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What is the most critical vascular event in acute inflammation?

Increased vascular permeability

The most frequently affected organs in mitochondrial inheritance are the ______, ______, and ______.

Study Notes

Pathology - Marrow Edition 8

  • The book is a comprehensive resource for medical students and healthcare professionals.
  • It provides free access to video lectures, books in PDF format, and other resources such as apps and softwares.
  • The website is at www.medicalstudyzone.com

General Pathology

  • Cell Adaptations: Covers cell injury, cell death, intracellular accumulations, acute inflammation, chronic inflammation, wound healing, tissue repair, hemodynamics.
  • Neoplasia: Covers the basics of neoplasia, types of carcinogenesis, neoplasia hallmarks, lab diagnosis of cancer, tumour diagnosis, genetics: basics, Mendelian & Non-Mendelian modes & pedigrees.
  • Genetics: Covers basics, Non-mendelian modes & pedigrees, chromosomal disorders, genetic disorders-diagnosis, hypersensitivity reactions, transplant pathology, immunodeficiency disorders, amyloidosis.
  • Hematology: Covers RBC: introduction, peripheral smear examination, microcytic hypochromic anemia, megaloblastic anemia, hemolytic anemia, WBC: introduction, acute lymphoblastic leukemia, acute myeloid leukemia, myeloid disorders, chronic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, plasma cell disorders, hemostasis, blood banking.
  • Cardiovascular System: Covers blood vessels: sclerosis, blood vessels: vasculitis, vascular tumors, cardiovascular system, cardiovascular system (part 1 and 2).
  • Genitourinary System: Covers kidney, nephritic syndrome, nephrotic syndrome, renal involvement in systemic diseases, kidney tumors.
  • Gastrointestinal System: Covers esophagus, intestinal disorders, inflammatory bowel disease, colorectal polyps and cancer, liver pathology.
  • Respiratory System: Covers obstructive lung diseases, restrictive lung diseases, granulomas and infections of lung, lung tumors.
  • Endocrine System and Breast: Covers thyroid: non-neoplastic lesions, thyroid tumors, adrenal medulla, pituitary and Parathyroid gland, breast pathology.
  • Skin and Musculoskeletal System: Covers dermatopathology, bone and soft tissue lesions.
  • Nervous System Includes CNS non-neoplastic lesions and CNS tumors.
  • Miscellaneous: Demonstration of instruments.

Cell Injury

  • Causes: Hypoxia (most common), ischemia (reduced blood supply), physical agents (radiation), chemical agents, infectious agents, and immune factors.
  • Cellular Response: Adaptation (reversible), reversible cell injury, and irreversible cell injury (necrosis or apoptosis).
  • Nuclear changes: Pyknosis, karyorrhexis, and karyolysis (important morphological feature of irreversible cell injury).
  • Free Radicals: Highly reactive molecules with unpaired electrons, causing cell damage through lipid peroxidation.
  • Formation & Effects: Production of ROS from radiation, toxins and reperfusion and their effects (Membrane damage, Oxidative protein modifications, DNA damage, Mutations).
  • Protective mechanisms: Exogenous/endogenous antioxidants.
  • Misfolded Proteins: Accumulation of misfolded proteins in the endoplasmic reticulum, leading to diseases like cystic fibrosis, familial hypercholesterolemia, and Alzheimer's Disease.

Cell Death

  • Types: Apoptosis, necrosis, pyroptosis, ferroptosis, and necroptosis.
  • Mechanism: Necrosis: Enzymatic digestion of cells. Apoptosis: Genetically programmed cell death.
  • Morphology: Densely eosinophilic cells (necrosis), glassy/shiny (necrosis) appearance, moth-eaten (necrosis).
  • Types: Coagulative necrosis, Liquefactive necrosis, Caseous necrosis, Fat necrosis, Fibrinoid necrosis, Gangrenous necrosis.

Intracellular Accumulations

  • Substances: Glycogen, lipids, proteins, water, hyaline, calcium, pigments.
  • Conditions: Glycogen storage disorders, renal cell carcinoma, diabetic nephropathy, and others.

Wound Healing and Tissue Repair

  • Tissue Regeneration: Dead cells replaced by same parenchymal cells (liver as an example).
  • Tissue Repair: Involves infiltration by inflammatory cells (lymphocytes, macrophages), fibrosis, and neovascularization.
  • Permanent Cells: Don't regenerate (neurons, cardiac & skeletal muscles).
  • Stable Cells: Can regenerate under specific conditions (e.g., liver cells).
  • Labile Cells: Continuously divide and can easily regenerate (e.g., epithelial cells).
  • Healing by 1st intention: Apposed wound edges, minimal scarring; 2nd intention: Gap in wound edges, more scarring.

Hemodynamics

  • Hyperemia: Increased blood flow to tissues (redness);
  • Congestion: Reduced blood flow out of tissues.
  • Thrombosis: Blood clot within a blood vessel.
  • Embolism: Movement of blood clot or other material through the blood stream to a site distant from its origin.
  • Infarction: Area of ischemic tissue death.
  • Virchows Triad: 3 components: endothelial damage, blood flow abnormalities (stasis/turbulence) and hypercoagulability necessary for thrombus formation.

Blood Banking and Transfusion Medicine

  • Blood Groups: ABO (A, B, O) and Rh (positive, negative).
  • Blood components: Whole blood, packed red blood cells (PRBCs), fresh frozen plasma (FFP), cryoprecipitate, and platelets.
  • Donation & storage methods: Methods for blood types and components as well as safety standards. Preservation & storage of different components.

Lab Diagnosis of Cancer

  • Cytology: Examination of cells (FNAC).
  • Biopsy: Excisional or incisional removal of tissue to study.
  • IHC: Immunohistochemistry (Antibody markers to identify cells).
  • Frozen section: Rapid microscopic examination to quickly determine the tumor type during surgery.
  • Other investigations: Serum tests, x-rays for identifying abnormal markers in cancer.

Genetics: Basics and Mendelian Modes

  • Gene: A segment of DNA that contains the code for a protein.
  • Chromosome: A structure of DNA containing genes.
  • Alleles: Different forms of a gene.
  • Homozygous: Having two identical alleles for a gene.
  • Heterozygous: Having two different alleles for a gene.
  • Dominant: An allele that is expressed in the phenotype even if only one copy is present.
  • Recessive: An allele that is only expressed in the phenotype if two copies are present.
  • Inheritance pattern: Pattern of how genes are passed down from one generation to the next. Includes autosomal dominant, recessive, x linked, and non-mendelian (mitochondrial, trinucleotide repeat expansions).
  • Mutations: Heritable changes in DNA.

Genetics: Non-Mendelian Modes and Pedigree

  • Mitochondrial inheritance: Inherited through the maternal line.
  • Gonadal mosaicism: A rare condition in which a mutation occurs in the germ cells of only one parent, resulting in a genetic characteristic that skips generations in the pedigree.
  • Trinucleotide repeat expansion: Diseases in which a section of DNA is repeated multiple times affecting the offspring.

Genetics: Chromosomal Disorders

  • Structural abnormalities: Insertion, deletion, inversion, translocation, and ring chromosomes.
  • Numerical abnormalities: Trisomy, monosomy, and polyploidy.

Tumor Diagnosis

  • Features: Well-differentiated, moderately differentiated, and poorly differentiated.
  • Microscopic: Different types depending on what the tumor cells look like.
  • Other investigations: Serum tests, X-rays, IHC, genetic analysis.

Other Mechanisms of Neoplasia

  • Limitless replicative potential: Telomerase activity in cancer cells.
  • Evasion of apoptosis: Resistance to programmed cell death.
  • Sustained angiogenesis: Increased blood supply to facilitate tumor growth.
  • Altered cellular metabolism: Warburg effect (increased glucose uptake and metabolism).
  • Invasion and metastasis: Spreading and dissemination of tumors to other parts of the body.
  • Escape of immune recognition Mechanisms for avoiding recognition and destruction by the immune system

Immunodeficiency Disorders

  • Primary (Inborn): Defects in the development, activation, or maturation of immune cells.
  • Secondary (Acquired): Immune deficiencies due to infections (HIV), malnutrition, or certain diseases.
  • Common Variable Immunodeficiency (CVID): Defects in B cell maturation and antibody production, resulting in recurrent sinopulmonary infections, autoimmunity.
  • Hyperimmunoglobulinemia M syndrome (HIM): Problems with specific antibody class switching.
  • Isolated IgA deficiency: Most common primary deficiency Wiskott-Aldrich Syndrome (WAS): X-linked recessive
  • Chronic Granulomatous Disease (CGD): The phagocytes do not kill microorganisms via an oxidative pathway.

Amyloidosis

  • Description: Extracellular deposition of abnormal protein fibrils in various tissues and organs, creating a characteristic 'hyaline' staining.
  • Pathogenesis: May be primary (from plasma cells), or secondary (associated with other conditions like chronic inflammation or malignancy).
  • Types: AL and AA.
  • Clinical Features: Kidney involvement is a common cause of death, other features include organomegaly and waxy appearance.
  • diagnosis Use microscopy/stained using Congo red.

Hematology: RBC Introduction

  • Size: Normal range, smaller (microcytic), or larger (macrocytic)
  • Life Span: 120 days
  • Shape: Biconcave, central pallor
  • Components: Hemoglobin, spectrin
  • Erythropoiesis: The process of making red blood cells (RBCS). Stages (Proerythroblast, early, intermediate, late normoblasts, reticulocytes).

Hematology: Peripheral Smear Examination

  • Stains: Romanowsky stains (ie Leishman, Giemsa, Wright), used to visualize the cells and their contents.
  • Reporting components: RBC, WBC, Platelets, and abnormal cell types. These are important to be able to observe and identify the components of the sample.

Hematology: Microcytic Hypochromic Anemia

  • Causes: Iron deficiency, thalassemia, sideroblastic anemia, anemia of chronic disease.
  • Iron requirements: Daily requirements, forms in body (haeme vs non-haeme).
  • Absorption factors: Acidic pH, vitamin C
  • Important proteins in iron metabolism: Transferrin (transport), Hepcidin (inhibitor)
  • Investigations: CBC, serum iron studies, serum ferritin, TIBC (total iron-binding capacity), serum electrophoresis
  • Stage of anemia: Iron deficiency, Iron-deficient erythropoiesis, Iron-deficiency anemia; Based on severity, using reticulocyte and serum iron profiles.

Hematology: Megaloblastic Anemia

  • Causes: Vitamin B12 and folate deficiency affect cell maturation leading to megaloblastic anemia.
  • Mechanism of absorption: Absorption of vitamin B12 involves intrinsic factor, and folate absorption is enhanced by presence of certain digestive enzymes.
  • Presentation: Pancytopenia (reduction in RBCS, WBCs, and platelets), macrocytic RBCs, and morphological abnormalities in various cell types.

Hematology: Hemolytic Anemia (Part 1 & 2)

  • Type/Causes: Hereditary defects (e.g., HS, elliptocytosis, G6PD deficiency, haemoglobinopathies).
  • Acquired mechanisms: Immune-mediated (e.g., AIHA), non-immune mediated (e.g., mechanical injury, infections).
  • Features (Intravascular vs Extravascular): Site of hemolysis, spleen involvement, presence of haemoglobinuria
  • Investigations: Hemoglobin electrophoresis.
  • Management: Treatment of the underlying cause, blood transfusions, splenectomy.

Blood Banking and Transfusion Medicine

  • **Blood groups:**ABO and Rh.
  • Blood components: Whole blood, packed RBCs (PRBC), FFP, and platelets.
  • Pre-transfusion testing: Screen donor and recipient blood for antigens/antibodies; ABO compatibility.
  • Transfusion protocol: Temperature, time, and type of tubing for blood/blood components during transfusion.
  • Blood components storage: Storage requirements for each blood component.

Cardiovascular System: Part 1 & 2

  • Blood circulation & layers of heart: Overview of circulation, layers of the heart (pericardium, myocardium, endocardium).
  • Heart Failure: Types and Pathophysiology (Left vs right heart failure).
  • Ischemic Heart disease: Features, diagnosis, and management/treatment.
  • Cardiomyopathies: Types, causes, and clinical features.

Vascular Tumors

  • Benign: Hemangioma, Lymphangioma, Glomus tumor
  • Malignant: Hemangiopericytoma, Angiosarcoma.

Renal Cell Carcinoma

  • Risk factors: Smoking, obesity, exposure to asbestos.
  • Features: Flank pain, hematuria, palpable abdominal mass.
  • Microscopic Features: Clear cells, granular/chromophilic, papillary.

Male Genital System: Penis and Prostate

  • Penis: Condylomas, SCC, Bowen's disease.
  • Prostate: BPH (benign prostatic hyperplasia), adenocarcinoma

Female Genital Tract: Vulva, Vagina, and Cervix

  • Vulva: Paget's disease; condyloma acuminatum (genital warts).
  • Vagina: Pre-malignant conditions: embryonal rhabdomyosarcoma
  • Cervix: Cervical intraepithelial neoplasia (CIN)

Female Genital Tract: Uterus and Endometrium

  • Endometriosis: Presence of endometrial glands outside the uterus.
  • Endometrial Hyperplasia: ↑ in the ratio of endometrial glands: stroma.
  • Endometrial Cancer: Types, clinical features, and risk factors.

Female Genital Tract: Ovaries

  • Ovarian tumors: Surface epithelial, germ cell, and sex cord stromal tumors; Clinical features for each type.

Miscellaneous Topics:

  • Organisms in foamy macrophages: May be associated with infections like TB (tuberculous), Whipple's disease (T. whipplei organism).
  • Micro RNAs: Non-coding RNA molecules, affecting various cellular functions.
  • Immunohistochemistry markers: Useful tools in identifying cell types and diagnosing tumors (e.g., using markers for epithelial cells, mesenchymal cells).
  • Demonstration of instruments: Includes different types of vacutainers and bone marrow needles.

CNS: Non-neoplastic Lesions

  • Glial cells: Types, functions, and response to injury/disease.

CNS Tumors

  • Classification: Based on tissue of origin, differentiation, and associated genetic alterations/syndromes.
  • Grading: Different grades associated with various cancer types.

Specific diseases and conditions covered in the notes:

  • Important cancer types: Breast carcinoma (different types and associated genes), renal cell carcinoma, prostate cancer, lung cancer, and other malignancies.
  • Inflammatory bowel diseases (IBD) Specifics about Crohn's and ulcerative colitis, including associated features.
  • Important Hematological and other conditions discussed (e.g., various anemias, leukemias, lymphomas, immunodeficiencies, coagulation disorders).
  • Important syndromes associated with specific conditions or cancers (mentioned in the various sections)

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