Nutritional Anemia

dr. Mardiana,M.Kes, Sp.GK

Department of Clinical Nutrition
Hasanuddin University
Makassar

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 Definition of Anemia
A condition in which the hemoglobin level is below
normal standard
HEMOGLOBIN CUT-OFF POINT ( WHO 1968 & 1972)

Age Hb Ht MCHC

6 mo – 6 yrs 11 33 34

6 – 14 yrs 12 36 34

Adult Male 13 39 34

Adult Female 12 36 34

Pregnant Woman 11 33 34
 ETIOLOGY

1. Diminished erythropoiesis due to

nutritional def or BM failure
2. Blood loss
3. Increased hemolysis, hereditary or
acquired
 Nutritional Anemia
Anemia due to nutritional deficiency which
is critical in erythropoesis (RBC synthesis)

Fe, vit.B.12, vit.B6, Vit.C, Cu and Co,

Folic acid and protein (vit. A ?)
ETIOLOGY of Nutritional Anemia

Inadequate intake( Primary)

Malabsorption ( TGI disease )

Increased Utilisation (Malignancy, infection)

Increased requirement (Pregnancy)

Increased excretion ( Liver disease)

Increased Destruction (malaria)

 Signs and Symptoms
• Depend less on its severity than on the pace of
its development
• Pallor of skin and mucous membrane
• Easily fatigue or poor exercise tolerance
• Resting tachycardia, Palpitations
• Dizziness, Syncope
• Amenorrhea
• Systolic ejection murmur

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 Signs & Symptoms
Nutritional anemias often accompanied by
vitamins and minerals deficiency
Vit C and folic acid coexist in many foods ---
anemia + scurvy
Anemia not usually an isolate finding ---limits
RBC production usually affect other high
turnover cells such as leukocytes, platelets, and
enterocytes

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Morphologic Classification of
Nutritional Anemia
(Based on Blood smear assessments)

Hypochromic Microcytic Anemia

Due to iron deficiency

Hyperchromic Macrocytic Anemia or

Megaloblastic anemia
Related to B12 and Folic acid
deficiency
 Etiologies

Category (MCV) Nutritional causes Other causes

Microcytic (<80 u3) Iron deficiency (common), Chronic diseases,

Pyridoxine def (uncommon), thalassemias,
Copper def (uncommon) hemoglobin E disorders,
sideroblastic anemia
(Lead toxicity)

Normocytic (80-100 PEM Chronic diseases

u3 )

Macrocytic (>100 u3) Folic acid def, Vit B12 Def Alcoholism, Liver disease,
hemolysis

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 ETIOLOGIES

• Microcytic and macrocytic can coexist; patient

can have both iron and folic acid def.

• In these cases MCV may normal and suggest a

normocytic anemia but the blood smear shows
dimorphic RBCs

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 Diagnostic steps
Patient history
Physical examination
Lab: blood smear, blood count, Ht, MCV, BM

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 Microcytic anemia
Common cause is iron def
Iron def: inadequate intake, absorption,
excessive loss/bleeding
Iron def is the most common nutritional anemia
and the most common nutritional deficiency.

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 PATHOPHYSIOLOGY
Iron in the body: functional and storage form
Iron incorporated into heme and myoglobin
Part of enzymes : COX, catalase, peroxidase
Storage form: ferritin and hemosiderin
Dietary iron: heme iron from animal/meat and
nonheme iron from vegetables and cooking
vessels
Largely absorbed in the duodenum

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 THE PATHOGENESIS OF NUTRITIONAL DEFICIENCY DISEASE

Secondary
Inadequacy

Nutritional Tissue Biochemical Functional

Inadequacy Depletion Lesions Changes

Nutrients
reserve

Primary Anatomic
Inadequacy Lesions
• Heme iron 20% bioavailable, nonheme iron 3%
available
• Net absorption of the two forms combined is
10%
• Each day, about 1 % RBC is destroyed releasing
about 30 mg of Iron into RES and circulation
• Of 30 mg released, about 29 mg salvaged and
only 1 mg must be replaced
• 1 mg can be absorbed from 10 mg iron
contained-diet (RDA)

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Premenopausal women need additional 0.5
mg/day to compensate menstrual loss----1.5 mg
---15 mg RDA
The group with greatest risk:
- (1) 6 mo---4 y.o
- (2) Early adolescence
- (3) Menstrual women
- (4) Pregnant women

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 Lab
Injury, infection,
Lab finding chronic Iron deficiency PEM
inflammation

Serum iron Low Low Generally Low

Serum TIBC Normal or Low High Low

Serum Ferritin Normal or slightly Low Generally Low

high

Marrow and Present Absent Low to absent

liver iron store

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 Treatment
Fe sulfate 325 mg (60 mg elemental iron) 1-3
x/d with meals
Theraphy should be continued for 4 to 6 mo to
restore normal Hb and iron stores.
IV injection can be given as iron-dextran
provides 50 mg/ml (Imferon) when oral theraphy
is ineffective

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 Macrocytic anemia
When caused by defic. of Folic acid or vit B12----
megaloblastic anemias because large, immature
RBC precursors (megaloblasts) accumulate in
the BM
Not all macrocytic anemias are megaloblastic;
anemias in alcoholism, liver disease, and
hemolysis, the RBCs are large but megaloblasts
are not present in the BM.
In addition, macrocytosis without anemia can be
caused by cold agglutinins, hyperglycemia, and
marked leukocytosis

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 Anemia of Chronic Diseases
The most common Anemia in hospitalized
patients due to inflammation, infection, and
malignancy occurs because there is decreased
RBC production, possibly as a result of
disordered iron metabolism
It may be due to the presence of Inflammatory
cytokines such as IL-1 and TNF-alpha which
(1)decrease Iron absorption and (2)erythroblast
activity, (3)inadequate mobilisation from storage
IL-1 and TNFa also (4) inhibit division of
erythroid progenitors and may (5) inhibit
erythropoetin production
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Ferritin levels are normal or increased, but
serum iron levels and TIBC are low
In arthritis, depletion of stored iron develops
partly because of reduced iron absorption from
the gut
Recombinant erythropoetin therapy usually
corrects this anemia

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TNFa increases expression of hepcidin, a
protein which inhibits ferroportin (iron membrane
transporter)
TNFa decreases expression of ferroportin
Hepcidin in duodenum inhibits iron absorption

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 IRON DEFICIENCY IN CHILD
 Can be found in both developed and developing
countries

 Causes
 Limited iron reserve
 Accelerated growth
 Less varied diets
 Delayed food supplement
 Increased metabolism
 Decreased absorption
 ETIOLOGY OF ANEMIA IN CHILD

Baby < 6 Months

• Inadequate iron reserve
• Delayed of food supplements
1 - 2 years child
• GI and respiratory tract infection
• Inadequate intake
5 year Child
• Parasite infection ( ankylostomiasis, trichuris,
amubiasis )
ANEMIA IN ADULT FEMALE

Increased requirement during

menstruation

Pregnancy

Lactation
 Pregnancy and Lactation

Loss of iron during normal pregnancy

• Foetus iron 400 mg
• Delivery 325 mg
• Lactation 175 mg
– Total 900 mg

Need additional iron of 2 mg /day for 460 days to

offset the losses
Pathogenesis of Iron deficiency
in women

Altered metabolism of iron during

pregnancy
Other causes
• Change in blood composition
• alteration in bone marrow
• Growth and development of foetus
• Inadequate intake
• Low iron pool (Consecutive
pregnancy)
 Total Iron in the Body
4-5gr (Adult) & 400mg (Baby)

RBC 60%
Ferritin & hemosiderin 30%
Myoglobin 5-10%
Haem enzymes <1%
Plasma iron 0.1%
 IRON LOSS FROM THE BODY

Baby 0.3-0.4mg/hr

Child aged 4 – 12 th 0.4-1.0/hr

Adult male 1.0-1.5/hr

Adult Female 1.0-2.5/hr

Pregnant women 2.7mg/hr

 IRON
 Human body contains 3 to 5 g iron
 Approximately 2 g as Hemoglobin and 8 mg as
enzymes
 Well conserved by the body ; approximately 90% is
recovered and reused extensively.
 Highly reactive element that can interact with oxygen
to form intermediates able to damage cell membrane
or degrade DNA.
 Iron must be tightly bound to proteins to prevent
destructive effects.
 IRON COMPOUND IN THE BODY
 METABOLIC PROTEIN
Heme Proteins
Hemoglobin Oxygen transport from lungs to tissues
Myoglobin Transport & store oxygen in muscle
Enzymes - Heme
cytochromes Electron transport
Cytochrom P-450 Oxidative degradation of drugs
Catalase Convert H2O2 to O2 and H2O
Enzymes-Nonheme
Iron sulfur & metalloproteins : Oxidative metabolism
Enzymes-iron dependent
Tryptophan pirrolase : Oxidation of tryptophan
 IRON COMPOUND IN THE BODY

TRANSPORT AND STORAGE PROTEINS

Transferrin : Transport of iron and other minerals

Ferritin : Storage
Hemosiderin : Storage
 Two Types of IRON in Food

 Heme-Iron:
In animals product (hemoglobin & myoglobin)
Well absorbed
about 10% of iron consumed

 Nonheme-iron :
Mainly in plants
Main source of iron in the diet (~90%)
Absorption variable
affected by other factors
 IRON CONT………

 95% is associated with proteins e.g hemoglobin & myoglobin

 Functions:
 Respiratory transport of O2 & CO2
(Oxygen binding component of hemoglobin and myoglobin)
 Co-factor for enzymes
 Involved in the immune function and cognitive
performance

 Absorption : Well regulated

 Transported : Transferrin
 Sources : Meat, seafood, some vegetables
 Iron Absorption
 Healthy Individuals: 5-10% absorbed
 Iron deficiency : Up to 40% absorbed
 Factors that affect absorption:
enhancing factors:
acid in the stomach
heme iron
high body demand
low body stores
meat protein factor (MPF)
vitamin C
 IRON ABSORPTION, CONT….
Inhibiting factors
dietary fiber (phytate)
tannin in tea
Ca in Milk (?)
Antacids
Calcium helps to remove phosphate, oxalate
and phytate that would combine with iron and
inhibit its absorption
 IRON ROUTES IN BODY
 Most iron is recycled.
Some lost with body tissues and must be replaced by eating iron-
containing food
 Intestinal cells:
Store excess in ferritin; if body not need iron.
Some losses in shed intestinal cells.
Package iron in transferrin (transport protein)
 Blood:
Transferrin carries Fe in blood; some losses via urine, sweat, skin;
some Fe delivered to myoglobin of muscle cells; bone marrow
puts Fe into haemoglobin of red blood cells; stores excess in
ferritin and haemosiderin
 Liver/lien;
Dismantle red blood cells and package Fe into transferrin, stores
excess as ferritin / haemosiderin
 Iron Deficiency and Toxicity
 Deficiency:
 Decreased blood hemoglobin (anemia)
 Low plasma iron
 Increased transferrin and reduction in tissue iron
 Lethargy

 Toxicity
 Not common, usually due to a genetic disorder
 SOURCE OF IRON

 Adequate diet contains no more than 6

mg/1000kcal of iron
 Indonesian RDA (2004): Adult male 13 mg/day,
female 26 mg/day
 Dried beans and green leafy vegetables are the
best plant sources
 Best sources dietary iron
 Liver, heart, kidney, lean meat
 oysters, shellfish
 Fish
 Poultry
Adult Female :
- Menstruation --- loss 30 mg --- need 0.5-1 mg Fe/d
- Pregnancy --- 900 mg for fetus storage, delivery
and lactation, require 2 mg Fe/d

Prevention :
1. Fe prophylaxis
2. Improve diet
3. Family Planning
4. Food Fortification
5. Eradication of infection & parasite
infestation
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Indonesian RDA for Fe (2013)

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Indonesian RDA for Fe (2013)

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 Fe Sources
Meat and alternative
Liver ( 300 mg) : 5.3 mg
Hamburger : 2.3
Soybean (2 cups) : 2.9
Fish 300 mg : 0.3
Chicken 300 mg : 0.9

Vegetables
 Spinach 1 cup : 1.7 mg
 Asparagus 1 cup : 1.2 mg
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MEGALOBLASTIC ANEMIA IN CHILD
FOLIC ACID – Synthesis of RNA & DNA
 Etiology :
1. Inadequate intake
2. Malabsorption : steatoroe idiopatik, tropical
sprue, celiac disease, other GIT disorders
3. Antagonist folic acid : metotrexate, primetamin,
oral contraception

 Therapy :
1. Therapy of etiology and diet
2. Folic acid 3 x 5 mg/hr or 3 x 2,5 mg for baby
3. Blood Transfusion when needed
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MEGALOBLASTIC ANEMIA IN ADULT

= An Perniciosa Addison

 Etiology :

Malabsorption of Vitamin B12 due to intrinsic

factor deficiency on gaster mucosa

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 MEGALOBLASTIC ANEMIA

1. Primary : inadequate intake of B12 & Folic acid

2. Secondary :
a. Malabsorption; lack of intrinsic factor, oral
contraseption – hinder folic acid absorption
b. Increased requirement ; Hb-nopathi,
hemolysis, anticonvulsant

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Therapy
1. Folic acid 5-10 mg/hr
2. Cyanocobalamine 1000 ug 2 x/wk – 250
ug/wk-normal
During Pregnancy :
1. Folic acid 10 mg/d
2. Severe Anemia ---- transfusion
3. Fe
Prevention in pregnancy
1. 300-500 ug folic acid with
2. 60 mg elemental Fe/d during trimester
III
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 FOLATE (Vit B-9)
Group of compounds. Active form is
tetrahydrofolate (THF)
Source : intestine: small amount produced
by bacteria
Animal food: absorbed unaltered
Plant food: conjugated with glutamic acid
One of the most unstable vitamins

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 FOLIC ACID
RDA, 2013 (Adult)
 Male 400ug
 Female 400ug
Functions
 Coenzymes in transport of carbon atoms
essential for bio-synthesis of nucleic acids
 Essential for normal maturation of RBC
 Convert B12 to coenzyme form
 Functions as co-enzyme: tetrahydrofolate (THF)
 Other enzymatic reaction
Indonesian RDA for Folic acid (2013)

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Indonesian RDA for Folic acid (2013)

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SOURCE OF FOLIC ACID
Green leafy vegetable,
Organ meats (liver),
lean beef,
Wheat, dry beans,
lentils, cowpeas
Asparagus, broccoli,
collards, yeast
Small amount is synthesized by
intestinal tract
 SOURCE OF FOLATE

Vegetables (per 100 g):

Asparagus 265 ug
Spinach 130 ug
Broccoli 160 ug

Fruits
Orange juice 75 ug
Rice 20 ug

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Sources of folate

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 Folate : deficiency/toxicity

 Deficiency : the most common vitamin deficiency in Australia

 Causes: low dietary intake

- Destruction in food preparation

- Poor intestinal absorption

 Impairment of DNA replication

 Immature RBC cannot divide and become megaloblasts

 Symptoms: megaloblastic (macrocytic) anemia

 At risk: pregnant women, elderly, alcoholics,

 Is linked with neural tube defect in foetus

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 Vitamin B12 (Cobalamin)
 Group of compounds that contain cobalt
 Source : synthezised only by microorganisms
 Found in food of animal origin
 Not in plants
 Functions: coenzyme in only 2 reactions:
 Isomerisation of methylmalonyl CoA --- succinyl
CoA
 Methylation of homocysteine (bloop pressur
inducer) --- methionine
 Converts folate to active form
 Maintains sheath that surrounds nerve fibres

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 B12 Vitamin

Involved in the metabolism of single carbon

fragment
Essential for biosynthesis of nucleic acid and
nucleoproteins
Role in metabolism of nervous tissue
Involved with folate metabolism
Related to growth
 Vitamin B12-deficiency

Rare in developed countries except among strict

vegetarians
Pernicious anemia: megaloblastic (macrocytic
anemia) and neurological disturbances
Causes:
Malabsorption
Lack of intrinsic factor (in stomach)
Inadequate intake (vegans, alcoholics)

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 B12 Vitamin cont’d

RDA 2.4 ug

Source: (animal only)

Liver, kidney
Eggs, fish
Milk and dairy product
Vegans require supplement
Indonesian RDA for Vit B12 (2013)

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Indonesian RDA for Vit B12 (2013)

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 SOURCE OF B12

Meats / 300 g
Liver : 6.8 ug
Beef : 2.2
Lamb : 1.8
Tuna : 1.8
hamburger :1.5
telur (1 butir) : 0.6

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 SOURCE OF B12

Milk and Milk products

Skim milk (1 cup) : 1.0 ug
Whole milk (1 cup) : 0.9
yogurt : 0.8
Cheese : 0.2-0.5

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COPPER (Cu)-DEFICIENCY ANEMIA
 Copper is a component of many enzymes
 Copper and other heavy metals are essential
for the proper formation of hemoglobin
 Oxidizing iron before it is transported
(ceruloplasmin, copper containing protein,
required for normal mobilization of iron from its
storage site to the plasma)
 Iron cannot be released----low serum iron & Hb
in the presence of normal iron stores
 Plays role in mitochondrial energy production,
protection from oxidants, and synthesis of
melanine and cathecolamine
Indonesian RDA for Cu (Tembaga) (2013)

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Indonesian RDA for Cu (Tembaga) (2013)

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 SOURCE OF COPPER

 Most diet provide 2 mg/day

 RDA 1.5 – 3 mg/day
 Food high in copper
 Oysters, shellfish
 Liver, Kidneys
 Chocolate
 Nuts
 Dried legumes, Dried foods
 Cereals
 Poultry
 COBALT (Co)
 A component of vitamin B12 (cobalamin)
 This vitamin is essential for maturation of red
blood cells and normal functioning of all cells
 Requirement expressed in terms of Vit B12 : 2.4
ug daily
 Toxicity : intake of 10 to 20 ug/kg Body weight :
high intake cobalt in animal diet produce
polycytemia, bone marrow hyperplasia,
reticulocytosis, and increased blood volume
 Deficiency: related to Vit B12 deficiency ---
macrocytic anemia
 SOURCE OF COBALT

RDA 1.4 - 2.0 ug/day

Liver, kidney,
Oysters, clams
Poultry
Milk
 PYRIDOXINE (VIT. B6)
 Active form of vitamin B6 is Pyridoxal
phosphate (PLP), a coenzyme for numerous
enzymes involved in practically all reactions in
the metabolism of amino acids and in several
aspects of the metabolism of neurotransmitters,
glycogen, sphingolipids, heme, and steroids
Sideroblastic anemia has inherited defect in the
formation of 8-aminolevulinic acid synthetase,
an enzyme involved in heme
synthesis( pyridoxal-5-phosphate is necessary in
this reaction)

70
Indonesian RDA for Vit B6 (2013)

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Indonesian RDA for Vit B6 (2013)

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 SOURCES OF PYRIDOXINE
Vitamin B6 is widely distributed in foods, occurring in greatest
concentrations in meats, whole grain products (especially
wheat), vegetables, and nuts. Animal origin has better bioavailability
RDA = 1.3 mg/day

Ready-to-eat cereals Up to 3.6

Potato, baked, I 0.63
Banana, I 0.43
Rice, white, cooked, I cup 0.30
Chicken, light meat, fried,,3 oz 0.53
Pork chop, baked, 3 oz 0.44
Baked beans, vegetarian, I cup 0.34
Beef, hamburger, broiled, 3 oz 0.32
Chicken, dark meat, fried,3 oz 0.31
Tuna. canned. 3 oz 0.10
Sunflower seeds, kernels, 7+ cup 0.26
Avocado, California, 1 oz 0.08
Whole wheat bread. I slice 0.05

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 Vitamin K (K-1 and K-2)
Source: K-1: green plant leaves
K-2 produced by bacteria in human
intestine
Function: Clotting of Blood. Involved in the
formation of prothrombine and blood
clotting factors (II, VII, IX, X)
Deficiency: Hemorrhage rarely seen in Australia.
May occur in newborn (low at birth).
Can be secondary to disease or drug
treatment

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Indonesian RDA for Vit K (2013)

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Indonesian RDA for Vit K (2013)

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