ANEMIA

Mentor :dr. Pulung M. Silalahi, Sp. A

Written by : Dicky Lesmana 1102010077

Faculty of Medicine YarsiPediatric DepartmentRumah Sakit Bhayangkara tk.I R.S. Sukanto-JakartaPeriode: 1 Desember 2014 30 January 2015

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FOREWORD

Praise and gratitude we say to Allah SWT upon completion referat entitled vomiting in children.This academc writing is given as a part of clinical practice duty as a Co-Ass in RS Bhayangkara Tingkat 1 Raden Said Sukanto, in the Pediatrics department.The sources that I use for the writing contain information from textbooks, journals and online references. The author would like to give special mention to mentor, dr Pulung M. Silalahi, Sp. A, for guiding author throughout the entire writing process. I hope that this writing can be a positive use to the readers, be it as an additional information or future references. I realize that the writing is still lacking in many areas but I hope the readers can give critical remarks so that further improvement can be made in the future.

Jakarta, Januari 2015

authorTABLE OF CONTENTSFOREWORD iTABLE OF CONTENTS ii

CHAPTER I INTRODUCTION 11.1 Background 11.2 Purpose of Writing 11.3 Problems 21.4 Benefits of the article 2

CHAPTER II LITERATURE REVIEW 22.1 Definition2.2 Etiology2.3 Pathophysiology 2.4 Classification2.5 Clinical Manifestations 2.6 Diagnosis 2.7 Treatment 2.8 Complication 2.9Prognosis....

2.10 Prevention.......

CHAPTER III7

CHAPTER IV...16

CHAPTER V22

CHAPTER VI...27

CHAPTER VII CONCLUSION 347.1 Conclusion 34ACKNOWLEDGEMENTS 35

CHAPTER IINTRODUCTION

Anemia is a medical problem that is most often found in clinics around the world, especially in developing countries. It is estimated that more than 30% of the world population, or 1500 million people suffer from anemia. These disorders have a major impact on the social and economic well-being and physical health.Anemia is not a disease entity in itself, but a symptom of various diseases base. Therefore, the determination of underlying disease is also important in the management of anemia cases, because without knowing the underlying causes, anemia can not be given a thorough treatment.Indonesian doctors competency standards created by the College of Education Standards Division of the Indonesian Doctors, GPs are expected to make a diagnosis of anemia (iron deficiency, megaloblastic, aplastic, hemolytic) based on history, physical examination, and laboratory. For iron deficiency anemia, general practitioners should be able to do the treatment. For megaloblastic anemia, aplastic, hemolytic, general practitioners refer only to a point, and knowing the complications of the disease. Therefore, in this referat will discuss the four types of anemia.

CHAPTER IIANEMIA

2.1 DefinitionsAnemia is functionally defined as a decrease in the number of red cell mass (red cell mass) and so can not fulfill its function is to carry oxygen in sufficient quantities to peripheral tissues.

2.2 CriteriaThe most common parameter to indicate a decrease in red cell mass is hemoglobin levels, followed by hematocrit and erythrocyte count. The normal price varies hemoglobin physiologically dependent on sex, age, pregnancy and height of residence.

2.3 ClassificationAnemia can be classified based on morphology and etiology. Classification morphology is based on the size and hemoglobin content. According to the etiology, anemia can be classified into three kinds, namely impaired production of red blood cells in the bone marrow (hipoproliferasi), impaired maturation of red blood cells (erythropoiesis ineffective), and decreased life span of red blood cells (blood loss or hemolysis).1. Hipoproliferatif. Hipoproliferatif is the highest cause of anemia. anemiahipoproliferatif This can be caused by:a) Bone marrow damage. This condition can be caused by drugs, infiltrative disease (eg, leukemia, lymphoma), and bone marrow aplasia.b) iron deficiencyc) Stimulation of erythropoietin (EPO) which is inadequate. This situation occurs in impaired renal functiond) Suppression of EPO production induced by inflammatory cytokines (eg, interleukin 1)e) Decreased need for oxygen network (eg on hypothyroid state)In this type usually found normositer normokrom erythrocytes, but can also be found mikrositer hypochromic erythrocytes picture, namely the mild to moderate iron deficiency and inflammatory diseases. Both of these circumstances can be distinguished by examination of inventory and storage of iron.

2. Impaired maturationIn the circumstances this type of anemia usually found reticulocyte levels "low", disruption cell morphology (macrocytic or microcytic), and abnormal erythrocyte indices. Maturation disorders can be classified into two kinds:a.Impaired maturation coreIn this situation usually ditmukan morphological abnormalities such as macrocytic. The cause of the disorder is the core maturation deficiency of folic acid, vitamin B12 deficiency, drugs that affect the metabolism of DNA (such as methotrexate, alkylating agents), and myelodisplasia. Alcohol can also cause core maturation, but this situation is caused by a deficiency of folic acid.b. Cytoplasmic maturation disordersIn this situation usually ditmukan morphological abnormalities in the form of microcytic and hypochromic. Causes of cytoplasmic maturation disorder is severe iron deficiency, disorders of globin synthesis (eg thalassemia), and heme synthesis disorders (eg sideroblastic anemia)3. Decreased red blood cell survival timeThis type of anemia can be caused by blood loss or hemolysis. In both these objec will get an increase in the number of reticulocytes. Blood loss can be acute or chronic. In the acute phase, have not found a significant increase in reticulocytes because it takes time for an increase in erythropoietin and proliferation of cells from the bone marrow. While the chronic phase will resemble the picture of iron deficiency anemia.Overview of hemolytic anemia can vary, can be acute or chronic. In anemia of chronic hemolysis, as in hereditary spherocytosis, the patient came not because of the state of anemia itself, but because of complications caused by the breakdown of red blood cells in the long term, such as splenomegaly, aplastic crisis, and gallstones. In circumstances caused by autoimmune, hemolysis can occur episodically (selflimiting)

Figure 1: Classification of anemia based index of erythrocytec. Mean Cell Hemoglobin Concentration (MCHC) = hemoglobin x 10 hematocrit(N: 33 + 2%)C. Leukocytes (N: 4500-11000 / mm3)D. Platelets (N: 150000-450000 / mm3)2. Preparations Apus Blood Banka.cell sizeb. anisocytosisc. Poikolisitosisd. Polikromasia 3. Calculate the reticulocyte (N: 1-2%) 4. Inventory Irona. Serum iron (N: 9-27mol / liter)b. Total Iron Binding Capacity (N: 54-64 mol / liter)c. Serum ferritin (N : 30 mol / liter; : 100 mol / liter)5. Bone Marrow Examinationa. aspiration- E / G ratio- cell morphology- staining Feb. biopsy- cellularity- morphologyI. Examination Complete Blood Count (CBC)The criteria whether a person suffering from anemia can be seen in the levels of hemoglobin and hematocrit. In addition, erythrocyte indices can be used to assess abnormalities of erythrocyte size and hemoglobin synthesis defects.If MCV 100 can be referred to as macrocytosis. While the MCH and MCHC can assess any defect in hemoglobin synthesis (hypochromia)II. Blood smear preparations Bank (SADT)SADT will provide important information if there is an interruption or defect in the production of red blood cells. The term anisocytosis shows erythrocytes varying sizes, while poikilositosis shows the shape of erythrocytes diverse.III. reticulocyte countThis is an initial screening examination to differentiate the etiology of anemia. Normally, reticulocytes is the new red blood cells released from the bone marrow. Reticulocytes containing residual RNA will be metabolized within 24-36 hours (time to live in circulating reticulocytes). Normal levels of reticulocytes 1-2% which shows daily replacement of approximately 0.8-1% of the total number of red blood cells in circulation.Reticulocyte index is a calculation of the production of red blood cells. Reticulocyte value will be adjusted to the level of hemoglobin and hematocrit of patients based on age, gender, Working and other corrections if found premature release of reticulocytes (polikromasia). This is because the life time of reticulocytes premature longer so as to generate value as if a high reticulocyte.Correction factor for:Ht 35%: 1.5Ht 25%: 2.0Ht 15%: 2.5Description: RI 2.5%: excessive destruction of red cellsIV. Supplies and Storage IronTransferrin saturation is obtained by dividing the serum iron by TIBCmultiplied by 100 (N: 25-50%). In the measurement of plasma levels and percent saturation Fe transferrin, there is a diurnal variation with a peak at 9:00 am and 10:00 am.Serum ferritin is used to assess total body iron reserves. However, ferritin is also an acute phase reactant, and in a state of acute and chronic inflammation, levels can be increased.V. Bone Marrow ExaminationThis check can be used to assess whether there is interference on the bone marrow for example myelofibrosis, maturation disorders, or infiltrative disease. The increase or decrease in the comparison of a group of cells (myeloid or erythroid) can be found from the counts nucleated cells in bone suumsum (erythroid ratio and granuloid).

CHAPTER IIIIRON DEFICIENCY ANEMIAIron deficiency anemia is the most common type of anemia found especially in developing countries. Causes include:- Nutritional factors: the low total iron intake or bioavailability of iron in the diet consumed less good (food fiber, low in meat, and low in vitamin C).- Increased need, such as in premature infants, children in growth, pregnant and lactating mothers.- Impaired absorption of iron: gastrectomy, chronic colitis, or achlorhydria.- Iron loss due to chronic bleeding, such as bleeding peptic ulcer, malignancystomach / colon, hemorrhoids, infection worms mine, menometrorraghia, hematuria, or hemaptoe.A. Metabolism of IronTotal iron in the human body healthy adults ranges from 2 grams (in women) and 6 grams (in men) are scattered in three compartments, namely 1). Functional iron, such as hemoglobin, myoglobin, cytochrome enzymes, and catalase, is 80% of the total iron contained body tissues. 2). Iron reserves, is 15-20% of the total iron in the body, such as ferritin and hemosiderin. 3). Iron transport, namely iron binding to transferrin.Sources of iron in the diet is divided into two forms:1. heme iron, found in meat and fish. High absorption levels (25% of its iron content can be absorbed) because it is not affected by the inhibiting factors.2. Non-heme iron, derived from plants. Absorption level is low (only 1-2% of its iron content which can be absorbed). Absorption mechanism is very complex and not yet fully understood. Absorption is influenced by the presence of absorption promoters factors (factors meat, vitamin C) and inhibiting factors (fiber, phytat, tannic).Iron absorption process is divided into 3 phases:- Luminal Phase: iron in foods processed by the stomach (gastric acid cause heme regardless of apoproteinnya) until ready to be absorbed.- Mucosal phase: the process of iron absorption in the intestinal mucosa. Sections of intestine plays an important role in iron absorption is the duodenum and proximal jejunum. However, a small portion also occurs in the stomach, ileum and colon. Iron absorption is done by absorptive cells that are at the height of the intestinal villi. Heme iron that has been digested by the stomach acids directly absorbed by the absorptive cells, whereas for the non-heme iron that occurs very complex mechanism. There are at least three proteins involved in the transport of non-heme iron from the intestinal lumen to the cytoplasm of the absorptive cells. Luminal mucin acts to bind non-heme iron in order to remain soluble and can be absorbed even in alkaline atmosphere duodenum. In order to enter the cell, the cell brush border changes ferry into ferrous iron by ferry reductase enzyme mediated by duodenal cytochrome b protein-like (DCYTB). Transport through the membrane is facilitated by divalent metal transporter (DMT-1 or Nramp-2). Arriving in the cytoplasm of intestinal cells, cytosolic proteins (mobilferrin) iron catch the ferry. Most of the iron will be stored in the form of ferritin in intestinal mucosal cells, a fraction passed through the intestinal capillaries into the basolateral transporter (ferroportin or IREG 1). Passed iron will experience a reduction of ferrous molecules into the ferry by enzyme ferooksidase, then binds to apotransferin in intestinal capillaries.

Figure 4: The process of iron absorption-Phase corporeal: includes the transport of iron in the circulation process, iron utilizationby cells that need, and storage of iron in the body.In circulation, iron never be in the form of free metal, but rather binds to a glycoprotein (-globulin) iron-binding produced by the liver (transferrin). Free iron has properties such as free radicals and can damage tissue. Role of transferrin iron transport to the cells that need especially erythrocyte progenitor cells (normoblas) in the bone marrow. Normoblas surface transferrin receptor which has a very high affinity to the iron in transferrin. Then the iron will enter the cell by endocytosis towards mitochondria. Here the iron is used as a raw material the formation of hemoglobin.Excess iron in the blood is stored in the form of ferritin (iron-apoferitin complex) and hemosiderin in all cells of the body, especially the liver, spleen, bone marrow, and skeletal muscle. In the liver ferritin mainly derived from transferrin and stored at parenkimnya cells, whereas in other organs, ferritin mainly present in mononuclear phagocytic cells (macrophages monocytes) and derived from the demolition of erythrocytes. If the total amount of iron exceeds apoferitin ability to contain the iron is stored in the form of insoluble (hemosiderin). If the number is very low plasma iron, iron is released from ferritin is very easy, not so in hemosiderin. Ferritin in very small amounts in the plasma, where it can be detected levels indicate insufficient iron stores in the body.

Figure 5: Distribution of iron in the bodyB. Synthesis of HemoglobinHemoglobin synthesis began pronormoblas stage, but only few of hemoglobin chains are formed. Similarly, on the stage normoblas basophils. New on the stage of the cell cytoplasm normoblas polikromatofil gets filled with hemoglobin ( 34%). This synthesis continues until reticulocytes are released into the bloodstream.In the first stage of the formation of hemoglobin, 2 succinyl Co-A derived from Krebs cycle binds to two molecules of glycine to form a pyrrole molecule. Four pyrrole combine to form protoporfin IX, which would then be joined to form a compound heme iron. Finally each heme compound will join the long polypeptide chains (globin) to form chains of hemoglobin. Hemoglobin chain has several sub-units depending on the amino acid composition of the polypeptide. Form of hemoglobin that are most numerous in adults is hemoglobin A (combination of two chains and two chains). Each subunit has a heme molecule, therefore, the first chain of hemoglobin requires four iron atoms.Each iron atoms bonded to one oxygen molecule (O2 atom 2).

Figure 6: formation of hemoglobinC. Classification of Degrees of Iron Deficiency and PathogenesisBased on the severity of iron deficiency in the body, iron deficiency can be dividedinto 3 levels:1. Depletion of iron (iron depleted state)A decline in the body's iron reserves, but the provision for erythropoiesis undisturbed. In this phase there is a decrease in serum ferritin, increased iron absorption from the gut, and iron staining on reduced bone marrow smear.2. Iron deficient erythropoiesisEmpty iron stores in the body, but not cause anemia in laboratory due to meet the need for iron, bone marrow did mechanism reduces the cytoplasm so that normoblas formed into shreds, even found normoblas who do not have the cytoplasm (naked nuclei). In addition, the first abnormalities that can be found is the progressive increase in the levels of free protoporphyrin in erythrocytes, transferrin saturation decreased, total iron binding capacity (TIBC) increases. Another very specific parameter is an increase in serum transferrin receptor.

Figure 7: Overview of the bone marrow smear iron deficiency anemia patients3. Iron deficiency anemiaWhen iron will continue to diminish erythropoiesis increasingly disturbed, thus decreasing hemoglobin levels followed by a decrease in the number of erythrocytes. Consequently mikrositer hypochromic anemia. At this time there is also a shortage of iron in the epithelium, nails, and some enzymes that cause a variety of symptoms.Some of the negative effects of iron deficiency, in addition to anemia, among others:

1. neuromuscular systemA decline in the function of myoglobin, cytochrome enzymes, and glycerophosphate oxidase which cause disruption of glycolysis resulting in the accumulation of lactic acid which accelerates muscle fatigue.

2. Impaired cognitive and non-cognitive development in childrenDue to a disruption of enzyme aldehyde oxidase and monoamine oxidase, resulting in accumulation of serotonin and catecholamines in the brain.

3.Defisiensi iron causes reduced neutrophil myeloperoxidase enzyme activityThere by reducing cellular immunity. Especially when regarding pregnant women, will be increase the risk of prematurity and parturition disorders.

D. Symptoms of iron deficiency anemiaClassified into three major categories:1. Common symptoms of anemia (anemic syndrome)Encountered when the hemoglobin level falls below 7 g / dl. In the form of weakness, lethargy, fatigue, and eye-berkunang berkunang. In iron deficiency anemia Hb decline is gradual so that the syndrome is not too flashy.2. Typical symptoms of iron deficiency,: Koilonychia (such as spoon nails, brittle, vertical striped) Atrophy of the optic disc tongue Cheilosis (angular stomatitis) Dysphagia, caused by epithelial damage resulting hypopharynx Web formation Atrophy of the gastric mucosa, causing aklorhidria Symptoms of anemia hypochromic-mikrositer, dysphagia, and atrophy of the optic disc tongue, Called Plummer Vinson syndrome or Paterson Kelly.3. Symptoms due to the underlying diseaseFor example, disruption of BAB in anemia due to Ca-colonE. LaboratoryLaboratory abnormalities that can be found are:1. Levels of hemoglobin and erythrocytes index:Mikrositer hypochromic anemia (decrease in MCV and MCH)MCHC decreased in iron deficiency anemia are more severe and lastslong timeIf the SADT are anisocytosis, an early sign ofiron deficiencyIn extreme mikrositer hypochromic anemia are poikilositosis (cellrings, pencil cells, target cells)2. Concentrations decreased serum iron and TIBC increasedTIBC showed apotransferin to iron saturation levels, whiletransferrin saturation is calculated from:

Serum iron concentration has a diurnal cycle, reaching peak levelsat 8-10 am.3. Decreased serum ferritin levelsSerum ferritin is a laboratory test for the diagnosis of iron deficiency anemia are the most powerful, reliable and practical enough. Figures normal serum ferritin can not rule out the diagnosis of iron deficiency, but serum ferritin> 100 mg / dl has been able to make sure there is no deficiency.4. Increased erythrocyte protoporphyrinFigures normal 100 mg / dl indicate the presence of iron deficiency.5. The increase in serum transferrin receptor (normal 4-9 g / dl), is used to distinguish iron deficiency anemia with anemia of chronic disease.6. Description of bone marrow smear shows the number of basophils normoblasincreased, accompanied by a decrease in the next stage.There is also mikronormoblas (little cytoplasm and irregular shapes. Painting bone marrow with Prussian blue is the gold standard of diagnosis of iron deficiency that would yield negative sideroblasts (normoblas ferritin-containing granules in the cytoplasm, the normal 40-60%).7. Examination of finding the cause of deficiency, eg stool examination, bariumenema, colon in loops, etc.F. DiagnosisThree stages to diagnose an iron deficiency anemia: 1). Determine the presence of anemia 2). Ensuring the presence of iron deficiency 3). Determining the cause of the deficiency. In laboratory used Kerlin modification criteria for diagnosis: hypochromic anemia mikrositer on SADT OR MCV