Calcium, phosphate and magnesium Flashcards
What can imbalances in calcium, phosphate and magnesium cause?
number of serious clinical complications including arrhythmias, seizures, coma and respiratory arrest
What are the roles of calcium?
cell signalling and 2nd messenger
neurotransmitter and hormone release
exocytosis of proteins
muscle contraction
blood clotting
biomineralization
What are the roles of phosphate ?
integral component DNA and RNA
energy source for cellular functions (ATP)
What are the roles of magnesium?
DNA and protein synthesis, oxidative phosphorylation, enzyme function, ion channel regulation and neuromuscular excitability
What are the normal serum conc for Ca,HPO4, Mg?
Ca = 2.2-2.6mmol/L HPO4 = 0.8-15 Mg = 0.7-1
What organ systems play an important role in metabolism ?
kidney
skeleton
GI tract
parathyroid gland
What regulatory factors that play an important role in the metabolism of Ca, HPO4 and Mg?
PTH Vit D FGF-23 PTH related protein calcitonin
What is the Ca/Mg sensing receptor?
member of G coupled receptor family= important regulator of Ca and Mg homeostasis
What does the feedback mechanism for calcium rely on and why is this important?
free (ionised) fraction = physiologically important
- [calcium] depends on [protein]
- for each g of albumin it binds 0.02 mmol/L calcium
What does a low or high pH cause in terms of calcium levels?
decreased pH increases Ca
increased pH decreases Ca
What are common causes of hypocalcaemia?
chronic and acute renal failure vit D deficiency hypoparathyroidism acure pancreatitis magnesium deficiency artefact - wrong tube
What happens when there is low plasma Ca?
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
What is rickets/osteomalacia?
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
What are the signs/symptoms of rickets and osteomalacia?
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
How does the treatment of hypocalcaemia vary?
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
What happens when you have hypercalcaemia?
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
What are the causes of hypercalcaemia?
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
What are the different types of hyperparathyroidism?
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
What are the clinical features of primary hyperparathyroidism?
most are asymptomatic
younger pts may develop:
- osmotic symptoms = thirst, polyuria, constipation
- aches and pains
- neuropsychiatric = lethargy/depression, confusion/coma
- renal stones, osteoporosis. pancreatitis
What are the mechanisms of malignancy associated hypercalcaemia?
humoral hypercalcaemia
- PTHrP related or non-PTHrP related
Bone invasion
Rare causes = drug related (retinoids), immobilisation, PTH carcinoma
What is the tx for malignancy associated hypercalcaemia?
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
What happens when you have low PO4?
reduce PTH release so this will increase PO4 reabsorption in the kidney, and also increase release from bone, increase gut absorption
What are the causes of hyperphosphataemia?
decreased renal excretion
acute phosphate load
redistribution to ECS
pseudohyperphosphataemia
What are the clinical features of hyperphosphataemia?
most pts are asymptomatic
Acute
- tetany - hypocalcaemia, seizures and hypotension
Chronic
- secondary hyperparathyroidism - soft tissue calcification- kidneys, cornea, skin
What are the causes of Mg deficiency?
GI disorders
renal loss
endocrine and metabolic disorders
What are the clinical manifestations of hypomagnesia?
<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
What is usually the cause of hypomagnesemia?
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
What is gitelman syndrome?
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
What causes magnesium excess?
acute renal failure
severe diabetic ketoacidosis
addison’s disease
supplements
What can be seen clinically with magnesium excess?
loss of deep tendon reflexes
increased PR interval
but only a problem when >2
How should you monitor patients with severe mineral imbalance?
fluid balance - fluid intake - output - daily weight ECG monitor (arrhythmias) renal function and electrolytes at least daily
