Download Nutritional Deficiency Anemias - University of Illinois at Chicago

Nutritional Deficiency
Anemias
Darshan Mehta, MD
Department of Internal Medicine
University of Illinois-Chicago
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
Mechanisms of Anemia

Marrow production defects (hypoproliferation)



Red cell maturation defects (ineffective
erythropoiesis)



Low reticulocyte count
Little or no change in red cell morphology (a
normocytic, normochromic anemia
Slight to moderately elevated reticulocyte count
Macrocytic or microcytic anemia
Decreased red cell survival (blood loss/
hemolysis).
Classification of anemias by MCV

Microcytic (<80 fL)




Iron deficiency
Thalassemia
Anemia of chronic disease
Macrocytic (>100 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
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

Nutrient Roles in Erythropoesis
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)

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
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


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



Heme iron> Organic iron (Ferrous gluconate) > Inorganic iron (ferrous
sulfate)
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
Dietary Sources of Iron
•
Red meat > 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
Iron Exchange
80% of iron passing
through the plasma
transferrin pool is
recycled from brokendown red cells
 Absorption of about 1
mg/d is required from
the diet in men, 1.4
mg/d in women to
maintain homeostasis

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
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
Iron Deficiency Anemia
Hypochromic red cell
 Microcytic cell
 Target cell

Stages of Iron Deficiency
Treatment of Iron Deficiency
Red Blood Cell Transfusion
 Oral Iron Therapy

 Ferrous
sulfate
 Ferrous fumarate
 Ferrous gluconate

Parenteral Iron
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 4–5
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

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


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)



Disorders of terminal ileum




Pernicious anemia
Total gastrectomy
Sprue
Regional enteritis
Intestinal resection
Competition for cobalamin



Fish tapeworm (Diphyllobothrium latum)
Bacteria: "blind loop" syndrome
Drugs: p-aminosalicylic acid, colchicine, neomycin
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
Megaloblastic Anemia
Macrocytic RBC
 Hypersegmented
Neutrophil

Vitamin B12 Absorption – Oral Phase
Vitamin B12 Absorption – Gastric
Phase
Vitamin B12 Absorption – Intestinal
Phase
Vitamin B12 Deficiency

Any interruption along this path can result
in cobalamin deficiency
 Gastrectomy
results in low production of IF
 Terminal ileal resection (>100 cm), decreases
the site of absorption of B12-IF complex
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

Diagnosis of Vitamin B12 Deficiency
Macrocytosis
 Peripheral blood smear
 Cobalamin levels
 Elevated serum methylmalonic acid and
homocysteine levels
 Schilling Test

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

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 > 7% of radiolabeled B12
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

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

Stage 4
If pancreatic insufficiency exists, B12
malabsorption may occur
 Normalization after pancreatic enzyme
therapy suggests pancreatic origin

Causes of Megaloblastic Anemia

Folate Deficiency
Inadequate intake: unbalanced diet (common in alcoholics, teenagers, some
infants)
 Increased requirements








Malabsorption



Pregnancy
Infancy
Malignancy
Increased hematopoiesis (chronic hemolytic anemias)
Chronic exfoliative skin disorders
Hemodialysis
Sprue
Drugs: Phenytoin, barbiturates, (?) ethanol
Impaired metabolism



Inhibitors of dihydrofolate reductase: methotrexate, pyrimethamine, triamterene,
pentamidine, trimethoprim
Alcohol
Rare enzyme deficiencies: dihydrofolate reductase, others
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
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
Stages of folate deficiency
1.
2.
3.
Negative folate balance (decreased
serum folate)
Decreased RBC folate levels and
hypersegmented neutrophils
Macroovalocytes, increased MCV, and
decreased hemoglobin
Diagnosis of folate deficiency
Peripheral blood and bone marrow biopsy
look exactly like B12 deficiency
 Plasma folate <3 ng/ml—fluctuates with
recent dietary intake
 RBC folate—more reliable of tissue stores
<140 ng/ml
 Only increased serum homocysteine levels
but NOT serum methylmalonic acid levels

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 1·4 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
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