NUTRITIONAL ANEMIAS

Mansyur Arif
Dept. of Clinical Pathology, Fac. of Medicine,
Hasanuddin University, Makassar

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 I. INTRODUCTION

Nutritional Anemia (NA) 

decreased conc. of Hb or number
of RBCs  lack of a substance
obtained and replenished by
ingestion of foodstuffs (see table1)

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 Tab 1. Nutrients required for normal erythropoiesis
Iron
Vit B12 (cobalamin)
Folic acid
Proteins, amino acid, calories
Vit B6
Vit B2 (riboflavin)
Nicotinic acid (niacin)
Vit C (ascorbic acid)
Vit A
Vit E
Copper
Cobalt

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 II. IRON DEFICIENCY

A. Total body iron content

1. N : 3-4 g for an adult.
Typically : men  50 mg/kg
woman  35 mg/kg
2. < 0.2% of total body iron  in plasma
 carried bound to a transport protein
(transferrin)

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 • ± 75%  in heme compounds (Hb
67%, myoglobin 3%)
• ± 29% of remaining iron (nonheme
iron)  stored as ferritin and
hemosiderin
a. ferritin  major storage, nontoxic
form & available for future use
b. Hemosiderin  water soluble of
iron

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c. Heme-containing enzymes (cytochromes,
catalase, peroxidase) & iron transport
compartment contain <1% of TBI
3. Packed RBC contain 1 mg/ml of iron,
each unit of PRC used for transfusion
contain 200-223 mg of iron. Every gram
of Hb contains 3.3 mg of iron

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B. Iron metabolism

• Dominated by its role in Hb synthesis. In

this process, iron is used over and over
again.
1. Iron absorbed from the duodenum and
prox. jejenum or modified from iron
stores in the liver enters the plasma
2. The circulating iron is transported from
plasma to cells that have capacity to
make Hb (e.g., in BM)
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 1. The iron is part of Hb in mature erythro-
cyte  delivered to the circulation
2. At the end of RBC lifespan, RBCs is
engulfed by macrophage of RES
(spleen >>) & iron is extracted from Hb
3. Some  stored in macrophage as
ferritin or hemosiderin.
4. >> delivered to plasma & bound to
transferrin

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• Each day  ± 30 mg (normal man) of iron
completes the iron cycle. <2%  leaves
the plasma to enter hepatic parenchymal
cells & other tissue  used for synth of
tissue heme proteins.
Components of the iron cycle
a. Iron absorption
1. American  diet contains 7 mg of iron
per 1.000 kcal (10-15 mg/day)  only
10% (1-2 mg) is absorbed
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 2. Iron absorption increases with diminish-
ed body iron stores, erythropoiesis
activity (& vice versa)
b. Iron transport : transferrin
1. Transferrin (1-globulin)  major
physiologic transport protein
2. Transferrin has capacity to bind ± 300
(250-450 µg Fe/dL)  total iron-binding
capacity (TIBC)

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 3. Transferrin saturation proportion of
available sites on transferrin for iron
binding.
4. Factors can affect serum transferrin
levels & TIBC :
• iron deficiency, pregnancy &
estrogen therapy  TIBC levels
• Inflammation, malignancy, liver
disease, nephrotic syndrome &
malnutrition   TIBC levels
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 c. Cellular iron use
1. Transferrin-bound iron is delivered to
RBCs by binding to specific transferrin
receptors
2. After transferrin bind to transferrin
receptors, transferrin-transferrin
receptors are endocytosed
3. Inside cells  iron is released into
cytosol & transferrin is released back
into the plasma
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d. Iron excretion
• no physiologic mechanism for iron
excretion. Iron is lost from the body only
when cells are lost, especially epithelial
cells from the GIT, skin and renal tub.
 normally 1-2 mg of iron is lost each day
 Menstruating women  0.006 mg/kg/day
 Pregnant woman  3.5 x that of normal
men

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• Regulation of TBI content depends on
control of absorption because there is
little control on iron excretion
C. Etiology of iron deficiency anemia
1. Clinical situation can lead to iron def :
a.  iron requirements  physiologic
stresses (growth, pregnancy, lactation)
b.  iron requirements  pathologic
causes (e.g., blood loss)

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 c. inadequate iron supply (consumption
of low in iron, impaired absorption, abn
transferrin function)
2. Iron def. in adult is almost always due
to blood loss
D. Clinical presentation of iron def. anemia
• Asymptomatic or present with sign and
symptoms of anemia : fatigue,
weakness, pallor, palpitation, headaches,
etc.
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• Some patient  have associated with
underlying cause such as GI symptoms
(e.g.,ulcers, gastritis, malignancy) or
bleeding (e.g.,menorrhagia, melena,
hemoptysis, hematemesis etc)
• History and physical exam.  reflect the
effects of iron def on nonhematopoietic
tissues : glossitis, angular cheilitis,
esophageal webs and strictures, pica etc

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E. Laboratory evaluation of iron def. anemia
1. Complete blood count (CBC)
a.  Hb & Hm  last even to occur in
the progressive depletion of body
iron stores
b. Early signs   RDW
2. Serum iron, TIBC and percent transferrin
saturation
a. SI level  & TIBC  after storage iron
is depleted
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 a. Transferrin sat. <10% +  TIBC  iron
def
b. SI & TIBC levels are reduced by
inflammation, infection, malignancy
3. Serum ferritin
a. Reflects total body iron stores
b. <12 µg/dl  iron def
c. May be elevated in inflammation,
infection, malignancy, hemolysis.

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 4. BM aspiration
• Gold standard for evaluating BM
iron stores & the most sensitive
indicator of iron def
• The diagnosis of iron def
requires the complete absence
of intracellular iron deposits in an
adequate BM specimen

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F. Treatment of iron def. anemia

• Directed at underlying associated conditi-

on (e.g., blood loss)
• Oral iron replacement is the therapy of
choice (e.g., ferrous sulfate, other iron salt
or preparation)
• Parenteral iron (e.g., iron dextran, iron
gluconate)  associated risks & toxicities
 should be reserved for spec. situation

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 III. MEGALOBLASTIC ANEMIA

A. General features
1. Characterized by a distinct morphologic
pattern in the hemopoietic cells  defect
in DNA synth, RNA <<
2. Unbalanced cell growth & impaired cell
division  immature-appearing nucleus,
mature-appearing cytoplasm & cell vol
above normal
3. Vit B12 & folic acid def  most common

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B. Clinical presentation of MA
1. Anemia
2. Nonhematologic manifestation may
appear on epithelial tissues : beefy,
red, smooth tongue (B12 & FA def) and
neuropsychiatric manifestation (B12
def. only) : peripheral neuropathies,
subacute combined degeneration of
spinal cord, optic atrophy, psychiatric
syndrome etc

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C. Hematologic manifestation of MA
1. CBC and PB smear examination
- Increase MCV + anisopoikilocytosis
- PMN nuclear hypersegmentation
- Mild to moderate leukopenia &
thrombocytopenia

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 2. BM aspiration
• hypercellular with hyperplasia of all
three major h.poietic cell lines & abn
appearance
• h.poietic cell abn  always confused
with acute erythroblastic leukemia
D. Diff. Diagnosis of macrocytic anemia
- diff between megaloblastic & nonme-
galoblastic causes important
- table 2
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Tab 2. DD/ of macrocytic anemia

Clinical condition Diff. diagnosis

Megaloblatosis Inherited disordes of DNA synth,
thiamine-responsive meg.
anemia
CDA
Erythroleukemia, etc
Other macrocyic anemia Reticulositosis
Hepatic disease
Aplastic anemia
Post splenectomi, etc
Artifactual macrocytosis Cold agglutinins
Marked hyperglycemia

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 IV. COBALAMIN (B12) DEFICIENCY

A. Cobalamin metabolism
• Essential factor for two enzymatic reactions: the
version of methylmalonyl-coenzyme A (CoA) to
succinyl-CoA and conversion of homocystein to
methionine  for DNA synth
• Produced in nature only by microorganism
(bacteria & fungi)
• Stored in tissues in its coenzyme forms
• Total body content : 2-5 mg, ± 1 mg in liver

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B. Etiology of cobalamin def.
1. Cob. def can result from defects at any
step of cob. metabolism
2. Possible causes :
• Inadequate dietary intake
• Inadequate absorption
• Reduced number of function of ileal
receptors for IF-cobalamin complexes
• Zollinger- Ellison syndrome
• Bacterial or parasitic competition
• Inactivation of cob (e.g., nitrous oxide)
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C. Clinical presentation of cob. def.
(see slide 22)
D. Laboratory evaluation of cob. def
1. Serum cobalamin (vit B12) level
2. Serum homocystein and
methylmalonic acid levels
3. Schilling test
4. IF and parietal cell a.body

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E. Treatment of B12 def
1. Underlying cause should be treated
2. Parenteral form of cyanocobalamin 
1 mg (IM) daily for 3-7 days, then 1 mg
IM for 4-8 weeks, then 1 mg IM monthly
for life
3. Oral replacement  specific condition
(e.g., pancreatic insufficiency)

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 V. Folic Acid deficiency

A. FA metabolism
• FA def  >> malnourished individual
• Stored : 5-10 mg  adequate for 2-4
months
• Daily requirements : adult 100 ug, child
50 ug, pregnant or lactating 300-400
ug

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B. Etiology
• Abn in FA metabolism
• Possible causes :
- nutritional factors (e.g., inadequate
intake, increased requirements)
- intestinal malabsorption
- drugs
- defective cellular uptake of FA (<<)
C. Clinical presentation of FA def. (slide 22)

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D. Laboratory evaluation of FA def.
• FA level
• Serum homocystein and
methylmalonic acid levels
E. Treatment of FA def.
1. Underlying cause should be treated
2. Oral FA  1-5 mg daily  until
complete hematologic recovery
3. Prophylactic FA

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 G.Night Sweet Heart

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