Overview of Iodine metabolism.

• Diet –> absorbed from GIT into circulation–>  500mcg/L

T3 / T4 synthesis / secretion.

• More amount of T4 secreted than T3 but T3 is more biologically active.
• T3 is made at site of action by deiodinating T4.
• Reverse T3 is not biologically active
• At interface between thyrocyte and colloid, iodide undergoes organification.
  • Iodide –> iodine
  • Incorporated into carbon 3 of thyroglobulin molecule in colloid (thyroid peroxidase on thyrocyte apical membrane)
  • The thyroid hormone sythesised remains in colloid and when required the thyrocytes endocytose part of the colloid–> lysosomal degradation–> free T4 and T3 released into circulation
  • TPO generates reactive iodine species which react with thyroglobulin–> first product is MIT monoiodotyrosine
  • MIT is then iodinated at carbon 5 –> di-iodotyrosine(DIT) (by iodotyrosine deiodinase)
  • DIT +DIT = T4 + alanine
  • MIT + DIT = T3 + alanine

 

Effects of T3 / T4.

• T3 bind to receptor in nucleus (T4 binds less avidly) –> T3/receptor complex binds DNA –> transcription of cell proteins to effect functions.
• Stimulate O2 consumption
• Control level of metabolism
• Help regulate lipid and carbohydrate metabolism
• Influence body mass and Mentation

Regulation of T3 / T4 secretion.

• Throtrophin releasing hormone from hypothalamus
• Thyroid stimulating hormone from anterior pituitary
• T3 and T4 from thyroid which negatively feeds back to the other 2.

 

Hypothyroidism

• In neonatal or fetal period –> mental retardation, inhibition of growth
• Weight gain
• Slowing of mentation
• Slowing of metabolism
• Cold intolerance
• Hair coarsening

 

Hyperthyroidism

• Tremor
• Hyper-reflexia
• Increased appetite
• Weight loss
• Heat intollerance
• Agitation, nervousness
• tachycardia

 

Overview of Ca2+ metabolism

• Young adult has 1100g of Ca
• 99% in skeleton
• Plasma ca is partly bound to protein
• Free ionized calcium in bodily fluids is the key second messenger
• Needed in nerve function, muscle contraction and blood coagulation

 

Overview of bone physiology.

• A readily exchangeable pool of 100mmol in bone
• Stable pool of 27200mmol –> slower to mobilise
• Osteoclasts break down bone
• Osteoblasts lay down new osteo matrix which gets calcified.

 

Vitamin D and OH-Cholecalciferols.

• Increases gut absorption of calcium
• Increase renal  reabsorption of Ca
• Increases activation of osteoblasts (Vit D needed for normal bone ossification) –> secondary increased activity of osteoclasts.
• 7 dehydrocholesterol –> Vit D3 in skin under UV light(vit D3 also ingested) –> 25 hydroxycholecalciferol (in liver by p450) –> 1,25 dihydroxycholecalciferol in kidney (by 1alpha hydroxylase)= calcitriol
• High plasma PO4 inhibits Vit D by inhibiting 1alpha hydroxylase

 

PTH.

• Actions.
  • Increase 1alpha hydroxylase –> increase vit D
  • Increase phosphate excretion in kidney
  • Stimulate osteoblasts and osteoclasts
  • The increased renal Calcium reabsorption maybe offset by the increase in filtered calcium

• Regulation of secretion.
  • Low plasma ionised Ca –> increased PTH release
  • Negative feedback via Ca binds G protein receptor –> phosphoinositide turnover–> inhibit PTH release
  • 1,25dihydroxycholecalciferol acts on parathyroid to decrease preproPTH mRNA
  • Increased palsma phosphate lowers plasma free Ca–> increased PTH release
  • Mg required for normal PTH secretion
  • Made as preproPTH and cleaved before secretion into plasma

 

Calcitonin.

• Made by the parafollicular cells/clear cells of thyroid
• T 1/2 10mins

• Actions.
  • Inhibits osteoclasts –> decrease bone resorption –> Lower plasma calcium
  • Increases calcium excretion in urine

• Regulation of secretion.
  • Secreted when plasma Ca is high
  • Secretion starts when Ca is 9.5mg/dL

• Stimulants
  • Beta-adrenergic agonists, dopamine, oestrogens, Gastrin, cholecystokinin, glucagon, and secretin
  • gastrin being the most potent stimulus
    • plasma calcitonin level is elevated in Zollinger–Ellison syndrome and in pernicious anemia

 

Viva questions:

1. Tell me about the thyroid gland and thyroid hormones.
   • T3 T4
   • Calcitonin
2. Tell me about the metabolism of calcium.
3. Tell me about Vitamin D and its role in calcium metabolism