Calcium Homeostasis and Hypercalcaemia

Question 1

the role of the small intestine in calcium homeostasis

Answer 1

where dietary calcium is absorbed

Question 2

the role of the bone in calcium homeostasis

Answer 2

acts as a vast reservoir of calcium

stimulating net resoprtion of bone mineral (osteoclasts break down tissues and release minerals) releases calcium and phosphate into the blood

suppressing this effect allows calcium to be deposited into the bone

Question 3

the role of the kidney in calcium homeostasis

Answer 3

under normal blood calcium concentrations, almost all of the calcium that enters the glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood calcium levels

Question 4

PTH action

Answer 4

to increase the blood concentration of calcium

• production of biologically active form of vitamin D within the kidney
• facilitates mobilisation of calcium and phosphate from bone. to prevent detrimental increase in phosphate, PTH also causes the kidenys to eliminate phosphate
• maximises tubular reabsorption of calcium within the kidney - reduction of loss from the kidney

overall effect is increased calcium and decreased phosphate

Question 5

vitamin D action

Answer 5

acts to increase blood concentrations of calcium

• facilitates absorption of calcium from the small intestine
• in concert with PTH, enhances fluxes of calcium out of bone

Question 6

formation of vitamin D

Answer 6

UV exposure allows the conversion of 7- dehydroxy-cholesterol in the skin to vitamin D3 (cholecalciferol) by keratinocytes

Question 7

what is calcitriol

Answer 7

1-25 OH vitamin D - the active form of vitamin D formed in the kidney

Question 8

calcitonin action

Answer 8

to reduce blood calcium levels

made in the C cells in the thyroid, and is secreted in response to hypercalcaemia

• suppression of renal tubular reabsorption of calcium (eg pee more out)
• inhibition of bone resorption, which minimises fluxes of calcium from bone into blood

Question 9

acute symptoms of hypercalcaemia

Answer 9

stones, bones, groans and psychotic moans

thirst, dehydration, confusion, polyuria

Question 10

chronic symptoms of hypercalcaemia

Answer 10

stones, bones, groans and psychotic moans

myopathy, osteopeania, fractures, depression, hypertension, abdominal pain (renal stones, ulcers, pancreatitis), constipation

Question 11

what are the most common causes of hypercalcaemia

Answer 11

malignancy (eg from bone metastases, myeloma and PTHrP) and primary hyperparathyroidism

Question 12

other causes of hypercalcaemia

Answer 12

drugs: vitamin D and thiazides

granulomatous conditions eg sarcoidosis, TB

familial hypocalciuric hypercalcaemia

high bone turnover: bedridden, thyrotoxic, Paget’s

others

tertiary hyperparathyroidism

Question 13

how does one diagnosis hypercalcaemia due to primary hyperparathyroidism

Answer 13

raised serum calcium

raised serum PTH (or inappropriately normal)

increased urine calcium excretion (this is a regulatory response) - ensure vitamin D is replete

Question 14

diagnosis of hypercalcaemia due to malignancy

Answer 14

lowered albumin, Cl^-, K⁺ and alkalosis

increased phosphate and ALP

X ray, CT, MRI and isotope bone scan

Question 15

what are the mechanisms for malignancy causing hypercalcaemia

Answer 15

metastatic bone destruction

PTHrP secretion from solid tumours

osteoclast activating factors

Question 16

treatment of acute hypercalcaemia

Answer 16

diagnose and treat underlying cause. If Calcium >3.5mmol/L and symptomatic:

1. correct dehydration if present with 0.9% saline

2. biphosphonates prevent bone resorption by inhibiting osteoclast acitivity. a single dose of pamidronate will lower calcium over 2-3 days, maximum effect is a week

3. further management

Question 17

further management in the acute treatment of hypercalcaemia

Answer 17

chemotherapy will help in malignancy

steroids are used in sarcoidosis

salmon calcitonin acts similarly to biphosphonates, and has a quicker onset. rarely used now

furosemide - ? helps to promote renal excretion of calcium but can exacerbate the hypercalcaemia by worsening dehydration. only consider once fully rehydrated and with concomitant IV fluids

Question 18

what does of steroids is used in eg sarcoidosis

Answer 18

40-60mg prednisolone a day

Question 19

if a patient has a raised albumin and urea, what is the likely cause of hypercalcaemia

Answer 19

dehydration

Question 20

if a patient has a normal albumin, normal/high PTH and normal/low phosphate and decreased urine calcium, what is the likely cause of hypercalcaemia

Answer 20

FHH

Question 21

how do granulomatous diseases cause hypercalcaemia

Answer 21

• Due to dysregulated production of 1,25 OH calcitriol by activated macrophages trapped in pulmonary alveoli and granulomatous inflammation – excess activation of vitamin D

Question 22

milk alkali syndrome

Answer 22

hypercalcaemia due to excessive Ca intake

Question 23

PTH level in hypercalcaemia due to malignancy

Answer 23

low eg myeloma and bone metastases

Question 24

causes of raised ALP

Answer 24

• Liver
• Paget’s
• Osteomalacia
• Bone mets
• Hyperparathyroidism
• Renal failure

Question 25

causes of raised ALP and raised calcium

Answer 25

bone mets and hyperparathyroidism

Question 26

causes of raised ALP and low calcium

Answer 26

renal failure and osteomalacia