Week 4- Regulation of Calcium & Phosphate Flashcards
What is the recommended adult intake of calcium?
1000mg per day
What are the 3 key hormones in calcium regulation? Do they increase or decrease calcium?
Parathyroid hormone (increases calcium) Vitamin D (increases calcium) Calcitonin (decreases calcium)
Where is parathyroid hormone secreted?
Parathyroid glands
Where is vitamin D synthesised?
In the skin (or intaken via diet)
Where is calcitonin secreted?
Thyroids parafollicular cells
What are the 2 sources of vitamin D?
Ergocalciferol ie D2 (intaken via diet)
Cholecalciferol ie D3 (made in skin with sunshine)
When measuring Vit D levels what do we measure?
25 (OH) cholecalciferol ie unactive form
What 3 areas does calcitriol work on and what does it do?
Increases calcium absorbtion and phosphate reabsorbtion in the kidney
It works on the small intestine increasing phosphate and calcium absorbtion
Increases reabsorbtion of calcium in bones and stimulates osteoblasts (important for bone health)
How many parathyroid glands are there and where are they located?
4- located at the back of the thyroid
What is the precursor for parathyroid hormone?
Pre-pro-PTH
What does PTH do?
Drives calcium to increase, when it does PTH switches off
What happens when there is high extracellular calcium?
Binding of calcium to receptors on parathyroid gland cells inhibits PTH
What happens when there is low extracellular calcium?
Less binding of calcium to receptors of parathyroid gland cells stimulates PTH secretion
What 3 main areas does PTH effect and what does it do?
Kidney- increases calcium absorption and stimulates loss of phosphate. Stimulates action of 1 alpha hydroxylase allowing more active vit D (calcitriol) formation
Bone- stimulates calcium reabsorbtion
Gut- increases reabsorbtion of calcium and phosphate
What do osteoblasts do?
Build bone
What do osteoclasts do?
Consume bone
How are osteoblasts converted to osteoclasts?
Binding of PTH to receptors causes osteoclast activating factors to be expressed turning the osteoblasts to clasts
What are the 2 ways PTH regulated?
Increased serum calcium reduces PTH secretion
As PTH stimulates production of calcitriol, the calcitriol negatively feeds back onto parathyroid cells
What does calcitonin do? What is special about it
It reduces serum calcium but it is possible to live without it
What are the 2 mechanisms by which calcitonin works?
Increases calcium excretion from kidney
Lowers osteoclast activity on the bone
What are the 2 mechanisms by which FGF23 inhibits phosphate reabsorbtion?
1- directly inhibits the cotransporter that reabsorbs phosphate that would otherwise be urinated
2- indirectly by inhibiting calcitrol production
What happens to membrane excitability in hypercalcaemia?
Blocks Na influx so less excitability
What happens to membrane excitability in hypocalcaemia?
Enables greater Na influx so more membrane excitability
What are symptoms of hypocalcaemia? What mnemonic do we use to remember them?
Parasthesia (pins and needles) around lips, hands, mouths
Convulsions
Arrhythmia
Tetany (muscles contract then cant relax)
Cats go numb
What is Chvostek’s sign and why is it used?
Tap the facial nerve (just below zygomatic arch) and facial muscle will twitch
Indicates hypocalcaemia
What is Trousseaus sign and why is it used?
Inflation of the BP cuff for several mins induces a carpopedal spasm
Indicates hypocalcaemia
What is it called when PTH levels are low?
Hypoparathyroidism
What are the 2 main causes of hypocalcaemia and how do they arise?
Low PTH levels (due to neck surgery, autoimmunity, magnesium deficiency, congenital)
Vit D deficiency
What are the 5 causes of Vit D deficiency?
Dietary insufficiency Inadequate sun exposure Liver disease Renal disease Vit D receptor defects (rare)
What is vit D deficiency called in children and in adults? What are the symptoms in each
Children- rickets (soft bones that bow)
Adults- osteomalacia (fractures, proximal myopathy)
What is the phrase we use to describe the symptoms of hypercalcaemia? Describe the symptoms
Stones, abdominal moans and psychic groans
Reduced neuronal excitability
Stones- renal effects ie kidney stones, renal colic
Abdominal moans- GI effects ie nausea, dyspepsia, constipation
Psychic groans- CNS effects ie coma, fatigue, depression
What are the causes of hypercalcaemia?
Primary hyperparathyroidism (too much PTH)
Malignancy (bone metastases activate osteoclasts and some cancers secrete peptides that act at PTH receptors)
Vit D excess (rare)
How is calcium distributed in the body?
99% in the skeleton and teeth
Very small amount of extracellular calcium that is tightly regulated
Why is calcium important in the body?
Muscle contraction
Bone strength
Intracellular 2nd messenger and coenzyme
Blood coagulation
Why are phosphates required in the body?
They are essential components of high energy compounds eg ATP, 2nd messengers and fundamental molecules eg RNA/DNA
What is the link between extracellular calcium and phosphate?
Their levels are inversely proportional to each other and they are regulated by the same hormones
What 2 forms does serum calcium exist as?
Unbound (ie free/ionised) and bound
What is the normal serum calcium level for unbound calcium and how much of total serum calcium is found unbound?
Normal level: 1.25mM
% of total serum calcium: 50%
What is the normal serum calcium level for bound calcium and how much of total serum calcium is found bound?
Normal level: 1.13 mM
% of total serum calcium: 45%
What is the other name by which vitamin D2 is known?
Ergocalciferol
What is the other name by which vitamin D3 is known?
Cholecalciferol
How do we gain vitamin D2?
Via diet
How do we gain vitamin D3?
Make it from sunshine in the skin
Describe the general process by which vitamin D is metabolised
Skin cells absorb UVB light from the sun
This triggers conversion of 7 dehydrocholesterol to pre vitamin D3 which is converted to vit D3
Vit D3 alongside vit D2 from diet is transported to the liver and hydroxylated at position 25 to form 25 hydroxylase which is not active
The enzyme 1 alpha hydroxylase carries out the 2nd hydroxylation step forming calcitriol, the active form of vitamin D
What type of sunlight does the skin absorb?
UVB
What 2 molecules are synthesised before vit D3 is made in the skin?
7 dehydrocholesterol and pre vitamin D3
Where is the first hydroxylation step of vit D metabolisation carried out?
Liver
Where is the second hydroxylation step of vit D metabolisation carried out?
Kidney
What is the name of the enzyme that carries out the second hydroxylation step during vitamin D metabolisation?
1 alpha hydroxylase
What is the active form of vitamin D known as?
Calcitriol
What type of receptor detects changes in calcium and where is it found?
G protein coupled receptors in parathyroid glands
What is the relationship between PTH secretion and serum calcium?
PTH secretion is inversely proportional to serum calcium levels
Where is calcitonin secreted from?
Parafollicular cells of the thyroid gland
