Anemia Types and Iron Metabolism Quiz

Common Red Blood Cell Disorders and Aplastic Anemia

• Common Red Blood Cell Disorders:

  • Nutritional anemia: iron deficiency anemia (IDA), megaloblastic anemia
  • Hemolytic anemia:
    • Immune: autoimmune hemolytic anemia (AIHA)
    • Non-immune: paroxysmal nocturnal hemoglobinuria (PNH), methemoglobinemia (MAHA)
    • Enzymatic deficiency: glucose-6-phosphate dehydrogenase (G6PD) deficiency anemia
    • RBC membrane defect: hereditary spherocytosis, elliptocytosis, etc.
    • Thalassemia and hemoglobinopathies
  • Bone marrow disease: aplastic anemia (AA)

• RBC Disorders Approach by MCV:

  • Microcytic anemia: IDA, thalassemia, sideroblastic anemia (lead poisoning)
  • Normocytic anemia: hemolytic disorders (AIHA, PNH, RBC membrane defect, G6PD deficiency anemia), anemia of chronic disease, AA.
  • Macrocytic anemia: megaloblastic anemia

Iron Deficiency Anemia (IDA)

• Prevalence: Most common cause of anemia globally, especially in women, children, and under-resourced/middle-income countries.
• Essential Nutrient: Iron is crucial for RBC production.
• Dietary Sources: Iron is found in various foods.
• Iron Forms:
  • Ferrous (Fe2+): heme iron (animal products)
  • Ferric (Fe3+): non-heme iron (plant-based foods)
• Rich Iron Foods: List includes examples like pork, chicken, liver, egg yolk, broccoli, dried beans, etc.

Healthy Iron Requirements and Turnover

• Daily Iron Turnover: 20–25 mg/day for erythropoiesis.
• Dietary Iron Absorption: 1-2 mg/day primary in duodenum and proximal jejunum
• Iron in Blood: 0.5 mg per mL of blood.
• Losses = Iron sloughed with senescent enterocytes and skin cells.
• Menstruation in women of child bearing age ( 1800 mg)

Iron Transport Overview

• Iron Absorption: Uptake of iron occurs in the enterocytes, using DMT1.
• Iron Storage: Storage of iron happens via Ferritin.
• Iron Exporter: Ferroportin is the iron exporter
• Regulation: Key role of hepcidin in iron regulation and homeostasis.

Iron Regulation

• Hepcidin: A key protein regulating systemic iron homeostasis; Internalizes and degrades ferroportin. (important)

Iron and Erythropoietin: Vital for RBC Production

• Erythropoietin: Essential for RBC production
• RBC Production Timeline: Stages from Pluripotent Stem Cell to mature RBC

Various Etiologies of Iron Deficiency Anemia

• Causes: The list includes factors like increased iron demand (infancy, pregnancy, growth spurts) and decreased iron absorption from the digestive or genitourinary tract. Drug-induced and chronic blood loss are also cited.
• Etiologies: There are several causes, such as malnutrition, frequent blood donation, infections, cancers, and surgeries. Physiologic causes include menstruation and/or pregnancy.

Clinical Manifestations of Iron Deficiency

• Symptoms including fatigue, heart palpitations, shortness of breath, poor focus and restless leg syndrome, weakness, headaches , brittle nails, and cold intolerance.
• Other clinical symptoms like alopecia, pica, angular cheilitis, and atrophic glossitis.

Plummer-Vinson Syndrome (Paterson-Kelly Syndrome):

• Dysphagia: Difficulty swallowing due to a post-cricoid web.
• Glossitis: Inflammation of the tongue.
• Koilonychia: Spoon-shaped nails.

Iron Deficiency and Iron Deficiency Anemia

• Diagnostic Criteria: Blood tests (serum iron, % saturation, HCT, and RBC morphology) are used to detect anemia and iron deficiency. Various values are defined as ‘normal’ or ‘deficient’. The severity of iron-deficiency is classified by evaluating blood properties and storage sites for iron.
• BM iron > Plasma iron > MCV > Hb
• MCV < 80 fl

Diagnostic Criteria for Iron Deficiency Anemia

• Serum Ferritin Levels: Levels help determine iron stores; above 30 µg/L suggests sufficient stores.
• Diagnostic Testing: Additional tests like the Transferrin Saturation (TSAT) and soluble transferrin receptor (sTfR) are useful in inconclusive cases. Bone marrow study using Prussian blue staining is used for final definitive diagnosis of IDA.

Types of Iron Deficiency Anemia and Diagnostic Thresholds in Adults (Table):

RBC disorders approach by MCV (Summary):

• Microcytic anemia: IDA, thalassemia
• Normocytic anemia: hemolytic disorder (AIHA, PNH, RBC membrane defect, G6PD deficiency anemia), anemia of chronic disease, AA.
• Macrocytic anemia: megaloblastic anemia

Sideroblastic Anemia

• Acquired: Causes such as exposure to certain drugs (isoniazid, etc.) or heavy metals (lead). Underlying diseases (chronic neoplastic disease) or nutritional deficiencies (copper deficiency) are listed too.
• Hereditary: Genetic defects in enzymes like ALAS2 are listed as part of the causes. Mitochondrial disorders are listed too (like Pearson marrow-pancreas syndrome).

Lead Poisoning

• Mechanism: Defect in heme synthesis (ferrochelatase).
• Sources: Battery factories and metal processing/manufacturing facilities are common sources of lead exposure

Hemolytic Anemia

• The various types of Hemolytic Anemia and relevant laboratory tests are listed (Table 1).
• The processes of Extravascular and Intravascular hemolysis are discussed.

Autoimmune Hemolytic Anemia (AIHA)

• Mechanism: Autoantibodies (AutoAb) attack and destroy red blood cells (RBCs) via mechanisms that are either direct complement mediated or phagocytosis via splenic macrophages.

Mechanisms of Immune Hemolysis

• Intravascular: IgM or IgG antibodies that fix complement; Complement cascade activates MAC, leading to RBC lysis.
• Extravascular: IgG antibodies bind to RBCs, recognized by Fc receptors on macrophages, resulting in phagocytosis predominantly in the spleen and liver.

IgG and IgM Antibodies

• IgG: Typically associated with warm-reacting antibodies and intravascular hemolysis.
• IgM: Typically associated with cold-reacting antibodies, often extravascular, targeting liver with spleen as a minor contributor. Intravascular destruction is possible with IgM

Investigations of G6PD Deficiency Anemia

• Tests and findings are described for the diagnosis of this condition, including anemia, and decreased haptoglobin, increased reticulocytes, increased LDH, and hyperbilirubinemia.

Treatment of G6PD Deficiency Anemia

• The treatment is based on identifying and addressing the cause of the hemolysis. Aggressive hydration, blood transfusion, and folic acid supplementation are common treatments.

Microangiopathic Hemolytic Anemia (MAHA)

• Causes: Conditions like disseminated intravascular coagulopathy (DIC), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS).

Microvascular and Macrovascular Causes of MAHA:

• A range of vascular disorders, from disseminated intravascular coagulopathy (DIC) to malignant hypertension (HT)
• A range of vascular disorders, from large vascular malformations (AVMs) to prosthetic heart valve issues (prosthetic valve/IE) are referenced.

Disseminated Intravascular Coagulation (DIC):

• Causes: Infections, trauma, cancers, etc. are listed as causes
• Laboratory and Treatment details are described

Thrombotic Thrombocytopenic Purpura (TTP)

• ADAMTS13 deficiency: acquired (autoAb); congenital
• Clinical Findings; Fever, renal insufficiency, and neurologic manifestations
• Laboratory findings; Thrombocytopenia, MAHA
• Treatment; Urgent plasma exchange, Immunosuppressive treatment, avoiding platelet transfusion except in significant bleeding situations.

Hemolytic Uremic Syndrome (HUS)

• Causes: Often triggered by an infection, notably Shiga toxin-producing bacteria, complement defects, and autoimmunity.
• Clinical Findings : Clinical presentation with MAHA, thrombocytopenia, AKI, and often a preceding diarrheal illness

Anemia of Chronic Disease (ACD) / Anemia of Inflammation

• Mechanism: Increased hepcidin production (blocks iron release), inadequate erythropoietin response.
• Causes: Numerous listed, including infections, cancers, autoimmune disorders

Aplastic Anemia (AA)

• Pathology: Characterized by the failure of blood cell production due to damaged or absent hematopoietic stem cells (HSC).
• Causes: Listed including cytotoxic drugs and radiation, viral infections, and other infectious agents,
• Diagnosis: Bone marrow study is the gold standard.
• Treatment: The list includes supportive care, hematopoietic growth factors, hematopoietic stem cell transplantation, Immunosuppressive therapies and sometimes sex hormones.

Megaloblastic Anemia

• Causes: Vitamin B12 deficiency (e.g., pernicious anemia) and folate deficiency, often from dietary insufficiency or malabsorption.
• Characteristics: Marked macrocytosis (large red blood cells), hypersegmented neutrophils, and ineffective erythropoiesis.
• Diagnosis; Macrocytic anemia, anisocytosis, an elevated red blood cell distribution width (RDW), and often pancytopenia.
• Laboratory findings; Elevated LDH and indirect bilirubin.
• Treatment: Supportive treatment: Oral folic acid, or intramuscular vitamin B12 for severe deficient situations.

Test your knowledge on various types of anemia and iron metabolism. This quiz covers key concepts such as iron deficiency, red blood cell production, and the role of specific proteins in iron homeostasis. Perfect for students in medical or health sciences courses!