Chromosomal Abnormalities • Aneuploidy: An abnormal number of chromosomes, either extra or missing. • Down Syndrome: Associated with trisomy 21 (an extra chromosome 21). • X Chromosome Abnormalities: Includes conditions like Turner Syndrome (monosomy X) and Klinefelter Syndrome (XXY). Genetic Disorders • Dominant Trait: • A trait expressed with just one copy of a dominant allele. • Inheritance: Passed down if one parent has the dominant gene. • Recessive Trait: • A trait expressed only when two copies of the recessive allele are present. • Inheritance: Both parents must carry the recessive gene. • Polygenic Disorders: Traits influenced by multiple genes (e.g., diabetes, heart disease). • Gene Interactions: Multiple genes interact to determine phenotypes, leading to complex traits or disorders. Genetic Testing • Karyotyping: A test to examine the number and structure of chromosomes. • Amniocentesis: A procedure to collect amniotic fluid for detecting genetic disorders. • Chorionic Villus Sampling (CVS): A test that involves sampling cells from the placenta to detect genetic issues. • Errors in Morphogenesis: • Agenesis: Failure of an organ to develop. • Hypoplasia: Underdevelopment of an organ or tissue. • Dysraphic Anomalies: Failures in fusion during development, e.g., spina bifida. • Spina Bifida: A neural tube defect due to incomplete spinal cord development. • Involutional Failures: Failure of tissues to regress after their function is complete (e.g., persistent thyroglossal duct). • Divisional Failures: Lack of proper division during development, leading to abnormalities like syndactyly (fused fingers or toes). • Atresia: Absence or closure of an opening, such as in intestines. • Ectopia or Heterotopia: Tissues located in the wrong place. Childhood Tumors • Hamartoma: A benign tumor-like growth made up of an abnormal mix of normal tissues. • Common Malignant Tumors in Children: Includes Wilms tumor, neuroblastoma, and retinoblastoma. Organ Immaturity in Newborns • Respiratory Distress Syndrome (RDS): • Caused by insufficient surfactant production in the lungs. • If unresolved, it can lead to chronic lung disease or death. • Neonatal Jaundice: • Caused by immature liver unable to process bilirubin efficiently. Congestion • Active vs. Passive Congestion: • Active Congestion: Increased blood flow due to arteriolar dilation (e.g., during inflammation). • Passive Congestion: Reduced blood outflow, often due to heart failure or venous obstruction. • Heart Failure Cells: Macrophages in the lungs filled with hemosiderin, resulting from chronic passive congestion. Thrombosis • Outcomes of Thrombosis: 1. Resolution: Thrombus dissolves completely. 2. Organization and Recanalization: New channels form within the thrombus. 3. Propagation or Embolization: Thrombus grows or breaks off, traveling to another site. • Marantic Endocarditis: Non-infective endocarditis, associated with cancer or chronic illnesses, leading to sterile thrombi on heart valves. • Risk Factors for Thrombosis: • Virchow’s Triad: Endothelial injury, hypercoagulability, abnormal blood flow. • Embolism: A fragment of a thrombus or another material (e.g., fat, air) travels through the bloodstream and lodges in a vessel. Edema • Pressures Determining Edema: 1. Hydrostatic Pressure: Drives fluid out of capillaries. 2. Oncotic Pressure: Pulls fluid into capillaries (due to proteins like albumin). • Inflammatory vs. Non-inflammatory Edema: • Inflammatory Edema: Caused by increased vascular permeability (e.g., in infections). • Non-inflammatory Edema: Caused by imbalances in hydrostatic or oncotic pressure (e.g., heart failure, nephrotic syndrome). Hemostasis • Primary Hemostasis and Arachidonic Acid: • Thromboxane A2 is the arachidonic acid metabolite involved, promoting platelet aggregation. • DIC (Disseminated Intravascular Coagulation) and Hemorrhage: • DIC leads to widespread clotting, depleting clotting factors and platelets, causing uncontrolled bleeding. Type I Hypersensitivity • Cells Involved: • Mast cells, basophils, and eosinophils. • Initial Exposure: • Antigen triggers IgE production, which binds to mast cells and basophils. • Subsequent Responses: • Re-exposure leads to rapid degranulation of mast cells, releasing histamine and other mediators. • Examples: • Allergic reactions (e.g., hay fever, asthma, anaphylaxis). Type II Hypersensitivity • Cells Involved: • Phagocytes, NK cells, and complement proteins. • Role of Antibodies: • IgG or IgM binds to antigens on cell surfaces, marking them for destruction. • Role of Complement: • Complement activation leads to cell lysis or opsonization. Type III Hypersensitivity • Immune Complex Formation: • Antigen-antibody complexes form in the bloodstream. • Deposition: • Complexes are deposited in tissues like kidneys, joints, or blood vessels. • Steps in Vasculitis: 1. Complex deposition. 2. Complement activation. 3. Recruitment of inflammatory cells. 4. Tissue damage from enzymes and reactive oxygen species. Type IV Hypersensitivity • Differences from Type II: • Type IV is cell-mediated (T-cells), not antibody-mediated. • Role of Lymphocytes: • Helper T-cells (CD4+) release cytokines to activate macrophages. • Cytotoxic T-cells (CD8+) destroy target cells directly. Neoplasia: Clinical 1. Benign vs. Malignant Tumors: • Benign Tumors: • Non-cancerous. • Grow slowly and do not invade nearby tissues or spread (no metastasis). • Malignant Tumors: • Cancerous. • Grow rapidly, invade nearby tissues, and can spread to other parts of the body (metastasis). 2. Tumor “Grade”: • Refers to how abnormal the tumor cells look under a microscope. • Low Grade: Cells look more like normal cells (less aggressive). • High Grade: Cells look very abnormal (more aggressive). 3. Tumor “Stage”: • Describes the size and spread of the tumor. • Stages: • Localized: Tumor is confined to its original site. • Regional: Tumor has spread to nearby tissues or lymph nodes. • Distant: Tumor has metastasized to other parts of the body. 4. Prognosis and Tumor “Grade” & “Stage”: • Higher Grade: Typically worse prognosis due to more aggressive behavior. • Advanced Stage: Poorer prognosis because of greater spread. 5. Immunochemistry in Tumor Characterization: • Uses antibodies to detect specific proteins in cells. • Helps identify the type of tumor and its origin (e.g., breast cancer markers like HER2). Hypersensitivity Reactions (Chapter 4): 1. Type I Hypersensitivity: • IgE-mediated reaction. • Involves degranulation of mast cells and basophils, releasing histamine. • Example: Allergies, anaphylaxis. 2. Type II Hypersensitivity: • Involves antibodies binding to cell surfaces, leading to destruction. • Example: Hemolytic anemia. 3. Type III Hypersensitivity: • Immune complexes form and deposit in tissues, causing inflammation. • Example: Lupus, rheumatoid arthritis. 4. Type IV Hypersensitivity: • Does not involve antibodies; mediated by T-cells. • Example: Contact dermatitis, tuberculosis test. Key Differences: • Antibody Involvement: • Types I, II, III involve antibodies. • Type IV does not involve antibodies (cell-mediated). • Complex Formation: • Type III is characterized by immune complex formation. • Type II vs. III: • Type II: Antibodies target specific cells. • Type III: Immune complexes deposit in tissues. Neoplasia (Chapter 5): 1. Tumor “Stage”: • Indicates the size and spread of the tumor. • Higher stage = more advanced disease. 2. Tumor “Grade”: • Describes how abnormal the tumor cells look. • Higher grade = more aggressive tumor. 3. Prognosis: • Higher grade and stage usually mean poorer prognosis. Mode of Inheritance Problems (Chapter 6): 1. Example Problem: • A woman is a carrier for an X-linked recessive trait, and her partner has a normal phenotype. • Probability for Male Offspring: • 50% chance of inheriting the disease. Thrombosis and Embolization (Chapter 7): 1. Thrombosis: • Formation of a blood clot in vessels. • Possible outcomes: • Dissolution (resolves). • Propagation (growth). • Embolization (breaks off and travels). 2. Embolization: • Blockage caused by a traveling clot or other material. Study Tips: • Focus more on the new material, as there will only be a few questions on old material. • Pay special attention to hypersensitivity reactions and their key differences. • Practice mode of inheritance problems for better understanding. • Understand the distinctions between tumor grade and stage