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Megaloblastic Anemia

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Megaloblastic anemia
Sep 16, 2015 • Download as PPTX, PDF
163 likes • 80,485 views

Megaloblastic anaemia is a red blood cell


disorder due to the inhibition of DNARead
… more

Oduenyi Christian…

15/09/2015

Definition

•Megaloblasticanaemiaisaredblood
celldisorderduetotheinhibitionof
DNAsynthesisduringerythropioesis.
-Mitotically,theinhibitionoftheDNA
synthesisimpairestheprogressionofthe
cellcycledevelopmentfromG2to(M)
stage. AsogwaUka

15/09/2015

Pathophysiology
WhenvitaminB12orfolateisdeficient,thymidinesynthasefunctionis
impairedandDNAsynthesisisinterruptedbutRNAsynthesisremains
unimpaired.TheinabilitytosynthesizeDNAleadstoineffectual
erythropoiesisresultinginexcesshemoglobinandenlargederythroid
precursorsbeingproduced.Thedevelopingredcellhasdifficultyin
undergoingcelldivisionbutRNAcontinuestobetranslatedand
transcribedintoproteinleadingtogrowthofthecytoplasmwhilethe
nucleuslagsbehind.Oftenoneormorecelldivisionareskipped
leadingtoalargerthannormalcell.
Thereisoftenerythroidhyperplasiainthemarrowbutmostofthese
immaturecellsdiebeforereachingmaturityleadingto-elevated
LactateDehydrogenase(LDH)andhyperbilirunemia.

AsogwaUka

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Megaloblastic anemia
1. MEGANOBLASTIC ANEMIA PRESENTED BY ASOGWA
UKAMAKA DEPT. OF MEDICAL LABORATORY SCIENCE
FEDERAL MEDICAL CENTRE MAKURDI 15/09/2015 Asogwa
Uka1
2. Megaloblastic Anemia Outline Definition Etiology
of megaloblastic anemia Pathophysiology Clinical
presentation of megaloblastic anemia Laboratory
Diagnosis Sources of Vitamin B12 and Folic Acid
15/09/2015 Asogwa Uka 2
3. Definition 15/09/2015 Asogwa Uka 3 Megaloblastic
anaemia is a red blood cell disorder due to the inhibition
of DNA synthesis during erythropioesis. Mitotically, the
inhibition of the DNA synthesis impaires the progression of
the cell cycle development from G2 to (M) stage.
4. Etiology of megaloblastic anemias a. Vitamin B12 or
Cobalamin deficiency. b. Folic acid deficiency c. a and b
deficiency. 15/09/2015 Asogwa Uka 4
5. VITAMIN B12 DEFICIENCY Inadequate intake: This is
common among pure vegetarians, old and bed ridden
patients Inability to absorb vitamin B12: a!er gastric
surgery, lack of hydrochloric acid in gastric juice, lack of
intrinsic factor due to auto antibodies to parietal cells.
Competition for intestinal vit.B12 : Competitive absorption
of the vitamin by fish tape worm (Diphyllobothrium latum)
and bacteria overgrowth in blind-loop syndrome,
intestinal stasis. Drugs Inhibition: Metformin, Proton
pump inhibitors 15/09/2015 Asogwa Uka 5
6. FOLATE DEFICIENCY Inadequate intake: a poor
diet Old and bed ridden patients ICU patients. over
cooked food especially vegetable Increased
requirements pregnancy and lactating mothers.
Growing infants Hemolytic anemic patients. Drugs
Folic acid antagonists: Methotrexate Chronic alcoholism:
It inhibits folic acid absorption. It increases folate
excretion through the urine Inability to absorb folic acid:
Following gastric surgery, chronic diarrhoea. 15/09/2015
Asogwa Uka 6
7. Pathophysiology When vitamin B12 or folate is
deficient, thymidine synthase function is impaired and
DNA synthesis is interrupted but RNA synthesis remains
unimpaired. The inability to synthesize DNA leads to
ine"ectual erythropoiesis resulting in excess hemoglobin
and enlarged erythroid precursors being produced. The
developing red cell has di"iculty in undergoing cell
division but RNA continues to be translated and
transcribed into protein leading to growth of the
cytoplasm while the nucleus lags behind. O!en one or
more cell division are skipped leading to a larger than
normal cell. There is o!en erythroid hyperplasia in the
marrow but most of these immature cells die before
reaching maturity leading to - elevated Lactate
Dehydrogenase (LDH) and hyperbilirunemia. 15/09/2015
Asogwa Uka 7
8. Megaloblastic precursor cells versus Normoblastic
precursor 15/09/2015 Asogwa Uka 8 Fig.1a. Megaloblastic
precursors, showing the asynchrony between the nucleus
and the chromatin; the cytoplasm of most cells is
extremely basophilic. Fig.1b.Normoblastic erythropoiesis
with a polychromatophilic normoblast (arrow).
9. CLINICAL PRESENTATION Anaemia symptoms
Neurological symptoms Gastro- intestinal complain
Symptoms of Anemia weakness, palpitation, fatigue, light-
headedness,,shortness of breath, premature graying of
hair, jaundice and pallor. Severe pallor and slight jaundice
combine to produce a telltale lemon-yellow skin in patient
with megaloblastic anemia. 15/09/2015 Asogwa Uka 9
10. 15/09/2015 Asogwa Uka 10 Fig 2a,b “Lemon yellow”
pallor Fg .2d Neura tube defects e.g. Spina Bifida Clinical
signs in pictures
11. Neurological symptoms The syndrome usually
begins with paraesthesia (numbness and tingling) in the
feet and fingers, di"iculties in balance and walking.
Vitamin B12 deficiency causes a demyelinization of the
peripheral nerves, the spinal cord, and the brain, resulting
in more severe neurological symptoms. When it a"ects
the spinal cord it causes spastic ataxia( sti"ness of the
muscles with uncoordinated movement). At the brain it
results in dementia, psychotic depression and paranoid
schizophrenia. This has been termed “megaloblastic
madness.” 15/09/2015 Asogwa Uka 11
12. Gastro- intestinal complains : symptom include loss
of appetite, glossitis (red, sore, smooth tongue) and
diarrhoea 15/09/2015 Asogwa Uka 12
13. Laboratory diagnosis of megaloblastic anemias Full
Blood Count ( FBC): ↓ Hb/Hct, ↑ MCV, ↓ retics, ↓WBC,
↓Plts, macroovalocytosis , anisocytosis, poikilocytosis,
hypersegmentation of granulocytes. Also there may be
variable thrombocytopenia. Bone marrow smear: Bone
marrow examination reveals myeloid cell changes (giant
bands, metamyelocytes and hypertsegmentation) and
megakariocytes are decreased and show abnormal
morphology. 15/09/2015 Asogwa Uka 13
14. Fig. 3a. Peripheral smear from a patient with
megaloblastic anemia. Note the hypersegmented
neutrophils and the macro-ovalocytes. Fig. 3b
Megaloblastosis (Giant Band Forms in Bone Marrow)
15/09/2015 Asogwa Uka 14
15. Biochemistry Test: hyperbilirubinemia ↑lactate
dehrogenase (LDH) Schilling test: The Schilling test is used
to determine whether there is faulty absorption of vitamin
B12. 15/09/2015 Asogwa Uka 15
16. 15/09/2015 Asogwa Uka 16
17. Sources of Vitamin B12 and Folic Acid Vitamin B12 •
Meat, liver, kidney, clams, fish • Eggs, cheese, and other
dairy products Folic Acid • Green leafy vegetables • Broccoli
• Fruit • Whole grains • Dairy products 15/09/2015 Asogwa
Uka 17
18. 15/09/2015 Asogwa Uka 18

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