Ca and Phosphate Regulation Flashcards
What is the source of PTH?
Parathyroid gland (sits behind the thyroid gland)
Summarise calcium homeostasis.
What are the three main functions of PTH on calcium homeostasis?
- Kidneys –> reduced Ca excretion
- Kidneys 1-alpha-hydroxylase –> more calcitriol (active VitD) production so more Ca absorption from gut
- Bones –> more release of Ca and phosphate
Summarise phosphate regulation in the kidneys.
- Proximal convoluted tubule
- PTH and FGF23 inhibiting Na+/PO3- co-transporter - less reabsorption of phosphate –>more excretion
- FGF23 inhibiting calcitriol action –> less absorption of phosphate from gut
What is FGF23 and where is it made?
FGF23: Fibroblast growth factor 23 from osteocytes
Describe the regulation of PTH secretion.
High Ca–> Ca binds to sensor receptor on the surface of parathyroid cells –> inihibtion of PTH release.
Vice versa.
Summarise the production of vitamin D in the body.
- UVB on the skin forming Vit D3 in liver (cholecalciferol)
- or Vit D2 from diet (ergocalciferol)
- These are converted in the kidney to Calcitriol by 1-ALPHA-HYDROXYLASE (which is regulated by PTH)
List 4 actions of calcitriol (1,25dihydroxyD2).
- -ve feedback on PTH
- Gut - Increased Ca absorption in gut
- Kidney - Increased renal Ca absorption
- Bone - Ca maintanance in bone
List 5 causes of Vit D deficiency.
- Diet or GI malabsorption of dietary D2 eg coeliac disease, inflam bowel disease,
- Lack of sunlight (so lack of UVB)
- Renal failure (so no conversion to active form)
- Liver failure (no D3 synthesis)
- Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)
How do changes in EC calcium affect nerve and skeletal muscle excitability?
To generate an AP in nerves/skeletal muscle requires Na+ influx across cell membrane which can be affected by extracellular Ca:
HYPERcalcaemia = Ca2+ blocks Na+ influx, so LESS membrane excitability
HYPOcalcaemia = enables GREATER Na+ influx, so MORE membrane excitability
What is the normal range for Ca?
2.2-2.6mmol/L
What are the signs and symptoms of hypocalcaemia?
SENSITISES excitable tissue: CATs go numb:
- Parasthesia (numbness of hands, mouth, feet , lips)
- Convulsions
- Arrhythmias
- Tetany (inability to relax a muscle)
What tests would you do clinically to test for hypocalcaemia? What are the positive results?
Chvostek’s Sign – tap facial nerve below zygomatic arch -> twitching of facial muscles = (positive sign)
Trousseau’s sign – inflate BT cuff for several minutes ->carpopedal spasm (positive sign). This is inducing tetany (clawing of the hand).
These show neuromuscular irritability due to hypocalcaemia.
What are the causes of hypocalcaemia?
- VIT D DEFICIENCY
- PTH LEVELS LOW - hypoparathyroidism
- Surgical – neck surgery
- Auto-immune
- Magnesium deficiency – Mg is needed for PTH to work
- RECEPTORS - PTH resistance e.g. pseudohypoparathyroidism (rare)
- RENAL failure –> impaires 1alpha hydroxylation so less 1,25 dihydroxyD3 formation
What are the signs and symptoms of hypercalcaemia?
“Stones, abdominal moans, psychic groans” - REDUCED NEURONAL EXCITABILITY (atonal muscles)
- Stones – renal effects (you excrete Ca in kidneys)
- Polyuria & thirst, nephrocalcinosis, renal colic, chronic renal failure
- Abdominal moans - GI effects
- Anorexia, nausea, dyspepsia, constipation, pancreatitis
- Psychic groans - CNS effects
- Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
What is the most common cause of hypercalcaemia?
Tumours/metastases which can secrete PTH-like peptide
What are the common causes of hypercalcaemia?
PRIMARY hyperparathyroidism - autonomous PTH secretion despite hypercalcaemia
MALIGNANCY – tumours/metastases often secrete a PTH-like peptide or metastases in bone can cause high Ca but low PTH
CONDITIONS with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)
Vitamin D EXCESS (rare)
What are the biochemical features of
a) primary parathyroidism?
b) hypercalcaemia of malignancy
Primary hyperparathyroidism:
- Raised Ca
- Low phosphate
- Raised (unsuppressed) PTH
Hypercalcaemia of malignancy
- Raised Ca
- Suppressed PTH
What is the consequence of Vit D deficiency states? In adults and children?
Lack of MINERALISATION of bone –> “softening” of bone, deformities, bone pain, proximal myopathy.
Children –> rickets (bowing of legs)
Adults–> osteomalacia
What is the difference between primary and secondary hyperparathyroidism?
- PRIMARY = no negative feedback, autonomous PTH release despite hypercalcaemia
- SECONDARY = vitamin D deficiency so low hypocalcaemia but high PTH which tries to normalise the serum calcium
What are the biochemical features of Vitamin D deficiency(e.g. rickets)?
- LOW inactive Vit D in plasma (25(OH)D3)*
- LOW plasma Ca2+ (but may be normal is secondary hyperparathyroidism has developed)
- LOW plasma phosphate from reduced gut absorption
- HIGH PTH - secondary hyperparathyroidism
*(NB we don’t measure 1,25 dihydroxy vitamin D (1,25 (OH)2 D) to assess body vitamin D stores)
How would you treat vitamin D deficiency?
- If normal renal function…
- Give 25hydroxy-vitaminD
- Ergocalciferol (D2)
- Cholecalciferol (D3)
- Give 25hydroxy-vitaminD
- If renal failure… = inadequate 1alpha hydroxylation so can’t give inactive form
- Alfacalcidion = 1alpha hydroxycholecalciferol
What are the causes of vitamin D excess (intoxication)?
Excessive Alfacalcidiol treatment (active metabolites of Vit D)
Granulomatous disease e.g. sarcoidosis, leprosy, TB (macrophages in granuloma –> 1-alpha hydroxylase production –> 25(OH)D to active 1,25(OH)2D)
Give 2 consequences of Vit D excess.
- Hypercalcaemia
- Hypercalciuria (Ca is excreted in urine)
This is due to increased intestinal absorption of Ca.
What is the treatment for rpimary hyperparathyroidism?
Parathyroidectomy
