to bones by nutrient arteries through nutrient foramina. Nutrients then diffuse through canaliculi of ostecytes.

Front 19

What is the approximate total amount of calcium in the body?

Back 19

+- 1kg

Front 20

Describe the distribution of calcium in the body.

Back 20

1) 99% in bones

2) Rest - soft tissue, teeth and ECF

Front 21

What are the 3 types of calcium in circulation?

Back 21

1) Free ionised, unbound calcium - 47%. Physiologically important, acts like a ligand.

2) Protein bound (mostly to albumin) - 47%.

3) Complexed calcium, bound to phosphate and citrate - 6%.

Front 22

What is the normal range of total calcium concentration?

Back 22

2.20 - 2.60 mmol/l in the population

Narrower in individuals

Front 23

What is the formula for adjusted calcium?

Back 23

Ca(adj) = Ca(tot) + 0.2(normal alb - alb)

Normal albumin = 40 or 45

alb = recorded value of albumin

Front 24

What are the major organs involved in calcium metabolism and homeostasis?

Back 24

Liver

Kidneys

Bone

paarthyroid glands

Front 25

What are the major hormones involved in calcium metabolism and homeostasis?

Back 25

Parathyroid hormone (PTH)

1.25 dihydroxyvitamin D, also called 1.25 dihydroxycholecalciferol (1.25 DHCC or calcitriol)

Front 26

What is PTH?

Back 26

An 84-amino acid, single chain peptide hormone, secreted by chief cells of parathyroid glands. Its production is stimulated by low ionised calcium or high phosphate concentrations.

Front 27

How is vitamin D made in the body?

Back 27

1) Cholecalciferol is made in the skin (UV + diet)

2) 25-hydroxycholecalciferol is then made in the liver

3) Finally, 1.25 dihydroxycholecalciferol is made in the kidneys

Front 28

Where and how is calcium absorbed?

Back 28

Absorbed in the gut (duodenum and jejunum) by either passive diffusion or cell-mediated active transport, which can be influenced by 1.25 DHCC.

Front 29

How does PTH control calcium metabolism?

Back 29

1) G-protein coupled receptors in the parathyroid glands and renal tubules sense changes in calcium concentration.

2) A drop in calcium concentration stimulates PTH production.

3) PTH and 1.25 DHCC increase calcium resorption from bone and PTH increases calcium reabsorption in the kidney.

Front 30

Where in the nephron is calcium reabsorbed?

Back 30

1) 65% is reasbsorbed in the PCT together with other solutes like Na.

2) 15% is reabsorbed in the DCT.

3) 20% is reabsorbed in the thick ascending limb of Henle's loop.

* 2 and 3 are controled by PTH.

Front 31

What are the causes of hypocalcaemia?

Back 31

1) PTH problem: deficiency due to hypoparathyroidism caused by neck surgery, Mg deficite or idiopathic.

2) 1.25 DHCC problem: deficiency due to malabsorption or insufficient UV or renal failure and inability to synthesise active 1.25 DHCC.

Front 32

What are the causes of hypercalcaemia?

Back 32

1) PTH problem:

hyperthyroidism due to adenoma (high Ca and PTH on blood test)

malignancy - production of PTH related peptide (high Ca but suppressed PTH)

2) 1.25 DHCC problem: inadequate dose

Front 33

What is the distribution of phosphate in the body?

Back 33

1) 85% in bone matrix.

2) Rest in predominantly intracellular: membranes, nucleic acids, enzyme cofactors, ATP.

3) 1% in ECF, 30% of which in inorganic.

Front 34

What are the organs involved in phosphate metabolism?

Back 34

1) Kidney

2) Gut

3) Bone

Front 35

What are the main hormones involved in phosphate metabolism?

Back 35

1) PTH

2) Fibroblast growth factor 23 (FGF 23)

3) 1,25(OH)2 Vitamin D

Front 36

What are the significats points about phosphate absorption in the gut? (4 points)

Back 36

1) Less regulated than that of Ca.

2) Entire small intestine is involved.

3) Rate of absorption is increased by 1.25(OH)2 Vitamin D

4) Phosphate is more plentiful in diet than calcium.

Front 37

Where in the kidney is PO4 reabsorbed?

Back 37

1) 75% in the PCT

2) 25% in the DCT

Front 38

What happends when phosphate levels rise too high?

Back 38

1) When PO4 rises Ca falls.

2) Then PTH and FGF 23 levels increase.

3) Both hormones induce PO4 excretion in the urine.

Front 39

What are the 4 phases of bone remodelling?

Back 39

1) Quiescence

2) Resorption

3) Reversal

4) Formation

Front 40

How much of bone is being remodeled at any one time?

Back 40

10%

Front 41

How long does a single remodelling cycle last?

Back 41

About 6 months:

10 - 14 days of resorption and approx. 150 days of formation.

Front 42

What do osteocytes secrete in quiescence phase to inhibit wnt signalling and osteoclast activation?

Back 42

Sclerostin

Front 43

Which molecules are responsible for osteoclast formation?

Back 43

1) Early differentiation:

PU-1 and M-CSF - maturation of early osteoclast precursor from stem cells.

2) Later differentiation:

C-fos, nuclear factor kappa B (NfkB), receptor activator of NFkB (RANK), and its ligand (RANKL).

Front 44

Outline the process of osteoclast maturation. (6 points)

Back 44

1) Nearby osteocytes undergo apoptosis.

2) Lining cells form canopy with blood vessels.

3) Sclerostin is no longer released.

4) IL-3 stimulates pre-osteoblasts and M-CSF stimulates pre-osteocytes. Both are released by stromal cells.

5) Pre-osteoblasts proliferate, secrete factors, e.g. Wnt, and express RANK-L on their surfaces and extracellulary.

6) RANK receptors on osteclasts are stimulated, causing them to fuse into mature osteoclasts.

Front 45

Which molecule inhibits RANK - RANKL interaction and what is it released by?

Back 45

Osteoprotegerin (OPG) is the RANKL inhibitor released by osteoblasts, and also other cells in the body, to prevent osteoclast formation and thus decrease bone resorption.

Front 46

Outline the process of bone resorption. (3 points)

Back 46

1) A tight seal is formed by mature osteoclasts over the bone surface.

2) Osteoclast release HCl to digest hydroxyapatite and proteolytic enzymes to break down the matrix.

3) Osteoclasts undergo apoptosis heralding the beginning of bone formation.