Calcium and Phosphate Metabolism 15/11 Flashcards
(26 cards)
Why is plasma calcium (especially ionised calcium) maintained in narrow limits?
To maintain the integrity of the neuromuscular system
What is hypocalcaemia and how does it effect the excitability of neurons?
Low plasma Ca2+ levels
Increases neuronal permeability to Na+ = neurons depolarise = nervous system becomes hyperexcitable
What is hypercalcaemia and how does it effect the excitability of neurons?
High plasma Ca2+ levels
Depresses neuromuscular activity
What are the 3 compartments of plasma calcium?
- Ionized calcium Ca2+ - biologically active (50% of total Ca)
- Complexed calcium - bound to phosphate, citrate, bicarbonate and other anions (5% of total Ca)
- Protein-bound calcium - bound to albumin, globulins and lipoproteins (45% of total Ca)
Describe the intracellular role of ionized calcium.
It is a critical intracellular signalling entity through movement from one intracellular compartment to another
It is part of the intracellular matrix holding cells together at tight junctions
What are the inter and intra individual ranges for plasma calcium.
Interindividual (population) range = 2.10 - 2.55mmol/L
Intraindividual (individual) range = +/- 0.12mmol/L
What are the inter and intra individual ranges for plasma phosphate.
Interindividual (population) range = 0.6 - 1.2mmol/L
Intraindividual (individual) range = +/- 0.15mmol/L
Describe the CaSR and where is it expressed?
A G-protein 7TM receptor that responds to ionized calcium levels across a narrow concentration range
Expressed on parathyroid and thyroid glands, kidney, bone, gut, nervous system and many other organs
What are the 3 major organs responsible for Ca homeostasis and what is their role?
Kidney - filters 250mmol of Ca per day but only 96-98% is reabsorbed
Bone - provides Ca to ECF during fasting (stores Ca)
Small intestine - involves saturable (vitamin D mediated) and non saturable absorption mechanisms
How is calcium lost in the body and why is it an essential daily nutrient.
Ca is lost from the kidney (due to the inability to reabsorb 100% of filtered Ca), the intestine (lost through intestinal secretions and inability to reabsorb 100%), and the skin through sweat
The bone is a storage bank for calcium and daily Ca intake must be sufficient to maintain bone stores to meet its mechanical and structural roles of the body
What are the 3 calciotropic (calcium regulating) hormones?
- Parathyroid hormone (PTH)
- Calcitonin
- Vitamin D
Where is PTH produced from?
Parathyroid gland
Where is Calcitonin produced from?
Thyroid gland
How does PTH regulate Ca levels?
Responds to a fall in Ca2+ Acts on kidney - increase Ca reabsorption - decrease phosphate reabsorption - stimulate synthesis of 1,25D Acts on bone - acts on osteoblasts (bone forming) to activate osteoclastogenesis (osteoclast formation) and stimulates resorption on bone by osteoclasts
How does Calcitonin regulated Ca levels?
Responds to increase in Ca2+ Acts on kidney - inhibits tubular reabsorption of Ca Acts on bone - receptors localized on osteoclast cell surface inhibit osteoclast bone resorption of Ca
How is Vitamin D synthesized?
UV rays act on 7-dehydrocholesterol to produce vitamin D3 - the liver converts vitamin D3 into 25D - the kidney converts 25D to active 1,25(OH)2D which circulates in the plasma
How does Vitamin D regulate Ca levels?
Responds to increased and decreased Ca levels
Responds to increased levels by acting on the PTG to inhibit PTH synthesis
Responds to decreased levels by
Acting on intestine - to regulate saturable Ca absorption system
Acting on kidney - increase tubular reabsorption of Ca
Acting on bone - acts on osteoblasts to increase osteoclast bone resorption
How is body phosphorous estimated?
By measuring total inorganic phosphate anions in plasma
Where does regulation of plasma phosphate levels occur at?
The kidneys
What causes hyperphosphataemia?
Chronic Kidney Disease
Diabetes (deranged glucose metabolism)
Release of phosphate from RBC haemolysis
What causes hypophosphataemia?
Dialysis or renal leak
Starving or vomiting
High CHO meal
What are the 3 hormones that regulate phosphate levels?
- FGF23.
- PTH
- Vitamin D
Where is FGF23 synthesized?
Osteoclasts
How does FGF23 control phosphate levels?
Lowers plasma phosphate levels by decreased renal tubular reabsorption
Lowers plasma 1,25D levels by inhibiting renal synthesis (conversion of 25D to 1,25D)
