Calcium, Phosphate and Magnesium Homeostasis Flashcards
What is EDTA? What is its use?
A chemical that binds metal ions such as calcium, magnesium, lead and iron
What colour lid does a sample bottle containing EDTA have?
Purple
Function of EDTA in medicine?
- Prevent blood samples clotting
- Removes calcium and lead from the body
- Keeps bacteria from forming a biofilm
If a calcium sample is contaminated with EDTA, what can this result in?
This can cause a falsely low result; EDTA has bound to calcium
What tis the physiological importance of calcium?
- Blood clotting
- Muscle contraction
- Neuronal excitation
- Enzyme activity (Na/K ATPase, hexokinase etc.)
How is calcium involved in clotting?
Calcium ions (Ca2+) play a major role in the tight regulation of coagulation cascade that is paramount in the maintenance of haemostasis.
Other than platelet activation, calcium ions are responsible for complete activation of several coagulation factors, including coagulation Factor XIII (FXIII)3
Weight of calcium in human body?
Calcium accounts for 1 to 2 percent of adult human body weight.
Over 99 percent of total body calcium is found in teeth and bones.
Describe the distribution of calcium in the human body
99% bone
1% intracellular
0.1% extracellular
Regarding total plasma calcium:
a) What are normal ranges?
b) How is total plasma calcium distributed?
c) What form is biologically active?
d) What plasma protein is calcium predominantly bound to?
a) 2.2-2.6 mmol/L
b) 50% ionised ‘free’ Ca2+, 41% bound to plasma proteins, 9% complexed t anions
c) Ionised ‘free’ Ca2+
d) albumin
Above and below which levels for calcium is a medical emergency?
Calcium <1.6 or >3.5 mmol/L
How does low albumin levels affect calcium?
- Ionised calcium remains the same
- Protein-bound calcium decreases
- Total calcium decreases
- As albumin levels increases, so does total calcium
When should calcium levels be adjusted? Why?
The calcium level should be corrected in patients with low serum albumin levels:
Adjusted Ca = Total Ca + [(40 - Alb) x 0.025]
Why should calcium levels be adjusted in patients with low albumin?
Relationship between albumin and calcium isn’t valid at such a low value
What should be used for calcium measurement instead in patients with low albumin?
In these cases; recommend measuring ionised calcium on a point-of-care blood gas analyser.
Is phosphate predominantly intracellular or extracellular?
Intracellular
Physiological importance of phosphate?
o The P in ATP – our fuel!
o Intracellular signalling
o Cellular metabolic processes e.g. glycolysis
Structural importance of phosphate?
o Backbone of DNA
o Component of hydroxyapatite Ca₁₀(PO₄)₆(OH)₂
o Membrane phospholipids
Describe the distribution of calcium in the human body
85% bone
14% intracellular
1% extracellular
What are the 2 forms of phosphorus in the blood?
- Organic form (covalently bound) 70%
2. Inorganic form as phosphate 30%
If an analyte (e.g. calcium or phosphate) is above or below the reference range, what are the 3 main questions to ask?
- Is it due to increased/decreased intake?
- Is it due to increased/decreased output?
- Is it due to tissue redistribution/storage?
What are the 2 main controlling factors for calcium homeostasis?
o Parathyroid hormone (PTH)
o Vitamin D and metabolites
Where is PTH released from?
Released from 4 parathyroid glands in neck
What is PTH released in response to?
Low serum calcium
Which mineral is required for the secretion of PTH?
magnesium
PTH has 2 direct actions and 1 indirect action.
What are the 2 direct actions?
- Bone: drives resorption –> releases Ca and PO4 from bone mineral
- Kidney: increases reabsorption of Ca from filtrate but increases excretion of PO4
What is indirect action of PTH on kidneys?
Increases conversion of vitamin D to its active form –> this then increases Ca and PO4 absorption from the gut
What are the net effects of PTH on serum calcium and phosphate?
o Increase serum calcium
o Decrease serum phosphate (effect on kidneys is larger)
What is the feedback loop of Ca on PTH?
o High calcium inhibits PTH release by negative feedback (via CaSR)
o Low calcium stimulates PTH release
How does a high phosphate affected PTH release?
PTH release is also stimulated (to a lesser extent) by high phosphate
What is the active form of vitamin D?
1,25(OH)2
Calcium homeostasis is also affected by FGF23. What is this? How does it affect calcium?
FGF23 is a member of the fibroblast growth factor (FGF) family:
1) Suppresses activation of vitamin D by kidney
2) Increases renal phosphate excretion (i.e. suppresses reabsorption)
What is FGF23 secreted by?
Secreted by osteocytes in response to increase in active form of vitamin D
Calcium homeostasis is also affected by calcitonin.
How does calcitonin affect calcium levels?
What is calcitonin secreted by?
Secreted by c cells of thyroid gland in response to increased serum calcium
Opposes the effect of PTH by acting on osteoclasts to inhibit bone resorption
Function is usually insignificant in the regulation of normal calcium homeostasis
Calcium homeostasis is also affected by oestrogen.
What is effect of oestrogen on calcium?
Inhibits bone resorption; reduced bone density after menopause
What is calcium and phosphate homeostasis the result of a balance of?
o GI uptake
o Bone storage
o Renal clearance
What are the 2 ways humans get vitamin D?
- Obtained from diet
* Can be made from cholesterol by action of UV-B sunlight on skin
How is vitamin D synthesised in humans?
• Can be made from cholesterol by action of UV-B sunlight on skin
o This requires hydroxylation in liver (this is the main circulating form)
o This is further hydroxylated in kidney (this is now the active form)
What is the activation of vitamin D in the kidney stimulated by?
PTH
When measuring vitamin D levels, which form is measured? Why?
•The vitamin D hydroxylated by the liver is the one that is measured
o More stable
o Present in circulation at much greater concentration
What are the effects of vitamin D on the:
a) intestine?
b) bone?
c) immune cells
a) Increases absorption of Ca2+ and phosphate
b) Increases bone mineralisation
c) Induces differentiation
What are the effects of vitamin D on cancer?
Inhibits proliferation
Induces differentiation
Inhibits angiogenesis
What % of 4-18 year olds in the UK have insufficient vitamin D levels?
29%; recent resurgence of rickets