Megaloblastic Anaemia – B. Pharma 2nd Semester Pathophysiology notes pdf

Megaloblastic Anaemia



At the end of the PDF Notes, the students will be able to

       Define  megaloblastic anemia

       Discuss  the etiology of megaloblastic anemia

       Describe  the epidemiology of megaloblastic anemia

       Explain the pathogenesis of megaloblastic anemia

Megaloblastic Anaemia

       It is caused by impaired DNA synthesis and others by folate and vitamin B12 deficiency

       Abnormality in the haematopoietic precursors in the bone marrow – maturation of the nucleus is delayed relative to that of the cytoplasm.

       Formation of morphologically abnormal nucleated red cell precursor called megaloblast in the bone marrow

       Anaemia described is hyperchromic macrocytic

Etiological Classification of Megaloblastic Anaemia


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.


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, 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

Pernicious Anemia

Pernicious anemia is an autoimmune condition where the body destroys the cells that produce intrinsic factor, a substance required for the absorption of vitamin B12. Without intrinsic factor, the body can’t use vitamin B12 effectively, resulting in megaloblastic anemia.

Symptoms of Megaloblastic Anemia

Megaloblastic anemia can present with various symptoms, which may include:

  • Fatigue and Weakness: Individuals often experience extreme tiredness.
  • Pale Skin: A paler complexion can be observed due to reduced oxygen-carrying capacity of RBCs.
  • Shortness of Breath: Oxygen delivery to the body’s tissues is compromised.
  • Neurological Symptoms: In severe cases, neurological problems may arise, such as numbness and tingling in the extremities.

Pathophysiology of Megaloblastic Anaemia

       The common feature in megaloblastosis is a defect in DNA synthesis in rapidly dividing cells.

        RNA and protein synthesis are impaired.

        Unbalanced cell growth and impaired cell division occur since nuclear maturation is arrested.

        More mature RBC precursors are destroyed in the bone marrow prior to entering the blood stream (intramedullary hemolysis)

Vitamin B12

       Vitamin B12 or cobalamin is a complex organometallic compound having a cobalt atom situated within a corrin ring.

       The liver is the principal storage site of vitamin B12

       Major source of loss is via bile and shedding of intestinal epithelial cells.

        A major part of the excreted vitamin B12 is reabsorbed in the ileum by the IF resulting in enterohepatic circulation

Sources of Vitamin B12

      Micro-organisms (Soil, water animal intestine)

    Man and animals intestinal lumen but not  absorbed 3-5µg excreted daily in faeces

      Non veg foods: Muscle, liver, kidney, oysters,fish, egg yolk

Vegetable source: is pulses (legumes)

—  Dairy milk in smaller amounts

—  Daily requirement: 1-3 µg,

— Pregnancy & lactation 3-5 µg

— Commercial source: Streptomyces Griseus

Sources of Vitamin B12

Functions of B12

Vitamin B12 plays an important role in general cell metabolism

       Essential for normal haematopoiesis and for maintenance of integrity of the nervous system.

      Vitamin B12 acts as a co-enzyme

Functions of B12

Pharmacokinetics of B12


Ø  Cobalamins in food are in bound form inactive, released by cooking (heat) and by proteolysis in stomach & intestine.

Ø  Vit B12 is not soluble so absorption depends on  various transfer factors

       R- Factor, Intrinsic factor & Transcobolamin II

Pharmacokinetics of B12

Metabolic functions of Vit B12

Metabolic functions of Vit B12

C: Purine biosynthesis reduced , defective DNA

—  Methyl THF trapping & lack of S- adenosyl  methionine can cause this

D: Cell growth & multiplication (Poultry)

E: Role in folate uptake & storage

B12 Deficiency Symptoms

—  Atrophic glossitis (shiny tongue)

—  Shuffling broad gait

— Anemia and related sx

—  Vaginal atrophy

—  Malabsorption

—  Jaundice

—  Personality changes

—  Hyperhomocysteinemia

—  Neurologic symptoms (next slide)

—  Copper deficiency can cause similar neurologic symptoms

Folate Metabolism

       BIOCHEMISTRY: Folate or folic acid, a yellow compound, is a member of water-soluble B complex vitamins –pteroyl glutamic acid

       ABSORBTION: from the duodenum and upper jejunum

Folate Metabolism

       TISSUE STORES. The liver and red cells are the main storage sites of folate, largely as methyl THF polyglutamate form

       Total folate in body = 5 to 10 mg (1/3 in liver  as methyl folate)

       FUNCTIONS: acts as a co-enzyme for 2 important biochemical reactions

  1. Thymidylate synthetase reaction. Formation of deoxy thymidylate monophosphate (dTMP) from its precursor form, deoxy uridylate monophosphate (dUMP).

2.       Methylation of homocysteine to methionine. This reaction is linked to vitamin B12 metabolism

Folate Metabolism

Causes of Folate Deficiency

       Malnutrition: Destroyed by heat during cooking

       Alcoholism (decreased in 2-4 days): impairs enterohepatic cycle and inhibits absorption

       Increased requirement in hemolytic anemia, pregnancy, exfoliative skin disease

       IBD, celiac sprue


      Trimethoprim, Methotrexate, Primethamine (inhib DHFR)

      Phenytoin: blocks FA absorption, increases utilization (mech unknown)

Folate deficiency symptoms

       Similar symptoms as B12 save for neurologic symptoms

       Presentation is different classically:


      Very poor dietary intake



      Living alone

Diagnosis and Testing

To diagnose megaloblastic anemia, several tests may be conducted, including:

  • Blood Tests: A complete blood count (CBC) can reveal the presence of large, abnormal RBCs.
  • Bone Marrow Examination: In some cases, a bone marrow biopsy may be necessary.
  • Intrinsic Factor Antibody Test: This test helps identify if pernicious anemia is the cause.

Treatment Options

The treatment of megaloblastic anemia primarily involves addressing the underlying cause. The common treatment options include:

  • Vitamin B12 Supplements: For vitamin B12 deficiency, supplements can help restore normal RBC production.
  • Folate Supplements: Folate supplements are used when folate deficiency is the cause.
  • Dietary Changes: Incorporating foods rich in vitamin B12 and folate into the diet can be beneficial.

Preventing Megaloblastic Anemia

Preventing megaloblastic anemia is possible through:

  • Maintaining a Balanced Diet: Consuming a variety of foods rich in vitamin B12 and folate.
  • Regular Health Check-ups: Periodic check-ups can detect deficiencies early on.

Living with Megaloblastic Anemia

Coping with megaloblastic anemia involves managing symptoms and seeking support when needed. It’s essential for individuals with this condition to:

  • Cope with Symptoms: Learning to manage fatigue and other symptoms.
  • Seek Support and Resources: Support groups and medical professionals can provide valuable assistance.

Complications Associated with Megaloblastic Anemia

Megaloblastic anemia can lead to various complications, including:

  • Increased Risk of Heart Disease: The decreased oxygen supply can strain the heart.
  • Potential Nerve Damage: Severe cases may result in nerve damage.

Megaloblastic Anemia in Pregnancy

Pregnant women with megaloblastic anemia require special attention, as it can pose risks to both the mother and the developing fetus. Proper management and monitoring are crucial during pregnancy.

FAQs on Megaloblastic Anemia

What is megaloblastic anemia?

Megaloblastic anemia is a type of anemia characterized by large, immature red blood cells, often caused by vitamin B12 or folate deficiency.

What are the common symptoms of megaloblastic anemia?

Common symptoms include fatigue, pale skin, shortness of breath, and, in severe cases, neurological symptoms.

How is megaloblastic anemia diagnosed?

Megaloblastic anemia is diagnosed through blood tests, bone marrow examination, and intrinsic factor antibody tests.

Can megaloblastic anemia be prevented?

Yes, it can be prevented by maintaining a balanced diet rich in vitamin B12 and folate, and through regular health check-ups.

What are the treatment options for megaloblastic anemia?

Treatment options include vitamin B12 and folate supplements, as well as dietary changes.


Megaloblastic anemia is a condition that affects the quality of life, but with proper diagnosis, treatment, and lifestyle changes, individuals can effectively manage this condition. Maintaining a healthy diet, seeking regular medical check-ups, and understanding the importance of essential nutrients are key steps in preventing and addressing megaloblastic anemia.