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M 272 HLS Module Hemato-Lymph System Community Medicine 1 Anemia is ignored in most developing countries even though it is one of the most prevalent public health problems and has serious consequences for national development. What is Anemia? A state of tissue hypo-oxygenation, attributed to lower levels of healthy RBCs or Hb. 3 Anemia Etiology : Outline Impaired Erythropoiesis (Production): * nutritional inadequacies and deficiencies ( > 95 % of ALL cases) * bone marrow injury, whether idiopathic (e.g., inheritance) or acquired. Blood loss: * acute haemorrhage (placental, cord, visceral, wound etc) * chronic haemorrhage (hookworm, amoebiasis, GI disease) Shortend Life Span of RBCs : (destruction) * intra-corpuscular cause: e.g., familial spherocytosis , hemoglobinopathies * extracorpuscular cause: infection / inflamation: e.g., malaria, sepsis (e.g., AIDS) drug susceptibility : due G6PD. 4 The -INACG- 8 Major Causes in Developing Communities 5 All Anemias @ Community Level Developing vs World Developed World Prevalence of Anemia (100 % of Cases) Nutritional Non-nutritional 6 Nutritional Anemia A Basic Concept Total amount of a body micronutrient = circulating + reserve (store or pool) In “–ve” balance, reserve is mobilized to circulation Stages of development of deficiency anemia : 1. normal status ► store depletion ► deficiency state 2. deficiency state ► anemia (mild ►moderate ► advanced) 7 IDA (Iron Deficiency Anemia) The Most Common Nutritional Anemia 8 Iron deficiency causes at least 50% of all anemia, and almost a million deaths a year; three-quarters of the deaths occur in Africa and South-East Asia. Iron deficiency anemia (IDA) is in the "top ten" risk factors contributing to the global burden of disease. Worldwide, $50 billion is lost annually in low-Estimates of Economic Losses from Iron Deficiency Anemia (Cognitive & Productive) Iron is present in greatest concentration in meat and dark green vegetables. The U.S. Recommended Daily Allowance for adults is 10 mg for males, 18 mg for menstruating females. The average daily American diet contains about 10 mg iron, of which only about 1 mg is absorbed. IDA @ Community Level Developing vs Iron deficiency Developed Iron deficiency IDA IDA Anemia Anemia 11 IDA : Diagnosis Morphologically, it is microcytic , and hypochromic Hb level & serum ferritin (Normal blood levels are 30-300 ng/mL for males and 15-200 ng/mL for females. 12 ID (Iron Deficiency) Etiology ? Inadequate absorption low intake, poor bioavailability, Malabsorption Increased requirements, – due to high loss (e.g., disease or bleeding) 13 ID (Iron Deficiency) - continued Iron Sources: animal origin (mainly heme forms) plant origin (organic salts) 14 Iron Deficiency, ID : Selected Outcomes Microcytic, hypochromic anemia Lack of energy (easy fatigue) Decreased mental performance Decreased immunity 15 Iron Bioavailability : Determinants Individual’s iron status (deficient individuals show higher absorbability) Nature of foods in diet (absorption from plant foods = 1 % ; from animal foods = 20 %). % of food from animal sources (absorption from balanced diet is about 10 %) . Fe Oxidation state (only Fe+2 is absorbed) Enhancers (reducing agents : ascorbate, reducing sugars, gastric acidity) Depressors (high dietary fiber, PO4, phytates, calicium) Note: Iron from milk and egg has Low Bioavailability (% reaches the circulation) 16 Iron : Determinants of Requirements - RBC iron recycles ( 90- 95 %) Requirements = obligatory loss + growth need+other losses. Obligatory loss : - feces, skin, and urine Variability : (5-10% ) for man and woman ≈ 1mg/day. Average menstruation loss ≈ 0.5 mg/d). In some cases menstruation loss may mount upto 2 mg/d Total maternity requirement (loss) averages 3 mg/d 17 Iron Requirement in Infancy - Growth requirement: 0.5 mg per kg gain; Loss is negligible in infancy Predisposition to IDA: depends on 1. Birth endowment (depends on prematurity + maternal nutrition) - 2. Infant’s growth rate Prolonged excessive milk feeding milk Anemia 18 Reference Man's Maximum Body Content of Iron* Hemoglobin Store In tissues myoglobin enzymes Transported (in blood) 2000 mg 1000 mg 130 mg 8 mg 3 mg * Values for a reference woman are generally lower 19 Vulnerability to IDA increased significantly during: age period 6-24 months; pregnancy & lactation, & girls-late adolescence . serum ferritin drops rapidly starting from mid pregnancy below 12 ng/ml; at 28 gestation weeks, median ferritin averages 6 ng/ml. (Normal value=15200 ng/ml) 20 Iron Deficiency, ID First, iron stores start dropping down, as assessed only by biochemical tests If dropping down reached a significantly low and critical level, then the reduction in Hb concentration starts to be apparent ID is NOT detectable by Hb / Hct tests alone 21 IDA : the Hematological Tests and Indices Morphologic RBC Hb, Examination count Hemoglobin , PCV, Hematocrit, MCV, Mean Corpuscular Volume MCHC, Mean Corpuscular Hemoglobin Concentration 23 Anemia, Hb and Ferritin Low Hb means Anemia. Low Hb is not necessarily an IDA. Low Hb assesses only non specific anemia . Hb alone does not assess for iron deficiency, ID. Both low serum ferritin and Hb may diagnose IDA. 24 Folate Deficiency anemia anemia is a decrease in red blood cells (anemia) due to a lack of folate. The red cells are abnormally large (megaloblastic anemia). 25 Causes of this anemia are: a. Certain medications (e.g. phenytoin) b. Diseases such as celiac disease (sprue), which reduce absorption of folic acid from the diet c. Poor dietary intake of folic acid (FA is available in green leafy vegetables, citrus fruits, beans, whole grains, and liver) Because folate is not stored in the body in large amounts, a continual dietary supply of this vitamin is needed to maintain normal levels. 26 Folate deficiency in a pregnant mother can lead to problems for the infant during the first four weeks of formation of the neural tube and this can lead to problems in higher mental function later in life. 27 Prevention Good dietary intake of folate (better steamed food than normal cook) for the at risk population groups, and folic acid supplementation during pregnancy may help prevent this anemia. Prevention of neural tube defect can be fairly easily corrected by supplementation with a folic acid supplement. The annual number and prevalence of NTDs (i.e., spina bifida and anencephaly) in Puerto Rico declined significantly (p<0.05) from 93 (14.7 per 10,000 live births) in 1996 to 27 (5.3 per 10,000) in 2003 28 The folic acid campaign in Puerto Rico continues. Campaign staff members attend health fairs throughout the year; and each October on Folic Acid Awareness Day, they distribute educational materials to students at 30 university campuses. In 2006, promotional activities were extended to all public primary and secondary schools. During National Birth Defects Prevention Month in January, articles are placed in newspapers, television interviews are conducted, and partner organizations help to disseminate educational materials. The campaign has developed educational materials on birth defects prevention for health professionals and teachers. However, despite these measures, only approximately one fourth of women of childbearing age in Puerto Rico consume a vitamin containing folic acid daily, suggesting that other factors might affect behavior. Treatment The goal is to identify and treat the cause of the folate deficiency. Folic acid supplements may be given orally or intravenous on a short-term basis until the anemia has been corrected. In the case of poor absorption by the intestine -- replacement therapy may be lifelong. Dietary treatment consists of increasing the intake of green, leafy vegetables and citrus fruits. 31 B12 deficiency anemia 1. The etiology of B12 deficiency is more complicated than that of folate deficiency. One can develop deficiency through either of the following mechanisms Dietary deficiency B12 is only found in animal products, but it is plentiful. Therefore, nutritional deficiency is seen almost exclusively in vegans. Unlike the situation with folate, B12 body reserves can last for years. 2. Malabsorption states By far, this is the most common mechanism of disease development. The absorption of B12 is much more complicated than that of folate and iron. B12 is absorbed only in the terminal ileum. 3. 4. Intrinsic factor not produced Infestation with the fish tapeworm, Diphyllobothrium latum, Other Nutrients in Erythropoiesis 1. Retinol : It has a special implication with IDA. 2. Tocopherol (E): maintains integrity of RBC’S membrane; supplementation prevents haemolytic anaemia in infants fed PUFA-rich formulas. (polyunsaturated fatty acids). 3. Riboflavin (B2) : its coenzyme helps in : - synthesis of glutathione (GSH), needed for maintenance of cell stability - activation and release of Fe from ferritin. 4. Ascorbic acid: it protects the active form of folic acid , & assists in iron transfer from transferrin to ferritin 34 Other Nutrients in Erythropoiesis 4. Pyridoxine (B6) : works at the initiation level of heme synthesis. 5. Copper : it is bound to ceruloplasmin; it serves in transfer of Fe++ from ferritin to transferrin ; copper deficiency impairs iron absorption, and increases iron accumulation in storage tissues. 6. Zinc, 6. Other B-vitamins. 35 Retinol Correlates with Erythropoiesis Modern Research: serum retinol strongly correlates with - blood Hb, & - serum ferritin. Literature: Vitamin A Deficiency, VAD, can cause IDA. Jordan : VAD is a common finding in some poor areas 36 VAD - IDA - Interaction In VAD - Affected Populations Anemia may not respond to iron supplements unless linked with Vit A supplementation. VAD suppresses child growth and immunity. In illness conditions, VA supplementation promotes recovery rather than prevention. During illness the body utilizes vitA to combat infection, so that WHO guidelines call for replacement in cases of infection (diarrhea, ARI) in children under one year. 37 Jordan Map Most Underpriviliged Areas shown in pink 38 Grounds for Deficiencies in Community 1. 2. 3. Deficient maternal education Lack of physicians’ awareness Poverty 39 Nutritional Anemia Prevalence in Jordan 1996 1 year old infants : more than 60 % (in rural areas) In other children : 20 % affected (in poor areas) In pregnants : 27 % affected 40 Anemia in U5y-Children, 2002 (6-59 months) 34% are anemic: mild moderate severe * 21 % 13 % 0.2 % 2002 Jordan Population and Family Health Survey> Department of Statistics, ORC Macro 41 JPFHS 2002 - Conclusion Anemia in Jordanian children is… higher in rural (40%) compared to urban (32%). lower in first birth order (29%) compared with any higher birth order (35%). * 2002 Jordan Population and Family Health Survey> Department of Statistics, ORC Macro, 2002 42 Prevalence of Vitamin A Deficiency (VAD) Jordanian U5y- Children VAD Prevalence = 15.2 % VAD is a Public Health Problem in Jordan 43 Findings on Vitamin A Intake VAD is caused by : i) inadequate intake , and/or ii) infection (causes depletion of body – Vit A stores). Retinol from traditional Vitamin A /sources as the orange and yellow or red fleshed vegetables and fruits shown less bio-available than previously thought. It is very difficult / almost impossible for young children to meet needs through consumption of vegetables alone . Fortified foods are designed for the general population, but These do not meet the needs of infants and young children. 44 Breast Feeding Prevents IDA Breast milk, not only provides adequate iron but also vitamin A. Breast milk is the only reliable source of vit A for the U2y child. Vitamin A levels in breast milk is related to maternal stores In VAD areas breast milk may be unreliable. Supplementation for women after delivery guarantees the supply for sucklers for the first 6 months. It is important to continue BF for 2 years as U2y cannot consume enough vegetable sources to meet Vit A needs. IVACG, WHO 45 Intervention 1. Supplementation 2. Fortification 3. Programming (other apropriate tactics) 46 What is Food Fortification ? Fortification of food is deployment of biological weapons of mass protection 47 Fortification in Jordan Modified Wheat Flour Fortification Program has been going on since March 2006. The fortificants are 9 micronutrients 48 Prevalence of Anemia in Children* Age-months 6 to 9 10 or 11 12 to 23 24-35 36-47 48-59 Sex Male Female Anemia 23 24 0.4 22 0.6 8 0.2 6 51% 22% 14 18% 13 23 14 13 29 31% 20 11 0 0.2 43 65% 21 0 0.1 47% 18 Mild Moderate Severe 37% 31% * 2002 Jordan Population and Family Health Survey> Department of Statistics, ORC Macro, 2002 0.3 49 Anemia & VAD (1) Children aged 24-59 months with VAD are often anemic, stunted, and occasionally wasted. To address severe VAD in these children, vitamin A capsule distribution is the most practical immediate response. If the magnitude and pervasiveness of VAD among preschool-aged children is considerable, there is a likelihood that this problem extends to older children and adults; then, a comprehensive, longterm program is indicated. CDC-Morbidity and Mortality Weekly Report .Vitamin A Deficiency Among Children -Federated States of Micronesia, 2000. MMWR Morb Mortal Wkly RepJune 22, 2001/ 50(24);509-512 50 Anemia & VAD (2) The adequacy of observed intakes for vitamin A is compromised by the low lipid content of many complementary food of young children. This indicates that dietary quality rather than quantity is the key aspect of complementary food diets that needs to be improved. Lutter CK, Rivera JA.Nutritional status of infants and young children and characteristics of their diets. J Nutr. 2003 Sep; 133(9):2941S-9S. 51 Anemia & VAD (3) Women with low serum vitamin A levels had 1.8 times greater risk of being anemic than did the women with normal vitamin A status. Ahmed F, Mahmuda I, Sattar A, Akhtaruzzaman M. Anaemia and vitamin A deficiency in poor urban pregnant women of Bangladesh. Asia Pac J Clin Nutr. 2003;12(4):460-6.. 52 Anemia & VAD (4) Vitamin A fortification of foods had a favorable effect on iron metabolism and nutritional status. Mejia LA, Arroyave G.The effect of vitamin A fortification of sugar on iron metabolism in preschool children in Guatemala. Am J Clin Nutr. 1982 Jul;36(1):87-93. 53 Anemia & VAD (6) Anemia prevention programs among young children should focus on feasible strategies to improve intakes of bioavailable Fe and vitamin A, and reduce infection. Osorio MM, Lira PI, Ashworth A. Factors associated with Hb concentration in children aged 6-59 months in the State of Pernambuco, Brazil. Br J Nutr. 2004 Feb;91(2):307-15 54 Anemia & VAD (7) The importance of iron deficiency anemia (IDA) is adequately recognized; yet, it is far from being under control. Literature reviews continue to report that direct combat against IDA has attained only partial success [1] This may be explained by the roles of other factors, such as VAD. VAD, through different mechanisms [1-3], can adversely affect the utilization of available-iron and consequently the process of blood formation. 1. 2. 3. Underwood BA. Perspectives from micronutrient malnutrition elimination/ eradication programes. Bull World Health Organ 1998;76 Suppl 2:34Underwood BA and Arthur P. The contribution of vitamin A to public health. FASEB J 1996 Jul;10(9):1040-8 . Sommer A, Davidson FR; Annecy Accords. Assessment and control of vitamin A deficiency: the Annecy Accords. J Nutr 2002 Sep;132(9 Suppl):2845S-2850S 55