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Questions and Answers
What characterizes the macrocytes in non megaloblastic macrocytic anemias?
What characterizes the macrocytes in non megaloblastic macrocytic anemias?
Which of the following conditions does NOT cause non megaloblastic macrocytic anemia?
Which of the following conditions does NOT cause non megaloblastic macrocytic anemia?
In non megaloblastic macrocytic anemia, what underlying issue is primarily responsible for macrocytosis?
In non megaloblastic macrocytic anemia, what underlying issue is primarily responsible for macrocytosis?
What is the primary difference between megaloblastic and non megaloblastic macrocytic anemia in terms of pathophysiology?
What is the primary difference between megaloblastic and non megaloblastic macrocytic anemia in terms of pathophysiology?
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Which of the following statements about the macrocytes seen in non megaloblastic macrocytic anemia is accurate?
Which of the following statements about the macrocytes seen in non megaloblastic macrocytic anemia is accurate?
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What is a common characteristic of hereditary elliptocytosis?
What is a common characteristic of hereditary elliptocytosis?
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Which enzyme is deficient in G6PD enzyme deficiency?
Which enzyme is deficient in G6PD enzyme deficiency?
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What does G6PD primarily reduce while oxidizing glucose-6-phosphate?
What does G6PD primarily reduce while oxidizing glucose-6-phosphate?
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Which of the following is NOT a consequence of defective red cell metabolism?
Which of the following is NOT a consequence of defective red cell metabolism?
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What is the common presentation of most cases with G6PD enzyme deficiency?
What is the common presentation of most cases with G6PD enzyme deficiency?
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What specific advantage do female heterozygotes have regarding Falciparum malaria?
What specific advantage do female heterozygotes have regarding Falciparum malaria?
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Which geographic regions are primarily affected by the races associated with Falciparum malaria resistance in female heterozygotes?
Which geographic regions are primarily affected by the races associated with Falciparum malaria resistance in female heterozygotes?
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Which of the following statements about Falciparum malaria and female heterozygotes is NOT true?
Which of the following statements about Falciparum malaria and female heterozygotes is NOT true?
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Which factor is most likely responsible for the advantage that female heterozygotes have against Falciparum malaria?
Which factor is most likely responsible for the advantage that female heterozygotes have against Falciparum malaria?
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What type of genetic trait is associated with the advantage in female heterozygotes against Falciparum malaria?
What type of genetic trait is associated with the advantage in female heterozygotes against Falciparum malaria?
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What characteristic defines the neutrophils in this condition?
What characteristic defines the neutrophils in this condition?
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How is the bone marrow typically characterized in this condition?
How is the bone marrow typically characterized in this condition?
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Which feature of the erythroblasts is noted in this condition?
Which feature of the erythroblasts is noted in this condition?
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What is the significance of normal cytoplasmic hemoglobinization in the erythroblasts?
What is the significance of normal cytoplasmic hemoglobinization in the erythroblasts?
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What type of chromatin pattern is observed in the erythroblasts?
What type of chromatin pattern is observed in the erythroblasts?
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What is the main cause of hereditary spherocytosis (HS)?
What is the main cause of hereditary spherocytosis (HS)?
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Which of the following cell types is associated with hereditary spherocytosis?
Which of the following cell types is associated with hereditary spherocytosis?
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The interaction between which components is disrupted in hereditary spherocytosis?
The interaction between which components is disrupted in hereditary spherocytosis?
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Which of these statements accurately describes elliptocytes?
Which of these statements accurately describes elliptocytes?
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Which structures in red blood cells are primarily affected in hereditary spherocytosis?
Which structures in red blood cells are primarily affected in hereditary spherocytosis?
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What is the ratio of females to males affected by the condition discussed?
What is the ratio of females to males affected by the condition discussed?
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At what age does the peak occurrence of the condition typically occur?
At what age does the peak occurrence of the condition typically occur?
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Which of the following autoimmune diseases is often associated with the condition mentioned?
Which of the following autoimmune diseases is often associated with the condition mentioned?
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Which population group has a higher prevalence of the condition?
Which population group has a higher prevalence of the condition?
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Considering the epidemiological data, how might age affect the incidence of the condition?
Considering the epidemiological data, how might age affect the incidence of the condition?
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Study Notes
Hematology
- Hematology is the study of blood and blood disorders.
- Lecture 3&4, Dr Sura Al Shamma, Pathology department, 2024.
Macrocytic Anemias
- These anemias occur when red blood cells (RBCs) have a mean corpuscular volume (MCV) greater than 98 fl.
- Two groups of macrocytic anemias exist:
- Megaloblastic anemia
- Non-megaloblastic macrocytic anemia
Non-Megaloblastic Macrocytic Anemias
- These disorders are characterized by macrocytosis not due to vitamin B12 or folate deficiency.
- Red blood cells are round in these cases.
- Conditions that can cause this include:
- Reticulocytosis
- Hypothyroidism/myxedema
- Myelodysplastic syndrome
- Scurvy (Vitamin C deficiency)
- Liver disorders
- Excess alcohol consumption (MCV not >110).
- Congenital dyserythropoietic anemia (CDA I & III)
- Erythrolukemia
- Neonates
Megaloblastic Anemia
- Megaloblastic anemia is characterized by abnormal erythroblasts in the bone marrow, with delayed nucleus maturation relative to cytoplasm.
- The underlying cause of this is a deficiency of vitamin B12 or folate, which is crucial for DNA synthesis.
- Macrocytes in this condition are typically oval-shaped, thus also called macro-ovalocytes.
Causes of Megaloblastic Anemia
- Vitamin B12 deficiency
- Folate deficiency
- Abnormalities of vitamin B12 or folate metabolism (e.g., transcobalamin deficiency, nitrous oxide, antifolate drugs)
- Other defects of DNA synthesis
- Congenital enzyme deficiencies (e.g., orotic aciduria)
- Acquired enzyme deficiencies (e.g., alcohol, therapy with hydroxyurea, cytosine arabinoside)
Vitamin B12
- Dietary sources include meats, fish, eggs, and dairy.
- Daily adult requirement is 1-2 µg.
- Body stores 2-3 mg, sufficient for 2-4 years.
- Absorption involves binding to intrinsic factor (IF) in the duodenum and jejunum, followed by absorption in the terminal ileum.
- Autoimmune gastric atrophy, leading to decreased intrinsic factor production, is a frequent cause of deficiency.
- Other causes include gastrectomy, ileal resection, ileitis, Zollinger-Ellison syndrome, blind loop syndrome, and fish tapeworm infestation, and pancreatic insufficiency.
Vitamin B12 Absorption
- Vitamin B12 in food is initially bound to proteins.
- Stomach acid and enzymes release vitamin B12.
- Intrinsic factor (IF) produced by stomach cells binds to B12.
- The IF-B12 complex binds to receptors in the ileum, the small intestine where absorption occurs.
- Some unbound vitamin B12 is absorbed passively.
- Colon bacteria can synthesize B12 that is not absorbed.
Causes of Severe Vitamin B12 Deficiency
- Nutritional (vegan diets)
- Malabsorption (gastric problems, intestinal disorders, surgical procedures)
- Intestinal (intestinal stagnant loop syndrome, blind-loop syndrome, chronic tropical sprue, ileal resection, Crohn's disease)
- Other factors (malabsorption of food B12, atrophic gastritis, proton pump inhibitors or metformin, severe pancreatitis, gluten-induced enteropathy, HIV infection).
Folic Acid
- Dietary sources include green vegetables, fruits, meat, and liver.
- Daily adult needs range 100-150 mcg.
- Body stores 10-12 mg, enough for 3-4 months.
- Primarily absorbed in the jejunum.
- Causes of deficiency include:
- Decreased intake (alcohol use disorders, malnutrition, elderly patients, institutionalized patients)
- Increased demand (pregnancy, hemolysis, hemodialysis, malabsorption)
- Medications (anticonvulsants, anticancer agents)
Causes of Folic Acid Deficiency
- Nutritional (especially in geriatric patients, in hospitalised patients, institutional care)
- Malabsorption (tropical sprue, gluten-induced enteropathy, partial gastrectomy, extensive jejunal resection, Crohn's disease)
- Excess utilization (pregnancy, lactation, prematurity)
- Pathological (haematological diseases, inflammatory diseases, malignant diseases, excess urinary folate loss)
- Drugs (anticonvulsants, sulfasalazine)
- Mixed (liver disease, alcoholism, intensive care)
Biochemical Basis for Megaloblastic Anemia
- Folate deficiency inhibits thymidylate synthesis, crucial for DNA synthesis, due to the role of 5,10-methylene-THF polyglutamate as a coenzyme.
- Vitamin B12 plays an indirect role in DNA synthesis by converting methyl-THF to THF, which is needed for folate polyglutamate synthesis.
Clinical Features of Megaloblastic Anemia
- Onset is gradual and insidious with progressive anemia symptoms.
- Common feature is a defect in DNA synthesis affecting rapidly dividing cells in bone marrow and other tissues.
- Diagnosis often occurs as an incidental finding during routine blood tests.
- Symptoms can include:
- Anemia(shortness of breath, muscle weakness, pale skin, icterus, loss of appetite, weight loss, diarrhoea, nausea, fast heartbeat)
- Specific signs (glossitis, jaundice & splenomegaly, neurological signs (peripheral neuropathy, paraesthesia, dementia), neural tube defects, purpura, etc.)
Pernicious Anemia
- Autoimmune destruction of gastric epithelium, leading to vitamin B12 deficiency.
- Common among Northern Europeans, typically occurring in individuals aged 60-70 years old.
- Associated with:
- Chronic gastric inflammation
- Achlorhydria
- Lack of intrinsic factor secretion
Laboratory Diagnosis of Megaloblastic Anemia
- Complete blood count (decreased Hg, MCV > 100-140 fL in severe cases, macrocytes are typically oval)
- Bone marrow examination (hypercellularity, large erythroblasts with primitive chromatin pattern)
- Biochemistry (Serum B12 levels low, Serum and erythrocytic Folate levels low, Homocysteine and Methylmalonic acid levels increased, LDH and unconjugated bilirubin levels).
Laboratory Diagnosis of Pernicious Anemia
- Checking serum vitamin B12 levels.
- Detect antibodies against intrinsic factor or parietal cells.
- Schilling test (not as commonly used now)
Treatment of Megaloblastic Anemia
- Vitamin B12 deficiency: Hydroxocobalamin, intravenously or intramuscularly. Maintenance doses.
- Folate deficiency: Oral administration of folic acid.
Haemolysis
- Hemolytic anemias are due to accelerated red blood cell (RBC) destruction.
- Two primary mechanisms exist: extravascular and intravascular haemolysis.
- Red blood cell destruction occurs after an average lifespan of 120 days when cells are removed extravascularly via macrophages or intravascularly (directly in the circulation).
Hereditary Hemolytic Anaemias
- These conditions include defects in red blood cell membranes or metabolic pathways.
- Types Include: Membrane defects (congenital spherocytosis, hereditary elliptocytosis), Metabolic defects (G6PD deficiency), hemoglobin defects (qualitative defects - sickle cell anaemia, quantitative defects – Thalassaemia).
Membrane Defects
- Includes hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and other related disorders.
- Characterized by intrinsic abnormalities in red blood cell membranes.
- Genetic defects lead to abnormalities in red blood cell shape and function.
- These abnormal red blood cells are removed by the reticuloendothelial system more quickly than normal cells.
Hereditary Spherocytosis (HS)
- Common hereditary hemolytic anemia in Northern Europeans, characterized by genetic defects impacting membrane proteins (e.g., ankyrin, spectrin, band 3).
- These defects lead to spherocytic red cells that are less flexible and more fragile, resulting in their premature destruction by the spleen.
- Typically have autosomal dominant inheritance.
Clinical Features of Hereditary Spherocytosis
- Inheritance: Autosomal dominant, sometimes autosomal recessive.
- Age of onset: Infancy to adulthood.
- Symptoms: Jaundice, splenomegaly, pigment gallstones.
Laboratory Findings of Hereditary Spherocytosis
- Anemia (normochromic)
- Reticulocytosis (5-20%)
- Presence of spherocytes (smaller, denser red blood cells) on blood film.
- Increased bilirubin (unconjugated), LDH levels.
Other Investigations of Hereditary Spherocytosis
- Osmotic fragility test.
- Autohemolysis test.
- Flow cytometry (eosin-5-maleimide test).
Treatment of Hereditary Spherocytosis
- Splenectomy (removal of spleen).
- Folic acid supplementation in severe cases to prevent folate depletion.
G6PD Deficiency
- X-linked recessive disorder affecting red blood cell metabolism.
- G6PD enzyme is essential for reducing NADPH, needed for the production of reduced glutathione (GSH) against oxidant stress.
Clinical Features of G6PD Deficiency
- Usually asymptomatic.
- Acute hemolytic episodes in response to oxidative stress (drugs, fava beans, infections).
- Neonatal jaundice is possible.
Diagnostic Features of G6PD Deficiency
- Normal blood counts between hemolytic crises.
- Blood tests (G6PD assay, peripheral blood film).
Pyruvate Kinase (PK) Deficiency
- Autosomal recessive disorder affecting red blood cell energy production.
- PK is necessary to make ATP for RBC function and survival.
- Dehydrated, distorted red blood cells, often appearing as "prickle cells" or echinocytes, are observed on peripheral smears.
- These cells have a reduced lifespan and are removed by the spleen.
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Test your knowledge on non-megaloblastic macrocytic anemias with this quiz. Explore the characteristics of macrocytes, differences in pathophysiology, and related conditions. Assess your understanding of G6PD enzyme deficiency and its implications.
