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DANYLO HALYTSKI LVIV NATIONAL MEDICAL UNIVERSITY DEPARTMENT OF PATHOPHYSIOLOGY Methodical guide for English-speaking students 3 rd – year in studying of General medicine in practical training on the theme “Pathophysiology of endocrine system.” On the subject Pathological Physiology Lviv-2014 3 DANYLO HALYTSKYI NATIONAL MEDICAL UNIVERSITY OF LVIV DEPARTMENT OF PATHOPHYSIOLOGY Methodical guide for English-speaking students 3 rd – year in studying of General medicine in practical training on the theme “Pathophysiology of endocrine system.” On the subject Pathological Physiology Subject Pathological physiology Module 2 Pathophysiology of organs and systems. Year of study 3rd Faculty Medical Lviv-2014 4 Methodical instructions for practical classes in pathological physiology - section “Pathophysiology of endocrine system” intended for medical students have been prepared by: Prof. M.S.Reheda MD, assist. prof. Sementsiv N.G., assist. prof. M.A. Kolishetska, assist. prof. Baida M.L. Methodical guide for practical training of medical students on the theme ˝ Pathophysiology of endocrine system.˝ is compiled in accordance with the demands of typical curriculum program on pathophysiology syllabus for the students of higher educational medical establishments of the ІІ-ІІІ levels of accreditation, Kyiv 2006. Reviewed by : Associate professor of the Department of Pathological Anatomy with the course of Forensic Medicine of Danylo Halytski Lviv National Medical University Servetnyk M.I. Associate professor of the Department of Pharmacology of Danylo Halytski Lviv National Medical University Havryluk I.M. Associate professor head of the Department of Foreign languages of Danylo Halytski Lviv National Medical University Isayeva O.S. Approved and recommended for publication at the sitling of the Cycle Methodical Commission in Danylo Halytski Lviv National Medical University Proceedings №1 2014 5 Pathophysiology of endocrine system. I. SIGNIFICANCE OF THE THEME The endocrine system relates the most important regulatory systems. It carries out regulatory influence with the help of hormones practically on all functions of an organism – metabolism , growth, reproduction, mental activity, adaptation, functional activity of all organs. The endocrine system contains a highly integrated and widely distributed group of organs that orchestrates a state of metabolic equilibrium, or homeostasis, between the various tissues of the body. Signaling by extracellular secreted molecules can be classified into three types: autocrine, paracrine, or endocrine, based on the distance over which the signal acts. In endocrine signaling, the secreted molecules, which are frequently called hormones, act on target cells distant from their site of synthesis. An endocrine hormone is frequently carried by the blood from its site of release to its target. Increased activity of the target tissue often down-regulates the activity of the gland that secretes the stimulating hormone, a process known as feedback inhibition. Several processes may disturb the normal activity of the endocrine system, including impaired synthesis or release of hormones, abnormal interactions between hormones and their target tissues, and abnormal responses of target organs to their hormones. Endocrine diseases can be generally classified as diseases of underproduction or overproduction of hormones and their resulting biochemical and clinical consequences, and diseases associated with the development of mass lesions, which may be nonfunctional or may be associated with overproduction or underproduction of hormones. The study of endocrine diseases requires integration of morphologic findings with biochemical measurements of the levels of hormones, their regulators, and other metabolites. II. CONCRETE TEACHING GOALS Students have to: 1. Know the main etiological factors and mechanisms of the functional activity of endocrine glands violations. 6 2. Know the role of the hypothalamic-pituitary-adrenal system for nonspecific resistance of the organism. (H. Selie theory) 3. The role of the genetic factors and infant infection in endocrine pathology creation; dependence of endocrine violations on human age. 4. The role of intoxication, infection and quantitative changes of content of some food minerals and environment minerals in an etiology of endocrine diseases. 5. Know the main hypothalamic and pituitary syndromes, to explain their development. 6. Reproduct Gally-Maininy and Torn reactions and to explain the contact character between the pituitary and peripheral glands in normal and pathological conditions on the base of the results. 7. Define the pathological disease and protective and adaptive disease in case of different endocrine violations. III. BASIC KNOWLEDGE, ABILITIES AND SKILLS NECESSARY TO COMPREHEND THE THEME (interdisciplinary integration) Names of previous subjects Normal anatomy Histology Normal physiology Obtained knowledge and skills Structural and functional features of endocrine glands. Kinds, properties and mechanisms of hormonal action. IV. ASSIGNMENTS FOR INDEPENDENT WORK TO BE DONE WHILE PREPARING FOR THE PRACTICAL CLASS 1. Basic terms, parameters and characteristics necessary to learn while preparing for the practical class № 1 2 3 4 Term Endocrine glands Definition Special composites of secretory cells that create and secrete their specific products – hormones into the blood. Hormones Biologically active substances; their genesis is nonprotein or protein; they are secreted by special cells groups and separated organs; they are contained in the blood and they make distant effects on target cells Endocrine hyperfunction Increasing the production of hormones by the endocrine glands. Endocrine hypofunction Decreasing in hormone production 7 5 Endocrine dysfunction 6 Stress 7 8 General adaptation syndrome Adaptation diseases 9 10 Hypopituyitarism Panhypopituyitarism 11 12 Hyperpituyitarism Hyperaldosteronism 13 14 Goiter Hypothyroidism 15 Hyperthyroidism Discordant changes in the endocrine glands function. Stressful state of non-specific adaptation mechanisms that is caused in case of pathogen factors action for organism. Stress that is a complex of structural, functional and biochemical changes. Diseases that are caused by excessive stress and stress injury mechanism. Hypofunction of adenohypophysis Decreasing of the adenohypophysis hormones creation. Hyperfunction of adenohypophysis Pathological state that is resulted from the hyperfunction of adrenal cortex glomerular zone. A great increasing of the thyroid State in case of deficiency of thyroid hormones in the body Syndrome after increasing of thyroid function 2. Theoretical questions for the practical class: 1. General characteristic of functional activity of endocrine system violations: hyperfunction, hypofunction, glands dysfunction, primary and secondary endocrinopathies. 2. Reasons of creation and development mechanism of endocrinopathies. 3. Knowledge about stress as nonspecific, stereotyped adaptive reaction to stimulator actions. Development levels of general adaptation syndrome. Long-term adaptation mechanisms. Knowledge about stress injuries and “adaptation diseases”. Preventing principles of stress injuries. 4. Dysregulatory endocrinopathies: nervous, endocrine neuroendocrine and metabolic regulation of the endocrine glands violation. Forward and backward communications regulatory violation. 5. Glandular endocrinopathies: reasons and mechanisms of the synthesis, deposition and hormones secretion violation. 6. Peripheral disorders of endocrine function. Violation of the hormonal transportation and metabolic inactivation. 8 7. Hormonal reception violation, mechanisms of desensitization and hormonal resistance (prereceptor, receptor, postreceptor). 8. Hypothalamic-pituitary system pathology. Reasons and development mechanisms of the pituitary hormones excess and deficiency syndrome. 9. The main characteristic of such system activity violation as hypothalamic-pituitarythyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary- gonadal. 10.Etiology, pathogenesis, clinical manifestations of panhypopituitarism. 11.Reasons, mechanisms and clinical manifestations of partial deficiency of hormones of the adenohypophysis. (HGH, TSH, ACTH, gonadotropins). 12.Etiology, pathogenesis, clinical manifestations of partial overactivity of adenohypophysis (HGH, TSH, ACTH, gonadotropins, prolactin). 13.The neurohypophysis pathophysiology. Diabetes insipidus: reasons, mechanisms and clinical manifestations. 14.Adrenal glands pathology. An insufficiency of the adrenal gland cortex: types (primary, secondary, acute, chronic), etiology, pathogenesis, clinical manifestations. 15.Hyperfunction of the adrenal gland cortex: types (primary, secondary), etiology, pathogenesis, clinical manifestations. Itsenko-Cushing syndrome, Conn's syndrome, adrenogenital syndrome. 16.Types, reasons, mechanisms and clinical manifestations of an activity of the adrenal medulla violation. 17.Thyroid pathologies. Hypothyroidism: reasons, mechanisms and pathogenesis of the main violations in organism. 9 18.Hyperthyroidism: reasons, mechanisms and pathogenesis of the main violations in organism. 19.Goiter: types (endemic, sporadic, nodular and diffuse toxic), their etiology and pathogenesis; violations of gland functions. 20.Violations of parathyroid glands functions: types, reasons, mechanisms, clinical and pathophysiological manifestations. 21.Violations of genital glands functions: primary and secondary states of hypogonadism and hypergonadism. Reasons, mechanisms, extragenital manifestations of genital glands functions violations. 22.Violations of an endocrine function of the pancreas. 23.Epiphysis pathology: hypofunction, hyperfunction, the main manifestations. 24.Principles of diagnosis and treatment methods of endocrine glands pathology. 3. Practical work (assignments) to be done during the class: Test 1. To investigate the changes of the functional state of the adrenal cortex in case of stressful situation. (Thorne’s sample) Task Prescription Determine the number of eosinophilic The granules are colored in black, 3 granulocytes in the rat at 1 mm of blood. cytoplasm becomes in pink color. Collect blood from the tail vein in to melanger for counting leukocytes to the level of 0,5. Dilute liquid Winckelmann to the level of 11. Eosinophils are counted in the FuchsRosenthal chamber. The result is multiplied by 6.25. It is multiplied by 50 in the Hemocytometer(Goriaeva chamber). For making the result at International System of Units, to multiply it by 106 granulocytes. Provide a cold stress to the rat. Put it into the refrigerator with temperature +4o C in 10 30 minutes. Then determine the number of eosinophilic granulocytes in this rat again. Show the result in the chart. Notice the number of eosinophilic granulocytes in the rat’s blood before and after cold stress. Explain an eozynopenic reaction’s mechanism in case of stress. Write about reaction’s absence and reaction’s changes in case of an adrenal cortical substance hall’s hypo- and hyperfunction. Make a decision. Test 2. To investigate a gonadotrophins influence on the frog’s spermatogenesis. (Galli-Mainini reaction). Task Examine the frog’s cloacal contents for the spermatozoon presence. Prescription Pour a drop of cloacal contents on the substantive glass. At first observe it under low microscope magnification (×10), then under high microscope magnification (×40). When spermatozoons are absent to enter Enter the urine into dorsal lymph sac in the first frog 4-5ml of pregnant the direction from the head to the hind women’s urine, to use the second frog limbs. for a control Investigate the cloacal contents in an hour. Omit a condenser. Show result as a picture. Make a decision. Explain an appearance of spermatozoons in male frog using the pregnant women’s urine. 11 V. CONTENT OF THE THEME Disorders of endocrine gland regulation Regulation of endocrine gland activity can be carried out with the help of four mechanisms: 1. Nervous (impulse-mediators) or parahypophysis regulation. With the help of direct nervous influences the activity of following structures is regulated: а) adrenal medulla; b) neuroendocrine structures of hypothalamus; c) epiphysis. 2. Neuroendocrine or transhypophysar regulation. It is carried out by neuroendocrine cells of hypothalamus, which transform nervous impulses in specific endocrine process. Along releasing-hormones, which regulate activity of adenohypophysis are synthesized and get secreted in the system of portal vessels of hypophysis . 3. Endocrine regulation. It is that some hormones influence on synthesis and other influence secretion of the others. An example of this mechanism is the influence of adenohypophysis tropic hormons on activity of adrenal cortex, thyroid gland, sexual glands. 4. Non-endocrine humoral regulation is carried out by unspecific humoral factors, in particular by metabolites, ions. Structure-logical scheme 1 12 Hereditary disorders of endocrine gland structure and biosynthes is of hormones Pathophysiology of endocrine system Hyperfunction Dysfunction Trauma Disorders of biosynthesis and secretion of hormones Tumor Autoimmune aggression Intoxication Infection Vascular disorders (thrombosis) Disorders of central regulation of endocrine function Infl am mati on Hypofunction Disorders of transport, metabolism and biological action of hormone Disorders of the intracellular messengers Disorders of inactivation of hormones and their metabolism in the liver and in the tissues Disorders of binding of hormones with blood proteins Hereditary Acquired Disorder of hypothalamus regulation and mechanism of reverse connections Disorder of cortex regulation, emotion VI. MATERIALS FOR SELFCONTROL A. Assignments for self-control № Assignments Instructions for the assignments 1 Point the main reasons of the genetic Point 5-6 defects. damage to the thyroid hormones synthesis. 2 Mechanism of the autoimmune thyroiditis Show as a scheme. development. 3 Give an example of diseases that are Write what exchange is violated connected with an adrenal cortex hypo- or at this pathology. hyper-function. 4 Point the syndromes that are connected Write hormones and diseases with hypophysis affection. 5 Explain the diabetes insipidus symptoms. Write symptom and its mechanism. 13 6 Characterize the stages of the general 3 stress stages and the main adaptation syndrome pathogenetic processes that may cause to the adaptation diseases. B. Tasks for self-control: Task 1. A patient aged 23 complains of headache, changes of his appearance (increase of size of feet, fingers, features of the face), hoarseness of the voice, worsening of the memory. The disease has begun 3 years ago without any causes. Increase of superciliarry arches, nose, and tongue were found during physical examination of this patient; the blood sugar was normal; the urinalysis is out of changes. What pathology develops in this patient? Task 2. A women aged 44 complains of general malaise, pain in the heart area, and considerable increase of body weight. At examination of this patient following symptoms are revealed: lunar face, hirsutism, BP 165/100 mmHg, height is 164 cm, weight is 103kg, the adipose deposits mainly on the neck, shoulders, abdomen, persistent hyperglycemia. What is the mechanism of hyperglycemia in this case? Task 3. A woman complains of increased irritability, perspiration, weakness, loss of body weight, tremor of extremities, increased heartbeat rate, and exophthalmia. What endocrine gland functions are impaired and what direction in? Task 4. In a patient excessive development of bones and soft tissues of his face, enlargement of his tongue, and widened interspaces between teeth in enlarged teeth arch were found out. What is called this pathology? Task 5. Persistent hyperglycemia developed in a patient with Cushing’s syndrome under the influence of excessive amount of glucocorticoids. What are the difference between Cushing’s syndrome and Cushing’s disease? Task 6. A patient aged 41 complains of weakness, sweating, fever, tremor of hands, BP160/90 mm Hg. Diffuse toxic goiter was diagnosed (Basedow’s disease). What is the leading part of pathogenesis of this state? Task 7. A patient aged 50 complains of thirst, he drinks much water, has marked polyuria. His blood glucose - 4.8 mmol/L, glucose and acetone bodies are absent in the urine; urine is colourless, its specific gravity - 1.002-1.004. What pathology does this patient suffers from? Task 8. A woman aged 40 complains of general malaise, pain in the heart area, increase of body weight. At examination of the patient: she is 164 cm height and 104 kg weight; she has predominant deposits of fat at face, neck, shoulders, and abdomen; her BP – 165/100 mmHg; content of glucose in her blood – 7.8 mmol/L. 14 What pathology develops in this patient and what hormone secretion is connected with? Task 9. After physic exertion a patient with with pheochromocytoma complains of tachycardia, increased arterial pressure, and sharp pain in epigastric area. What is origin of this tumor? Task 10. The examined has the following results of glucose-tolerance test: level of sugar in blood fasting is 7.0 mmol/l, in 1 hour after reception of glucose it equals to 8,8 mmol/l, in 2 hours after reception of glucose – 7.2 mmol/l. What do these results testify about? Task 11. The experimental models of diabetes mellitus are received by the way of pancreas removal, introduction of allocsan, somatotropic hormone, glucagon. In what cases does absolute insulin insufficiency is occurred in what - relative? Task 12. Parathyreoid gland are removed during the operation on thyroid gland. What pathological state will be the consequence of this operation? Task 13. A woman with primary hyperparathyroidism has periodically repeated attacks of renal colic. Ultrasound examination shows presence of small stones in her kidneys. What is the cause of the formation of these stones? C.Tests for self-control: 1. The height of an adult is 100cm, in proportional constitution and normal mental development. What hormone insufficiency do the indicated signs characterize? A. Growth hormone B. Thyroxin C. Antidiuretic D. Mineralocorticoids E. Gonadotropic hormone. 2. Under the influence of harmful ecological factors the normal formation of lysosomes is inhibited in thyrocytes. What stage of hormone production of thyroid gland will be impaired? A. Synthesis of colloid B. Iodinisation of colloid C. Synthesis of thyroglobulin D. Reabsorption of colloid E. Proteolysis of phagocytosed colloid from follicles. 3. Diabetes insipidus appeared in a patient after cerebral infarction with impairment of hypothalamus nuclei. What is the cause for increased urination in this patient? A. Decrease of reabsorption of sodium B. Acceleration of glomerular filtration 15 C. Decrease of water reabsorption D. Decrease of arterial pressure E. Hyperglycemia 4. What hormone stimulates inclusion of calcium in osteoblasts of bone tissue in tooth? A. Insulin B. Thyroxin C. Parathormone D. Hydrocortisone E. Calcitonin 5. A 10-year-old child has a height of 178 cm and weight of 64 kg. What endocrine gland disorder does this connected with? A. Sexual glands B. Adrenal glands C. Parathyroid glands D. Pituitary gland E. Thyroid gland. 6. A patient with thyrotoxicosis has hyperthermia, bulimia, and loss of weight. What kind of impairment does this connected to? A. Reaction of fat synthesis B. Lyses of adenosintriposphoric acid C. Conjunction oxidation and phosphorylation D. Reaction of citric acid cycle E. Reaction of beta-oxidation of fatty acid. 7. During an experiment on animals the nervous tracts leading to the crus of hypophysis were broken. That impaired the entrance of the fallowing hormones into the blood. A. Hypophysis hormones B. Vasopressin and oxytocin C. Adenohypophysis hormone D. Thyrotropic hormone E. Adenocorticotropic hormone 8. A careless student suddenly meets his dean. What hormone concentration will be increased in student’s blood more rapidly? A. Somatotropin B. Hydrocortisone C. Corticotropin D. Thyroliberine E. Adrenalin 16 9. A women aged 44 complains of general malaise, pain in the heart area, and considerable increase of body weight. At examination of this patient following symptoms are revealed: lunar face, hirsutism, BP 165/100 mmHg, height is 164 cm, weight is 103kg, the adipose deposits mainly on the neck, shoulders, abdomen. What is the main pathogenic mechanism of the woman’s obesity? A. Decrease of thyroid hormone production B. Decrease of glycogen production C. Increase of glucocorticoid production D. Increase of insulin production E. Increase of minerelocorticoid production. 10. A child has a time disturbance of teeth eruption, enamel anomalies, and its lips and tongue are enlarged. What hormone deficiency causes these changes? A. Thyroxin B. Parathormone C. Thyrocalcitonin D. Insulin E. Somatotropin 11. At clinical examination of a woman it was determined increase of basal metabolism rate by 40%, increased perspiration, tachycardia, and leanness. What endocrine gland functions are impaired and what direction in? A. Sexual glands, hypofunction B. Cortical substance of adrenal glands, hyperfunction C. Medulla of adrenal glands, hyperfunction D. Thyroid gland, hyperfunction E. Pancreatic gland, hyperfunction 12. A young man aged 17 has the signs of retention of sexual development; his height is 184 cm; he is asthenic; his secondary sexual characters are weakly developed. Sex chromatin is absent in this patient’s cells. At the age of 4 he endured epidemic parotitis. What was the cause of hypogonodism? A. Deficiency of gonadoliberine B. Deficiency of gonadotropin C. Cryptorchism D. Orchitis E. Chromosomal anomalies (XXY) 13. A patient aged 20 complains of polydipsia and abundant urination (up to 10 liters for 24 hrs); concentration of glucose in his blood is normal; in his urine glucose is absent. What hormone absence may cause such clinical picture? A. Oxytocin B. Vasopressin C. Insulin D. Hydrocortisone 17 E. Triiodothyronine 14. A woman with primary hyperparathyroidism has periodically repeated attacks of renal colic. Ultrasound examination shows presence of small stones in her kidneys. What is the cause of the formation of these stones? A. Hypercholesterolemia B. Hyperuricemia C. Hyperkalemia D. Hyperphosphatemia E. Hypercalcemia 15. Substances which imitate morphine effects but which are produced in CNS may be used for analgesia. Indicate them: A. Somatotropin B. Oxytocin C. Beta-endorphin D. Vasopressin E. Calcitonin 16. Dilated pupils, dryness of mucous membranes, accelerated heart rate, constipation, and tremor are observed in some people during emotional exertion. What system activation will lead to such changes in the organism? A. Pituitary-adrenal system B. Sympathetic nervous system C. Sympathoadrenal system D. Somatic nervous system E. Parasympathetic nervous system 17. In ancient India those people who were suspected in committing crimes were given swallow a handful of dry rice. Criminals couldn’t swallow rice due to decreased salivation (oligosalivation) caused by: A. Decrease of blood supply of salivary glands B. Activation of sympathoadrenal system C. Activation of parasympathetic nucleus of glossopharyngeal nerve D. Inhibition of sympathoadrenal system E. Activation of parasympathetic nucleus of facial nerve 18. A patient aged 23 complains of headache, changes of his appearance (increase of size of feet, fingers, features of the face), hoarseness of the voice, worsening of the memory. The disease has begun 3 years ago without any causes. Increase of superciliarry arches, nose, and tongue were found during physical examination of this patient; the blood sugar was normal; the urinalysis is out of changes. What is the cause of such condition? A. Excessive production of corticosteroids B. Excessive production of somatotropin 18 C. Insufficiency of aldosterone D. Insufficiency of glucagon E. Insufficiency of thyroxin 19. Adrenalin is used to prolong Novocain action in infiltration anesthesia. What adrenalin action is this effect connected with? A. Potentiation of Novocain action at the level of CNS B. Inhibition of function of nerve ending and conductors C. Dilatation of vessels D. Constriction of vessels E. Inhibition of tissue esterases 20. A patient aged 80 complains of increased appetite, thirst, excretion of large amount of urine, and worsening of general condition after taking sweet food. What disease is it? A. Hypercorticoidism B. Hyperthyroidism C. Hypothyroidism D. Diabetes insipidus E. Diabetes mellitus ANSWERS: 1.-A2.-E3.-C4.-E5.-D6.-C7.-B8.-E9.-C10.-A11.-D12.-D13.-B14.-E15.-C16.C17.-B18.-B19.-D20.-E 19