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MACROCYTIC ANEMIAS
MACROCYTIC ANEMIAS
 These are the anemias in which the RBC
have an MCV of greater than 100fl
 There are 2 groups of macrocytic anemias
1. Megaloblastic anemia
2. Non megaloblastic macrocytic anemia
Requirements for Red Blood Cell
Production
 Erythropoeitin
 Proteins, required for globin synthesis
 Iron
 Vitamin B12 and folic acid
 Vitamin B6
 Vitamin C
 Thyroid hormones, estrogens and
androgens
MEGALOBLASTIC
ANEMIA
 These are a group of disorders in which the
cause the anemia is due to deficiency of
vitamin B12 and folic acid
 The macrocytes in this condition is usually
“oval” - hence they are also called as
MACRO OVALOCYTES
NON MEGALOBLASTIC
MACROCYTIC ANEMIAS



1.
2.
3.
4.
5.
6.
These are disorders in which the macrocytosis is not due
to vitamin B12 or folic acid deficiency
Here the macrocytes are “ROUND”
The conditions in which such round macrocytes are seen
are
Reticulocytosis
Hypothyroidism / myxedema
Myelodysplastic syndrome
Scurvy (Vit-C dif)
Sideroblastic anemia
Liver disorders
MEGALOBLASTIC
ANEMIA
 Vitamin B12 and folic acid are important
nutrients required in the process of nuclear
maturation
 They are required during erythropoiesis
(during DNA synthesis)
 These anemias may be caused because of a
nutritional deficiency or impaired
absorption mainly.
MEGALOBLASTIC
ANEMIA
 Impaired DNA synthesis leading to
defective cell maturation and cell division
 Nuclear maturation delays from the
cytoplasmic maturation – NUCLEAR
CYTOPLASMIC ASYNCHRONY
 Abnormally large erythroid precursors and
red cells
MEGALOPLASTIC
ANAEMIA.
Affect all marrow elements.
Neurologic symptoms (dorsal
columns)
Ineffective erythropoiesis:
High indirect bilirubin
Very high LDH
 Folic Acid:
– It a vitamin which yellow in colour, water soluble,
necessary for the production of the RBC, WBC and
platelets.
– It is not synthesized in the body.
– It is found in large number of green fresh vegetables,
fruits.
 Daily requirement:
The human body needs about 100-150 µg daily.
Absorption:
It is absorbed in the Duodenum and Jejunum.
 Transportation:
Weakly bound to albumin.
METABOLIC FUNCTION
1. Purine synthesis
2. Conversion of homocysteine to
methionine ( which also requires B12 )
FOLIC ACID DEFICIENCY
1. INCREASED DEMAND
2. DECREASED INTAKE
3. DECREASED ABSORPTION
4. METABOLIC INHIBITION
INCREASED DEMAND
 Pregnancy
 Lactation
 Infancy
 Puberty and growth period
 Patients with chronic hemolytic anemias
 Disseminated cancer
DECREASED INTAKE
 Elderly
 Lower socio economic status
 Chronic alcoholics
DECREASED
ABSORPTION
 Acidic food substances in foods like
legumes, beans
 Drugs like phenytoin, oral contraceptives
 Celiac disease which affect the gut
absorption
 Heat sensitive – more loss during cooking
METABOLIC INHIBITION
Vitamin B12:
 This vitamin is synthesized in nature by
micro-organism in the intestine of man and
animals, but we can not obtain it from the
bacteria in our bodies, because it is
synthesizing in the large colon after the site of
absorption and it is wasted in the faeces in
about 5µg/day. So we obtain it from animal
food such as liver, kidney, meat and dairy
products as milk and cheese.
VITAMIN B12
 Abundant in animal foods
 Microorganisms are the ultimate origin of
cobalamin
 It is stored in liver for many years
 It is efficiently reabsorbed from bile
 It is resistant to cooking and boiling
Diary requirements:
The human body needs about 1-2 µg daily.
Absorption:
B12 is combined with glycoprotein called the
intrinsic factor (IF), which is synthesized in
the gastric cells. The absorption occurs in the
distal ileum.
Transportation:
Transport by a protein synthesized in the
liver called Transcobalamine II, which carry
vitamin B12 to liver, nerves and bone
VITAMIN B12 DEFICIENCY
 INCREASED REQUIREMENT
 DECREASED INTAKE
 IMPAIRED ABSORPTION
INCREASED DEMAND
 Pregnancy
 Lactation
 Puberty
 Growth period
 Hyperthyroidism
 Disseminated cancer
DECREASED INTAKE
 Inadequate intake
 Vegetarian diet
IMPAIRED ABSORPTION
 INTRINSIC FACTOR DEFICIENCY due
to
chronic gastritis or antibodies against
stomach cells.
- PERNICIOUS ANEMIA
- GASTRECTOMY
 Malabsorption states
 Diffuse intestinal diseases. Eg., lymphoma,
systemic sclerosis
 Competitive parasitic uptake – fish tapeworm
 Bacterial overgrowth
CLINICAL FEATURES
 Patients develop all general symptoms and
signs of the anaemia.
 Knuckle pigmentation
 Angular stomatitis
 Atrophic glossitis- “beefy” tongue
 Neurological disorders: sever deficiency of
the folic acid causes neuropathies diseases.
 Deficiency during pregnancy causes neural
tube defect.
PERIPHERAL BLOOD
FINDINGS
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Hemoglobin – decreased
Hematocrit – decreased
RBC count – decreased/normal
MCV - >100fl ( normal 82-98fl)
MCH –increased
MCHC – NORMAL
Reticulocytopenia.
Total WBC count – normal / low
Platelet count – normal/ low
Pancytopenia, especially if anaemia is sever.
PERIPHERAL SMEAR
 RBC:
 Poikilocytosis - tear drops and schistocytes
 Anisocytosis - oval macrocytes
-Macro ovalocytes (macrocytic normochromic)
-well hemogloibised, thicker than normal
-inclusions like HOWELL JOLLY BODIES,
basophilic stippling, Cabot rings
PERIPHERAL SMEAR
 WBC:
Normal count or reduced count
Hypersegmented neutrophils (>5 lobes)
MACRO POLYMORPHO NUCLEAR CELLS
(Macropolys)
 PLATELETS:
Normal or decreased
BONE MARROW
 Markedly hypercellular
 Myeloid : erythroid ratio decreased or
reversed. (Normally, there are three myeloid
precursors for each erythroid precursor resulting in
a 3:1 ratio, known as the M:E (myeloid to
erythroid) ratio)
 Erythropoiesis : MEGALOBLASTIC
MEGALOBLAST
1. Abnormally large precursor
2. Deeply basophilic royal blue cytoplasm
3. Fine chromatin with prominent nucleoli
4. Nuclear cytoplasmic asynchrony
5. Abnormal mitoses
6. Maturation arrest
BIOCHEMICAL FINDINGS
 Increase in serum unconjugated bilirubin-
because of ineffective erythropoiesis
 Increase is LDH
 Normal serum iron and ferritin
TESTS FOR FOLATE AND
B12 DEFICIENCY
 Serum folate assay
 Red cell folate assay
 Serum B12 assay
PERNICIOUS ANEMIA
 Scandinavian countries more prevalent
 Disease of elderly – 5th to 8th decades
 Genetic predisposition
 Tendency to form antibodies against
multiple self antigens
PATHOGENESIS



a)
b)
c)

Immunologically mediated, autoimmune destruction of
gastric mucosa
CHRONIC ATROPHIC GASTRITIS – marked loss of
parietal cells
Three types of antibodies:
Type I antibody- 75% - blocks vitamin B12 and IF
binding
Type II antibody – prevents binding of IF-B12 complex
with ileal receptors
Type III antibody – 85-90% patients – against specific
structures in the parietal cell
Associated with other autoimmune diseases like
autoimmune thyroiditis
DIAGNOSTIC FEATURES
1.
2.
3.
4.
5.
6.
7.
8.
9.
Moderate to severe megaloblastic anemia
Leucopenia with hypersegmented neutrophils
Mild to moderate thrombocytopenia
Mild jaundice due to ineffective erythropoiesis
and peripheral hemolysis
Neurologic changes
Low levels of serum B12
Elevated levels of homocysteine
Striking reticulocytosis after parenteral
administration of vitamin B12
Serum antibodies to intrinsic factor