04 Cat. Sistema Endocrino II


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04 Cat. Sistema Endocrino II

  1. 2. Contenido y Distribución del Calcio, Fosfato y Magnesio 40 % 60 % 22-25 g Magnesio 15-20% 80-85% 600-6500g Fosfato 1-2% 98-99% 1000-1200 g Calcio % extraoseo % en hueso Total corporal
  2. 3. Funciones Fisiológicas del Calcio <ul><li>Celulares </li></ul><ul><li>Crecimiento división celular </li></ul><ul><li>Estabilización de membranas </li></ul><ul><li>Excitabilidad y permeabilidad de las membrana plasmática </li></ul><ul><li>Transporte de iones a través de la membrana plasmática </li></ul><ul><li>Regulación enzimática </li></ul><ul><li>Excitabilidad nerviosa </li></ul><ul><li>Secreción de hormonas </li></ul><ul><li>Secreción exocrina </li></ul><ul><li>Neurotransmisores </li></ul><ul><li>Contracción muscular </li></ul><ul><li>Extracelulares </li></ul><ul><li>Mineralización </li></ul><ul><li>Cofactor de factores de coagulación </li></ul>
  3. 4. Calmodulina <ul><li>4 puntos de unión para el Ca+2. </li></ul><ul><li>2 Ca +2 citosol se adhiere a la molécula </li></ul><ul><ul><li>1er cambio conformacional </li></ul></ul><ul><li>Calmodilina 2Ca+2 se asocia a una proteína efectora inactiva, </li></ul><ul><ul><li>2do cambio conformacional </li></ul></ul><ul><li>Incorporación de los siguientes 2 Ca+2 </li></ul><ul><ul><li>3er cambio conformacional </li></ul></ul><ul><li>Forma activa y cataliza la reacción correspondiente. </li></ul>
  4. 5. <ul><li>ATPasa dependiente de Ca+2 </li></ul><ul><ul><li>Mem. plasmática </li></ul></ul><ul><ul><li>Expulsar Ca+2 </li></ul></ul><ul><li>ATPasa dependiente de Ca+2 </li></ul><ul><ul><li>Sarcoplasma </li></ul></ul><ul><ul><li>Introducir Ca+2 </li></ul></ul><ul><li>Contratransporte: 1Ca+2 y 2 Na+2 </li></ul>
  5. 7. Glándula Paratiriodea - Parathormona <ul><li>Forma ovalada, diametro menor 6-7mm, 5 mm ancho y 2 mm grosor </li></ul><ul><li>Peso: 20-50mg </li></ul><ul><li>Se encuentran ramificadas por la arteira tiroidea superior e inferior </li></ul><ul><li>Liberacion de H a vena tiroidea </li></ul><ul><li>Polipeptido 84aa; cromosoma 1 </li></ul><ul><li>Sintetizada en el RER </li></ul><ul><li>Precursor pre-pro-PTH (115aa) </li></ul>
  6. 8. Colecalciferol (Vitamina D3) 25-hidroxicolecalciferol 1,25-dihidroxicolecalciferol Prot. unión calcio ATPasa dependiente de calcio Fosfatasa alcalina Absorción Ca++ Hormona paratiroidea activación inhibición inhibición Higado
  7. 9. Figure 24-24 Parathyroid adenomas are almost always solitary lesions. Technetium-99m-sestamibi radionuclide scan demonstrates an area of increased uptake corresponding to the leftinferior parathyroid gland (arrow) . This patient had a parathyroid adenoma. Preoperative scintigraphy is useful in localizing and distinguishing adenomas from parathyroid hyperplasia, where more than one gland would demonstrate increased uptake.
  9. 12. Figure 24-26 Cardinal features of hyperparathyroidism. With routine evaluation of calcium levels in most patients, primary hyperparathyroidism is often detected at a clinically silent stage. Hypercalcemia from any other cause can also give rise to the same symptoms.
  10. 13. HIPOPARATIROIDISMO El hipoparatiroidismo produce hipocalcemia La hipocalcemia aguda produce un aumento de la excitabilidad neuromuscular El aumento de la excitabilidad neuromuscular de cualquier causa se llama TETANIA
  11. 14. Hipocalcemia
  12. 16. Figure 24-27 Hormone production in pancreatic islet cells. Immunoperoxidase staining shows a dark reaction product for insulin in b cells (A), glucagon in a cells (B), and somatostatin in d cells (C). D, Electron micrograph of a b cell shows the characteristic membrane-bound granules, each containing a dense, often rectangular core and distinct halo. E, Portions of an a cell (left) and a d cell (right) also exhibit granules, but with closely apportioned membranes. The a-cell granule exhibits a dense, round center. (Electron micrographs courtesy of Dr. A. Like, University of Massachusetts Medical School, Worcester, MA.)
  13. 17. Figure 24-28 Insulin synthesis and secretion. Intracellular transport of glucose is mediated by GLUT-2, an insulin-independent glucose transporter in b cells. Glucose undergoes oxidative metabolism in the b cell to yield ATP. ATP inhibits an inward rectifying potassium channel receptor on the b-cell surface; the receptor itself is a dimeric complex of the sulfonylurea receptor and a K+ -channel protein. Inhibition of this receptor leads to membrane depolarization, influx of Ca2+ ions, and release of stored insulin from b cells. Figure 24-29 Metabolic actions of insulin in striated muscle, adipose tissue, and liver.
  14. 18. Figure 24-30 Insulin action on a target cell. Insulin binds to the a subunit of insulin receptor, leading to activation of the kinase activity in the b-subunit, and sets in motion a phosphorylation (i.e., activation) cascade of multiple downstream target proteins. The mitogenic functions of insulin (and the related insulin-like growth factors) are mediated via the mitogen-activated protein kinase (MAP kinase) pathway. The metabolic actions of insulin are mediated primarily by activation of the phosphatidylinositol-3-kinase (PI-3K) pathway. The PI-3K-signaling pathway is responsible for a variety of effects on target cells, including translocation of GLUT-4 containing vesicles to the surface; increasing GLUT-4 density on the membrane and rate of glucose influx; promoting glycogen synthesis via activation of glycogen synthase; and promoting protein synthesis and lipogenesis, while inhibiting lipolysis. The PI-3K pathway also promotes cell survival and proliferation.
  15. 19. TABLE 24-6 -- Classification of Diabetes Mellitus •••••• Neoplasia •••••• Cystic fibrosis •••••• Hemachromatosis •••••• Fibrocalculous pancreatopathy •••••• Pancreatectomy •••••• Chronic pancreatitis • 5. Exocrine pancreatic defects •••••• Insulin receptor mutations •••••• Insulin gene mutations •••••• Defects in proinsulin conversion • 4. Genetic defects in insulin processing or insulin action •••••• Mitochondrial DNA mutations ••••••• Neurogenic differentiation factor 1 [Neuro D1] (MODY6) ••••••• Hepatocyte nuclear factor 1b [HNF-1b] (MODY5) ••••••• Insulin promoter factor [IPF-1] (MODY4) ••••••• Hepatocyte nuclear factor 1a [HNF-1a] (MODY3) ••••••• Glucokinase (MODY2) ••••••• Hepatocyte nuclear factor 4a [HNF-4a] (MODY1) •••••• Maturity-onset diabetes of the young (MODY), caused by mutations in: • 3. Genetic defects of b -cell function • 2. Type 2 diabetes (insulin resistance with relative insulin deficiency) •••••• Idiopathic •••••• Immune-mediated • 1. Type 1 diabetes (b-cell destruction, leads to absolute insulin deficiency)
  16. 20. Data from the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetic Care 25 (suppl. 1):S5–S20, 2002. 10. Gestational diabetes mellitus •••••• Turner syndrome •••••• Kleinfelter syndrome •••••• Down syndrome • 9. Genetic syndromes associated with diabetes •••••• Phenytoin •••••• Nicotinic acid •••••• Thiazides •••••• b-adrenergic agonists •••••• Protease inhibitors •••••• a-interferon •••••• Thyroid hormone •••••• Glucocorticoids • 8. Drugs •••••• Coxsackie virus B •••••• Cytomegalovirus • 7. Infections •••••• Glucagonoma •••••• Pheochromocytoma •••••• Hyperthyroidism •••••• Cushing syndrome •••••• Acromegaly • 6. Endocrinopathies
  17. 21. Figure 24-31 Stages in the development of type 1 diabetes mellitus. The stages are listed from left to right, and hypothetical b-cell mass is plotted against age. (From Eisenbarth GE: Type 1 diabetes: a chronic autoimmune disease. N Engl J Med 314:1360, 1986. Copyright © 1986, Massachusetts Medical Society. All rights reserved.)
  18. 22. Figure 24-33 Obesity and insulin resistance: the missing links? Adipocytes release a variety of factors (free fatty acids and adipokines) that may play a role in modulating insulin resistance in peripheral tissues (illustrated here is striated muscle). Excess free fatty acids (FFAs) and resistin are associated with insulin resistance; in contrast, adiponectin, whose levels are decreased in obesity, is an insulin-sensitizing adipokine. Leptin is also an insulin-sensitizing agent, but it acts via central receptors (in the hypothalamus). The peroxisome proliferator-activated receptor gamma (PPARg) is an adipocyte nuclear receptor that is activated by a class of insulin-sensitizing drugs called thiazolidinediones (TZDs). The mechanism of action of TZDs may eventually be mediated through modulation of adipokine and FFA levels that favor a state of insulin sensitivity.
  19. 23. Figure 24-34 Long-term complications of diabetes.
  20. 24. Figure 24-40 Sequence of metabolic derangements leading to diabetic coma in type 1 diabetes mellitus. An absolute insulin deficiency leads to a catabolic state, eventuating in ketoacidosis and severe volume depletion. These cause sufficient central nervous system compromise to lead to coma and eventual death if left untreated.
  21. 25. TABLE 24-8 -- Type 1 Versus Type 2 Diabetes Mellitus (DM) Mild b-cell depletion b-cell depletion atrophy and amyloid deposition Marked atrophy and fibrosis Focal No insulitis Insulitis early Islet cells Absolute insulin deficiency b-cell dysfunction and relative insulin deficiency Insulin resistance in skeletal muscle, adipose tissue and liver Autoimmune destruction of b-cells mediated by T cells and humoral mediators (TNF, IL-1, NO) Pathogenesis Linkage to candidate diabetogenic genes (PPARg, calpain 10) No HLA linkage Linkage to MHC Class II HLA genes 50–90% concordance in twins 30–70% concordance in twins Genetics Ketoacidosis rare; nonketotic hyperosmolar coma Ketoacidosis common No anti-islet cell antibodies Anti-islet cell antibodies Increased blood insulin early); normal to moderate decreased insulin (late) Markedly decreased blood insulin Obese Normal weight Onset: >30 years <20 years Clinical Onset: Type 2 DM Type 1 DM