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Nutritional Anemia

dr. Agussalim Bukhari,M.Med, PhD, Sp.GK(K)


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 Iron deficiency Chronic diseases,


u3) (common), Pyridoxine thalassemias,
def (uncommon), Copper hemoglobin E
def (uncommon) disorders,
sideroblastic anemia
(Lead toxicity)

Normocytic (80- PEM Chronic diseases


100 u3)

Macrocytic (>100 Folic acid def, Vit B12 Alcoholism, Liver


u3) Def 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, Iron
Lab finding PEM
chronic deficiency
inflammation

Serum iron Low Low Generally Low

Serum TIBC Normal or Low High Low

Serum Ferritin Normal or Low Generally Low


slightly 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 (2013): 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 AKG 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
AKG, 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 (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 pressure
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 contd

RDA 2.4 ug

Source: (animal only)


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

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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
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)

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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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