Medical Nutrition

Therapy for Anemia

 Anemia
• Definition: deficiency in size or number
of red blood cells or amount of
hemoglobin they contain
• Defined as a hemoglobin concentration
below the 95th %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 formation
Classification of Anemia
Based on cell size (MCV)
• Macrocytic (large) MCV 100+ fl
(femtoliters)
• Normocytic (normal) MCV 8-99 fl
• Microcytic (small) MCV<80 fl
Based on hemoglobin content (MCH)
• Hypochromic (pale color)
• Normochromic (normal color)
 Iron Deficiency Anemia

• Characterized by the production of small

(microcytic) erythrocytes and a
diminished level of circulating
hemoglobin
• Last stage of iron deficiency
• Represents the end point of a long period
of iron deprivation
Causes of
Iron Deficiency Anemia
• Inadequate ingestion
• Inadequate absorption
• Defects in release from stores
• Inadequate utilization
• Increased blood loss or excretion
• Increased requirement
Stages of Iron Deficiency
• Stage 1: moderate depletion of iron stores;
no dysfunction
• Stage 2: Severe depletion of iron stores; no
dysfunction
• Stage 3: Iron deficiency
• Stage 4: Iron deficiency (dysfunction and
anemia)
Tests for Iron Deficiency
• 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
Tests for Iron Deficiency
• 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)
• Not affected by hematocrit or other
causes of anemia; specific to iron
deficiency
Tests for Iron Deficiency
• Total iron binding capacity (TIBC)—capacity of
transferrin to bind iron
• Transferrin—globulin that binds/transports Fe
from gut wall to tissues
• Percent saturation of transferrin (calculate by
dividing serum iron by the TIBC)
• TIBC increases in iron deficiency

• As stored iron falls, saturation of transferrin

decreases
Iron Deficiency:
Clinical Findings
Early Late
• Inadequate muscle • Defects in epithelial
function tissues
• Growth abnormalities • Gastritis
• Epithelial disorders • Cardiac failure
• Reduced
immunocompetence
 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.)
Supplementation for
Iron Deficiency Anemia
• Oral iron salts
• Ferrous forms better absorbed than ferric
(ferrous sulfate, ferrous lactate, ferrous
fumarate)
• Best 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 children
• Generally supplement for 3 months (4-5 months
if taken with meals)
Nutritional Management of Iron-
Deficiency Anemia
• Increase absorbable iron in the diet
• Include vitamin C at every meal
• Include meat, fish or poultry at every meal
• Decrease tea and coffee consumption
Restoring Iron Levels
Factors to consider:
• Bioavailability of iron—the lower the Fe
stores, the greater the rate of absorption
• Vitamin C—binds iron to form a readily
absorbed complex
• Heme sources (meat, poultry, fish)—
about 15% absorbable
• Nonheme iron (grains, vegetables,
eggs)—about 3% to 8% absorbable
Supplementation for
Iron Deficiency Anemia
If patient fails to respond
• May not be taking supplements
• May not be absorbing iron (celiac disease,
steatorrhea, hemodialysis)
• May be bleeding
• May need IV iron dextran (can cause
allergic reactions)
Hemochromatosis
A genetically determined form of iron
overload that results in progressive
hepatic, pancreatic, cardiac, and other
organ damage
Hemochromatosis
• 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 blacks
• Present 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 frequently
• Homozygotes absorb three times more iron
from food than other people
• Even heterozygotes may be at risk for iron
overload, increasing risk of heart disease
Hemochromatosis: Risk Factors
• Higher 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 may develop symptoms in their 30s but
may not be diagnosed until their 50s
• Women often develop symptoms after
menopause
Hemochromatosis: Symptoms
• Joint pain
• Fatigue
• Lack of energy
• Abdominal pain
• Loss of sex drive
• Heart problems
• Abnormal pigmentation of the skin,
making it look gray or bronze
Hemochromatosis:
if untreated, may result in
• Arthritis
• Liver disease: cirrhosis, cancer,
liver failure
• Damage to the pancreas, leading
to diabetes
• Heart abnormalities, including
arrhythmias and heart failure
• Impotence or early menopause
• Thyroid or adrenal problems
Hemochromatosis:
Diagnosis and Treatment
• Testing: 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
iron
• Avoidance of iron supplements and sources of iron
in the diet, especially heme iron
• Awareness of iron cooking vessels
Disorders Associated with
Iron Toxicity
• Thalassemias
• Sideroblastic anemias
• Chronic hemolytic anemia
• Aplastic anemia
• Ineffective erythropoiesis
• Transfusional iron overload
• Alcoholic cirrhosis
Megaloblastic Anemias
• A 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 B12 deficiency
Static Test for Folate/B12 Status

Folate
• Measured 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)
• Can also test serum in fasting patient
B12
• Measured in serum
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 B6
• 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 malabsorption
Pernicious Anemia
A macrocytic, megaloblastic anemia caused by a
deficiency of vitamin B12.
• Usually secondary to lack of intrinsic factor
(IF)
• May 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 disease
Symptoms of
Pernicious Anemia
• Paresthesia (especially numbness and
tingling in hands and feet)
• Poor muscular coordination
• Impaired memory and hallucinations
• Damage can be permanent
Vitamin B12 Depletion
• Stage I—early negative vitamin B12 balance
• Stage II—vitamin B12 depletion
• Stage III—damaged metabolism: vitamin B12
deficient erythropoiesis
• Stage IV—clinical damage including vitamin B12
anemia
• Pernicious anemia—numbness in hands and feet;
poor muscular coordination; poor memory;
hallucinations
Causes of Vitamin B12 Deficiency
• Inadequate ingestion
• Inadequate absorption
• Inadequate utilization
• Increased requirement
• Increased excretion
• Increased destruction by antioxidants
Treatment of B12 Deficiency
• Before 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 necessary
• Also 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 vegetables
Folic Acid Deficiency
• Tropical sprue; pregnancy; infants born to
deficient mothers
• Alcoholics
• People taking medications chronically that affect
folic acid absorption
• Malabsorption syndromes
Causes of Folate Deficiency
• Inadequate ingestion
• Inadequate absorption
• Inadequate utilization
• Increased requirement
• Increased excretion
• Increased destruction
• Vitamin B12 deficiency can cause folate
deficiency due to the methylfolate trap
Methylfolate Trap
• 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
THFA
Stages of Folate Depletion and
Deficiency
• Stage I—early negative folate balance (serum
depletion)
• Stage II—negative folate balance (cell
depletion)
• Stage III—damaged folate metabolism with
folate-deficient erythropoiesis
• Stage IV—clinical folate deficiency anemia
Diagnosis of Folate Deficiency
• Folate stores are depleted after 2-4
months on deficient diet
• Megaloblastic anemia, low leukocytes
and platelets
• To differentiate from B12, measure serum
folate, RBC folate (more reflective of
body stores) serum B12
• High formiminoglutamic acid (FIGLU) in
the urine also diagnostic
Other Nutritional Anemias
• Copper deficiency anemia
• Anemia of protein-energy malnutrition
• Sideroblastic (pyridoxine-responsive) anemia
• Vitamin E–responsive (hemolytic) anemia
Copper Deficiency
• Copper 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
normal
• Copper 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 copper
• Diagnosis is important, since more iron won’t
help and may interfere with copper absorption
Sideroblastic Anemia
• Microcytic, hypochromic form
• Inherited defect of heme synthesis enzyme
• High serum and tissue iron levels
• Buildup of immature sideroblasts—hence the
name
• B6 is essential—must replace 25 to 100 times
the RDA; may need lifelong replacement
• Pyridoxine-responsive anemia, distinguished
from anemia caused by pyridoxine deficiency
Hemolytic Anemia
• Oxidative damage to cells—lysis occurs
• Vitamin E is an antioxidant that seems to be
protective.
• This anemia can occur in newborns,
especially preemies.
Nonnutritional Anemias
• Sports anemia (hypochromic microcytic
transient anemia)
• Anemia of pregnancy: dilutional
• Anemia of inflammation, infection, or
malignancy (anemia of chronic disease)
• Sickle cell anemia
• Thalassemias
Sports Anemia
• Transient—usually in athletes who are runners;
from compression of RBCs in feet until they
burst, releasing hemoglobin
• Check lab values
• Counsel about a proper diet
Sickle Cell Anemia
• Protein-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
absorption
• Promote foods high in copper, zinc and folate as
needs are increased due to constant replacement
of erythrocytes
• Zinc supplements may be useful
Thalassemia
• Severe 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 changes
• Iron buildup due to transfusions requires chelation
therapy to remove excess iron
Medical and Nutritional
Management of Anemia
• It is important to be familiar with the
etiology and treatment of nutritional and
non-nutritional anemias
• Many non-nutritional anemias have
nutritional implications
• It is critical to DIAGNOSE before treating
anemias with nutritional or non-nutritional
therapies