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Welcome back to the tasty morsels of critical care podcast.
It is with trepidation that I approach any topic that involves the negative feedback loops of endocrine control as I really struggle to keep it all straight in my head, but today I’m going to try and cover the basics of calcium in the critically ill from Oh Chapter 63.
We’ll start from some very basic physiology. 99% of the calcium is held in the bones. Of the calcium not in the bones, most of the rest is in the cells. So as an important starter, the serum level of calcium does not tell us much about overall levels in the body. In the plasma itself, 50% is ionised, 40% is plasma bound and 10% is chelated to various anions. There is a large gradient between the ionised calcium in the plasma and the tiny ionised fraction in the cells. Finally the ionised fraction is the active bit and the determining factor of endocrine regulation.
At a level somewhat below medical student level, calcium is controlled as follows. A low serum Ca stimulates PTH, this in turn stimulates osteoclastic activity and renal reabsorption. It also stimulates renal production of calcitriol (an active metabolite of vitamin D) which encourages gut absorption of calcium. Calcitonin produced by the thyroid acts as a kind of PTH antagonist dampening things down a bit if the calcium level gets too high.
Now let’s turn to hypercalcaemia, a fairly common diagnostic issue in the ICU. The major causes to consider are:
- Malignancy (both from bony mets and probably more commonly from PTHrP that mimics PTH in raising the Ca)
- High calcium following hypoCalcaemia (eg pancreatitis and recovery from rhabdo)
- primary hyperPTH
- granulomatous diseases such as sarcoid
Management of high calcium involves 2 mains steps
- increasing urinary excretion, either with fluids alone or fluids and loop diuretics. Though the addition of loops is somewhat controversial as loops themselves have been known to cause HyperCa.
- reduction in Ca resorption from bone. This can be done with bisphosphonates working by inhibiting osteoclasts. Or by calcitonin which inhibits osteoclasts and reduces renal reabsorption of calcium. Steroids can be helpful by reducing gut absorption and inhibiting the inflammatory production of calcitriol. Finally on the list is denosumab which as the name suggests is a monoclonal that prevents bone resorption
Hypocalcaemia on the other hand produces quite a prolonged differential including
- citrate (low ionised, high total)
- massive transfusion (which is just citrate again)
- high phos
- sepsis (multiple mechanisms including PTH suppression)
- thyroid or neck surgery
- low vitamin D (poor sun exposure, low intake, malabsorption, liver disease, renal failure)
- drug induced (bisphosphonates, propofol, EDTA, ethylene glycol, protamine, gentamicin)
- MRI contrast can cause a form of pseudo hypocalcemia (niche and irrelevant..)
Many of the above are associated with alkalosis and indeed a separate differential can be formed for HypoCa in the context of acidosis
- AKI
- tumour lysis
- rhabdomyolysis
- pancreatitis
- ethylene glycol
- hydrofluric acid
Management of hypocalcaemia is both straightforward in that you just replace the calcium but at the same time desperately complicated in that you need to treat the cause which is often incredibly challenging.
A final mention is warranted of Vitamin D in critical illness given that it has been spread across the literature in recent years and is currently subject to lots of ongoing work. It is thought to have what is best described as “pleiotropic effects”. It is also similar to cortisol in that serum levels probably don’t reflect cellular activity. Either way there is no clear role for it in the ICU as yet.
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