Calcium disorders Flashcards
Describe the normal physiology of calcium
Calcium - distributed between bone and the intra- and extra-cellular compartments
Decreased extracellular calcium is detected by the calcium-sensing receptor (CaSR) on the parathyroid gland. The receptors is turned off causing PTH released
The parathyroid glands respond to the fall in serum calcium by releasing PTH from the chief cells
- PTH stimulates the resorption of calcium from bone,
- Causes activation of vitamin D (leads to calcium absorption from enterocytes)
- increased renal tubular reabsorption of calcium
- increases phosphate excretion
A rise in extracellular calcium detected by the CaSR has the opposite effect. Th receptor is turned on which inhibits the release of PTH
It leads to a reduction in the release of PTH and stimulates the release of calcitonin.
This combined effect helps decrease bone resorption and promotes calcium excretion in the kidneys.
Where is most of the calcium in the body found?
Bone
Intracellular calcium is divided into 3 categories, what are they?
Ionised (~ 50%) - metabolically active, or ‘ionised’, free pool of calcium.
Bound (~ 41%) - bound to albumin (90%) and globulin (10%).
Complexed (~ 9%) - forms complexes with phosphate and citrate.
What is the meaning of the term corrected calcium?
When serum calcium is adjusting for the albumin level.
Because a lot of calcium is bound to albumin so the albumin level is taken into account
List the 6 main causes of hypercalcemia
- Malignant hypercalcaemia
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Thyrotoxicosis
- Hypervitaminosis D
- Milk alkali syndrome
What is Malignant hypercalcaemia?
- most common cause of hypercalcaemia in hospital
- Hypercalcaemia commonly occurs due to release of parathyroid related peptide (PTHrP), which mimics the action of PTH.
- Other mechanisms include osteolytic damage to bone or activation of vitamin D.
What is Primary hyperparathyroidism?
- most common cause of hypercalcaemia in the general population
- occurs due to excess release of PTH, which leads to bone resorption and excess calcium release
- commonly occurs secondary to a parathyroid adenoma or or by diffuse hyperplasia of the glands
- Other mechanisms include parathyroid hyperplasia and rarely parathyroid cancer. Primary hyperparathyroidism may be part of aMultiple endocrine neoplasia.
What is secondary hyperparathyroidism? What would the blood tests show regarding calcium?
When hypocalcaemia causes the hypertrophy of all parathyroids. This is to compensate and produce more calcium.
Occurs in chronic kidney disease or vitamin D deficiency
PTH levels are raised but calcium levels are low or normal, and PTH falls to normal after correction of the cause of hypocalcaemia where this is
What is tertiary hyperparathyroidism?
What would the blood tests show regarding calcium?
Autonomous PTH excess due to parathyroid hyperplasia in response to longstanding secondary hyperparathyroidism - seen in patients with chronic kidney disease.
Plasma calcium and phosphate are both raised, the latter often grossly so
How does Thyrotoxicosis cause hypercalcemia?
Elevated thyroid hormones can lead to thyroid hormone-mediated bone resorption. Causes mild hypercalcaemia
How does Hypervitaminosis D cause hypercalcaemia?
High concentrations of vitamin D lead to hypercalcaemia by increasing calcium absorption and bone resorption. This usually occurs due to inadvertent ingestion of excess amounts of vitamin D or continuing a high loading dose for too long.
Some conditions lead to excess endogenous production of activated vitamin D, which include:
Granulomatous disorders (e.g. sarcoidosis, tuberculosis) Cancers (e.g. lymphoma)
What is Milk alkali syndrome and how does it cause hypercalcaemia?
Milk alkali syndrome is due to the excess ingestion of milk or calcium containing compounds (e.g. calcium carbonate).
The full syndrome is characterised by:
Hypercalcaemia
Metabolic alkalosis
Acute kidney injury
Hypercalcaemia is compounded by metabolic alkalosis, which affects calcium excretion in the distal convoluted tubule of the nephron. In addition, the high calcium levels cause renal vessel vasoconstriction that causes renal impairment and further compounds calcium excretion.
Which drugs can cause hypercalcaemia?
Thiazide diuretics
Vitamin D analogues
Lithium administration (chronic)
Vitamin A
Where endocrine conditions cause hypercalcemia?
Thyrotoxicosis
Addison’s disease
Mild only
Name the genetic cause of hypercalcaemia. How is this condition inherited?
Familial hypocalciuric hypercalcaemia
autosomal dominant
What is the pathophysiology of Familial hypocalciuric hypercalcaemia?
mutation to calcium-sensing receptors (CaSR)
Parathyroid gland: CaSRs enable the parathyroid gland to sense changes to calcium levels and respond appropriately.
Kidneys: CaSRs have a number of complex functions that appear to increase calcium excretion in the urine when serum levels are raised.
causes a mildly elevated calcium with a PTH that is either mildly elevated or at the upper limit of normal.