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Thyroid Hormone (TH) Structures Iodine Synthesis Secretion Regulation Metabolism Actions Hypo- & hyper- thyroidism follicle Reverse T3 Activity: T3 > T4 >> rT3 iodine iodised salt … no salt sale in the shops of Dushanbe Blood I– T3T4 Thyroglobin 90% T4, 9% T3, 1% rT3 Regulation of Thyroid Hormone Concentrations Cold (neonates) + Hypothalamus Thyrotrophin Releasing hormone (TRH) + Anterior Pituitary Thyroid hormone (TH) Thyroid Stimulating Hormone (TSH) = Thyrotrophin + (1) Thyroid Gland 1. TH synthesis 2. TH release 3. number & size of cells Thyroid stimulating immunoglobulins (TSI) Metabolism 33% T4 45% * * T3 di-iodothyronines rT3 I– split off In: liver, kidney, pituitary * Regulation: T4 T3 inhibition by: propylthiouracil, propanolol ( blocker) glucocorticoids burns, trauma, renal failure, infarct food intake In Blood protein TH + (thyroid binding (T4, T3) globulin & others) free Free % Protein bound—T4 or T3) most small < 0.5 % gets into cells – biologically relevant Thyroid Hormone Effects T3 > 4–5 times Mechanism: T4 >> rT3 inert steroid hormone-like intracellular receptor modulation of RNA synthesis slow on-off effects Thyroid Hormone Effects 1. Calorigenic actions effect on intermediary metabolism CHO / fat / protein effect on growth & development 2. Sympathomimetic effects facilitates actions of catecholamines (adrenalin, noradrenalin) Calorigenic actions Heat producing e.g. basal metabolic rate heat production energy use O2 consumption number & size mitochondria Metabolism Glucose: rate absorption uptake to cells Fat: clearance lipoproteins turnover Protein: amino acid uptake protein synthesis • If T4 or T3 is too high, then protein catabolism Vitamins:B12 absorption carotene Vit. A • If T4 or T3 is too high, then vitamin deficiencies Protein Synthesis net too little [ TH ] too much Growth and development in utero CNS & neonates Sympathomimetic Effects Relationship to catecholamines: • some similar effects • T4 / T3 adrenergic receptors (number & affinity) • some effects of T4 / T3 can be treated with blockers Excess T4 / T3 jumpy, anxious tremor pulse rate bounding pulse, systolic P diastolic P peripheral vasodilation Thyroid stimulating immunoglobulins = Thyroid stimulating hormone No negative feedback Hypothyroidism: • thyroid disease • I– deficiency Fetus: impaired CNS development Child: height, metal retardation & cold intolerance, impaired mental function, coarse hair, dry skin, husky voice, reflexes Goitre = size thyroid gland • euthyroid • hyperthyroid e.g. TSI • hypothyroid e.g. I– deficiency, autoimmune thyroiditis I– deficiency T4 / T3 negative feedback pituitary TSH secretion number & size thyroid cells Summary • T4, T3, (rT3) • synthesis in colloid • negative feedback regulation pituitary & hypothalamus • regulated metabolism • free concentrations low but biologically relevant • steroid hormone like – slow on-off • actions: calorigenic on intermediary metabolism potentiation of catecholamines actions