Disregulation of calcium Flashcards
Which hormones increase serum calcium?
Vitamin D and PTH
Which hormones decrease serum calcium?
Calcitonin - but no negative effects if removed
How does Vitamin D3 get activated?
Vitamin D3 goes to liver (25-hydroxylase) to kidney (1-alpha-hydroxylase) to become 1,25(OH)2 cholecalciferol (aka calcitriol)
What are the three effects of calcitriol?
Ca2+ & PO43- absorbed from the kidney and gut, and osteoclast increased (to reabsorb calcium from bone)
What are the four effects of PTH? (stimulates calcitriol)
CA2+ & PO43- absorbed from gut,
renal secretion of phosphate in kidney,
osteoblast and 1-alpha-hydroxylase activity
How does PTH affect renal excretion of phosphate and why?
Increased renal excretion, inhibits Na+/PO43- cotransporter, more released in urine (acts as homeostasis - PO43- stimulates PTH release, so need to remove to prevent overproduction of PTH)
Why does PTH lead to proximal myopathy?
Bone Ca2+ absorption leads to osteomalacia which causes weakness in limbs (proximal myopathy)
What demographic of patients are more at risk of proximal myopathy?
Lactovegetarian Asian patients
What other molecule regulates phosphate levels and where is it released?
FGF23 // in the bones
What are the two effects of FGF23?
Inhibits Na+/PO43- cotransporter (more phosphate release in urine), inhibits synthesis of calcitriol
decreases serum phosphate
What are the four signs of hypocalcaemia?
(excitation)
CATs go numb - convulsions, arrhythmias, tetany, parasthesia
What are two signs in the presentation of hypocalcaemia?
Trosseau’s Sign (carpopedal spasm), inflating bp cuff, cannot relax the hand
Chvostek’s sign (facial parasthesia)
What are the two hormone deficiencies that may cause hypocalcaemia and what causes them?
Hypoparathyroidism - autoimmune, magnesium deficiency, congenital and surgical (neck surgery) //
Vitamin D deficiency - poor diet, renal failure, lack of UV
What are the 3 signs of Hypercalcaemia (aka the rhyme - flattened)
Kidney stones (nephrocalcaemia causes renal colic), due to filtration issue
Abdominal moans (anorexia, nausea, dyspepsia, pancreatitis and constipation), atonal gut - no peristalsis
Psychic groans (fatigue, depression, low concentration) and atonal muscles
What are the three causes of Hypercalcaemia and the relative proportions?
Primary hyperparathyroidism (90%),
Malignancy - bony metastases, certain cancers secrete PTH related peptide
Vitamin D excess (rare)
How does primary hyperparathyroidism work?
Parathyroid adenoma - continual increase of PTH regardless of calcium levels (no negative feedback)
Normal relationship between calcium and PTH
Inverse relationship
High calcium = low PTH
High PTH = low calcium
Biochemistry of primary hyperparathyroidism
High calcium
Low phosphate, increased renal phosphate excretion
High PTH
How would you treat kidney stones and depression in hospital?
IV Saline Hydration
How do you treat primary hyperparathyroidism?
Parathyroidectomy
What are two conditions formed from not treating primary hyperparathyroidism?
Osteoporosis (low phosphate, calcium extracted), Hypercalcaemia
How does secondary hyperparathyroidism work?
Low vitamin D means low calcium, PTH will increase as a result // can be due to renal failure as they cannot make calcitriol
Secondary hyperparathyroidism
Normal physiological response to hypocalcemia
usually due to vit D deficiency
What are the two drugs you’d give for secondary hyperparathyroidism?
Vitamin D3,
Alfacalcidol (kidney failure) - have faulty 1-alphahydroxylase .: give them active vit D
How does tertiary hyperparathyroidism work?
Chronic vit D deficiency .: no calcitriol
Chronic renal failures (as a progression from secondary) - low calcium, PTH increases too much (hyperplasia of parathyroid gland), Hypercalcaemia due to autonomous PTH secretion
How would you treat tertiary hyperparathyroidism?
Parathyroidectomy
Mechanism of malignancy hypercalcaemia?
Suppressed PTH (aka physiological response - has nothing to do with parathyroid gland) - negative feedback is normal
high calcium in the bloodstream
Bone mets make PTH related peptides which stim osteoclasts
Impact of Primary hyperparathyroidism on PTH and renal fct?
High PTH but normal renal function
What is the diagnostic approach for tertiary hyperparathyroidism?
High PTH and hyperplasia of organs and abnormal renal function
What is the diagnostic approach for secondary hyperparathyroidism?
High PTH, low vitamin D and calcium
How to measure calcium levels
Not calcitriol
measure 25-cholecalciferol in the blood
Not useful with patients with chronic renal failure
Hypercalcaemia treatment
Hydration, via IV saline solution
Bisphosphonate, inhibit osteoclasts to stop bone reabsorption and decrease calcium (zoledronate)
