Unformatted text preview: Endocrine System 1 Nervous System and Endocrine System • The Nervous System and the Endocrine System Coordinate Functions of the Body Systems – The nervous system controls homeostasis through nerve impulses that trigger the release of neurotransmitters whose effect results in either the excitation or inhibition of other neurons, muscle fibers, or gland cells. – The endocrine system releases hormones into the bloodstream which travels to the target organ were it alters the physiological 2 activity of the cells. 3 Three General Classes Of Hormones Lipid soluble derivatives – steriods derived from cholesterol and are synthesized in the smooth ER • sex hormones estrogen, progesterone, testosterone – eicosanoids derived from fatty acids • leukotrienes has mostly local action and is involved in tissue inflammation • prostaglandinshas local action and is involved in inflammation, smooth muscle contraction, blood flow, intensify pain, and promote fever. (Aspirin and ibuprofen [Motrin] inhibit prostaglandin synthesis.) Water soluble derivatives • Amino acid derivatives • Peptide and Proteins 4 5 Endocrine Glands • The body has two types of glands – Exocrine glands secrete their products into ducts that carry the secretions into body cavities or on to Exocrine gland picture body surfaces. • Sweat glands (sudoriferous glands) • oily glands (sebaceous glands) • mucous glands • digestive galnds – Endocrine glands ductless glands that secrete their products (hormones) into the extracellular space around the secretory cells (local action) which then diffuse into the blood vessels (distant action) 6 Endocrine gland picture Back Next slide 7 Endocrine System Endocrine glands of the body that constitute the endocrine system • Pituitary gland • Thyroid • Parathyroid • Adrenal • Pineal Tissues that contain cell that secrete hormones but not considered endocrine glands exclusively – – – – – – – – – – – – – Hypothalamus Thymus Pancreas Ovaries Testes kidneys Stomach Liver Small intestine Skin Heart Adipose tissue placenta
8 Circulating and Local Hormones Circulating hormones hormones that pass into the blood stream and act on distant target cells. • Linger in the blood and exert their effects for a few minutes or a few hours – Are inactivated by the liver and excreted by the kidney Local hormones those that act locally without first entering the bloodstream. – Paracrines hormones that act on neighboring cells – Autocrines those that act on the same cell that secreted them. • Are usually inactivated quickly • Ex: nitric oxide (NO) released by endothelial cell which causes relaxation of nearby vascular smooth muscle, in turn causing vasodilation and increased 9 blood flow Endocrine Cell 1. Circulating Hormone blood stream
Hormone Receptor 2. Paracrine cell Nearby target cell 3. Autocrine cell 10 Chemical Classes of Hormones Water–soluble Hormones • Monoamine (biogenic amines) hormones synthesized by modifying certain amino acids – Catecholamines (made from tyrosine) epinephrine, norepinephrine, and dopamine – Histamine from histadine by mast cells and platelets – Serotonin and melatonin from tryptophan • Peptide and protein hormones synthesized on the rough ER and consist of chains 3200 amino acids – Ex: Thyroidstimulating hormone (TSH)
11 Chemical Classes of Hormones Eicosanoid hormones chemical mediators derived from arachidonic acid (a 20 carbon fatty acid) located in the phospholipids in the plasma membrane • leukotrienes mediates allergic reactions – derived from the enzyme lipoxygenase action on arachidonic acid 12 Cyclooxygenase (COX) converts arachidonic acid to three other types of eicosanoids • Prostacyclin produced by the walls of blood vessels, where it inhibits blood clotting and vasoconstriction • Thromboxanes produced by blood platelets – in the event of injury, they override prostacyclin and stimulate vasoconstriction and clotting • Prostaglandins are the most diverse eicosanoid – thought to be produced in most organs of the body – promotes fever and pain in inflammation – has differing other effects, depending on the organ
13 • Non steroidal antiinflammatory drugs stop the action of cyclooxygenase, thus blocking prostaglandin synthesis thereby reducing – fever and pain in inflammation (decreased prostaglandin) – decrease blood clotting (decreased production of prostcyclin)
14 Hormone Transport in the Blood • Most water soluble hormone molecules circulate in the blood in the free from (not attached to a protein) • Most lipid soluble hormones bind to transport proteins • Transport proteins are albumin and globulins synthesized by the liver and have three functions – Improve the transportability of the lipidsoluble hormones by making them temporarily watersoluble – Retard passage of the small hormone molecules through the filtering mechanism in the kidneys, thus slowing the rate of hormone loss in the urine – Provide a ready reserve of hormone, already present 15 in the bloodstream • they protect circulating hormones from being broken down by enzymes in the blood plasma and liver – free hormones may be broken down or cleared from the blood in minutes, whereas bound hormones may circulate for hours or weeks. Hormone Transport • Bound hormone hormones attached to a transport protein • Unbounded (free) hormone one that is not attached to a transport protein • Only the free hormone can leave a blood capillary and get to a target cell. 16 Hormone Transport in the Blood • Up to 10% of the molecules of a lipid hormone are not bound to a transport protein, i.e. free fraction • It is the free fraction that diffuses our to capillaries, binds to receptors, and triggers responses. • Transport proteins release new ones to replenish the free fraction
17 Example of transport proteins: • Thyroid hormone binds to three transport proteins – albumin – albuminlike protein called thyretin – an alpha globulin named thyroxine binding globulin (TBG) • binds the greatest amount – 99.8% of T3 and T4 are protein bound – bound TH serves as a longlasting blood reservoir • Steroid hormones bind to globulins such as transcortin, the transport protein for cortisol.
18 Mechanisms of Hormone Action • Hormone response depends on the both the hormone and the target cell • Hormone may elicit different responses in different target cells – Ex: insulin stimulates glycogen synthesis in the liver and triglyceride synthesis in fat cells • Depending on whether a hormone is lipidsoluble or watersoluble, its target cell receptors may be either inside the cell or in the plasma membrane • Hormone responses may include – Synthesis of new molecules – Changing the permeability of the plasma membrane – Stimulating the transport of substances into or out of the cell – Altering the rate of specific metabolic reactions – Causing contraction of smooth or cardiac muscle 19 Action of Lipidsoluble Hormones • Diffuses through the lipid bilayer of the plasma membrane • Will bind to and activate receptors located within the cytosol or nucleus • Activated receptor then alters gene expression by turning on or off specific genes in the DNA • New messenger RNA is transcribed from which new protein are synthesized at the ribosomes • The new proteins alter the cell’s activity and cause the typical physiological responses of that 20 hormone 21 Action of Watersoluble Hormone • Binds at the membrane receptor (first messenger) • A second messenger is released within the cell where hormonestimulated responses can take place • One common second messenger is cylic AMP (cAMP), which is synthesized from ATP • Gprotein link receptors on the outer surface of the membrane to the adenylate cyclase on the inner surface – The binding of a hormone to its receptor activates many Gprotein molecules, which in turn activate molecules of adenylate cyclase. – Unless activated by more hormone, Gprotein slowly deactivates, thus stopping hormone response
22 23 24 Clinical Application Cholera Toxin and G Protein • Cholera toxin produces massive watery diarrhea in which a person can rapidly die of dehydration • Toxin modifies G protein in the intestinal epithelial cells such that they become locked in an activated state. – Results in large intracellular concentration of cAMP • Effect is to stimulate an active transport pump that ejects chloride inos from the cells into the lumen followed by water (osmosis) and sodium ions • Treatment consist of replacement of lost fluids, either intravenously or by mouth, plus antibiotics (tetracycline)
25 26 27 Hormone Interactions • Responsiveness to a target cell to a hormone depends on – The hormone concentration – The abundance of the target cell’s hormone receptors – Influences exerted by other hormones • Permissive effect when the actions of a hormone on target cells require a simultaneous or recent exposure to a second hormone. – Ex: Epinephrine alone only weakly stimulates lipolysis, but when small amounts of thyroid hormones are also present, the same amount of epinephrine stimulates 28 lipolysis much more powerfully Hormone Interactions • Synergistic effects when the effect of two hormones acting together is greater or more extensive than the sum of each hormone acting alone • Antagonistic effects when one hormone opposes the activation of another hormone. – Ex: Insulin promotes glycogen synthesis by the liver cells and glucagon stimulates glycogen breakdown
29 Enzyme Amplification • one hormone molecule does not trigger the synthesis of just one enzyme molecule • It activates thousands of enzymes molecules through a cascade called enzyme amplification • This enables a very small stimulus to produce a very large effect. • Hormones are therefore needed in very small quantities – their circulating concentrations are very low compared to other blood substances: on the order of nanograms per deciliter of blood • Because of amplification, target cells do not need a great number of hormone receptors
30 Hormone Clearance • Hormone signals, like nervous signals, must be turned off when they have serves their purpose – Most hormones are taken up and degraded by the liver and kidneys and then excreted in the bile or urine – Some are degraded by the target cells • The rate of hormone removal is called the metabolic clearance rate (MCR) • Half life the length of time required to clear 50% of the hormone from the blood – the faster the MCR the shorter the half life 31 Modulation of Target Cell Sensitivity • Hormones affect only target cells – Cells that carry specific receptors that bind the recognized hormone • Down regulation when receptor quantity decrease when hormone is in excess Down reg – Decreases responsiveness to hormone slide • Up regulation when receptor quantity increases when hormone is deficient – Makes target cell more sensitive to hormone 32 Next slide Receptor Down Regulation 33 back Clinical Application Blocking Hormone Receptors With Abortion Pill RU486 (mifepristone), the abortion pill •Blocks progesterone receptors in the endometrium, preventing endometrial growth. •Endometrial sloughs off with embryo 34 Control of Hormone Secretion • Most hormones are released in short burst, with little or know secretion in between. • Increased stimulation causes more frequent burst, thereby increasing blood concentration • Hormone secretion is regulated by – Signals from the nervous system – Chemical changes in the blood – Other hormones • Ex: nerve impulses to the adrenal medulla regulate the release of epinephrine • Blood calcium regulates the release of parathyroid hormone • Adrenocorticotropic hormone from the pituitary gland stimulates the release of cortisol by the adrenal cortex
35 Control of Hormone Secretion (cont) Disorders of the endocrine system often involve either – Hyposecretion inadequate release of hormone – Hypersecretion excessive release of hormone – Hormone receptors • Most cases are due to – Faulty control of secretion – Faulty hormone receptors – Inadequate number of receptors • Most hormonal regulatory systems work via negative feedback Negative feedback • Occasionally a positive feedback system contributes of regulation – In child birth, where oxytocin stimulates contractions of the uterus and the uterus in turn stimulates more oxytocin release. 36 Next slide 37 Back Hypothalamus and Pituitary Gland • Hypothalamus – The major integrating link between the nervous and endocrine system – Receives input from • • • • • • • Limbic system Cerebral cortex Thalamus Reticular activating system Sensory input from internal organs Retina Painful, stressful, and emotional experiences cause changes in hypothalamus activity
38 Hypothalamus and Pituitary Gland (cont) • Hypothalamus controls – Autonomic nervous system – Regulates body temperature – Thirst – Hunger – Sexual behavior – Defense reaction such as fear and rage • Is a crucial endocrine gland – Synthesizes at least nine different hormones
39 Hypothalamus and Pituitary Gland (cont) • Pituitary gland (hypophysis) – Pea shaped structure that lies in the sella turcica of the sphenoid bone – Attaches to the hypothalamus by a stalk called the infundibulum 40 41 Hypothalamus and Pituitary Gland (cont) • Has two anatomical and functionally separate parts – Anterior pituitary (adenohypophysis, anterior lobe) 75% of weight of gland – Posterior pituitary (neurohypophysis, posterior lobe) • Contains axons and axon terminals whose cell bodies are located in the hypothalamus – Pars intermedia atrophies during fetal development • Ceases to exist as a separate lobe in adults
42 Pituitary Gland • Arises from two embryologically separate structures – adenohypophysisarises from an outgrowth of ectoderm called the hypophyseal pouch that grows upward from the pharynx – neurohypophysis arises as a ectodermal downgrowth of the brain, the neurohypophyseal bud • They come to lie side by side and are closely joined that they look like a single gland 43 44 45 • The adenohypophysis constitutes the anterior ¾ of the pituitary. • It has three parts – a large anterior lobe called the pars distalis because it is the most distal to the pituitary stalk – pars tuberalis a small mass of cells adhering to the anterior side of the stalk – Pars intermedia only seen in the embryo and other animals • secretes melanocyte stimulating hormone (MSN) which influences pigmentation of skin, hair, or feathers (not produced in humans) • humans produce proopiomelanocortin (POMC), which is processed within the pit. to yield smaller fragments such as ACTH and endorphins 46 47 • The hypothalamus is connected to the ant.pituitary by a complex of blood vessels called the hypophyseal portal system (carries blood between two capillary beds without going through the heart) • The vacular network begins as primary capillaries in the hypothalamus, leading to portal venules that travel down the pituitary stalk to a complex of secondary capillaries in the anterior pituitary. 48 • The primary capillaries picks up releasing hormones from the hypothalamus • The venules deliver them to the anterior pituitary, • The releasing hormones act on anterior pituitary secretory cells to cause release of stimulating hormones that leave the circulation at the secondary capillaries
49 50 • The neurohypophysis constitutes the posterior quarter of the pituitary. • Has three parts – an extension of the hypothalamus called the median eminence – stalk – posterior lobe (pars nervosa) the largest part
51 • The neurohypophysis is not a true gland but a mass of neuroglia and nerve fibers. • The nerve fibers arise from cell bodies in the hypothalamus, travel down the stalk as a bundle called the hypothalamo hypophyseal tract and end in the posterior lobe • The hypothalamic neurons synthesize hormones, transport them down the stalk, and store them in the post pit. until a nerve signal triggers their release
52 53 Anterior Pituitary Gland (Adenohypophysis) • Hormone secretion regulated by 1. releasing hormones and inhibiting hormones from the hypothalamus 2. Negative feedback from hormones of target glands that act on Ant. Pit and thypothalamus 54 Hypothalamus produces nine hormones • Seven of them travel through the portal system and regulate the activities of the ant. pit. – Five are releasing hormones that stimulate the ant. pit to secrete its hormones • • • • • gonadotropin releasing hormone thyrotropin releasing hormone corticotropin releasing hormone prolactin releasing hormone growth hormone releasing hormone – Two are inhibiting hormones that suppress pituitary secretion • prolactin inhibiting hormone • somatostatin • Most of these hypothalamic hormones control the release of just one ant. pit. hormone – Accept gonadotropinreleasing hormone which controls the release of both FSH and LH
55 • The other two hypothalamic hormones are secreted by way of the posterior pituitary – Oxytocin made by the neurons in the paraventricular nuclei of the thalamus – antidiuretic hormone (vasopressin) produced mainly by the supraoptic nuclei 56 Posterior Pituitary • Nerve fibers fill most of the pars nervosa but they are not easily identifiable without special stains. • the main cell type here is a glial or supporting cell called a pituicyte . • The bulk of the pars nervosa consists of axons from neurons in the supraoptic and paraventricular nuclei of the hypothalamus 57 Posterior Pituitary • Herring Bodies – storage sites of the neurosecretory material of the pars nervosa neurons 58 Pituitary Gland • PARS INTERMEDIA – rudimentary in humans – lies between the pars distalis and pars nervosa. – consists mainly of colloid filled cysts lined by cuboidal epithelium.
59 5 Types of Anterior Pituitary Cells • Hormones secreted by cells that influence another endocrine gland are called tropic hormones or tropins • Thyrothrophs secrete TSH that controls the thyroid gland • Gonadotrophssecrete LH and FSH that controls the ovary and testes • Corticotrophssecrete ACTH that controls the adrenal gland function Nontropic • Lactotrophs secretes prolactin (PRL) that controls milk production in the breast • Somatotrophs secretes growth hormone (GH) that stimulates several tissues to secrete insulinlike growth factors, hormones that stimulate general body growth 60 Anterior Pituitary • The pars distalis is composed of two general cell types: chromophils (50%) and chromophobes (50%). • The chromophils can be further subdivided into acidophils (40%) and basophils (10%). • The acidophils secrete GH (somatotropes) and prolactin (mammotropes). • ). Basophils secrete TSH (thyrotropes), LH (gonadotropes), FSH (gonadotropes), and ACTH (corticotropes). 61 • The hormonal relationship between the hypothalamus, pituitary, and a more remote endocrine gland is called an axis. • There are 3 axis – hypothalamicpituitarygonadal axis – hypothalamicpituitarythyroidal axis – hypothalamicpituitaryadrenal axis 62 Actions of Pituitary Hormones Anterior Pituitary • FSH (produced by gonadotropes) stimulates the ovary to develop eggs and sperm production in males • LH (produced by gonadotropes) stimulates ovulation and the corpus luteum to secrete estrogen and progesterone – stimulates interstitial cells of the testes to secrete testosterone • TSH (produced by thyrotropes) stimulates growth of the thyroid gland and the secretion of thyroid hormone • ACTH (produced by corticotropes) stimulates the adrenal cortex to secrete its hormones (corticosterioids), especially cortisol, which regulates glucose, fat, and protein metabolism. It also plays a central role in stress.
63 Actions of Pituitary Hormones (cont) Anterior pituitary (cont) • Prolactin secreted by lactotropes, which increase greatly in size and number during pregnancy – has no effects until after birth – stimulates the mammary glands to synthesize milk – In males, it makes the testes more sensitive to LH, thus, it indirectly enhances the secretion of testosterone • Growth Hormone (somatotropin) (produced by somatotropes) has the general effect of promoting mitosis and cellular differentiation thus to promote widespread tissue growth
64 Human Growth Hormone from Somatotrophic Cells • Somatotrophs – most numerous cells in the ant. pit – secrete human growth hormone (hGH) or somatotropin – general effect is to promote wisespread tissue growth – Has widespread effects on the body, especially cartilage, bone, muscle, and fat – hGH stimulates these tissues to secrete insulinlike growth factors (IGFI or II) or somatomedins that causes cells to grow and multiply by • Increasing uptake of amino acids • Accelerating protein synthesis – GH is short lived (half life of 620 min), IGFs, by contrast, have life of about 20 hr., so they greatly prolong the effects of GH 65 60 Human Growth Hormone from Somatotrophic Cells Other Actions of IGFs • Decreases the breakdown of proteins and the use of amino acids for ATP production (protein sparing effect). – Promotes uptake of a.a. to make proteins • Enhances lipolysis in adipose tissue resulting in increase use of fatty acids for ATP production by body cells – Increases blood FFA • Decrease glucose uptake, there by decreasing the use of glucose for ATP production by most body cells (glucose sparing effect, causes hyperglycemia) – Spares glucose for use by neurons – Stimulate liver cells to release glucose into the blood • promotes Na+ , K+ , and Cl retention by the kidney, enhances Ca2+ absorption by the small intestine, and makes these electrolytes available to the growing tissues 66 Human Growth Hormone from Somatotrophic Cells • GH secretion occurs in a pulsatile fashion, and in a circadian rhythm with a maximal release in the second half of the night. • Release is controlled by two hypothalamic hormones – Growth hormone releasing hormone (GHRH) promotes secretion of hGH – Growth hormone inhibiting hormone (GHIH) (somatostatin) (SST) suppresses release 67 Human Growth Hormone Regulation Bood glucose levels a major regulator of GHRH and GHIH secretion is – Hypoglycemia stimulates hypothalamus to secrete GHRH, causing ant. pit. to release GH – Hyperglycemia stimulates hypothalamus to release GHIH, which inhibits the release of GHRH and causes the inhibition of the ant. pit. to release of GH • Results in decrease IGFs breakdown of glycogen in the liver
68 Human Growth Hormone Regulation • Factors that promote secretion of GH – Stress & exercisecausing increased activity of the sympathetic nervous system – hypoglycemia – and ingestion of protein (high levels of circulating amino acids) – Low levels of FFA – Deep sleep (stages 3 and 4 of nonrapid eye movements sleep) – Other hormones glucagon, estrogens, cortisol, and insulin
69 Factors that inhibit growth hormone secretion • High levels of glucose and FFA inhibits secretion • Decreased blood amino acids • Emotional deprivation • Obesity • Low levels of thyroid hormones • Rapid eye movement sleep • Human growth hormone through negative feedback 70 Human Growth Hormone from Somatotrophic Cells • Factors that inhibit hGH secretion – Increased blood fatty acids – Decreased blood amino acids – Rapid eye movement sleep – Emotional deprivation – Obesity – Low levels of thyroid hormones – hGH itself through negative feedback
71 Actions of Pituitary Hormones Posterior Pituitary • ADH acts on the kidney to increase water rentention, reduce urine volume, and help prevent dehydration – also called vasopressin because it causes vasoconstriction at high concentrations (these high concentrations are unnatural in humans, except in pathological states) – functions as a brain neurotransmitter • maybe called arginine vasopressin (AVP) 72 Actions of Pituitary Hormones Posterior Pituitary (cont) • Oxytocin has various reproductive roles – in childbirth, it stimulates smooth muscle of the uterus to contract, thus contributing to labor contraction. – In lactating mothers it stimulates milk let down by causing smooth muscle contraction of mammary glands – In both sexes OT secretion surges during sexual arousal and orgasm • may play a role in semen expulsion and uterine contraction that helps transport sperm up in to the female reproductive tract, and in the feeling of sexual satisfaction and emotional bonding 73 Oxytocin Stimulation 74 Thyroid Gland • Butterfly shaped organ located just inferior to the larynx • Composed of right and left lateral lobes that lie on each side of the trachea, connected by an isthmus anterior to the trachea • A small pyramidal shaped lobe sometimes extends upward from the ishtmus • Normal mass is about 30g (1oz) • Is highly vascularized 75 Thyroid Gland This is the normal appearance of the thyroid gland on the anterior trachea of the neck. The thyroid gland has a right lobe and a left lobe connected by a narrow isthmus. The normal weight of the thyroid is 10 to 30 grams. It cannot easily be palpated on physical examination. 76 Thyroid Gland • Thyroid follicles make up most of the thyroid gland – The wall of each follicle consists primarily of cuboidal to low columnar cells called follicular cells surrounded by a basement membrane • Parafollicular cells (C cells) lie between follicles that produce calcitonin which helps regulate calcium 77 Thyroid Gland • Thyroid follicle – consists of follicular epithelium (simple cuboidal) and a central mass, the colloid . 78 Thyroid Gland • Parafollicular cells or C cells – secrete calcitonin 79 Thyroid Gland
Follicular cells Parafollicular cells 80 Thyroid Gland • Thyrotropinreleasing hormone (TRH) from the hypothalamus controls the secretion of thyroid stimulating hormone (TSH) from the ant pit. • TSH stimulates the synthesis of thyroxine (T4) and triiodothyronine (T3) • T4 and T3 inhibit TRH by negative feedback • There is no thyrotropin inhibiting hormone 81 • Primary effect is to increase the body’s metabolic rate and as a result it: Thyroid Gland – raises body O2 consumption – increases heat production (calorigenic effect) – raises heart and breathing rate – increase breakdown of carbohydrates, fats, and protein for fuel and stimulates appetite – stimulates pit. to secrete GH • Factors that increase TSH secretion – Conditions that increase ATP demand • • • • Cold environement Hypoglycemia High altitude pregancy
82 Formation, Storage, and Release of Thyroid Hormones • Iodide trapping • Synthesis of thyroglobulin • Oxidation of iodide
2 I to I 2 • Iodination of tyrosine Coupling of T1 and T2 to form T3 or T4 • Pinocytosis and digestion of colloid • Secretion of thyroid hormones • Transport in the blood attached to thyroxinebinding globulin (TGB) • More than 99% of thyroid hormone is bound to carrier proteins 83 Secreted in greater quantity and converted to T3 in the cell More potent 84 Thyroid Gland Actions of Thyroid Hormones (cont) • Effects most body cells most body cells have receptors • Regulate – Basal metabolic rate (BMR) the rate of oxygen use at rest after an overnight fast increase by stimulating the use of cellular oxygen to produce ATP – Calorigenic effect increase body temperature by causing an increase use of ATP (by increasing Na/K pumps which are heavy users of ATP) – Regulate metabolism by stimulating • protein synthesis • increase use of glucose and fatty acids for ATP production • Increase lipolysis and enhanced cholesterol excretion (reducing cholesterol levels)
85 Thyroid Gland – Enhances actions of catecholamines (norepinephrine, and epipinephrine) by up regulating beta receptors (contributes to symptoms of hyperthyroidism) • Symptoms of hyperthyroidism – Increased heart rate – More forceful heartbeat or contractions – Increased blood pressure – Together with human growth hormone and insulin, thyroid hormones accelerates body growth, particularly the nervous tissue.
86 87 Congenital Hypothyroidism (Cretinism) • Severe mental retardation if not treated promptly (before aprox. 3 months of life) • Normal at birth because protected by maternal hormone that crosses the placenta to allow normal development • Most states require testing of all newborns • Oral hormone must be started soon after birth and continued for life
88 TABLE 2 Signs and symptoms of hypothyroidism in a newborn Sufferers have mental impairment and often suffer from dwarfism as their linear growth is affected. Facial puffiness Large tongue Large anterior or posterior fontanelle Cold hands or feet Hypotonia Lethargy Hypothermia Poor weight gain Poor feeding Respiratory distress in an infant weighing >2.5 kg Delayed passage of stools Prolonged unconjugated hyperbilirubinemia 89 6
Source: Brown RS Myxedema • Hypothyroidism during the adult years • Hallmark is edema that causes the facial tissues to swell and look puffy • Slow heart rate • Low body temperature • Sensitivity to cold • Dry hair and skin • Muscular weakness • General lethargy • Tendency to gain weight easily
90 Hyperthyroidism (Graves Disease) • Occurs seven to ten times more in females than males • Production of antibodies that mimic the actions of thyroid stimulating hormone – Continually stimulate the thyroid to produce thyroid hormone • Primary sign is enlarged thyroid • Exopthalmos edema behind the eyes, which cause the eyes to protrude – Caused by a extraocular muscle hypertrophy, ocular fat proliferation, and interstitial edema due to inflammatory infiltrate 91 Signs of Hyperthyroidism • diffuse goiter (enlarged thyroid gland) • rapid pulse • weight loss and trembling • ophthalmopathy (bulging eyes) • pretibial myxedema (swelling of shins) • Jitteriness, shaking, increased nervousness, irritability • Rapid heart beat or palpitations • Feeling hot Treatment • Thyroidectomy • Radioactive iodine (destroy thyroid tissue) • Antithyroid drugs to block synthesis of thyroid hormones • Fatigue, feeling exhausted • More frequent bowel movements • Shorter or lighter menstrual periods
92 • Pretibial myxedema is an infiltrative dermopathy that most frequently appears symmetrically on the anterior tibia and dorsa of the feet. 93 Graves’ disease 94 A simple, or endemic , goiter us caused by insufficient iodine in the diet. 95 Goiter This diffusely enlarged thyroid gland is somewhat nodular. This patient was euthyroid. This represents the most common cause for an enlarged thyroid gland and the most common disease of the thyroida nodular goiter. 96 Calcitonin • Produced by parafollicular cell of the thyroid • Decrease blood calcium levels by – inhibiting bone resorption by osteoclasts – Accelerating uptake of calcium and phosphates into bone
97 A slide showing stained parafollicular cells in the thyroid gland.
98 Parathyroid Gland • Embedded in the posterior surface of the lateral lobe of the thyroid gland • Contain two types of cells – Chief (principal cells) cells produce parathyroid hormone (PTH, parathormone) – Oxyphil cell – function unknown 99 100 Principal (Chief) cells secrete PTH Parathyroid Gland Oxyphil cells (unknown function) 101 102 Parathyroid Hormone • Low blood calcium stimulates chief cells to release PTH • PTH promotes resorption of bone matrix by increasing osteoclast activity, which release calcium into blood, •Decreases kidney loss of calcium and magnesium in urine •Increases loss of phosphate (HPO 2 ) 4 •Stimulates the kidney to synthesize calcitriol (active vitamin D) •Calcitriol stimulates increased absorption of calcium and magnesium from the GI tract 103 Adrenal Glands • Also called suprarenal glands • Sits like a cap on the superior pole of the kidney • Consists of two parts with different origins and functions – adrenal medulla – adrenal cortex
104 Adrenal Gland 105 Sectioning across the adrenals reveals a golden yellow outer cortex and an inner red to grey medulla. 106 Adrenal Medulla • Not fully formed until age 3 • Is a sympathetic ganglion consisting of modified neurons called chromaffin cells that lack dendrites and axons. • These cells are richly innervated by preganglionic fibers • Stimulation causes the secretion of catecholamines, especially epinephrine (3/4 of the output) and norepinephrine
107 Cortex Medulla 108 109 110 Zona Glomerulosa Mineralocorticoids (aldosterone) 111 Zona Fasciculata Glucocorticoids (cortisol) 112 Zona Reticularis Weak androgens (DHEA) 113 114 chromaffin cells modified post ganglionic sympathetic neurons that lack dendrites and axons. 115 Medulla & Zona Reticularis 1a.
116 Adrenal Medulla Chromaffin Cells 117 back Adrenal Medulla • Hormones supplement the effects of the sympathetic nervous system • Effects last much longer than NS because the hormones circulate in the blood. • They prepare the body for physical activity – raise the blood pressure and heart rate – increase circulation to the skeletal muscles – increase pulmonary airflow – Raises blood sugar by • stimulate glycogenolysis (hydrolysis of glycogen to glucose) • stimulate gluconeogenesis (the synthesis of glucose from amino acids and other substrates) – insures adequate glucose to the brain by • epiniphrine inhibits insulin secretion and thus, inhibits the use of glucose by the muscles and other insulin dependent organs (glucose sparing effects)
118 Adrenal Cortex • Has 3 layers of glandular tissue – outer zona glomerulosa – middle zona fasiculata – Inner zona reticularis • Cortex synthesizes more than 25 steroid hormones known collectively as the corticosteroids or corticoids
119 Adrenal Cortex: Zona glomerulosa Secretes • Mineralocorticoids act on the kidney to control electrolyte balance – Aldosterone the principal mineralcorticoid • promotes Na+ (thus water) retention and K+ excretion by the kidney – The two most significant regulators of aldosterone secretion are: – Concentrations of potassium ion in extracellular fluid: Small increases in blood levels of potassium strongly stimulate aldosterone secretion. – Angiotensin II: Activation of the reninangiotensin system as a result of decreased renal blood flow (usually due to decreased vascular volume) results in release of angiotensin II, which stimulates aldosterone secretion.
120 121 Adrenal Gland: Zona Glomerulosa 122 Zona Glomerulosa 123 Zona Glomerulosa 124 125 Adrenal Cortex: Zona fasiculata • Secretes glucocorticoids, especially cortisol (hydrocortisone) and corticosterone, a less potent relative • 10% free, most bound to corticosteroid binding globulin (transcortin) Actions of glucocorticoids • Promotes protein catabolism and mobilization of amino acids from extrahepatic tissues – These serve as substrates for gluconeogenesis.
126 Actions of glucocorticoids (cont) • Stimulation of gluconeogenesis, particularly in the liver • Stimulation of fat breakdown in adipose tissue All helps to adapt the body to stress and repair damaged tissues
127 • Other effects – have an antiinflammatory effects – long term secretion suppresses the immune system • As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and autoimmune diseases. • Important in fetal development – An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function.
128 • Excessive glucocorticoid levels resulting from administration as a drug effects on many systems. – inhibition of bone formation, – suppression of calcium absorption, – delayed wound healing, – susceptibility to infections. 129 130 Zona fasiculata 131 Zona fasiculata 132 133 Adrenal Cortex: Zona Reticularis Secretes sex steroids including • weak androgens which control many aspects of male development and reproductive physiology – dehydroepiandrosterone (DHEA) the principal androgen • has weak hormonal effects in its self • converted to the more potent androgen, testosterone, by other tissue • is a minor contributor of testosterone in men because of the testicles which produces so much more • in women the adrenal gland meets 50% of the total androgen required • acts to stimulate the development of pubic and axillary hair and apocrine scent glands at puberty and sustains the libido throughout adult life
134 Adrenal Cortex: Zona Reticularis • Smaller amount of estrogens (estradiol) • is of minor importance in women of reproductive age because of its small quantity compared to estrogen from the ovaries • After menapause it is the only remaining estrogen source • Both androgens and estrogens promote adolescent growth and help to sustain bone mass.
135 Zona reticularis 136 137 The Pancreas • Located retroperitoneally, inferior and dorsal to the stomach • Most of the pancreas is an exocrine digestive gland • has scattered endocrine tissue called pancreatic islets (islets of Langerhans) – Constitutes only 2% of the pancreatic tissue 138 The islets secrete • insulin secreted by beta cells of the islets – stimulates the cells to absorb glucose and amino acids – stimulates muscles and adipose to store glycogen and fat. – promotes liver synthesis of glycogen – antagonizes the effects of glucagon 139 • Glucagon secreted by alpha cells when blood glucose falls • in the liver it stimulates gluconeogensis, glycogenolysis, and the release of glucose into circulation • In adipose tissue, it stimulates fat catabolism and the release of free fatty acids in to circulation • secreted in response to rising amino acid levels after a high protein meal and promotes amino acid absorption and uptake for gluconeogenesis 140 Somatostatin • secreted by the delta cells when blood glucose and amino acids rise after a meal • is classified as an inhibitory hormone, whose main actions are to: • Inhibit the release of growth hormone (GH) • Inhibit the release of thyroidstimulating hormone (TSH) • Suppress the release of gastrointestinal hormones 141 Somatostatin • Lowers the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine. • Acts as a paracrine to suppress the release of pancreatic hormones – Inhibit the release of insulin – Inhibit the release of glucagon • Suppress the exocrine secretory action of pancreas. • Somatostatin opposes the effects of Growth HormoneReleasing Hormone (GHRH)
142 • Any hormone that raises blood glucose concentration is called a hyperglycemic hormone • Any hormone that lowers blood glucose is a hypoglycemic (insulin) 143 144 145 Gonads • Are both endocrine and exocrine • Exocrine products are eggs and sperm • Endocrine products are the gonadal hormones, most of which are steriods 146 Gonads: Ovaries The ovaries contains an egg cell surrounded by a wall of granulosa cells •granulosa cells produce an estrogen called estradiol •after ovulation the cells left behind are called the corpus luteum which secretes estradiol and progesterone for up to 12 days or 8 to 12 weeks in the event of pregnancy. •also secrete inhibin which suppresses FSH secretion by means of 147 negative feedback of the ant. pit. Ovary 148 Ovary Follicles 149 Ovary Corpus Luteum 150 Corpus Albicans 151 Gonads: Testes
• Testes consists of mainly of microscopic seminiferous tubles that produce sperm. • Nestled between them are clusters of cells called interstitial (Leydig) cells which produce testosterone and lesser amounts of weaker androgens and estrogens • Also have sustentacular (Sertoli cells) cells which secrete inhibin, which suppresses FSH secretion and stabilize the rate of sperm production 152 Testis Seminiferous Tubes 153 Testis • Leydig cells – found in clusters within the interstitial tissue between seminiferous tubules – produce testosterone
154 Testis Sortoli cells • Main function is to nurture the developing sperm cells through the stages of spermatogenesis. • Also secretes inhibin 155 Endocrine Functions of Other Organs Heart • secretes atrial natriuretic peptide (ANP) upon stretching of heart muscle by increased pressures – ANP increases sodium excretion and urine output and opposes the action of angiotensin II – In effect, lowering blood pressure
156 Endocrine Functions of Other Organs Kidneys • produces 85% of the body’s erythropoietin (EPO), a hormone that stimulates the bone marrow to produce red blood cells • converts the vitamin D precursor, 25hyroxy vitamin D3 to its active form, 1,25dihydroxy vitamin D3
157 Liver • secretes a hormone precursor called angiotensinogen which is converted to angiotensin I the kidney enzyme, renin. • Angiotensin I is converted to angiotensin II by the lung enzyme, angiotensinconverting enzyme (ACE) • ACE is a hormone that stimulates vasoconstriction and aldosterone secretion • Overall effect is to raise blood pressure • The liver is also a source of IGFI which mediates the action of growth hormone • It secretes about 15% of the body’s erythropoietin.
158 Actions of Angiotensen II 159 Skin • Keratinocytes of the epidermis produce vitamin D3, the first step in the synthesis of calcitrol. • The liver converts vitamin D3 to another precursor, 25hydroxy vitamin D3. • The kidney 25hydroxy vitamin D3 to the active form, calcitriol (1,25 dihydroxy vitamin D3)
160 Actions of Calcitriol: Active Vit. D 161 Pineal Gland • attached to the posterior aspect of the diencephalon • It consists of connective tissue , blood vessels , glial cells , and pinealocytes (which secrete melatonin). • W ith age, calcified formations appear in the pineal gland (brain sand or corpora aranacea ). 162 Mechanisms of Hormone Action • Hormones only stimulate those cells that have receptors for them • The receptors may be located on the plasma membrane, on mitochondria and other organelles in the cytoplasm, or in the nucleus. • The receptors act as switches to turn certain metabolic pathways on or off when the hormone binds to them • The target cell usually has a few thousand 163 receptors for a given hormone Mechanisms of Hormone Action • Receptorhormone interactions exhibit – specificity meaning that the receptor for one hormone will not bind other hormones – saturation the condition in which all the receptor molecules are occupied by hormone molecules, thus adding more hormone will not produce any greater effect. 164 Hydrophillic Hormones • These hormones easily penetrate the phospholipid plasma membrane and enter the cytoplasm. • They may enter the nucleus and bind to a receptor associated with the DNA • The receptor has 3 functional regions that explain its actions on the DNA – one that binds the hormone – one that binds to an acceptor site on the chromatin – one that activates DNA transcription at that site • Transcription produces new mRNA that leads to the synthesis of proteins, which then my alter the metabolism of the target cell
165 166 Mechanisms of Hormone Action • Hydrophilic hormones cannot penetrate into a target cell, so they must exert their actions indirectly. • Hormones bind to cellsurface receptors which are linked to secondmessengers systems on the other side of the plasma membrane. 167 168 169 Second Messenger: Cyclic AMP phosphodiesterase breaks down cAMP activate protein kinases which activates enzymes by attaching 70 1 a phosphate group Diacylglycerol (DG)and Inositol Triphosphate (IP3) as a second messenger • the binding of a hormone to a membrane receptor activates a G protein. • The G protein activates a membrane enzyme, phospholipase C. • Phospholipase breaks down membrane phospholipids into diacylglycerol and (IP3) • DG activates protein kinase • IP3 binds to gated calcium channels in the plasma membrane, admitting calciuim to the cell from the ECF or it triggers calcium release from the smooth ER. • Ca ions have a varitey of effects: can open other inon channels in the plasma membrane, can function as a cofactor that activates enzymes, or can bind to calmodulin, a protien that activates protein kinases. • Protein kinases exert the same variety of metabolic effects here as they do in the 171
cAMP system. Stress • Defined as any situation that upsets homeostasis and threatens one’s physical or emotional wellbeing. • The body’s reaction to stress is described as the stress response of the general adaptation syndrome (GAS) 172 Stress Three stages of stress • Alarm reaction mediates mainly by norepinephrine from the sympathetic nervous system and epinephrine from the adrenal medulla – they prepare the body to take action • causes a consumption of glycogen • aldosterone level rise to promote sodium and water conservation, which helps to offset possible losses by sweating and bleeding • angiotensin levels rise to raise the blood pressure
173 Stress • Stage of Resistance occurs when the bodies glycogen reserves are exhausted and the body begins to provide alternative fuels for metabolism. • This stage is dominated by cortisol which promotes the break down of fat and protein for gluconeogenesis. • It also inhibits protein synthesis, leaving the free amino acids available for gluconeogenesis – The immune system is depressed with long term cortisol exposure due to its heavy dependency of protein for the synthesis of antibodies and other products – W ounds heal poorly – gastric secretions increase leading to ulcers – depresses the secretion of sex hormones • This stage leaves the body more susceptible to disease 4 17
and cancer Stress • Stage of exhaustion when the fat stores are depleted and the body turns to protein for fuel • Leads to a progressive weakening and wasting away of muscle • eventually the adrenal cortex stops producing glucocorticoids, making fuel homeostasis impossible • At last, the effects of aldosterone begins to be detrimental to the body – increase retention of sodium and water creates hypertension – elimination of potassium and hydrogen causes hypokalemia and alkalosis resulting in nervous and muscular system dysfunction – death usually results from heart failure, kidney failure, or overwhelming infection
175 176 177 178 179 Hypothalamus Neurosecretory cells secrete releasing and inhibiting hormones into the primary plexus Primary plexus of the hypophyseal portal system Posterior Pituitary Superior hypophyseal artery Hypophyseal portal veins Anterior hypophyseal veins Secondary plexus of the hypophyseal portal s ystem Anterior Pituitary 180 Anterior Pituitary • Tropic (trop=turn on) hormones hormones that influence another endocrine gland • Ant pit hormones are stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus. • Hypo hormones reach the ant pit via the portal system
181 Hypothalamus Hypothalamohypophseal Tract Posterior hypophyseal veins Posterior Pituitary Inferior hypophyseal artery Anterior Pituitary 182 Nervous System and Endocrine System • The Nervous System and the Endocrine System Coordinate Functions of the Body Systems – The nervous system controls homeostasis through nerve impulses that trigger the release of neurotransmitters whose effect results in either the excitation or inhibition of other neurons, muscle fibers, or gland cells. – The endocrine system releases hormones into the bloodstream which travels to the target organ were it alters the physiological 183 activity of the cells. 184 185 186 187 188 The normal gross appearance of the pituitary gland removed from the sella turcica is shown here. The larger portion, the anterior pituitary (adenohypophysis), is toward the top. The image at the left shows the superior aspect of the pituitary with the stalk coming fro m the hypothala mus entering it. The inferior aspect of the pituitary is shown at the right. The posterior pituitary (neurohypophysis) is the smaller portion at the bottom. 189 190 191 192 193 Normal thyroid seen microscopically consists of follicles lined by a an epithelium and filled with colloid. The follicles vary somewhat in size. The interstitium, which may contain "C" cells, is not prominent. 194 This normal thyroid follicle is lined by a cuboidal follicular epithelium with cells that can add or subtract colloid depending upon the degree of stimulation from TSH (thyroid stimulating hormone) released by the pituitary gland. As in all endocrine glands, the interstitium has a rich vascular supply into which hormone is secreted. 195 Hyperthyroidism The most common cause of hyperthyroidism is Graves' disease. This occurs when the body's immune system overstimulates the thyroid. Common symptoms of hyperthyroidism are:
·Jitteriness, shaking, increased nervousness, irritability
·Rapid heart beat or palpitations
·Fatigue, feeling exhausted
·More frequent bowel movements
·Shorter or lighter menstrual periods In addition to symptoms of hyperthyroidism, some patients with Graves' disease develop eye symptoms such as a stare, eye irritation, bulging of the eyes and, occasionally, double vision or loss of vision. Involvement of the eyes is called Graves’ Ophthalmopathy 196 197 HYPOTHYROIDISM (Underactive thyroid) The most common cause of hypothyroidism is Hashimoto's thyroiditis. In this condition, the body's immune system mistakenly attacks the thyroid gland. Common symptoms of hypothyroidism are:
·Fatigue or lack of energy
·Dry skin and hair
·Heavy menstrual periods
198 Parathyroid hyperplasia is shown here. Three and onehalf glands have been removed (only half the gland at the lower left is present). Parathyroid hyperplasia is the second most common form of primary hyperparathyroidism, with parathyroid carcinoma the least common form. 199 200 201 202 G protein Adenylate cyclase Second Messenger ATP cAMP Phosphodiestrase Protein kinase Activated protein kinase Enzyme 1 ATP ADP Enzyme 2 P Enzyme 2 ATP ADP Enzyme 2 P 203 • GH – Increase a.a. uptake and protein synthesis 60 61 • Lowers blood a.a. levels (increase uptake) • Protein sparing effect (decrease breakdown) • Increase lipolysis (increase blood fatty acid) • Decrease glucose uptake (increase blood glucose) • Promotes electrolyte and Ca retention by kidney • Low a.a. levels inhibit 64 • High levels of a.a. promote • Increased blood FF inhibit • Decreased blood FF promote • Increased blood glucose inhibit • Decreased blood glucose 63 (hypoglycemia) promote – Release controlled by • Hypoglycemia increases secretion • Hyperglycemia decreases secretion • High levels of a.a. promotes release • Low levels of fatty acids promotes release 75 66 204 ...
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This note was uploaded on 12/08/2011 for the course AMY 2A taught by Professor Jamesivey during the Spring '06 term at Riverside Community College.
- Spring '06