??? ???? ?????? Abstract Background: Anaemia is common worldwide specially in developing countries where nutrient deficiencies are prevalent. It is a common problem in the outpatient set but it’s always neglected and taken lightly which can cause hyperdynamic circulation disturbances and raise the rate of morbidity and mortality. Aim: To determine the prevalence of microcytic Hypochromic anaemia in medicine emergency room casualty in academy teaching hospital. Method: This is a descriptive cross-sectional study which was done in the Academy Teaching Hospital in which 75 of the emergency room patients participated in the study.
The state of nutrition of the patients was evaluated by a questionnaire answered by the patients. Chapter One Introduction and Literature Review 1. 1 Introduction Anaemia Anaemia is defined as the reduction in the oxygen-transporting capacity of blood, which usually stems from a reduction of the total circulating red cell mass to below normal amounts. Blood haemoglobin level is below 13. 5 g/dl in an adult male and below 11. 5 g/dl in an adult female. (1) Classification: Classified according to: 1. Causes: a. Inadequate production of RBC. b. Blood loss anaemia: * Acute: due to acute hemorrhage. * Chronic: due to GIT bleeding, menorrhagia. . Excessive destruction of RBC (haemolysis). 2. Morphology: a. Microcytic: * Iron deficiency. * Thalassemia. * Sideroblastic. b. Microcytic: * Folate deficiency. * B12 deficiency. c. Normocytic: * Aplastic anaemia. * Myelodysplastic anaemia. There are many undiagnosed cases of anaemia that if left undetected can lead to several complications, those include: (2) 1. Infections: people with the anaemia are more susceptible to getting infections from viruses and bacteria. 2. Severe bleeding: if bleeding is severe, internal and excessive then death can ensue if a blood transfusion is not given and the cause of the bleeding is not treated. . Stroke: if haemoglobin is defective, it can damage the walls of the red blood vessels and this can result in narrowing or even blockages in the brain, which can lead to serious, life threatening strokes. (2) Microcytic Hypochromic Anaemia Microcytic anemia is a blood disorder characterized by small red blood cells (erythrocytes) which have insufficient haemoglobin and hence have a reduced ability to carry oxygen through the body. The red blood cells are small due to a failure of haemoglobin synthesis or insufficient quantities of haemoglobin available. (3) Classification: 1. Iron deficiency anaemia . Sideroblastic anaemia. 3. Thalassemia. Iron deficiency anaemia It’s estimated to be the main cause of anaemia affecting about 10% of the population in developed countries and 25-50% in developing countries. The prevalence of iron deficiency anemia in the United States was 2 percent in adult men, but was found to be more common in child-bearing women age. (4) Total body iron content is about 2gm for females, and 6gm for males. Most of the iron within the body is found in hemoglobin within erythrocytes (80%), with the remainder being found in myoglobin and iron containing enzymes.
Iron is stored in liver, spleen, bone marrow and skeletal muscle. This iron storage pool contains on average 15-20% of total body iron. (4) Iron is transported in the plasma by an iron binding protein called transferrin. In normal individuals, transferrin is about 33% saturated with iron. Dietary iron is obtained either from inorganic sources or animal sources. Dietary iron enters intestinal cells via specific transporters. The iron is then used by the cell, stored as ferritin or transferred to the plasma. (4) Erythropoiesis is the development process in which new erythrocytes are produced, through which each cell matures in about 7 days.
Through this process erythrocytes are continuously produced in the red bone marrow of large bones, at a rate of about 2 million per second in a healthy adult. The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin. The red blood cells of an average adult human male store collectively about 2. 5 grams of iron, representing about 65% of the total iron contained in the body. (5)(6) Causes: * Poor intake. * Decreased absorption (celiac disease, gastrectomy). * Increased demand in growing adolescents and pregnancy. * Blood loss from GIT due to: * Hookworm infestation. Erosions associated with NSAID, peptic ulcer or neoplastic disease. * Hemorrhoids. * Blood loss from irregular or excessive menstruation. Symptoms and signs (7) Symptoms may include: * Fatigue. * Shortness of breath * Lightheadedness. * Palpitations. * Dizziness. * Chest pain. * Blurred vision. * Sleep disturbance. Signs may include: * Rapid heart rate. * Low blood pressure. * Rapid breathing. * Pale conjunctiva. * Cold skin. * Enlargement of the spleen. Diagnosis of iron deficiency anaemia: * Complete blood count and color: with iron deficiency anaemia red blood cells are smaller and paler in color than normal. Hematocrit: This is the percentage of blood volume made up by red blood cells. Normal levels are generally 41% for adult women and 47% for adult men. These values may change depending on your age. * Haemoglobin: Lower than normal hemoglobin levels indicate anemia (12-16 g/dl in an adult male and 13. 7-17. 5 g/dl in an adult female). * Ferritin: This protein helps store iron in your body, and a low level of ferritin usually indicates a low level of stored iron. Some tests might be done to detect the underlying cause, like: * Endoscopy: Often to check for bleeding from a hiatal hernia, an ulcer or the stomach. Colonoscopy: To rule out lower intestinal sources of bleeding. * Ultrasound: Women may also have a pelvic ultrasound to look for the cause of excess menstrual bleeding, such as uterine fibroids. (8)(9) Sideroblastic anaemia It is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). [10] In Sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently.
Sideroblasts are atypical, abnormal nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in perinuclear mitochondria. [11] Sideroblasts are seen in aspirates of bone marrow. Causes: * Failure to completely form heme molecules, This leads to deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. * Toxins: lead, copper or zinc poisoning * Drug-induced: ethanol, isoniazid, chloramphenicol, cycloserine, Oral Contraceptives * Nutritional: pyridoxine (Vitamin B6) or copper deficiency * Diseases: Rheumatoid arthritis, or multiple myeloma Genetic: ALA synthase deficiency (X-linked, associated with ALAS2)[12] Symptoms and signs: * Pale skin, eyelids and lips. * Fatigue and weakness. * Dizziness. * Enlarged liver and/or spleen. Diagnosis: Ringed sideroblasts are seen in the bone marrow. Laboratory findings: * Increased ferritin levels * Normal total iron-binding capacity * Hematocrit of about 20-30% * Serum Iron: High * High transferrin saturation * The mean corpuscular volume or MCV is usually normal or low. * With lead poisoning, see coarse basophilic stippling of red blood cells on peripheral blood smear * Specific test: Prussian Blue stain of RBC in marrow.
Shows ringed sideroblasts. * can also cause microcytic hypochromic anemia. (12) Thalassemia It is a group of inherited autosomal recessive blood disorders that originated in the Mediterranean region. In Thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis, or no synthesis of one of the globins chains that make up hemoglobin. This can cause the formation of abnormal hemoglobin molecules, thus causing anemia, the characteristic presenting symptom of the Thalassemia. (13) Symptoms and signs: * Fatigue and weakness. * Shortness of breath. * Pale appearance. Irritability. * Yellow discoloration of the skin. * Facial bone deformities. * Slow growth. * Abdominal swelling. * Dark urine. (14) Diagnosis: * Blood tests. * Prenatal screening. (14) Laboratory findings: * A low level of red blood cells * Smaller than expected red blood cells * Pale red blood cells * Red blood cells that are varied in size and shape * Red blood cells with uneven hemoglobin distribution, which gives the cells a bull's-eye appearance under the microscope. (14) 1. 2 Literature Review A study was done in Italy about prevalence and incidence and types of mild anaemia in the elderly.
The objectives of this study were to estimate the prevalence and incidence of mild grade anemia and to assess the frequency of anemia types in the elderly. Design and Methods: This was a prospective, population-based study in all residents 65 years or older in Biella, Italy. Results: Blood test results were available for analysis from 8,744 elderly. Hemoglobin concentration decreased and mild anemia increased steadily with increasing age. Mild anemia (defined as a hemoglobin concentration of 10. 0-11. 9 g/dL in women and 10. 0-12. 9 g/dL in men) affected 11. % of the elderly included in the analysis, while the estimated prevalence in the entire population was 11. 1%. Before hemoglobin determination, most mildly anemic individuals perceived themselves as non-anemic. Chronic disease anemia, Thalassemia trait, and renal insufficiency were the most frequent types of mild anemia. (15) A study was done in emergency ward, Mulago Hospital, Uganda. Anaemia is a common problem in Africa, with prevalence ranging from 21. 1% to 64. 4% 16-21 and a significant impact on morbidity and mortality. 22,23 in patients with AIDS low haemoglobin levels are associated with poor outcomes. 4-27 However, anaemia in Africa has multiple causes, with infectious diseases such as HIV, tuberculosis and malaria contributing significantly to the anaemia burden. 28 Hookworm is a major contributor to anaemia and even light hookworm loads are associated with low haemoglobin levels, 29-33 although Lewis et al. reported that hookworm was not a common cause of anaemia among medical patients in Malawi. In a cross-sectional descriptive study 395 patients were recruited by systematic random sampling and their socio-demographic characteristics and clinical details collected.
A complete blood count and peripheral film examination were done and stool examined for hookworm ova.. Of the patients 255 (64. 6%) had anaemia. The prevalence was higher among males (65. 8%) than females (63. 7%). Fatigue (odds ratio (OR) 2. 1, confidence interval (CI) 1. 37 - 3. 24), dizziness (OR 1. 64, CI 1. 07 - 2. 44), previous blood transfusion (OR 2. 83, CI 1. 32 - 6. 06), lymphadenopathy (OR 2. 99, CI 1. 34 - 6. 66) and splenomegaly (OR 5. 22, CI 1. 78 - 15. 28) were significantly associated with anaemia. Splenomegaly, low body mass index (BMI) (<19) and being HIV positive were independently associated with anaemia.
The commonest type of anaemia was Hypochromic microcytic (34. 1%). Only 10. 6% of anemic patients had hookworm infestation. (34) A study was done in north Vietnam was proposed to assess the prevalence of iron deficiency and anemia and associated risk factors in a community-based sample of women living in a rural province of northwest Vietnam. A cross-sectional survey, comprised of written questionnaires and laboratory analysis of hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count, was undertaken, and the soluble transferrin receptor/log ferritin index was calculated. Of 349 non-pregnant women, 37. 3% were anemic (Hb < 12 g/dL), and 23. 10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present in 78. 15% of women, although heavy infection was uncommon (6. 29%). Iron deficiency was more prevalent in anemic than non-anemic women (38. 21% versus 14. 08%, P < 0. 001). Consumption of meat at least three times a week was more common in non-anemic women (51. 15% versus 66. 67%, P = 0. 042). Mean ferritin was lower in anemic women (18. 99 versus 35. 66 ng/mL, P < 0. 001). There was no evidence of a difference in prevalence (15. 20% versus 17. 23%, P = 0. 629) or intensity (171. 7 versus 129. 93 eggs/g, P = 0. 412) of hookworm infection between anemic and non-anemic women. (35) In the United States a study was done to determine the prevalence of iron deficiency and iron deficiency anemia in the US population. A total of 24 894 persons aged 1 year and older examined in the third National Health and Nutrition Examination Survey (1988-1994). Iron deficiency, defined as having an abnormal value for at least 2 of 3 laboratory tests of iron status (erythrocyte protoporphyrin, transferrin saturation, or serum ferritin); and iron deficiency anemia, defined as iron deficiency plus low hemoglobin.
Nine percent of toddlers aged 1 to 2 years and 9% to 11% of adolescent girls and women of childbearing age were iron deficient; of these, iron deficiency anemia was found in 3% and 2% to 5%, respectively. These prevalences correspond to approximately 700000 toddlers and 7. 8 million women with iron deficiency; of these, approximately 240 000 toddlers and 3. 3 million women have iron deficiency anemia. Iron deficiency occurred in no more than 7% of older children or those older than 50 years, and in no more than 1% of teenage boys and young men.
Among women of childbearing age, iron deficiency was more likely in those who are minority, low income, and multiparous. (36) Chapter Two Justification * Anaemia is common worldwide specially in developing countries where nutrient deficiencies are prevalent. * Nutritional iron deficiency anaemia is difficult to control in Sudan due to poor socio-economic status and this leads to the progression of it. * Anaemia is a common problem in the outpatient set but it’s always neglected and taken lightly. * Undetected anaemia can cause hyperdynamic circulation disturbances and raise the rate of morbidity and mortality.
Chapter Three Objectives: General: * To determine the prevalence of anaemia in medicine emergency room (ER) casualty in academy teaching hospital. Specific: * To determine the prevalence of microcytic Hypochromic anaemia in medicine emergency room casualty in academy teaching hospital. * To determine the greatest age group of the sample size that presents at the medicine emergency room. * To determine the number of meals per day in relation to the anaemia. * To determine the greatest gender risk group for the microcytic Hypochromic anaemia. Chapter Four Methodology 4. 1 Study Design:
A cross-sectional descriptive study. 4. 2 Study Period: The study was conducted in a period from the first of October till the end of December. 4. 3 Study Area: The study was done in the emergency room of the Academy Teaching Hospital located in Al-sahafa East. 4. 4 Study Population: Patients present at the medicine emergency room of the Academy Teaching Hospital were included in the study during the study period 2011-2012. Patients present at the outpatient were excluded. 4. 5 Variables: Background variables: * Type of the anemia. * Gender in relation to the anaemia. Causes in relation to the anaemia. * Age in relation to the anaemia. 4. 6 Sampling Technique: Simple random sampling of 75 patients was done based on: * Age between 16-45 years. * Negative previous history of anaemia. * No history of blood disorder. * No pregnancy. 4. 7 Sample Size: All patients were willing to participate. A total of 75 patients participated in the study. 4. 8 Data collection Techniques and Tools: * a questionnaire including demographic data, symptoms, medical history, physical examination and nutritional status is given to each patient to be filled by him/her or an assistant. On enrolment of patients into the emergency room, 3 ml of peripheral blood will be collected in plastic container. * Blood samples will be sent to the lab for screening of anemia and its specific morphology using complete blood count test and platelet count. 4. 9 Data management and Analysis: To analyze the collected data, Statistical Package for Social Sciences (SPSS research software) will be used. Used to calculate the prevalence of anemia, through a pre-coded system. 4. 10 Ethical Consideration: * Ethical approval for the study was obtained from the ethical committee at the University of Medical Sciences & Technology.
Verbal consent was taken from individuals under the study. * The information used in this study is confidential and only used for the purpose of this research. Chapter Five Recommendation 1. Mandatory screening of blood for anaemia and microcytic Hypochromic anaemia. 2. Investigation for the causes of anaemia and follow up. 3. Iron supplements under doctor’s prescription are recommended for patients with less than three meals per day. 4. Education and spreading of awareness about the important sources of iron and harmful sides of soft drinks, tea and coffee. Chapter Nine References: 1. Mohammad Inam Danish.
Medical diagnosis and management. Karachi institute of heart diseases, 2010. 2. Sited: http://www. vitalhealthzone. com/health/conditions/a/anaemia/06_complications_of_anaemia. html 3. Sited: http://www. websters-online-dictionary. org/definitions/microcytic+anemia 4. Vinay Kummar, Abul K. Abbas, Nelson Fausto. Basic pathology. 8th edition, 2007. 5. Laura Dean. Blood Groups and Red Cell Antigens. National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, 2005. 6. Kabanova S, Kleinbongard P, Volkmer J, Andree B, Kelm M, Jax TW .
Gene expression analysis of human red blood cells. International Journal of Medical Sciences 6, 2009 (4): 156–9. 7. Sited: http://www. emedicinehealth. com/anemia/page3_em. htm 8. Marks PW. Anemia. National Heart, Lung, and Blood Institute. Mayo Clinic, 2011 January 6. 9. Rochester, Minn. Laboratory reference values. Hematology group. Mayo Foundation for Medical Education and Research, 2011 January. 10. Sideroblastic Anemias: Anemias Caused by Deficient Erythropoiesis at Merck Manual of Diagnosis and Therapy Professional Edition 11. "Sideroblast" at Dorland's Medical Dictionary 12. Aivado M, Gattermann N, Rong A, et al.
X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood Cells Mo, 2006. Dis. 37 (1): 40–5 13. Hemoglobinopathies and Thalassemias. 14. .mayo clinic staff, thalassemia. Mayo Foundation for Medical Education and Research (MFMER). , 1998-2012. 15. Mauro Tettamanti, Ugo Lucca, Francesca Gandini. Prevalence, incidence and types of mild anemia in the elderly. Haematol, 2010 November 1. 16. Adam I, Khamis AH, Elbashir MI. Prevalence and risk factors for anaemia in pregnant women of eastern Sudan. Trans R Soc Trop Med Hyg 2005; 99(10): 739-743. 7. Asobayire FS, Adou P, Davidsson L, Cook JD, Hurrell RF. Prevalence of iron deficiency with and without concurrent anemia in population groups with high prevalences of malaria and other infections: a study in Cote d'Ivoire. Am J Clin Nutr 2001; 74(6): 776-782. 18. Charlton KE, Kruger M, Labadarios D, Wolmarans P, Aronson I. Iron, folate and vitamin B12 status of an elderly South African population. Eur J Clin Nutr 1997; 51(7): 424-430. 19. Dicko A, Mantel C, Thera MA, et al. Risk factors for malaria infection and anemia for pregnant women in the Sahel area of Bandiagara, Mali. Acta Trop 2003; 89(1): 17-23. 0. Leenstra T, Kariuki SK, Kurtis JD, Oloo AJ, Kager PA, ter Kuile FO. Prevalence and severity of anemia and iron deficiency: cross-sectional studies in adolescent schoolgirls in western Kenya. Eur J Clin Nutr 2004; 58(4): 681-891. 21. Sserunjogi L, Scheutz F, Whyte SR. Postnatal anaemia: neglected problems and missed opportunities in Uganda. Health Policy Plan 2003; 18(2): 225-231. 22. Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR. Impact of anemia on hospitalization and mortality in older adults. Blood 2006; 107(10): 3841-3846. 23. Ma JZ, Ebben J, Xia H, Collins AJ.
Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999; 10(3): 610-619. 24. Elliott AM, Halwiindi B, Hayes RJ, et al. The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia. Trans R Soc Trop Med Hyg 1995; 89(1): 78-82. 25. . Moore RD. Human immunodeficiency virus infection, anemia, and survival. Clin Infect Dis 1999; 29(1): 44-49. 26. O'Brien ME, Kupka R, Msamanga GI, Saathoff E, Hunter DJ, Fawzi WW. Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania.
J Acquir Immune Defic Syndr 2005; 40(2): 219-225. 27. Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JW. Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project. Blood 1998; 91(1): 301-308. 28. Morris CD, Bird AR, Nell H. The haematological and biochemical changes in severe pulmonary tuberculosis. Q J Med 1989; 73(272): 1151-1159. 29. Akhwale WS, Lum JK, Kaneko A, et al. Anemia and malaria at different altitudes in the western highlands of Kenya. Acta Trop 2004; 91(2): 167-175. 0. Bates I, McKew S, Sarkinfada F. Anaemia: a useful indicator of neglected disease burden and control. PLoS Med 2007; 4(8): e231. 31. Stoltzfus RJ, Albonico M, Chwaya HM, et al. Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children. Am J Trop Med Hyg 1996; 55(4): 399-404. 32. Sturrock RF. Hookworm studies in Uganda: investigations at Teboke in Lango District. East Afr Med J 1966; 43(10): 430-438. 33. Tatala S, Svanberg U, Mduma B. Low dietary iron availability is a major cause of anemia: a nutrition survey in the Lindi District of Tanzania.
Am J Clin Nutr, 1998; 68(1): 171-178. 34. Japheth E Mukaya, Henry Ddungu, Francis Ssali, Tim O'Shea, Mark A Crowther. Prevalence and morphological types of anaemia and hookworm infestation in the medical emergency ward. SAMJ, S. Afr. med. J, 2009 December vol. 99 no. 12 Cape Town, 35. Sant- Rayn Pasricha, Sonia R. Caruana, Tran Q. Phuc, Gerard J. Casey, Damien Jolley. Anemia, Iron Deficiency, Meat Consumption, and Hookworm Infection in Women of Reproductive Age in Northwest Vietnam. Am J Trop Med Hyg, 2008 March vol. 78 no. 3 375-381. 36. Anne C. Looker, Peter R. Dallman, Margaret D. Carroll, Elaine W.
Gunter, Clifford L. Johnson. Prevalence of Iron Deficiency in the United States. JAMA, 1997;277(12):973-976. Chapter Ten Appendix 10. 1. Questionnaire: Nutritional status: Prevalence of microcytic Hypochromic anaemia in medicine emergency room in Academy Teaching hospital ??? ???? ?????? ?????? ??????? ??????? : / /2011?. ????? :______ ????? : _____ ????? : ________ ??????? : ________________ ??????? : ___________ ??????? ??????? : ___________________________ ------------------------------------------------------------------------------ 1. ?? ??? ????? ??? ??? ???????? _____________________________________. 2. ?? ??????? ???? ???? ??? ??? ????? ??? ??? ???????? ____________________________________________________________________________________. 3. ??? ???? ??? ??????? ?? ??????? ____________________________________. 4. ?? ??? ????? ???? ?? ?????? ?? ??? ??????? __________________________________. ----------------------------------------------------------------- ?? ????? ?? ???? ??????? ???? ???? ???? ????? ?????? ???????. * ?????? ?????? ???????. _____________ * ??????. ______________ * ????? ?? ??????. ______________ * ?????? ????? ?????. ______________ * ?????? ?? ????? ??? ??? ?????? (????? , ????? ) ___________ * ?????? ???????. _____________ * ??? ?????? ??? ???????. _____________ * ??? ????? ?????? ?? ?????. _____________ * ???? ?? ??????. _____________ * ?????? ?? ?????. _____________ ?? ???? ???? ??????? ???? ?????? ?? ?? ????? ??????? _________________________. ?? ????? ?? ???? ????? ???????? ?? ????? ,????? ??? ?????? ?? ???????. ????? | ????? ?? | ??? ?? ??????? | ????? ?? ??????? | ??????? ???? | ??? | | | | | ??????? | | | | | ????? | | | | | ?????? ??????? | | | | | ?????? | | | | | ????? | | | | | ???? ????? | | | | | ????????? ??????? (?????????? ,????? ???????? ,?????? )| | | | | ???????? ??? ??????? ??????? (????? ,?????? ,?????? ,?????????????? ). | | | | | ??????? ??????? (?????? ,?????? ,????? ,????? ,????? )| | | | | ???????? , ??????? , ?????? ???? )| | | | | ?????? | | | | | ???????? (????? , ?????? )| | | | | ????????? ??????? | | | | | ?? ??? ??????? ???? ??? ??????? ?? ????? , ????????? ___________________________________________________________________________________. ---------------------------------------------------------------------------- ?? ??? ???? ???? : ????? : ____???. _____??. ?????? : ____???. _____??. ?? ????? ____???. _____??. ??? ???? _______________________. ?? ??? ?????? ?? ?????? ______________________. ?? ?????? ??????? ____???. _____??. ??? ???? __________________________. ?? ???????? ???? : ______????. _____??????. ??? ???? ,?? ??? ?????? ?? ?????? __________. ??? ?????? ,?? ??? ?????? ?? ???????? ___________. ?? ?? ??????? ___________________. ?? ?????? ???????? ____???. ______??. ??? ???? ______________________. ?? ??? ?????? ?? ?????? __________________. ?? ???? ??? ?? ??????? ???? ???? ?? ???? , ??? ??? ???????? ________________________________________. ?? ???? ??? ?? ??????? ???? ???? ??? ???? , ??? ??? ???????? _______________________________________.
