THE THYROID GLAND Medical Presentation

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Published on : Apr 09, 2019 | Views : 3191 | Downloads : 30

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Slide 1-

The Thyroid Gland
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Thyroid follicular cells morphologically & functionally polarized Each side/compartment has specific functions in the synthesis & release of TH: basolateral: Iodide uptake & T4 deiodination apical: Iodide efflux & iodination
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Iodide uptake Iodination Conjugation Endocytosis Proteolysis Secretion Hyperplasia
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Tg is a glycoprotein containing multiple tyrosine residues Synthesized in thyroid follicular cells & secreted through the apical membrane Storage: colloid A scaffold upon which TH synthesis takes place Once in the lumen, undergoes post-translational modifications Hormone (s): synthesis, storage, release, transport and regulation
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Iodide: readily absorbed from dietary sources Enters the thyroid follicular cell via the active, saturable, energy-dependent 2Na-I symporter located in the basolateral plasma membrane Since iodination occurs in the lumen, iodide leaves the cell thru apical efflux via the Cl-I transporting protein (iodide channel) Hormone (s): synthesis, storage, release, transport and regulation
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In the lumen, residues of Tg are iodinated by iodine Hormone (s): synthesis, storage, release, transport and regulation
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Release Conjugation Endocytosis Proteolysis/Cleavage of Tg Release from the basolateral membrane into the circulation T4 (90%) > T3 (10%) Most circulating T3 (75%) is formed peripherally by deiodination of T4 (liver and kidneys) Hormone (s): synthesis, storage, release, transport and regulation
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Transport Most (70%) of T4 & T3 circulate bound to thyroid-binding globulin (TBG). Others: TTR or transthyretin (10% of T4) Albumin (15% of T4, 25% of T3) 0.02% of T4 and 0.5% of T3 circulate in its free forms Hormone (s): synthesis, storage, release, transport and regulation
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Metabolism of TH Peripheral deiodination of T4 by deiodinases: ~40% of T4: deiodinated at carbon 5 in the outer ring  T3 (liver & kidney) ~33% of T4: deiodinated at carbon 5 in the inner ring  rT3 selenocysteine T4  T3 or rT3  T2 Hormone (s): synthesis, storage, release, transport and regulation
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Deiodinases, type 1 Catalyzes outer- and inner-ring deiodination of T4 & rT3 Liver, kidney & thyroid Primary deiodinase responsible for T4 to T3 conversion in hyperthyroid patients in the periphery Major source of circulating T3 Hormone (s): synthesis, storage, release, transport and regulation
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Deiodinases, type 2 Outer-ring activity only, T4  T3 Expressed in the brain, pituitary gland, brown adipose tissue, thyroid, placenta, skeletal & cardiac muscle Major source of T3 in the euthyroid state Important role in local production of T3 in tissues with this enzyme Hormone (s): synthesis, storage, release, transport and regulation
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Deiodinases, type 3 inner-ring activity only: T4  rT3, T3  T2 Expressed in the brain, placenta and skin Important feature in placenta protection of the fetus Hormone (s): synthesis, storage, release, transport and regulation
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Hormone (s): synthesis, storage, release, transport and regulation
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Hormone (s): synthesis, storage, release, transport and regulation
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Nuclear receptors intimately associated with chromatin (TRE) DNA-binding transcription factors that function as molecular switches in response to hormone binding TRβ , TRα (chromosomes 3 and 17, respectively) Receptors
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T3 is responsible for ~90% of the occupancy in thyroid receptors (TR) T4 is bound more tightly to plasma proteins Target cell converts T4, once it enters the cell, to T3 TR in the nucleus has ~10-fold greater affinity for T3 than T4 Receptors
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On calorigenesis Increases oxygen consumption of almost all metabolically active tissues. On carbohydrate metabolism Potentiates the action of insulin. Promotes glycogenolysis and glucose utilization. Increases rate of absorption of carbohydrate from the GIT Physiologic effects
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On protein metabolism Protein anabolic effect In large doses, has a protein catabolic effect On lipid metabolism Stimulates synthesis, mobilization and utilization of lipids Lowers circulating cholesterol Physiologic effects
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On vitamin metabolism Needed for metabolism of fat soluble vitamins Involved in vitamin A synthesis from carotene Involved in conversion of vitamin A to retinene Physiologic effects
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On growth and development Essential for bone growth and maturation Essential for maturation of neurological tissue On respiration Increases the respiratory rate, minute ventilation, and ventilatory responses to hypercapnia and hypoxia Physiologic effects
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On the CVS Increases cardiac output by increasing resting heart rate and stroke volume; this ensures sufficient oxygen delivery to the tissues Physiologic effects
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Key features of thyroid regulation & function TSH Binds to Gs protein –coupled receptor on thyroid cells Main second messenger is cAMP Stimulate all steps in TH synthesis: iodine uptake & organification production & release of TH promotion of thyroid growth
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Key features of thyroid regulation & function Thyroid Gland store 2-3 months supply of thyroid hormones in the thyroglobulin pool Produces more T4 than T3
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Key features of thyroid regulation & function Thyroid Hormone synthesis & release are under negative feedback regulation by hypothalamic-pituitary-thyroid axis T4 is converted to T3 in peripheral tissues Biologic activity of T3 > T4 Binds to nuclear receptors & modulates gene transcription
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The Parathyroid Glands
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Hormone (s): synthesis, storage, release, transport and regulation
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The dominant regulator of PTH is plasma Ca2+. Secretion of PTH is inversely related to [Ca2+]. Maximum secretion of PTH occurs at plasma Ca2+ below 3.5 mg/dL. At Ca2+ above 5.5 mg/dL, PTH secretion is maximally inhibited. Hormone (s): synthesis, storage, release, transport and regulation
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Hormone (s): synthesis, storage, release, transport and regulation
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Hormone (s): synthesis, storage, release, transport and regulation
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Bones Kidney Receptors
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On the bone: Rapid Phase (1-3hrs.) - osteocystic osteolysis Slow Phase (12-24hrs.) – osteoclastic osteolysis Physiologic effects
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Osteocystic Osteolysis Transfer of calcium from canalicular fluid into osteocytes Transfer of calcium via osteocyte syncytial processes to extracellular fluid Replenisment of canalicular fluid calcium from partially mineralized bone Phosphate is not mobilized Bone mass does not change Physiologic effects
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Osteoclastic Osteolysis Increased osteoclastic size and number Increased osteoclastic collagenase and lysosomal enzyme activity Increased osteoclastic acid phosphatase, carbonic anhydrase,l actic acid and citric acid concentrations Increased bone resorption Mobilization of calcium, magnesium and inorganic phosphate Physiologic effects
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ON BONE FORMATION Increased osteoblastic number Increased collagen synthesis Increased alkaline phosphatase activity Increased local growth factors: IGF and transforming factors Physiologic effects
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ON KIDNEY Increased calcium and magnesium reabsorption from ascending loop and distal tubule Increased chloride reabsorption from proximal tubule Decreased phosphate, sodium and bicarbonate reabsorption from the proximal tubule Increased proximal tubule 1-alpha-hydroxalase activity Physiologic effects
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