Parathyroid Hormone, calcium maintenance and bone

Question 1

What is the role of the parathyroids?

Answer 1

Regulate serum calcium and phosphate levels by secreting PTH in response to low serum calcium and high serum phosphate

Question 2

What are the actions of PTH

Answer 2

increase calcium absorption in the DCT

Increase intestinal calcium absorption through the activation of vitamin D

Increase Bone resorption through osteoclast activity

Decrease phosphate absorption (increased excretion)

Question 3

What is PTH where does it act?

Answer 3

Peptide hormone with short half life around 8 mins

Binds to GPCR’s in the kidney and on osteoclasts

Question 4

What is the response of the parathyroids to hypocalcemia?

Answer 4

Parathyroids detect low serum calcium

Increased PTH secretion

Question 5

What is the effect of PTH in the kidney?

Answer 5

Increased distal reabsorbtion of Ca2+

stimulates the production of active from of vitamin D3 1,25(OH)2D3

Question 6

What are the other effects (not kidney) of PTH relase?

Answer 6

increased intestinal absorption of both calcium and phosphate due to production of 1,25(OH)2D3

Increased bone resorption through stimulation of osteoclasts

Question 7

What is 25 hydroxyvitaminD3 25(OH)D3 ?

Answer 7

The inactive form of vitamin D3

Question 8

What is the active form of vitamin D3

Answer 8

1,25(OH)2D3

Question 9

How does vitamin D3 act what type of hormone is it

Answer 9

Steroid hormone

Binds to intracellular nuclear receptors acting as a transcriptional regulator

Question 10

What are the main sources of Vitamin D

Answer 10

Diet eggs oily fish herring etc and mushrooms

Majority from UV radiation

Question 11

How is vit D produced from UV radiation?

Answer 11

UV radiation causes the conversion of 7 dehydrocholesterol in the skin to vitamin D3 precursor then hydroxylated in the liver to 25(OH)D3 and then finally in the presence of PTH to 1,25(OH)2D3 in the kidney

Question 12

How is vitamin D measured?

Answer 12

Vitamin D inactive form commonly only tested for as it is much harder to measure active from

There is not a direct correlation between the two and there is much skepticism as to what is a healthy amount of vitamin D

Question 13

What is calcitonin & when and where is it produced?

Answer 13

Produced by thyroid C cells
Peptide hormone that is not essential to life
released in response to hypercalcemia

Question 14

What is the action fo calciitonin?

Answer 14

Inhibits bone resorption by action on osetocalsts

Question 15

What is FGF23?

Answer 15

fibrobalst growth factor 23

produced by osteocytes is a hormone

Question 16

What is the action onf FGF23 when is it realsed?

Answer 16

Released in response to high serum phosphate (hyperphosphatemia)

High phosphate triggers parathyroids to produce PTH increases urinary phosphate excretion yet PTH also stimulates production of 1,23(OH)2D3 that increases intestinal absorption of both calcium and phosphate

FGF23 kicks in here to override 1,25(OH)2D3 preventing phosphate absorption in the intestines and directly acts on the kidney to increase phosphate excretion

Question 17

What is the structure of bone

Answer 17

Type 1 Collagen that are calcified when hydroxyapatite crystal form

Non collagenous proteins osteocalcin osteopontin help to trap calcium and minerals in the matrix allowing for hydroxyapatite crystal formation

Question 18

What are osteocytes what is there role?

Answer 18

found embedded in calcified bone
Long processes allowing communication between other bones

Act as:
Mechanoreceptors detecting mechanical stress on bone so can trigger osteoblast and osteoclast activity

Maintain calcified matrix

Produce FGF23

Question 19

What are osteoblasts what is there role?

Answer 19

Bone forming cells produce rich matrix full of collagen known as osteoid

Osteoid is calcified upon formation of hydroxyapatite crystal formation

Question 20

What are osteoclasts what is their role?

Answer 20

Bone resorbing and remodelling cells

found in resorption lacunae

Giant multi nucleated and have a specialised sealing zone that allows attachment to the bone creating a small microenvironment in which hydrolytic enzymes are releases that reabsorb matrix and minerals from the bone

Activated by PTH

Question 21

How do osteoclasts develop what do they need to do this?

Answer 21

Requires osteoblasts to produce macrophage colony stimulating factor

RANK ligand

Both are essential for the differentiation of preosteoclasts to mature osteoclasts

Question 22

What is primary hyperparathyroidism?

Answer 22

Bengin secretory adenoma in parathyroid glan

Question 23

What are consequences of primary hyperparathyroidsm?

Answer 23

Causes hypercalcemia and low serum phosphate

Loss of negative feedback on PTH by raised calcium levels

Question 24

What are the symptoms of primary hyperparathyroidsm?

Answer 24

Lethargy
Polyuria
Polydipsia
Constipation
Joint pain and fractures
Depression
Hypertension
Kidney stones

Question 25

What is secondary hyperparathyroidism ?

Answer 25

Something wrong elsewhere causing increased production of PTH

Chronic renal failure:
failure to reabsorb calcium and excrete phosphate results in hyperphosphatemia increased levels of FGF23
to try to counteract this

Then as a result causes a reduction in production of 1,25(OH)2D3

Reduction in 1,25(OH)2D3
increased serum phosphate and low phosphate causes increased secretion of PTH

Question 26

What is the difference between rickets and osteomalacia?

Answer 26

Ricketes is when there is a vitamin D3 deficiency affecting the s growing skeleton

Osteomalacia is when there is a vitamin D3 deficiency affecting the adult skeleton

Question 27

What is rickets and osteomalacia?

Answer 27

Lack of mineralisation of osteoid of bone due to lack of Ca2+ absorption form the Gi tract
cause is lack of dietary vitamin D3

Question 28

What is the treatment of osteomalacia/ rickets

Answer 28

Vitamin D replacement therapy diet and sunlight

Question 29

What is osteoporosis

Answer 29

Loss of bone mass and density due to decrease in mineral and osteoid development

Question 30

What are two forms of osteoporosis?

Answer 30

Senile osteoporosis decline in bone density from adult peak until death

Postmenopausal osteoporosis
oestrogen decline increases bone resorption and remodelling rate as osteoclasts are not inhibited by insulin

Question 31

What is the treatment of osteoporosis

Answer 31

Bisphosphonates is the main form of treatment e.g. alendroninc acid
target osteoclast enter then and clog them up intracellular preventing release of hydrolytic enzymes

Intermittent use of PTH can help to stimulate bone remodelling

Inhibit osteoclast development by blocking RANKL protein and differentiation of osteoclasts

HRT

Question 32

What is tetany?

Answer 32

muscle cramps and spasms due to hypocalcemia.

The low serum calcium increases the sarcolemma permeability to sodium ions causing progressive depolarisation