Endo 12 - Ca and Phosphate regulation Flashcards
How many parathyroid glands are there
4
Vit D is stored in the liver as?
Calcidiol (25, OH-D)
Name 3 action of PTH
- Reduces Ca excretion in the kidneys
- Promotes bone resorption
- Stimulates 1a-hydroxylase in kidneys –> converts inactive Vit D —> active calcitriol
Describe phosphate regulation
Phosphate is regulated by the gut and kidneys.
- Phosphate is reabsorbed with Na+, via a cotransporter (from urine to PCT cell).
- FGF23 (made by osteocytes) and PTH inhibit the cotransporter —> meaning more phosphate lost in urine.
(Therefore in primary HPT, serum phosphate low due to increased excretion).
- FGF23 also inhibits calcitriol - which means less phosphate absorption from the gut.
Explain how PTH secretion is regulated.
Regulation occurs in parathyroid cells
High Ca conc in ECF/serum binds to PTH receptor —> receptor activation causes inhibition of PTH secretion
Low Ca conc in ECF/serum = less binding / receptor activation = less inhibition = more PTH secretion
Explain how calcitriol is synthesised
- Skin (7-dehydrocholesterol) —> Vitamin D3 - cholecalciferol (via UVB light and dietary Vitamin D)
- In liver, stores as 25-OH-D3 (inactive).
- In kidney, activated via renal 1a-hydroxylase to become 1, 25 (OH)2D3 (calcitriol - biologically active)
What are the main roles of calcitriol?(active vit d)
- Ca absorption in gut
- Ca maintenance in bone
- Increased renal Ca absorption
- Negative feedback on PTH (to prevent hypercalcaemia)
What are the causes of vitamin D deficiency
- Diet
- Lack of sunlight
- GI malabsorption (coeliac disease, IBD)
- Renal failure, liver failure
- Vit D receptor defects (autosomal recessive, rare, resistant to Vit D treatment)
How do changes in EC Ca affect nerve and skeletal muscle excitability?
- High EC Ca = hypercalcaemia = Ca blocks Na influx, so less membrane excitability
- Low EC Ca = hypocalcaemia = enables greater Na influx, more membrane excitability
What are the signs and symptoms of hypocalcaemia
- Parasthesia (numbness - hands, mouth, feet, lips)
- Convulsions
- Arrhythmias
- Tetany
CATs go numb
Name 2 signs of hypocalcaemia that we can use
- Chvosteks sign - tap facial nerve just below zygomatic arch - positive response = twitching of facial muscles
(Indicates neuromuscular irritability due to hypocalcaemia) - Trousseaus sign - Inflation of BP cuff for several minutes - induces carpopedal spasm - state of tetany as a result of neuromuscular irritability due to hypocalcaemia
What are the causes of hypocalcaemia
- Vit D deficiency
- HypoPT (due to surgery, auto-immune or Mg deficiency)
- PTH resistance - i.e. pseudoHypoPT
- Renal failure (causing impaired 1a-hydroxylation so less calcitriol production)
What are the signs and symptoms of hypercalcaemia
Stones, abdominal moans and psychic groans
- Stones - renal effects (polyuria and thirst, nephrocalcinosis, renal colic, chronic renal failure
- Abdominal moans - anorexia, nausea, dyspepsia, constipation, pancreatitis
- Psychic groans - fatigue, depression, impaired concentration, altered mentation, coma
What are the causes of hypercalcaemia
- Primary HPT
- Malignancy - tumours, metastases (often secrete PTH like peptide)
- Conditions with high bone turnover (hyperthyroidism, Paget’s, immobilised patient)
- Vit D excess (rare)
What are the features of primary HPT
- Raised Ca
- Low phosphate (less renal absorption)
- Raised (unsuppressed PTH due to no negative feedback)
What are the features of hypercalcaemia of malignancy
- Raised Ca
2. Suppressed PTH (due to negative feedback)
What is a vitamin D deficiency state
Lack of mineralisation in bone
Results in softening of bone, bone deformities, bone pain, severe proximal myopathy
Rickets in children
Osteomalacia in adults
Differentiate primary and secondary HPT
Primary HPT = no negative feedback, autonomous PTH secretion despite hypercalcaemia. Treated with parathyroidectomy
Secondary HPT = high PTH levels is the RESPONSE to low serum Ca (trying to normalise) e.g. due to Vit D deficiency
What are the biochemical findings in Vit D deficiency
- Plasma 25-OH-D3 (inactive Vit D) low
- Low plasma Ca (but may be normal if secondary HPT has developed)
- Low plasma phosphate
- PTH high (secondary HPT)
How is Vit D deficiency treated in patients without renal failure?
If patient has normal renal function - give 25,OH,D3. Patient converts it into calcitriol (1, 25-OH-D3). Can be ergocalciferol based (25, OH D2) or cholecalciferol based (25, OH, D3)
How is Vit D deficiency treated in patient with renal failure?
Renal failure = they cannot 1a hydroxylate and activate Vit D into Calcitriol
Give alfacalcidol - 1ahydroxycholecalciferol = acts as calcitriol substitute
What can Vit D excess cause
Hypercalcaemia and hypercalcuria due to excess intestinal Ca absorption
Name 2 causes of Vit D excess
- Excessive treatment with active metabolites of Vit D (e.g. alfacalcidol)
- Granulomatous diseases (rare) - sarcoidosis, leprosy and TB (macrophages in granuloma produce 1a hydroxylase - converts 25(OH)D into calcitriol)
