Anemia

Gizi
dr. Ancah CNM, Ph.D.
FK UNEJ
Blok 17 2014/2015
 Sel-sel Darah
Terdiri dari
Eritrosit (sel darah merah)
Leukosit (sel darah putih)
Trombosit (keping-keping darah)
Eritrosit

Erythros = merah
Kytos = ruang sel

Warna merah pada sel

dikarenakan adanya unsur
haem yang lebih dikenal dengan
kata Haemoglobin (Hb)
 ERITROSIT
= Sel Darah Merah
• Fungsi :
- membawa Hb u/ :
transport O2  HbO2
CO2  Hb CO2

- buffer/penyangga
 Eritrogenesis
• Dikontrol oleh :
Eritropoeitin ( EPO ) = haemopoeitin

• Diproduksi oleh : - ginjal 80-90 %

- hepar 10-20%

• Perangsang : -hipoksia, adrenalin, prostaglandin

 Zat-zat yang diperlukan untuk
eritrogenesis :

1. Zat Besi (Fe )  sintesa Hb

2. Asam Folat  pembentukan RNA

3. Vitamin B12  pendewasaan & pembelahan

inti

4. Faktor intrisik  terdapat di lambung u/

penyerapan vit B12 dan asam folat.
 Masa hidup eritrosit :
• manusia : 4 bulan ( 120 hari )
• anjing : 100- 130 hari
• kucing : 70-80 hari
• kuda : 140-150 hari
• ayam : 20-30 hari

• Σ eritrosit dalam sirkulasi terbatas

 Regulasi
Eritrogenesis
1. bukan o/ konsentrasi eritrosit dlm darah, ttp o/
kemampuan fungsional eritrosit u/
mentransport O2 ke jaringan.

2. Setiap keadaan yg menyebabkan  O2 yg

ditransport ke jaringan berkurang  me
kecepatan pembentukan eritrosit.
REGULASI ERITROSIT
 Hematokrit (HCt)

= PCV ( Packed Cell Volume )

• Banyaknya sel darah merah dalam presentase

rata-rata : 45 %
• Normal Adult Female Range: 36 - 46 percent
Normal Adult Male Range 41 - 53 percent
Normal Newborn Range: 49 - 61 percent
 Hb terdiri dari :
• 4 rantai polipeptida yang masing- masing
mengikat heme,

• tiap heme mengikat 1 atom Fe,

• tiap Fe mengikat 1 molekul O2

METABOLISME ZAT BESI
Normal Peripheral Smear
Zat Gizi yang berperan dalam
proses Erythropoiesis
 ZAT BESI (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)
 Distribusi besi pada
tubuh manusia (70 kg)
g %
Hemoglobin 2.5 68
Myoglobin 0.15 4
Transferrin 0.003 0.1
Ferritin tissue 0.1 27
Ferritin serum 0.0001 0.0004
Enzymes 0.02 0.6
Total 3.7 100
 Nutritional Iron Balance
• Excretion • Intake
o Gastrointestinal bleeding o Dietary iron intake
o Menses o Medicinal iron
• Losses can be as much as 4 - o Red cell transfusions
37mg/menstrual cycle o Injection of iron complexes
o Other forms of bleeding
o 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
o Heme iron> Organic iron (Ferrous gluconate) > 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
o intestinal mucosa
 o Acid pH and presence of reducing agents: ascorbic acid (vitamin C) reduces
Fe+++ to Fe++ which promotes passage across
• 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
o Absorption increase to 20% in iron-
deficient persons
 Pangan sumber zat besi
• Daging merah > unggas &
ikan
• Sayuran secara umum bkn
pangan sumber fe yg baik,
karena mengandung :
oxalate, phytate, tannins,
etc.
• Bayam mengandung ,
~780 mg oxalate/100 g
catatan :penyerapan Heme
iron dari diet tdk
dipengaruhi oleh ascorbate
atau phytate
Kandungan Besi berbagai bahan
pangan nabati (mg/100g)
Bahan pangan Kandungan besi
(mg/100mg)
Kacang hijau 7,5
Kacang kedele 10.0
Tempe kedelei murni 4.0
Tahu 3.4
Takwa 8.5
Kacang merah kering 10.3
Kacang tanah 5.7
Bayam 3.5
Kangkung 2.5
Pepaya 1.7
 Kandungan besi pada
pangan hewani (mg/100 mg)
Bahan pangan Kandunhgan besi
(mg/100mg)
Daging sapi 2.8
Daging ayam 1.5
Ikan segar 2.0
Telur bebek 5.5
Telur ayam 3.0
Terasi 78.5
Ugang segar 8.0
Hati sapi 6.6
Konsumsi pangan hewani dan vitamin C
Terhadap (%) penyerapan
Availability Konsumsi pangan Penyerapan (%)
Rendah Pangan hewani 3
< 100 gram
Atau
Vitamin C < 25 mg
Sedang Pangan hewani 100 – 5
300 gram
Atau
Vitamin C 25 – 75 mg
Tinggi Pangan hewani > 300 8
gram atauo vitamin C
> 75 gram
Atau
Pangan hewani > 100
gram dan vitamin C >
25 mg
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
I Anemia
 ANEMIA
• Suatu keadaan kekurangan eritrosit,
yang disebabkan oleh hilangnya darah
secara cepat atau lambatnya produksi
eritrosit.

• Kurang zat tertentu gizi : defisiensi besi,

Vit B12, asam folat. Tembaga, Zn dll

• Infeksi parasit : cacing

• Kerusakan Ginjal  eritropoietin tidak

terproduksi
 Klasifikasi anemia
berdasarkan etiologi
• Penurunan produksi sel darah merah (RBC)
o Sumsum tulang tidak mampu memproduksi dalam jumlah yang cukup
o Gangguan kematangan sel

• Meningkatnya kehilangan sel darah merah

o Perdarahaan

• Dektrusi sel darah merah

o Intrinsik (sikle cell)
o Ekstrinsik (mechanical cardiac valve)
o Kombinasi keduanya
Classification of anemias
by MCV
• Normocytic • Microcytic (<80 fL)
o Anemia of chronic o Iron deficiency
disease o Thalassemia
o Aplasia o Anemia of chronic
o Protein-energy disease
malnutrition • Macrocytic (>100 fL)
o Chronic renal failure
o Vitamin B12 deficiency
o Post-hemorrhagic
o Folate deficiency
o Myelodysplasia
o Chemotherapy
o Liver disease
o Increased reticulocytosis
o Myxedema
Klasifikasi anemia berdasarkan morfologi
sel darah merah (RBC)
1. Berdasarkan ukuran (size)
o Microcytic : penurunan MCV
o Normocytic : normal MCV
o Macrocytic : peningkatan MCV
2. Berdasarkan Warna
o Normochromic : normal
o Hypochromic : pucat
 Mekanisme terjadinya
anemia
• Marrow production defects/terganggunya
produksi sel darah merah pada sumsum
tulang belakang (hypoproliferation)
o Low reticulocyte count
o Little or no change in red cell morphology
(a normocytic, normochromic anemia )
 Mekanisme terjadinya
anemia
• Red cell maturation defects/terganggunya
proses kematangan sel darah merah
(ineffective erythropoiesis)
o Slight to moderately elevated reticulocyte count
o Macrocytic or microcytic anemia

• Decreased red cell survival (blood loss/ hemolysis).

 Reticulocytes ?
• Proses terjadinya RBC yg tidak matang
(Adolescent RBC)
o Sekresi erythropoietin dari ginjal
o Sumsum tulang merespon
o Reticulocyte di produksi
o Dilepas ke sirkulasi darah

• Percepatan produksi RBC

dapat menghasilkan reticulocyte yang lebih banyak
 Kapan retyculocyte
menurun ?
• Kadar normal : 1 – 2 % dari RBC adalah
reticulocyte
• Penurunan terjadi ketika sumsum tulang
tidak membuat RBC
o Defisiensi besi
o Anemia aplastik
o Infeksi kronis
o Anemia pernicious yang tidak diterapi
PATHOLOGY, SYMPTOMS, AND
SIGNS OF ANEMIA
II ANEMIA GIZI
 Anemia Gizi
• Anemia gizi : keadaan dimana kadar
hemoglobin, hematokrit dan sel darah
merah berada di bawah nilaI normal,
sebagai akibat dari defisiensi salah
satu atau lebih zat gizi esensial yang
dapat mempengaruhi terjadinya
defisiensi tersebut
ANEMIA DEFISIENSI BESI
II-1
Penyebab Defisiensi Besi
• Defisiensi besi : terjadi karena
interaksi dari berbagai faktor
penyebab yang menimbulkan
ketidakseimbangan antara
kebutuhan besi dengan jumlah
besi yang berhasil diserap tubuh
 Faktor kunci penyebab defisiensi besi
(Unicef/UNU/WHO/MI Technical Workshop)
• Diet (dietary)
1. Rendahnya konsumsi pangan sumber
besi
2. Rendahnya bioavailabilitas besi dari
pangan yang di konsumsi
3. Bentuk besi dalam pangan
(hewani/nabati=hem/nonheme)
4. Tingginya faktor inhibitor
5. Rendahnya faktor enhancers/pemicu
penyerapan
• Gaya hidup (life style)
1. Kehamilan yg berulang
2. Perdarahan yg ada hubungan sedangan
pemakaian alat kontrasepsi intrauterine
(IUDs)
3. Mestruasi yang berlebihan (perdarahan)
4. Meningkatan kebutuhan karena faktor
fisiologis (kehamilan, anak yang sedang
tumbuh, remaja)
5. Bayi defisiensi besi krn lahir dari ibu yg
defisiensi besi juga saat hamil
• Status penyakit (disease states)
• Kehilangan darah kronis
oInfestasi cacing
oSchistosomiasis
• Kehilangan darah patologis
oHaemorrhoids
oPetic ulcer
oPenyakit GI lainnya
o Adanya proses yang mengganggu
penyerapan dan
utilisasi/penggunaan besi dalam
tubuh
• Malabsorption syndromes
• Diare kronis atau berulang
• Faktor genetik
• Dampak dari status sosial ekonomi
yang rendah
1. Keamanan pangan
2. Kurangnya perawatan kesehatan
dan akses terhadap pelayanan
kesehatan
3. Sanitasi lingkungan yanhg buruk
4. Higiene perorang yang jelek
• Faktor genetik penyebab anemia
1. Penyakit sickle cell
2. Thalassemia mayor
3. Haemoglobinopathies
 Causes of Iron
Deficiency
• Decreased iron intake • Increased demand for
or absorption iron and/or
o Inadequate diet hematopoiesis
o Malabsorption from o Rapid growth in infancy
disease (sprue, Crohn's or adolescence
disease) o Pregnancy
o Malabsorption from o Erythropoietin therapy
surgery (post-
gastrectomy) • Increased iron loss
o Acute or chronic o Chronic blood loss
inflammation o Menses
o Acute blood loss
o Blood donation
o Phlebotomy as treatment
for polycythemia vera
Iron Deficiency Anemia
• Unique Physical Exam • Facts and Figures
findings o Most common
o Cheilosis cause of anemia
• fissures at the o 500 million cases
corners of the worldwide
mouth o Prevalence is
o Koilonychia higher in less
• spooning of the developed
fingernails countries
Iron Deficiency Anemia - koilonychia
 Tahapan perkembangan defisiensi besi –
anemia defisiensi besi (Gibson , 2005)
• Tahap 1 : Iron depletion
o Simpanan besi menurun (serum ferritin
menurun)
o Besi serum dan hemoglobin normal
• Tahap 2 : Iron deficient erythropoiesis (iron
deficiency without anemia)
o Serum ferrritin semakin menurun
o Besi serum dan transferrin menurun
o Hemoglobin menurun sedikit atau normal
• Tahap 3 : Iron deficiency anemia
o Serum ferritin semakin menurun atau
habis
o Besi serum, kejenuhan transferin (TS)
menurun
o Hemoglobin dan hematokrit
menurun
Stages of Iron Deficiency
 Iron Deficiency Anemia – Lab Findings

• Serum Iron
• LOW (< 60 micrograms/dL)

• Total Iron Binding Capacity (TIBC)

• HIGH ( > 360 micrograms/dL)

• Serum Ferritin
• LOW (< 20 nanograms/mL)
• Can be “falsely”normal in inflammatory states
 Nilai batas
normal

Indikator
Anemia berdasarkan tahapannya
 Tabel 1. Ambang batas Hemoglobin dan Hematokrit
menurut golongan umur dan jenis kelamin
(INACG/WHO/UNICEF, 1998)

Golongan Umur Hemogllobin Hematokrit

(g/dl) (%)
Anak (6 bln – 5 thn) 11.0 33
Anak (5 – 11 thn) 11.5 34
Anak (12 – 13 thn) 12.0 36
Laki-laki dewasa 13.0 39
Wanita dewasa tdk 12.0 36
hamil
Wanita hamil 11.0 33
Tabel 2. Tingkat keparahan anemia pada wanita

tdk hamil dan anak (6 – 14 thn) (WHO, 2000)

Tingkat anemia Hemoglobin Hematokrit
(g/dl) (%)
Mild 11.0 – 11.9 33 - 35
(ringan)
Moderate 8.0 – 10.9 24 - 32
(sedang)
Severe (berat) < 8.0
Tabel 3. Tingkat keparahan anemia pada wanita

hamil dan anak < 6 tahun (WHO, 2000)

Tingkat anemia Hemoglobin Hematokrit
(g/dl) (%)
Mild 10.0 – 10.9 30 - 32
(ringan)
Moderate 7.0 – 9.9 21 - 29
(sedang)
Severe < 7.0 < 21
(berat)
Tabel 4. Hubungan antara prevalensi anemia

dengan masalah kesehatan masyarakat

(WHO, 2001)

Kategori masalah Prevalensi anemia

kesehatan masyarakat (%)
Tinggi ≥ 40
Medium 20 - 40
Rendah 5.0 - 20
 Preschool age

Pregnant women

Non pregnant women

 Treatment of Iron
Deficiency
1. Red Blood Cell Transfusion
2. Oral Iron Therapy
o Ferrous sulfate
o Ferrous fumarate
o Ferrous gluconate

3. Parenteral Iron
 Iron Supplementation in special
populations
• Pregnant Women
o During the last two trimesters, daily iron
requirements increase to 5 to 6 mg
• Infancy
o Normal-term infants are born with sufficient iron
stores to prevent iron deficiency for the first 4–5
months of life
o Thereafter, enough iron needs to be absorbed to
keep pace with the needs of rapid growth
o Nutritional iron deficiency is most common
between 6 and 24 months of life
 DIETARY FACTORS THAT INFLUENCE IRON

BIOAVAILABILITY (Hurrell and Egli, 2010)

• INHIBITORS OF IRON ABSORPTION

o Phytate (myo-inositol hexakisphosphate) plant based
o Polyphenols  in plant foods and beverages, such as vegetables, fruit,
some cereals and legumes, tea, coffee, and wine.
o Calcium
o Proteins  animal proteins, such as milk proteins, egg proteins, and
albumin, soybean proteins

• ENHANCERS OF IRON ABSORPTION

o Ascorbic acid  fruits and vegetables
o Muscle tissue  meat, fish, or poultry
 ANEMIA
MEGALOBLASTIK
• Kelainan berkurangnya ∑ eritrosit
akibat adanya gangguan sintesis
DNA yg ditandai adanya sel
megaloblasti
• Sel yang paling dipengaruhi
adalah sel yang membelah cepat
: termasuk sel darah dan epitel
usus
• Kebanyakan disebabkan adanya
defisiensi vitamin B-12 dan asam
folat
• Kekurangan keduanya dapat
menyebabkan gangguan sintesa
DNA sehingga proses
pembelahan sel menjadi
terganggu.
 Megaloblastic Anemia
• Macrocytic RBC
• Hypersegmented
Neutrophil
Defisiensi vitamin b-12
II-2
Causes of Vitamin B 12
deficiency
o Inadequate intake: vegans (rare)
o Malabsorption
• Defective release of cobalamin from
food
• Gastric achlorhydria
• Partial gastrectomy
• Drugs that block acid secretion
• Inadequate production of intrinsic
factor (IF)
oPernicious anemia
oTotal gastrectomy
• Disorders of terminal ileum
oSprue
oRegional enteritis
oIntestinal resection
• Competition for cobalamin
oFish tapeworm
(Diphyllobothrium latum)
oBacteria: "blind loop" syndrome
oDrugs: p-aminosalicylic acid,
colchicine, neomycin
 Clinical Manifestations of Vitamin
B12 Deficiency
• Hematologic
o Macrocytic Anemia
• Gastrointestinal
o Glossitis
o Anorexia
o Diarrhea
• Neurologic (found in 3/4th of individuals with pernicious
anemia)
o Numbness and paresthesia in the extremities, Weakness, Ataxia
o Sphincter disturbances
o Disturbances of mentation
• Mild irritability and forgetfulness to severe dementia or frank psychosis.
o Demyelination, Axonal degeneration, and then Neuronal death
• Last stage is irreversible
Vitamin B12 affects
two Major Pathways
• Methylmalonyl CoA • Homocysteine

• Succinyl CoA • Methionine

 The effects of Vitamin B12
on the conversion of
homocysteine to methionine
Homocysteine

Methionine Synthase

Methylcobalamin

Methionine

5-methyltetrahydrofolate tetrahydrofolate
Tetrahydrofolate methyltransferase
 The effects of Vitamin B12
on the conversion of
Methylmalonyl CoA to Succinyl CoA
Methylmalonyl Co A

Methylmalonyl CoA mutase

Adenosylcobalamin

Succinyl CoA
 Vitamin B12 Deficiency
• homocysteine and methylmalonyl CoA

• Increase in methylmalonyl CoA

o Increased enzyme activity in fatty acid synthesis
• Build up of odd fatty acids around peripheral nerves

• Increase in homocysteine
o Vascular/nervous problems
 Vitamin B12 Deficiency
• Excess homocysteine & MMA excreted in urine
o Diagnosis for cobalamin deficiency

• Methylmalonyl CoA mutase & Methionine synthase affect

amino acid metabolism
o Amino acid metabolism inhibited by deficiency
 DEFISIENSI VITAMIN
B12
• Anemia
• Muka pucat mata kekuningan
• Kadar bilirubin meningkat
• Nyeri lidah, lidah papilnya halus dan
kemerahan.
• Anoreksia mungkin dengan diare
• Matirasa, kelemahan dan ataksia, mudah
lupa, sampai psikosis, reflek lutut menurun
Vitamin B12 Absorption – Oral Phase
Vitamin B12 Absorption – Gastric
Phase
Vitamin B12 Absorption – Intestinal
Phase
Terapi defisiensi vitamin
B12
• Kobalamin 1000 mikrogram tiap minggu sampai 6
minggu
• Bila membaik diberikan 1 bulan sekali
• Bisa dilanjutkan oral 2 mg/hari
• Bila perlu tranfusi PRC pelan pelan
• Pengobatan penyakit penyebab
• Asam folat oral dosis tinggi
 Sources of Vitamin B12
• Fish
• Eggs
• Meat
• Dairy Products
Defisiensi asam folat
II-3
 Causes of folat
deficiency
o Inadequate intake: unbalanced diet (common in alcoholics, teenagers,
some infants)
o Increased requirements
• Pregnancy
• Infancy
• Malignancy
• Increased hematopoiesis (chronic
hemolytic anemias)
• Chronic exfoliative skin disorders
• Hemodialysis
o Malabsorption
• Sprue
• Drugs: Phenytoin, barbiturates, (?)
ethanol
o Impaired metabolism
• Inhibitors of dihydrofolate reductase:
methotrexate, pyrimethamine,
triamterene, pentamidine, trimethoprim
• Alcohol
• Rare enzyme deficiencies:
dihydrofolate reductase, others
 Tahapan defisiensi
asam folat
1. Negative folate balance
(decreased serum folate)
2. Decreased RBC folate levels and
hypersegmented neutrophils
3. 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
 GEJALA KLINIS DEF
ASAM FOLAT

• Mirip def B12 tetapi tidak tampak gangguan

neurologis
 Vitamin B12 Deficiency Versus
Folate Deficiency
Vitamin B 12 Folate Deficiency
Deficiency
MCV > 100 > 100
Smear Macrocytosis Macrocytosis with
with hypersegmented
hypersegmented neutrophils
neutrophils
Pernicious Yes NO
anemia
Homocystine Elevated Elevated

Methylmalonic Elevated NORMAL

Acid
 Aspek gizi vitamin B12
dan asam folat
Vitamin B 12 Asam folatasupan
makanan
Asupan normal dalam 7 – 30 μg 600 – 1000 μg
makanan
Sumber pangan Pangan hewani Sebagian besar
pangan hewani
(hati), sayuran hijau
dan ragi
Efek pengolahan Sediikit pengaruh Mudah rusak
Kebutuhan min sehari 1 – 2 μg 100 – 200 μg
Simpanan tubuh 2 – 3 μg ( untuk 2 – 4 10 – 12 μg (untuk 4
tahun) bulan )
 Lanjutan …..
Vitamin B 12 Asam folate
Tempat penyerapan Ileum Duodenum dan
jejunum
Mekanisme Faktor intrinsik Dikonversi menjadi
penyerapan metiltetrahiklrofolat
Batas penyerapan 2 – 3 μg per hari 50 – 80 % kandungan
asam folat dalam
makanan
Bentuk fisiologis Metil dan adenosin Derivat poliglutamat
intrasel terutama cobalamin tereduksi
Bentuk terapeutik hidroksicobalamin Asam folat (
peterolglutamat)
 TERIMA KASIH
ATAS
PERHATIANNYA……….