T5-L5: Calcium, Phosphate and Magnesium Homeostasis

Question 1

What is the physiological role of Calcium?

Answer 1

• Blood clotting
• Muscle contraction
• Neural Excitation
• Enzyme Action
• Structure in bone

Question 2

Where is Calcium found in the body? What levels should we detect?

Answer 2

• 99% found in Bone
• 1% Found intracellularly
• 0.1% found Extracellularly

We should expect 2.2 - 2.6 mmol/L. Where 41% is in plasma, 50% bound to protein mainly albumin and 9% in comely anions.

Question 3

What levels of calcium is considered a medical emergency?

Answer 3

Calcium < 1.6 or > 3.5 mmol/L is a medical emergency requiring immediate treatment!

Question 4

What is adjusted calcium?

Answer 4

When the concentration of albumin changes - e.g. low due to surgery/nephrotic syndrome causes a reduce in the amount bound to albumin and the number of calcium but the fraction of ionised calcium remains the same.

As albumin increases the total calcium increases. We report adjusted calcium where calcium is corrected for changes in albumin. 

This give the value of what we would expect the calcium to be if the albumin was normal. The reference range is the same for total calcium (2.2. - 2.6). The equation is not valid if calcium folds below 20g/L. In this case we would measure ionised calcium.

Question 5

What is the physiological role of Phosphate?

Answer 5

• Part of ATP
• Intracellular signalling
• Cellular metabolic processes such as glycolysis
• Important in DNA, hydroxyapatite in the brain
• Membrane phospholipids

Deficiency can be fatal due to failure of respiratory muscles.

Question 6

Where is Phosphate found in the body? What levels should we detect?

Answer 6

• 85% in bones
• 14% Intracellularly
• 1% Extracellular - where 70% is found in the organic form covalently bound such as in phospholipids. 30% in the inorganic from.

Reference range is 0.8-1.5 mmol/L

Question 7

What are the key controlling factors in Calcium homeostasis?

Answer 7

• PTH
• Vitamin D and metabolites

Calcium and phosphate homeostasis is as result of a balance between GI uptake, bone storage, renal clearance.

Question 8

What is the role of PTH?

Answer 8

Magnesium is required for the release of PTH. PTH is released in low calcium.

1. PTH acts on bone to drive bone resorption of calcium and phosphate from the bone mineral
2. PTH acts to increase the resorption of calcium and increase the filtrate excretion of PO4 
3. PTH also acts on the kidney to increase conversation of Vitamin D to its active form which can increase calcium and phosphate absorption

PTH increase serum calcium and decreases serum phosphate. The effect is predominantly on the kidneys.

Question 9

How is Vitamin D metabolised?

Answer 9

Can be obtained form the diet and from cholesterol from UV on the skin. This uses an enzyme on the liver. It undergoes 2 hydroxylation to get to the active form.

Renal hydroxylation is stimulation from PTH. There is also some affect on negative feedback of Vitamin D on PTH. We measure the 25-hydroxyvitamin D which is more stable and more present in the circulation.

	Active vitamin D acts on the enterocytes to enhance absorption of calcium and phosphate. It is also important in bone health and effects in the immune system and anti-oncogenic effects.

Question 10

What factors can affect Viatmin D level?

Answer 10

• Ethnicity
• Latitude
• Season
• Suncreen
• Diet
• Body fat and BMI
• Clothing
• Age

Question 11

What other factors, to a lesser degree to PTH, regulate calcium and phosphate homeostasis?

Answer 11

• FCF23 (Fibroblast Growth Factor 23)- Secreted by osteocytes in response to the increase in active Vitamin D. Suppresses Vitamin D and increases phosphate excretion
  - Calcitonin - opposes the effects of PTH by acting on osteoclasts to inhibit bone resorption. Its function so insignificant in the regulation of normal calcium homeostasis
  - Oestrogen- inhibits bone formation

Question 12

What are common causes of hypocalcaemia?

Answer 12

• Vitamin D deficiency (liver or renal disease, can be dietary, due to sunlight or malabsorption)
• Inadequate dietary calcium intake
• hypoalbuminaemia
• High phosphate
• Hypoparathyroidism
• Hypomagnesaemia
• Spurious causes - contamination

Question 13

What are signs and symptoms of hypocalcaemia

Answer 13

• Tetany - Latent tetany can be demonstrated by Chvostek’s sign or Trouseau’s sign
  
  • Paraesthesia in the extremities
  • Cramps
  • Convulsions
  • Psychosis

Question 14

What are common causes of hypercalcaemia?

Answer 14

• Hyperparathyroidism - commonly caused by a parathyroid adenoma
  
  • Malignancy - some tumours can secrete PTH related peptide which has a similar effect. Tumour secreting osteoclast-activating cytokines (with or without bone mets), cells with 1alpha hydroxylase activity (activation of Vitamin D)

These make up 90%
Other causes include drugs, vitamin D excess, bone disease and hyperthyroidism.

Question 15

What are signs and symptoms of hypercalcaemia?

Answer 15

• Stones
• Bone pain and osteoporosis
• Moans - lethargy, fatigue and depression
• Groans (GI) - abdominal pain, constipation, nausea and vomiting

Question 16

What is the first line biochemical investigation of abnormal calcium?

Answer 16

• Simultaneous measurement of calcium and PTH
  
  • Look at albumin and look at adjusted calcium
  • Measure ionised calcium on blood gas analyser if calcium is too low
  • Look at bone profile (ALP - but can also be hepatic - adjusted calcium)
  • Vitamin D
    Magnesium

Question 17

Give causes of phosphate deficiency.

Answer 17

• Diet (intake) - malnutrition, malabsorption and alcoholism
• Excess loss - hyperPTH (drives phosphate excretion), renal tubular damage etc.
• Refeeding syndrome

Question 18

What are the signs and symptoms of phosphate deficiency?

Answer 18

• Haemolysis, thrombocytopenia and poor granulocyte function
  - Severe muscle weakness, respiratory muscle failure and rhabdomyolysis
  - Convulsions, coma, death
  - Chronic phosphate deficiency will cause rickets (children) / osteomalacia (adults)
  - If confirmed, treatment for acute phosphate deficiency is essential :
  • Oral phosphate
  •IV phosphate

Question 19

What is the most common cause of hyperphosphateamia?

Answer 19

Renal failure (due to lower filtration rate). It can also be caused by hypothyroidism. Signs and symptoms are due to hypocalcaemia.

Question 20

What is the role of Magnesium?

Answer 20

• Cofactor for ATP
  
  • Neuromuscular excitability
  • Enzymatic function
  • Regulates ion channels
  • Comprises 0.5 – 1% of bone matrix

Question 21

Where is Magensium found in the body? What levels should we detect?

Answer 21

• 54% in bone
• 45% Intracellularly
• 1% Extracellularly - of this 60% is free Magnesium, 25% bound to proteins predominately albumin and 15% bound to complex ions.

Question 22

Why is hypermagnesaemia rare?

Answer 22

It is are to see magnesium high above the reference range as the kidneys have a large capacity to get rid of excess magnesium.

Question 23

What can a very low magnesium level lead to?

Answer 23

Hypocalcaemia as it will inhibit PTH release.This will be resistant to supplementation until magnesium has been replaced.

Low magnesium can stimulate a release in PTH; a high magnesium can inhibit PTH (calcium is the most potent stimulus).

Question 24

What is hypomagesaemia often associated with?

Answer 24

• This is fairly common amongst hospital patients

Often associated with hypokalaemia, hyponatraemia, hypophosphatemia and hypocalcaemia

Question 25

What are causes of hypomagesaemia?

Answer 25

• Malnutrition (especially in alcoholics), malabsorption or inadequate total parental nutrition
• Renal loss - due to rare inherited diseases or due to drugs such as some antibiotics
• GI Loss - diarrhoea, (PPIs)
• Redistribution into cells during refeeding syndrome
• Spurious causes EDTA will collate magnesium

Question 26

What are signs and symptoms of hypomagesaemia?

Answer 26

• Can affect various systems:
  
  • Neuromuscular hyperexcitability (tremor, tetany, convulsions), muscle weakness,
  • CNS - depression, psychosis
  • Cardiovascular – ECG changes, reduced contractility, arrythmia
  • GI – nausea and anorexia
    Biochemical consequences: hypokalemia, hypocalcemia, with associated signs and symptoms

Question 27

What is refeeding syndrome?

Answer 27

This potentially lethal condition can be defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients. undergoing refeeding, whether orally, enterally, or parenterally.

During prolonged restriction of carbohydrate intact. Insulin is decreased and glucagon increased. Fat and protein are metabolised to produce energy. this leads to an intracellular loss of electrolytes  in particular as phosphate, magnesium and potassium. The serum levels do not drop much. Upon carbohydrate intake, insulin is released glycolysis is started requiring phosphate, magnesium and phosphate to move into the cells along with glucose. This leads to a notable drop in these minerals causing many problems such as heart dysfunction and respiratory failure.