Anemia Iron 1

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ANEMIA OF IRONABNORMAL

METABOLISM


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Etiologic Classification & Major DiagnosticFeatures of Anemia in Children

Etiologic Classification Diagnostic Features

I.Impaired red cell formationA.DeficiencyDecreased dietary intake (e.g, excessive milk-Iron-deficiency anemia, vegan-vit.B 12 deficiencyIncreased demand, e.g, growth (iron)Hemolysis (folic acid)Decreased absorptionSpecific: intrinsic factor lack (vit. B 12)Generalized: malabsorption syndrome ( e.g,Folic acid, iron)Increased lossAcute: hemorrhage (iron)Chronic: gut bleeding (iron)


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1 . Iron deficiency Hypochromic, microcyticred cell; low MCV, low MCH, lowMCHC, high RDW, a low serumferritin, high FEP, guaiac positivity

2. Folate deficiency Macrocytic red cell, highMCV, high RDW,megaloblastic marrow,

serum & red cell folate

3. Vitamin B 1 2 deficiency Macrocytic red cell, highMCV, high RDW,megaloblastic marrow, lowserum B 12 gastric acidity;Schilling test

4. Vitamin C deficiency Clinical scurvy5. Protein deficiency Kwashiorkor

6. Vitamin B 6 deficiency Hypochromic red cells,sideroblastic bone marrow,high serum ferritin


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7 . Thyroxine deficiency Clinical cretinism, low T 4,high TSH

B. Bone marrow failure1 .Failure of a single cell line

a. Megakaryocytes(1) Amegakaryocytic thrombocytopenic

purpurab. Red cell precursors(1) Congenital red cell aplasia

(Diamond-Blackfan anemia)(2) Acquired red cell aplasia (transient

erythroblastopenia of childhood,

TEC)

Limb abnormalities, absent

megakaryocytes

Absent red cell precusors

Absent red cell precusors

c. White cell precursors

(1) Congenital neutropenia Neutropenia, recurrentinfection


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3. Infiltrationa. De novo (e.g, leukemia)

b. Secondary (e.g, neuroblastoma,lymphoma)

Bone marrow:

Morphology,cytochemistry,immunologic markers,cytogenetics

VMA, skeletal survey,bone marrow

c. Dyshematopoietic anemia (decreasedErythropoiesis, decreased iron utilization

1. Infection2. Renal failure & hepatic disease

3. Disseminated malignancy4. Connective tissue diseases

Evidence of systemicIllnesBUN &liver-functiontestsClinical evidenceRheumatoid arthtritis


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II Bllod lossIII Hemolytic anemiaA. Corpuscular 1. Membrane defects (spherocytosis,

elliptocytosis)2. Enzymatic defects (pyrivate kinase, G6PD)

3. Hemoglobin defectsa. Hemeb. Globin(1) Qualitative (e.g, sickle cell)(2) Quantitative (e.g, thalassemia)

Overt or occult-guaiac

Morphology osmoticfragility

Autohemolysis, enzymeassays

Hb electrophoresisHbF, A 2 content

B. Extracorpuscular 1. Immunea. Isoimmuneb. Autoimmune

(1) Idiopathic

Coombs test

Coombs test, antibodyidentification


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(2) SecondaryImmunologic disorder (e.g, lupus)

One cell line (e.g, red cells)Multiple cell line (e.g, white bloodcells, platelets)

2. Nonimmune (idiopathic, secondary)

Decreased C 3, C 4, CH 50 ;positive ANA

Anemia: Coombs positiveNeutropenia

immunotropenia,thrombocytopenia-ITP

Cause of Iron-Deficiency Anemia

I. Deficiency intakeDietary (milk 0.75 mg iron/ L)

II. Increased demandGrowth (low birth weight, prematurity, low-birth-weight twinsor multiple births, adolescence, pregnancy),cyanotic heart disease


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III. Blood lossA. Perinatal1 . Placental

a. Transplacental bleeding inti maternalcirculation

b. Retroplacental(e.g, premature placental separation)

c. Intraplacentald. Fetal blood loss at or before birth

(e.g, placenta previa)e. Fetofetal bleeding


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2. Umbilicusa. Ruptured umbilical cord (e.g, vasa previa)b. Inadequate cord tyingc. Postexchange transfusion

B. Postnatal1

. Guta. Primary iron-deficiency anemiab. Hypersensitivity to whole cows milkc. Anatomic gut lesions

d. Gastritise. Intestinal parasitesf. Henoch-Schonlein purpura


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2. Gallbladder : hemocholecyst3. Lung : pulmonary hemosiderosis, Goodpastures syndrome,

defective iron mobilization with IgA deficiency4. Nose : recurrent epistaxis5. Uterus : menstrual loss6. Heart : intracardiac myxomata, valvular prostheses or patches7 . Kidney : traumatic hemolytic anemia, hematuria,

nephrotic syndrome (urinary loss of transferrin),hemosiderinurias-chronic intravascular hemolysis(e.g, paroxysmal nocturnal hemoglobinuria,paroxysmal cold hemoglobinuria march hemoglobinuria)

8. Extracorporeal : hemodialysis, traumaIV. Impaired absorption

Malabsorption syndrome, celiac disease,severe prolonged diarrhea, postgastrectomy,inflammatory bowel disease


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Anemia Of Abnormal IronMetabolism

Most frequent types of anemias

Iron deficiency anemia (IDA)Anemia of chronic disease


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Characteristics

Etiology related to abnormalitiesassociated with iron metabolismMaturation disorder Reticulocyte production index (RPI)


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Demographics & EtiologiesIDA

ChildrenIncreased iron needDiet

Pregnancy: Increased needLoss during lactation


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DietInadequate intakeAchlorhydria

Gastric acid required for proper absorption of ironNeeded to convert Fe +3 (non-absorbable form) toFe +2 (absorbable form)

Malabsorption Decrease in absorptivesurfaces of the intestine


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Men/postmenopausal women: Chronicblood loss

Gastrointestinal bleedingEsophageal varicesPeptic ulcer Gastrointestinal neoplasmHemorrhoidsBlood donationChronic intravascular hemolytic disease


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Pathophysiology: Natural CourseIron repletion : Normal iron stores

Iron depletion : Increased utilization of storage iron

Iron deficiencyAbsent bone marrow iron storesNo peripheral anemia

IDAAbsent bone marrow iron stores andPeripheral anemia and associated

morphology


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Hemogram Patterns

Moderate cases

q Hgb

q Hct q MCVq MCH

Normocytic/normochromic

S evere cases

q q q Hgb

q q q Hct q q q MCVq q q MCH

Microcytic/hypochromicPoikilocytosis


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Primary Laboratory Investigation

RBC morphologyAnisocytosis

PoikilocytosisMicrocytosisHypochromia

>1/3 Total Dia.


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Iron Deficiency Morphology

Moderate Severe


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Tissue Effects of Iron Deficiency

I. Gastrointestinal tractA. Anorexia common & early

1. Increased proportion of low-weight percentiles2. Depression of growth

B. Pica-pagophagia (ice), geophagia (sand)C. Atropic glossitisD. DysphagiaE. Esophageal webs (Kelly-Paterson syndrome)

F. Reduced gastric acidityG. Leaky gut syndrome1. Guaiac-positive stool, isolated2. Exudative enteropathy: gastrointestinal loss of protein,

albumin, immunoglobulins, coopper, calcium, red cells


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H. Malabsorption syndrome1. Iron only

2. Generalized malabsorption: xylose, fat, vit.A, duodenojejunalmucosal atrophy

I. BeeturiaJ. Decrease cytochrome oxidase activity & succinic dehydrogeneseK. Decrease disaccharidasesL. Increased absorption of lead & cadmiumM. Increased intestinal permeability index

II. Central nervous systemA. Irritability

B. FatigueC. Conduct disordersD.Lower mental & motor developmental test score on the Bayley Scale,

which may be long-lasting


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E. Increased tolerance to digitalisIV. Musculoskeletal system

A. deficiency of myoglobin & cytochrome CB. Impaired performance of a brief intense exercise taskC. Decreased physical performance in prolonged endurance workD. Rapid development of tissue lactic acidosis in exercise &

a decrease in mitocondrial E -glycerophosphate oxidase activityE. Radiographic changes in bone-widening of diploeic spacesF. Adverse effect on fracture healingV. Immunologic systemThere is conflicting information as to the effect on the immunologic

system of iron deficiency anemiaA. Evidence of increased propensity to infection1 . Clinical

a. Reduction of acute illness in iron-deficient childrenby iron treatment & improved rate of recovery


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b. Increased frequency of respiratory infection in iron deficiency2. Laboratory

a. Impaired leukocyte transformationb. Impaired granulocyte killing & nitroblue tetrazolium (NBT) reductionby granulocytes

c. Decreased myeloperoxidase in leukocytes & small intestined. Decrease cutaneus htpersensitivity.

e. Increased susceptibility tio infection in iron-deficient animalsB. Evidence of decreased propensity for infection

1 . Clinicala. Lower frequency of bacterial infection

b. Increased frequency of infection in iron overload2. Laboratory

a.Transferrin inhibition of bacterial growth by binding iron so that no freeiron is available for growth of microorganisms

b. Enhancement of growth of nonpathogenic bacteria by iron


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VI. Cellular changesA. Red cells

1. Infective erythropoiesis2. Decreased red cell survival3. Increased autohemolysis4. Increased red cells rigidity5. Increased susceptibility to sulfhydryl inhibitors6. Decreased heme production7. Decreased globin & E- chain synthesis8. Precipitation of E -globin monomers to cell membrane9. Decreased glutathione peroxidase & catalase activity

a. Inefficient H 2O 2 detoxificationb. Greater susceptibility to H 2O 2 hemolysisc. Oxidative damage to cell membraned. Increased cellular rigidity


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10. Increased rate of glycolysis: glucose 6-phosphatase dehydrogenase6 - phosphogluconate dehydrogenase, 2.3-diphosphoglycerate

(2.3-DPG), & glutathione

11. Increased in NADH-methemoglobin reductase12. Increased in erythrocyte glutamic oxaloacetic transaminase (EGOT)13. Increased in free erythrocyte protoporphyrin14. Impairment of DNA & RNA synthesis in bone marrow cells

B. Other tissues1. Reduction in heme-containing enzymes (cytochrome C, cytochrome oxidas2. Reduction in iron-dependent enzymes (succinic dehydrogenase aconitase)3. Reduction in monoamine oxidase (MAO)4. Increased excretion of urinary norepinephrine

5. Reduction in tyrosine hydroxylase (enzyme converting tyrosine todihydroxyphenylalanine)

6. Alterations in cellular growth, DNA, RNA, & protein7. Persistent deficiency of brain iron following short-term deprivation8. Reduction in plasma zinc


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Diagnosis:1. Hemoglobin : Hemoglobin is below2. Red cell indices : MCV, MCH, & MCHC are lower

RDW is one of the best screening tests for iron deficiency3. Blood smear:red cells are hypochromic & microcytic,

generally occuring only when Hb falls below 10 g/dl4. Reticulocyte count: usually normal5. Platelet count: the platelet count varies from

thrombocytopenia to thrombocytosis6. Free erythrocyte protoporphyrin: FEP level is elevated7. Serum ferritin : A concentration of less than 12 ng/ml

suggest irondeficiency8. Serum iron & iron saturation percentage9. Prussian Blue (iron) stain10.Serum transferrin receptor


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Prussian Blue (Iron) Stain

Assessment of storage iron in the bonemarrow

Blue-green stain indicates presence of storage iron

Storage iron mostly confined tomacrophages

Small percent in sideroblasts


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Prussian Blue (Iron) Stain

ConsiderationsPositive control films must be usedRinsing with tap water may causeoverstaining/false positives


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BMP IRON DEFICIENCY PRUSSIAN BLUE


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Treatment:

Nutritional Counseling

1. Maintain breast feeding at least 6 months, if possibl2.Use an iron-fortified (6-12 mg/l) infant formula until

1 year of age (formula is preferred to whole cows milk).Restrict milk to 1 pint/day

3. Use iron-fortified cereal from 6 months to 1 year 4.Use evaporated milk or soy-based formula when iron

deficiency is caused by hypersensitivity to cows milk5. Provide suplemental iron for low birth weight infant

a. Infants 1.5 2.0 Kg : 2mg/kg/day suplemental ironb. Infants 1.0 -1.5 Kg : 3mg/kg/day suplemental iron

c. Infants < 1.0 Kg : 4mg/kg/day suplemental iron6.Facilitators of iron absorption such vit.C-rich food, meat, fish,& poultry should be included in the diet, & inhibitors of iron absorption such as tea, phosphate, & phytates commonin vegetarian diets should be eliminated


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O ral Iron Medication

1.Product: ferrous iron (e.g, ferrous gluconate, ferrous ascorbate,ferrous lactate, ferrous succinate, ferrous fumarate,

ferrous glycine sulafate) is effective.

2. Dose: 1.5 2.0 mg/kg elemental iron three times daily.Older children : ferous sulfate (0.2g) or ferrous gluconate (0.3 g)given three times daily to provide 100-200 mg elemental iron

3. Duration: 6 8 weeks after Hb level is restored to normal


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Parenteral Therapy

Iron-dextran complex I.M (Imferon )Indications:

1. Noncompliance with oral administration of iron2. Severe bowel disease

(e.g inflammatory bowel disease) ;use of oral iron might aggravate

the underlying disease of the gut


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Anemia Iron 1