Lecture 25: Calcium Metabolism Flashcards
how is calcium homeostasis maintained
tightly regulated ion transport by GIT, bone and kidneys
what % of total plasma Ca2+ is free
50%
which form of Calcium is metabolically active and has biological effects
ionised (free) calcium
list the molecules that calcium binds to in the plasma
- anions
- albumin
- globulin
what are the 2 variables that affect the proportion of calcium that is free or bound
- albumin conc.
- blood pH
how does pH affect the proportion of free or bound plasma Ca2+
- H+ ions also bind to albumin
- H+ can displace Ca2+
- iCa2+ ^
name the 3 hormones that act to regulate Ca2+ homeostasis
- parathyroid hormone (parathormone)
- activated Vit D
- calcitonin
what are the 2 other names for activated Vit D
- -> 1,25-dihydroxycholecalciferol
- -> calcitriol
what stimulates release of parathyroid hormone
- low Ca2+
- ^ phosphate
- low Mg2+
name the cells on parathyroid glands that detect low calcium levels
chief cells
describe the action of parathyroid hormone in Ca2+ homeostasis
main role is to ^ Ca2+ levels in the blood
Bone
- short term: rapid exchange from bone pool to ECF
- long term: resorption by osteoclasts
Kidney
- reabsorption of Ca2+
- excretion of phosphate (reciprocal relationship)
- formation of 1,25-dihydroxycholecalciferol
Intestine
- Ca2+ reabsorption
name regulators for active Vit D
- PTH
- low phosphate
what type of hormone is Vit D
steroid hormone –> derived from cholesterol
name the main enzyme involved in Vit D activation in the kidneys
1 a-hydroxylase
describe the action of activated Vit D in Ca2+ homeostasis
Intestine
- ^ Ca2+ absorption
- ^ Ca2+ transport prots –> calbindin-D prots
Kidneys
- facilitates Ca2+ absorption
Bone
- ^ calcification and mineralisation
what mediates Vit D action
- receptors
- Vit D is a steroid hormone w/ genomic effects
- binds to receptor on nucleus
describe the difference between rickets and osteomalacia
rickets = Vit D deficiency in child
osteomalacia = Vit D deficiency in adult
list some causes of rickets and osteomalacia
- lack of dietary Vit D and/or sunlight
- malabsorption of fats
- failure to form calcitriol –> chronic renal failure
- mutation in 1 a-hydroxylase
- mutations in VDR
what are the 4 fat soluble vitamins
A,D,E,K
outline a basic difference between osteoporosis and osteomalacia
osteoporosis = normal bone just not enough
osteomalacia = abnormal soft bone which hasn’t been mineralised
what people are at risk of Vit D deficiency
- elderly people
- house-bound people
- those who cover up a lot in the sun
- those who where sunscreen all year
- those with dark skin
why are people with dark skin at risk of Vit D deficiency
- they require more sun exposure to make as much Vit D
- sunlight needs to penetrate through layer of melanin to layer that manufactures Vit D
where is calcitonin produced
in thyroid gland by C cells
name a regulator of calcitonin secretion
^ Ca2+
describe the action of calcitonin
Bone
- inhibits resorption
Kidneys
- ^ Ca2+ excretion
list some other hormones that influence bone (inc. or dec. bone growth)
increase
- androgens
- growth hormone and IGF
- thyroid hormone
- prolactin
decrease
- glucocorticoids
- inflammatory cytokines
what is a major pathogenic factor that causes faster bone loss in women over men
oestrogen deficiency
what is normal calcium levels
2.35-2.55 mmol/L
what is abnormal calcium levels
> 3.5 mmol/L –> hypercalcaemia
<1.9 mmol/L –> hypocalcaemia
what is hypocalcaemia
dec. serum Ca2+
give some causes of hypocalcaemia
- hypoparathyroidism
- pseudohypoparathyroidism
- Vit D deficiency
what are some clinical signs of hypocalcaemia
- neuromuscular excitability followed by tetany
- Chvostek’s sign
- Trousseau’s sign
explain how hypocalcaemia can result in tetany
- normally Ca2+ block Na+ from entering cells
- when Ca2+ low it’s easier for Na+ to enter cells
- cells depolarise easier
- tetany
explain how hypocalcaemia can result in tetany
- normally Ca2+ block Na+ from entering cells
- when Ca2+ low it’s easier for Na+ to enter cells
- cells depolarise easier
- reduced AP threshold
- tetany
what is Chvostek’s sign
tapping on face anterior to ear and below zygomatic bone causes ipsilateral facial twitching
what is Trousseau’s sign
inflation of BP cuff above SBP for several mins causes muscle contraction incl. flexion of wrist and MCP joints, hyperextension of fingers, and flexion of thumb on palm
what is hyperparathyroidism
^ PTH
what causes primary, secondary and tertiary hyperparathyroidism
1st = problem in gland itself e.g. PTH secreting adenoma
2nd = (stimulus is low Ca2+) problem in kidney/ kidney failure
3rd = chronic secondary hyperparathyroidism –> PT glands become autonomous and keep secreting PTH
give some clinical signs of hypercalcaemia
- bone pain
- kidney stones
- GI disruption e.g. abdominal pain, constipation
- CNS disturbance e.g. muscle weakness, lethargy
what would be seen on an ECG trace for hypo/hypercalcaemia
hypo = long QT interval
hyper = short QT interval
