Theme 5: Calcium, Phosphate and Magnesium homeostasis Flashcards
What is calcium physiologically important for?
- blood clotting
- muscle contraction
- neuronal excitation
- enzyme activity
What is calcium structurally important for?
hydroxyapatite - Ca₁₀(PO₄)₆(OH)₂ - is the predominant mineral in bone
Total plasma calcium (circulating calcium) is in 3 forms, what are they?
- ionised “free” ca2+ (50%) –> biologically active
- bound to plasma proteins (41%) –> predominantly bound to albumin
- Complexed to anions (9%) e.g phosphate, bicarbonate
How much of total body calcium is in bone?
99%
What is the relationship between total calcium and albumin?
as albumin increases, total calcium increases
What is adjusted calcium?
as total calcium concentration depends on albumin concentration, we report adjusted calcium, where calcium is corrected for changes in albumin
How do we calculate adjusted calcium?
Adjusted Ca = total Ca + [(40-Alb]) x 0.025
What is the reference range for adjusted calcium/ total plasma Ca
2.2-2.6 mmol/L
What is the physiological importance of phosphate?
- the P in ATP - our fuel!
- intracellular signalling
- cellular metabolic processes e.g glycolysis
What is the structural importance of phosphate?
- backbone of DNA
- component of hydroxyapatite
- membrane phospholipids
How much of total body phosphorous is in bone?
85% (rest is intracellular)
What two forms can phosphorous be found in the blood?
- organic form (covalently bound) - 70%
- inorganic form as phosphate - 30%
What are the two key controlling factors of calcium homeostasis?
- parathyroid hormone
- vitD and metabolites
When is PTH secreted?
when calcium is low (magnesium is also required for secretion of PTH)
What are actions of PTH?
- PTH acts on bone to drive resorption of Ca and PO4
- PTH acts on kidneys to increase reabsorption of Ca but increase excretion of PO4
- AND acts on kidneys to increase conversion of VitD to active vitD which increases Ca and PO4 absorption from the gut
What is the net effect of PTH is to?
- increase serum calcium
- decrease serum phosphate
How do we obtain VitD?
- from diet (esp oily fish)
- from cholesterol from action of UV-B sunlight on skin
What is the main circulating form of Vitd?
25-hydroxy vit D - this is what we measure
For bone health, how much 25-OH VitD is sufficient?
50-99 nmol/L
What factors affect your VitD level?
- season
- latitude/climate
- clothing
- use of sunscreen
- time spent indoors/outdoors
- skin tone
- age
- diet
- body fat & BMI
- malabsorption
What are the other regulators of calcium and phosphate homeostasis (other than PTH and VitD)
- FGF23 (fibroblast growth factor 23) - increases renal phosphate excretion
- calcitonin - opposes the effect of PTH by acting on osteoclasts to inhibit bone resoroption
- oestrogen - inhibits bone resorption
Give 6 causes of hypocalcaemia
- VitD deficiency
- Inadequate dietary calcium intake
- Hypoalbuminaemia
- High phosphate
- Hypoparathyroidism
- Spurious cases e.g EDTA contamination
What are the signs and symptoms of hypocalcaemia?
- tetany (muscle spasms)
- paraesthesia in the extremities
- cramps
- convulsions
- psychosis
How might tetany (muscle spasms) as a result of hypocalcaemia be demonstrated?
- chvostek’s sign = tapping on the facial nerve causes twitching of facial muscles
- trousseaus sign = compression of forearm causes painful spasm of wrist and hand
In a patient with VitD deficiency, what would the calcium and PTH levels be?
PTH will be increased in response to low calcium
What are 6 causes of hypercalcaemia?
- Hyperparathyroidism (most common)
- Malignancy (most common)
- tumours secreting PTH - Medications
- VitD excess
- hyperthyroidism
- bone disease / immobilisation
What are the signs and symptoms of Hypercalcaemia (stones, bones, moans and groans)
Stones:
-renal stones due to hypercalciuria, causing renal colic
Bones:
-bone pain and osteoporosis
Moans:
-lethargy, fatigue, depression
Groans:
-abdominal pain, constipation, nausea, vomiting
What are the first line biochemical investigations for hypo/hypercalaemia
- Ca & PTH
- adjusted Ca
- bone profile (adjusted calcium, phosphate, ALP)
- VitD
- magnesium
What are the causes of phosphate deficiency?
- low intake - malnutrition, malabsorption, alcoholism
- excess losses - hyperparathyroidism, renal tubular damage, diarrhoea
- ECF/ICG redistribution
What are the signs and symptoms of phosphate deficiency?
- haemolysis, thrombocytopenia and poor granulocyte function
- severe muscle weakness, respiratory muscle failure and rhabdomyolysis
- convulsions, coma, death
- chronic phosphate deficiency will cause rickets/osteomalacia
What are the common causes of hyperphosphataemia?
- renal failure: AKI and CKD
- hypoparathyroidism
What is the physiological importance of magnesium?
- cofactor for ATP - our fuel
- neuromuscular excitability
- enzymatic function
- regulates ion channels
How is total magnesium distributed in the body?
- bone (54%)
- intracellular (45%)
- extracellular (1%)
What are the 3 forms of magneisum found in the blood?
- ionised “free” Mg2+
- bound to plasma protein (mostly albumin)
- complexed to anions e.g phosphate, bicarbonate
Where does homeostasis of magneisum occur?
predominatly in the kidneys
How would severe hypomagnesaemia cause hypocalcaemia?
PTH release is magnesium-dependent, so severe hypomagnesaemia will inhibit PTH release and cause hypocalcaemia
What are the causes of hypomagneaemia?
inadequate intake:
- malnutrition
- malabsorption
renal loss:
-drugs e.g antibiotics, chemotherapy, diuretics
GI loss:
- diarrhoea
- PPIs
refeeding syndrome and EDTA contamination also could cause hypomagnesia
What are the signs and symptoms of magnesium depletion?
- neuromuscular hyperexcitability (tremor, tetany, convulsions), muscle weakness
- CNS - depression/psychosis
- cardiovascular - ECG changes, reduced contractility, arrythmias
- GI - nausea and anorexia
Why is hypermagneseamia rare?
kidneys have a large capacity to excrete excess
What levels of calcium is thought of as a medical emergency, requiring immediate treatment?
calcium > 3.5 or < 1.6
