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Nutritional Deficiency Anemias

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Title: Nutritional Deficiency Anemias


1
Nutritional Deficiency Anemias
  • Darshan Mehta, MD
  • Department of Internal Medicine
  • University of Illinois-Chicago

2
Anemia
  • Definition
  • Reduction in blood transport of oxygen due to a
    deficiency in red blood cells
  • Parameters of Anemia
  • Hematocrit Percentage of blood volume as RBCs
  • Hemoglobin Concentration of hemoglobin in blood
  • Mean Corpuscular Volume (MCV) Average size of
    RBC
  • Mean Corpuscular Hemoglobin (MCH) Average
    hemoglobin content of RBC
  • RDW range of deviation around average

3
Mechanisms of Anemia
  • Marrow production defects (hypoproliferation)
  • Low reticulocyte count
  • Little or no change in red cell morphology (a
    normocytic, normochromic anemia
  • Red cell maturation defects (ineffective
    erythropoiesis)
  • Slight to moderately elevated reticulocyte count
  • Macrocytic or microcytic anemia
  • Decreased red cell survival (blood loss/
    hemolysis).

4
Classification of anemias by MCV
  • Microcytic (lt80 fL)  
  • Iron deficiency  
  • Thalassemia 
  • Anemia of chronic disease
  • Macrocytic (gt100 fL)
  • Vitamin B12 deficiency
  • Folate deficiency  
  • Myelodysplasia
  • Chemotherapy
  • Liver disease   
  • Increased reticulocytosis
  • Myxedema
  • Normocytic
  • Anemia of chronic disease
  • Aplasia
  • Protein-energy malnutrition
  • Chronic renal failure
  • Post-hemorrhagic

5
Initial Evaluation
  • History and Physical Exam
  • Eating ice or clay
  • Dyspnea
  • Conjunctival pallor
  • Chest Pain
  • Medications
  • Laboratory evaluation
  • CBC with differential
  • Peripheral Smear
  • Reticulocyte count
  • Iron Studies

6
Nutrient Roles in Erythropoesis
7
Iron Stores
  • Humans contain 2.5 g of iron, with 2.0 - 2.5 g
    circulating as part of heme in hemoglobin
  • Another 0.3 g found in myoglobin, in heme in
    cytochromes, and in Fe-S complexes
  • Iron stored in body primarily as protein
    complexes (ferritin and hemosiderin)

8
Nutritional Iron Balance
  • Intake
  • Dietary iron intake
  • Medicinal iron
  • Red cell transfusions
  • Injection of iron complexes
  • Excretion
  • Gastrointestinal bleeding
  • Menses
  • Losses can be as much as 4 - 37mg/menstrual cycle
  • Other forms of bleeding
  • Loss of epidermal cells from the skin and gut

9
Iron Absorption
  • Dietary iron content is closely related to total
    caloric intake (approximately 6 mg of elemental
    iron per 1000 calories)
  • Iron bioavailability is affected by the nature of
    the foodstuff, with heme iron (e.g., red meat)
    being most readily absorbed
  • Heme irongt Organic iron (Ferrous gluconate) gt
    Inorganic iron (ferrous sulfate)
  • Average iron intake in an adult male is 15 mg/d
    with 6 absorption average female, the daily
    intake is 11 mg/d with 12 absorption
  • Acid pH and presence of reducing agents ascorbic
    acid (vitamin C) reduces Fe to Fe which
    promotes passage across intestinal mucosa
  • Vegetarians are at an additional disadvantage
    because certain foodstuffs that include phytates
    and phosphates reduce iron absorption by about
    50
  • Takes place in the mucosa of the proximal small
    intestine
  • Absorption increase to 20 in iron-deficient
    persons

10
Dietary Sources of Iron
  • Red meat gt poultry fish
  • In U.S., 20 mg iron added/lb of flour
  • Baked bread contains 28 mg iron/kg
  • Equivalent to the iron content of beef
  • Iron cooking pots
  • Plants are generally not good sources because of
    oxalate, phytate, tannins, etc.
  • Spinach has a lot of iron, but has 780 mg
    oxalate/100 g
  • Note - Heme iron absorption from diet not
    affected by ascorbate or phytate

11
Iron Exchange
  • 80 of iron passing through the plasma
    transferrin pool is recycled from broken-down red
    cells
  • Absorption of about 1 mg/d is required from the
    diet in men, 1.4 mg/d in women to maintain
    homeostasis

12
Iron Deficiency Anemia
  • Facts and Figures
  • Most common cause of anemia
  • 500 million cases worldwide
  • Prevalence is higher in less developed countries
  • Unique Physical Exam findings
  • Cheilosis
  • fissures at the corners of the mouth
  • Koilonychia
  • spooning of the fingernails

13
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14
Causes of Iron Deficiency
  • Increased demand for iron and/or hematopoiesis
  • Rapid growth in infancy or adolescence
  • Pregnancy
  • Erythropoietin therapy
  • Increased iron loss
  • Chronic blood loss
  • Menses
  • Acute blood loss
  • Blood donation
  • Phlebotomy as treatment for polycythemia vera
  • Decreased iron intake or absorption
  • Inadequate diet
  • Malabsorption from disease (sprue, Crohn's
    disease)
  • Malabsorption from surgery (post-gastrectomy)
  • Acute or chronic inflammation

15
Iron Deficiency Anemia
  • Hypochromic red cell
  • Microcytic cell
  • Target cell

16
Stages of Iron Deficiency
17
Treatment of Iron Deficiency
  • Red Blood Cell Transfusion
  • Oral Iron Therapy
  • Ferrous sulfate
  • Ferrous fumarate
  • Ferrous gluconate
  • Parenteral Iron

18
Iron Supplementation in special populations
  • Pregnant Women
  • During the last two trimesters, daily iron
    requirements increase to 5 to 6 mg
  • Infancy
  • Normal-term infants are born with sufficient iron
    stores to prevent iron deficiency for the first
    45 months of life
  • Thereafter, enough iron needs to be absorbed to
    keep pace with the needs of rapid growth
  • Nutritional iron deficiency is most common
    between 6 and 24 months of life

19
Megaloblastic Anemia
  • Due to impaired DNA synthesis
  • Affects cells primarily having relatively rapid
    turnover, especially hematopoietic precursors and
    gastrointestinal epithelial cells
  • Cell division is sluggish, but cytoplasmic
    development progresses normally, so megaloblastic
    cells tend to be large, with an increased ratio
    of RNA to DNA.
  • Megaloblastic erythroid progenitors tend to be
    destroyed in the marrow
  • Marrow cellularity is often increased but
    production of red blood cells (RBC) is decreased

20
Causes of Megaloblastic Anemia
  • Vitamin B12 Deficiency
  • Inadequate intake vegans (rare) 
  • Malabsorption 
  • Defective release of cobalamin from food 
  • Gastric achlorhydria
  • Partial gastrectomy
  • Drugs that block acid secretion 
  • Inadequate production of intrinsic factor (IF) 
  • Pernicious anemia
  • Total gastrectomy
  • Disorders of terminal ileum
  • Sprue
  • Regional enteritis
  • Intestinal resection
  • Competition for cobalamin 
  • Fish tapeworm (Diphyllobothrium latum)
  • Bacteria "blind loop" syndrome 
  • Drugs p-aminosalicylic acid, colchicine, neomycin

21
Clinical Manifestations of Vitamin B12 Deficiency
  • Hematologic
  • Macrocytic Anemia
  • Gastrointestinal
  • Glossitis
  • Anorexia
  • Diarrhea
  • Neurologic (found in 3/4th of individuals with
    pernicious anemia)
  • Numbness and paresthesia in the extremities,
    Weakness, Ataxia
  • Sphincter disturbances
  • Disturbances of mentation
  • Mild irritability and forgetfulness to severe
    dementia or frank psychosis.
  • Demyelination, Axonal degeneration, and then
    Neuronal death
  • Last stage is irreversible

22
Megaloblastic Anemia
  • Macrocytic RBC
  • Hypersegmented Neutrophil

23
Vitamin B12 Absorption Oral Phase
24
Vitamin B12 Absorption Gastric Phase
25
Vitamin B12 Absorption Intestinal Phase
26
Vitamin B12 Deficiency
  • Any interruption along this path can result in
    cobalamin deficiency
  • Gastrectomy results in low production of IF
  • Terminal ileal resection (gt100 cm), decreases the
    site of absorption of B12-IF complex

27
Pernicious Anemia
  • Most common cause of cobalamin deficiency
  • Caused by the absence of IF
  • Atrophy of the mucosa
  • Autoimmune destruction of parietal cells
  • Seen in individuals of northern European descent
    and African Americans
  • Men and women are equally affected
  • Disease of the elderly, the average patient
    presenting near age 60

28
Diagnosis of Vitamin B12 Deficiency
  • Macrocytosis
  • Peripheral blood smear
  • Cobalamin levels
  • Elevated serum methylmalonic acid and
    homocysteine levels
  • Schilling Test

29
Schilling Test
  • Measures B12 deficiency
  • Detects IF deficiency
  • Detects abnormal results in patients with genetic
    defects in B12 absorption, bacterial overgrowth
    of the small bowel, resection/bypass of terminal
    ileum, and pancreatic insufficiency

30
Stage 1
  • Oral dose of radiolabeled cobalamin given
    simultaneously with an IM injection unlabeled
    cobalamin
  • 24 Hour Urine collection
  • Amount radiolabeled activity is measured
  • Normal absorption of B12 and normal renal
    function will excrete gt 7 of radiolabeled B12

31
Stage 2
  • If stage 1 is abnormal, then test is repeated
    following 60 mg of oral IF
  • If the level of urinary radiolabeled B12
    normalizes, then this indicates pernicious anemia

32
Stage 3
  • Small intestine bacterial overgrowth may cause
    B12 malabsorption and an abnormal result in stage
    1 that is not corrected with IF administration in
    stage 2
  • Broad spectrum antibiotics are given for one week
    to eliminate intestinal bacteria and then stage 1
    should normalize

33
Stage 4
  • If pancreatic insufficiency exists, B12
    malabsorption may occur
  • Normalization after pancreatic enzyme therapy
    suggests pancreatic origin

34
Causes of Megaloblastic Anemia
  • Folate Deficiency
  • Inadequate intake unbalanced diet (common in
    alcoholics, teenagers, some infants) 
  • Increased requirements 
  • Pregnancy
  • Infancy
  • Malignancy
  • Increased hematopoiesis (chronic hemolytic
    anemias)
  • Chronic exfoliative skin disorders
  • Hemodialysis 
  • Malabsorption 
  • Sprue
  • Drugs Phenytoin, barbiturates, (?) ethanol  
  • Impaired metabolism
  • Inhibitors of dihydrofolate reductase
    methotrexate, pyrimethamine, triamterene,
    pentamidine, trimethoprim
  • Alcohol
  • Rare enzyme deficiencies dihydrofolate
    reductase, others

35
Treatment of Vitamin B12 Deficiency
  • Replacement therapy
  • Parenteral treatment given weekly intramuscularly
    for 8 weeks, followed by intramuscularly every
    month for the rest of the patient's life.
  • Daily oral replacement therapy

36
Folate Deficiency
  • More often malnourished than those with cobalamin
    deficiency
  • Gastrointestinal manifestations
  • More widespread and more severe than those of
    pernicious anemia
  • Diarrhea is often present
  • Cheilosis
  • Glossitis
  • Neurologic abnormalities do not occur

37
Stages of folate deficiency
  1. Negative folate balance (decreased serum folate)
  2. Decreased RBC folate levels and hypersegmented
    neutrophils
  3. Macroovalocytes, increased MCV, and decreased
    hemoglobin

38
Diagnosis of folate deficiency
  • Peripheral blood and bone marrow biopsy look
    exactly like B12 deficiency
  • Plasma folate lt3 ng/mlfluctuates with recent
    dietary intake
  • RBC folatemore reliable of tissue stores lt140
    ng/ml
  • Only increased serum homocysteine levels but NOT
    serum methylmalonic acid levels

39
Treatment of folate deficiency
  • Oral replacement therapy
  • Folate prophylaxis
  • Women planning pregnancy are advised to take 400
    g folic acid daily before conception and until 12
    weeks of pregnancy to prevent neural-tube defects
    (5 mg/day for women with a previous affected
    pregnancy)
  • Folate fortification of cereal grains at 14
    mg/kg has been made mandatory in the USA as an
    additional method of improving the folate status
    of the population.
  • Prophylactic folate is also recommended in other
    states of increased demand such as long-term
    hemodialysis and chronic haemolytic disorders

40
Inappropriate Treatment of Pernicious Anemia With
Folate
  • Vitamin B12 deficiency anemia can be temporarily
    corrected by folate supplementation
  • However, this does not correct the neurologic
    deficits
  • Folate draws vitamin B12 away from neurologic
    system for RBC production and can exacerbate
    combined systems degeneration
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