Endocrine System Module 12 PDF

1 Hormones are chemical messengers  each exert their action on a specific target. They are classified according to their structure: Amines and amino acids  epinephrine & nor-epinephrine, thyroid, dopamine Peptides, glycoproteins  growth hor...

1 Hormones are chemical messengers  each exert their action on a specific target. They are classified according to their structure: Amines and amino acids  epinephrine & nor-epinephrine, thyroid, dopamine Peptides, glycoproteins  growth hormone (GH), thyrotropin releasing hormone, insulin Steroids  derivatives of cholesterol and include the sex hormones such as estrogens and testosterones Fatty acid derivatives  arachidonic acid, leukotrienes, prostaglandins 2 General characteristics include: Specific rates and rhythms of secretion Affect only cells with appropriate receptors Liver metabolizes hormones  inactivating them & making them more water-soluble so that the kidneys can then excrete them Operate within a feed back system 3 Most of the control of hormones in the body operates by negative feedback Which operate similar to the thermostat on a heating system When the monitored value decreases below the set point…the feedback mechanism causes the value to increase And, whhen the monitored value is increased above the set point…the feedback mechanism cause it to decrease For example, in the negative feedback system that controls blood glucose levels: Increase in glucose  stimulates an increase in insulin which enhances the removal of glucose from the blood decreases blood glucose levels When blood glucose levels start to decrease  insulin secretion is inhibited & glucagon stimulates release of glucose from liver, which causes blood glucose levels to return to normal The lack of a negative feedback inhibition on hormonal release often results in pathologic conditions: This failure to “turn off” the system can cause excessive hormone production leading to pathologic condition 4 Hormones are released into the circulation by endocrine glands Water-soluble hormones circulate in the bloodstream in free forms (unbound). Examples would include include  insulin, pituitary, and hypothalamic hormones Have a short half-life Lipid soluble hormones Such as  cortisol, thyroid, adrenal andorogens are circulated bound to a protein So a large change in the concentration of binding protein can affect the concentration of free hormone available and, therefore, its effects Cortisol  10% free & ~ 75% bound to a corticosteroid-binding globulin When released into the bloodstream – it circulates and is distributed throughout the body – but only those cells that have the appropriate receptors are affected These cells are known as target cells The receptors are located in or on the cell membrane or in the intracellular component of the target cell Lipid – soluble hormones Are classified as Steroid hormones such as androgens, estrogens, glucocorticoids, mineralcorticoids and thyroid hormones Synthesized from cholesterol and diffuse across the cell membrane And bind to specific regions on the DNA Then activate Receptors for water soluble hormones are located on the cell membrane of the target cell. Hormones that bind to a receptor is referred to as a first messenger  it sets off the next step in the “cascade” to activate Signal transduction  process in which the hormones are communicated into the cell Process in which binding of hormone to receptor activates that receptor through enzymes which produce a “second messenger” The end result  activation of intracellular enzyme needed for hormone action They are the link between the hormone (first messenger) and the inside of the cell These second messengers include: Calcium Cyclic AMP Cyclic GMP 5 6 The hypothalamus is the part of the brain where the activity of the autonomic nervous system and the endocrine glands (which directly control various organ systems of the body) are integrated The pituitary gland is the partner to the hypothalamus  responds to input from the brain (via the hypothalamus) & the body (via the various peripheral endocrine glands) Together this is known as the hypothalamic-pituitary axis (or neuroendocrine axis) The hypothalamus is located in the floor and lateral walls of the third ventricle. It is connected to the pituitary gland by a stalk at the base of the brain. Some axons of hypothalamic neurons travel down the pituitary stalk. Their endings compromise the posterior pituitary gland. The posterior pituitary and anterior lobe of pituitary are distinct from each other: Upon stimulation from the hypothalamus via a nerve tract  the posterior pituitary neurons secrete the peptide hormones (oxytocin & vasopressin) directly into the systemic circulation & affect peripheral tissue directly Other hypothalamic neurons secrete hormones into a specialized capillary bed that flows directly to the anterior pituitary  stimulating the secretion of anterior pituitary hormones is stimulated These then travel through bloodstream and trigger the release of yet other hormones from particular endocrine glands Which in turn have effects on target tissues that influence growth, reproduction, metabolism and response to stress 7 The two major posterior pituitary hormones are: 1. Vasopression … also known as antidiuretic hormone (ADH) Has the role of helping control plasma osmolality  acts on the collecting tubules of the kidney making them more permeable to water 2. Oxytocin Play s role in stimulating uterine contractions and promoting lactation ? role in sperm motility in men 8  Anterior pituitary hormones  there is a hypothalamus releasing hormone for each hormone released by the anterior pituitary they then act on the anterior pituitary to “release” their hormone (these are known as tropic hormones) Growth hormones (GH) Regulated by hypothalamic growth-releasing hormone GH has direct actions stimulates the growth of cartilage Has insulin-like effects of promoting fuel storage in various tissues Thyrotropin (TSH) Produced upon stimulation of tRH from the hypothalamus TSH travels via the systemic bloodstream to the thyroid gland Stimulating synthesis of the thyroid hormones Thyroxine (T4) and tri- iodothyronine (T3) Thyroid hormones have effects on nearly every tissue in the body (especially CVS, respiratory, skeletal, & CNS) ACTH In response to variety of indicators of stress, hypothalamus release CRH (corticotrophin-releasing hormone) into the pituitary portal system CRH then stimulates the release of ACTH (adrenocorticotropin hormone) ACTH triggers synthesis & secretion of the corticosteroids from the adrenal cortex, androgens & mineralocorticoids 9 Alterations of Hormonal Regulation  can usually be divided into two categories: Hypofunction & Hyperfunction Dysfunction may involve: Feedback loop problems may fail to function properly or respond to inappropriate signals Decrease in production  secretory cells are unable to produce or obtain hormone precursors or convert those precursors to active hormone Change in degradation  or inactivated by antibodies before reaching target cells Excessive amounts  ectopic sources of hormones (hormones produced by non-endocrine tissues) We’re going to look at just two of the most common hormonal dysfunctions seen in the US: Diabetes and Thyroid alterations 10 The thyroid gland is composed of two lobes that lie on either side of the trachea, and inferior to the thyroid cartilage Lobes are joined by band of tissue called isthmus Gland is composed of cells called follicles  which synthesize and secrete the hormones Thyroid gland synthesis the hormones T4 (thyroxine) and T3 (tri-iodo-thyronine)  iodine containing amino acids that regulate the body’s metabolic needs. 11 The thyroid gland produces 90% T4 and 10% T3 In body tissues, the thyroid hormones enter the cell & within cell cytoplasm most of the T4 is converted to T3 T3 has the greatest metabolic effects Once released in circulation T3 and T4 are transported bound to one of three protein carriers 1. Thyroxine-binding globulin (TBG) 2. Thyroxine-binding prealbumin 3. Albumin in body Thyroid affects growth and maturation of tissues & affect cell metabolism (heat production & oxygen consumption). Thyroid dysfunction is one of the most common endocrine disorders encountered in clinical practice 12 Most commonly encountered thyroid dysfunction encountered is: Hyperthyroidism (also referred to as thyrotoxicosis) Caused by excess thyroid hormone Manifestations are related to increased oxygen consumption, the hypermetabolic state, and increase in sympathetic nervous system that occurs. So the individual will present with: Nervousness, irritability Weight loss despite large appetite Tachycardia, palpitations, heat intolerance Treatment  reducing thyroid hormone Eradication of gland (through radioactive iodine, surgical removal, drugs that block the conversion of T4 to T3 in tissues  prophylthiouracil (PTU) Beta blockers (propranalol) block effects on the sympathetic system Graves disease accounts for 80-90% of all hyperthyroidism State of hyperthyroidism with goiter & exophthalmos (triad) Autoimmune disease ( also associated with other autoimmune disease such as myasthenia gravis & pernicious anemia)  Graves disease is one of the most common autoimmune diseases in the US Affects about 1% of population under age 40. Key immune problem is a unique antithyroid antibody (an immunoglobulin) that acts like a thyroid stimulation hormone. It attaches to follicle epithelial cells and stimulates them to secrete thyroid hormones  hence, it is named thyroid-stimulationf immunoglobulin (TSI) and is detectable in blood by a lab test Exophthalmos is a key finding in Grave’s disease in which autoimmune antibodies act to cause an accumulation of fat behind the eyes, which pushes them out. This can cause severe eye problems which include: paralysis of extraocular muscles involvement of optic nerve leading to vision loss corneal ulcerations not all ocular changes are reversible even with treatment Thyroid storm is an extreme and life-threatening form of thyrotoxicoxis Occurs in individuals who have undiagnosed or partially treated severe hyperthyroidism Precipitated by stress such as infection, diabetic ketoacidosis, manipulation of gland during surgical removal Manifestations: Very high fever Extreme CVS effects  high output failure Severe CNS effects High mortality Treatment  cooling, beta blockers, glucocorticoids to correct relative adrenal insuff d/t high metabolic state Avoid ASA (aspirin)  increases the level of free thyroid hormones 13 Goiter  is an enlarged thyroid gland Goiter is ONLY a term that describes the size of the gland and says nothing about thyroid function Diffuse enlargement of the thyroid gland caused by prolonged elevation of TSH  seen in hypothyroidism. But can be seen in Grave’s disease d/t stimulation of the gland by other antibodies rather than TSH So, goiters can be associated with hyperthyroidism, hypothyroidism or normal function (this is called nontoxic goiter) In most instances, the cause of goiter is unknown. Iodine deficiency is the most common cause of goiter in developing nations Diet low in iodine hinders the synthesis of thyroid hormone Most goiters come to attention because of a mass in the lower anterior neck which may be noticed first by others as the patient takes a sip of a drink and the mass becomes visible, bobbing up and down with the swallow. 14 Hypothyroidism is a deficiency of thyroid hormone which can be either congenital or primary Etiologies of primary hypothyroidism Subacute  nonbacterial inflammation of the thyroid Often preceded by viral infection Last 2-4 months Spontaneous recovery Hashimito Most common cause of hypothyroidism (and goiter) Autoimmune disorder in which the thyroid may be totally destroyed by an auto immune process Predominantly seen in women (ratio 5:1)  almost exclusively in middle- aged women (90% of cases) At onset, only a goiter may be present In time, hypothyroidism becomes evident (as inflammation persists and the gland is destroyed) Painless thyroiditis  similar to subacute but pathologically identical to Hashimotos Post partum  occurs within 6 moths of delivery. Spontaneous recovery Myxedema coma  Medical emergency with client exhibiting diminished level of consciousness; hypothermia, hypoventilation, hypoglycemia. It has been associated with over use of narcotics and sedatives in hypothyroid individuals 15 Myxedema Indicative of severe or long-standing hypothyroidism Presence of non-pitting edema caused by increased mucopolysaccharide in connective tissues Face takes on puffy look, especially around the eyes Tongue becomes enlarged Voice is hoarse and husky Mucopolysaccharide deposits can also occur in heart  cardial dilatation, bradycardia, pleural & pericardial effusions Congenital hypothyroidism Result of absent thyroid tissue or defects in thyroid synthesis Common cause of preventable mental retardation affecting 1 in 4000 infants Important to identify – can be identified within first week of life through state mandated infant metabolic screenings (IMS) that are obtained on all newborns Manifestations of untreated are referred to as cretinism If identified and treated before 6 weeks of age  normal intelligence 16 Please make sure you review the video on Understanding thyroid tests that is posted in the week 12 module on Brightspace 17 Endocrine pancreas (produces hormones)  exocrine pancreas (produces digestive enzymes) We are going to look at the function of the endocrine pancreas which is composed of the islets of Langerhans  secrete hormones that help regulate much of carbohydrate metabolism in the body Three types of secreting cells Alpha cells  produce glucagon Glucagon breaks down glycogen to increase glucose levels in the blood Released with low glucose levels, stress, cold Beta cells  produce insulin Secreted in response to rise in blood glucose levels Also secreted in response to parasympathic stimulation Facilitates the rate of glucose uptake into cells Delta cells  produce somatastatin which can then stimulate the release of either insulin or glucagon 18 19 Diagram showing location and relative percentage of the secreting cells of the pancreas 20 Diabetes mellitus is the term used to describe a syndrome characterized by chronic hyperglycemia & other disturbances of CHO, fat & protein metabolism. The most common of which are Type I & II diabetes. Type I accounts for 10% of all diabetes (used to be called juvenile diabetes) Pancreatic atrophy & specific loss of beta cells Macrophages, T & B lymphocytes are present Two distinct types have been identified 1. Autoimmune  cell-mediated destruction of the beta cells 2. Nonimmune  occurs secondary to other diseases such as pancreatitis or a more fulminant disease 21 Genetic susceptibility Exact nature of genetic susceptibility not clearly known There are some markers associated (that are also assoc with other autoimmune diseases) It appears that individuals who have a genetic tendency to develop this disease experience an environmental trigger that initiates the autoimmune process Environmental factors Some viral infections have been implicated autoimmune destruction of beta cells  CMV, mumps, Epstein-Barr Cow milk intake in some individuals may trigger beta cell autoantibodies (felt to be in response to bovine serum albumin) In type I there is immune mediated destruction of beta cells; it is a slowly progressive T cell-mediated disease Accompanied by autoantibodies against pancreatic beta cells which are present in most individuals at the time of diagnosis of type 1 diabetes. Manifestations: Individuals who have type 1 diabetes show normal glucose handling before disease onset. In the past it was thought that type 1 developed suddenly and with little warning. Currently, however, it is thought that type 1 develops over the course of many years, with the presence of autoantibodies against beta cells and their steady destruction occurring well in advance of diagnosis. 80-90% of function of the insulin secreting beta cells must be lost before you start seeing the hyperglycemia. Other clinical manifestations include the glycosuria in which glucose appears in the urine as the renal threshold for glucose is exceeded  gives an osmotic diuresis  polydipsia & polyuria Because of lack of insulin protein & fat occur resulting in muscle wasting, weight loss One of the actions of insulin is the inhibition of lipolysis (fat breakdown) and release of fatty acids from fat cells. In the absence of insulin (as seen in type I diabetes) these fatty acids are released from triglyceride stores in adipose tissue... leading to the increase in serum lipid levels...due to these elevated fatty acids... which are then converted to ketones in the liver...leading to ketoacidosis. 22 Type 2  much more common than type 1 (was known as adult onset but now being seen much earlier – now in children Most common form of diabetes in the Unites States is type II insulin resistance is hallmark of the disorder Decreased binding of insulin to receptors Decreased number of receptors Decreased sensitivity of receptors to insulin patients have varying amts of residual insulin secretion that prevents severe hyperglycemia or ketoacidosis onset occurs at least 7 yrs before its diagnosis (50% of cases in US are undiagnosed) Pediatric consideration: In the past, type 2 diabetes was referred to as adult-onset diabetes because it typically occurred in individuals older than 30 years of age. Unfortunately, this distinction is becoming less and less true as more teenagers and preteens are developing insulin resistance, most likely related to the increasing prevalence of obesity in childhood. Several studies suggest that over 20% of American children are obese, a finding with enormous implications for health (and health care costs) as these children reach adulthood and experience the complications of long-term hyperglycemia. 23 Read slide 24 Metabolic syndrome is a term that is used (it is not a disease itself) that signifies the individual has a collection of certain signs and symptoms. And, when you put these s & s together they equal metabolic syndrome and we know that individuals who have metabolic syndrome have increased risk to go on and develop Type II diabetes and/or heart disease. Basically, it’s a marker for worse thing to come unless that individual makes some lifestyle management changes. So, what are the s & s that lead to the diagnosis of metabolic syndrome (if the individual has any three of the following): Abdominal obesity with waist circumference greater than 40 inches in men and greater than 35 in women Triglyceride level greater than 150 mg/dL HDL