4.6: Regulation of calcium and phosphate Flashcards
What is the most abundant metal in the body
Calcium
Where does 99% of calcium reside in the body, what is it stored as
In the skeleton and teeth
Calcium hydroxyapatite crystals
What is Extracellular calcium
Calcium that is present in the bloodstream - measured during a blood test
Why is Extracellular calcium tightly regulated
Lives in circulation, often bound to albumin
Unbound ionised calcium is a
Biologically active component
Hormones involved in calcium control (increase)
Parathyroid hormone (PTH)
Vitamin D
What is parathyroid hormone secreted by
Parathyroid glands
How is vitamin D synthesised
In skin or intake via diet
How do Vit D and PTH regulate Ca and PO4 homeostasis
Via actions on kidney, bone and gut
What is calcitonin
Hormone that can reduce calcium acutely, but no negative effect if parafollicular cells are removed
Two types of Vitamin D
Ergocalciferol
Cholecalciferol
What is ergocalciferol derived from
UV irradiation of plants - consumed in vegetables
What is cholecalciferol derived from
UV irradiation of skin and certain foods (oily fish, egg yolk)
Vitamin D metabolism
1) UVB from the sun causes 7-dehydrocholesterol to convert to Pre-vitamin D3 in the skin
2) this is then converted to Vit D3 which enters the circulation
3) Vit D2 is present in the diet and absorbed from the gut
4) D3 and D2 pass into the liver (25-hydroxylase) and are hydroxylated at position 25 producing 25(OH)cholecalciferol
5) this is then hydroxylated again in the kidneys to form active vitamin D : using enzyme 1 alpha-hydroxylase
Active form of vitamin D is called
Calcitriol
2 Characteristics of serum 25-OH cholecalciferol
Biologically inactive
Good indicator of body vitamin status
How is Vitamin D synthesis regulated
1,25(OH)2cholcalciferol regulates own synthesis by decreasing transcription of 1 alpha-hydroxylase
Major role of calcitriol
Increase Ca2+ and PO4 ^3- reabsorption from the gut
Role of calcitriol in kidney
Increases Ca2+ and PO4 ^3- reabsorption, less lost in urine more in bloodstream
Role of 1,25(OH)2D3 in bone
Increased Ca2+ reabsorption from bone
What cells secrete PTH
Chief cells in parathyroid glands
What is PTH secreted as
Large precursor and cleaved to PTH
feedback (regulation) of PTH
G-protein coupled calcium sensing receptor on chief cells detect change in circulating calcium concentration
What is PTH secretion inversely proportional to
Serum calcium
High levels of ECF (Ca2+)
Ca2+ binds to receptors on parathyroid cells
PTH secretion inhibited
At low levels of ECF (Ca2+)
Less Ca2+ binding to receptors on parathyroid cells
PTH secreted
When serum calcium increases, what happens to parathyroid hormone (PTH)
PTH decreases
Function of osteoblast
Build bone
Function of osteoclast
Consume bone
PTH in bone
PTH binds to receptors
Osteoblast build bone
If osteoclast activating factors are present
Osteoblast turns into osteoclasts
Causing bone reabsorption
Calcitriol action in bone depend on
Serum calcium
During low serum calcium calcitriol has a ___ effect
Calcitriol works with PTH to increase calcium reabsorption from bone
Osteoclast > osteoblasts
During normal serum calcium levels, calcitriol has a ___ effect
Calcitriol promotes bone formation
Osteoblast > osteoclasts
2 processes of Negative feedback in PTH regulation
PTH increase and 1,25 (OH)2D3 synthesis
Increased plasma Ca2+ and parathyroid cell’s increased PTH
Calcitonin is secreted from
Parafollicular cells of thyroid gland
Function of calcitonin
Reduces serum calcium
Calcitonin actions and regulation
Increased plasma Ca2+ detected by parafollicular cells of thyroid
Secretes calcitonin
Decreases osteoclast activity in bone
Increases Ca2+ excretion in kidneys
Both decrease claims Ca2+ limited effect
What is serum phosphate regulated by
FGF23
What is FGF23 secreted by
Bone cells
Function of FGF23 and two ways in which this occurs
Promotes phosphate loss:
Blocks sodium phosphate cotransporter in kidneys
Switches off calcitriol
More phosphate into urine
Hypercalcaemia is
High serum calcium
Hypocalcaemia is
Low serum calcium
Characteristics of the membrane during Hypercalcaemia
High Extracellular calcium, blocks Na+ influx so less membrane excitability
Characteristics of the membrane during hypocalcaemia
Low Extracellular calcium, so greater Na+ influx enables, so more membrane excitability
Signs and symptoms of hypocalcaemia (4)
Paraesthesia
Convolutions
Arrhythmias
Tetany
(CATs go numb)
Process of Chvosteks sign test
Tap facial nerve below zygomatic arch
Positive response = twitching of facial muscles = neuromuscular irritability due to hypocalcaemia
How to test for hypocalcaemia (2)
Chvosteks sign
Trousseaus sign
Process of trousseaus sign test
Inflation of BP cuff for several minutes
Induces carpopedal spasm
Neuromuscular irritability due to hypocalcaemia
2 Causes of hypocalcaemia
Low PTH levels = hypoparathyroidism
Vitamin D efficiency
4 causes of hypoparathyroidism
Surgical - neck surgery
Auto immune
Magnesium deficiency
Congenital (agenesis, rare)
5 Causes of vitamin D deficiency
Malabsorption or dietary insufficiency
Inadequate sun exposure
Liver disease
Renal disease
Vit D receptor defects (rare)
Consequences of vitamin D deficiency in children
Rickets (bowling of bones)
Consequences of vitamin D deficiency in adults
Osteomalacia
(Fractures, proximal myopathy)
Vitamin D deficiency effect on bones
Lack of bone mineralisation, leading to soft bones
Signs of Hypercalcaemia
Reduced neuronal excitability- atonal muscles
3 symptoms of Hypercalcaemia
Stones - renal effects : Nephrocalcinosis, kidney stones, renal colic
Adbominal moans - GI defects: anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects : fatigue, depression, impaired concentration, altered mentation, coma
3 causes of Hypercalcaemia
Primary hyperparathyroidism
Malignancy
Vitamin D excess (rare)
3 causes of primary hyperparathyroidism
Too much PTH
Parathyroid gland adenoma
No negative feedback- high PTH, but high calcium
Cause of malignancy
Bony metastases produce local factors to active osteoclasts, increasing calcium reabsorption from bone
