Calcium and phosphate regulation Flashcards
What is the role of parathyroid hormone (PTH) in calcium homeostasis?
Made by parathyroid glands (sense low serum calcium and increase PTH secretion).
Increases calcitriol formation and decreases excretion of calcium in the kidneys. Regulates conversion of inactive vitamin D (25-OH-D) to active vitamin D (1,25-(OH)2-D).
Stimulates release of calcium and phosphorus from bone.
Where is phosphate reabsorbed from?
Gut.
Kidneys.
How is phosphate reabsorbed from the kidneys?
Via sodium phosphate transporter cells.
Reabsorption of phosphate via these transporters results in less sodium excretion in the urine.
Increased phosphate loss in the urine would lower serum phosphate levels.
Which two factors inhibit renal phosphate reabsorption, and how?
PTH inhibits renal phosphate reabsorption by inhibiting sodium/phosphate transporters, so in primary hyperparathyroidism, serum phosphate is low due to increased urine phosphate excretion.
FGF23- derived from bone, also inhibits phosphate reabsorption in the kidneys by inhibiting sodium/phosphate transporters and also inhibits synthesis of calcitriol, causing less phosphate absorption from the gut.
What are the different causes of vitamin D deficiency?
Diet
Lack of sunlight
GI malabsorption
Coeliac disease
Inflammatory bowel disease
Renal failure
Liver failure
Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)
How do changes in extracellular calcium affect nerve and skeletal muscle excitability?
To generate and action potential in nerves/ skeletal muscle require Na+ influx across cell membrane.
High extracellular calcium (hypercalcaemia) = Ca2+ blocks Na+ influx, so less membrane excitability.
Low extracellular calcium (hypocalcaemia) = enables greater Na+ influx, so more membrane excitability.
What are the signs and symptoms of hypocalcaemia?
Sensitises excitable tissues
Muscle cramps/tetany
Tingling
Paraesthesia (hands, mouth, feet, lips)
Convulsions
Arrhythmias
What is the normal range of serum Ca2+?
2.2-2.6 mmol/L
What is Chvostek’s sign?
Tap facial nerve just below zygomatic arch.
Positive response = twitching of facial muscles.
Indicates neuromuscular irritability due to hypocalcaemia.
What is Trousseau’s sign?
Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia.
What are the causes of hypocalcaemia?
Vitamin D deficiency.
Low PTH levels = hypoparathyroidism (surgical- neck surgery; autoimmune; magnesium deficiency).
PTH resistance, e.g. pseudohypoparathyroidism.
Renal failure (impaired 1 alpha hydroxylation; decreased production of 1,25-(OH)2-D3).
What are the signs and symptoms of hypercalcaemia?
‘Stones, abdominal moans and psychic groans’.
Reduced neuronal excitability.
Atonal muscles.
Stones- renal effects: • 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 are the possible causes of hypercalcaemia?
Primary hyperparathyroidism.
Malignancy- tumours/metastases often secrete a PTH-like peptide.
Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone- immobilised patient).
Vitamin D excess (rare).
What are the different vitamin D deficiency states and their characteristics?
Lack of mineralisation in bone.
Results in ‘softening’ of bone, bone deformities, bone pain, severe proximal myopathy.
In children- rickets (leg bowing).
In adults- osteomalacia.
What are the biochemical findings in vitamin D deficiency?
Plasma [25(OH)D3] usually low- don’t measure 1,25-dihydroxy-vitamin D (1,25-(OH)2-D) to assess body vitamin D stores.
Plasma [Ca2+] low (may be normal if secondary hyperparathyroidism has developed).
Plasma [PO43-] low (reduced gut absorption).
[PTH] high (secondary hyperparathyroidism).
