ENDOCRINOLOGY - PARATHYROID DISEASE Flashcards
What are the 3 forms of calcium in the blood that make up total calcium?
40% bound to albumin
45% is ionised calcium which is active
15% is bound to anions such as phosphate
What can cause pseudohypocalcaemia?
Reduction in amount of albumin will reduce the amount of calcium
What are the 3 controls of calcium homeostasis?
Vitamin D
parathyroid hormone
Calcitonin
How does vitamin D regulate calcium levels?
Calcitriol can be released into the blood stream and stimulate intestinal epithelial cells to increase the synthesis of calbindin-D proteins which increase intestinal absorption of calcium by facilitating the transport of calcium.
How does parathyroid hormone regulate calcium levels?
- Increases bone resorption
• Increases renal reabsorption of calcium
• Increasing synthesis of calcitriol
How does parathyroid hormone increase bone resorption?
PTH upregulates osteoblasts expression of RANK-L which stimulates pre-osteoclasts to differentiate into osteoclasts.
How does parathyroid hormone increase renal reabsorption of calcium?
PTH upregulates expression of specific channels in the DCT leading to increased reabsorption of calcium and increased excretion of phosphate.
How does parathyroid hormone increase synthesis of calcitriol?
PTH upregulates expression of 1-alpha hydroxylase which catalyses the conversion of inactive 25-hydroxycholecalciferol into calcitriol
How does calcitonin regulate calcium levels?
parafollicular cells secrete calcitonin which can inhibit osteoclasts and reduce bone resorption.
How is calcitriol synthesised from a cholesterol precursor?
• 7-dehydrocholesterol is converted into vitamin D3 under the influence of UV radiation
• Vitamin D3 is converted to 25-hydroxyvitamin-D by 25 hydroxylase in the liver
• 1-alpha-hydroxylase converts 25-hydroxylase vitamin-D into 1,25-dihydroxyvitamin-D (calcitriol) - this is metabolically active
Whats the mechanism for preventing calcitriol toxicity?
If levels of calcitriol become excessive, it is converted to 24,25-dihydroxycholecalciferol which is less active
What causes hypoparathyroidism?
• Autoimmune
• Congenital e.g. Di George syndrome
• Radiation
• Surgery - thyroidectomy of parathyroidectomy
• Hypomagnesia - Mg is required for PTH secretion
• Pseudohypoparathyroidism - failure of target cells to respond to parathyroid hormone receptor
• Pseudopsuedohypoparathyroidism - morphological features of pseudohypoparathyroidism but with normal biochemistry
What are the biochemical abnormalities in hypoparathyroidism?
Low PTH
Hypocalcaemia
Hyperphosphataemia
What symptoms can hypoparathyroidism present with?
Paraesthesia of hands, feet and perioral
twitching facial muscles
Tetany
tiredness
mood changes, such as feeling irritable, anxious or depressed
dry, rough skin
coarse hair that breaks easily and can fall out
fingernails that break easily
What are some signs of hypoparathyroidism?
Chvosteks sign
Trousseaus sign