L47 - Calcium Homeostasis Flashcards
What are some facts about calcium in the human body?
- most abundant
- ~1100g (27.5 mol) calcium
- 99% in skeleton, 1% blood and other tissue
- total plasma calcium ~2.5mmol/L
What is the distribution of calcium in the blood?
- protein bound calcium
- cokmplexed calcium
- free ionised calcium
What calcium is physiologically active?
Ionised calcium
What are functions of calcium?
- nerve function
- muscle contraction
- blood clotting
- skeletal mineralisation
- cellular metabolism
- cell signaling
A
What regulates calcium homeostasis?
- calcitriol
- calcitonin
- parathryoid hormone
What is parathyroid hormone (PTH) produced by?
- chief cells
- of parathyroid gland
What is PTH?
- single chain polypeptide 84aa, MW 9500
- derived from larger precursor peptides (pre-proPTH and proPTH)
What are the types of regulation of PTH secretion?
- minute to minute
- long term
What is the minute to minute regulation of PTH secretion?
- CA2+ acting via GPC calcium sensing receptor (CaSR)
- dec in ionised (free) plasma Ca2+
- = inc in PTH secretion
What is the long term regulation of PTH secretion?
Calcitriol acts directly on parathyroid gland to dec preproPTH and mRNA
What does PTH secretion have an impact in?
- bone
- kidney
- intestine
What does PTH do in bones?
Inc bone resorption
What does PTH secretion do in the kidney?
- dec phosphate reabsorption (phosphaturia)
- inc Ca2+ reabsorption
- inc hydroxylation of 25 OH Vit D
What does PTH secretion do in the intestine?
inc Ca2+ absorption (indirect 1,25- dihydroxycholecalciferol)
What are the actions of PTH?
- inc action of osteoclasts by osteoblasts, inc release of Ca2+ into plasma
- inc reabsorption of Ca2+ into kidneys, red amount lost in urine
- inc activity of 1a-hydroxylase, dec 24-hydroxylase = inc intestinal abs of Ca2+ into blood
- lead to rise in plasma Ca2+
What 2 forms does Vit D exist in?
- Vit D2 derived from diet
- Vit D3 formed by action of UV radiation from sunlight on cholesterol derivative in the skin
What factors influence vit D synthesis in the skin?
- skin pigmentation
- geographic location
- sunscreen use
- season
- age
What is the synthesis and regulation of calcitriol (active Vit D)? FINISH
What is calcitriol?
- active metabolite of vit D3
- secosteroid
- only free fraction active
- t1/2 3-6hr
What is vit D3 converted to?
Calcidiol in liver
What are plasma levels of calcitriol determined by?
- rate of conversion of calcidiol to calcitriol (activation)
- rate of conversion of calcitriol to calcitroic acid (inactivation)
What are the actions of calcitriol?
- inc intestinal absorption of Ca2+ = inc conc in blood
- inc action of osteoclasts = inc release of Ca2+ into plasma
- inc reabsorption of Ca2+ to kidneys = red amount lost in urine
- rise in plasma Ca2+
What is calcitonin?
Single chain polypeptide 32 aa with MW 3500
What is calcitonin secreted by?
- parafollicular C cells of thyroid gland
- regulated by Ca2+
What is the link in Ca2+ to calcitonin?
Increased Ca2+ = inc calcitonin secretion
What are the actions of calcitonin?
- dec release Ca2+ from bone = osteoclast inhibit bone resorption
- kidneys decrease tubular reabsorption Ca2+
- no effect on Ca2+ absorption in SI
- fall in plasma Ca2+
What are physiological roles of calcitonin?
- protect against postprandial hypercalcaemia
- protect skeleton during pregnancy and lactation
- act to prevent excessive bone destruction
What is the endocrine regulation when Ca2+ levels fall?
- Parathyroid glands release PTH
- stimulates Ca2+ release from bones
- inc Ca2+ uptake in kidney
- inc Ca2+ uptake in intestine
What is the endocrine regulation when Ca2+ levels rise?
- thyroid gland release calcitonin
- stimulates Ca2+ deposition in bones
- red Ca2+ uptake in kidneys
What does calcitonin, PTH and calcitriol target?
- osteoclast
- osteocyte and osteoblast
- osteoblasts
What are the action of PTH and calcitriol on bone-resorbing cells? Mediated by?
- indirect
- by cells of the osteoblast lineage (bone-forming)
What is the effect of PTH on osteoblasts?
- PTH binds to osteoblast
- osteoclast precursors attach to RANKL
- form osteoclast
What are disorders of calcium metabolism?
- hypercalcaemia
- hypocalcaemia
What is hypercalcaemia?
- XS PT hormone
- // tumour of PT gland
- affects bones, kidneys, GI tract, neurological symptoms
What is hypocalcaemia?
- lack of PTH
- lack of vit D effect
- symptoms related to neuromuscular excitability
- long term lack of vit D affects bone growth
- // osteomalacia, rickets, osteoporosis
What is the endocrine regulation of Ca2+ when blood conc decreased?
- PTH secretion
- osteoclasts break down bone = Ca2+ released
- PTH increases Ca2+ reabsorption from urine, stimulates active vit D
- promotes Ca2+ absorption from SI
What is the endocrine regulation of Ca2+ when blood conc increased?
- calcitonin secretion from thyroid gland
- inhibits osteoclasts
- enhanes osteoblast uptake of Ca2+ from blood into bone
