Week 2 - Intro to Pathology (PDF)

INTRODUCTION TO PATHOLOGY CYTOPATHOLOGIC CHANGES IN DISEASE PATHOLOGY - study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease DIVISION OF SPECIALTY ANATOMIC CLINICAL PATHOLOGY PATHOLOGY Aut...

INTRODUCTION TO PATHOLOGY CYTOPATHOLOGIC CHANGES IN DISEASE PATHOLOGY - study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease DIVISION OF SPECIALTY ANATOMIC CLINICAL PATHOLOGY PATHOLOGY Autopsies Hematology Surgical Pathology Chemistry Cytology Microbiology Blood Bank FOUR ASPECTS OF PATHOLOGY 1. ETIOLOGY - origin of the disease 2. PATHOGENESIS – initial stimulus → ultimate expression of the disease 3. MORPHOLOGIC CHANGES - structural alterations in cells or tissues. 4. FUNCTIONAL DERANGEMENTS AND CLINICAL MANIFESTATIONS – signs and symptoms, cell-tissue-organ injury RUDOLF VIRCHOW “All diseases are the results of visible cell abnormalities.” https://www.britannica.com/biography/Rudolf-Virchow CELLULAR RESPONSES TO STRESS AND TOXIC INSULTS IMPORTANT TERMS: “-PLASIA” HYPER- HYPO- / A- META- DYS- ANA- IMPORTANT TERMS: “-TROPHY” HYPER- HYPO- / A- DYS- IMPORTANT TERMS: APOPTOSIS NECROSIS CELL DEATH “Reversible or irreversible injury” “Death is irreversible.” CELL ADAPTATION, INJURY, AND DEATH OBJECTIVES Cellular growth adaptations---Hyperplasia, Hypertrophy, Atrophy, Metaplasia Factors of cell injury and death --- O2, Physical, Chemical, Infection, Immunologic, Genetic, Nutritional Pathologic mechanisms at subcellular level---ATP, Mitochondria, Ca++, Free Radicals, Membranes APOPTOSIS and NECROSIS OBJECTIVES Subcellular responses to injury---Lysosomes, Smooth endoplasmic reticulum, Mitochondria, Cytoskeleton Identify common intracellular accumulations---Fat, Hyaline, Ca2+, Proteins, Glycogen, Pigments Understand aging and differentiate the concepts of preprogrammed death versus wear and tear. INTRODUCTION Injury or Stress Adaptation Increased demand Hyperplasia or hypertrophy Decreased stimulation or lack of nutrients Atrophy Chronic irritation Metaplasia ABNORMALITIES IN CELL GROWTH Retrogressive Changes - organs or tissues are smaller than normal A. Developmental Defects o Aplasia- incomplete or defective development of a tissue or organ represented only by a mass of fatty or fibrous tissue o Agenesia- complete non-appearance of an organ ABNORMALITIES IN CELL GROWTH Retrogressive Changes - organs or tissues are smaller than normal A. Developmental Defects o Hypoplasia- failure of an organ to reach its full mature or adult size due to incomplete development o Atresia- failure of an organ to form an opening ABNORMALITIES IN CELL GROWTH Retrogressive Changes - organs or tissues are smaller than normal B. Atrophy Ø Acquired decrease in size of a normally developed or a mature organ resulting from reduction in cell size or decrease in total number of cells or both. CAUSES OF ATROPHY DECREASED WORKLOAD DENERVATION DECREASED BLOOD FLOW DECREASED NUTRITION AGING (involution) PRESSURE “EXHAUSTION” ABNORMALITIES IN CELL GROWTH Progressive Changes - organs or tissues are larger than normal o Hyperplasia o Hypertrophy HYPERPLASIA Increase in the size of tissues and organs due to increase in the number of cells resulting from growth of new cells Physiologic hyperplasia- normal phenomenon Pathologic hyperplasia- brought about by disease HYPERTROPHY Increase in the size of tissues and organs due to increase in cell size o Physiologic Ø Increased workload (skeletal/cardiac muscle) Ø Hormone induced (uterus) o Pathologic PATHOLOGIC HYPERPLASIA PATHOLOGIC HYPERPLASIA DEGENERATIVE CHANGES DUE TO ABERRATIONS OF CELLULAR GROWTH PATTERNS  METAPLASIA is a reversible change involving the transformation in one type of normal adult cell to another COLUMNAR → SQUAMOUS (Respiratory tract) SQUAMOUS → COLUMNAR (Glandular) (Stomach) DYSPLASIA AKA Atypical hyperplasia Abnormal growth and differentiation manifested by variation in size, shape and orientation Pre-neoplastic ANAPLASIA AKA Dedifferentiation Marked regressive change in adult cells towards more primitive or embryonic cell types Irreversible NEOPLASIA Tumor continuous abnormal proliferation of cells without control represents a pathologic overgrowth of the tissue. CELL INJURY AND DEATH Reversible change → CELL INJURY REDUCED oxidative phosphorylation ATP depletion Cellular “SWELLING” If prolonged or severe, it can progress to CELL DEATH CELL INJURY AND DEATH Irreversible change → CELL DEATH MITOCHONDRIAL IRREVERSIBILITY IRREVERSIBLE MEMBRANE DEFECTS LYSOSOMAL DIGESTION CELL INJURY AND DEATH Usual cause Mechanism Hypoxia DECREASED ATP Physical agents MITOCHONDRIAL DAMAGE Chemical agents INCREASED Infectious Agents INTRACELLULAR CALCIUM Immunologic INCREASED FREE RADICALS Genetic INCREASED CELL Nutritional MEMBRANE PERMEABILITY CELL INJURY AND DEATH  NECROSIS General Characteristics Cells and organelles swell Control of intracellular environment is lost, cells rupture and spill contents INDUCES INFLAMMATION  NECROSIS Eosinophilia cytoplasm Nuclear patterns oKaryolysis oPyknosis oKaryorrhexis COAGULATIVE NECROSIS a less rapid coagulation of the cytoplasm. The outline of the dead cells are maintained and the tissue is somewhat firm Cell death is due to ischemia Seen in heart attacks, typhoid fever, and tetanus LIQUEFACTIVE NECROSIS fairly rapid total enzymatic dissolution of the cells BRAIN- MOST COMMONLY AFFECTED ORGAN FAT NECROSIS involves the peculiar destruction of adipose tissue, particularly found in pancreatic degenerations. Characterized by the formation of chalky white precipitates. PANCREAS- COMMONLY AFFECTED ORGAN FAT NECROSIS CASEOUS NECROSIS Special form of cell death produced by the Tubercle Bacillus The necrotic tissue has an appearance of soft, friable cheese Seen usually in TB infection, Syphilis, Tularemia, and Lymphogranuloma Inguinale GANGRENOUS NECROSIS Massive death or necrosis of tissue, caused by combination of ischemia and superimposed bacterial infection (necrosis plus putrefaction) 2 TYPES OF GANGRENE: Dry Gangrene Ø Caused by arterial occlusion Ø Less bacterial infection Ø Less odorous Ø Essentially NOT a real gangrene (sterile necrosis) Wet Gangrene Ø Caused by venous occlusion Ø Bacterial infection supervenes Ø Offensive and foul-odored MECHANISM OF NECROSIS Depletion of ATP Mitochondrial Damage Entry of Ca2+ into the cell Increase reactive oxygen species (ROS) Membrane Damage DNA damage, Protein misfolding EXAMPLES OF INJURY Ischemic (Hypoxic) → INFARCT Ischemia/Reperfusion Chemical Ø “Toxic” Chemicals, e.g CCl4 Ø Drugs, e.g Tylenol Ø Dose Relationship Ø Free radicals, organelle, DNA damage APOPTOSIS General Characteristics Ø Usually affects scattered individual cells Ø Cells shrink Ø Control of intracellular environment maintained APOPTOSIS MECHANISM Protein Digestion (Caspases) Lysosomal Auto-Digestion SER activation Mitochondrial “SWELLING” Cytoskeleton Breakdown DNA breakdown Phagocytic Recognition AUTOPHAGY INTRACELLULAR ACCUMULATION Lipids Ø Steatosis (fatty change) Ø Cholesterol and cholesterol esters ü Atherosclerosis ü Xanthomas ü Cholesterolosis ü Niemann-Pick disease Proteins- hyaline INTRACELLULAR ACCUMULATION Glycogen Pigments Ø Exogenous (tattoo, Anthracosis) Ø Endogenous (hemosiderin, melanin, lipofuscin, bile) PATHOLOGIC CALCIFICATION Dystrophic Calcification – occurs in areas of necrosis and atherosclerosis; often with FIBROSIS Metastatic Calcification – occurs in normal tissues when there is hypercalcemia ØExcess PTH ØDestruction of bone ØVitamin D disorders ØRenal failure