Chempath 10: Calcium Flashcards
Where does PTH act ?
- Kidneys directly (increased Ca reabsorption, increased PO4 excretion)
- Increases 1 alpha hydroxylase
- Bone (causes increased Ca and PO4 resorption)
What does 1° alpha hydroxylase do ?
Activates vitamin D 25-OH-D3 –> 25- (OH)2-D3
What is the most common cause of 1° hyperparathyroidism?
Parathyroid adenoma
What causes 2° hyperparathyroidism ?
Renal osteodystrophy
(chronic renal failure means less vitamin D activated, so less Ca resorption and less PO4 excretion. low calcium causes PTH release)
What causes 3° hyperparathyroidism ?
Prolonged CKD in 2° hyperparathyroidism causes hyperplasia of the Parathyroid causing autonomous PTH release even when Ca is high.
List 2 causes of hypoparathyroidism ?
1- Di George syndrome
2- Post thyroidectomy
What does vitamin D deficiency cause ?
Rickets in children
Osteomalacia in adults
Which metabolic bone disorder causes looser’s zone fractures and bowing ?
Osteomalacia
What happens in Paget’s disease?
Increased bone remodelling
high PTH
How can sarcoidosis cause hypercalcaemia ?
causes non-renal release of 1 alpha hydroxylase
What are the features of Pseudohypoparathyroidism?
- Type 1a = Albright’s hereditary osteodystrophy
- High PTH, low Ca, High PO4
- PTH resistance means low calcium
- syndromic features: low IQ, short stature, short 4th and 5th metacarpals
- Maternal imprinting of an autosomal dominant mutation
What are the features of pseudopseudohypoparathyroidism ?
- same syndromic features as Albright’s hereditary osteodystrophy
- Calcium is normal because no PTH resistance
- Paternal imprinting of autosomal dominant mutation
What is the management of hypercalcaemia?
1- Hydration with fluids
2- Bisphosphonates
3- Calcitonin (severe)
What is the management of hypocalcaemia ?
1-Give calcium
CKD: Alpha calcidiol
3- 10% Calcium gluconate IV
Why can Chronic pancreatitis cause Osteomalacia ?
- Chronic pancreatitis causes a reduction in emulsification of fats
- This means less fat soluble vitamins (ADEK) are absorbed from the G.I tract
- Causing a vitamin D deficiency and therefore osteomalacia
Why does Multiple Myeloma not cause a raised ALP ?
- Multiple myeloma only affects osteoclasts
- Osteoblast activity is what releases ALP
List 4 causes of a raised ALP?
- Cholestatic liver disease (also raised GGT)
- Pregnancy (Placenta releases ALP)
- Bone disease (Paget’s, Renal osteodystrophy fracture)
- Drugs (carbamazepine, phenytoin, erythromycin)
Why do we use corrected calcium ?
-Because normally 40% of calcium is bound to albumin, so if anything affects albumin it would also affect calcium levels.
Corrected calcium takes albumin into consideration
List 3 causes of hypocalcaemia with elevated phosphate ?
- CKD
- Hypoparathyroidism
- Hypomagnesaemia
- (Pseudohypoparathyroidism)
List 3 causes pf Hypocalcaemia with normal or low phosphate ?
- Osteomalacia
- Acute pancreatitis
- Respiratory alkalosis
Why does respiratory alkalosis cause Hypocalcaemia ?
- Respiratory alkalosis is most commonly due to hyper ventilation.
- The alkalosis causes increased binding of free calcium to albumin.
- Less free calcium causes hypocalcaemia seen with symptoms such as parasthesia, tetany etc
normal calcium concentration
2.2-2.6 mmol/L
forms of calcium in the serum
free (ionised) - 50% - BIOLOGICALLY ACTIVE
protein-bound - 40% - bound to albumin
complexed - 10% - citrate/phosphate
why do you measure corrected calcium
takes into account the serum albumin
describe the response to hypocalcaemia
hypocalcaemia detected by parathyroid glands
release PTH
calcium from - bone, gut, kidneys (and 1 alpha hydroxyls activation)
what is the rate limiting step in vitamin D activation
1 a hydroxylase
role of PTH
liberation of calcium from bone and kidneys
stimulates 1 a hydroxyls activity - calcitriol
stimulates renal phosphate excretion
role of calcitriol (1,25 (OH)2 D3)
increased calcium and phosphate absorption from the gut
bone remodelling
describe vitamin D synthesis
7 - dehydrocholesterol (+sun)
cholecalciferol (D3) (+25 hydroxylase in liver)
25-hydroxycholecalciferol (+ 1 a hydroxylase from kidneys)
1,25 dihydroxycholecalciferol
why can you get hypercalcaemia in sarcoidosis
lung can express 1 alpha hydroxylase
what are the roles of active vitamin D
increase intestinal Ca absorption
increase intestinal phosphate absorption
boen formatie
when are ALP levels raised
by -product of osteoblast activity
levels rise when bone resorption is stimulated by vitamin D or PTH
features of vitamin D deficiency bone disorders
defective bone mineralisation
children - rickets
adults - osteomalacia
features of osteomalacia
bone and muscle pain
increased fracture risk
low calcium, low phosphate, high ALP
losers zones (pesudofractures)
features of rickets
bowed leges
costochondral swelling
widened epiphyses at wrists
myopathy
other causes of osteomalacia
renal failure - lack of 1 a hydroxylase means you cannot activate vitamin D (can give pre-activates)
anticonvulsants (bd vitamin D)
physic acid - chelates vitamin D, chapatis
features of osteoporosis
fractures preset loss of bone mass disuse of bones collie's fracture (wrist), hip, spine calcium and phosphate normal
DEXA scan - T score, Z score
T and Z score values for osteoporosis and osteopenia
osteoporosis - T score
list causes of osteoporosis
sedentary lifestyle alcohol low BMI hyperprolactinaemia thyrotoxicosis bushings steroids prolonged recurrent illness
treatment for osteoporosis
vitamin D
bisphosphonates
teriparatide (PTH derivative)
what is the most common cause of hypercalacemia
parathyroid adenoma
parathyroid hyperplasia (MEN1)
parathyroid carcinoma
(all primary hyperparathyroidism)
features of familial benign hypercalcaemia
caused by a mutation in the CaSR this detect calcium levels increase in the set point for PTH release causes mild hypercalcaemia benign no kidney stones
list 3 types of hypercalacemia of malignancy
humour hypercalcaemia of malignant (eg small cell lung cancer) - PTHrp release
bone mets - eg breast cancer - local bone osteolysis
haem malignancy - eg myeloma - cytokines
list causes of non-PTH driver hypercalacemia
sarcoidosis thyrotoxicosis (thyroxine increases bone resorption) hypoadrenalism thiazide diuretics excess vitamin D
treatment for hypercalcaemia
fluids
bisphosphonates
treat underling cause
primary cause of secondary hyperparathyroidism
renal osteodystrophy low/n Ca high PO4 high PTH high alk phos normal vitamin D
cause of tertiary hyperparathyroidism
autonomous PTH secretion post renal transplant high Ca low PO4 high PTH high/n alk phos normal vit D
causes of hypoparathyroidism
low levels pTH - primary Di George
secondary - post thyroid surgery
low Ca
high PO4
low/n alk phos
normal vit D
hypercalacemia - low/n albumin - high phosphate, causes?
high alp - bone mets, thyrotoxicosis, sarcoidosis
normal alp - myeloma, excess vitami D, sarcoid, milk alkali
cause of hypercalcaemia high albumin
urea high = dehydration
cause of hypocalcaemia normal/ low phosphate
osteomalacia
acute pancreatotos
over hydration
resp alkalosis
cause of hypocalcameia with high phosphate
CKD
hypoparathyroidism (inc post thryroid surgery)
pseudohyperparathyroisim
hypomagnesaemia
symptoms of hypocalcaemia
perioral paraesthesia, carpopedal spasm, nm excitability, T+ C sign
treatment for hypocalacemia
oral calcium supplement eg sandocal
CKD 0 alfacalcidiol
severe - 10% calcium gluconate, then calcium infusion
