(endo) calcium dysregulation Flashcards
review phase 1a calcium + phosphate regulation cards before these ones
review phase 1a ‘regulation of calcium and phosphate’ cards before this deck
good going champ
how does the parathyroid gland respond to low serum calcium levels?
low serum calcium levels
= detect by the calcium-sensing receptors on chief cells
= increase PTH secretion
= stimulates more Ca2+ reabsorption in the gut and kidney and more bone resorption
= increases serum Ca2+
how does the parathyroid gland respond to high serum calcium levels?
high serum calcium levels
= detect by the calcium-sensing receptors on chief cells
= reduce PTH secretion
= results in less Ca2+ reabsorption in the gut and kidney and less bone resorption
= reduces serum Ca2+
what are the three types of hyperparathryoidism?
primary, secondary and tertiary hyperparathyroidism
what is primary hyperparathyroidism?
parathyroid adenoma autonomously producing too much PTH
calcium increases continuously due to lack of negative feedback system
what blood test results are expected in a patient w primary hyperparathyroidism?
PTH = extremely elevated calcium = extremely elevated phosphate = low
why are PTH and calcium elevated in primary hyperparathyroidism?
calcium increases in response to increased PTH by cannot stop increasing as the pituitary adenoma does not respond to negative feedback
why is phosphate low in primary hyperparathyroidism?
increased PTH so increased inhibition of the renal apical sodium-phosphate co-transporter
= so increased urinary loss of phosphate
what is the impact of PTH on phosphate levels in a normal healthy state?
on kidney = increased phosphate EXCRETION
on gut = increased phosphate ABSORPTION
(usually, these two action are balanced)
what is the impact of PTH on phosphate levels in a hyperparathyroid state?
pathology overtakes and more PTH acts on the kidney to stimulate more excretion
(overall excretion»_space; absorption)
how is primary hyperparathyroidism treated?
parathyroidectomy
what are the risks of untreated hyperparathyroidism?
1) osteoporosis
2) renal caliculi (stones)
3) psychological impacts of hypercalcaemia = altered mentation, depression
why does hyperparathyroidism lead to kidney stones?
excess PTH
= excess calcium
= excess calcium in urine
= increased risk of calcium kidney stone formation
why does hyperparathyroidism lead to osteoporosis?
excess PTH
= increased stimulation of OAFs (osteoclast activating factors) via osteoblasts
= increased osteoclastic bone resorption
what is secondary hyperparathyroidism?
the normal physiological response to hypocalcaemia
how does primary hyperparathyroidism compare to secondary?
primary = elevated PTH, elevated Ca
secondary = low Ca, elevated PTH
what blood test results are expected in a patient w secondary hyperparathyroidism and why?
PTH = elevated Ca = low
hypocalcaemia is sensed by the calcium-sensing receptors of the chief cells that stimulates in turn, PTH secretion
what are the causes of secondary hyperparathryoidism?
causes of hypocalcaemia: less PTH (not possible), less vitamin D (MAIN cause)
so, causes of vitamin D deficiency
- malabsorption or poor dietary intake
- inadequate sun exposure
- renal failure
- liver failure
- vit D receptor defects
what is the most common cause of secondary hyperparathyroidism?
vitamin D deficiency
explain how vitamin D deficiency leads to secondary hyperparathyroidism
calcitriol deficiency
= less Ca2+ absorption in the gut and kidney
= reduced serum Ca2+ levels
= parathyroid glands respond by increasing PTH secretion significantly
how is secondary hyperparathyroidism treated in patients with NORMAL renal function?
give 25-OH vitamin D (either ergocalciferol or cholecalciferol)
with normal renal function, they can 1-alpha hydroxylase it to form calcitriol
how is secondary hyperparathyroidism treated in patients with IMPAIRED renal function?
give alfacalcidol (1-alpha hydroxycholecalciferol = an analogue of vitamin D)
with impaired renal function, they cannot 1-alpha hydroxylase it themselves so better to directly give vitamin D (analogue)
differentiate between cholecalciferol and ergocalciferol
ergocalciferol (from diet) = 25-hydroxy vitamin D2
cholecalciferol (from skin) = 25-hydroxy vitamin D3
what is tertiary hyperparathyroidism?
an overactive parathyroid gland as a result of chronic renal failure or chronic vitamin D deficiency
what are the two main reasons for tertiary hyperparathyroidism?
1) chronic renal failure
2) chronic vitamin D deficiency
explain the pathophysiology of tertiary hyperparathyroidism
in chronic renal failure/vitamin D deficiency
= impaired function of 1-alpha hydroxylase
= chronic lack of calcitriol synthesis
= low serum Ca2+ levels
= PTH increases (hyperparathyroidism)
= parathyroid glands enlarge (hyperplasia)
= continuous autonomous PTH secretion
how is tertiary hyperparathyroidism treated?
parathyroidectomy
what is the main consequence of tertiary hyperparathyroidism?
continuous, autonomous secretion of PTH from the hyperplastic parathyroid glands
= HYPERCALCAEMIA
how common is tertiary hyperparathyroidism?
extremely rare
= only happens in the context of CKD/chronic renal failure/chronic vit D deficiency
what is the normal response to hypercalcaemia?
hypercalcaemia
= causes PTH to fall
what do the following blood results indicate:
- elevated Ca2+
- low/suppressed/undetectable PTH
could be
1) normal physiological response to hypercalcaemia
OR//
2) hypercalcaemia of malignancy
what is hypercalcemia of malignancy?
hypercalcaemia caused either by
1) bony metastases that activate OAFs to stimulate osteoclastic bone resorption
2) certain cancers that produce PTH-related peptides that act on the PTH receptors of osteoblasts
= both ultimately result in increased serum calcium
how can hypercalcaemia of malignancy and primary hyperparathyroidism be differentiated?
hypercalcaemia of malignancy
= high Ca2+, low/undetectable PTH
primary hyperparathyroidism
= high Ca2+, high PTH
what is the most likely diagnosis if a patient with hypercalcaemia has a high PTH?
if renal function is normal = primary hyperparathyroidism (e.g. parathyroid adenoma)
if chronic renal failure = tertiary hyperparathyroidism (all four glands are hyperplastic)
what blood report is expected for a patient with vitamin D deficiency?
Ca2+ = low
PTH = elevated
25-OH cholecalciferol = low
= secondary hyperparathyroidism (secondary to the hypocalcaemia)
in what form is vitamin D measured and why?
measure 25-OH cholecalciferol
as calcitriol (1,25-dihydroxycholecalciferol) is very difficult to measure
summarise primary hyperparathyroidism
autonomous secretion of PTH by a parathyroid adenoma, hypercalcaemia and high PTH
summarise secondary hyperparathyroidism
due to low vitamin D, calcium falls, PTH increases (secondary to low calcium)
summarise tertiary hyperparathyroidism
- a complication of chronic renal failure
- unable to make calcitriol (active vitamin D) over a prolonged period
- parathyroid glands become hyperplastic and autonomous
- high PTH drive causes hypercalcaemia
when you spot hypercalcaemia, what should you look at first?
PTH levels
what is the most likely cause of hypercalcaemia and suppressed PTH?
hypercalcaemia of malignancy
what is the most likely cause of hypercalcaemia and elevated PTH?
in renal function normal = primary hyperparathyroidism
if chronic renal failure = tertiary hyperparathyroidism
what is the most likely cause of hypocalcaemia and elevated PTH?
vitamin D deficiency
