anemia and its type

1. MEGALOBLASTIC ANEMIA
Dr sandeep

2. Megaloblastic anemia
 Anaemia due to impaired DNA synthesis which lead
to delayed nuclear maturation relative to the
cytoplasm.
 Megalobalsts –large nucleated red cell, functionally
and structurally abnormal (Ehrlich ,1880)-
macrocytes in blood

3. Megaloblastic macrocytosis
Vit B 12 deficiency
Folic acid deficiency
Combined deficiency

4. Vit B12 metabolism
 Two active forms – Methyl cobalamin & Adenosyl
cobalamin
 Sources – animal protein, milk, fish, meat, egg
 Daily reqiurement – 2-4 µg.
 Stores : Liver is principle site. Stores about 2mg
 Absorption : Ileum

6. Biochemical function of Vit B12
 In two reactions:
 As methyl cobalamin
Homocysteine Methionine

7.  As adenosyl cobalamin
Propionyl CoA
Methyl melonyl CoA Succinyl CoA
 Increase in these results synthesis of certain fatty acids
which incorporated into myelin responsible for
neurological complications.

8. Causes of Vit B12 def.
 Decreased intake
 Inadequate diet, vegetarianism
 Impaired absorption
 Intrinsic factor deficiency
 Pernicious anemia
 Gastrectomy
 Malabsorption states
 Diffuse intestinal disease, e.g., lymphoma, systemic
sclerosis
 Ileal resection, ileitis
 Competitive parasitic uptake Fish tapeworm infestation
 Bacterial overgrowth in blind loops
 Diverticula of bowel

9.  Increased requirement
 Pregnancy, hyperthyroidism, disseminated cancer

10. Folate metabolism
 Sources : Green leafy vegatables, fruits,liver , kidney
 Absorption: Duodenum and proximal jejunum.
 In food it is in the form of Polyglutamates which is
cleaved in to mono and di glutamates form in the
enterocytes.
 In plasma it is circulated in the form of methyl THF.
 Stores: Liver and RBCs , 10-12mg adequate for 4
months
 Very sensitive to heat, boiling, steaming or frying for
5-10 min. destroys about 95% of folate content.

11. Biochemical functions of folate
 Act as middle man for transfer of one carbon
moieties in
 Purine synthesis
 Conversion of homocysteine to methionine
 For synthesis of deoxythymidylate monophosphate
(dTMP)

13. Causes of folate deficiency
1. Decreased intake :
Inadequate diet , alcoholism, infancy
2. Impaired absorption :
Malabsorption states
Intestinal disease
Anticonvulsants
Oral contraceptives
3. Increased requirement :
Pregnancy , Infancy, disseminated CANCER
4. Impaired utilization
Folic acid antagonists

14. Pernicious anemia -Pathogenesis
Autoreactive T- cell response
Gastric mucosal injury
Triggering autoantibody production
exacerbate mucosal injury
Autoantibodies production : Type I- Blocks binding of Vit B12 to IF
Type II- Prevents binding of Vit b12 –IF complex to ileal
receptor
Type III- Antibodies to gastric proton pump located on
parietal cells

15. Clinical features
 Features of anemia
 Glossitis – smooth beefy red tongue
 Neurological –
 Subacute combined degeneration of spinal cord
 Peripheral neuropathy due to demylenation of peripheral
nerves, spinal cord and cerebrum
 Numbness, paraesthesia, weakness, ataxia, poor finger
coordination, decreased reflexs

16. GLOSSITIS ANGULAR CHEILOSIS

17. PERNICIOUS ANEMIA – GASTRIC
BIOPSY
NORMAL ATROPHIC GASTRITIS

18. Lab Findings
PBS findings:
 Decreased Hb
 RBCs: – macrocytosis,
macro-ovalocytes ,
anisocytopokilosis,
basophilic stippling
Howell Jolly body
Cabot ring , occasional normoblast
 WBC – Total count dec., Hypersegmented
neutrophil
 Platelets: Reduced in no, Giant platelet
 Pancytopenia

19.  Absolute indices –
 MCV, MCH increased
 MCHC normal
 Reticulocytes – low/ Normal
 Platelets – bizarre forms may be seen

20. OVAL MACROCYTES HYPERSEGMENTED NEUTROPHIL
MACRO POLYMORPH HOWELL – JOLLY BODIES

22. BM finding
 Bone marrow –
 Significant in diagnosis
 Hypercellular marrow with erytheroid hyperplasia
 M: E ratio: reduced or reversed
 Megaloblastic erythropoisis
 Giant metamyelocytes & band cells
 Dysplasia in all series
 Iron stores : increased

23. PROERYTHROBLAST
BASOPHILIC
ERYTHROBLAST
POLYCHROMATIC
ERYTHROBLAST
ORTHOCHROMATIC
ERYTHROBLAST RETICULOCYTE
MATURE
RED CELL
MEGALOBLASTIC CHANGES OVAL MACROCYTE
NUCLEAR AND CYTOPLASMIC ASYNCHRONISM

24. BONE MARROW

26. DYSMEGAKARYOPOIESIS

27. Biochemical findings
 Unconjugated bilirubin - ↑
 Serum LDH -↑
 Serum Fe & ferritin – normal
 Serum B12 (200-900pg/ml) - ↓
 Serum folate (6-12ng/ml) - ↓
 Red cell folate assay – more reliable indicator,
30-50 times more than serum-↓
 Serum Homocysteine level -↑
 Serum MMA -↑
Ineffective erythropoiesis

28. Parameter Vit B12 deficiency Folate deficiency
Usual cause Inadequate absorption Inadequate intake,
Peripheral
neuropathy
May + --
Sr. Vit B12 Low Normal / mild ↓
Sr. Folate Normal/↑ Low
Red cell folate Low Low
Sr.
homocysteine
↑ ↑
Sr. MMA ↑ Normal
Lab findings

29. LAB DIAGNOSIS
 Schilling test:
Part I – orally RL Vit B12
2 hr later im unlabelled Vit B12
24 hr urine sample collected & radioactivity
measured ( Normal >7% excreted)
Part II- repeat test with IF
Pernicious anemia/IF
deficiency
Malabsorption
Part I Low Low
Part II Normal Low

30. Schilling test: cont.
 Part III – Test is repeated after giving antibiotics
and anti inflammatory drugs
 Normal – Blind loop syndrome

31. Striking retic response to Vit B 12
neurological improvement with Vit B 12
Urinary MMA
Serum antibodies to intrinsic factor
Urinary FIGLU excretion
LAB DIAGNOSIS

32. Non megaloblastic macrocytosis
 Liver disease
 Alcoholism
 Down syndrome
 Hypothyroidism
 Post spenectomy