Clinical Calcium Homeostasis Flashcards by Graeme Miller

What are the functions of calcium?

Bone formation

Cell division and growth

Muscle contraction

Neurotransmitter release

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What are some dietary sources of calcium?

Milk, cheese and other dairy foods

Green leay vegetables (broccoli, cabbage, not spinnach)

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Where does most of the plasma go once it enters the body?

Out again (as faeces)

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How does the level of albumin affect the level of calcium?

Increased albumin decreases free calcium

Decreased albumin increases free calcium

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How do we calculate the calcium concentration from the concentration of albumin?

– Adjust Ca2+ by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l

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How does acidosis affect calcium?

Acidosis increases ionised calcium - predisposing to hypercalcaemia

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What are the sources of vitamin D?

Oily fish - salmon, sardines and mackrel

Eggs

Fortified fat spreads

Fortified breakfast cereals

Some powdered milks

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What groups are at risk of vitamin D deficiency?

Children

Pregnant woman

People in nursing homes / constitutions

People of colour

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When is PTH released?

In response to a fall in calcium

Alterations in ECF calcium levels are transmitted into the parathyroid cells via calcium sensing receptor (CaSR)

Chief cells respond directly to changes in calcium concentrations

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What are the effects of parathyroid hormone?

Promote reabsorption of calcium from the renal tubes and bone

PTH mediates the covnersion of vitamin D from its inactive form to its active form

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What is the metabolic process of forming the active form of vitamin D?

25 (OH) vitamin D (inactive) + 25(OH) alpha hydroxylase = 1,25 (OH)2 vitamin D (active)

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What is the reference range for serum calcium?

2.20 - 2.60

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What are the acute features of hypocalcaemia?

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What are chovstek’s sign and trosseau’s sign?

Chvostek’s sign is the twitching of the facial muscles in response to tapping over the area of the facial nerve.

Trousseau’s sign is carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes

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What are the chronic features of hypocalcaemia?

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What are the causes of hypocalcaemia?

Disruption of parathyroid gland due to total thyroidectomy. May be temporary or permanent

Following selective parathyroidectomy (usually transient & mild)

Severe vitamin D deficiency

Mg2+ deficiency (such as omeprazole)

Cytotoxic drug-induced hypocalcaemia

Pancreatitis, rhabdomyolysis and large volume blood tranfusions

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What effect does respiratory alkalosis have on calcium?

Causes hypocalcaemia

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What are relevant things to note when making a diagnosis of hypocalcaemia?

Neck surgery / scars

Diet

Medications

Autoimmune disroders

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What are the low PTH versus high PTH causes of hypocalcaemia?

Low PTH is hypoparathyroidism:

Causes include:

Genetic disorders

Post - surgical (thyroidectomy, parathyroidectomy, radical neck dissection)

Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)

Hungry bone syndrome (post parathyroidectomy)

HIV infection

High PTH (secondary hyperparathyroidism) - this is in response to low calcium

Vitamin D deficiency

Pseudoparathyroidism

Hypomagnesia

Renal disease

Acute pancreatitis

Acute respiratory alkalosis

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What are the relevant investigations for hypocalcaemia?

ECG (Prolonged QT, arrhythmias)

Serum calcium

Albumin

Phosphate

PTH

U and E’s

Vitamin D

Magnesium

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How do levels of phosphate and PTh vary between vitamin D deficiency and hypoparathyroidism?

Vitamin D: Phosphate is low and PTH is high

Hypoparathyroidism: Phosphate is high ad PTH is low

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What are the causes of hypoparathyroidism?

Agenesis

Destruction (neck surgery or autoimmune disease)

Infiltration (haemochromatosis or Wilson’s disease)

Reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesia)

Resistance to PTH

What is pseudohypoparathyroidism?

Target organ (kidney and bone) does not respond to PTH

What are the blood tests for pseudohypoparathyroidism?

Hypocalcaemia

Hyperphosphataemia

Elevated PTH

What are the clinical features of pseudohypoparathyroidism?

Albrights hereditary osteodystrophy (AHO) Obesity Short stature Shortening of the metacarpal bones

What is treatment of milf hypocalcaemia? asymptomatic - greater than 1.9 mmol/l Reference range is 2.2-2.6

Oral calcium tablets Post thyroidectomy - repeat calcium 24 hours later If vitamin D deficient - start vitamin D If low magnesium, stop any precipitating drug and replace magnesium

What is the treatment for severe hypocalcaemia?

This is a medical emergency Administer IV calcium gluconate Initial bolus (10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV over 10 minutes with ECG monitoring) Calcium gluconate infusion Treat the underlying cause

How do we increase the amount of vitamin D in a patient who has severe renal impairment?

Alfacalcidol Or Calcitrol Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy

What are the parathyroid mediated causes of hypercalcaemia?

Either MEN 1 or MEN 2A

What are the non-parathyroid mediated causes of hypercalcaemia?

What medicatinos can cause hypercalcaemia?

Thiazide like diuretics Lithium Theophyline toxicity

What are the miscellaneous reasons for hypercalcaemia?

Hyperthyroidism Acromegaly Pheochromocytoma Adrenal insuficiency Immobilisation Parenteral nutrition

What systems does hypercalcaemia affect?

Bones, stones, groans and psychic moans Clinical features come under 5 categories Renal, Gastrointestinal, MSK, Neurological and Cardiovascular

What are the renal manifestations of hypercalcaemia?

Polyuria Polydipsia Nephrolithiasis (kidney stones)

What are the GI manifestations of hypercalcaemia?

Anorexia Nausea and vomiting Bowel hypomobility and constipation

What are the MSK manifestations of hypercalcaemia?

Muscle weakness Osteoporosis

What are the neurological clinical features of hypercalcaemia?

Decreased concentration, confusion

What are the CVS manifestations of hypercalcaemia?

Short QT Bradycardia Hypertension

What arew the important considerations when making a diagnosis of hypercalcaemia?

Examine the lymph nodes - concerns about malignancy

What are the important investigations when dealing with hypercalcaemia?

U and E's Calcium Phosphate Alk Phosphate Myeloma screen Serum ACE (this is to check for sarcoidosis which is a non-parathyroid cause of hypercalcaemia) PTH

What are the causes of hypercalcaemia when there is normal/increased PTH?

Primary hyperparathyroidism Familial hypocalciuric hypercalcaemia Tertiary hypercalcaemia (renal failure)

What causes hypercalcaemia when PTH is low?

Malignancy or Drugs

What are the causes of hyperparathyroidism?

Most cases are sporadic but has been associated with neck irradiation or prolonged lithium use * 85% parathyroid adenoma * 15% four gland hyperplasia * \<1% MEN type 1 or 2A * \<1% parathyroid carcinoma * Often present for years prior to diagnosis

What are common presentatinos of primary hyperparathyroidism?

Nephrolithiasis Bone disease Asymptomatic

What are the relevant investigations for hyperparathyroidism?

Calcium, PTH U and E's: Check renal function (tertiary hyperparathyroidism - renal failure) Abdominal imaging: Renal calculi Dexa: Osteoporosis 24 hour urine collection for calcium - to exclude familial hypocalciuiric hypercalcaemia Vitamin D

What are the relevant imaging techniques for hyperparathyroidism?

Parathyroid ultrasound SESTAMIBI

What are the indications for surgical treatment in primary hyperparathyroidism?

Presence of symptoms due to hypercalcaemia Serum calcium: 0.25 mmol/L above the upper limit of normal Skeletal: Osteoporosis on DEXA Renal: eGFR less than 60 or presence of kidney stones Age: Less than 50

What is the treatment for primary hyperparathyroidism?

– Generous fluid intake – Cinacalcet (acts as a calcimetic, i.e. mimics the effect of calcium on the calcium sensing receptor on Chief cells, this leads to a fall in PTH and subsequently calcium levels)

What is familial hypocalciuric hypercalcaemia?

Autosomal dominant disorder of the calcium sensing receptor Benign, no therapy indicated Positive family history, screen young family members for diagnosis. **PTH may be normal or slightly elevated** No evidence of abnormal parathyroid tissue on ultrasound or isotope scan

Give two examples of malignancy that can cause hypercalcaemia

Humoural hypercalcaemia of malignancy The causal agent is PTHrP Features in squamous cell cancer (including lung), renal, ovarian, endometrial and breast cancer Local osteolytic hypercalcaemia Causal agent is cytokines, chemokines and PTHrP

What multple endocrine neoplasias result in hyperparathroidism?

MEN1 - \>95% of MEN 1 will have hyperparathyroidism MEN type 2A - 20-30 % of MEN2A have hyperparathyroidism

What is the management of hypercalcaemia?

What is second line management for hypercalcaemia?

What are the drugs that can cause hypocalcaemia?