Calcium Flashcards
HYPERCALCAEMIA - Causes
Hypercalcaemia: causes
The most common causes of hypercalcaemia are malignancy (bone metastases, myeloma, PTHrP from squamous cell lung cancer) and primary hyperparathyroidism
Other causes include
- Sarcoidosis*
- Vitamin D intoxication
- Acromegaly
- Thyrotoxicosis
- Milk-alkali syndrome
- Drugs: thiazides, calcium containing antacids
- Dehydration
- Addison’s disease
- Paget’s disease of the bone**
*other causes of granulomas may lead to hypercalcaemia e.g. Tuberculosis and histoplasmosis
**usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
HYPERCALCAEMIA - Mx
Hypercalcaemia: management
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates
steroids in sarcoidosis
There is a limited role for the use of furosemide in hypercalcaemia. It may be useful in patients who cannot tolerate aggressive fluid rehydration
Hypocalcaemia - Causes
Hypocalcaemia: causes and management
The clinical history combined with parathyroid hormone levels will reveal the cause of hypocalcaemia in the majority of cases
Causes
vitamin D deficiency (osteomalacia)
chronic renal failure
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
Acute pancreatitis may also cause hypocalcaemia. Contamination of blood samples with EDTA may also give falsely low calcium levels
Hypocalcaemia - Mx
Management
acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause
Hypocalcaemia and Alcoholism - Example Question
You are asked to review a 42- year- old alcoholic who has been admitted to the medical ward following 48hrs of vomiting, generalised muscle weakness and palpitations. Despite two calcium infusions, the most recent measured calcium is still 1.89 mmol/l. On examination his blood pressure is 95/60 mmHg, pulse is 95 beats per minute and regular. You note intermittent runs of SVT on his cardiac monitor.
Other urea and electrolytes are shown below:
Na+ 132 mmol/l K+ 3.7 mmol/l Urea 5.4 mmol/l Creatinine 82 µmol/l Glucose 5.2 mmol/l
Which of the following is the most appropriate next step?
IV calcium > IV magnesium IV potassium IV phosphate IV glucose
Long term alcoholism as well as leading to falls in serum calcium, can also lead to significant falls in magnesium, which can account both for the persistently decreased calcium despite replacement, and for the runs of SVT seen here. The most appropriate next step is magnesium replacement, which is likely to facilitate both an improvement in calcium and resolution of SVT.
Further IV calcium will be ineffective without first replacing magnesium, and potassium is within the normal range, as is glucose. Phosphate replacement may be required in the treatment of alcoholism, but this is usually in the context of refeeding syndrome.
Hypocalcaemia - Post Parathyroidectomy Cx: Example Question
A 50-year-old woman with a history of Grave’s disease is reviewed on the surgical ward some 12hrs after parathyroidectomy. She has begun suffering from episodes of carpopedal spasm and pins and needles affecting both hands and around her mouth. On examination on the ward, her blood pressure is 115/72 mmHg, and pulse is 88 beats per minute. Her serum calcium is measured at 1.85 mmol/l.
Which of the following is the most appropriate intervention?
Intravenous diazepam > Intravenous calcium Intravenous magnesium Oral calcium Oral vitamin D
This patient has symptomatic hypocalcaemia, most likely due to an acute fall in parathyroid hormone after surgery. This is considered a medical emergency and calcium replacement IV is essential:
IV calcium gluconate is administered initially with 20 ml of 10% calcium gluconate in 50-100 ml of 5% dextrose IV, given over 10 minutes with ECG monitoring.This can be repeated until the patient is asymptomatic. It should be followed up with a calcium gluconate infusion where 100ml of 10% calcium gluconate is diluted in 1 litre of normal saline or 5% dextrose and infused at 50-100 ml/hr.
Not intervening with respect to the electrolyte disturbance risks significant sequelae including cardiac arrhythmia, diazepam is therefore not appropriate. IV magnesium is most useful where hypocalcaemia is resistant to correction, and oral interventions would take too long to elevate serum calcium levels.
Hypercalcaemia Mx - Example Question
A middle age woman is being treated for symptomatic hypercalcaemia associated with a squamous cell lung cancer (serum calcium 3.60 mmol/L). She is slow to respond to initial measures of saline hydration and intravenous pamidronate. Whilst awaiting surgical resection for her underlying cancer what may be the next best step in her management?
Na+ 142 mmol/l K+ 4.3 mmol/l Urea 7.0 mmol/l Creatinine 89 µmol/l Glucose 4.8 mmol/l
What is the most appropriate management?
High dose loop diuretics
> Calcitonin 4 units/kg
Insulin actrapid 50 units in 50% dextrose
IV colloid administration instead of crystalloid
Plasma exchange
General symptoms of hypercalcaemia may include malaise, lethargy, depression, dehydration and can lead to depressed consciousness. Bone pain and abdominal pain may feature and can be summarised by the classic ‘bones, stones, moans and abdominal groans’.
Alongside searching for the underlying cause, management initially involves aggressive rehydration, typically 4-6 L saline on the first day. Bisphosphonates act by interfering with osteoclastic bone resorption and typically IV pamidronate is used at a dose of 60-90mg over 2-4 hours. Calcitonin (extracted from salmon) also interferes with osteoclast activity as well as increasing renal calcium excretion.
Diuretics may lead to further dehydration. Dialysis may be a last line treatment for life threatening hypercalacemia, but not plasma exchange.
Familial Benign Hypocalciuric Hypercalcaemia
Familial benign hypocalciuric hypercalcaemia
Familial benign hypocalciuric hypercalcaemia is a rare autosomal dominant disorder characterised by asymptomatic hypercalcaemia. It is due to a defect in the calcium sensing receptor
Familial Benign Hypocalciuric Hypercalcaemia - Example Question
A 60-year-old man attends a medical health check-up at his GP surgery. He was fit and well with a past medical history of childhood asthma and osteoarthritis in his fingers. His observations were included a blood pressure of 129/80 mmHg, pulse of 82 bpm, and oxygen sats of 97%.
Blood tests were performed and revealed:
Hb 138 g/l Platelets 190 * 109/l WBC 7.6 * 109/l Na+ 139 mmol/l K+ 3.9 mmol/l Urea 4.1 mmol/l Creatinine 9.2 µmol/l Bilirubin 15 µmol/l ALP 52 u/l ALT 26 u/l γGT 58 u/l Albumin 40 g/l Serum corrected calcium 2.77 mmol/L Serum phosphate 0.90 mmol/l Parathyroid hormone 5.9 pmol/L normal range 1.2-5.8 pmol/L
A 24 hour urinary calcium test was performed based on the results above and revealed a result of 0.5 mmol/24 hours (normal range 2.4-7.4 mmol/24 hours)
What is the most likely diagnosis?
Primary hyperparathyroidism Secondary hyperparathyroidism Vitamin D toxicity Multiple endocrine neoplasia type A > Familial benign hypocalciuric hypercalcaemia
The most likely diagnosis in this scenario is familial benign hypocalciuric hypercalcaemia. Most cases are asymptomatic and blood test reveals hypercalcaemia with a reduced calcium urinary excretion rate (of under 0.02 mmol/L). There may also be normal to high parathyroid hormone, despite the elevated serum calcium levels.
Hypercalcaemia Mx: Example Question
A 67 year old woman with a known history of breast cancer with bony metastases is admitted to hospital unwell. She has confusion, headache, abdominal pain, generalised bony pain and significant nausea with vomiting.
Blood tests reveal:
Sodium 132mmol/L Albumin 22mmol/L Potassium 4.1mmol/L Calcium (adj) 3.89mmol/L Urea 19.2mmol/L Phosphate 1.01mmol/L Creatinine 191µmol/L Magnesium 0.86mmol/L ALP 212U/L
She is aggressively fluid resuscitated with 0.9% sodium chloride 125ml/hour for 48 hours and given 90mg intravenous pamidronate.
Repeat blood tests demonstrate an improvement in the renal function but the adjusted calcium is still greater than 3.0mmol/L.
What is the next most suitable step in this patients management?
Repeat infusion 90mg pamidronate 200mg intravenous hydrocortisone four times daily > 100 units subcutaneous calcitonin three times daily 250ng oral calcitriol single dose Refer to ITU to commence haemofiltration Refractory hypercalcaemia of malignancy may be treated with subcutaneous calcitonin if therapy with fluids and pamidronate fails
Disturbance of calcium homeostasis is a relatively common finding, especially in patients with underlying malignancies. In normal physiology, body calcium is kept in a fine balance between blood stores and bone stores with more than 99% stored in the bony matrix. Calcium is absorbed from the diet and also excreted renally. When blood calcium levels fall, the parathyroid glands release parathyroid hormone (PTH) which increases blood calcium stores by stimulating release from bone by indirect action on osteoclasts, reduces renal excretion, and also activates vitamin D which is necessary to absorb dietary calcium. Activated vitamin D, also known as 1,25-dihydroxycolecalciferol, or calcitriol, is activated by enzymes in the kidney. In end stage renal disease, hypocalcaemia occurs because activation of vitamin D cannot occur and so exogenous calcitriol may be given to ensure adequate calcium levels.
The inverse peptide to PTH produced by the body is calcitonin which is release by the parafollicular cells of the thyroid and essentially performs the opposite functions to PTH when blood calcium levels rise; it increases renal excretion of calcium, it inhibits vitamin D activation and so prevents dietary uptake, and it stimulates osteoblast activity to promote bony uptake of calcium as well as inhibiting osteoclasts from bony turnover. In vivo, its effects are not as significant as PTH in calcium metabolism, however it can be extracted from salmon and administered to patients as a second line agent in the treatment of hypercalcaemia where fluids and bisphosphonates have failed.
Bisphosphonates themselves (such as pamidronate) are drugs which inactivate osteoclasts and hence inhibit bone turnover. While osteoblasts continue to remodel new bone and hence reduce hypercalcaemia, unbalanced bone production can lead to pain and fractures, particularly in patients with metastatic bony disease. The maximum dose of pamidronate is 90mg in any four week period due to the risk of this occurring.
Steroids have been postulated as adjuncts in the management of hypercalcaemia. Unfortunately, there is little evidence that they reduce serum calcium significantly. Current NICE guidelines recommend their use only in patients with hypercalcaemia related to lymphoma and myeloma.
Although theoretically haemofiltration could be used to treat hypercalcaemia, it rarely is. In refractory cases it may be tried but other options should be exhausted first. Generally, the mainstay of current guidance is to use fluids, with or without concurrent diuresis, first, then pamidronate and then calcitonin.
Consideration for the underlying cause of the hypercalcaemia should be addressed; this may require chemotherapy or radiotherapy
Hypocalcaemia Diagnosis - Example Question
A 45-year-old woman with chronic alcohol abuse admitted 3 days ago for nausea and severe diarrhoea now complains of peri-oral and finger tingling. She was admitted for hydration after 1 week of severe watery diarrhoea. She has been receiving intravenous hydration and dextrose but has not been able to take oral nutrition secondary to continued nausea. Her blood pressure is 130/74 mmHg, pulse is 68/min, and respiratory rate is 16/min. She is afebrile.
Physical examination is significant for facial twitching on percussion of her facial nerve just anterior to the ear, as well as the induction of carpal spasm after the inflation of a blood pressure cuff on her arm.
Which of the following is most likely to have caused these findings?
Hyperuricaemia Hypernatraemia > Hypomagnesaemia Hypophosphataemia Hypouricaemia
This patient is displaying classic signs of hypocalcaemia, including hyperexcitability of her facial nerve (Chvostek’s sign), induced carpal spasm (Trousseau’s sign), and tingling of the extremities and lips. Calcium homeostasis is a complicated process involving PTH, vitamin D, albumin and numerous electrolytes. Acquired hypoparathyroidism is the most common form of true hypocalcaemia, most often occurring transiently after thyroid surgery or after the removal of a parathyroid adenoma. Occasionally, hypomagnesaemia can produce hypocalcaemia by decreasing both the body’s production of PTH and its sensitivity to the hormone. In this case, it is likely that the patient became magnesium depleted from her course of watery diarrhoea, likely baseline poor nutritional status and alcohol abuse.
Choice 1: Hyperuricaemia is not a cause of hypocalcaemia. Chronic kidney disease, however can lead to hypocalcaemia in the setting of secondary hyperparathyroidism, but there is no evidence of renal failure in this patient.
Choice 2: Fluid balance (hyper- or hyponatraemia) does not play a role in calcium homeostasis.
Choice 4: Hypophosphataemia is not a cause of hypocalcaemia. Actually, hypocalcaemia often leads to hyperphosphataemia secondary to increased PTH-mediated bone resorption. Elevations in phosphate may also contribute to hypocalcaemia by complexing with circulating calcium and suppressing conversion of 25-OH to 1, 25-OH vitamin D.
Choice 5: Urate levels do not affect calcium homeostasis.
Hypercalcaemia - Example Question
A 50-year-old female is referred to the clinic with hypercalcaemia found coincidentally during routine investigations. On further questioning she admits that she is taking a lot of antacid preparations (for her reflux oesophagitis) and calcium and vitamin D for protection against osteoporosis as her mother and sister have osteoporosis for which they are taking alendronate.
On examination there were no relevant findings.
Investigations reveal:
Serum sodium 135 mmol/L Serum potassium 3.5 mmol/L Serum urea 4.2 mmol/L Serum creatinine 77 mol/L Serum calcium 2.8 mmol/L Serum phosphate 0.8 mmol/L Plasma PTH 5.4 pmol/L (0.9-5.4) 24-h urinary calcium 1.5 mmol/24hr (2.5-7.5)
What is the most likely diagnosis?
Primary hyperparathyroidism Milk- alkali syndrome Hypervitaminosis D > Familial hypocalciuric hypercalcaemia Tertiary hyperparathyroidism
Familial hypocalciuric hypercalcaemia is an autosomal dominant disease characterized by asymptomatic hypercalcaemia with hypocalciuria and a normal PTH level. Most cases are discovered incidentally.
Hypercalcaemia - Example Question
A 45-year-old lady is admitted to hospital with abdominal pain and malaise. She has no past medical history and takes no regular medications or supplements. Bloods tests show:
Ca 2++ 2.70 mmol/l
PO4 + 1.2 mmol/l
Creatinine 60 µmol/l
Chest X-ray - normal appearances
She denies taking any medications or supplements. Her chest X-ray is normal in appearance,and renal function normal. You ring the GP and find out her calcium was also slightly raised 8 years ago. What is the most likely diagnosis?
Secondary hyperparathyroidism Malignancy with bony metastasis Primary hyperparathyroidism > Familial hypocalciuric hypercalcaemia Sarcoidosis
PO4 would normally be low in primary hyperparathyroidism. Her renal function is normal excluding secondary hyperparathyroidism. Sarcoidosis is unlikely with a normal CXR. This leaves malignancy or familial hypocalciuric hypercalcaemia. Although malignancy is possible her raised Ca2+ 8 years makes familial hypocalciuric hypercalcaemia more likely.
Hypocalcaemia - Example Question
A 32-year-old alcoholic presents with abdominal pain and vomiting. His amylase is 1200 U/l and he is being treated for acute pancreatitis. You are called to see him as the nursing staff report the patient is becoming restless. He complains of numbness around his mouth and appears to be in some discomfort.
Your foundation year 2 colleague notes this morning’s blood results:
Adjusted calcium 1.8mmol/l Na+ 136 mmol/l K+ 3.7 mmol/l Urea 6.9 mmol/l Creatinine 81 µmol/l
What’s the next step in management?
Parathyroid hormone Oral calcium supplementation Calcitonin assay > Intravenous 10% calcium gluconate Serum magnesium
In the acute setting of a patient with symptomatic hypocalcaemia intravenous replacement with 10% calcium gluconate would be the most sensible next step. Typically this is given over 10-30 minutes ideally with cardiac monitoring.
Checking the serum magnesium would be very useful as hypomagnesaemia would require replacement to also correct hypocalcaemia.
Oral calcium replacement would be an option in asymptomatic hypocalcaemic patients.
Calcium Metabolism
2 Hormones control Calcium Metabolism
1) Parathyroid Hormone (PTH) ACTIONS: - Increase plasma Ca2+ - Decrease plasma phosphate - Increase renal tubular reabsorption of calcium - Increase osteoclast activity - Increase renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol - Decrease renal phosphate reabsorption
2) 1,25-Dihydroxycholecalciferol = Calcitriol = the active form of Vit D ACTIONS: - Increase plasma Ca2+ - Increase plasma phosphate - Increase renal tubular reabsorption and gut absorption of Ca2+ - Increase osteoclast activity - Increase renal and gut phosphate reabsorption
NB Regulation of Serum Phosphate - confusing:
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney,[21] which means more phosphate is excreted through the urine.
However, PTH also enhances the uptake of phosphate from the intestine and bones into the blood.
In the bone, slightly more calcium than phosphate is released from the breakdown of bone.
In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium.
The end result of PTH release is a small net drop in the serum concentration of phosphate.
