1. Medical Nutrition Therapy for Anemia

2. Anemia Definition: deficiency in size or number of red blood cells or amount of hemoglobin they containDefinition: deficiency in size or number of red blood cells or amount of hemoglobin they contain Defined as a hemoglobin concentration below the 95 th %ile for healthy reference populationsDefined as a hemoglobin concentration below the 95 th %ile for healthy reference populations Not a disease but a symptom of conditions including extensive blood loss, excessive blood cell destruction, or decreased blood cell formationNot a disease but a symptom of conditions including extensive blood loss, excessive blood cell destruction, or decreased blood cell formation

3. Classification of Anemia Based on cell size (MCV) Macrocytic (large) MCV 100+ fl (femtoliters)Macrocytic (large) MCV 100+ fl (femtoliters) Normocytic (normal) MCV 8-99 flNormocytic (normal) MCV 8-99 fl Microcytic (small) MCV<80 flMicrocytic (small) MCV<80 fl Based on hemoglobin content (MCH) Hypochromic (pale color)Hypochromic (pale color) Normochromic (normal color)Normochromic (normal color)

4. Iron Deficiency Anemia Characterized by the production of small (microcytic) erythrocytes and a diminished level of circulating hemoglobinCharacterized by the production of small (microcytic) erythrocytes and a diminished level of circulating hemoglobin Last stage of iron deficiencyLast stage of iron deficiency Represents the end point of a long period of iron deprivationRepresents the end point of a long period of iron deprivation

5. Causes of Iron Deficiency Anemia Inadequate ingestionInadequate ingestion Inadequate absorptionInadequate absorption Defects in release from storesDefects in release from stores Inadequate utilizationInadequate utilization Increased blood loss or excretionIncreased blood loss or excretion Increased requirementIncreased requirement

6. Stages of Iron Deficiency Stage 1: moderate depletion of iron stores; no dysfunctionStage 1: moderate depletion of iron stores; no dysfunction Stage 2: Severe depletion of iron stores; no dysfunctionStage 2: Severe depletion of iron stores; no dysfunction Stage 3: Iron deficiencyStage 3: Iron deficiency Stage 4: Iron deficiency (dysfunction and anemia)Stage 4: Iron deficiency (dysfunction and anemia)

7. Tests for Iron Deficiency Serum iron: poor indicator, highly variable day to day and during the day Serum iron: poor indicator, highly variable day to day and during the day Ferritin - most sensitive—chief storage form of iron; directly proportional to iron stored in cells Ferritin - most sensitive—chief storage form of iron; directly proportional to iron stored in cells

8. Tests for Iron Deficiency Zinc protoporphyrin/heme ratio (ZPPH) protoporphyrin binds iron to form heme or zinc to form zinc protoporphyrin Zinc protoporphyrin/heme ratio (ZPPH) protoporphyrin binds iron to form heme or zinc to form zinc protoporphyrin In the presence of iron deficiency, ratio will rise (iron deficiency defined as ratio>1:12,000) In the presence of iron deficiency, ratio will rise (iron deficiency defined as ratio>1:12,000) Not affected by hematocrit or other causes of anemia; specific to iron deficiency Not affected by hematocrit or other causes of anemia; specific to iron deficiency

9. Tests for Iron Deficiency Total iron binding capacity (TIBC)—capacity of transferrin to bind iron Total iron binding capacity (TIBC)—capacity of transferrin to bind iron Transferrin—globulin that binds/transports Fe from gut wall to tissues Transferrin—globulin that binds/transports Fe from gut wall to tissues Percent saturation of transferrin (calculate by dividing serum iron by the TIBC) Percent saturation of transferrin (calculate by dividing serum iron by the TIBC) TIBC increases in iron deficiency TIBC increases in iron deficiency As stored iron falls, saturation of transferrin decreases As stored iron falls, saturation of transferrin decreases

10. Iron Deficiency: Clinical Findings Early Inadequate muscle functionInadequate muscle function Growth abnormalitiesGrowth abnormalities Epithelial disordersEpithelial disorders Reduced immunocompetenceReduced immunocompetence Late Defects in epithelial tissues Gastritis Cardiac failure

11. Koilonchia—A Sign of Iron Deficiency (From Callen JP, Greer KE, Hood AF, Paller AS, Swinyer LJ. Color Atlas of Dermatology. Philadelphia: W.B. Saunders, 1993.)

12. Supplementation for Iron Deficiency Anemia Oral iron saltsOral iron salts Ferrous forms better absorbed than ferric (ferrous sulfate, ferrous lactate, ferrous fumarate)Ferrous forms better absorbed than ferric (ferrous sulfate, ferrous lactate, ferrous fumarate) Best absorbed on an empty stomach but if irritation occurs, give with mealsBest absorbed on an empty stomach but if irritation occurs, give with meals Dosage 50-200 mg of elemental iron for adults; 6 mg/kg body weight for childrenDosage 50-200 mg of elemental iron for adults; 6 mg/kg body weight for children Generally supplement for 3 months (4-5 months if taken with meals)Generally supplement for 3 months (4-5 months if taken with meals)

13. Nutritional Management of Iron- Deficiency Anemia Increase absorbable iron in the dietIncrease absorbable iron in the diet Include vitamin C at every mealInclude vitamin C at every meal Include meat, fish or poultry at every mealInclude meat, fish or poultry at every meal Decrease tea and coffee consumptionDecrease tea and coffee consumption

14. Restoring Iron Levels Factors to consider: Bioavailability of iron—the lower the Fe stores, the greater the rate of absorptionBioavailability of iron—the lower the Fe stores, the greater the rate of absorption Vitamin C—binds iron to form a readily absorbed complexVitamin C—binds iron to form a readily absorbed complex Heme sources (meat, poultry, fish)— about 15% absorbableHeme sources (meat, poultry, fish)— about 15% absorbable Nonheme iron (grains, vegetables, eggs)—about 3% to 8% absorbableNonheme iron (grains, vegetables, eggs)—about 3% to 8% absorbable

15. Supplementation for Iron Deficiency Anemia If patient fails to respond May not be taking supplementsMay not be taking supplements May not be absorbing iron (celiac disease, steatorrhea, hemodialysis)May not be absorbing iron (celiac disease, steatorrhea, hemodialysis) May be bleedingMay be bleeding May need IV iron dextran (can cause allergic reactions)May need IV iron dextran (can cause allergic reactions)

16. Hemochromatosis A genetically determined form of iron overload that results in progressive hepatic, pancreatic, cardiac, and other organ damage

17. Hemochromatosis It is one of the most common genetic disorders in the U.S.It is one of the most common genetic disorders in the U.S. Present in heterozygous (one gene) form in 12% of nonblacks and 30% of blacksPresent in heterozygous (one gene) form in 12% of nonblacks and 30% of blacks Present in homozygous form (2 gene) in 1 in 200 nonblacks and 1 in 100 blacksPresent in homozygous form (2 gene) in 1 in 200 nonblacks and 1 in 100 blacks Homozygotes will die of iron overload unless they give blood frequentlyHomozygotes will die of iron overload unless they give blood frequently Homozygotes absorb three times more iron from food than other peopleHomozygotes absorb three times more iron from food than other people Even heterozygotes may be at risk for iron overload, increasing risk of heart diseaseEven heterozygotes may be at risk for iron overload, increasing risk of heart disease

18. Hemochromatosis: Risk Factors Higher risk in people of northern European descentHigher risk in people of northern European descent Men tend to manifest symptoms earlier because they have no way to dispose of excess iron (menstruation, pregnancy, lactation)Men tend to manifest symptoms earlier because they have no way to dispose of excess iron (menstruation, pregnancy, lactation) Men may develop symptoms in their 30s but may not be diagnosed until their 50sMen may develop symptoms in their 30s but may not be diagnosed until their 50s Women often develop symptoms after menopauseWomen often develop symptoms after menopause

19. Hemochromatosis: Symptoms Joint painJoint pain FatigueFatigue Lack of energyLack of energy Abdominal painAbdominal pain Loss of sex driveLoss of sex drive Heart problemsHeart problems Abnormal pigmentation of the skin, making it look gray or bronzeAbnormal pigmentation of the skin, making it look gray or bronze

20. Hemochromatosis: if untreated, may result in ArthritisArthritis Liver disease: cirrhosis, cancer, liver failureLiver disease: cirrhosis, cancer, liver failure Damage to the pancreas, leading to diabetesDamage to the pancreas, leading to diabetes Heart abnormalities, including arrhythmias and heart failureHeart abnormalities, including arrhythmias and heart failure Impotence or early menopauseImpotence or early menopause Thyroid or adrenal problemsThyroid or adrenal problems

21. Hemochromatosis: Diagnosis and Treatment Testing: serum ferritin and transferrin saturation can reveal excess stores of iron; followed by HFE (genetic) test and possible liver biopsyTesting: serum ferritin and transferrin saturation can reveal excess stores of iron; followed by HFE (genetic) test and possible liver biopsy Treatment: regular phlebotomy to remove excess ironTreatment: regular phlebotomy to remove excess iron Avoidance of iron supplements and sources of iron in the diet, especially heme ironAvoidance of iron supplements and sources of iron in the diet, especially heme iron Awareness of iron cooking vesselsAwareness of iron cooking vessels

22. Disorders Associated with Iron Toxicity ThalassemiasThalassemias Sideroblastic anemiasSideroblastic anemias Chronic hemolytic anemiaChronic hemolytic anemia Aplastic anemiaAplastic anemia Ineffective erythropoiesisIneffective erythropoiesis Transfusional iron overloadTransfusional iron overload Alcoholic cirrhosisAlcoholic cirrhosis

23. Megaloblastic Anemias A form of anemia characterized by the presence of large, immature, abnormal red blood cell progenitors in the bone marrowA form of anemia characterized by the presence of large, immature, abnormal red blood cell progenitors in the bone marrow 95% of cases are attributable to folic acid or vitamin B 12 deficiency95% of cases are attributable to folic acid or vitamin B 12 deficiency

24. Static Test for Folate/B12 Status Folate Measured in whole blood (plasma and cells) and then in the serum aloneMeasured in whole blood (plasma and cells) and then in the serum alone Difference is used to calculate the red blood cell folate concentration (may better reflect the whole folate pool)Difference is used to calculate the red blood cell folate concentration (may better reflect the whole folate pool) Can also test serum in fasting patientCan also test serum in fasting patientB12 Measured in serumMeasured in serum

25. Functional Tests for Macrocytic Anemias Homocysteine: Folate and B12 are needed to convert homocysteine to methionine; high homocysteine may mean deficiencies of folate, B12 or B6Homocysteine: Folate and B12 are needed to convert homocysteine to methionine; high homocysteine may mean deficiencies of folate, B12 or B6 Methylmalonic acid measurements can be used along with homocysteine to distinguish between B12 and folate deficiencies (↑ in B12 deficiency)Methylmalonic acid measurements can be used along with homocysteine to distinguish between B12 and folate deficiencies (↑ in B12 deficiency) Schilling test: radiolabeled cobalamin is used to test for B12 malabsorptionSchilling test: radiolabeled cobalamin is used to test for B12 malabsorption

26. Pernicious Anemia A macrocytic, megaloblastic anemia caused by a deficiency of vitamin B 12. Usually secondary to lack of intrinsic factor (IF)Usually secondary to lack of intrinsic factor (IF) May be caused by strict vegan dietMay be caused by strict vegan diet Also can be caused by ↓gastric acid secretion, gastric atrophy, H-pylori, gastrectomy, disorders of the small intestine (celiac disease, regional enteritis, resections), drugs that inhibit B12 absorption including neomycin, alcohol, colchicine, metformin, pancreatic diseaseAlso can be caused by ↓gastric acid secretion, gastric atrophy, H-pylori, gastrectomy, disorders of the small intestine (celiac disease, regional enteritis, resections), drugs that inhibit B12 absorption including neomycin, alcohol, colchicine, metformin, pancreatic disease

27. Symptoms of Pernicious Anemia Paresthesia (especially numbness and tingling in hands and feet)Paresthesia (especially numbness and tingling in hands and feet) Poor muscular coordinationPoor muscular coordination Impaired memory and hallucinationsImpaired memory and hallucinations Damage can be permanentDamage can be permanent

28. Vitamin B 12 Depletion Stage I—early negative vitamin B 12 balanceStage I—early negative vitamin B 12 balance Stage II—vitamin B 12 depletionStage II—vitamin B 12 depletion Stage III—damaged metabolism: vitamin B 12 deficient erythropoiesisStage III—damaged metabolism: vitamin B 12 deficient erythropoiesis Stage IV—clinical damage including vitamin B 12 anemiaStage IV—clinical damage including vitamin B 12 anemia Pernicious anemia—numbness in hands and feet; poor muscular coordination; poor memory; hallucinationsPernicious anemia—numbness in hands and feet; poor muscular coordination; poor memory; hallucinations

29. Causes of Vitamin B 12 Deficiency Inadequate ingestionInadequate ingestion Inadequate absorptionInadequate absorption Inadequate utilizationInadequate utilization Increased requirementIncreased requirement Increased excretionIncreased excretion Increased destruction by antioxidantsIncreased destruction by antioxidants

30. Treatment of B12 Deficiency Before 1926 was incurable; until 1948 was treated with liver extractBefore 1926 was incurable; until 1948 was treated with liver extract Now treatment consists of injection of 100 mcg of vitamin B12 once per week until resolved, then as often as necessaryNow treatment consists of injection of 100 mcg of vitamin B12 once per week until resolved, then as often as necessary Also can use very large oral doses or nasal gelAlso can use very large oral doses or nasal gel MNT: high protein diet (1.5 g/kg) with meat, liver, eggs, milk, milk products, green leafy vegetablesMNT: high protein diet (1.5 g/kg) with meat, liver, eggs, milk, milk products, green leafy vegetables

31. Folic Acid Deficiency Tropical sprue; pregnancy; infants born to deficient mothersTropical sprue; pregnancy; infants born to deficient mothers AlcoholicsAlcoholics People taking medications chronically that affect folic acid absorptionPeople taking medications chronically that affect folic acid absorption Malabsorption syndromesMalabsorption syndromes

32. Causes of Folate Deficiency Inadequate ingestionInadequate ingestion Inadequate absorptionInadequate absorption Inadequate utilizationInadequate utilization Increased requirementIncreased requirement Increased excretionIncreased excretion Increased destructionIncreased destruction Vitamin B12 deficiency can cause folate deficiency due to the methylfolate trapVitamin B12 deficiency can cause folate deficiency due to the methylfolate trap

33. Methylfolate Trap In the absence of B12, folate in the body exists as 5- methyltetrahydro- folate (an inactive form)In the absence of B12, folate in the body exists as 5- methyltetrahydro- folate (an inactive form) B12 allows the removal of the 5- methyl group to form THFAB12 allows the removal of the 5- methyl group to form THFA

34. Stages of Folate Depletion and Deficiency Stage I—early negative folate balance (serum depletion)Stage I—early negative folate balance (serum depletion) Stage II—negative folate balance (cell depletion)Stage II—negative folate balance (cell depletion) Stage III—damaged folate metabolism with folate-deficient erythropoiesisStage III—damaged folate metabolism with folate-deficient erythropoiesis Stage IV—clinical folate deficiency anemiaStage IV—clinical folate deficiency anemia

35. Diagnosis of Folate Deficiency Folate stores are depleted after 2-4 months on deficient dietFolate stores are depleted after 2-4 months on deficient diet Megaloblastic anemia, low leukocytes and plateletsMegaloblastic anemia, low leukocytes and platelets To differentiate from B12, measure serum folate, RBC folate (more reflective of body stores) serum B12To differentiate from B12, measure serum folate, RBC folate (more reflective of body stores) serum B12 High formiminoglutamic acid (FIGLU) in the urine also diagnosticHigh formiminoglutamic acid (FIGLU) in the urine also diagnostic

36. Other Nutritional Anemias Copper deficiency anemiaCopper deficiency anemia Anemia of protein-energy malnutritionAnemia of protein-energy malnutrition Sideroblastic (pyridoxine-responsive) anemiaSideroblastic (pyridoxine-responsive) anemia Vitamin E–responsive (hemolytic) anemiaVitamin E–responsive (hemolytic) anemia

37. Copper Deficiency Copper is required for mobilization of iron from storage sitesCopper is required for mobilization of iron from storage sites In copper deficient state, result is low serum iron and hemoglobin, even when iron stores are normalIn copper deficient state, result is low serum iron and hemoglobin, even when iron stores are normal Copper is widespread in foods and needed in tiny amountsCopper is widespread in foods and needed in tiny amounts Sometimes occurs in infants fed deficient formula or cow’s milk, adults and children with malabsorption or on TPN without copperSometimes occurs in infants fed deficient formula or cow’s milk, adults and children with malabsorption or on TPN without copper Diagnosis is important, since more iron won’t help and may interfere with copper absorptionDiagnosis is important, since more iron won’t help and may interfere with copper absorption

38. Sideroblastic Anemia Microcytic, hypochromic formMicrocytic, hypochromic form Inherited defect of heme synthesis enzymeInherited defect of heme synthesis enzyme High serum and tissue iron levelsHigh serum and tissue iron levels Buildup of immature sideroblasts—hence the nameBuildup of immature sideroblasts—hence the name B 6 is essential—must replace 25 to 100 times the RDA; may need lifelong replacementB 6 is essential—must replace 25 to 100 times the RDA; may need lifelong replacement Pyridoxine-responsive anemia, distinguished from anemia caused by pyridoxine deficiencyPyridoxine-responsive anemia, distinguished from anemia caused by pyridoxine deficiency

39. Hemolytic Anemia Oxidative damage to cells—lysis occursOxidative damage to cells—lysis occurs Vitamin E is an antioxidant that seems to be protective.Vitamin E is an antioxidant that seems to be protective. This anemia can occur in newborns, especially preemies.This anemia can occur in newborns, especially preemies.

40. Nonnutritional Anemias Sports anemia (hypochromic microcytic transient anemia)Sports anemia (hypochromic microcytic transient anemia) Anemia of pregnancy: dilutionalAnemia of pregnancy: dilutional Anemia of inflammation, infection, or malignancy (anemia of chronic disease)Anemia of inflammation, infection, or malignancy (anemia of chronic disease) Sickle cell anemiaSickle cell anemia ThalassemiasThalassemias

41. Sports Anemia Transient—usually in athletes who are runners; from compression of RBCs in feet until they burst, releasing hemoglobinTransient—usually in athletes who are runners; from compression of RBCs in feet until they burst, releasing hemoglobin Check lab valuesCheck lab values Counsel about a proper dietCounsel about a proper diet

42. Sickle Cell Anemia Protein-energy malnutrition common; may have poor intake and increased energy needsProtein-energy malnutrition common; may have poor intake and increased energy needs Be careful not to overdo iron in diet or supplements; iron stores are often high due to frequent transfusions; avoid iron rich foods, alcohol, and ascorbic acid which enhance iron absorptionBe careful not to overdo iron in diet or supplements; iron stores are often high due to frequent transfusions; avoid iron rich foods, alcohol, and ascorbic acid which enhance iron absorption Promote foods high in copper, zinc and folate as needs are increased due to constant replacement of erythrocytesPromote foods high in copper, zinc and folate as needs are increased due to constant replacement of erythrocytes Zinc supplements may be usefulZinc supplements may be useful

43. Thalassemia Severe inherited anemia affecting mostly people of Mediterranean extractionSevere inherited anemia affecting mostly people of Mediterranean extraction Defective globin formation in hemoglobin leads to increased blood volume, splenomegaly, bone marrow expansion, facial deformities, osteomalacia, bone changesDefective globin formation in hemoglobin leads to increased blood volume, splenomegaly, bone marrow expansion, facial deformities, osteomalacia, bone changes Iron buildup due to transfusions requires chelation therapy to remove excess ironIron buildup due to transfusions requires chelation therapy to remove excess iron

44. Medical and Nutritional Management of Anemia It is important to be familiar with the etiology and treatment of nutritional and non-nutritional anemiasIt is important to be familiar with the etiology and treatment of nutritional and non-nutritional anemias Many non-nutritional anemias have nutritional implicationsMany non-nutritional anemias have nutritional implications It is critical to DIAGNOSE before treating anemias with nutritional or non-nutritional therapiesIt is critical to DIAGNOSE before treating anemias with nutritional or non-nutritional therapies