Parathyroid Hormone, calcium maintenance and bone Flashcards
What is the role of the parathyroids?
Regulate serum calcium and phosphate levels by secreting PTH in response to low serum calcium and high serum phosphate
What are the actions of PTH
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)
What is PTH where does it act?
Peptide hormone with short half life around 8 mins
Binds to GPCR’s in the kidney and on osteoclasts
What is the response of the parathyroids to hypocalcemia?
Parathyroids detect low serum calcium
Increased PTH secretion
What is the effect of PTH in the kidney?
Increased distal reabsorbtion of Ca2+
stimulates the production of active from of vitamin D3 1,25(OH)2D3
What are the other effects (not kidney) of PTH relase?
increased intestinal absorption of both calcium and phosphate due to production of 1,25(OH)2D3
Increased bone resorption through stimulation of osteoclasts
What is 25 hydroxyvitaminD3 25(OH)D3 ?
The inactive form of vitamin D3
What is the active form of vitamin D3
1,25(OH)2D3
How does vitamin D3 act what type of hormone is it
Steroid hormone
Binds to intracellular nuclear receptors acting as a transcriptional regulator
What are the main sources of Vitamin D
Diet eggs oily fish herring etc and mushrooms
Majority from UV radiation
How is vit D produced from UV radiation?
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
How is vitamin D measured?
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
What is calcitonin & when and where is it produced?
Produced by thyroid C cells
Peptide hormone that is not essential to life
released in response to hypercalcemia
What is the action fo calciitonin?
Inhibits bone resorption by action on osetocalsts
What is FGF23?
fibrobalst growth factor 23
produced by osteocytes is a hormone
What is the action onf FGF23 when is it realsed?
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
What is the structure of bone
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
What are osteocytes what is there role?
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
What are osteoblasts what is there role?
Bone forming cells produce rich matrix full of collagen known as osteoid
Osteoid is calcified upon formation of hydroxyapatite crystal formation
What are osteoclasts what is their role?
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
How do osteoclasts develop what do they need to do this?
Requires osteoblasts to produce macrophage colony stimulating factor
RANK ligand
Both are essential for the differentiation of preosteoclasts to mature osteoclasts
What is primary hyperparathyroidism?
Bengin secretory adenoma in parathyroid glan
What are consequences of primary hyperparathyroidsm?
Causes hypercalcemia and low serum phosphate
Loss of negative feedback on PTH by raised calcium levels
What are the symptoms of primary hyperparathyroidsm?
Lethargy Polyuria Polydipsia Constipation Joint pain and fractures Depression Hypertension Kidney stones
What is secondary hyperparathyroidism ?
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
What is the difference between rickets and osteomalacia?
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
What is rickets and osteomalacia?
Lack of mineralisation of osteoid of bone due to lack of Ca2+ absorption form the Gi tract
cause is lack of dietary vitamin D3
What is the treatment of osteomalacia/ rickets
Vitamin D replacement therapy diet and sunlight
What is osteoporosis
Loss of bone mass and density due to decrease in mineral and osteoid development
What are two forms of osteoporosis?
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
What is the treatment of osteoporosis
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
What is tetany?
muscle cramps and spasms due to hypocalcemia.
The low serum calcium increases the sarcolemma permeability to sodium ions causing progressive depolarisation
