parathyroid function

Question 1

what concentration must serum calcium be kept at? and how can we regulate it?

Answer 1

• between 2.1-2.6 mM
• GIT (Vitamin D stimulates increased uptake from diet)
• Kidney produces PTH, Vit D and FGF23
• Bone PTH/Vit D has action here

Question 2

describe the parathyroid gland

Answer 2

• 4 of them
• found on the thyroid gland of the neck
• secrete PTH in response to hypcalceamia or high phosphate levels
• regulates both Ca and Po4 levels

Question 3

actions of PTH include ?

Answer 3

• increase Ca absorption in the renal DCT
• Increased intestinal Ca absorption (indirectly via activation of vit D)
• increased bone resorption ( stimulated osteoclast activity)–> only if serum levels have not recovered so is seen as a last resort
• decreased po4 reabsorption

Question 4

describe the structure of PTH

Answer 4

• is an 84 AA peptide hormone
• biological activity is in the first 34 AA
• cleaved to smaller active peptides

Question 5

underline the actions of PTH in the kidneys

Answer 5

• increases distal tubular reabsorption of calcium (inhibiting Po4 reabsorption)
• stimulates production of the active form of vit D (1,25 (OH)2D)

Question 6

how are PTH levels regulated via negative feed back?

Answer 6

• PTH transcription (mRNA production) is inhibited by 1,25 D3)
• PTH translation is inhibited by high serum Ca levels

Question 7

explain the steps of vit D synthesis

Answer 7

• skin (7-dehydrocholesterol) —> vitD3 –> Liver ( 25-OHD3)—> kidney ( 1,25OH2D3)-> active form

steroid hormone that binds to an intracellular nuclear receptor

Question 8

what is the normal reference range for vit D?

Answer 8

• 7.5 nmol/L (assayed for 25 (OH)D3)

- active form rarely measured

Question 9

what is the normal adult range for PTH levels?

Answer 9

• 1.6–> 6.9 pmol/L

Question 10

what does calcitonin do?

Answer 10

• produced by the parafollicular cells of the thyroid gland
• released in response to hypercalcaemia
• inhibits bone resorption via osteoclasts
• not essential for life
• essentially reverses all the actions of PTH on the periphery

Question 11

what is FGF23?

Answer 11

produced by cells of the bone (osteocytes and osteoblasts)

• response to high serum Po4
• increases renal excretion of po4 and suppresses renal synthesis of active (1,25 OH2D3)
• ITS main inducer is 1,25D3
• levels become elevated during stages of kidney disease and dialysis
• dominant effects on kidney reverses high po4 levels

Question 12

what do osteocytes do?

Answer 12

Osteocytes - embedded In calcified bone matrix with long processes which contact other osteocytes and osteoblasts

Question 13

what do osteoblasts do?

Answer 13

bone forming cells which produce matrix constituents and aid calcification
Originate from mesenchymal stem cells (bone marrow stem cells or connective tissue mesenchymal cells).

Question 14

what are osteoclast cells?

Answer 14

bone resorbing cells usually found in contact with calcified bone surface – in lacunae
Multinucleated - originate from bone marrow lineage
Produce acid (to resorb mineral) and enzymes (to resorb matrix) - to release Ca

Question 15

briefly outline the bone resorption cycle

Answer 15

1) resting surface
2) resorption pit formed by osteoclast cells via release of acid and digestive enzymes to resorb the EC matrix
3) release of Ca
4) reversal phase –> formation of a cement line via osteoblast cells
5) bone reformation (production of osteoid composed of collagen T1)

6) osteoid mineralization is completed via the action of Ca –> formation of hydroxyapatite crystals

Question 16

what is primary HPT?

Answer 16

• metabolic bone disease –> increased bone resorption
• caused by adenomas of the PTH glands (benign)
• loss of feedback control
• hypercalcaemia

Question 17

what is secondary HPT?

Answer 17

• increased serum po4 (hyperphospataemia)
• decreased activation of VitD3
• reduced serum Ca
• increased serum po4 stimulates FGF23 of which increases inhibition of vitD3 production
• seen in renal osteodystrophy/ CKD-MBD
• elevated secretion of PTH in response to hyperP (kidney disease) , hypoCa (kidney disease) and decreased active vitD3 (increased FGF23 activity)

Question 18

what is rickets ?

Answer 18

• affects growing skeletons
• lack of mineralization of collagen content (osteoid)
• failure to absorb sufficient Ca from GIT due to dietary deficiency of vitD3 (lack of sunlight too)
• rarely inherited ( mutations to VDR, 1-alpha OHlase)

Question 19

during rickets

Answer 19

• there is weak osteoid growth at growth plates

- with growth plate expansion to compensate leading to swollen joints

Question 20

during osteomalacia

Answer 20

• affects adult skeleton

- there is bone pain and pseudo fractures

Question 21

treatment of rickets via?

Answer 21

vitamin D replacement therapy

Question 22

how can CKD-MBD be treated?

Answer 22

• by po4 binders

- vitD analogues

Question 23

what is spinal osteoporosis?

Answer 23

• loss of collagen and mineral component of bone
• as with increasing age, the digging pit and cement phase becomes less efficient ( less filling in)
• compression fractures within the spinal vertebrae

Question 24

what is osteoporosis ?

Answer 24

• both mineral and osteoid decreased

- increased fracture risk

Question 25

osteoporosis of ageing is?

Answer 25

• affects males and females

- gradual decline in bone density from early adult peak

Question 26

postmenopausal osteoporosis is?

Answer 26

• rapid decline in female bone density following decline in oestrogen levels at the menopause
• oestrogen increases bone remodelling rate and degree of bone resorption