endocrine control of plasma calcium Flashcards
roles of calcium
- Structural component of bones and teeth (99% total calcium)
- Maintains normal excitability of nerve and muscle cells
- Involved in neurotransmitter and hormone release
- Muscle contraction (skeletal and cardiac)
- Activation of many enzymes
- Coagulation of blood
- Milk production… and more!
therefore must be in narrow physiological range
where is calcium found in the body
0.1 % in the extra cellular fluid (ECF)
1 % in the cells
The rest (app. 99 %) in the skeleton: hydroxyapatite
what forms is calcium found in within the body?
- Protein-bound calcium
- cannot diffuse through membranes and thus is not usable by tissues
- Ionized or free calcium
- is the physiologically active form
- Complexed or chelated calcium
- is bound to phosphate, bicarbonate, sulfate, citrate, and lactate
why is plasma calcium regulation so important
what occurs when too low / too high
- Free (ionized) calcium is tightly regulated (±5%)
- Too low = neuronal hyper-excitability (tetany)
- Low ionized calcium levels in the extracellular fluid increase the permeability of neuronal membranes to sodium ion,
- causing a progressive depolarization,
- which increases the possibility of action potentials
- ‘claw hand feature’ - muscles are constantly contracting
- Low ionized calcium levels in the extracellular fluid increase the permeability of neuronal membranes to sodium ion,
- Too high = depression & kidney damage/stones
- Deposition within kidneys
control points for calcium
Absorption – Via intestines
Excretion – Via Kidney/urine
Temporary storage – Via bones
how is normal calcium levels balanced
- Constant exchange between cells and ECF
- When there is not enough calcium in them
- Calcium drawn from bones
- Osteoclast activity to release calcium ions
- Has to be replaced
- Excretion of some amount
- Calcium must be in a soluble and ionized form before it can be absorbed
- Regulation of calcium is closely associated with phosphate.
why do pregnant women who are 18 years or younger require more calcium than those who are 19 years old or older and pregnant
- 18 years or younger
- Growth plates are still open
- Calcium deposition is still required here
- Therefore require more calcium than those 19 years older and pregnant
- Also with breastfeeding
acute control of calcium levels
Must maintain constant free Ca2+ concentration in the plasma
Mostly by rapid exchange between bone and ECF
chronic control of calcium levels
- Maintain total level in the body long term
- Stimulate vitamin D activation
- Adjust GIT absorption and urinary excretion
how is plasma Ca2+ concentration regulated?
- is determined by:
- Net absorption of Ca2+ from the GIT
- Net excretion of Ca2+ in urine
- Exchange of Ca2+ with bone
what hormones control plasma Ca2+ concentration
- Parathyroid hormone
- Responsible for raising plasma calcium levels
- 1,25-dihydroxycholecalciferol
- Calcitriol (activated vitamin D)
- Inactivated form cannot regulate calcium
- Responsible for raising plasma calcium levels
- Calcitonin
- Responsible for lowering plasma calcium levels
what role does parathyroid gland have in regulation of calcium
- has chief cells
- has calcium sensing receptors
- responsible for synthesis and secretion of Parathyroid hormone during hypocalcium
characteristics of parathyroid hormone
where is it stored
when is it secreted & at what rate
where does it have effect
- peptide hormone
- stored within chief cells
- short half life - rapidly inactivated
- secreted continuously at a low rate
- released in response to low blood calcium
- exerts its effects on bone, git and kidneys
- has a direct effect on bone and kiney
- indirect effect on GIT
action of parathyroid hormone on kidney and bone
- increase reabsorption of calcium from the urine
- Fast acting; decrease in urinary calcium in minutes
- increase the expression of the enzyme 1α-hydroxylase (activates vitamin D)
- Bone: increase osteoclast activity (Indirectly) causing increase in bone resorption
how is the effect of parathyroid hormone on bone indirect?
osteoblasts have receptors for parathyroid hormone
osteoblasts then release factors which stimulate osteoclast activity
how is plasma calcium regulated by parathyroid hormone ??
- Low plasma calcium
- Parathyroid gland produces parathyroid hormone
- Activation of osteoclasts
- Increase in plasma calcium levels
- Also acts on kidney
- Stops secretion of calcium
- Reabsorbing more calcium in kidney nephron
- Stimulates expression of enzyme 1α-hydroxylase
- Activates vitamin D
- Increases plasma calcium levels also
- Activation of osteoclasts
- Parathyroid gland produces parathyroid hormone
simple negative feed back
actions of calcitriol (1,25 dihydroxycholecalciferol)
Acts on cells on the GIT to increased production of calcium transport proteins
Leads to an increase in Calcium uptake from GIT
The only mechanism that can increase calcium stores
effect of calcitriol on bone
- increasing rate of bone resorption
- Increases the secretion of osteoclast activating factors
- Increases osteoclast activity
effect of calcitriol on kidney
Minor effect in decreasing urinary loss of calcium
how is plasma calcium regulated - overall
what supplements should kidney failure patients take to regulate calcium levels and why
- Take supplements of active form of vitamin D3
- Kidney does not produce 1a hydroxylase
- No conversion to calcitriol
how is calcitonin secreted and what is its roles
- Secreted by the C-cells (parafollicular cells) of the thyroid gland. Minor importance in adults.
- Lowers the level of free plasma calcium
- Osteoclasts have receptor for calcitonin
- Inhibition of osteoclast activity: bone resorption reduced (direct effect)
- Dont release plasma calcium into circulation
- Increased excretion of calcium and phosphate by the kidneys
what was used to treat osteoporosis in postmenopausal women
how did it work
calcitonin
in osteoporosis = Normal bone density but reduction in bone mass
Stop osteoclast activity to preserve bone mass
what happens when plasma calcium levels are too high
- calcitonin is secreted
- parathyroid gland secretes parathyroid hormone
pathological effects of excess or lack of calcitonin
- no pathological consequence
- regulation is very good as PTH is able to lower or raise calcium levels in plasma
- only small consequence in pregnant women
- mostly issues in animals
what other hormones are involved in the regulation of plasma calcium??
- Major hormonal regulators:
- PTH, 1,25-(OH)2D3, and possibly calcitriol
- Others:
- Growth hormone, adrenal glucocorticoids & thyroid hormones
- Oestrogen and androgens
how is (primary) hyperparathyroidism caused?
pathological
elevated PTH and raised serum calcium
- caused by single parathyroid adenoma
- only needs to be on 1 of the parathyroid glands
-
autonomous secretion of PTH
- leads to raised levels
- may be hereditary
presentation of (primary) hyper parathyroidism:
Bones, stones, abdominal groans and psychic moans
- Bones :
- Osteoclast activity
- Lead to brown tumours
- Radiolucent areas with no calcium
- Common in long bones
- Stone
- Kidney stones
- Abdominal groans
- Digestion problems
- Activation of calcium transport proteins
- Psychic moans
- Nervous system problems
- Associated with depression
examples of hypocalcaemia
vitiamin D deficiency :
- rickets in children
- osteomalacia in adults
what effect does vitamin D deficiency have in children and adults?
in both
- reduction in bone mineral density
- due to reduction in available calcium
children
- skeletal deformities
- weight bearing bones
adults
- softening of bone
causes of vitamin D deficiency
- Poor diet
- Not taking in calcium
- Malabsorption
- Conditions
- Unable to absorb calcium in GIT
- Conditions
- Decreased sunlight
- Liver or kidney disease
- 1a-hydroxylase is affected
Is hypocalcaemia in vitamin D deficient patients likely to become severe………. ??
No
Parathyroid gland senses that they are hypocalcaemic
Keep using bone stores
Causes osteomalacia
last column = chronic renal disease
radiographic presentation of hyperparathyroidism
effect of hyperparathyroidism in model of osseous structure
- Elevated PTH in HPT patients reduces cortical bone and protects trabecular bone.
- In combination with the biomechanical forces particular to the oral cavity, cortical bone loss and trabecular expansion result in an increased incidence of tori.
