Calcium Pathophysiology and Clinical Aspects Flashcards
What are some dietary sources of calcium?
Milk, cheese, and other diary
Green leafy vegetables
Soya beans, tofu, nuts, bread and fish with bone
What are the functions of calcium?
Bone formation
Cell division and growth
Muscle contraction
Neurotransmitter release
What percentage of calcium is found where?
1% in cells
0.1% in extracellular fluid
98.9% in bones
What is the normal range of plasma calcium?
2.2-2.6 mmol/l - total
Free calcium is calculated by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l ex. if 2.55mmol/l then free is 2.75
What are some sources for vitamin D?
Oily fish, eggs, fortified fat spreads, fortified cereals and some powdered milks
How is parathyroid hormone stimulated?
Chief cells respond to change in calcium conc.
There is calcium sensing receptors in parathyroid cells
PTH is secreted in fall of Ca conc.
What are the effects of PTH?
Has direct effects that promote reabsorption of calcium from renal tubules and bone
Mediates conversion of Vitamin D from inactive to active form
What are some clinical features of hypocalcaemia?
Paraesthesia, muscle twitching, seizures, laryngospasm, and bronchospasm
Cardiac - hypotension, papilledema and prolonged QT interval
When do symptoms for hypocalcaemia usually show?
When adjusted serum calcium levels are below 1.9mmol/l
What 2 signs can show hypocalcaemia?
Chvostek’s (facial nerve) and Trousseau’s sign
What are some causes of hypocalcaemia?
Disruption of parathyroid gland by thyroidectomy
Severe vitamin D deficiency
Mg deficiency
Cytotoxic drug induced hypocalcaemia
Pancreatitis, rhabdomyolysis and large volume blood transfusions
What are some causes of low PTH?
Genetic disorders
Post surgical
Autoimmune
Infiltration
Radiation induced
HIV infection
What blood results are used for hypocalcaemia?
ECG, serum calcium, PTH, albumin, phosphate, U+E, vitamin D and Mg
What are the investigations for hypocalcaemia?
Confirm with adjusted calcium and check PTH
Then if high (appropriate) - check urea and creatine - if normal then check Vit D but if high then renal failure
If low PTH (inappropriate) - Check Mg
What investigation results are predicted in Vit D deficiency?
Low total calcium
Low ionised calcium
Low phosphate
High PTH
What investigation results are predicted in hypoparathyroidism?
Low total and ionised calcium
High phosphate
Low PTH
What could hypoparathyroidism result from?
Agenesis
Destruction
Infiltration
Reduced secretion of PTH
Resistance to PTH
Describe pseudo-hypoparathyroidism
Presents in childhood - heterogeneous disorders defined by target organ which is unresponsive to PTH
Hypocalcaemia, hyperphosphatemia and hypoparathyroidism
Elevated PTH
What is the treatment for mild hypocalcaemia?
Commence with oral calcium tablets
If post thyroidectomy then repeat calcium 24hrs later
Start vitamin D if deficient
Also if low Mg then replace
What is the treatment for severe hypocalcaemia?
Medical emergency
Administer IV calcium gluconate
This is repeated until patient is asymptomatic
Treat underlying cause
Describe vitamin D replacement if patient has severe renal impairment
Alfacalcidol and Calcitriol
As these are the hydroxylated derivatives that would have been hydroxylated in kidneys
How much vitamin D should everyone over 5 take every day in winter months?
10micrograms a day
What is the calcium level of acute hypercalcaemia?
<3 mmol/l - often asymptomatic
3-3.5
>3.5 then required urgent correction
What are some main causes of hypercalcaemia?
Primary hyperparathyroidism
Renal failure
Familial hyperparathyroidism
Malignancy
Vit D intoxication
Chronic granulomatous disorder
What are the clinical features of hypercalcaemia?
Bones, stones, groans and psychic moans
Polyuria, polydipsia, nephrolithiasis, anorexia, N/V, constipation and muscle weakness
Decreased concentration and shortening of QT interval
What blood are done for hypercalcaemia?
U+Es, Ca, PO4, Alk phosphate, myeloma screen, serum ACE and PTH
Describe the investigations for hypercalcaemia
Ca and albumin
Then check PTH
If normal or increased (inappropriate) - primary hyperparathyroidism and familial tertiary hyperparathyroidism
If PTH low - malignancy or drug causes
Describe primary hyperparathyroidism
More females 3:1
Incidence is 50-60 years
Mostly asymptomatic at diagnosis
Most cases are sporadic with neck irradiation or prolonged lithium use
85% parathyroid adenoma and 15% four gland hyperplasia
What are the investigations for primary hyperparathyroidism?
Ca, PTH, U+Es, abdominal imaging, DEXA, spot urinary calcium/ creatine ratio, 24hr urinary calcium and Vitamin D
US, $D CT and Sestamibi
What are the indications for surgery in primary hyperparathyroidism?
Presence of symptoms due to hypercalcaemia
Serum Ca > 0.25mmol/l
Osteoporosis
eGFR <60 or presence of kidney stones
< 50 years
What is the medical treatment for primary hyperparathyroidism?
Generous fluid intake
Vit D replacement
Cinacalcet - mimics effect of Ca on calcium sensing receptor on chief cells so fall in PTH and Ca levels
What are the risks of surgical treatment for primary hyperparathyroidism?
Bleeding
Hypocalcaemia
Recurrent laryngeal nerve injury
Describe familial hypocalciuric hypercalcaemia
Autosomal dominant disorder of Ca sensing receptor
Low levels of urinary calcium
Benign - no therapy
Positive family history
PTH my be normal or elevated
Describe prognosis of hypercalcaemia from malignancy
Most tumour associated hypercalcaemia is mild
Unless an endocrine tumour then prognosis is poor
Describe MEN1
Primary hyperparathyroidism, pancreatic and pituitary
95% will have hyperparathyroidism
MENIN mutation
Presents in 20-40s
Multi gland involvement and high recurrence rate
Describe MEN Type 2A
Medullary thyroid cancer, pheochromocytoma and primary hyperparathyroidism
RET mutation
20-30% have hyperparathyroidism
What is the management for hypercalcaemia?
Rehydration - 0/9% saline 4-6l
Intravenous bisphosphonates - zoledronic acid
Consider dose reduction in renal impairment
What is 2nd line management for hypercalcaemia?
Glucocorticoids
Calcitonin
Calcimimetics
Parathyroidectomy
