Endocrinology 12 - Calcium Homeostasis Flashcards
How is phosphate regulated?
- Reabsorption of phosphate from the urine is inhibited by PTH and FGF23
- FGF23 inhibits calcitiol production, and therefore reduced phosphate reabsorption from the gut
How is PTH secretion regulated?
- Ca++ binds to receptors, which inhibits PTH secretion
- In low calcium, there is no inhibition so PTH is secreted
What is the role of vitamin D in calcium homeostasis?
- Increases renal Ca++ reabsorption from the kidney
- Negative feedback on PTH
- Increases gut absorption
List the causes of Vitamin D deficiency
- Receptor defects
- Malabsorption or dietary insufficiency (Coeliac, inflammatory bowel disease)
- Lack of UVB light
- Liver disease
- Renal disease
How do changes in extracellular calcium affect nerve and skeletal muscle exitability?
- To generate AP in nerves/skeletal muscle requires Na+ influx across cell membrane
- High EC calcium blocks sodium influx, so there is less membrane excitability
- Low EC calcium enables greater Na+ influx, so more membrane exitability
List the signs and symptoms of hypocalcaemia
CATs go numb
- Paraesthesia (hands, mouth, feet and lips)
- Convulsions
- Arrhythmias
- Tetany
- Sensitises excitable tissues - muscle cramps, tetany and tingling
What is chvosteks sign?
- Tap facial nerve just below zygomatic arch
- Positive response results in twitching of facial muscles
- Indicates neuromuscular irritability due to hypocalcaemia
What is trousseaus sign?
- Inflation of BP cuff for several minutes induces caropedal spasm (neuromuscular irritability due to hypocalcaemia)
List the causes of hypocalcamia
- Vitamin D deficiency
- Low PTH levels (hypoparathyroidism - neck surgery, auto-immune or magnesium deficiency)
- PTH resistance (pseudohypoparathyroidism)
- Renal failure (impaired 1a hydroxylation (dereased production of 1,25(OH)2D3))
List the signs and symptoms of hypercalcaemia
- Stones (renal effecs - polyurea and thirst, nephrocalcinosis, renal colic and renal failure)
- Abdominal moans (anorexia, nausea, dyspepsia or heart burn, constipation, pancreatitis)
- Psychic groans (fatigue, depression, impaired concentration, altered mentation, coma)
- Reduced neuronal excitability causing atonal muscles
List the causes of hypercalcaemia
90% are the top 2 on this list
- Primary hyperparathyroidism
- Malignancy (tumours/metastases) - often secrete a PTH-like peptide
- Conditions with high bone turnover (hyperthyroidism, pagets disease of bone, immobilised patient)
- Vitamin D excess (rare)
What is seen in primary hyperparathyroidism?
- Raised calcium
- Low phosphate
- Raised (unsuppressed) PTH
What is seen in hypercalcaemia of malignancy?
- Raised calcium
- Suppressed PTH (no problem with the PT gland, too much calcium being released from the bone)
What is seen in vitamin deficiency states?
- Lack of mineralisation in bone
- Results in softening of bone, bone deformities, bone pain, severe proximal myopathy
- Rickets in children
- Osteomalacia in adults
Compare primary and secondary hyperparathyroidism
- Primary hyperparathyroidism causes no negative feedback, autonomous PTH secretion despite hypercalcaemia (adenoma)
- Secondary hyperparathyroidism is vitamin D deficiency or renal failure (high PTH, in an attempt to normalise serum calcium - this is where the calcium is low to begin with, not associated with high calcium)
How is primary hyperparathyroidism treated?
- Parathyroidectomy
- Increase fluids initially, and decrease calcium by loop diuretics
List the biochemical findings in vitamin D deficiency
- Plasma vitamin D is usually low
- Plasma Ca2+ is low (or normal is secondary hyperparathyroidism has developed)
- Plasma phosphate is low (decreased gut absorption)
- PTH is high (secondary hyperparathyroidism)
How is vitamin D deficiency treated in patients with normal renal function?
- Give 25 hydroxy vitamin D
- Patient converts this inactive vitamin D to 1,25 dehydroxy vitamin D via 1a hydroxylase
- Ergocalciferol
- Cholecalciferol
How is vitamin D deficiency treated in patients with renal failure?
- Inadequate 1a hydroxylation
- Can’t activate 25 hydroxyl vitamin D preparations
- Give alfacalcidol (1alpha hydroxycholecalciferol)
What can vitamin D excess cause?
- Hypercalcaemia
- Hypercalciuria
- Due to increased intestinal absorption of calcium
How is calcium regulated?
- Vitamin D (active, calcitriol - increase calcium, inactive vitamin D has no effects until hydroxylation in the kidney)
- PTH (Increased calcium - reabsorption from bone, kidney reabsorption, regulates production of active vitamin D)
Describe the stages of vitamin D production
- Skin produces 25 OH-D3 in response to UV B light, vitamin D2 is from the diet
- Stored in the liver
- This is not a useful form, so second hydroxylation takes place via renal 1 alpha-hydroxylase, stimulated by PTH to make active vitamin D (1,25 (OH)2H3 - calcitriol)
Why does low magnaesium cause hypocalcaemia?
- Magnesium is needed to make PTH
- PTH increases calcium levels in the blood
List the causes of high vitamin D
- Can occur due to treatment with vitamin D active metabolites
- Can occur due to granulomatous diseases
What is tertiary hyperparathyroidism?
- Chronic low calcium in the plasma
- Chronic kidney disease
- PTH raises, production becomes autonomous as the parathyroid glands are active for so long. Calcium is overproduced and raises above normal.
