Endocrine System Physiology and Pathophysiology PDF

Endocrine System Physiology & Pathophysiology Dr. Mohamed Shebl Amer PhD in Human Physiology, Leeds Uni, UK Faculty of Pharmacy 2024 - 2025  O...

Endocrine System Physiology & Pathophysiology Dr. Mohamed Shebl Amer PhD in Human Physiology, Leeds Uni, UK Faculty of Pharmacy 2024 - 2025  Objectives  At the end of this lecture, the student will be able to:  Discuss pituitary gland hormones.  Explain thyroid gland hormones.  Compare functions of pancreatic hormones.  Discuss adrenal gland hormones & their functions.  Discuss sex gland hormones & their functions  Explain the pathophysiology of growth hormone disturbance.  Explain the pathophysiology of diabetes mellitus.  Explain the pathophysiology of thyroid malfunctions.  Regulation of body functions The body functions are controlled mainly by two systems: 1. Nervous system: Rapid onset but short lasting 2. Endocrine system: Slow onset but long lasting  Endocrine System It consists of a group of endocrine glands that secrets hormones.  What is Hormone? Hormone is a chemical substance secreted directly into blood by an endocrine gland in small amounts to affect far tissues. Endocrine glands: They are ductless glands that put their secretions directly into blood. Generally, hormones act on enzymes by; Increasing their activity Increasing their synthesis Increasing both mechanisms. The hormone  Transport of Hormones Hormones are transported in blood in two forms: 1. Bound to plasma proteins mainly albumin and globulin (Inactive form). 2. Free hormone (Active form).  Chemical Nature of Hormone 1. Proteins: These hormone are composed of amino acids such as insulin, oxytocin & growth hormones. 2. Amino acid derived hormone: Such as thyroxine (derived from tyrosine) & epinephrine (derived from tryptophan) 3. Steroids: (Cholesterol derived hormones) Such as cortisol, aldosterone, testosterone, estrogen and progesterone. (All hormones of adrenal cortex, testes, ovaries and placenta).  Mechanism of action of hormones 1. Protein and amino acid derived hormones: They are lipid insoluble. They bind to a specific receptor on the cell membrane and generates a second messenger inside the cell such as growth, thyroxine and epinephrine hormones. 2. Steroid hormones: They are lipid soluble. They enter inside the cell and affect the transcription and translation of proteins at the nucleus (protein synthesis) such as all steroid hormones. 1. Protein and amino acid derived hormones act by Second messenger 2. Steroid hormones act by affecting Protein synthesis  Pituitary gland Small gland at the base of the skull. Formed of anterior and posterior lobes. Connected and controlled by the hypothalamus. It is called the Master endocrine Gland because it controls the activity of other endocrine glands and play a central role in maintaining the hormonal balance in the body. Hormones secreted by the Pituitary gland Growth H Prolactin H Thyroid Stimulating H (TSH) Antidiuretic H ACTH Oxytocin H Gonadotrophic H (GTH)  1. Anterior Pituitary Hormones HORMONE TARGET FUNCTION Growth Hormone Many tissues Stimulates linear growth before closure of the epiphyses and stimulates bone thickness after closure of the epiphyses. Anabolic on protein metabolism. Stimulate lipolysis. Elevates blood glucose level. Thyroid Stimulating Thyroid gland Stimulate the structural integrity of thyroid gland (TSH) and stimulates the synthesis & Release of thyroxine hormone Adrenocorticotropic Adrenal cortex Stimulates structural integrity and steroid (ACTH) hormone secretion from adrenal cortex. Prolactin (PRL) Breast Stimulate milk production from lactating breast. Inhibits gonadotropins and may prevent ovulation in lactating women.  1. Anterior Pituitary Hormones HORMONE TARGET FUNCTION Follicle Stimulating Gonads In male: hormone (FSH) (Testes & Ovaries) Stimulates spermatogenesis In the female: Stimulates ovarian follicular growth and development. Luteinizing (LH) Gonads In the male: stimulates testosterone (Testes & Ovaries) production by testicular interstitial cells (of Leydig). In the female: promotes maturation of ovarian follicles and sustains their secretion of estrogens. LH surge causes ovulation and the formation of the corpus luteum.  2. Posterior Pituitary Hormones They are synthetized in the hypothalamus then transported and released from the posterior pituitary.  2. Posterior Pituitary Hormones 1. Oxytocin hormone: Targets: Smooth muscles of uterus and breast Functions : 1. Contraction of the uterine muscles during labor 2. Milk ejection 2. Antidiuretic hormone (ADH) or Vasopressin Target: Kidneys (Renal tubules) Function: Water reabsorption Target: Blood vessels: Function: Vasoconstriction  Gigantism It is the pathological condition that is caused by increasing the growth hormone release in children (before closure of the epiphyseal plates). It is characterized mainly by increasing the length of bones.  Acromegaly It is the pathological condition that is caused by increasing the growth hormone release in adults (after closure of the epiphyseal plates). It is characterized mainly by increasing the thickness of bones. The progression of Acromegaly  Pituitary Dwarfism It is the pathological condition that is caused by decreasing the growth hormone release in children. Dwarfism is characterized mainly by: 1. Short stature 2. Mentality is normal 3. Sexually is fertile  Regulation of Pituitary hormonal secretion 1. Hypothalamic control: a) Hypothalamic cell bodies secrete the hormones of the posterior pituitary: ADH from the Supraoptic nuclei. Oxytocin from Paraventricular nuclei. b) Hypothalamus secretes: Releasing hormones that stimulate the production of the anterior pituitary hormones And /Or Inhibiting hormones that inhibit the production of the anterior pituitary hormones Regulation of hormonal secretion  2. Feedback Control of the Anterior Pituitary Anterior pituitary and hypothalamic secretions are controlled by the hormone of the target glands by Negative feedback at 2 levels: a) The target gland hormone can act on the hypothalamus and inhibit the secretion of its corresponding releasing hormones. b) The target gland hormone can act on the anterior pituitary and inhibit its response to the releasing hormone. Feedback Control of the Anterior Pituitary (continued) Thyroid & Parathyroid Glands Histology of Thyroid Gland  Thyroid & parathyroid Glands They are present in the lower part of the neck. Thyroid gland consists of two connected lobes; right and left lobes. Thyroid gland Secretes: a) Thyroxine hormones (T3 and T4) from the follicular cells. b) Calcitonin hormone from the para-follicular cells. It is a calcium lowering hormone. Parathyroid glands secrete: Parathormone that is a calcium raising hormone.  Functions of thyroxine hormone 1. Increases the energy level in the cells. 2. Stimulates the skeletal growth. 3. Essential for mental development in infants. 4. Increases glucose level in the blood. 5. Stimulate protein synthesis. 6. Decreases cholesterol level in the blood. 7. Stimulates different body functions such as: Increases the heart rate, myocardial contractility, cardiac output, blood pressure, respiratory rate, rate of metabolism, total heat production, and oxygen consumption.  Goiter It means an enlargement of thyroid gland Causes: 1. Physiological: a) Puberty b) Pregnancy 2. Pathological: 1. Iodine deficiency: In people who live inland or at high elevations. 2. Graves' disease: Autoimmune disease in which hyperthyroidism occurs due to antibodies that mistakenly attack the thyroid gland. 3. Hashimoto's disease: Autoimmune disease in which hypothyroidism occurs due to antibodies that mistakenly attack the thyroid gland 4. Cancer of thyroid. 5. Inflammation of thyroid. Goiter  Thyrotoxicosis It means hypersecretion of thyroxine hormones Major clinical manifestations: 1. Sweating 2. Tremors 3. Exophthalmos (Extortion of the eyes) 4. Loss of weight 5. Palpitations (Increase pulse rate) 6. Anxiety 7. Goiter 8. Hyperglycemia (Secondary DM) 9. Dyspnea 10.Hot intolerance  Myxedema It is the pathological condition that is caused by decreasing the secretion of thyroxine hormones in adults Major clinical manifestations: 1. Thickening and swelling of the skin 2. Lethargy 3. Weight gain 4. Fatigue 5. Depression 6. Cold intolerance  Cretinism (Congenital Hypothyroidism) It is the pathological condition that caused by decreasing the thyroxine hormones release in infants. Cretinism is characterized by: 1. Short stature 2. Mentality is retarded 3. Sexually is infertile  Functions of parathyroid glands They are responsible for secretion of parathormone hormone that controls the ionized calcium level in blood. Parathormone (PTH) is a calcium raising hormone Functions of parathormone: 1. Increases the serum calcium levels by: a) Stimulating the bone resorption via activating osteoclasts. b) Stimulating the calcium reabsorption in renal tubules. 2. Decreases the blood phosphate level by increases its excretion. 3. Stimulates the conversion of vitamin D to the active form that stimulates the absorption of calcium and phosphate from the GIT. Adrenal Glands  Adrenal Glands Adrenal glands are located at the top of the kidneys. Outer part: is the cortex. It secretes: 1. Cortisol 2. Aldosterone: It is responsible for salt and water retention at the renal tubules to maintain the blood pressure 3. Androgens such as testosterone (male sex hormone) Inner part: is the medulla. It secretes: Epinephrine and Nor-epinephrine: Act similar to the sympathetic nervous system (during fight and flight)  Functions of cortisol Physiological effects: 1. Increases blood glucose level. 2. Increases protein breakdown (catabolic and anti-anabolic). 3. Increases lipolysis in adipose tissue particularly in limbs. 4. Inhibits the immune response but stimulates erythropoiesis and elevates circulating levels of platelets and neutrophils. 5. Stimulates gastric acid and pepsin secretion & inhibits the production of protective mucus, thereby favoring development of gastric ulcers. Pharmacological uses: 1. Anti-inflammatory 2. Anti-allergic 3. Anti-immunity  Cushing's syndrome It is a metabolic disorder caused by excess cortisol hormones by the adrenal cortex or due to overuse of corticosteroid medications. Clinical manifestations include: 1. Weight gain 2. Fatty deposits (moon face and buffalo hump) 3. Purple stretch marks on the arms, abdomen, and thighs 4. Muscle weakness 5. Hyperglycemia (Secondary Diabetes Mellitus) 6. Osteoporosis (Bone loss) 7. Hypertension 8. Fluid retention (Edema) 9. Recurrent infections 10. Peptic ulcer Cushing's syndrome The Pancreas  Function of Pancreas Exocrine function: It is responsible for the secretion of the pancreatic juice that digest carbohydrates, proteins and fats. Endocrine function: It is responsible for the secretion of insulin and glucagon hormones. Insulin is a glucose lowering hormone. Glucagon is a glucose raising hormone by stimulating glycogenolysis.  Functions of Insulin 1. On carbohydrate metabolism: Insulin effectively lowers the level of blood glucose by enhancing the transport and peripheral utilization of glucose in muscles mainly. Insulin increases muscle and liver glycogen while inhibiting glycogenolysis. It also inhibits gluconeogenesis. 2. On protein metabolism: Insulin is strongly anabolic. 3. On lipid metabolism: Insulin stimulates lipogenesis and inhibits lipolysis.  Diabetes Mellitus (DM) It is caused by: decreasing insulin secretion from the pancreas or secretion of non-effective hormone (insulin resistance) causing high blood glucose level. Types of Diabetes: 1. Type Ι (Insulin dependent DM): It is also called juvenile diabetes. It is treated only by insulin. 2. Type ΙΙ (Non-insulin dependent DM): It can be treated orally. It occurs mainly due to insulin resistance. Major clinical manifestations of DM: 1. High blood glucose level (Hyperglycemia) (fasting and post-prandial) 2. Glucosuria: Glucose in urine 3. Polyuria: Increased frequency of micturition and the amount of urine 4. Polydipsia: Excessive water intake 5. Polyphagia: Excessive food intake 6. Loss of weight  Thank You Faculty of Pharmacy 2024 - 2025