Endocrine System PDF

ENDOCRINE SYSTEM Part 1  HORMONES Hormones are defined as the compounds that are produced in a secretory tissue and transported in the blood to target tissues, where they induce functional changes. Hormones can be produced by tissues other than glands with inte...

ENDOCRINE SYSTEM Part 1  HORMONES Hormones are defined as the compounds that are produced in a secretory tissue and transported in the blood to target tissues, where they induce functional changes. Hormones can be produced by tissues other than glands with internal secretion (for instance osteoblasts, adipocytes and kidneys), and that the signaling can occur outside the circulatory (autocrine or paracrine effects,). HORMONES HORMONES HYPOTHALAMUS  VASOPRESSIN Vasopressin or antidiuretic hormone (ADH) or arginine vasopressin (AVP) is a nonapeptide synthesized in the hypothalamus. It can play an essential role in the control of the body’s osmotic balance, blood pressure regulation, sodium homeostasis, and kidney functioning. ADH primarily affects the ability of the kidney to reabsorb water- induces expression of water transport proteins in the late distal tubule and collecting duct to increase water reabsorption and thus elevates blood pressure.  OXYTOCIN Oxytocin is released from the posterior pituitary gland – from neurons located within the supraoptic and paraventricular nucleus of the hypothalamus. Besides the key role during birth and breastfeeding, oxytocin controls social-emotional processes- is associated with empathy, trust, sexual activity, and relationship-building. Oxytocin is also a neurotransmitter and can function an anti- inflammatory and an antioxidant molecule influencing the autonomic nervous system and the immune system. PITUITARY GLAND  GROWTH HORMONE Human growth hormone (HGH), also known as somatotropin, is a polypeptide produced by somatotropic cells within the anterior pituitary gland. Its production is regulated through several complex feedback mechanisms in response to stress, exercise, nutrition, sleep, and growth hormone itself. The primary regulation factors are growth hormone-releasing hormone (GHRH) produced in the hypothalamus, somatostatin, produced in various tissues throughout the body, and ghrelin, which is produced in the GIT. HGH has two mechanisms of action: direct and indirect. The direct effects are through action on binding to target cells to stimulate a response. The indirect effects occur primarily by the action of insulin-like growth factor-1, which hepatocytes primarily secrete in response to elevated HGH binding to surface receptors.  GROWTH HORMONE Insulin-like growth factor-1 binds to its receptor, IGF-1R, on the cellular surface and phosphorylates various proteins in cells leading to increased metabolism, anabolism, and cellular replication and division. Furthermore, it acts to inhibit apoptosis of the cell, thus prolonging the lifespan of existing cells. HGH suppresses the ability of insulin to stimulate the uptake of glucose in peripheral tissues and causes an increased rate of gluconeogenesis in the liver, leading to an overall hyperglycemic state. GROWTH HORMONE  THYROID HORMONES Thyroid hormones affect every organ in the body, including the heart, CNS, autonomic nervous system, bones, GIT, and also metabolism. When the thyroid hormones bind to their intranuclear receptor, it activates the genes for increasing metabolic rate and body temperature. Increasing metabolic rate involves increased oxygen and energy consumption. Thyroid hormones are lipophilic and circulate bound to the transport proteins. Only a small fraction (approximately 0.2%) of the thyroid hormone (free T4) is unbound and active.  THYROID HORMONES P H Y S IOLOGI C A L E F F E C T S  They increase the basal metabolic rate.  Depending on the metabolic status, they can induce lipolysis or lipid synthesis.  Stimulation the metabolism of carbohydrates- thyroid hormones do not change the blood glucose level, but they can cause increased glucose reabsorption, gluconeogenesis, glycogen synthesis, and glucose oxidation.  Thyroid hormones can also induce catabolism of proteins in high doses.  Permissive effect on catecholamines- it increases the expression of beta-receptors to increase heart rate, stroke volume, cardiac output and contractility.  The impact of thyroid hormones on CNS is important. During the prenatal period, they are needed for the maturation of the brain. In adults, they can affect mood and memory.  Thyroid hormones affect fertility, ovulation, and menstruation.  HYPERTHYROIDISM Disorders of the thyroid gland can result in excess T3 and T4 production along with the compensatory decrease of TSH. There is an ectopic production of thyroid hormone in some conditions, leading to increased thyroid hormones and compensatory TSH decrease. Graves disease is the most common cause of hyperthyroidism. It is an autoimmune disease caused by the production of TSH receptor antibodies that stimulate thyroid gland growth and thyroid hormone release. Patients will have abnormally increased T4 and T3 levels and a decrease in TSH.  GRAVES’ DISEASE Antibodies can also activate orbital fibroblasts leading to their proliferation and differentiation to adipocytes. As a result, there is increased production of hyaluronic acid and glycosaminoglycan (GAG), leading to an increased volume of intraorbital fat and muscle tissue.  HYPOTHYROIDISM In primary hypothyroidism, decreased production of thyroid hormones by the thyroid gland causes a compensatory increase of TSH. Secondary hypothyroidism is caused by pituitary disorders causing decreased TSH release and decreased T3/T4 levels. Tertiary hypothyroidism is caused by hypothalamic disorders, resulting in decreased TRH levels, decreased TSH, and T3/T4 levels.  HASHIMOTO DISEASE It is caused by autoimmune-mediated destruction of the thyroid gland. CD8+ T- cells cause thyroid follicular cell death. Decreased basal metabolic rate can present as cold intolerance, weight gain, poor appetite, hair loss, cold and dry skin, constipation. The other signs are: muscle stiffness, cramps, delayed deep tendon reflex relaxation, hoarse voice with difficulty articulating words. Neuropsychiatric signs: fatigue, apathy, anxiety, depression, emotional instability, insomnia, depression, impaired concentration and memory.  CALCITONIN Calcitonin is a hormone protein that lowers blood calcium and inhibits osteoclast action. It can lower blood calcium levels by directly inhibiting bone resorption and by increasing calcium excretion by the kidney. Calcitonin mainly lowers higher calcium level after meals. Calcitonin is used in treatment of osteoporosis and other bone diseases.  PARATHYROID HORMONE Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland, that is important in the maintenance of normal calcium levels. It is released in response to low calcium levels and takes part in the synthesis of active vitamin D and calcitriol (1,25-dihydroxycholecalciferol) in the kidneys. In the kidneys most of the physiologic calcium reabsorption in the nephron takes place in the proximal tubule and additionally at the ascending loop of Henle. Circulating PTH targets the distal tubule and collecting duct, directly increasing calcium reabsorption and decreases phosphate reabsorption at the proximal tubule. Phosphate ions in the blood form salts with calcium that are insoluble, resulting in decreased plasma calcium.  PROLACTIN Prolactin is a polypeptide hormone that has a key role in lactation and breast development. Prolactin release is regulated via negative feedback from dopamine and also acts in a self-regulatory manner by promoting dopamine release. Dopamine is secreted by neurons in the arcuate nucleus of the hypothalamus and acts on dopamine receptors (D2) in the anterior pituitary to inhibit prolactin synthesis and secretion. The presence of prolactin receptors in nearly all organs suggests complex systemic effects of prolactin far beyond its role in reproduction, reclassifying it as a unique circulating hormone with autocrine, paracrine, and endocrine effects. Higher level of PRL: 1/ pregnancy and lactation 2/ stress and exercises- mechanism is not well understood- stress may induce changes in dopamine and serotonin levels, increasing PRL release. PROLACTIN PANCREATIC HORMONES  INSULIN EFFECTS Adipose tissue: increased glucose entry, fatty acids synthesis, triglyceride deposition, glycerol phosphate synthesis, K ions uptake and activation of lipoprotein lipase Muscles: increased glucose entry, glycogen synthesis, amino acids uptake, protein synthesis, K ions and ketones uptake decreased protein catabolism Liver: increased protein and lipid synthesis decreased synthesis of ketones and glucose output Increased cell growth in a whole body. DIABETES DIABETES- COMPLICATIONS GLUCAGON GLUCAGON ADRENAL GLANDS ADRENAL HORMONES  CATECHOLAMINES Noradrenaline- a transmitter Adrenaline- a hormone Dopamine-a metabolic precursor of adrenaline and noradrenaline and also a transmitter and neuromodulator in CNS. They are released from adrenal medulla in response to stress, exercise, cold, low blood glucose level. Catecholamines increase: the degradation of glycogen and triacylglycerol blood pressure contractility and rate of contractions of heart muscle that increase output of the heart relaxation of smooth muscles of the bronchi  GLUCOCORTICOIDS Glucocorticoids (cortisol) are steroid hormones synthesized and released by the adrenal glands in a circadian manner, in response to physiological events and stress. The majority of glucocorticoids circulate in an inactive form, bound to either corticosteroid-binding globulin (CBG) or albumin. Glucocorticoids are main stress hormones that regulate a variety of physiologic processes and are essential for life. The actions of glucocorticoids are predominantly mediated through the classic glucocorticoid receptors expressed throughout the body.  CORTISOL FUNCTIONS Immune response- They induce apoptosis of proinflammatory T cells, suppress B cell antibody production, and reduce neutrophil migration during inflammation. Stress response -The amygdala sends a stress signal to the hypothalamus. The hypothalamus subsequently activates the sympathetic nervous system, and the adrenal glands release catecholamines (adrenalin) which increase heart rate and respiratory rate. Glucose and protein homeostasis- Cortisol increases the availability of blood glucose to the brain. It acts on the liver, muscle, adipose tissue, and pancreas. In the liver, high cortisol levels increase gluconeogenesis and decrease glycogen synthesis. In adipose tissues, cortisol increases lipolysis. Lipolysis is a catabolic process that results in the release of glycerol and free fatty acids. These free fatty acids can be used in B oxidation and as an energy source for other cells as they continue to produce glucose. Lastly, cortisol acts on the pancreas to decrease insulin and increase glucagon. Additionally, cortisol enhances the activity of glucagon, epinephrine, and other catecholamines.  ALDOSTERONE Aldosterone is a mineralocorticoid hormone that influences water and salt regulation in the body. Aldosterone's primary function is to act on the late distal tubule and collecting duct of nephrons in the kidney, favoring sodium and water reabsorption and potassium excretion while also contributing to acid-base balance. Aldosterone affects blood pressure by regulating the sodium gradient in the nephron to either increase or decrease the water reabsorbed to contribute to the volume of the extracellular fluid (ECF). ALDOSTERONE