Cell Injury Lecture Notes 2025 PDF

CELL INJURY Dr M Mwange Division of Anatomical Pathology February 2025  Prescribed Reading YOUR NOTES – eReader Recommended: Underwood’s Pathology: A Clinical Approach Optional Reading Robbins and Cotran Pathologic Basis of disease. Slides prepared...

CELL INJURY Dr M Mwange Division of Anatomical Pathology February 2025  Prescribed Reading YOUR NOTES – eReader Recommended: Underwood’s Pathology: A Clinical Approach Optional Reading Robbins and Cotran Pathologic Basis of disease. Slides prepared by Prof. Dhirendra Govender  LECTURE OUTLINE Steady state Injurious agents Targets/sites of cell injury Cellular responses to injury ❑ Cellular adaptation ❑ Reversible injury ❑ Irreversible injury (Contd.)  CELLULAR INJURY Requirements for STEADY STATE: A. adequate metabolites - oxygen, nutrients B. integrity of metabolic pathways - normal enzyme content C. intact membranes and transmembrane proteins D. intact genome - intact DNA  Injurious agents Capillary 2 Reoxygenation/reperfusion injury Congenital, 3 Physical Agents Chromosomal 8 4 Immune 1 Hypoxia, reactions Drugs, anoxia 7 chemicals, 5 Infectious agents poisons 6 Nutritional imbalances CELL Targets and Mechanisms of Cellular Injury Membrane damage Free radicals Deficiency of metabolites Glucose Oxygen Hormones Metabolic pathways Disruption in protein synthesis Respiratory toxins/poisons DNA damage or loss Free radicals Cytotoxic agents Radiation Failure of membrane functional integrity Damage to ion pumps Alteration in membrane lipids  Cellular Responses to Injury STRESS Increased / Decreased functional demand CELLULAR ADAPTATIONS Hypertrophy Hyperplasia Atrophy Metaplasia  ? A B  Cellular adaptations (refer Growth disorders) HYPERTROPHY - increase in size of cells  Cellular adaptations (refer Growth disorders) HYPERPLASIA - increase in number of cells  Cellular adaptations (refer Growth disorders) ATROPHY - decrease in size and number and function of cells Left Right  Cellular adaptations (refer Growth disorders) METAPLASIA - reversible change where one adult cell type (epithelial or mesenchymal) changes to another adult cell type  Cellular Responses to Injury STRESS Increased / Decreased functional demand CELLULAR ADAPTATIONS Persistent stress REVERSIBLE CELL INJURY relief of stress NORMAL CELL  Cellular Responses to Injury Subcellular alterations – ultrastructural (EM) Lysosomes Smooth Endoplasmic Reticulum Abnormalities of cytoskeleton, contractile proteins, and membrane skeleton  Cellular Responses to Injury Reversible Injury Intracellular accumulations water fat - triglycerides fat – cholesterol & cholesterol esters proteins glycogen Other Hyaline Myxoid Fatty loading/infiltration  REVERSIBLE INJURY Intracellular accumulations HYDROPIC/VACUOLAR DEGENERATION Failure of Na-K pump – accumulation of intracellular H2O and Na+ Minor degree – cloudy swelling Cytoplasm becomes pale and swollen Increase in fluid – small clear cytoplasmic vacuoles – may herald irreversible change  REVERSIBLE INJURY HYDROPIC/VACUOLAR DEGENERATION Examples: Renal tubular epithelium: Hypokalaemia Liver: Hepatitis - ballooning degeneration  HYDROPIC/VACUOLAR DEGENERATION Liver: hepatitis  REVERSIBLE INJURY Intracellular accumulations FATTY CHANGE (STEATOSIS) Definition: abnormal accumulation of fat (triglycerides) within parenchymal cells. Commonest form of degeneration. Can involve different organs. Commonly seen in liver. Also seen in heart and kidney.  REVERSIBLE INJURY FATTY CHANGE (STEATOSIS) Causes of Fatty change of liver: 1. Alcoholism 2. Protein calorie malnutrition – Kwashiorkor 3. Obesity 4. Diabetes mellitus 5. Drugs eg. tetracycline 6. Inborn errors of metabolism eg. galactosaemia 7. Hepatotoxins eg. CCl4  REVERSIBLE INJURY FATTY CHANGE (STEATOSIS) Pathology: Liver Macroscopy: Mild fatty change may not affect gross appearance or cellular function. Progressive accumulation - organ enlarges - soft, yellow, greasy. May reach 3 to 5 kg. (N = up to 1.6kg)  REVERSIBLE INJURY FATTY CHANGE (STEATOSIS) Pathology: Liver Microscopy: Fatty change begins with tiny membrane bound cytoplasmic inclusions = microvesicular fatty change Vacuoles coalesce = macrovesicular fatty change  Intracellular accumulations LIPOID DEGENERATION Definition: Intracellular accumulations of cholesterol and cholesterol esters in histiocytes Strawberry Gallbladder / Cholesterolosis Foam cells: histiocytes containing cholesterol  Intracellular accumulations PROTEINS ❑ Immunoglobulins in plasma cells = Russell bodies  Intracellular accumulations GLYCOGEN/CARBOHYDRATE Diabetes mellitus Glycogen storage diseases  HYALINE DEGENERATION Definition: Any alteration within cells or in the extracellular space, which results in a translucent, homogenous, structureless, glassy pink appearance on routine H&E stain.  HYALINE DEGENERATION Examples: 1. Connective tissue origin (extracellular space) Walls of blood vessels eg. atrophic organs/ senile Hyalinised (sclerosed) glomeruli in chronic glomerulonephritis 2. Epithelial origin (intracellular) Mallory’s hyaline in hepatocytes Mallory’s hyaline  REVERSIBLE INJURY MYXOID DEGENERATION Accumulation of mucopolysaccharides. Example: connective tissue / mesenchymal tumours Accumulation of mucopolysaccharides in the extracellular space  FATTY LOADING (Fatty Infiltration) Accumulation of adipocytes in tissue not normally associated with them Adipocytes present within the myocardium  Cellular Responses to Injury STRESS Increased functional demand CELLULAR ADAPTATIONS Persistent stress REVERSIBLE Severe CELL INJURY (Threshold) relief of IRREVERSIBLE stress mild CELL INJURY NECROSIS NORMAL CELL APOPTOSIS IRREVERSIBLE CELL INJURY  NECROSIS Definition: death of cells in the living organism due to: denaturation of cellular proteins and/or enzymatic digestion of the cell  NECROSIS Recognition of necrosis: Nuclear pyknosis: shrinks to a small, dense, mass of tightly packed chromatin Karyorrhexis: fragmentation of nucleus Karyolysis: progressive dissolution of nucleus (DNAases) Cytoplasmic changes: increasing eosinophilia due to: loss of RNA increased binding of eosin to denatured proteins Thank you