Megaloblastic Anemia and Vitamin Deficiencies

Microcytic & Macrocytic Anaemia

• This lecture defines anaemia and outlines mechanisms behind microcytic and macrocytic anaemia.
• Aims include describing the importance of iron, vitamins B12 and folate for blood cell production, explaining normal iron and B12/folate metabolism, and how labs diagnose these conditions.
• Anaemia is when haemoglobin concentration falls below the normal range for age and sex.
• Reference ranges for haemoglobin are 13.3-16.7 g/dL for males and 11.8-14.8 g/dL for females.
• Students should know the difference between anaemia, polycythaemia and erythrocytosis.

General Signs & Symptoms

• Common symptoms across most anaemias include fatigue, dizziness, fainting, low blood pressure, palpitations, rapid heart rate, chest pain, angina, and heart attack.
• Symptoms particular to a specific type of anaemia can include paleness, coldness, yellowing, shortness of breath, muscular weakness, changes in stool colour, and an enlarged spleen.
• Pallor of the conjunctiva and nail bed are common features of severe anaemia.

Normal Values For Blood Cells And Haematinics

• This table lists reference ranges for various blood cells and related factors (e.g., haemoglobin, red blood cells, PCV, MCV, MCH, reticulocytes, white blood cells, serum iron, serum ferritin, serum vitamin B12, serum folate, red cell folate).
• The tables provide numerical values based on gender.

FBC-Classification and Laboratory Findings in Anaemia

• Leucocyte and platelet counts aid in distinguishing between pure anaemia and pancytopenia.
• A high reticulocyte count signifies anaemia.
• Microcytic hypochromic anaemia is defined by MCV <80fL and MCH <27pg, often caused by iron deficiency, thalassemia, or lead poisoning.
• Normocytic normochromic anaemia has MCV 80-95fL and MCH ≥27pg, commonly resulting from haemolytic anaemia, chronic anaemia, and renal disease.
• Macrocytic anaemia is determined by MCV >95fL, often due to vitamin B12 or folate deficiency.

Causes Of Microcytic Anaemia

• Causes of microcytic anaemia include iron deficiency, chronic disease anaemia, thalassemia, and lead poisoning.
• Specific characteristics of each cause are detailed in charts presenting mean cell volume, haemoglobin, ferritin, red blood cell count, blood film characteristics and history for each cause.

Features of Iron Deficiency Anaemia

• Features common to other types of anemia include fatigue, dizziness, headache, shortness of breath, palpitations, angina, intermittent claudication, pallor, tachycardia, and flow murmur, congestive cardiac failure.
• Specific features include glossitis, koilonychia, angular stomatitis, and pica.
• Atrophic gastritis and Plummer-Vinson or Paterson-Kelly syndrome can occur alongside iron deficiency anaemia.

Sources of Iron

• Iron is obtained from dietary sources like liver, meat, seafood, eggs, vegetables, and dried foods.
• Iron absorption can be influenced by factors like age, gender, pregnancy, and menstruation, impacting iron requirements accordingly.

Iron Uptake, Storage And Utilization For HB Synthesis

• Dietary iron is absorbed into the body and combined with protein to form ferritin.
• Iron is transported to the marrow, where it can be used to produce haemoglobin. Hemoglobin is broken down when red blood cells wear out and iron is recycled.

Iron level stores

• When iron absorption is low, the body utilizes stored iron, leading to a negative balance.
• Decreased iron supply or increased requirement (e.g., menstruation, pregnancy) can lead to iron deficiency.

Laboratory Findings in Iron deficiency Anaemia

• Common lab findings for iron-deficient anaemia include low haemoglobin, red blood cell count, mean corpuscular haemoglobin (MCH) and mean cell volume (MCV).
• Specific characteristics include microcytosis, hypochromia, elliptocytosis, tear drop poikilocytosis, and anisocytosis.

Treatment

• Treatment options primarily include iron supplements, with ferrous sulphate being the most prevalent choice.
• Severe cases may require blood transfusions and iron therapy, combined with vitamin C.
• Birth control pills may also affect iron levels.

Macrocytic Anaemia

• Red blood cells (RBCs) are abnormally large (MCV >98fL) in this type of anaemia.
• It encompasses both megaloblastic and non-megaloblastic causes.
• Based on the appearance of developing erythroblasts in the bone marrow.

Sources of B12 (Cobalamin)

• This table details the vitamin B12 content in various foods like beef liver, rainbow trout, salmon, beef, tuna, yogurt, fortified cereal, milk, swiss cheese, and eggs.
• The recommended daily allowance (RDA) and sources (animals/microorganisms bound to protein like methycobalamin) are also noted.

Role of B12 within the body

• Explain the function of vitamin B12 as a cofactor for two key enzymes: the conversion of L-methylmalonyl coenzyme A to succinyl-coenzyme A, and the methylation of homocysteine to methionine.

B12 Absorption Summary

• Vitamin B12 combines with intrinsic factor (IF) before being absorbed by the ileum.
• After absorption, B12 binds with receptors on enterocytes.
• Endocytosis of the complex occurs within the distal ileum, destroying IF.

B12 Transport

• B12 is transported within the body using transcobalamin and haptocorrin.

Causes of Deficiency of Vitamin B12

• Causes include malnutrition (inadequate dietary intake), malabsorption (lack of intrinsic factor, gastrointestinal diseases, surgical removal of IF synthesis sites, drug-induced issues, or increased pregnancy requirement), and immune disorders such as pernicious anaemia (immune system attacks stomach cells producing intrinsic factor).

Pernicious anaemia

• Pernicious anaemia results from immune system attacks on stomach cells producing intrinsic factor.
• This leads to vitamin B12 malabsorption.
• Helicobacter pylori infection may initiate autoimmune gastritis, potentially leading to iron deficiency in younger individuals and pernicious anemia in older individuals.

Lab Diagnosis-B12 deficiency

• Diagnostic steps and values for serum B12 levels are included in a table to aid in pinpointing B12 deficiency.

Folate

• The table lists the folate content of different foods such as mustard greens, chicken liver, asparagus, okra, romaine lettuce, collard greens, spinach, broccoli, beef liver, kale and egg yolks.

Folate vs Vitamin B12

• Vitamin B12 and folate are compared across parameters like normal dietary intake, main food sources, cooking method effects, minimal adult daily requirement, body stores, absorption sites, and metabolic pathways (e.g., folate recycling)

Causes of Folate deficiency

• Causes of folate deficiency include inadequate dietary intake (folate is heat-labile), intestinal malabsorption (such as in celiac disease), increased requirements (during pregnancy), and drug-induced interference with absorption or metabolism (e.g., alcohol consumption or use of medications like methotrexate).

Why Are Large Cells Produced In Macrocytic Anaemia?

• Explains the importance of folate in nucleotide production and the impact on DNA synthesis.
• It also describes how inadequate folate or vitamin B12 leads to issues with DNA replication, resulting in larger cells.

Biochemical Basis of Megaloblastic Anaemia

• Inadequate amounts of dUMP/dTMP disrupt DNA synthesis, resulting in fewer cell divisions and larger cells.

Additional reading

• Lists specific chapters in relevant reference books for additional information on anaemia.
• Includes specific URLs of articles on the subject.