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Management therapy

folic acid and vit B12 in


anemia
Lab farmasi FK Unud

Management folic acid and


vit B12 deficiency
Pencegahan
Terapi

Anemia

Etiologi

Penyebab tersering dari anemia


adalah kekurangan zat gizi yang
diperlukan untuk sintesis eritrosit,
antara lain besi, vitamin B12 dan
asam folat.

folic acid deficiency


or vitamin B12 deficiency.

anemia
irreversible

neurological disorders.

TESTS FOR FOLATE AND B12


DEFICIENCY
Serum

folate assay
Red cell folate assay
Serum B12 assay

PERAN Folate/B12

Folate

Folic acid
deficiency
use
drug

interactions with folic acid

FOOD SOURCES OF FOLATE


Leafy vegetables
Oranges/orange juice
Legumes (kacang polong)
Wheat germ
Fortified grain products (folic
acid)

ABSORPTION
Natural

food source (polyglutamate):


conjugase in the small intestines lumen
converts polyglutamates (low absorption)
to monoglutamates for absorption
absorbed by both active and passive
transport
the average absorb 50 -200ug per day
(about 10 -25% of dietary intake)
storage is in the form of 5-methyl THF (5
-20 mg)

DISTRIBUTION
Tetrahydrofolate

(THF) and its


derivatives distribute to all body
tissues
N5-methyl-THF is the major storage
form of folate in the body (i.e. ~50% in
liver)
Normal total folic acid di serum adalah
5-15 ng/mL,
- < 4 ng/mL suggests deficiency

Ekskresi :

Lebih

dari 90% folic acid diekskresikan


di urine dalam bentuk metabolit
Sebagian besar metabolit muncul di
urine setelah 6 jam dan ekskresi
lengkap dalam 24 jam.
Folic Acid juga dieksresikan melalui air
susu ibu

CURRENT RECOMMENDED
INTAKE OF FOLATE

Adults

19 and older: 0,400 mg


Pregnant women: 0,600 mg
Lactating women: 0,500 mg

HOW DOES FOLIC ACID


WORK?
Folic

acid is converted to its active


coenzyme form, THF, which behaves
as a donor or receiver of a one
carbon entity in different oxidation
states (formyl, methylene, or methyl)

Biochemical functions
one carbon fragment transfer (formyl,
methyl, hydroxymethyl)
conversion

of homocysteine to methionine
conversion of serine to glycine
synthesis of thymidylic acid
synthesis of purines
histdine metabolism
synthesis of glycine

FOLATE DEFICIENCY

Megaloblastic anemia
Neural tube defects
Elevated blood
homocysteine

Folic acid deficiency anemia


Inadequate intake:
Chronically malnourished
Older adults
Alcoholics
Drug addicted persons
Increased need:
Pregnant women: neural tube defects in fetus
Persons experiencing rapid growth
Malabsorption disorders: Celiac sprue
Persons taking methotrexate and other
chemotherapy

Therapy of folic acid def

Therapy FOLIC ACID DEFICIENCY

ANEMIA
Oral administration
of Ac. folicum 1 mg per
day, for 3 months, and maintance therapy if
its necessary.
Bentuk sedian
Tablet 0.4 mg, Tablet 0.8 mg, Tablet 1 mg,
Injeksi 5 mg/ml
Dosis terapi pada penderita anemia
megaloblastik adalah 25O-4O00 g/hari.
Terapi dikatakan berhasil bila kadar
hemoglobin mulai meningkat pada minggu
pertama, dan sembuh dalam 12 bulan

Kontra indiasi
Penderita

dengan anemia pernisiosa


tidak boleh diobati dengan asam
folat sebelum diberikan vitamin B12
suplemen asam folat khususnya
dengan dosis tinggi akan menutupi
tanda dan gejala kelainan yang
progresif

Vitamin B12

Vitamin B12
cyanocobalamin
hydroxocobalamin
function
deficiency
hematological

sequelae
neurological sequelae

Vitamin B12
the

only vitamin that possesses a


metal ion (cobalt) as part of its
structure
the major cofactor form of B12 is
adenosylcobalamin
small amounts of methylcobalamin
as cofactor in methyl transfer
reactions

Vitamin B12
synthesized

by bacteria only
Vitamin B12 is bound to the protein in foods. During
digestion, HCl releases the B12 from the protein.
absorbed only in the presence of the intrinsic
factor (a glycoprotein released by parietal
cells)
transported to tissues via transcobalamin II
present in foods such as liver, fish, eggs, milk
absent in vegetables and fruits
stored in the liver as the coenzyme

Important of Vitamin B12


Part of the complex of B vitamins, vitamin

B12 is one of the most intricate vitamins.


It is important to help the brain and
nervous system work properly
It involves in blood formation.
It plays an important role in cell
metabolism, particularly in DNA
regulation and synthesis.

Folate/B12 DNA Synthesis

Sources of Vitamin B12


Fish

Eggs
Meat
Dairy

Products

Absorption and transport of


vitamin B12
Absorption and transport of vitamin B12
Vitamin B12 binds a glycoprotein (intrinsic factor) in stomach.
I.F. is secreted by the parietal cells.
Vitamin-intrinsic factor complex recognises surface receptors of
mucosal cells in ileum and is absorbed.
It is transported around the body bound to specific a B12 binding
protein (transcobalamin).
It is stored mainly in the liver as adenosylcobalamin in
amounts (3-5mg) sufficient to last a couple of years.

Vitamin B12(cyanocobalamine)

Vitamin B12 Derivatives


Cyanocobalamin

(digested form)
Hydroxycobalamin
Chlorocobalamin
Methylcobalamin
Adenosylcobalamin
(5-deoxyadenosylcobalamin)

Diet

Factor cause B12

Gastric

deficiency
Failure

Pernicious

Anemia
Total gastrectomy
Ileal

Failure

Regional

enteritis (Crohn's disease)


Ileal resection
Tropical sprue
Competing
Bacterial

organisms

overgrowth
Diphyllobothrium latum

Serum ---- B12 is 150-600 pmol/L.


Serum vitamin B12 (pmol/L)

Probability of symptomatic
deficiency

< 75

high

75 - 150

moderate

150 - 220

low

> 220

rare

Manifestation of B12 deficiency


macrocytic

megaloblastic anemia

megaloblasts

are abnormal erythroid precursors


in bone marrow (most cells die in the bone
marrow)
reticulocyte index is low
hyperchromic macrocytes appear in blood
anemia reflects impaired DNA synthesis
other cells may be involved (leukopenia,
thrombocytopenia

spinal

cord degeneration (irreversible)

swelling,

demyelination, cell death


neurological disease
results from deficient methylmalonyl-CoA mutase
this cannot be treated with folic acid!!

Causes of Vit B12 deficiency and associated


conditions
Causes
associated conditions
Lack of IF (Instrisik
fact)
gastrectomy
Ileum Surgical
resection
Malabsorption
Pancreative
insuffiency
Drug (omiprazole,
neomycin, colchicine)
Crohns disease

Causes of Vit B12 deficiency and associated


conditions
Causes
associated conditions
Intestinal parasite
(diphylobothrium
Biologic
latum)
competition
Bacterial overgrowth
Strict vegetarian diet
Nutrional
malnutrition
diciency
Poor diet on Pregnant
women
Transcobalamine II
deficiency
Impaired

Diagnosis of B12 deficiency


Schilling

test

distinguishes

deficiency caused by pernicious


anemia with that caused by malabsorption
compares absorption in radiolabeled B 12 with
intrinsic factor and radiolabeled B12 without
intrinsic factor
in pernicious anemia the B12 with intrinsic
factor will be absorbed while the B12 by itself
will not
in malabsorption neither will be absorbed

Therapy Vit B12 DEFICIENCY


ANEMIA

Treatment
Supplements
Oral

pills
Intramuscular
Intranasal
Sublingual

Schedule for Vitamin B12 Therapy


Route of
Initial dosage
administration

Maintenance dosage

Oral

1,000 to 2,000 mcg per


day
for one to two weeks

1,000 mcg per day for


life

intramuscular

100 to 1,000 mcg every


100 to 1,000 mcg every
day
one to three months
or every other day for one
to two weeks
AMERICAN FAMILY PHYSICIAN

Ringkasan
VITAMIN B12 AND FOLIC ACIDPHYSIOLOGIC CONSIDERATIONS
Vitamin B12

Sources

Daily require
Body stores

Places of
absorption

meat, fish

Folic acid

Gr
vegetables,
yeast
2-5 ug
50-100 ug
3-5 mg (liver) 10-12mg
(liver)
duodenum
and proxymal
ileum
segment of
small

The recommended daily


allowance (RDA)
RDA (g/day)*
VITAMIN

Men

women

Pregnancy

Folat

400

400

600

B 12

2,4

2,4

2,6

Table adapted from: Health Canada Dietary


Reference Intakes, Reference Values for
Vitamins

Vit. B12 deficiency anemia


Causes:
Pernicious anemia:
lack of intrinsic
factor
ileal resections,
loss of pancreatic
secretions, chronic
gastritis
Strict vegetarians

Diagnostics:
Schilling test
Medications:
Vit. B12 parenteral