Lecture 12: Clinical Calcium Homeostasis Flashcards
list dietary sources of calcium
- milk, cheese and oher dairy foods
- green leafy vegetables: broccoli, cabbage and okra
- soya beans
- tofu
- nuts
- bread and anything made with fortified flour
- fish where you eat the bones such as sardines and pilchards
list the functions of calcium
- bone formation
- cell division & growth
- muscle contraction
- neurotransmitter release
what is the normal range of plasma calcium?
2.20-2.60 mmol/l
describe the process of stimulating parathyroid hormone secretion
- Chief cells respond directly to changes in calcium concentrations.
- alterations in ECF Ca2+ levels are transmitted into the parathyroid cells via calcium-sensing receptor (CaSR).
- PTH is secreted by chief cells in response to a fall in calcium.
What are the functions of parathyroid hormone?
- PTH has direct effects that promote reabsorption of calcium from renal tubules and bone.
- PTH mediates the conversion of vitamin D from its inactive to active form.
What bone problem
might lengthy exposure
to inappropriate levels of
PTH lead to?
osteoporosis
where in the body does the conversion of vitamin D from its inactive to active form take place?
kidney
what is considered hypocalcaemia?
serum calcium < 2.20
list the causes of hypocalcaemia
- diruption of parathyroid gland due to total thyroidectomy, may be temporary or permanent.
- following selective parathyroidectomy (usually transient and mild).
- severe vitamin D deficiency
- Mg2+ deficiency
- cytotoxic drug-induced hypocalcaemia
- pancreatitis, rhabdomyolysis and large volume blood transfusions
clinical features of hypocalcaemia
SPASMODIC E
- Spasms (Trousseau’s sign)
- Perioral parasthaesia
- Anxiety/irritability
- Seizures
- Muscle tone increase (colic, dysphagia)
- Orientation impairment (i.e. confusion)
- Dermatitis
- Impetigo herpetiformis
- Chvostek’s sign
- ECG shows prolonged QTc
what investigations are performed for suspected hypocalcaemia
- ECG
- serum calcium
- albumin
- phosphate
- PTH
- U&es
- vitamin D
- magnesium
causes of hypoparathyroidism
- agenesis (e.g. DiGeorge syndrome)
- destruction (neck surgery, autoimmune disease)
- infiltration (e.g. haemochromatosis or Wilson’s disease)
- reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesaemia)
- resistance to PTH
describe pseudohypoparathyroidism
- refers to a group of heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH.
- characterised by hypocalcaemia, hypophosphatemia and, in contrast to hypoparathyroidism, **elevated rather than reduced PTH concentrations. **
features of Albright’s hereditary osteodystrophy (AHO)
- obesity
- short stature
- shortening of metacarpal bones
- can occur in patients with pseudohypoparathyroidism
what does Albright’s hereditary Osteodystrophy (AHO) alone without abnormalities of calcium or PTH indicate?
pseudo-pseudohypoparathyroidism
describe the treatment of ‘mild’ hypocalcaemia
asymptomatic, > 1.9mmol/L
- commence oral calcium tablets
- if post-thyroidectomy repeat calcium 24 hours later
- if vitamin D deficient, start vitamin D
- if low Mg2+, stop any precipitating drug and replace Mg2+
describe the treatment of ‘severe’ hypocalcaemia
symptomatic or < 1.9mmol/L
- 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)
- The initial bolus can be repeated until the patient is asymptomatic and/or calcium levels significantly increased
- A Calcium gluconate infusion can then follow (100ml of 10% calcium gluconate in 1litre of 0.9% saline or 5% dextrose and infuse at 50-100ml/h)
- Aim to achieve normocalcaemia
- Treat the underlying cause
when would active vitamin D be prescribed?
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
clinical features of hypercalcaemia
- renal, GI, musculoskeletal, neurological, cardiovascular
Renal:
- polyuria
- polydipsia
- nephrolithiasis
Gastrointestinal:
- anorexia
- nausea and vomiting
- bowel hypomotility and constipation
Musculoskeletal:
- muscle weakness
- bone pain
- oesteoporosis
Neurological:
- decreased concentration
- confusion
Cardiovascular
- shortening of QT interval
- bradycardia
- hypertension
hypercalcaemia investigations
- U&Es
- Ca
- PO4
- Alk phos
- Myeloma screen
- serum ACE
- PTH
- consider ECG
two main causes of hypercalcaemia
- primary hyperparathyroidism (parathyroid adenoma - 85%, four gland hyperplasia - 15%)
- hypercalcaemia of malignancy
primary hyperparathyroidism investigations
- Ca, PTH
- U&Es: check renal function
- abdominal imaging: renal calculi
- DEXA (bone density scan): osteoporosis
- spot urinary calcium/creatine ratio
- 24hr urinary calcium
- vitamin D
primary hyperparathyroidism treatment
- surgery
- generous fluid intake
- vitamin D replacement
- cinacalcet (acts as a calcimetic, i.e. mimic the effect of calcium on the calcium sensin receptor on chief cells, this leads to a fall in PTH and subsequently calcium levels)
describe familial hypocalciuric hypercalcaemia (FHH)
- autosomal dominant disorder of the calcium sensing receptor.
- benign, no therapy indicated
- low levels of urinary calcium
describe MEN type 1
Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disorder that causes tumours to develop in the:
- parathyroid glands (> hyperparathyroidism)
- pituitary gland
- pancreas
- caused by MENIN mutation (chromosome 11)
describe MEN type 2A
Multiple endocrine neoplasia ype 2A is a genetic disorder that can cause:
- primary hyperparathyroidism (due to hyperplasia or adenomas)
- medullary thyroid cancer
- phaeochromocytoma
RET mutation
hypercalcaemia acute management
- 0.9% saline 4-6 litres over 24 hours
- monitor for fluid overload
- consider dialysis if severe renal failure
- after rehydration > IV bisphosphonates e.g. zolendronic acid
second line management of hypercalcaemia
- glucocorticoids
- calcitonin
- calcimimetics
- parathyroidectomy
