MEGALOBLASTIC

ANEMIA
Asst.Prof.IMRAN A KHAN
The megaloblastic anaemias are disorders caused by
impaired DNA synthesis and are characterised by a
distinctive abnormality in the haematopoietic precursors in
the bone marrow in which the maturation of the nucleus is
delayed relative to that of the cytoplasm. Since cell division
is slow but cytoplasmic development progresses normally,
the nucleated red cell precursors tend to be larger which
YOGENDRAN NATH Ehrlich in 1880 termed megaloblasts. Megaloblasts are both
SAXENA COLLEGE OF morphologically and functionally abnormal with the result
PHARMACY that the mature red cells formed from them and released
into the peripheral blood are also abnormal in shape and
RAMPUR BHOOR ROAD size, the most prominent abnormality being macrocytosis.
HASANPUR, AMROHA The underlying defect for the asynchronous maturation of
the nucleus is defective DNA synthesis due to deficiency of
8059479108 vitamin B12 (cobalamin) and/or folic acid (folate).

khanimran@gmail.com

4/24/2020
MEGALOBLASTIC ANAEMIA
 Condition in which bone marrow forms large structurally abnormal and immature RBC’s
is termed as megaloblastic anemia.
 The megaloblastic anaemias are disorders caused by impaired DNA synthesis and are
characterised by a distinctive abnormality in the haematopoietic precursors in the bone
marrow in which the maturation of the nucleus is delayed relative to that of the
cytoplasm.
 Since cell division is slow but cytoplasmic development progresses normally, the
nucleated red cell precursors tend to be larger.
 Which Ehrlich in 1880 termed megaloblasts. Megaloblasts are both morphologically and
functionally abnormal with the result that the mature red cells formed from them and
released into the peripheral blood are also abnormal in shape and size, the most
prominent abnormality being macrocytosis.
 The underlying defect for the asynchronous maturation of the nucleus is defective DNA
synthesis due to deficiency of vitamin B12 (cobalamin) and/or folic acid (folate).

ETIOLOGY AND CLASSIFICATION OF MEGALOBLASTIC ANAEMIA

I. VITAMIN B12 DEFICIENCY

A. Inadequate Dietary Intake e.g. Strict Vegetarians, Breast-Fed Infants.
B. Malabsorption
1. Gastric Causes: Pernicious Anaemia, Gastrectomy, Congenital Lack of Intrinsic Factor.
2. Intestinal Causes: Tropical Sprue, Ileal Resection, Crohn’s Disease, Intestinal Blind Loop
Syndrome, Fish-Tapeworm Infestation.

II. Folate Deficiency

A. Inadequate Dietary Intake e.g. In Alcoholics, Teenagers, Infants, Old Age, Poverty.
B. Malabsorption e.g. In Tropical Sprue, Coeliac Disease, Partial Gastrectomy, Jejunal
Resection, Crohn’s Disease.
C. Excess Demand
1. Physiological: Pregnancy, Lactation, and Infancy.
2. Pathological: Malignancy, Increased Haematopoiesis, Chronic Exfoliative Skin Disorders,
Tuberculosis, And Rheumatoid Arthritis.
D. Excess Urinary Folate Loss e.g. In Active Liver Disease, Congestive Heart Failure.

III. OTHER CAUSES

A. Impaired metabolism
B. Unknown etiology

2 ASST PROF. IMRAN A KHAN| YOGENDRAN NATH SAXENA COLLEGE OF

PHARMACY
EPIDEMOLOGY
Megaloblastic anemia is not rare, but data are insufficient regarding its prevalence. The condition
is more prevalent in countries where malnutrition is a significant problem. the prevalence
increases in older people and during pregnancy.

PATHOPHYSIOLOGY
 The pathophysiology of this group of anemia is ineffective erythropoiesis secondary to
intramedullary apoptosis of hematopoietic cell precursors, which results from DNA
synthesis abnormalities.
 Both vitamin B12 and folate deficiencies may cause defective DNA synthesis.
Subsequently, the nucleus and cytoplasm do not mature simultaneously.
 The cytoplasm (in which hemoglobin synthesis is unaltered) mature at the normal rate,
and the nucleus (with DNA impairment) is not fully mature.

3 ASST PROF. IMRAN A KHAN| YOGENDRAN NATH SAXENA COLLEGE OF

PHARMACY
Fig.1.Biochemical Basis Of Megaloblastic Anaemia (THF = Tetrahydrofolate; DHF =
Dihydrofolate; PGA = Pteroyl Glutamic Acid; Dump = Deoxy Uridylate Monophosphate; Dtmp =
Deoxy Thymidylate Monophosphate

PERNICIOUS ANEMIA

 Pernicious anemia is a deficiency in red blood cells caused by lack of vitamin B12 in
the blood. Pernicious anemia is defined as a type of vitamin B12 deficiency that results
from impaired uptake of vitamin B-12 due to the lack of a substance known as intrinsic
factor (IF) produced by the stomach lining.
 Pernicious anemia is a condition caused by too little vitamin B12 in the body. It is one
form of vitamin B12 deficiency anemia.
 Vitamin B12 helps the body make healthy red blood cells and helps keep nerve cells
healthy. It is found in animal foods, including meat, fish, eggs, milk, and other dairy
products.
 The most common cause of pernicious anemia is the loss of stomach cells that make
intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. The
loss of parietal cells may be due to destruction by the body's own immune system.
 Pernicious anemia can cause permanent damage to nerves and other organs if it goes on
for a long time without being treated. It also raises the risk for developing stomach
cancer.

SYMPTOMS

 Shortness Of Breath
 Muscle Weakness
 Abnormal Paleness Of The Skin
 Glossitis (Swollen Tongue)
 Loss Of Appetite/Weight Loss
 Diarrhea
 Nausea
 Fast Heartbeat
 Smooth Or Tender Tongue
 Tingling In Hands And Feet
 Numbness In Extremities

4 ASST PROF. IMRAN A KHAN| YOGENDRAN NATH SAXENA COLLEGE OF

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TREATMENT

The treatment of both type of anemia is

VITAMIN B-12 DEFICIENCY

 In the case of megaloblastic anemia caused by vitamin B-12 deficiency, you may need
monthly injections of vitamin B-12. Oral supplements may also be given.
 Adding more foods with vitamin B-12 to your diet can help. Foods that have vitamin B-
12 in them include:
 Eggs
 Chicken
 Fortified Cereals (Especially Bran)
 Red Meats (Especially Beef)
 Milk
 Shellfish

FOLATE DEFICIENCY

 Megaloblastic anemia caused by a lack of folate may be treated with oral or intravenous
folic acid supplements. Dietary changes also help boost folate levels. Foods to include in
your diet include:
 Oranges
 Leafy Green Vegetables
 Peanuts
 Lentils
 Enriched Grains

5 ASST PROF. IMRAN A KHAN| YOGENDRAN NATH SAXENA COLLEGE OF

PHARMACY