Clinical calcium homeostasis Flashcards
Dietary sources of calcium
milk, cheese and other dairy foods
green leafy vegetables– such as broccoli, cabbage and okra, but not spinach
soya beans
Tofu
nuts
bread and anything made with fortified flour
fish where you eat the bones– such as sardines and pilchards
Functions of calcium (4)
Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter release
Normal range of Calcium in the blood in clinical practice
2.20 - 2.60 mmol/l
What effect does increased albumin have on free calcium
free calcium decreases
How does acidosis lead to hypercalcaemia
acidosis increases ionised (free) calcium
Groups at risk of vitamin D deficiency
infants and children
pregnant and breastfeeding women, particularly teenagers and young women
Elderly
What types of cells respond directly to changes in calcium concentrations
Parathyroid Chief cells
Alterations in ECF Ca2+ levels are transmitted into the parathyroid cells via which receptor
Calcium-sensing receptor
Which hormone is secreted in response to a fall in calcium? what is it’s direct effect
Parathyroid hormone
promotes reabsorbtion of calcium from renal tubules & bone into the blood
What bone problems can persistent high PTH level lead to
Osteopenia
Osteoporosis
How does PTH affect vitamin D
It mediates the conversion of vit D from its inactive to active form
Where does vitamin D activation occur?
In the kidney
Pathway of vitamin D
Sunlight/diet
converted first into vit d 25-hydroxylase in the liver (inactive form)
Moves to kidney - here it becomes activated. It then moves to the gut
Hypocalcaemia clinical range
Serum calcium <2.20
Clinical features of hypocalcaemia
Neuromuscular irritability (tetany)
Spasms - carpopedal spasm
Anxious/irritable
cardiac problems (arrhythmias, HF, hypotension), papilloedema
Symptoms typically develop when serum calcium <1.9mmol/L
Clinical signs of hypocalcaemia
Chovstek’s sign
Trosseau’s sign
What is Trosseau’s sign/how do you test it?
carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes
Hand curls inwards at wrist
What is Chovstek’s sign/how do you test it?
Ask patient to relax facial nerves. Tap the facial nerve just anterior to earlobe or below the zygomatic arch + corner of mouth
+ response = twitching of the lip at the corner of the mouth to spasm of all facial muscles, depending on severity of hypocalcaemia
What surgery can cause damage to the parathyroid gland?
total thyroidectomy
Causes of hypocalcaemia (6)
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
Cytotoxic drug-induced hypocalcaemia
Pancreatitis, rhabdomyolysis and large volume blood tranfusions
Most common causes of low PTH
Gentic disorders
Autoimmune
HIV infection
Most common causes of high PTH - secondary hyperparathyroidism in response to hypocalcaemia
Vit D deficiency
Pseudohypoparathyroidism
Hypomagnesemia
Renal disease
Acute pancreatitis
Acute respiratory alkalosis
Most common drugs causing hypocalcaemia
Inhibitors of bone resorption - bisphosphonates
Investigations done to diagnose hypocalcaemia (8)
ECG Serum calcium Albumin Phosphate PTH U&Es - check if PTH is high Vitamin D Magnesium - check if PTH is low or normal
What is the link between serum albumin and calcium?
If serum albumin levels fall so do the calcium levels
If magnesium levels are normal but you have low/normal PTH then what are the probable diagnoses
hypoparathyroidism or calcium sensing receptor defect
If you have high PTH and high levels of creatinine what is the probable diagnosis
Renal failure
Vitamin D deficiency:
what results would you expect for total calcium, ionised calcium, phosphate and PTH
Total calcium = low
Ionised calcium = low
Phosphate = low
PTH = high (due to low Ca2+)
Link between PTH and calcium
Parathyroid hormone is secreted by the parathyroid glands and is the most important regulator of blood calcium levels
Low calcium levels stimulate PTH secretion, whereas high calcium levels prevent the release of PTH
Function of vitamin D
Vitamin D promotes calcium absorption in the gut and maintains blood calcium levels to enable normal mineralization of bone and prevent abnormally low blood calcium levels that can then lead to tetany
So increase in vit d => increase in Ca2+
less vit D = less Ca2+ being absorbed
Hypoparathyroidism:
What results would you expect for total calcium, ionised calcium, phosphate and PTH?
Total calcium = low
Ionised calcium = low
Phosphate = High (low PTH means low calcium levels so serum phosphorus increases as its function is to help the body absorb and utilise calcium
PTH = low
How might hypoparathyroidism result (5)
Agenesis (DiGeorge syndrome - underdeveloped parathyroid glands)
Destruction (neck surgery, autoimmnue disease)
Infiltration (haemochromatosis or Wilson’s disease)
Reduced secretion of PTH
Resistance to PTH
What is pseudohypoparathyroidism?
Group of diseases defined by target organ unresponsiveness to PTH
Presents in childhood
What is pseudohypoparathyroidism characterised by?
Hypocalcaemia
Hyperphophataemia
Elevated PTH (not binding to target organs so staying in blood)
What are symptoms of Albright’s heriditary Osteodystrophy
Obesity, short stature, shortening of the metacarpal bones
What is it called if you have AHO alone without abnormalities of calcium or parathyroid hormone
pseudo-pseudohypoparathyroidism
Treatment of mild hypocalcaemia (asymptomatic >1.9 mmol/L)
Commence oral calcium tablets
If post thyroidectomy repeat calcium 24 hours later
If vit D deficient, start vitamin D
If low Mg2+, stop any precipitating drug and replace Mg2+
What types of drugs can cause hypomagnesemia
antibiotics
chemotherapeutic agents
diuretics
proton-pump inhibitors
Treatment of severe hypocalcaemia emergency
Administer IV calcium gluconate - repeat if needed
ECG monitoring
Treat underlying cause like respiratory alkalosis
In patients with severe renal impairment require vitamin D therapy what should you give them and why?
Alfacalcidol or calcitriol
These are already in active form
In renal disease kidney isn’t functioning properly so can’t hydroxylate vitamin D into active form
A calcium level of >3.5 mmol/L requires what?
Urgent correction due to risk of dysrhthmia and coma
Main causes of hypercalcaemia (2)
Primary hyperparathyroidism
Malignancy
Clinical features of hypercalcaemia (6)
Polyuria Thirst Anorexia Nausea + vomiting Muscle weakness Constipation
Phrase that helps you remember hypercalcaemia symptoms
Bones, stones, groans + psychic mones
Renal stones
Muscle weakness
Confusion/decreased concentration
Depression
Example patient presenting with hypercalcaemia of malignancy
Weight loss Changed bowel habit Low PTH High Calcium Heavy smoker + chronic cough
Investigations for Hypercalcaemia (8)
U&Es
Ca2+
PO4 - increased points to cancer diagnosis
Alk phos
Myeloma screen
Serum ACE
PTH - if high then points to hyperparathyroidism, if low => cancer
consider ECG
Most common causes of Primary hyperparathyroidism
Adenoma
Hyperplasia of all glands
Investigations for primary hyperparathyroidism (6)
Ca2+ and PTH
U+E
Abdominal imaging
DEXA for osteoporosis
24hr urine collection for Ca2+
Vit D
Parathyroid USS, CT, PET
When would a patient be indicative for parathyroid surgery?
If patient is <50, has osteoporosis on DEXA, normal serum calcium, kidney stones, has symptoms of hypercalcaemia
Treatment of primary hyperparathyroidism
Parathyroid surgery
Medical management - generous fluid intake, Cinacalcet - mimics effect of Ca2+ on calcium sensing receptor on Parathyroid chief cells causing fall in PTH and subsequently low Ca2+ levels)
What is Familial Hypocalciuric
Hypercalcaemia
Autosomal dominant inherited disorder that causes hypercalcemia and hypocalciuric (low levels of urinary Ca2+)
Affects the calcium sensing receptor
Positive family history, screen young family members for diagnosis.
No evidence of abnormal parathyroid tissue on ultrasound or isotope scan
Multiple Endocrine
Neoplasia type 1 (MEN-1)
Main causes: Primary hyperparathyroidism (>95%) Pancreatic or Pituitary
MENIN mutation on chromosome 11
Multiple Endocrine
Neoplasia type 2 (MEN-2)
Associated with:
Medullary thyroid cancer
Phaeochromocytoma
Primary hyperparathyroidism
RET mutation
What are Multiple Endocrine
Neoplasias
Syndromes where there are functioning hormone-producing tumours in multiple organs, these are:
MEN-1
MEN-2
Management of hypercalcaemia
Rehydration - monitor for fluid overload, consider dialysis if severe renal failure
after rehydration - IV bisphophonates
2nd line management of hypercalcaemia
Glucocorticoids
Calcitonin
Calcimimetics
Parathyroidectomy
