PRINCIPLES OF ENDOCRINOLOGY www.freelivedoctor.com
<ul><li>The specialty of endocrinology encompasses  the study of glands and the hormones they produce. </li></ul>www.freel...
<ul><li>Hormones play an important functional role in all organ system </li></ul>www.freelivedoctor.com
Hormone <ul><li>Describes the dynamic actions of these circulating substances as they elicit cellular responses and regula...
<ul><li>The management of endocrine disorders requires an understanding: </li></ul><ul><ul><li>Areas as intermediary metab...
Scope of endocrinology <ul><li>Classic endocrine glands pituitary, thyroid, parathyroid, pancreatic islets,  adrenal and g...
<ul><li>Through the production of hypothalamic  releasing factors, the central nervous system exerts a major regulatory in...
<ul><li>The immune and endocrine systems are also intimately intertwined. </li></ul><ul><li>Hormones play an important rol...
New hormones <ul><li>Inhibin </li></ul><ul><li>Ghrelin </li></ul><ul><li>Leptin </li></ul>www.freelivedoctor.com
NATURE OF HORMONES www.freelivedoctor.com
Five  major classes <ul><li>Amino acid derivatives </li></ul><ul><li>Small neuropeptides </li></ul><ul><li>Large proteins ...
<ul><li>Amino acid derivatives </li></ul><ul><ul><li>dopamine </li></ul></ul><ul><ul><li>catecholamines </li></ul></ul><ul...
<ul><li>Small neuropeptides </li></ul><ul><ul><li>gonadotropin-releasing hormone (GnRH) </li></ul></ul><ul><ul><li>thyrotr...
<ul><li>Large proteins </li></ul><ul><ul><li>insulin </li></ul></ul><ul><ul><li>luteinizing hormone (LH) </li></ul></ul><u...
<ul><li>Steroid hormones </li></ul><ul><ul><li>cortisol </li></ul></ul><ul><ul><li>strogen </li></ul></ul><ul><ul><ul><li>...
<ul><li>Vitamin derivatives </li></ul><ul><ul><li>retinoids (vitamin A) </li></ul></ul><ul><ul><li>vitamin D </li></ul></u...
HORMONE AND     RECEPTOR FAMILIES www.freelivedoctor.com
<ul><li>Amino acid derivatives and peptide hormone interact with  cell-surface membrane receptors. </li></ul><ul><li>Stero...
Cell-surface membrane   receptors www.freelivedoctor.com
G protein-coupled seven-transmembrane  (GPCR) www.freelivedoctor.com
<ul><li>The glycoprotein hormone family consisting of TSH, FSH, LH and hCG, they are heterodimers that share the    subun...
Receptor Tyrosine Kinase www.freelivedoctor.com
Cytokine receptor linked kinase www.freelivedoctor.com
Intracellular nuclear receptors www.freelivedoctor.com
<ul><li>Specificities for DNA binding sites, the nuclear receptor family can be subdivided: </li></ul><ul><ul><li>Type 1 r...
<ul><li>With few exception, hormone binding is highly specific for a single type of nuclear receptor. </li></ul>www.freeli...
Hormone Synthesis and Processing www.freelivedoctor.com
Peptide hormones <ul><li>Synthesis of peptide hormones and their receptors occurs through a classic pathway of gene expres...
<ul><li>Endocrine genes contain regulatory DNA elements similar to those found in many other genes, their exquisite contro...
<ul><li>Many hormones are embedded within larger precursor polypeptides that are proteolytically processed to yield the bi...
<ul><li>Synthesis of most steroid hormones is based on modifications of the precursor, cholesterol. Multiple regulated enz...
Hormone secretion, transport and degradation. www.freelivedoctor.com
Peptide hormones <ul><li>GnRH, insulin, GH: are stored in secretory granules. As these granules. </li></ul><ul><li>As thes...
Steroid hormones <ul><li>Diffuse into the circulation as they are synthesized. </li></ul><ul><li>Their secretory rates are...
Serum binding proteins <ul><li>Many hormones circulate in association with serum-binding proteins. </li></ul><ul><ul><ul><...
Hormone Action Through Receptors <ul><li>Two major classes </li></ul><ul><ul><li>Membrane receptors: Peptide hormones and ...
<ul><li>Hormones bind to receptors with specificity and a high affinity that generally coincides with the dynamic ranger o...
<ul><li>Low concentrations of free hormone rapidly associate and dissociate from receptors in a biomolecular reaction, suc...
<ul><li>Receptor numbers vary greatly in different target tissues, providing one of the major determinants of specific  ce...
Functions of hormones www.freelivedoctor.com
<ul><li>The physiologic functions of hormones can be divided into three general areas: </li></ul><ul><ul><li>Growth and di...
Growth <ul><li>Multiple hormones and nutritional factors mediated the complex  phenomenon of growth. </li></ul><ul><ul><li...
Maintenance of Homeostasis  <ul><li>Thyroid hormone-controls about 25% of basal metabolism in most tissues. </li></ul><ul>...
Reproduction <ul><li>Sex determination during fetal development. </li></ul><ul><li>Sexual maturation during puberty </li><...
Feedback control <ul><li>Negative and positive is a fundamental feature of endocrine systems. </li></ul><ul><li>Each of th...
Hormonal Rhythms <ul><li>Seasonal changes, the daily occurrence of the light-dark cycle, sleep, meals, and stress are exam...
Hormone measurements and endocrine testing <ul><li>Radioimmunoassays are the most important diagnostic tool in endocrinolo...
Pathologic Mechanisms of Endocrine Disease www.freelivedoctor.com
<ul><li>Endocrine diseases can be divided into three major types of conditions: </li></ul><ul><li>Hormone excess </li></ul...
Hormone excess <ul><li>Syndromes of hormone excess can be caused by neoplastic growth of endocrine cells, autoimmune disor...
Hormone deficiency <ul><li>Most examples of hormone deficiency states can be attributed to glandular destruction caused by...
Hormone resistance <ul><li>Most severe hormone resistance syndromes are due to inherited defects in membrane receptors, nu...
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Principles of endocrinal disorders

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Principles of endocrinal disorders

  1. 1. PRINCIPLES OF ENDOCRINOLOGY www.freelivedoctor.com
  2. 2. <ul><li>The specialty of endocrinology encompasses the study of glands and the hormones they produce. </li></ul>www.freelivedoctor.com
  3. 3. <ul><li>Hormones play an important functional role in all organ system </li></ul>www.freelivedoctor.com
  4. 4. Hormone <ul><li>Describes the dynamic actions of these circulating substances as they elicit cellular responses and regulate physiologic processes through feedback mechanisms. </li></ul>www.freelivedoctor.com
  5. 5. <ul><li>The management of endocrine disorders requires an understanding: </li></ul><ul><ul><li>Areas as intermediary metabolism, reproductive physiology, bone metabolism, and growth. </li></ul></ul><ul><ul><li>Hormone secretion, hormone action, and principles of feedback control systems. </li></ul></ul>www.freelivedoctor.com
  6. 6. Scope of endocrinology <ul><li>Classic endocrine glands pituitary, thyroid, parathyroid, pancreatic islets, adrenal and gonads communicate broadly with other organs through the nervous system, hormones, cytokines, and growth factors. </li></ul>www.freelivedoctor.com
  7. 7. <ul><li>Through the production of hypothalamic releasing factors, the central nervous system exerts a major regulatory influence over pituitary hormone secretion. </li></ul>www.freelivedoctor.com
  8. 8. <ul><li>The immune and endocrine systems are also intimately intertwined. </li></ul><ul><li>Hormones play an important role in maintenance of blood pressure, intravascular volume, and peripheral resistance in the cardiovascular system. </li></ul>www.freelivedoctor.com
  9. 9. New hormones <ul><li>Inhibin </li></ul><ul><li>Ghrelin </li></ul><ul><li>Leptin </li></ul>www.freelivedoctor.com
  10. 10. NATURE OF HORMONES www.freelivedoctor.com
  11. 11. Five major classes <ul><li>Amino acid derivatives </li></ul><ul><li>Small neuropeptides </li></ul><ul><li>Large proteins </li></ul><ul><li>Steroid hormones </li></ul><ul><li>Vitamin derivatives </li></ul>www.freelivedoctor.com
  12. 12. <ul><li>Amino acid derivatives </li></ul><ul><ul><li>dopamine </li></ul></ul><ul><ul><li>catecholamines </li></ul></ul><ul><ul><li>thyroid hormone </li></ul></ul>www.freelivedoctor.com
  13. 13. <ul><li>Small neuropeptides </li></ul><ul><ul><li>gonadotropin-releasing hormone (GnRH) </li></ul></ul><ul><ul><li>thyrotropin-releasing hormone (TRH) </li></ul></ul><ul><ul><li>somatostatin </li></ul></ul><ul><ul><li>vasopressin </li></ul></ul>www.freelivedoctor.com
  14. 14. <ul><li>Large proteins </li></ul><ul><ul><li>insulin </li></ul></ul><ul><ul><li>luteinizing hormone (LH) </li></ul></ul><ul><ul><li>PTH </li></ul></ul>www.freelivedoctor.com
  15. 15. <ul><li>Steroid hormones </li></ul><ul><ul><li>cortisol </li></ul></ul><ul><ul><li>strogen </li></ul></ul><ul><ul><ul><li>Are synthesized from cholesterol-based precursors </li></ul></ul></ul>www.freelivedoctor.com
  16. 16. <ul><li>Vitamin derivatives </li></ul><ul><ul><li>retinoids (vitamin A) </li></ul></ul><ul><ul><li>vitamin D </li></ul></ul>www.freelivedoctor.com
  17. 17. HORMONE AND RECEPTOR FAMILIES www.freelivedoctor.com
  18. 18. <ul><li>Amino acid derivatives and peptide hormone interact with cell-surface membrane receptors. </li></ul><ul><li>Steroids, thyroid hormones, vitamin D and retinoids are lipid-soluble and interact with intracellular nuclear receptors. </li></ul>www.freelivedoctor.com
  19. 19. Cell-surface membrane receptors www.freelivedoctor.com
  20. 20. G protein-coupled seven-transmembrane (GPCR) www.freelivedoctor.com
  21. 21. <ul><li>The glycoprotein hormone family consisting of TSH, FSH, LH and hCG, they are heterodimers that share the  subunit in common, the  subunits are distinct and confer specific biologic actions. </li></ul>www.freelivedoctor.com
  22. 22. Receptor Tyrosine Kinase www.freelivedoctor.com
  23. 23. Cytokine receptor linked kinase www.freelivedoctor.com
  24. 24. Intracellular nuclear receptors www.freelivedoctor.com
  25. 25. <ul><li>Specificities for DNA binding sites, the nuclear receptor family can be subdivided: </li></ul><ul><ul><li>Type 1 receptors:; GR, MR, AR, ER, PR; that bind steroids. </li></ul></ul><ul><ul><li>Type 2 receptors: TR, VDR, RAR, PPAR; that bind thyroid hormone, vitamin D, retinoic acid or lipid derivatives. </li></ul></ul>www.freelivedoctor.com
  26. 26. <ul><li>With few exception, hormone binding is highly specific for a single type of nuclear receptor. </li></ul>www.freelivedoctor.com
  27. 27. Hormone Synthesis and Processing www.freelivedoctor.com
  28. 28. Peptide hormones <ul><li>Synthesis of peptide hormones and their receptors occurs through a classic pathway of gene expression: </li></ul><ul><ul><li>Transcription mRNA protein </li></ul></ul><ul><ul><li>posttranslational protein processing in-tracellular sorting, membrane integration or secretion </li></ul></ul>www.freelivedoctor.com
  29. 29. <ul><li>Endocrine genes contain regulatory DNA elements similar to those found in many other genes, their exquisite control by other hormones also necessitates the presence of specific hormone response elements. </li></ul>www.freelivedoctor.com
  30. 30. <ul><li>Many hormones are embedded within larger precursor polypeptides that are proteolytically processed to yield the biologically active hormone. </li></ul><ul><li>Examples: proopiomelanocortin (POMC) ACTH; proglucagon glucagon; proinsulin insulin; pro-PTH PTH. </li></ul>www.freelivedoctor.com
  31. 31. <ul><li>Synthesis of most steroid hormones is based on modifications of the precursor, cholesterol. Multiple regulated enzymatic steps are required for the synthesis of testosterone, estradiol, cortisol and vitamin D. </li></ul><ul><li>This large number of synthetic steps predisposes to multiple genetic and acquired disorders of steroidogenesis. </li></ul>www.freelivedoctor.com
  32. 32. Hormone secretion, transport and degradation. www.freelivedoctor.com
  33. 33. Peptide hormones <ul><li>GnRH, insulin, GH: are stored in secretory granules. As these granules. </li></ul><ul><li>As these granules mature, they are poised beneath the plasma membrane for imminent release into the circulation. </li></ul><ul><li>Stimulus for hormone secretion is a releasing factor or neural signal that induces rapid changes in intracellular calcium concentrations. </li></ul>www.freelivedoctor.com
  34. 34. Steroid hormones <ul><li>Diffuse into the circulation as they are synthesized. </li></ul><ul><li>Their secretory rates are closely aligned with rates of synthesis. </li></ul>www.freelivedoctor.com
  35. 35. Serum binding proteins <ul><li>Many hormones circulate in association with serum-binding proteins. </li></ul><ul><ul><ul><li>T4 and T3 binding to thyroxine-binding globulin (TBG). </li></ul></ul></ul><ul><ul><ul><li>Cortisol binding to cortisol-binding globulin (CBG). </li></ul></ul></ul><ul><ul><ul><li>Androgen and strogen binding to sex hormone-binding globulin (SHBG). </li></ul></ul></ul><ul><ul><ul><li>IGF-I and II binding to multiple IGF-binding proteins (IGFBPs). </li></ul></ul></ul><ul><ul><ul><li>GH interactions with GH-binding protein (GHBP) </li></ul></ul></ul>www.freelivedoctor.com
  36. 36. Hormone Action Through Receptors <ul><li>Two major classes </li></ul><ul><ul><li>Membrane receptors: Peptide hormones and catecholamines. </li></ul></ul><ul><ul><li>Nuclear receptors: Small molecules (that can diffuse across the cell membrane) such as thyroid hormone, steroids, and vitamin D. </li></ul></ul>www.freelivedoctor.com
  37. 37. <ul><li>Hormones bind to receptors with specificity and a high affinity that generally coincides with the dynamic ranger of circulating hormone concentrations. </li></ul>www.freelivedoctor.com
  38. 38. <ul><li>Low concentrations of free hormone rapidly associate and dissociate from receptors in a biomolecular reaction, such that the occupancy of the receptor at any given moment is a function of hormone concentration and the receptor´s affinity for the hormone. </li></ul>www.freelivedoctor.com
  39. 39. <ul><li>Receptor numbers vary greatly in different target tissues, providing one of the major determinants of specific cellular responses to circulating hormones. </li></ul><ul><ul><ul><li>ACTH receptors are located almost exclusively in the adrenal cortex. </li></ul></ul></ul><ul><ul><ul><li>FSH receptors are found only in the gonads. </li></ul></ul></ul><ul><ul><ul><li>In contrast, insulin and thyroid hormone receptors are widely distributed reflecting the need for metabolic responses in all tissues. </li></ul></ul></ul>www.freelivedoctor.com
  40. 40. Functions of hormones www.freelivedoctor.com
  41. 41. <ul><li>The physiologic functions of hormones can be divided into three general areas: </li></ul><ul><ul><li>Growth and differentiation </li></ul></ul><ul><ul><li>Maintenance of homeostasis </li></ul></ul><ul><ul><li>Reproduction. </li></ul></ul>www.freelivedoctor.com
  42. 42. Growth <ul><li>Multiple hormones and nutritional factors mediated the complex phenomenon of growth. </li></ul><ul><ul><li>Short stature may be caused by GH deficiency, hypothyroidism, Cushing`s syndrome, precocious puberty or malnutrition. (Understanding these hormonal interactions is important in the diagnosis and management of growth disorders). </li></ul></ul>www.freelivedoctor.com
  43. 43. Maintenance of Homeostasis <ul><li>Thyroid hormone-controls about 25% of basal metabolism in most tissues. </li></ul><ul><li>Cortisol-exerts a permissive action for many hormones in addition to its own direct effects. </li></ul><ul><li>PTH-regulates calcium and phosphorus levels </li></ul><ul><li>Vasopressin-regulates serum osmolality by controlling renal free water clearance. </li></ul><ul><li>Mineralocorticoids-control vascular volume and serum electrolyte (Na+, K+) concentrations. </li></ul><ul><li>Insulin-maintains euglycemiain the fed and fasted states. </li></ul>www.freelivedoctor.com
  44. 44. Reproduction <ul><li>Sex determination during fetal development. </li></ul><ul><li>Sexual maturation during puberty </li></ul><ul><li>Conception, pregnancy, lactation and child-rearing. </li></ul><ul><li>Cessation of reproductive capability at menopause. </li></ul><ul><li>Each of these stages involves an orchestrated interplay of multiple hormones </li></ul>www.freelivedoctor.com
  45. 45. Feedback control <ul><li>Negative and positive is a fundamental feature of endocrine systems. </li></ul><ul><li>Each of the major hypotalamic-pituitary -hormone axes is governed by negative feedback. </li></ul>www.freelivedoctor.com
  46. 46. Hormonal Rhythms <ul><li>Seasonal changes, the daily occurrence of the light-dark cycle, sleep, meals, and stress are examples of the many environmental events that affect hormonal rhythms. </li></ul>www.freelivedoctor.com
  47. 47. Hormone measurements and endocrine testing <ul><li>Radioimmunoassays are the most important diagnostic tool in endocrinology, as they allow sensitive, specific, and quantitative determination of steady-state and dynamic changes in hormone concentrations. </li></ul><ul><li>Radioimmunoassays use antibodies to detect specific hormones. </li></ul>www.freelivedoctor.com
  48. 48. Pathologic Mechanisms of Endocrine Disease www.freelivedoctor.com
  49. 49. <ul><li>Endocrine diseases can be divided into three major types of conditions: </li></ul><ul><li>Hormone excess </li></ul><ul><li>Hormone deficiency </li></ul><ul><li>Hormone resistance </li></ul>www.freelivedoctor.com
  50. 50. Hormone excess <ul><li>Syndromes of hormone excess can be caused by neoplastic growth of endocrine cells, autoimmune disorder, and excess hormone administration </li></ul>www.freelivedoctor.com
  51. 51. Hormone deficiency <ul><li>Most examples of hormone deficiency states can be attributed to glandular destruction caused by autoimmunity, surgery, infection, inflammation, infarction, hemorrhage or tumor infiltration. </li></ul><ul><li>Mutations in a number of hormones, hormone receptors, transcription factors, enzymes, and channels can also lead to hormone deficiencies. </li></ul>www.freelivedoctor.com
  52. 52. Hormone resistance <ul><li>Most severe hormone resistance syndromes are due to inherited defects in membrane receptors, nuclear receptors, or in the pathways that transduce receptor signals. </li></ul><ul><li>In addition to these relatively rare genetic disorders, more common acquired forms of functional hormone resistance include insulin resistance in type 2 diabetes mellitus, leptin resistance in obesity, and GH resistance in catabolic states. </li></ul>www.freelivedoctor.com
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