CEP WK6 - PARATHYROID GLAND & CA HOMEOSTASIS Flashcards
JOBS OF SKELETON
- protect vital organs
- support muscles
- provide reservoir of calcium
CALCIUM HOMEOSTASIS
- must maintain serum calcium conc. of 2.1-2.6 mM
- can be absorbed back (after being released to) from bone, intestine, kidney
NORMAL BODY LEVELS
PTH = 1.6-6.9 pmol/L
Serum Ca = 2.1-2.6mM
1,25D3 = 50-150 pmol/L
Creatinine = 74.3-107 mmol/L
PARATHYROID GLANDS
secrete PTH in response to low calcium or high phosphate
JOBS OF PTH
- binds to GPCR in kidney or osteoblast to do response
KIDNEY - increase calcium reabsorption in renal distal tube
INTESTINE - increase calcium reabsorption indirectly (by activating vit D)
BONE increase calcium release from bone (by stimulating osteoclast activity) - decrease phosphate reabsorption
HYPOCALCAEMIA (low Ca level)
- low Ca = more PTH secretion in parathyroid glands to kidney to decrease Ca in urine, increase phosphate in urine & produce 1,25D3 enzyme which produces vitamin D (goes to intestine to increase Ca absorption)
- in very worst case scenario, we can reabsorb calcium from bone (not ideal)
LOOK AT DIAGRAM ON CEP W7
HOW PTH REGULATED
- PTH transcription inhibited by 1,25D3 (high 1,25D3 production lowers amount of PTH)
- PTH translation inhibited by increased serum calcium (less PTH made if low calcium)
CALCITONIN
- produced by C-cells in thyroid in response to hypercalcaemia & works by inhibiting bone reabsorption
- not essential to life as shown by no problems after a thyroidectomy
VITAMIN D FROM?
- obtained from diet or UV (hits skin & converts 7-dehydrocholesterol to vit D3) & D3 enters blood then converted to 25D3 in liver then converted to 1,25D3 by PTH in kidney
- Active form is 1,25D3 & inactive is 25D3
EFFECTS OF VIT D
binds to vit D receptors (intracellular & is a steroid receptor) & acts as TF &
- promotes Ca & PO4 intestine absorption
- promotes bone resorption (increase osteoclast number) - inhibits PTH transcription
SIGNS OF VITAMIN D DEFICIENCY
bone pain, seizures, renal signs, osteomalacia
OTHER THAN VIT-D & PTH, WHAT INFLUENCES BONE STATUS (4)
- age (bone density decreases with age)
- oestrogen levels (oestrogen deficiency following menopause increases bone remodelling rate & degree of bone reabsorption)
- levels of phosphate & calcium
- steroid therapy (risk of bone loss due to steroid meds)
HYPERCALCAEMIA
parathyroid glands clock the high Ca so decrease PTH secretion which leads to these things below to decrease the serum calcium level
- less bone resorption
- less urine phosphate & 1,25D3 production BUT higher urinary calcium
- lower calcium & phosphate absorption in intestine
HYPERPHOSPHATAEMIA (HIGH SERUM PO4)
- FGF23 produced by osteocytes (bone cells) & released in response to high serum PO4 to increase urinary PO4 & suppress renal synthesis of active vitamin D (1,25D3) to decrease
- FGF23 effectively overrides effects of PTH
- FGF23 os inhibited by 1,25D3
STRUCTURE OF BONES
- main bone growth & activities happens in epiphysis
- strong part of bone is in diaphysis
WHAT IS BONE MADE OF
specialised connective tissue, extracellular matrix, collagen
OSTEOCYTES
- produce FGF 23
- have long processes used to communicate with other osteocytes & osteoblasts
OSTEOBLASTS
- bone forming cells
- produce matrix constituents & aid calcification
OSTEOCLASTS
- bone reabsorbing cells
- produce acid (to reabsorb minerals) & enzymes (to reabsorb matrix)
- have integrins to attach to bone surface
HOW CALCIUM CONC RELATED TO SPASMS
low plasma calcium increases permeability of membranes to NA= which leads to depolarisation. If Ca2+ conc. is less than 50% of normal, AP may be spontaneously generated which leads to involuntary contraction of muscles
OSTEOCLAST DEVELOPMENT
- osteoblasts have a RANK ligans which goes to osteoclast precursor (has a RANK receptor) to form an osteoclast
- drugs that can bind to RANK receptor to inhibit this are denosumabs & OPG’s
BONE REMODELLING
osteoclasts bind to bone -> bone resorption -> resorption pit formed -> Ca2+/PO4/collagen all taken out of bone -> osteoblasts come in to form a new layer of mineralised bone (using collagen & PO4 & calcium)
HYPERPARATHYROIDISM (raised serum PTH)
PRIMARY - caused by parathyroid tumour & leads to hypercalcaemia & low serum PO4 (loss of negative feedback loop from hypercalcaemia)
- treated by surgery
SECONDARY - caused by kidney disease & leads to increased phosphate and decreased activation of vitamin D
- treated with phosphate binders to bring phosphate level down
LOOK AT PG6 OF CEPW7
OSTEOMALACIA
- vitamin D & calcium deficiency due to diet & lack of sunlight
- leads to lack of mineralisation of collagen component of bone (osteoid) & failure to absorb sufficient calcium from GI tract
- symptoms are legs curving out at knees (bow-legs)(as osteoid at growth plate is weak) & swollen joints (growth plate expands to compensate)
- treated by giving vitamin D
OSTEOPOROSIS
- loss of bone mass/density due to lack of mineral (you have normal bone but just less of it so increased fracture risk)
- all bad effects are due to the osteoclasts
- happens at ageing (less bone density as older), postmenopausal (decline in female bone density following oestrogen decline), steroid-induced (using steroids leads to decline in bone density)
- prevented by exercise (enhanced osteocyte activity through bone stress)
TREATING OSTEOPOROSIS
- hormone replacement (replace oestrogen)
- inhibit osteoclast development using RANK antibody e.g. denosumab (to block RANK receptor so less differentiation of pre-osteoclasts)
- inhibition of osteoclast activity using bisphosphonates (disrupt intracellular enzymes needed for osteoclast activity)
- stimulation of osteoblast activity
