Microcytic Anemias Quiz

Anemia of Chronic Disease & Sideroblastic Anemia

• Anemia of Chronic Disease (ACD) is the second most common type of anemia after iron deficiency anemia.
• It's a common finding in hospitalized patients.
• Etiology includes chronic inflammation/infections (e.g., rheumatoid arthritis, tuberculosis), alcoholism, and malignancy.

Interpretation of Iron Related Investigations

• Serum Iron: Bound to transferrin; normal level ~100 µg/dL. Transferrin, a liver-synthesized protein, binds iron. The amount of iron entering macrophages equals the amount leaving to bind with transferrin. Decreased serum iron occurs in iron deficiency (IDA). Increased serum iron occurs in iron overload diseases (sideroblastic anemia and hemochromatosis).
• Total Iron-Binding Capacity (TIBC): Correlates with transferrin; normal ~300 µg/dL. Decreased ferritin stores lead to increased liver transferrin synthesis. Iron deficiency increases transferrin and TIBC.

Interpretation of Iron Related Investigations (Ferritin)

• Ferritin is a soluble iron-binding storage protein synthesized by bone marrow macrophages and hepatocytes. Iron is stored in a non-toxic form.
• Macrophages are the primary storage site for ferritin from senescent red blood cells in the bone marrow.
• 1 μg/L serum ferritin correlates with 8 mg of storage iron.
• Inflammation increases ferritin production.
• Decreased serum ferritin is a sign of iron deficiency.
• Increased serum ferritin occurs in ACD and iron overload diseases (e.g., hemosiderosis, hemochromatosis).

Interpretation of Iron Related Investigations (Hemosiderin)

• Hemosiderin is an insoluble product of ferritin degradation in lysosomes.
• Decreased and increased hemosiderin levels correlate with ferritin changes.
• Stains blue with Prussian blue stain.

Red Blood Cell Distribution Width (RDW)

• RDW reflects variations in red blood cell size (anisocytosis).
• Increased RDW is significant.
• Increased RDW signifies an irregular mixture of microcytic and normocytic cells as seen in iron deficiency anemia.

Mean Corpuscular Hemoglobin Concentration (MCHC)

• MCHC is the average hemoglobin concentration in red blood cells.
• Decreased MCHC correlates with decreased hemoglobin synthesis, which can signify microcytic anemia (e.g., iron deficiency). Red cells have less hemoglobin (hypochromasia).
• Increased MCHC reflects hereditary spherocytosis. Spherocytes lack a central pallor (hyperchromasia / hyperchromia).

Hematologic Cluster of Differentiation Markers ("CDs")

• CDs are differentiation markers of blood cells.
• Different CDs identify different cell types (e.g., T lymphocytes, monocytes, granulocytes).

Example: PBS in Microcytic Hypochromic in Iron Deficiency

• Image of a peripheral blood smear showing microcytic hypochromic red blood cells indicative of iron deficiency.

Pathophysiology of Microcytic Anemias (Including Sideroblastic Anemia)

• Decreased hemoglobin synthesis is a hallmark of all microcytic anemias.
• Microcytic anemia is from decreased production of heme and/or globin chains.

Anemia of Chronic Disease (ACD)

• ACD is the second most common anemia after iron-deficiency anemia.
• Common in hospitalized patients.
• Causes include chronic inflammation (e.g., rheumatoid arthritis), infections (e.g., tuberculosis), and chronic renal disease.
• It also occurs in alcoholism and malignancy.

Regulation of Iron Absorption

• Diagram illustrating iron absorption regulation. Key elements, such as heme carrier protein 1, ferroportin 1, hepcidin, liver, mucosa ferritin, DMT1, plasma transferrin, erythroid marrow, are vital in the process.

Pathogenesis of Anemia of Chronic Disease (ACD)

• Decreased heme synthesis
• Decreased erythropoietin (EPO) production
• Hepcidin increased production by the liver.

Comparison Between IDA and ACD

• Comparison table showing differences in serum iron, TIBC, transferrin saturation, and serum ferritin levels between iron deficiency anemia (IDA) and ACD.

Treatment of ACD

• Treating the underlying disease is crucial.
• Erythropoietin (EPO) injections can improve red blood cell production, particularly in chronic kidney disease.
• Hepcidin antagonists are a relatively new treatment option.

Laboratory Studies to Differentiate Microcytic Anemias

• Table showing laboratory differences in ferritin, serum iron, TIBC, and transferrin saturation levels between different microcytic anemias (iron deficiency, thalassemia, and ACD).

Sideroblastic Anemia

• Sideroblastic anemia is an iron overload type of anemia.
• Due to a defect in heme synthesis within red blood cell precursors' mitochondria.
• Causes: chronic alcoholism, pyridoxine deficiency, lead poisoning, and hereditary types.
• Pathogenesis: heme's negative feedback on 6-aminolevulinic acid synthase (ALA); iron accumulation.

Sideroblastic Anemia: Morphology

• Ringed sideroblasts are a defining characteristic.
• Dark blue iron granules surround the nucleus.

Lead Poisoning and Sideroblastic Anemia

• Lead poisoning affects children mainly and can cause sideroblastic anemia.
• Lead-based paint, old homes, homemade pottery glazes can be sources.
• Causes pica (abnormal cravings).
• Peripheral blood smear reveals coarse basophilic stippling.
• Lead denatures ribonuclease, which causes ribosomes to persist in the cytoplasm.

Laboratory Findings in Common Types of Microcytic Anemias

• Table comparing different tests, like MCV, serum iron, TIBC, ferritin, RDW, Hb electrophoresis, etc., in various microcytic anemias.

Megaloblastic and Aplastic Anemias

• Megaloblastic and aplastic anemias are distinct. Megaloblastic anemias are due to impaired DNA synthesis (vitamin B12 or folate deficiency). Aplastic anemia reflects bone marrow failure.

Megaloblastic Anemia

• Defined by large, abnormal-appearing erythroid precursors (megaloblasts) in the bone marrow.
• Results from vitamin B12 or folate deficiency affecting DNA synthesis, causing replication delay but normal cytoplasmic maturation.

Roles of Vitamin B12 and Folate in DNA Synthesis

• Diagram outlining the roles of Vitamin B12 and folate in DNA synthesis pathways.

Megaloblastic Anemia: Laboratory Abnormalities

• Pancytopenia: decreased red, white, and platelets.
• Oval macrocytosis: enlarged red blood cells (MCV >110).
• Hypersegmented neutrophils: increased number of lobes .
• Megaloblastic hyperplasia: significant red cell precursor changes in bone marrow.

Pernicious Anemia

• Autoimmune gastritis is the most common cause.
• Leads to lack of intrinsic factor, hindering Vitamin B12 absorption.
• Often affects older individuals.
• Symptoms include subacute combined degeneration of the spinal cord, peripheral neuropathy, and macrocytic anemia.

Vitamin B12 Deficiency

• Subacute combined degeneration (SACD) of the spinal cord is a severe complication of B12 deficiency.
• Posterior column dysfunction diminishes vibratory sensation and proprioception (joint sense).
• Lateral corticospinal tract dysfunction causes spasticity.
• Dorsal spinocerebellar tract dysfunction results in ataxia.

Folic Acid (Folate Deficiency) Anemia

• Similar to B12 deficiency; predisposes to megaloblastic anemia.
• Mechanisms causing folate deficiency include dietary deprivation, pregnancy, phenytoin use, oral contraceptives, chemotherapy, increased demand, and intestinal malabsorption.

Clinical Features of B12 Deficiency

• Anemia symptoms
• Glossitis (smooth, sore, inflamed tongue).
• Neurologic disease: peripheral neuropathy, subacute combined degeneration (SACD), dementia, and in some cases, even neurological symptoms without accompanying anemia (20%).

Pernicious Anemia and Lab Findings

• Yellowish-lemon skin with significant pallor is a common sign of pernicious anemia.
• Laboratory findings include decreased serum vitamin B12, increased serum homocysteine and methylmalonic acid, peripheral blood smear showing pancytopenia, oval macrocytes, and hypersegmented neutrophils, bone marrow showing megaloblastic cells, and a Schilling test to determine the cause of B12 deficiency.

Megaloblasts and Bone Marrow Aspirate

• Image of a bone marrow aspirate showing megaloblasts, indicating a lack of nuclear maturation associated with megaloblastic anemia.

Clinical and Laboratory Findings in Vitamin B12 and Folic Acid Deficiencies

• Table comparing the presence/absence of laboratory and clinical findings in pernicious anemia, other B12 deficiencies, and folic acid deficiency.

Peripheral Blood Smear in Different Subtypes of Anemia

• Examples of peripheral blood smears representing different anemias: iron deficiency, thalassemia, megaloblastic anemia, and others.

Where is the Marrow?

• Overview of hematopoietic marrow location according to developmental stage (embryonic, newborn, childhood, adult).

Aplastic Anemia

• Characterized by bone marrow hypocellularity (empty marrow) with a significant decrease in all hematopoietic cells.
• Causes include immunologic alterations in myeloid stem cells leading to cytokine-mediated destruction, mutations in TERT gene, and certain environmental factors.

Aplastic Anemia: Etiology

• Idiopathic (unknown cause) is common.
• Drugs (e.g., alkylating agents, antimetabolites) can be a factor, as are certain toxic chemicals, infections (EBV, CMV), physical agents (radiation), and some other causes.

Aplastic Anemia: Clinical Features

• Fatigue, breathlessness due to anemia.
• Fever due to infection (neutropenia).
• Bleeding due to thrombocytopenia.
• Pancytopenia, and reticulocytopenia in peripheral blood smear.

Aplastic Anemia: Management

• Discontinuation of the offending drug (if drug-related).
• Transfusions (if needed), and blood should be irradiated.
• Immuno-suppressive therapies.
• Bone marrow transplantation (good prognosis for young patients if a matched donor is available).

Fanconi Anemia

• Fanconi anemia (FA) is a hereditary bone marrow failure syndrome with significant DNA damage sensitivity.
• 15 genes are implicated (FANC genes, such as FANCD1/BRCA2)
• Can lead to myelodysplastic syndromes, acute myeloid leukemia (AML), and epithelial tumors.
• Immunosuppressive treatments are not effective.

Pure Red Cell Aplasia "PRCA"

• A rare type of aplasia affecting only red blood cell precursors.
• Acute, self-limited cases occur in association with viral infections (e.g., parvovirus B19), while others are chronic and congenital.
• Drug-induced (e.g., phenytoin).
• Other causes include thymomas and certain leukemias.

Reprogramming of Mature Cells to Induced Pluripotent Stem Cells

• Technique of generating induced pluripotent stem cells (iPS cells) from mature cells using stem cell genes (SOX2, c-Myc, KLF4, and Nanog).

Test your knowledge on microcytic anemias and their characteristics. This quiz covers various aspects including conditions associated with anemia, laboratory findings, and the effects of vitamin deficiencies. Perfect for students or healthcare professionals studying hematology.