Download folate deficiency

MEGALOBLASTIC ANEMIA ,L2.
These are caused by either vitamin B12 or folic acid
deficiency,or
from
disturbances
in
folic
acid
metabolism.This deficiency leads to the production of cells
with arrested nuclear maturition but normal cytoplasmic
developement:so-called nucleo-cytoplasmic asynchrony.
All proliferating cells will exhibit megaloblastosis;
..Intramedullary hemolysis results in a raised bilirubin and
LDH but no reticulocytosis.Iron stores are usually
raised.The mature red cells are large and oval.Giant
metamyelocytes appear and contain a large sausage-shape
nucleus. The mature neutrophils show hypersegmentation of
their nuclei with some cells containig 6 or more lobes.
If severe, pancytopenia is present in the peripheral blood .
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CLINICAL FEATURES OF B12 Defficiency;
SYMPTOMS: These may include malaise, breathlessness,
parasthesia, sore mouth, altered skin pigmentation , grey
hair, poor memory , depression, Impotence, hallucination
and visual disturbances.
SIGNS: smooth tongue, angular cheilosis, vitiligo, skin
pigmentation, heart failure in severe cases.Neurological
signs include; p. neuropathy ; sensory disturbances,Loss
ankyle reflex. Spinal cord; dorsal column loss, subacute
combined degeneration of the cord,Bilateral upper motor
neuron sign.cerebrum lesion ; optic atrophy ,Dementia &
Ataxia.autonomic neuropathy .
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DIAGNOSTIC FEATURES
1. Hb:often reduced,may be very low.
2. MCV:usually raised,commonly above 120fl.
3. RBC count:low
4. Reticulocyte count:low for degree of anemia.
5. Leucocyte count :low or normal.
6. Platelet count:low or normal.
7. Blood film:oval macrocytosis,poikilocytosis,red cell
fragmentation,neutrophil hypersegmentation.
8. Bone marrow:increased cellularity,megaloblastic changes in
erythroid series,giant metamyelocytes,dysplastic
megakaryocytes,increased iron in stores,pathological non-ringed
sideroblasts.
9. iron Serum:elevated.
10. Iron-binding capacity:increased saturation.
11. Serum ferritin:elevated
12. Plasma LDH: elevated,often markedly.
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VITAMIN B12 ABSORPTION
The average daily diet contains 5-30ug of vit B12 mainly
in meat, fish,eggs and milk.The daily requirement of
B12 is 1ug.In the stomach,gastric enzymes release
vit.B12 from food and at gastric PH it binds to a carrier
protein termed R protein.The gastric parietal cells
produce acid and intrinsic factor.Intrinsic factor is a
B12-binding protein which optimally binds B12 at PH
8.As gastric emptying occurs,pancreatic secretions
raises the PH and B12 switches from R protein to
intrinsic factor.The vit.B12 intrinsic factor complex
binds to specific receptore in the terminal ilium and
vit. B12 is actively transported by the enterocytes to the
plasma..The liver stores enough B12 to supply the daily
requirement for 3 years and this means that B12
deficiency takes years to become manifest even if all
dietary intake stopped.
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CAUSES OF VITAMIN B12 DEFICIENCY
1.Dietary deficiency: only vegans.
2.Gastric factors:hypoclorhydria, gastrectomy ...
3.Pernicious anemia:this is an autoimmune disorder in
which the gastric mucosa is atrophic with loss of
parietal cells causing intrinsic factor deficiency. Antiparietal cell a.b are present in over 90% of cases but
are also prsent in20% of normal females over the age
of 60 years.A positive result supports the diagnosis
but not diagnostic. Antibodies to intinsic factor are
found in the serum of 60% of patients and are
diagnostic.
4.Small bowel factors: pancreatic insufficiency .
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5. Motility disorders or hypogammaglobulinemia can
result in bacterial overgrowth which leads to
consumption of vit.B12 and it's deficiency.This can be
corrected to some extent by a course of antibiotics.
6.Infestation with the fish tapeworm Diphyllobothrium
latum which consumes vit.B12 can lead to vit .B12
deficiency.
7. Inflammatory disease of the terminal ilium such as
Crohn's disease or ileal resection can result in vit.
B12 deficiency.
8-Schilling test is used for the diagnosis of the cause of
vit.B12 deficiency.
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FOLATE ABSORPTION
Folates are produced by plants and bacteria;hence
leafy
vegetables
(spinach,lettuce,),
fruits
(bananas,melons) are rich sources. Animal
proteins like kidney and liver are also good
sources. in the upper small bowel (jejunum)
absorbed there. Total body stores of folate are
small and deficiency can occur in a matter of
weeks.Vit B12 is essential for the metabolism of
folate.
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FOLATE DEFICIENCY
Causes:
1. increased demands .
a)pregnancy-induced folate deficiency;( twin pregnancies, multiparity and
hyperemesis graviderum).
b) cell proliferation e.g Hemolysis
2.Dietary deficiency (poor intake of vegetables) especially in the edantulous
elderly or psychiatric patients.
3.Malabsorption eg. coeliac disease.
4.Drugs
a)certain anticonvulsants eg . phenytoin
b)contraceptive pills.
c)certain cytotoxic drugs e.g .methotrexate.
Serum folate is very sensitive to dietary intake ;a single meal can nomalise it in
a
patient
with
true
folate
deficiency.
While anorexia,alcohol,and anticonvulsant therapy can reduce it in the
absence of megaloblastosis. for this reason red cell folate levels are a more
accurate indicator of folate stores and tissue folate deficiency.
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DIAGNOSTIC FEATURES OF FOLIC ACID
DEFICIENCY
Diagnostic findings
1-Low fasting serum folate level.
2-Red cell folate level low (but may be normal if
folate deficiency is very recent).
3-Macrocytic dysplastic blood picture.
4-Megaloblastic bone marrow.
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MANAGEMENT
Where a patient with severe megaloblastic anemia is very ill
and treatment must be started before vit.B12 and red cell
folate levels are available, always treat with B12 and folic
acid. The use of folic acid alone in the presence of B12
deficiency results in worsening of neurological defects
although the anemia may improve.
In patients with angina or heart failure blood transfusion can
be given with diuretic cover.
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VitB12 deficiency
Give vit.B12 (hydroxycobalamine)1000ug.i.m in 5 doses 23 days apart followed by maintenance therapy of 1000ug
every 3 months for life.The reticulocyte count will peak
by 5-10 days after therapy and may be as high as
50%.The Hb will rise by 1g/dl every week. The response
of the marrow is associated with a fall of plasma
potassium levels and rapid depletion of iron stores. If the
initial response is not maintained and the blood film is
dimorphic,The patient may need additional iron therapy.
A sensory neuropathy may need 6-12 months to correct
and recovery may be incomplete.
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FOLATE DEFICIENCY
Oral folic acid 5mg daily for 3 weeks , then 5mg once weekly as
maintenance therapy.
PROPHYLAXIS WITH FOLATE
1. In pregnancy to prevent megaloblastosis in women at risk(twin
pregnancy, multiparity and hyperemesis graviderum).Folic acid
supplimentation may reduce the risk of neural tube defects.
2. In chronic hematological diseases associated with reduced red cell
life
span(e.g
autoimmune
hemolytic
anemia
and
hemoglobinopathies).
3. There is evidence that supraphysiological supplementation
(400ug/day) can reduce the risk of coronary and cerebrovascular
disease by reducing plasma Homocysteine levels.
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