(endo) calcium dysregulation

Question 1

review phase 1a ‘regulation of calcium and phosphate’ cards before this deck

Answer 1

good going champ

Question 2

how does the parathyroid gland respond to low serum calcium levels?

Answer 2

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+

Question 3

how does the parathyroid gland respond to high serum calcium levels?

Answer 3

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+

Question 4

what are the three types of hyperparathryoidism?

Answer 4

primary, secondary and tertiary hyperparathyroidism

Question 5

what is primary hyperparathyroidism?

Answer 5

parathyroid adenoma autonomously producing too much PTH

calcium increases continuously due to lack of negative feedback system

Question 6

what blood test results are expected in a patient w primary hyperparathyroidism?

Answer 6

PTH = extremely elevated
calcium = extremely elevated
phosphate = low

Question 7

why are PTH and calcium elevated in primary hyperparathyroidism?

Answer 7

calcium increases in response to increased PTH by cannot stop increasing as the pituitary adenoma does not respond to negative feedback

Question 8

why is phosphate low in primary hyperparathyroidism?

Answer 8

increased PTH so increased inhibition of the renal apical sodium-phosphate co-transporter
= so increased urinary loss of phosphate

Question 9

what is the impact of PTH on phosphate levels in a normal healthy state?

Answer 9

on kidney = increased phosphate EXCRETION

on gut = increased phosphate ABSORPTION

(usually, these two action are balanced)

Question 10

what is the impact of PTH on phosphate levels in a hyperparathyroid state?

Answer 10

pathology overtakes and more PTH acts on the kidney to stimulate more excretion

(overall excretion&raquo_space; absorption)

Question 11

how is primary hyperparathyroidism treated?

Answer 11

parathyroidectomy

Question 12

what are the risks of untreated hyperparathyroidism?

Answer 12

1) osteoporosis
2) renal caliculi (stones)
3) psychological impacts of hypercalcaemia = altered mentation, depression

Question 13

why does hyperparathyroidism lead to kidney stones?

Answer 13

excess PTH
= excess calcium
= excess calcium in urine
= increased risk of calcium kidney stone formation

Question 14

why does hyperparathyroidism lead to osteoporosis?

Answer 14

excess PTH
= increased stimulation of OAFs (osteoclast activating factors) via osteoblasts
= increased osteoclastic bone resorption

Question 15

what is secondary hyperparathyroidism?

Answer 15

the normal physiological response to hypocalcaemia

Question 16

how does primary hyperparathyroidism compare to secondary?

Answer 16

primary = elevated PTH, elevated Ca

secondary = low Ca, elevated PTH

Question 17

what blood test results are expected in a patient w secondary hyperparathyroidism and why?

Answer 17

PTH = elevated
Ca = low

hypocalcaemia is sensed by the calcium-sensing receptors of the chief cells that stimulates in turn, PTH secretion

Question 18

what are the causes of secondary hyperparathryoidism?

Answer 18

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

Question 19

what is the most common cause of secondary hyperparathyroidism?

Answer 19

vitamin D deficiency

Question 20

explain how vitamin D deficiency leads to secondary hyperparathyroidism

Answer 20

calcitriol deficiency
= less Ca2+ absorption in the gut and kidney
= reduced serum Ca2+ levels
= parathyroid glands respond by increasing PTH secretion significantly

Question 21

how is secondary hyperparathyroidism treated in patients with NORMAL renal function?

Answer 21

give 25-OH vitamin D (either ergocalciferol or cholecalciferol)

with normal renal function, they can 1-alpha hydroxylase it to form calcitriol

Question 22

how is secondary hyperparathyroidism treated in patients with IMPAIRED renal function?

Answer 22

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)

Question 23

differentiate between cholecalciferol and ergocalciferol

Answer 23

ergocalciferol (from diet) = 25-hydroxy vitamin D2

cholecalciferol (from skin) = 25-hydroxy vitamin D3

Question 24

what is tertiary hyperparathyroidism?

Answer 24

an overactive parathyroid gland as a result of chronic renal failure or chronic vitamin D deficiency

Question 25

what are the two main reasons for tertiary hyperparathyroidism?

Answer 25

1) chronic renal failure | 2) chronic vitamin D deficiency

Question 26

explain the pathophysiology of tertiary hyperparathyroidism

Answer 26

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

Question 27

how is tertiary hyperparathyroidism treated?

Answer 27

parathyroidectomy

Question 28

what is the main consequence of tertiary hyperparathyroidism?

Answer 28

continuous, autonomous secretion of PTH from the hyperplastic parathyroid glands = HYPERCALCAEMIA

Question 29

how common is tertiary hyperparathyroidism?

Answer 29

extremely rare | = only happens in the context of CKD/chronic renal failure/chronic vit D deficiency

Question 30

what is the normal response to hypercalcaemia?

Answer 30

hypercalcaemia | = causes PTH to fall

Question 31

what do the following blood results indicate: - elevated Ca2+ - low/suppressed/undetectable PTH

Answer 31

could be 1) normal physiological response to hypercalcaemia OR// 2) hypercalcaemia of malignancy

Question 32

what is hypercalcemia of malignancy?

Answer 32

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

Question 33

how can hypercalcaemia of malignancy and primary hyperparathyroidism be differentiated?

Answer 33

hypercalcaemia of malignancy = high Ca2+, low/undetectable PTH primary hyperparathyroidism = high Ca2+, high PTH

Question 34

what is the most likely diagnosis if a patient with hypercalcaemia has a high PTH?

Answer 34

if renal function is normal = primary hyperparathyroidism (e.g. parathyroid adenoma) if chronic renal failure = tertiary hyperparathyroidism (all four glands are hyperplastic)

Question 35

what blood report is expected for a patient with vitamin D deficiency?

Answer 35

Ca2+ = low PTH = elevated 25-OH cholecalciferol = low = secondary hyperparathyroidism (secondary to the hypocalcaemia)

Question 36

in what form is vitamin D measured and why?

Answer 36

measure 25-OH cholecalciferol as calcitriol (1,25-dihydroxycholecalciferol) is very difficult to measure

Question 37

summarise primary hyperparathyroidism

Answer 37

autonomous secretion of PTH by a parathyroid adenoma, hypercalcaemia and high PTH

Question 38

summarise secondary hyperparathyroidism

Answer 38

due to low vitamin D, calcium falls, PTH increases (secondary to low calcium)

Question 39

summarise tertiary hyperparathyroidism

Answer 39

- 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

Question 40

when you spot hypercalcaemia, what should you look at first?

Answer 40

PTH levels

Question 41

what is the most likely cause of hypercalcaemia and suppressed PTH?

Answer 41

hypercalcaemia of malignancy

Question 42

what is the most likely cause of hypercalcaemia and elevated PTH?

Answer 42

in renal function normal = primary hyperparathyroidism if chronic renal failure = tertiary hyperparathyroidism

Question 43

what is the most likely cause of hypocalcaemia and elevated PTH?

Answer 43

vitamin D deficiency