Clinical Calcium Homeostasis Flashcards
What are the functions of calcium?
Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter release
What are some dietary sources of calcium?
Milk, cheese and other dairy foods
Green leay vegetables (broccoli, cabbage, not spinnach)
Where does most of the plasma go once it enters the body?
Out again (as faeces)
How does the level of albumin affect the level of calcium?
Increased albumin decreases free calcium
Decreased albumin increases free calcium
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
How does acidosis affect calcium?
Acidosis increases ionised calcium - predisposing to hypercalcaemia
What are the sources of vitamin D?
Oily fish - salmon, sardines and mackrel
Eggs
Fortified fat spreads
Fortified breakfast cereals
Some powdered milks
What groups are at risk of vitamin D deficiency?
Children
Pregnant woman
People in nursing homes / constitutions
People of colour
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
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
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)
What is the reference range for serum calcium?
2.20 - 2.60
What are the acute features of hypocalcaemia?
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
What are the chronic features of hypocalcaemia?
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
What effect does respiratory alkalosis have on calcium?
Causes hypocalcaemia
What are relevant things to note when making a diagnosis of hypocalcaemia?
Neck surgery / scars
Diet
Medications
Autoimmune disroders
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
What are the relevant investigations for hypocalcaemia?
ECG (Prolonged QT, arrhythmias)
Serum calcium
Albumin
Phosphate
PTH
U and E’s
Vitamin D
Magnesium
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
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?
