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DANYLO HALYTSKYI LVIV NATIONAL MEDICAL UNIVERSITY DEPARTMENT OF PATHOPHYSIOLOGY Methodical guide for individual study of English speaking students of Medical Faculty for preparing to practical classes on the theme “HYPOXIAS” on the discipline “Pathological Physiology” Lviv - 2014 1 DANYLO HALYTSKYI LVIV NATIONAL MEDICAL UNIVERSITY DEPARTMENT OF PATHOPHYSIOLOGY Methodical guide for individual study of English speaking students of Medical Faculty for preparing to practical classes on the theme “HYPOXIAS” Subject Module # 2 Thematic module # 2 Year of study Faculty Pathological Physiology Pathology organs and systems Pathology of organs and systems 3 Medical Lviv - 2014 2 Methodical guide has been complited by: prof. Regeda M. S., as prof. Kachmarska M.O.,ass. Sementsiv N.G., ass. Baida M.L., ass. Kolichetska M,A. In the methodical guide for individual study for English speaking students of Medical Faculty for preparing to practical classes on the theme “Hypoxias” containst basic theoretical information in full volume and according to the curriculum educational “Pathological Physiology”. Responsible for edition: First vice-rector on scientific-and-academic work of Danylo Halytski Lviv National Medical University acad. Gzhegotsky M.R. Reviewed by : Associate professor of the department of Pathological Anatomy with the course of Forensic Medicine of Danylo Halytskyi Lviv National Medical University Vovk V.I. Associate professor of the department of Pharmacology of Danylo Halytskyi Lviv National Medical University Havryluk I.M. Associate professor head of the department of Foreign languages of Danylo Halytskyi Lviv National Medical University Isayeva O.S. Approved and recommended for publication at the sitling of the Cycle Methodical Commission in Danylo Halytskyi Lviv National Medical University Protocol 2 2014 3 HYPOXIAS I. ACTUALITY OF THE THEME Tissue breathing is a process of consumption of oxygen by tissues. In providing tissues with oxygen the following systems participate: cardiovascular, blood and the apparatus of external breathing. Hence, violations which happen in these systems reflect on the functions of tissue breathing. At the same time violation of functioning one system is compensated by increasing functioning of the other one. At deficiency of compensatory reactions and at violation of abilities of tissues to utilize oxygen hypoxia arises. Hypoxia is an oxygen tissue starving, a state, which emerges in the organism as a result of violation of oxygen delivery to tissues and assimilation of it in tissues. Division of hypoxias into hypoxic, breathing, circulating, bloody, tissue and mixed reflects a vast circle of diseases, at which it can develop. Study of the pathogenesis of hypoxias, adaptive-protective mechanisms and pathological changes at it is essential for choosing pathogenetic therapy of hypoxic states. II. STUDY AIM 1. To know general conformities to law of the arising, development, and finishing of hypoxic states. 2. To be able to divide adaptive-compensatory phenomena at hypoxia and adaptation in the system of oxygen utilization and its transporting. 3. On experimental models to assess state of reactivity of the organism, initial level of metabolic processes in endurance of the organism in the terms of oxygen starving. 4. To know that professional poisonings may be the reason of oxygen starving. III. BASIC KNOWLEDGE AND SKILLS FOR PREPARATION TO THE TOPIC (interdisciplinary integration) Disciplines Knowledge acquired Structure of cell, tissues, tissue breathing Histological structure of respiratory organs, heart, and blood Anatomical structure of respiratory, cardio-vascular systems and blood Functions of the respiratory, cariovascular systems and blood Biology Histology Normal Anatomy Normal physiology 4 IV. TASKS FOR SELF-PREPARATION 1. List of main concepts, parameters, characteristics, which a student must master during preparation to a lesson Concept Definition This is a typical pathological process, which arises due to insufficient supply of oxygen to tissues or as a result of its insufficient utilization by tissues This is an oxygen deprivation that arises due to decrease partial oxygen pressure in the air inhaled This is an oxygen deprivation due to disorder of haemodynamics or abnormal local circulation This is an oxygen deprivation due to decrease in oxygen capacity in the blood This is an oxygen deprivation that emerges as a result of abnormal oxygen utilization by cells This is an oxygen deprivation due to increased functional load Hypoxia Hypoxic hypoxia Circulatory hypoxia Blood hypoxia Tissue hypoxia Load hypoxia 2. Theoretical questions to lesson 1. Principles of hypoxic states classification. 2. Mechanisms of development of hypoxia. 3. Etiology and pathogenesis of hypoxic hypoxia. 4. Etiology and pathogenesis of breathing hypoxia. 5. Etiology and pathogenesis of circulating hypoxia. 6. Etiology and pathogenesis of bloody hypoxia. 7. Etiology and pathogenesis of tissue hypoxia. 8. Immediate and long-lasting adaptive reactions of the organism at hypoxia. 9. Mechanism of hypoxic injury of cell. 10.Oxygen therapy and toxic properties of oxygen. Hyperbaric oxygenation. 11.Resistance of some organs and tissues to hypoxia. 5 3. Practical work (tasks) performed during practical lesson # 1. 2. Task To reproduce in experiment hypoxia at frog Indications to the task Fix and form the results of the experiment. Make conclusions. To reproduce in an experiment on rats model of acute cardiolungs insufficiency Draw and describe shortly the changes, which are observed. Write down in a protocol the results received. Fix and form the results of the experiment. Make conclusions. Insert 3 ml of 10% solution of Na nitrate under the skin of frog’s back. Perform dissection of thoracic and abdominal cavities. Dissect the heart. Inject 1 ml of 0.1% solution of adrenalin intraabdominally to a rat. Observe after development of cardio-lungs insufficiency Draw and shortly describe the picture observed. Write down in a protocol the results received. Orientation chart for organization of students’ independent work with educational literature # Task Indications to the task 1 Mechanisms of the Indicate properties development of metabolism violation during hypoxias 2 Ways of pharmacological correction of the breathing insufficiency 6 Treatment: Entering of oxygen Stimulation of the systems of oxygen transporting 7 Compensation-adaptive reactions In systems of oxygen utilization Specific antihypoxic cures Intoxication with products of metabolism Glycolysis Violations of matters exchange Stimulation of the systems of oxygen utilization Bloody Activation of freeradical oxidization Disconnection of oxidization and phosphorylation Inactivation of tissue enzymes As a result of hemoglobin deactivation Anemic Violation of perfusion Ischemic Violation of diffusion ation Breathing Metabolic acidosis Deficiency of energy Strengthening of glycolysis Fight for O2 Increased number of mitochondria In systems of oxygen transportation Oxyhemoglobin dissociation Violation of perfusion Violation of ventilation Breathing with the air with an increased contents of O2 Hypoxic Activation of breathing enzymes Pathogenesis: Oxyhemoglobin dissociation Polycythemia Etiology: Climbing on height Types: Increasing of blood circulation Hyperventilation V. CONTENT OF THE TOPIC Structurally-logical scheme of the theme’s content HYPOXIA Tissue Pathological violations Violations in organs and systems PATHOPHYSIOLOGY SINGS AND SYMPTOMS OF HYPOXIA After mixing with water vapor and expired CO2 in the lungs, oxygen diffuses down a pressure gradient to enter arterial blood where its partial pressure is around 100 mmHg (13.3 kPa). Arterial blood flow delivers oxygen to the peripheral tissues, where it again diffuses down a pressure gradient into the cells and into their mitochondria. These bacteria-like cytoplasmic structures strip hydrogen from fuels (glucose, fats and some amino acids) to burn with oxygen to form water. The fuel's carbon is oxidized to CO2, which diffuses down its partial pressure gradient out of the cells into venous blood to be exhaled finally by the lungs. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 40 mmHg (5.3 kPa) or below. If oxygen delivery to cells is insufficient for the demand (hypoxia), hydrogen will be shifted to pyruvic acid converting it to lactic acid. This temporary measure (anaerobic metabolism) allows small amounts of energy to be released. Lactic acid build up (in tissues and blood) is a sign of inadequate mitochondrial oxygenation, which may be due to hypoxemia, poor blood flow (e.g., shock) or a combination of both.] If severe or prolonged it could lead to cell death. The symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of altitude sickness, where hypoxia develops gradually, the symptoms include headaches, fatigue, shortness of breath, a feeling of euphoria and nausea. In severe hypoxia, or hypoxia of very rapid onset, changes in levels of consciousness, seizures, coma, priapism, and death occur. Severe hypoxia induces a blue discoloration of the skin, called cyanosis. Because hemoglobin is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red color that it has when bound to oxygen (oxyhemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye. In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic 8 Structure-logical scheme 2 MECHANISMS OF RESPIRATORY HYPOXIA Disorders of regulation of the external respiration Disorders of the osteomuscular apparatus of the thoracic cage Inflammatory, dystrophic and tumour processes in the lungs Chang function alveolarmemb RESPIRATORY HYPOXIA Disorders of blood oxygenation ↓ tension of oxygen in the tissues ↓ supply of oxygen to the tissues 9 ↓ shares of oxide phosphorylation in the metabolism of cells Structure-logical scheme 9 PRINCIPLES OF HYPOXIA TREATMENT Oxygen therapy with normal partial pressure of oxygen in the gas mixture or oxygen-barotherapy Administration of antihypoxic agents that produce beneficial effects on the processes of biological oxidation in the tissues Administration of antihypoxic agents which inhibit the processes of free-radical oxidation of the membraneous lipids Symptomatic therapy – administration of pharmacological agents whose action is directed at the recovery of impaired functions of physiological systems of the organism (cardio-vascular, hematologic, respiratory, CNS etc.) Transfusion of blood or mass of erythrocytes in order to increase oxygen volume in the blood in hemic type of hypoxia Antidote therapy in poisoning with cyanides and nitrates 10 VI. MATERIAL FOR SELF-CONTROL Situation tasks: 1. Alpinists slowly climbed the mountain slope. Behind them were 6 hours of climbing. Because of general weakness every stem required a lot of efforts. Breathing became very difficult, heart beating became intensive and reached 140 beats per min. Dizziness, head aches, depression, decrease of appetite, meteorism. 1.What is direct cause of these disarrangements in the alpinists? 2.What is the name of this syndrome? 3.What is the mechanism of accelerating the heart beating and breathing? 2. With the help of external cooling hypothermia of various rates was caused at two experimental animals. In one animal decrease of temperature was 10 Co, and in other the external cooling did not caused hypothermia yet (compensatory stage of hypothermia). 1.Elucidate how the sensibility to oxygen starving will change in these animals in these terms? 3. With the help of different methods the state of hypoxia was caused at two experimental rabbits: at one rabbit – with help of altitude chamber, at the other – with the help of experimental causing of lung swelling. 1.Which adaptive reactions are working at the rabbits? 2.What is the difference between them? 4. Coming from the pathogenesis of hypoxia, propose ways of artificial improving of resistance of the organism to hypoxia, name the most perspective ways of specific antihypoxic means. 5. The group of patients from sanatorium went to the mountains for excursion. Tachycardia and breathlessness developed in part of them in two hours after beginning of excursion. 1.Which type of hypoxia do those disturbances result from? 2.What is the mechanism developmenthypoxya 6. A driver slept in garage in a car with working engine. When he woke he had headache and later vomiting began in him. 1.What compound formation in blood caused this state? 2.Which type of hypoxia do those disturbances result from? 11 Tests: 1. A man constantly lives in mountains. What changes of blood test indices can found in him? A. Increased red blood cells number B. Decreased reticulocytes count C. Decreased color index D. Appearance of erythroblasts in blood E. Decreased hemoglobin content 2. After autopsy a forensic medical expert established that death of 20-year-old woman resulted from cyanide poisoning. What process disorder caused the death? A. Tissue respiration B Oxygen transport by hemoglobin C. Hemoglobin synthesis D. Urea synthesis E. Oxidative phosphorilation 3. Increased number of erythrocytes in blood test was revealed in people residing in village, which is situated in mountains at the altitude of 3000 m. What is the reason for changes in their blood? A. Increased erythropoietin production B. Blood clotting C. Change of spleen function D. Increased vitamin B12 synthesis E. Increased circulating blood volume 4. Which sportsman will have highest content of lactic acid in the blood? A.. Who just had run 5000 m B. Who just had run 100 m C. Weight-lifter D. Who put the shot E. Jumper with pole 5. A 40-years-old man took cyanic potassium by mistake. He died instantly. What mitochondrial enzymes do cyanides block? A. NAD-dependent Dehydrogenases B Cytochrome Oxydase C. Cytochrome B D. Cytochrome C E. FAD-dependent enzymes 6. Pain in muscles appears after physical exertion in people, who move a little (have hypodynamia) for a long time. What is the possible reason for this? A. Accumulation of lactic acid in muscles B. Increased content of ATP in muscles 12 C. Accumulation of creatinin in muscles D Decreased content of lipids in muscles E. Enhanced decay of muscle proteins 7. The number of erythrocytes in alpinist’s blood before going to mountains is 4,5x1012/L. What changes of erythrocytes number can develop at the altitude of 2500 m above sea level? A. Absolute erythrocytosis B. Absolute erythropenia C. Relative erythropenia D. Relative erythrocytosis E. There won’t be any changes 8. Dyspnea, increased heart beat rate, weaken of attention, foolishness occurred in sportsmen without acclimatization during the ascent to the altitude of 3000 m. Then weakness and disturbance of muscular coordination occurred. What was the reason for that condition? A. Hypoxic hypoxia B. Circulatory hypoxia C. Respiratory hypoxia D. Hemic hypoxia E. Hypercapnia 9. Total respiratory insufficiency was noticed on examination of blood gases partial pressure in a patient with bronchial asthma. What is the reason of respiratory hypoxia in this case? A. Decreased ventilation B. Decreased diffusion C. Increased ventilation D. . Increased perfusion E. Increased diffusion 10. Total respiratory insufficiency developed in a patient with lung disease. It manifested by decreased pO2 and increased pCO2 in patient’s blood. What caused development of respiratory hypoxia and pronounced respiratory insufficiency? A. Frequent shallow respiration B. Excessive hyperventilation C. Oxygen deficit in inspired air D. Uneven ventilation of the lungs E. Functional blood shunting in the lungs 11. Disorders of oxyhemoglobin formation have led to development of hemic hypoxia. What are the reasons for hemic hypoxia development? A. Methemoglobin formation 13 B. Inhibition of dehydrogenases C. Pronounced polycytemia D. Activation of Glutation Peroxidase E. Deficiency of riboflavinum 12. Which factors increase hypoxic injury of a cell under hypoxic conditions? A. Catecholamines B. Inhibitors of proteolysis C. Glucocorticoids D Chinon derivations E. Glutation-peroxidase 13. Symptoms of poisoning such as sharp weakness, dizziness, headache, vomiting, dyspnea, tachycardia, cyanosis of lips, ears, distal phalanges of fingers occurred in one child from group of children, who had eaten sweet juicy watermelon. Laboratory test of watermelon showed high level of nitrates. What is leading mechanism in pathogenesis of only one child poisoning? A. Methemoglobin reductase deficiency B. Cytochrome oxidase blockade C. Glutathione peroxidase deficiency D. Superoxide dismutase deficiency E. Catalase deficiency 14. A man has been living high in mountains for a long time. What changes in his blood would develop? A. Increase in quantity of hemoglobin B. Increase in diameter of blood vessels C. Decrease in number of leukocytes D. Increase in number of leukocytes E. Rare pulse 15. Tachypnea and hypopnoe developed in tourists, which had climbed to the altitude of 3000 m. These changes are consequence of stimulation of A. Chemoreceptors of carotid sinus B. Mechanoreceptors of pulmonary alveoli C. Baroreceptors of arch of aorta D. Neurons of the cerebral cortex E. Motoneurons of spinal cord All correct ansvers - A 14 REFERENCE Educational: 1) Pathological physiology. After redaction of A.I. Bereznyakova. Charkiv: Zoloti storinky. 2003 2) Pathological physiology. After redaction of M.N. Zayka, Yu.V.Byts. Kyiv: Vyshcha shkola, 1995. 3) Pathological physiology. After redaction of A.D. Ado, V.V. Novytsky, Tomsk: Un-ta. 1994 4) Pathological physiology. The course of lectures. After redaction of P.F. Letvitsky, M.:Medicina.1995 5) Agadganyan N.A. Organism and gas environment. M., 1972 6) Big medical encyclopedia. 15