Fisiologi Thyroid dan Parathyroid

Fisiologi Thyroid dan ParathyroidIsa BasukiIntroductionThe thyroid secretes two major hormones:Thyroxine (T4)Triiodothyronine (T3)These hormones profoundly increase the metabolic rate of the body Thyroid secretion is controlled primarily by thyroid-stimulating hormone (TSH) secreted by the anterior pituitary glandThe thyroid gland also secretes calcitoninThe physiology of calcium and phosphate metabolism, formation of bone and teeth, and regulation of vitamin D, parathyroid hormone (PTH), and calcitonin are all closely intertwined2Iodine MetabolismThe average daily iodine requirement is 0.1 mgIn the stomach and jejunum, iodine is rapidly converted to iodide and absorbed into the bloodstreamIodide is actively transported into the thyroid follicular cells by an adenosine triphosphate (ATP)dependent processThe thyroid is the storage site of >90% of the body's iodine content Plasma iodine is cleared via renal excretion F. Charles Brunicardi et al. Schwartzs Principles of Surgery. 9th ed. New York/US: McGraw-Hill Education - Europe, 2009. 3Overview of Thyroid HormonesThe metabolically active hormones secreted by the thyroid gland is 93 % thyroxine 7 % triiodothyronineThe functions of these two hormones are qualitatively the same, but they differ in rapidity and intensity of actionTriiodothyronine four times as potent as thyroxine, but it is present in the blood in much smaller quantities and persists for a much shorter time than does thyroxineIodine Is Required for Formation of Thyroxine 50 milligrams of ingested iodine in the form of iodides are required each year (1 mg/week)4Synthesis, Secretion and Transport of Thyroid HormonesSynthesis within the thyroglobulin complex is controlled by several enzymes, in distinct steps:trapping of inorganic iodide from the blood;oxidation of iodide to iodine;binding of iodine with tyrosine to form iodotyrosines;coupling of monoiodotyrosines and di-iodotyrosines to form T3 and T4When hormones are required, the complex is resorbed into the cell and thyroglobulin is broken down.T3 and T4 are liberated and enter the blood, where they are bound to serum proteins:Albuminthyroxine-binding globulin (TBG)Thyroxine-binding prealbumin (TBPA)Norman S. Williams, Christopher J. K. Bulstrode, P. Ronan OConnell, editors. Bailey and Loves Short Practice of Surgery. 25th ed. London/GB: Taylor & Francis Ltd; 2008. 5

Physiological Functions of the Thyroid HormonesThe general effect of thyroid hormone is to activate nuclear transcription of large numbers of genes generalized increase in functional activity throughout the bodyIncrease Cellular Metabolic Activity Increase the Number and Activity of Mitochondria Increase Active Transport of Ions through Cell Membranes Effect of Thyroid Hormone on Growth :Hypothyroid the rate of growth is greatly retardedHyperthyroid excessive skeletal growth often occurs but the bones also mature more rapidly and the epiphyses close at an early ageTo promote growth and development of the brain during fetal life and for the first few years of postnatal life

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Thyroid hormone activation of target cells. Thyroxine (T4) and triiodothyronine (T3) readily diffuse through the cell membrane. Much of the T4 is deiodinated to form T3, which interacts with the thyroid hormone receptor, bound as a heterodimer with a retinoid X receptor, of the thyroid hormone response element of the gene. This causes either increases or decreases in transcription of genes that lead to formation of proteins, thus producing the thyroid hormone response of the cell. The actions of thyroid hormone on cells of several different systems are shown. mRNA, messenger ribonucleic acid.Physiological Functions of the Thyroid HormonesEffects of Thyroid Hormone on Specific Bodily Mechanisms Stimulation of Carbohydrate Metabolism Stimulation of Fat Metabolism Thyroid hormone increased cholesterol, phospholipids, and triglycerides in the plasma decreasedIncreased Requirement for Vitamins Increased Basal Metabolic Rate Decreased Body Weight

9Physiological Functions of the Thyroid HormonesEffect of Thyroid Hormones on the Cardiovascular System Increased Blood Flow and Cardiac Output Increased Heart Rate Increased Heart Strength Increased Respiration Increased Gastrointestinal Motility Excitatory Effects on the Central Nervous System Slight increase muscles react with vigor but when thyroid hormone becomes excessive muscles become weakenedFine muscle tremorIncreases the rates of secretion of several other endocrine glands

10Regulation of Thyroid Hormone Secretion TSH (from the Anterior Pituitary Gland) Increases Thyroid Secretion:Increased proteolysis of the thyroglobulin Increased activity of the iodide pumpIncreased iodination of tyrosine Increased size and increased secretory activity of the thyroid cellsIncreased number of thyroid cells Cyclic Adenosine Monophosphate Mediates the Stimulatory Effect of TSH Anterior Pituitary Secretion of TSH Is Regulated by Thyrotropin-Releasing Hormone (TRH) from the Hypothalamus Feedback Effect of Thyroid Hormone to Decrease Anterior Pituitary Secretion of TSH

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Parathyroid Hormone provides a powerful mechanism for controlling extracellular calcium and phosphate concentrations Excess activity rapid absorption of calcium salts from the bones hypercalcemia in the extracellular fluidHypofunction hypocalcemia tetany13Calcium PhysiologyCalcium exists in extracellular plasma in a free ionized state, as well as bound to other moleculesThe biologically inert bound fraction (55% of the total) binds to proteins.45% of the total calcium is biologically active and exists in the ionized form, with a normal level of 4.5 to 5.0 mg/dL.Ionized calcium levels are inversely affected by the pH of blood a 1-unit rise in pH will decrease the ionized calcium level by 0.36 mmol/literLevels of calcium are highly modulated through a delicate interplay among PTH, calcitonin, and vitamin D acting on target organs such as bone, kidney, and the gastrointestinal (GI) tractCourtney M. Townsend, Jr., R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox. Sabiston Textbook of Surgery. 19th ed. Elsevier Saunders; 14Calcium PhysiologyChief cells in the parathyroid glands secrete PTH, an 84amino acid protein, whenever serum calcium levels fall.PTH binds to its peripheral receptors and stimulates: osteoclasts to increase bone resorption, to the kidney to increase calcium resorption and renal production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and to the intestine to increase absorption of calcium and phosphate.The recently cloned calcium-sensing receptors (CaSRs) in the parathyroid glands detect changes in calcium levels, which results in a negative feedback loop that decreases PTH production.

Courtney M. Townsend, Jr., R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox. Sabiston Textbook of Surgery. 19th ed. Elsevier Saunders; 16Calcitonin PhysiologyCalcitonin is a 32amino acid protein secreted by the parafollicular cells of the thyroid gland in response to high calcium levels.Calcitonin rapidly inhibits bone resorption, transient decrease in serum calcium levels.Although calcitonin plays a significant homeostatic function in other species, its effects on calcium metabolism in humans is not significant when a person is exposed to chronically elevated calcitonin levels.

Courtney M. Townsend, Jr., R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox. Sabiston Textbook of Surgery. 19th ed. Elsevier Saunders; 17Vitamin D PhysiologyVitamin D is ingested or synthesized in precursor form then undergoes two hydroxylation steps before becoming biologically active.The first hydroxylation at carbon 25 occurs in the liver and the second hydroxylation at carbon 1 occurs in the kidney in response to increased PTH levels.1,25(OH)2D3 increases calcium and phosphate resorption from the GI tract and stimulates bone resorption, which raises calcium levels

Courtney M. Townsend, Jr., R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox. Sabiston Textbook of Surgery. 19th ed. Elsevier Saunders; 18Effects of Parathyroid Hormone The main effects of increased PTH secretion in response to decreased extracellular fluid calcium ion concentration:PTH stimulates bone resorption release of calcium into the extracellular fluidPTH increases reabsorption of calcium and decreases phosphate reabsorption by the renal tubules, decreased excretion of calcium and increased excretion of phosphatePTH is necessary for conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol increases calcium absorption by the intestines

Summary of effects of parathyroid hormone (PTH) on bone, the kidneys, and the intestine in response to decreased extracellular fluid calcium ion concentration. CaSR, calcium sensing receptor.

ReferenceJohn E. Hall PhD. Guyton and Hall book of Medical Physiology. 12th ed. Saunders; 2010. F. Charles Brunicardi, Dana K. Andersen, Timothy R. Billiar, David L. Dunn, John G. Hunter, Raphael E. Pollock, et al. Schwartzs Principles of Surgery. 9th ed. New York/US: McGraw-Hill Education - Europe; 2009. Norman S. Williams, Christopher J. K. Bulstrode, P. Ronan OConnell, editors. Bailey and Loves Short Practice of Surgery. 25th ed. London/GB: Taylor & Francis Ltd; 2008. Courtney M. Townsend, Jr., R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox. Sabiston Textbook of Surgery. 19th ed. Elsevier Saunders;