NURA 510 Advanced Pathophysiology Endocrine System PDF

NURA 510 Advanced Pathophysiology Linda Wunder, PhD, CRNA, APRN, FAANA Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc.  Endocrine System ˜ Functions Ø Differentiation of the reproductive and central nervous systems in the developing f...

NURA 510 Advanced Pathophysiology Linda Wunder, PhD, CRNA, APRN, FAANA Copyright © 2014, 2010, 2006 by Mosby, Inc., an imprint of Elsevier Inc.  Endocrine System ˜ Functions Ø Differentiation of the reproductive and central nervous systems in the developing fetus Ø Stimulation of sequential growth and development during childhood and adolescence Ø Coordination of the male and female reproductive systems Ø Maintenance of an optimal internal environment Ø Initiation of corrective and adaptive responses when emergency demands occur Copyright © 2019, Elsevier Inc. All rights reserved. 2 Endocrine System (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 3  Hormones ˜ Chemical messengers that are released by glands ˜ General characteristics Ø Specific rates and rhythms of secretion Diurnal or circadian, pulsatile and cyclic, and patterns, depending on circulating substrates Ø Operate within feedback systems Ø Affect only cells with appropriate receptors Ø Are inactivated by the liver or directly excreted by the kidneys Copyright © 2019, Elsevier Inc. All rights reserved. 4  Regulation of Hormone Release ˜ Hormones are released Ø In response to an alteration in the cellular environment Ø To maintain a regulated level of certain substances or other hormones ˜ Chemical, endocrine, or neural factors: regulate hormones ˜ Negative feedback: most common ˜ Positive feedback Copyright © 2019, Elsevier Inc. All rights reserved. 5 Regulation of Hormone Release (Cont.) ˜ Negative feedback Copyright © 2019, Elsevier Inc. All rights reserved. 6  Hormone Transport ˜ Hormones are released into the circulatory system by endocrine glands and distributed throughout the body. Ø Water-soluble hormones circulate in free, unbound forms. Ø Lipid-soluble hormones are primarily transported bound to a carrier or transport protein. Copyright © 2019, Elsevier Inc. All rights reserved. 7  Hormone Receptors ˜ Target cells Ø Recognize and bind with a high affinity to hormones Ø Initiate a signal Ø The more receptors, the more sensitive the cell ˜ Up-regulation Ø Low concentrations of hormones increase the number of receptors per cell. ˜ Down-regulation Ø High concentrations of hormones decrease the number of receptors. Copyright © 2019, Elsevier Inc. All rights reserved. 8  Hormone Receptors (Cont.) ˜ Up-regulation and down-regulation Copyright © 2019, Elsevier Inc. All rights reserved. 9  Hormone Receptors (Cont.) ˜ Are located in or on the plasma membrane or in the intracellular compartment of the target cell ˜ Water-soluble hormones Ø Have a high molecular weight Ø Cannot diffuse across the plasma membrane ˜ Lipid-soluble hormones Ø Easily diffuse across the plasma membrane and bind to cytosolic or nuclear receptors Copyright © 2019, Elsevier Inc. All rights reserved. 10 Plasma Membrane Receptors and Signal Transduction First Messenger Hormone that carries the message to the target cell Signal Transduction Process by which this message is communicated into the target cell Involves several steps Copyright © 2019, Elsevier Inc. All rights reserved. 11  Plasma Membrane Receptors and Signal Transduction (Cont.) ˜ Signal transduction Ø Steps Receptor activation or binding of a hormone to its receptor Activation of a G protein (transducer) and membrane- associated enzyme (effector enzyme) Production of a second messenger Activation of an intracellular enzyme, such as protein kinase A or C Alterations in gene transcription and the resulting target cell response to the hormone Copyright © 2019, Elsevier Inc. All rights reserved. 12  Plasma Membrane Receptors and Signal Transduction (Cont.) ˜ Hormone binding Copyright © 2019, Elsevier Inc. All rights reserved. 13  Plasma Membrane Receptors and Signal Transduction (Cont.) ˜ Second messengers Ø Are the initial link between the first signal (hormone) and the inside of the cell Ø Examples Cyclic adenosine monophosphate (cAMP): must activate adenylyl cyclase Cyclic guanosine monophosphate (cGMP): is activated by the enzyme guanylyl cyclase Calcium (Ca++): binds with calmodulin, a regulatory protein Ø Associates with inositol trisphosphate (IP3) and diacylglycerols (DAG) to produce physiologic effects Copyright © 2019, Elsevier Inc. All rights reserved. 14  Plasma Membrane Receptors and Signal Transduction (Cont.) ˜ First and second messengers Copyright © 2019, Elsevier Inc. All rights reserved. 15 Steroids (Lipid-Soluble) Hormones ˜ Are synthesized from cholesterol ˜ Examples Ø Androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, vitamin D, retinoid ˜ Diffuse across the plasma membrane and bind to cytoplasmic or nuclear receptors. ˜ Activate Ø Ribonucleic acid (RNA) polymerase Ø Deoxyribonucleic acid (DNA) transcription Copyright © 2019, Elsevier Inc. All rights reserved. 16  Hormone Effects ˜ Three routes stimulate hormone effects 1. Acting on preexisting channel-forming proteins to alter membrane channel permeability 2. Activating preexisting proteins through a second messenger system 3. Activating genes to cause protein synthesis ˜ Two general effects 1. Direct 2. Permissive Copyright © 2019, Elsevier Inc. All rights reserved. 17  Hypothalamic-Pituitary Axis Structure Functions ˜ Hypothalamus ˜ Forms the structural and ˜ Pituitary gland functional basis for integrating the neurologic Ø Anterior pituitary and endocrine systems (adenohypophysis) (neuroendocrine system) Ø Posterior pituitary ˜ Produces releasing or (neurohypophysis) inhibitory hormones and tropic hormones Copyright © 2019, Elsevier Inc. All rights reserved. 18 Hypothalamic-Pituitary Axis (Cont.) ˜ Pituitary gland Copyright © 2019, Elsevier Inc. All rights reserved. 19  Hypothalamus ˜ Is located at the base of the brain ˜ Is connected to the anterior pituitary by portal blood vessels ˜ Is connected to the posterior pituitary by a nerve tract (hypothalamohypophysial tract) Copyright © 2019, Elsevier Inc. All rights reserved. 20  Hypothalamus (Cont.) ˜ Produces hormones Ø Prolactin-inhibiting factor (PIF) Ø Thyrotropin-releasing hormone (TRH) Ø Gonadotropin-releasing hormone (GnRH) Ø Somatostatin Ø Growth hormone-releasing factor (GRF) Ø Corticotropin-releasing hormone (CRH) Ø Substance P Copyright © 2019, Elsevier Inc. All rights reserved. 21  Hormones of the Anterior Pituitary Corticotropin- Somato- Minor Related Hormones Glycoproteins mammotropins Corticotropin Adrenocorticotropic Thyroid-stimulating Growth hormone β-Lipotropin- hormone (ACTH) hormone (TSH) (GH) fat catabolism Follicle-stimulating hormone (FSH) Melanocyte- Luteinizing Prolactin β-Endorphins-pain stimulating hormone (LH) perception hormone (MSH) Copyright © 2019, Elsevier Inc. All rights reserved. 22 Hormones of the Posterior Pituitary ˜ Synthesized in the nuclei of the hypothalamus ˜ Stored and secreted by the posterior pituitary Ø Antidiuretic hormone (ADH, arginine vasopressin) Controls plasma osmolality Causes water reabsorption into the blood Is released when plasma osmolality is increased or intravascular volume is decreased Ø Oxytocin Causes uterine contractions and milk ejection in lactating women Acts on uterus to stimulate contractions Copyright © 2019, Elsevier Inc. All rights reserved. 23  Pineal Gland ˜ Is located within the brain itself ˜ Is made up of photoreceptive cells that secrete melatonin Ø Melatonin regulates circadian rhythms and reproductive systems, including secretion of GnRH and the onset of puberty. Ø Plays an important role in immune regulation Ø Possibly affects the aging process Copyright © 2019, Elsevier Inc. All rights reserved. 24  Thyroid and Parathyroid Glands ˜ Thyroid gland Ø Two lobes lateral to the trachea Ø Isthmus Ø Follicles (follicle cells surrounding the colloid) Ø Parafollicular cells (C cells) Secrete calcitonin, which lowers serum calcium levels Copyright © 2019, Elsevier Inc. All rights reserved. 25 Thyroid and Parathyroid Glands (Cont.) ˜ Regulation of thyroid hormone secretion Ø TRH stimulates the release of the thyroid-stimulating hormone (TSH). Ø TSH increases release of stored thyroid hormones. iodide uptake and oxidation. thyroid hormone synthesis. synthesis and secretion of prostaglandins by the thyroid gland. Copyright © 2019, Elsevier Inc. All rights reserved. 26 Thyroid and Parathyroid Glands (Cont.) ˜ Thyroid hormones Ø T4 production by the thyroid gland is 90%. Ø T3 production is 10%. Ø Are bound to thyroxine-binding globulin, thyroxine-binding prealbumin, lipoproteins, or albumin Ø Affect the growth and maturation of tissues, cell metabolism, heat production, cardiac functioning, and oxygen consumption If the results show that TSH is high and T-4 is low, then the diagnosis is hypothyroidism A low TSH level typically indicates hyperthyroidism; a low TSH means the pituitary gland is signaling the thyroid to produce less hormone because there is already too much circulating in the body Copyright © 2019, Elsevier Inc. All rights reserved. 27 Thyroid and Parathyroid Glands (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 28 Thyroid and Parathyroid Glands (Cont.) ˜ Parathyroid glands Ø Are small glands located behind the thyroid gland Ø Produce parathyroid hormone (PTH) Regulates serum calcium Increases serum calcium concentration Decreases serum phosphate level Serves as co-factor with vitamin D to increase calcium absorption Is an antagonist of calcitonin Copyright © 2019, Elsevier Inc. All rights reserved. 29 Thyroid and Parathyroid Glands (Cont.) ˜ Parathyroid glands (cont.) Ø Parathyroid hormone-related peptide (PTHrP) Has properties similar to PTH Important for endochondral bone formation and bone remodeling Copyright © 2019, Elsevier Inc. All rights reserved. 30  Endocrine Pancreas ˜ Pancreas Ø Endocrine gland: produces hormones Ø Exocrine gland: produces digestive enzymes Ø Houses the islets of Langerhans Secretion of glucagon and insulin † Alpha cells: glucagon † Beta cells: insulin and amylin † Delta cells: somatostatin and gastrin † F cells: pancreatic polypeptide Copyright © 2019, Elsevier Inc. All rights reserved. 31 Endocrine Pancreas (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 32  Endocrine Pancreas (Cont.) ˜ Insulin Ø Is regulated by chemical, hormonal, and neural mechanisms Ø Secretion is promoted by increased blood glucose levels. Ø Facilitates the rate of glucose uptake into the body’s cells Sensitivity of the insulin receptor is a key component in maintaining normal cellular function (insulin resistance). Glucose transporter-type 4 (GLUT 4) facilitates glucose diffusion. Ø Facilitates the intracellular transport of potassium Ø Is an anabolic hormone: synthesizes proteins, carbohydrates, lipids, and nucleic acids Copyright © 2019, Elsevier Inc. All rights reserved. 33  Endocrine Pancreas (Cont.) ˜ Amylin Ø Is a peptide hormone Ø In response to nutrient stimuli, is co-secreted with insulin by beta cells Ø Regulates blood glucose by: Delaying gastric emptying Suppressing glucagon secretion after meals Ø Has a satiety effect Ø Has an antihyperglycemic effect Copyright © 2019, Elsevier Inc. All rights reserved. 34  Endocrine Pancreas (Cont.) ˜ Glucagon Ø Is an insulin antagonist Ø Secretion is promoted by decreased blood glucose levels. Ø Increases glucose by stimulating glycogenolysis and gluconeogenesis Ø Stimulates lipolysis Copyright © 2019, Elsevier Inc. All rights reserved. 35  Endocrine Pancreas (Cont.) ˜ Somatostatin Ø Is produced by delta cells of the pancreas Ø Is essential in carbohydrate, fat, and protein metabolism Ø Should not to be confused with hypothalamic somatostatin Ø Regulates alpha-cell and beta-cell function by inhibiting the secretion of insulin, glucagon, and pancreatic polypeptide ˜ Gastrin Ø Likely controls the secretion of glucagon Copyright © 2019, Elsevier Inc. All rights reserved. 36  Endocrine Pancreas (Cont.) ˜ Incretins Ø Glucagon-like peptide-1 (GLP-1) and glucose- dependent insulinotropic polypeptide (GIP) Ø Control postprandial glucose levels by: Promoting glucose-dependent insulin secretion Inhibiting glucagon synthesis Promoting hepatic glucose secretion Delaying gastric emptying Ø Cause enhancement of beta-cell mass and replenishment of intracellular stores of insulin Copyright © 2019, Elsevier Inc. All rights reserved. 37  Endocrine Pancreas (Cont.) ˜ Ghrelin Ø Stimulates growth hormone secretion Ø Controls appetite Ø Regulates insulin sensitivity ˜ Pancreatic polypeptide Ø Is released by PP cells in response to hypoglycemia and protein-rich meals Ø Promotes gastric secretion, and antagonizes cholecystokinin Copyright © 2019, Elsevier Inc. All rights reserved. 38  Adrenal Glands ˜ Two pyramid-shaped organs above the kidneys ˜ Adrenal cortex Ø 80% of an adrenal gland’s total weight Ø Zona glomerulosa Ø Zona fasciculata Ø Zona reticularis ˜ Adrenal medulla Ø Inner portion of the gland Copyright © 2019, Elsevier Inc. All rights reserved. 39 Adrenal Glands (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 40  Adrenal Glands (Cont.) ˜ Adrenal cortex Ø Stimulated by adrenocorticotropic hormone (ACTH) Ø Glucocorticoid hormones: cortisol, cortisone, and corticosterone Increase blood glucose Cause protein breakdown Have antiinflammatory, growth-suppressing effects Decrease immune response, resulting in increased likelihood for infection and poor wound healing Cortisol: is the most potent naturally occurring glucocorticoid hormone Copyright © 2019, Elsevier Inc. All rights reserved. 41  Adrenal Glands (Cont.) ˜ Adrenal cortex (cont.) Ø Mineralocorticoid hormones: aldosterone Affect ion transport by epithelial cells: cause sodium retention and potassium and hydrogen loss Are regulated by the renin-angiotensin-aldosterone system † Is activated by sodium and water depletion, increased potassium levels, and diminished effective blood volume † Angiotensin II is the primary stimulant of aldosterone synthesis and secretion. Copyright © 2019, Elsevier Inc. All rights reserved. 42  Adrenal Glands (Cont.) ˜ Renin-angiotensin-aldosterone system Copyright © 2019, Elsevier Inc. All rights reserved. 43  Adrenal Glands (Cont.) ˜ Adrenal cortex (cont.) Ø Adrenal estrogens and androgens Secretes weak androgens † Androgens are converted by peripheral tissues to stronger androgens such as testosterone. † Adrenal insufficiency -Addison disease † Over act rive adrenal gland -Cushing's Copyright © 2019, Elsevier Inc. All rights reserved. 44  Adrenal Glands (Cont.) ˜ Adrenal medulla Ø Chromaffin cells (pheochromocytes) Secrete the catecholamines epinephrine and norepinephrine Ø Release of catecholamines has been characterized as a “fight or flight” response. Ø Catecholamines promote hyperglycemia. Copyright © 2019, Elsevier Inc. All rights reserved. 45 Neuroendocrine Response to Stressors ˜ Endocrine system reacts with the nervous system to respond to stressors. ˜ Stress response also involves the immune system. ˜ Response is influenced by CRH from the hypothalamus. Copyright © 2019, Elsevier Inc. All rights reserved. 46  Tests of Endocrine Function ˜ Radioimmunoassay (RIA) Ø Measures minute quantities of hormones in the blood that uses antibodies and radiolabeled hormones to determine the quantity of hormone ˜ Enzyme-linked immunosorbent assay (ELISA) Ø Is less expensive and easier to conduct than RIA ˜ Bioassay Ø Uses graded doses of hormone in a reference preparation, and compares the results with an unknown sample Copyright © 2019, Elsevier Inc. All rights reserved. 47  Aging and the Endocrine System ˜ Endocrine changes: consequence or cause? ˜ Thyroid gland Ø Glandular atrophy, fibrosis, nodularity, and increased inflammatory infiltrates, decreased TSH ˜ Pancreas Ø Impaired glucose tolerance and diabetes Ø Pancreatic cells replaced with fat Ø Decreased insulin secretion of the beta cells and insulin receptors Ø Increased insulin resistance Copyright © 2019, Elsevier Inc. All rights reserved. 48 Aging and the Endocrine System (Cont.) ˜ Growth hormone and insulin-like growth hormone Ø Both decline with aging, called the somatopause; are linked to decreases in muscle size and function, fat and bone mass, and changes in reproductive and cognitive functions. ˜ Parathyroid glands Ø Are related to alterations in calcium balance Inadequate intake, malabsorption, or renal changes Copyright © 2019, Elsevier Inc. All rights reserved. 49 Aging and the Endocrine System (Cont.) ˜ Adrenal glands Ø Clearance of cortisol is decreased. Ø Plasma levels of adrenal androgens gradually decrease but dramatically decrease with age; called the adrenopause. ˜ Antidiuretic hormone Ø Hyponatremia Ø SIADH common in elderly Copyright © 2019, Elsevier Inc. All rights reserved. 50 51