Week 4 - Endocrine System III PDF

End ocrin e S ystem III H LT H 1 0 30 – A n at o my a n d P h y s i o l o g y o f B o d y S y st e m s Melandri Vlok S chool of Heal th S ci ences Sy dney | Uni vers it y of Not re Dame Austr alia mel andr i.v [email protected] du.a...

End ocrin e S ystem III H LT H 1 0 30 – A n at o my a n d P h y s i o l o g y o f B o d y S y st e m s Melandri Vlok S chool of Heal th S ci ences Sy dney | Uni vers it y of Not re Dame Austr alia mel andr i.v [email protected] du.au A CK NO WL ED GE ME NT OF CO UN TRY The University of Notre Dame Australia is proud to acknowledge the traditional owners and custodians of this land upon which our University sits. The University acknowledges that the Fremantle Campus is located on Wadjuk Country, the Broome Campus on Yawuru Country and the Sydney Campus on Cadigal Country. Anterior pituitary hormones Cells in anterior Hormone secreted pituitary Somatotrophs hGH Anterior Corticotrophs ACTH and MSH pituitary Gonadotrophs LH and FSH Thyrotrophs TSH Lactotrophs PRL Corticotrophs Thyrotrophs Somatotrophs Lactotrophs Gonadotrophs Thyroid Anatomy Ventral surface of the trachea Comprised of 2 lateral lobes Pyramidal lobe Isthmus connecting two lateral lobes Blood supply via the superior and inferior thyroid arteries Thyroid gland histology Principal cells = Follicular cells Trap iodide (I-) Formation of colloid (iodothyroglobulin) Production of T3 and T4 Parafollicular cells = C-cells Lie adjacent to follicles in basal lamina Produce calcitonin principal cells Parafollicular cells/ C-cells Calcitonin secretion triggered by hypercalcaemia Increases Ca2+ uptake by bone -> promotes bone formation by the osteoblasts Inhibits bone removal by the osteoclasts Calcitonin Decreases renal Ca2+ reabsorption -> Causes decreased plasma Ca2+ C-cells of thyroid osteoclasts Wheater’s Functional Histology, 4th Ed. osteoblasts 13 Wheater’s Functional Histology, 4th Ed. Wheater’s Functional Histology, 4th Ed. +ve thyroglobulin colloid thyroxine (T4) BMR, growth, maturation tri-iodothyronine (T3)  Thyroid hormones (TH) TRH 1. Increases Basal Metabolic Rate 2. Stimulate synthesis of Na+/K+ATPase receptors 3. Increases body heat production 4. Regulates tissue growth and development TSH 5. Stimulates lipolysis 6. Maintaining blood pressure Parathyroid 7. Modulates appetite & food intake s Thyroid TH is critical for normal development of the musculoskeletal Thyroid hormones system, normal brain development Metabolism, heat production, growth Thyroid hormones (TH) + Low hypothalamic Hypothalamus neurons temperature TRH stimulates Increased TRH the thyrotrophs in body the anterior temperature TSH pituitary to thyrotrop secrete thyroid Anteriorhs stimulating pituitary hormone (TSH) Thyroid hormones TSH then stimulates the thyroid to Thyroid release thyroid hormones, which subsequently cause an increase in body temperature Imbalances - Hyperthyroidism Graves disease: Autoimmune disease Production of too much thyroid hormone Symptoms High Basal Metabolic Rate Tachycardia Loss of weight, anxiety, sweating Possible treatments Throidectomy (partial, total) Antithyroid drugs Histology of colloid: contains bubbles Imbalances - Hypothyroidism Hashimoto's disease: Autoimmune disease Underactive thyroid gland Symptoms Puffy appearance of face Low basal Metabolic Rate Bradycardia Low temperature Lethargy and muscular weakness ~5 x more common in females Treatment - hormone replacement = TH tablets Parathyroid Glands Involved in Calcium homeostasis Thyroid Four separate glands posterior to Thyroid Each gland 3-4 mm in diameter Parathyroid glands Anatomically in close vicinity to thyroid but different structures & function Produce Parathyroid hormone (PTH) Parathyroid Hormone (PTH) 1. Releases parathyroid hormone (PTH) in response to plasma Ca2+ 2. Increases Ca2+ reabsorption in kidneys 3. Promotes bone reabsorption to release Ca2+ 4. Stimulates production of active i amin D ( calci i l ) b kidne 5. Active vitamin D increases absorption of Ca2+ in gastrointestinal (GI) tract from foods Adrenal glands Both the cortex and medulla have an endocrine function, but different hormones secreted The Cortex (3 zones) Zona glomerulosa Zona fasciculata Cortex Zona reticularis Aldosterone & Medulla Glucocorticoids Epinephrine & Norepinephrine including Cortisol The Medulla glomerulosa glomerulosa fasciculata C C reticularis medulla M C C=cortex Wheater’s Functional Histology, 4th Ed. M=Medulla Mineralcorticoids - Aldosterone Aldosterone exerts 90% of the mineralocorticoid activity Steroid hormone produced/released at adrenal cortex Release stimulated by presence of Angiotensin II through RAAS Facilitates Na+ reabsorption and K+ secretion at distal nephron Indirectly leads to increased water reabsorption through increased ECF osmolarity Glucocorticoids - Cortisol Hormone produced in response to long term stress Reduction of protein storage in all cells except those of liver ein ca ab li m & protein synthesis Cortisol increases liver & plasma proteins Mobilizes amino acids from non-hepatic cells, thus increase blood amino acid level amin acid transport to liver cells & amin acid transport into other cells Increases blood pressure (keeping blood volume constant). Suppresses immune cell activation. Treatment with Corticosteroids What are the Direct (intended) actions? 1. Anti-inflammatory 2. Anti-allergy 3. Anti-immunity For most clinical purposes synthetic glucocorticoids are used Hydrocortisone used for: orally for replacement therapy, i.v. for shock and asthma, topically for eczema (ointment) and enemas (ulcerative colitis) Prednisolone the most widely used drug given orally in inflammation and allergic diseases Striking improvements can be obtained, but severe adverse, but highly predictable, effects are ensued Side-effects of Corticosteroids General side-effects Raised blood pressure Fluid retention (leg swelling) Weight gain Long-term side effects Cataracts Asthma Diabetes Lupus Osteoporosis/fractures Eczema Poor wound healing and bruising Psoriasis Ulcerative colitis C hing nd me Excess production of glucocorticoids Characterised by rapid weight gain Can cause - flushed skin of face M n face Hyperglycaemia High BP Poor wound healing Also can result in osteoporosis, muscle wastage and depression Addi n di ea e Insufficient steroid hormones produced Individual with Addison's disease Quite rare in comparison Hyperpigmentatio n in distal nails Primary adrenal insufficiency (Chronic) Causes weight loss, hyperpigmentation, fatigue Hyponatremia Individual without Addison s disease Hyperkalemia Adrenal Medulla Produces two similar hormones (catecholamines) Epinephrine Norepinephrine Secreted from the chromaffin cells These hormones prepare the body to deal with short-term stress Stored in electron-dense granules stimulated by Ach, have a similar effect to sympathetic stimulation Effects of catecholamines 1. Take less than 30 seconds to kick in and last several minutes 2. Stimulates the figh figh reaction Stimulates Blood flow to heart, skeletal muscles (for action) 3. Increased plasma glucose levels 4. Increased heart rate and contraction force (both increase cardiac output), thus increased blood pressure 5. Increased metabolic function 6. Bronchodilator (increasing oxygen exchange) 7. Decreased gastrointestinal and genitourinary function Campbell s BIOLOGY, fourth edition  Recommended Reading Lecture Objectives Tortora G et al. (2022) Chapter 17 Describe the location and function of the thyroid, parathyroid and adrenal glands Ability to describe the structure of thyroid follicles and how thyroid hormones are synthesized and secreted by thyroid follicles Explain what effects thyroid hormones have on the body and how their release is regulated Explain how the secretion of glucocorticoids (e.g. cortisol) is regulated and the effects of cortisol on the body Understand the role of epinephrine (adrenaline) and norepinephrine (noradrenaline), their release and functions Describe disorders of the thyroid gland and adrenal glands  End ocrin e S ystem IV H LT H 1 0 30 – A n at o my a n d P h y s i o l o g y o f B o d y S y st e m s Melandri Vlok S chool of Heal th S ci ences Sy dney | Uni vers it y of Not re Dame Austr alia mel andr i.v [email protected] du.au The Pancreas 15-25 cm long Location: retro-peritoneum Extends in an oblique, transverse position Parts of pancreas: head, neck, body and tail Primarily involved with the digestive system (exocrine function) Role in regulating blood glucose concentrations (endocrine) The Pancreas Islets of Langerhans endocrine function Pancreatic acinar cells exocrine function  The Pancreas Endocrine pancreas: Islets of Langerhans -> make and secrete hormones into the blood 25% glucagon producing alpha cells Pancreatic islet 60% insulin producing beta cells 10% somatostatin producing delta cells comprise 1-2% of pancreatic mass Same islet of Langerhans stained with different antibodies predominance of insulin secre ing - cells Stain for Stain for Stain for insulin glucagon somatostatin Insulin One of the most studied molecules ever! Insulin mRNA is translated as a single chain precursor called pre-proinsulin and removal of its signal peptide generates pro-insulin Cleavage of pro-insulin generates mature form of insulin Insulin Inhibition of phosphoenolpyruvate carboxykinase = Inhibits gluconeogenesis Acts on tissues (especially liver, skeletal muscle, adipose) to increase uptake of glucose and amino acids Increases glycogen production Stimulates lipid synthesis from free fatty acids Increased activity of glucose transporters = Moves glucose into cells Control of intermediary metabolism Regulation of Insulin Secretion 2 Regulation of Insulin Secretion 2 Pancreatic β-cell Regulation of Insulin Secretion Stimulation 1. Major stimulus: increased blood glucose levels 2. Amino acids and keto acids also stimulate insulin 3. Some neural stimuli Inhibition 1. Inhibited by stress-induced responses  Glucose = GLUT1 Glucose = GLUT4 Glucose Glucose Glucose Glucose Glucose Fat and Skeletal Muscle Cells have GLUT4 Nucleus INSULIN Glucose = GLUT1 = GLUT4 Glucose Insulin binds its cell surface receptor Glucose GLUT4 vesicles travel to PM Nucleus  INSULIN Glucose = GLUT1 = GLUT4 Glucose Glucose Glucose Glucose Glucose Lots of glucose inside cell Nucleus Immunohistochemistry for Insulin Blood Glucose Concentration The normal fasting blood glucose concentration in humans and most mammals is 80-90 mg per 100 ml Glucose is liberated from dietary carbohydrate within the SI, and is then absorbed into the blood Almost immediately after the infusion begins, plasma insulin levels increase dramatically Glucagon Peptide hormone that antagonises insulin Synthesized as proglucagon and proteolytically processed to yield glucagon within alpha cells of the pancreatic islets Controls two key processes 1. Promotes breakdown of glycogen in the liver 2. Promotes synthesis of glucose from simpler molecules (e.g. amino acids) - Process called gluconeogensis Promotes breakdown of triglycerides (stored fat) from adipose tissue and release of fatty acids into the blood Regulation of Glucagon Secretion During hypoglycemia Pancreatic α-cell GLUT 1 1. Little uptake of uptake of glucose by Pancreatic -cells via glucose transporter 1 (GLUT1) 2. Intracellular glucose concentration falls 3. Reduction in glycolysis-generated ATP 4. Closes ATP-sensitive K+ channels 5. Intracellular K+ -> depolarizes cell membrane 6. Opening of voltage-dependent Ca2+ channels 7. Influx of Ca2+ -> increased intracellular Ca2+ 8. Triggers secretion of glucagon through exocytosis Immunohistochemistry for Glucagon Summary of Blood Glucose Regulation Control involves liver (makes and exports glucose) and pancreas (releases insulin and glucagon) Parasympathetic nervous system Stimulates insulin secretion Sympathetic nervous system Stimulates glucagon secretion Type I Diabetes Known as insulin dependent diabetes mellitus Diabetes affects ~ 200 million people -> 10% of these cases type 1 diabetes Results in hyperglycaemia because glucose cannot enter cells Juvenile-onset - genetic susceptibility - infection Immune system destroys beta cells in pancreas Course of Type I Diabetes Environmental Trigger Beta Cell Destruction Starts Glucose Intolerance Insulin Dependence Ongoing Beta Cell Attack Complications (Atkinson and Eisenbarth, Lancet 2001) Type II Diabetes Progressive condition in which body becomes resistant to normal effects of insulin Represents 85 90 per cent of all cases of diabetes Usually develops >45 years but increasingly occurring in younger ages Associated with (modifiable) lifestyle risk factors, and (non-modifiable) genetic and family related risk factors Managed with a combination of regular physical activity, healthy eating and weight reduction Diabetes Transplant of Beta Cells Benefits Reduces Hyperglycemia Reduces Long-Term Risk of Complications Helps Achieve Good Glycemic Control Limitations Shortage of Islets Immune Suppressive Therapy High Costs Long-Term Insulin Independence Shapiro et al, N England J Med, 2007 Stem Cell Treatments Appear to have significant success in some people Costly procedures Immune rejection Does it solve the initial problem? Voltarelli et al, 2007, JAMA IPSC/ESC Precursor cell Beta cell Somatostatin Secreted by delta cells of islets of Langerhans GH secretion is controlled by the interaction of SS and GHRH SS appears to act primarily in a paracrine manner to inhibit the secretion of both I and glucagon Injection of SS into the brain of rodents leads to such things as increased arousal and decreased sleep, and impairment of some motor responses It is also sometimes in to treat gigantism and acromegaly, due to its ability to inhibit GH secretion Why is this a bad idea? Same islet of Langerhans stained with different antibodies predominance of insulin secreting -cells Stain for Stain for Stain for insulin glucagon somatostatin Paracrine Interactions between Islet Cells Ghrelin and Leptin plays a role in meal initiation Increases hunger Leptin Mediator of long-term regulation of energy balance Secreted primarily from adipose tissue Decreases hunger  Recommended Reading Lecture Objectives Tortora G et al. (2022) Chapter 17 Explain how endocrine cells of the pancreas are distributed and list the different hormones produced Describe the functions/effects of insulin and how insulin facilitates these functions Understand the role of glucagon Explain how insulin and glucagon reciprocally regulate blood glucose Distinguish between the 2 common forms of diabetes Ability to describe typical complications occurring during diabetes and current research/treatment QUESTI ONS