Physiology Exam 2

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Physiology Exam 2
2013-09-29 05:30:31

Physiology Exam 2 cards; primarily definitions, not mechanisms
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  1. Endocrine system
    internal secretory system, utilizing ductless endocrine glands to secrete chemical messengers into the blood
  2. Hormones
    Secreted by the endocrine system, chemical signals that circulate through the bloodstream.

    Some specialized cells can also secrete hormones, giving them secondary endocrine function
  3. Neurocine signaling
    when nerve terminals of certain neurons secrete hormones directly into the blood
  4. Promiscuous hormones / receptors
    The concept that a single signal can have multiple effects throughout the body, such as epinephrine's "fight or flight" responses in the heart (increased heart rate, relaxation rate, contractile force, metabolism), circulation (peripheral vasoconstriction, coronary vasodilation), liver (increased glucose release), and adipose tissue (lipolysis)
  5. Beta-adrenergic receptor
    Coupled to c-AMP formation, one of the three adrenergic receptors
  6. Alpha1-adrenergic receptor
    coupled to IP3 formation and calcium mobilization
  7. Alpha2-adrenergic receptor
    Coupled to inhibition of cAMP formation
  8. Hypothalamus
    Neurocrine signaling - controls pituitary endocrine secretions
  9. Pituitary
    neurocrine and endocrine - controls other endocrine glands and has direct effects on peripheral tissues
  10. Pineal gland
    regulates circadian rhythms
  11. Thyroid
    controls metabolic rate and growth
  12. Parathyroid
    regulates calcium and phosphorous homeostasis
  13. Adrenal (cortex and medulla)
    regulate metabolism, mineral balance and stress responses
  14. Pancreatic islets of Langerhans
    regulate metabolism and energy balance
  15. Ovaries and Testes
    control maturation and development, sexual function and pregnancy
  16. Hormone types
    Peptides - insulin, glucagon, FSH, vasopressin

    Steroids - testosterone, estrogen, progesterone - typically lipid soluble

    Thyroid hormones - thyroxine - altered Amino Acid compositions

    Catecholamines and other biogenic amines - epinephrine, serotonin, dopamine, ACh, histamine
  17. Peptide hormone synthesis
    produced during normal translational processes, undergo extensive post-translational modification and follow secretory protein pathways. Stored in secretory granules
  18. Steroid hormone synthesis
    Synthesized through a series of enzyme steps from cholesterol. Lipophylic, released directly from cells when synthesized (generally not stored)
  19. Thyroid hormone synthesis
    synthesized from tyrosine residues of a protein (thryoglobulin) precursor that is stored in a colloidal form in the thyroid gland. Proteolysis of the precursor stimulates release. Lipophylic
  20. Catecholamines and other biogenic amine hormone syntheses
    synthesized from various amino acids and other small molecule biochemical precursors. Stored in secretory granules and released when needed. Primarily synthesized from tyrosine
  21. Secretory granule secretion
    A: initiated by Ca2+ or cAMP level increase through an external stimulus

    B: secretory granules associate with cytoskeleton and translocate to the plasma membrane

    C: secretory granule fuses with plasma membrane

    D: fusion releases hormones into extracellular environment
  22. Specific binding globulins
    Proteins with high affinity for an individual hormone, bind to lipophylic hormones to carry them to their destination via blood
  23. Nonspecific binding globulins
    lower affinity "catch-all" binding proteins that bind to lipophylic proteins, most important of which is albumin
  24. Half-life
    the amount of time for a hormone to be nullified by the body:

    reputake by secretory cell

    internalization of receptor-coupled hormone by target cell

    metabolic degadation

    excretion, primarily in urine
  25. Hormone overview
  26. Hormone dose-response:
    maximal response: largest possible effect of a hormone, increased by hormone saturation, decreased through receptor down-regulation

    sensitivity: measured as the hormone dose giving a half-maximal response, decreased through receptor down-regulation or receptor affinity for hormone binding decrease (competitive inhibitors)
  27. Negative feedback
    the key to homeostatic regulation by hormones

    A: an increase in hormone secretion stimulates a greater output of product from the target cell, the product feeds back on the gland to suppress hormone secretion, limiting hormone excess

    B: decrease in product relieves the inhibition of hormone secretion, increasing hormone output, increasing target cell product production
  28. Hypothalamus
    part of CNS, interface between the brain and the endocrine system. Controls the pituitary gland
  29. Pituitary gland
    composed of distinct neural and endocrine tissues; receives both neuronal and endocrine signals from the hypothalamus and secretes hormones that circulate to the rest of the body
  30. Modes of Hypothalamic control over endocrine system
    1. hypothalamic neurons secrete regulatory (primary) hormones that stimulate release of secondary hormones from endocrine cells in anterior pituitary

    2. hypothalamic neurons release hormones directly into the blood via the posterior pituitary

    3. hypothalamus exerts direct neural control over the endocrine cells of the adrenal medullae
  31. Pituitary gland regulation
    direct regulation over: water balance, metabolic rate, lactation, milk secretion, body growth

    control secretion and growth of: thyroid gland, adrenal gland, reproductive gland
  32. Posterior pituitary
    neurohypophysis - neural in origin and contains axons that project directly from the hypothalamus to nerve terminals that release hormones into the blood; derived from neuroectoderm
  33. Anterior pituitary
    adenohypophysis - contains endocrine cells regulated indirectly by neuroendocrine signals from the hypothalamus that are released in the median eminence; derived from oral ectoderm
  34. Median eminence
    neurovascular region that houses secreted regulatory hormones from the hypothalamus. These hormones then regulate the endocrine cells in the anterior pituitary.

    Delivered to the anterior pituitary via the portal vein
  35. Posterior pituitary neurohormones
    vasopressin (ADH)- key role in regulation of body fluid volume by enhancing the retention of free water by the kidney

    oxytocin (OCT) - stimulates the ejection of milk from the lactating mammary gland; can also stimulate the contraction of the uterus
  36. Diabetes insipidus
    caused by decreased ADH levels, leads to high blood osmolality and excessive water loss, and increasing blood volume / pressure
  37. Oxytocin release regulation
    suckling stimulates oxytocin release through afferent senory neuronal signals to the hypothalamus.

    in pregnancy, oxytocin release is stimulated at term by uterine contractions and distention of the cervix, eliciting neuronal signals to the hypothalamus to induce oxytocin release; increases uterine contractility and enhances involution of the uterus after parturition
  38. Regulation of anterior pituitary hormone secretion by hypothalamus
    go to pg. 22-23 for summary of hormones
  39. Feedback control of pituitary hormone secretion
    Secondary hormones engage in negative feedback by acting on the hypothalamus / pituitary gland
  40. Growth hormone
    polypeptide hormone secreted by the somatotroph cells of the anterior pituitary

    plays a key role in the stimulation of growth and development of children

    important for regulating metabolism (continues into adults)

    regulated by both positive and inhibitory factors from the hypothalamus (GHRH, GHIH - somatostatin)
  41. Growth Hormone Releasing Hormone
    GHRH - stimulates release of GH from anterior pituitary
  42. Somatostatin
    GHIH - inhibits GH release from anterior pituitary
  43. Growth hormone
    peptide hormone that acts on peripheral tissues directly, also stimulates release of secondary peptide hormones called somatomedins (IGF1, IGF2) from the liver and other tissues. Some elements directly oppose the actions of insulin, making it diabetogenic. See pg. 25 for explanation
  44. Somatomedins
    insuline-like growth factors - stimulate anabolic responses of bone, muscle and other organs to increase protein synthesis and enhance cell proliferation and growth, also negatively regulates GHRH and upregulates GHIH
  45. Acromegaly
    excessive secretion of GH in adults. REsults in variety of physical changes, including accumulation of soft tissue, widening of bones, thickening of skin and hair, coarser facial features, enlarged hands and feet, muscle overdevelopment, and possibly diabetes
  46. Prolactin
    PRL - polypeptide hormone structurally related to GH

    stimulates breast development and milk production. Levels increase during pregnancy, further stimulated by nursing

    Hypothalamic regulation of PRL primarilyi through dopamine (PIF), which is an inhibiting hormone, as well as TRH and VIP

    negative feedback through prolactin stimulation of dopamine release

    estrogen positively regulates prolactin release by acting directly on mammotrophs of anterior pituitary
  47. Pituitary gland hormone overview
    Pg. 28
  48. Thyroid hormones
    hypothalamus thyrotropin releasing hormone (TRH) stimulates release of thyroid stimulating hormone (TSH, thyrotropin) from the anterior pituitary, which acts on the thyroid. T3 and T4 inhibit release of TSH and TRH secretion
  49. Thyroid gland overview
    Pg. 30

    C cells - secrete calcitonin

    Thyroid follicles - units of function within the thyroid

    colloid - glycoprotein space within the follicular cells

    follicular cells - secrete thyroid hormone

    capillary - eventually carry thyroid to the rest of the body
  50. Thyroid hormone
    Three forms:

    T4 - 3,5,3',5' iodonized - primary form of thyroid hormone

    T3 - 3,5,3' iodonized - most active form of thyroid hormone, T4 converted to T3 to increase activity

    rT3 - 3,3',5' iodonized - inactive form, T4 converts to T3 to reduce activity
  51. Thyroid hormone synthesis / release
    1. active transport of iodine by follicular cell

    2. synthesis and internal secretion of thyroglobulin into the colloid

    3. iodinization of thyroglobulin tyrosine residues within the colloid

    4. coupling of two iodotyrosine residues of the thyroglobulin

    5. cellular uptake of iodinated thyroglobulin by reabsorption from the colloid

    6. proteolytic release of iodinated thyronines in the lysozomes

    7. release of T4 and T3 into the blood
  52. I-/Na+ channels
    responsible for accumulating iodide within follicular cells via secondary active transport, along the gradients established via NA/K-ATPase
  53. Thyroglobulin
    precursor to T3 / T4 with ~123 tyrosine residues, synthesized in the ER of the follicular cells. Secreted with thyroid peroxidase, which catalyzes iodinization
  54. Thyroid peroxidase
    originates in follicle cells, becomes active in the colloid space when it is combined with iodine. Catalyzes inter/intramolecular coupling of MIT and DIT residues to make T3 and T4
  55. T3 / T4 release
    endocytosis at the apical membrane of the follicular cells of thyroglobulin. Colloid vacuoles fuse with lysozymes, which partially proeolyse the thyroglobulin to release free T4 / T3
  56. Deiodinases
    responsible for deionidating T4. 5' deiodinase converts T4 to T3, 5 deiodinase converts T4 to rT3. A single deiodinization from T4 to T3 is considered an activation step, because T3 is more active than T4. Further deiodinization is considered an inactivation step
  57. Thyroxine-Binding Globulin
    TBG - primary plasma protein binding to thyroid hormones. Very high affinity for T4, slightly lower affinity for T3
  58. Transerythrin and Albumin
    Thyroid hormone binding plasma proteins. Transerythrin binds to ~20% of plasma T4 and ~1% of plasma T3, while Albumin binds to ~13% T4, 53% T3. Albumin is far more concentrated in blood plasma than Transerythrin or TBG
  59. Homeostatic regulation of thyroid gland
    Thyrotropin-Releasing Hormone (TRH) from the hypothalamus stimulate synthesis and secretion of TSH in anterior pituitary. Thyroid Stimulating Hormone (TSH) primarily regulates the thyroid gland, increases synthesis and secretion of T3, T4.

    T3, T4 inhibit TRH / TSH secretion
  60. Thyroid-stimulating hormone
    TSH - several effects on the thyroid:

    increase release of T3 / T4

    increase rate of iodide uptake

    increase rate of tyrosine iodination and coupling

    increase endocytosis of colloid

    increase thyroglobulin proteolysis

    increase follicular cell height
  61. Thyroid hormone targets
    T3 / T4 have same essential function, with T3 being more potent. Act by binding to intracellular receptors, principally activation of gene transcription at the DNA level
  62. Effects of thyroid hormones on development
    Essential for growth and development in childhood

    enhance bone growth and epiphysial closure

    stimulate growth hormone secretion and potentiate its tissue effects

    necessary for brain development, especially cerebral cortex

    required for proper formation of the cochlea

    pg. 39 for descriptive charge of thyroid secretion patterns throughout development
  63. Effects of thyroid hormones in adults
    elevate Basal Metabolic Rate (BMR)

    increase heat production

    activate mitochondrial metabolism

    enhance absorption of carbohydrates from intestine

    increase breakdown of carbohydrates and lipids

    stimulate O2 dissociation from hemoglobin (which increases 2,3-DPG)

    enhance sensitivity to catecholamines, such as epinephrine / norepinephrine

    pg. 40: summary of metabolic effects of thyroid hormones
  64. Cretinism
    hypothyroidism during pre and postnatal development of children

    characterized by mental retardation, dwarfism, deaf-mutism and other physical abnormalities

    caused by maternal iodine deficiency, fetal congenital abnormalities of the thyroid / pituitary / hypothalamus, or maternal antithyroid antibodies that cross the placenta
  65. Adult hypothyroidism
    low metabolic rate, poor cold tolerance, drying and yellowing of the skin, thinning hair and sometimes mental symptoms

    can lead to the development of a goiter in cases of iodine deficiency, because low thyroid hormone leads to elevated TSH, which stimulates hypertrophy of the thyroid gland
  66. Hyperthyroidism
    increased BMR, increased food intake, weight loss, heat-intolerance, sweating, nervousness

    typically caused by Grave's Disease, autoimmune antibodies that stimulate TSH receptor. Stimulated thyroid often leads to development of a goiter / protusion of the eyeballs
  67. Endocrine pancreas
    ~2% of the pancreas, contained within Islets of Langerhans
  68. Islets of Langerhans
    endocrine functions of the pancreas, small groups of cells scattered throughout the pancreas. Four types of cells:

    Alpha cells - 20% of islet, secret glucagon, which raises plasma glucose and mobilizes hepatic glycogen and fat

    Beta cells - 60-75% of islet, secrets insuline, which raises cellular glucose uptake and deposition of glycogen and fat

    Delta cells - <5% of islet, secretes somatostatin, which lowers insulin and glucagon secretion, lowers exocrine gastric secretions

    F cells - <5% of islet, secrets pancreatic polypeptide, which lowers food absorption
  69. Insulin
    preproinsuline is turned into proinsuline following the signal sequence being cleaved. Single polypeptide chain (proinsulin), cleaved into B chain, C chain, and A chain. A and B chain are held together with disulfide bonds, while C chain is removed and becomes inactive. Packaged into secretory vessicles with zinc. Secreted half-life is ~5 minutes
  70. Insulin and Glucagon secretion levels
    pg. 47. Insulin secretion increases when blood glucose raises above 5.5 mM, glucagon increases when blood glucose falls below 5.5 mM
  71. Glucose regulation of Insulin secretion
    Pg. 48
  72. Insulin secretion modulation by metabolic and hormonal signals
    pg. 48
  73. Insulin receptor signaling
    pg. 49
  74. Insulin activation of Glucose transport
    Glut 4 transporters (which allow for glucose transport) are internalized within endosomes. Insulin binding to insulin receptors causes activation of phosphoinositide 3-kinase, which translocates the Glut 4 containing endosomes into the cell membrane
  75. Glucose transporters in mammals
    pg. 50
  76. Metabolic actions of insulin
    Rapid (seconds): increased transport of glucose, amino acids, and K+ into insuline sensitive cells

    intermediate (minutes): stimulation of protein synthesis

    inhibition of protein degadation

    activation of glycolytic enzymes and glycogen synthase

    inhibition of glycogen phosphorylase and gluconeogenic enzymes

    increased lipogenesis, inhibition of lipolysis

    delayed (hours): increase in mRNAs for lipogenic and other enzymes
  77. Insulin effect on metabolic flux
    increases tissue uptake of glucose and amino acids, tissue release of glucose, amino acids and free fatty acids is inhibited by insulin, as is ketogenesis. Results in net decrease in plasma levels of these substrates
  78. Glucagon
    Opposite of insulin

    peptide hormone synthesized in the alpha-cells of the endocrine pancreas

    it is synthesized initially as a preprohormone, similar to insulin

    half-life of ~5-10 minutes, degraded by its major target organ, the liver. Released into the portal vein, little aside from Liver is exposed to glucagon
  79. Regulation of glucagon secretion
    pg. 52
  80. Effects of glucagon on metabolic fluxes
    Pg. 53
  81. Somatostatin
    produced in delta-cells of the pancreas, also formed in the hypothalamus

    stimulated by the same stimuli that increase insulin secretion

    principle effect of pancreatic somatostatin is to inhibit the release of other islet hormones, primarily insulin and glucagon

    dereases glucose transport across the gut wall and decreases blood flow in the GI tract
  82. Metabolic effects of epinephrine and norepinephrine
    pg. 55
  83. Cortisol in metabolism
    stimulates the mobilization of amino acids (primarily from muscle) and their converstion to glucose (in the liver). Glucose is stored as glycogen and released for use by other tissues

    inhibits the stimulation of glucose uptake by insulin in muscle and fat

    causes mobilization of fat from adipose tissue but can also facilitate fat storate in selected adipose tissue sites

    hyperglycemic (increases blood glucose), but also stimulates deposition of glycogen
  84. Leptin
    endocrine hormone from adipose tissue, made in proportion with amount of adipose tissue in the body

    Leptin expression increases as adipose tissue increases, inhibiting hunger center in the brain, reducing appetite and decreasing food intake, increasing basal energy expenditure, obligatory thermogenesis, and modulating the secretion of hormones to decrease the lipogenic activity and increase the lipolytic activity of adipose tissue
  85. Major metabolic hormones summary
    pg. 57
  86. Diabetes Mellitus
    diabetes, one of two basic forms, type 1 and type 2

    type 1: insulin-dependent, primary failure of insulin secretion by the endocrine pancreas

    type 2: non-insulin dependent, loss of insulin sensitivity of the tissues, typically accompanied by reduced insulin secretion

    polyuria (excessive urine), polydipsia (excessive thirst), polyphagia (excessive eating), hyperglycemia, glucosuria (glucose in urine)

    failure of glucose uptake and metabolism in peripheral tissues
  87. Metabolic syndrome
    abdominal obesity

    high plasma triglycerides

    low HDL- and high LDL- cholesterol

    high fasting blood glucose

    insulin resistance

    elevated blood pressure

    risk for:

    type 2 diabetes

    coronary artery disease