Calcium, phosphate and magnesium

Question 1

What can imbalances in calcium, phosphate and magnesium cause?

Answer 1

number of serious clinical complications including arrhythmias, seizures, coma and respiratory arrest

Question 2

What are the roles of calcium?

Answer 2

cell signalling and 2nd messenger

neurotransmitter and hormone release

exocytosis of proteins
muscle contraction
blood clotting
biomineralization

Question 3

What are the roles of phosphate ?

Answer 3

integral component DNA and RNA

energy source for cellular functions (ATP)

Question 4

What are the roles of magnesium?

Answer 4

DNA and protein synthesis, oxidative phosphorylation, enzyme function, ion channel regulation and neuromuscular excitability

Question 5

What are the normal serum conc for Ca,HPO4, Mg?

Answer 5

Ca = 2.2-2.6mmol/L
HPO4 = 0.8-15
Mg = 0.7-1

Question 6

What organ systems play an important role in metabolism ?

Answer 6

kidney
skeleton
GI tract
parathyroid gland

Question 7

What regulatory factors that play an important role in the metabolism of Ca, HPO4 and Mg?

Answer 7

PTH
Vit D
FGF-23
PTH related protein 
calcitonin

Question 8

What is the Ca/Mg sensing receptor?

Answer 8

member of G coupled receptor family= important regulator of Ca and Mg homeostasis

Question 9

What does the feedback mechanism for calcium rely on and why is this important?

Answer 9

free (ionised) fraction = physiologically important

• [calcium] depends on [protein]
• for each g of albumin it binds 0.02 mmol/L calcium

Question 10

What does a low or high pH cause in terms of calcium levels?

Answer 10

decreased pH increases Ca

increased pH decreases Ca

Question 11

What are common causes of hypocalcaemia?

Answer 11

chronic and acute renal failure 
vit D deficiency 
hypoparathyroidism 
acure pancreatitis 
magnesium deficiency 
artefact - wrong tube

Question 12

What happens when there is low plasma Ca?

Answer 12

stimulates PTH release which acts on bone to increase Ca release, acts on Kidney to increase reabsorption of Ca and acts on gut to increase Ca absorption

Question 13

What is rickets/osteomalacia?

Answer 13

deficiency of active vit D
- rickets = affects growing skeleton
- osteomalacia = affects adult skeleton
bone is unduly soft in both

lack of mineralization of collagen component of bone (osteoid)
failure to absorb sufficient calcium from GIT

dietary/lack of sunligh, rarely inherited

Question 14

What are the signs/symptoms of rickets and osteomalacia?

Answer 14

rickets - osteoid at growth plate is weak = bow legs
growth plate expands to compensate = swollen joints

osteomalacia = bon pain and pseudofractures

tx= vit D replacement

Question 15

How does the treatment of hypocalcaemia vary?

Answer 15

type and route of tx depends on:
- state of pt symptoms
(acutely ill with neuromuscular symptoms = IV calcium, whereas mildly symptomatic - oral calcium)
level and duration of calcium
underlying cause - e.g. if vit D deficient then replace that and if hypoparathyroisim then add 1,25 D3 products

Question 16

What happens when you have hypercalcaemia?

Answer 16

reduce secretion of PTH and increase calcitonin release to reduce bone resorption
also increase urinary excretion of calcium and reduce ca absorption in the intestine

Question 17

What are the causes of hypercalcaemia?

Answer 17

primary hyperparathyroidism (high PTH)
malignancy (low PTH)

rare

• familial hypocalcuric hypercalcaemia
• sarcoid (low PTH)
• drugs - vit D toxicity
• prolonged immobilisation (low PTH)
• adrenal failure (low PTH)
• milk alkali

Question 18

What are the different types of hyperparathyroidism?

Answer 18

primary
- increased secretion of PTH = single or multiple adenoma (common), parathyroid hyperplasia (less common), parathytoid carcinoma

Secondary

• renal failure
• vit D deficiency

Tertiary
- as a result of prolonged secondary hyperparathyoidism - renal transplant

Question 19

What are the clinical features of primary hyperparathyroidism?

Answer 19

most are asymptomatic
younger pts may develop:
- osmotic symptoms = thirst, polyuria, constipation
- aches and pains
- neuropsychiatric = lethargy/depression, confusion/coma
- renal stones, osteoporosis. pancreatitis

Question 20

What are the mechanisms of malignancy associated hypercalcaemia?

Answer 20

humoral hypercalcaemia
- PTHrP related or non-PTHrP related

Bone invasion

Rare causes = drug related (retinoids), immobilisation, PTH carcinoma

Question 21

What is the tx for malignancy associated hypercalcaemia?

Answer 21

if renal failure = dialysis with low ca bath
aggressive IV hydration - if volume overload then give loop diuretics
IV bisphosphonate +/- calcitonin
refractory cases - gallium nitrate or denosumab

Question 22

What happens when you have low PO4?

Answer 22

reduce PTH release so this will increase PO4 reabsorption in the kidney, and also increase release from bone, increase gut absorption

Question 23

What are the causes of hyperphosphataemia?

Answer 23

decreased renal excretion
acute phosphate load
redistribution to ECS
pseudohyperphosphataemia

Question 24

What are the clinical features of hyperphosphataemia?

Answer 24

most pts are asymptomatic
Acute
- tetany - hypocalcaemia, seizures and hypotension

Chronic
- secondary hyperparathyroidism - soft tissue calcification- kidneys, cornea, skin

Question 25

What are the causes of Mg deficiency?

Answer 25

GI disorders
renal loss
endocrine and metabolic disorders

Question 26

What are the clinical manifestations of hypomagnesia?

Answer 26

<0.74
non-specific lethargy and weakness
increased neuromuscular excitability e.g. tremors, carpopedal spasm, muscle cramps, tetany, generalised seizures
can cause cardiac arrhythmias - A and V tachycardia, prolonged QT interval and torsades depointes

Question 27

What is usually the cause of hypomagnesemia?

Answer 27

decreased oral intake, increased GIT or renal losses
acquired disorder - only in rare instances - does have an underlying hereditary aetiology

urinary magnesium helps to differentiate renal from extrarenal causes of magnesium wasting

Question 28

What is gitelman syndrome?

Answer 28

hypomagnesemia and renal magnesium wasting are distinctive features
AR caused by mutation in SLC12A3 gene encoding sodium chloride cotransporter which is expressed in the DCT

Question 29

What causes magnesium excess?

Answer 29

acute renal failure
severe diabetic ketoacidosis
addison’s disease
supplements

Question 30

What can be seen clinically with magnesium excess?

Answer 30

loss of deep tendon reflexes
increased PR interval
but only a problem when >2

Question 31

How should you monitor patients with severe mineral imbalance?

Answer 31

fluid balance
- fluid intake 
- output
- daily weight 
ECG monitor (arrhythmias) 
renal function and electrolytes at least daily