Title Pathology Notes.pdf ✅

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Cell Injury - 4 interrelated cell systems especially susceptible to injury o Membranes (cellular and organellar) o Aerobic system o Protein synthesis (enzymes, structural proteins, etc) o Genetic apparatus (DNA, RNA, etc) - Mechanisms for cell injury o Loss of Ca++ homeostasis o Membrane permeability defects o ATP depletion o O2 and O2 derived free radicals - Causes of Cell Injury o Hypoxia (ischemia – block in blood flow, hypoxemia – decreased partial pressure of oxygen in blood, anemia – decreased oxygen carrying capacity)  Block in ventilation( foreign body), oxygen diffusion (pneumonia, pulmonary edema), perfusion (pulmonary embolus), decreased cardiac output o Free radical damage o Chemicals, drugs, toxins o Infections o Physical agents o Immunologic reactions o Genetics o Nutritional imbalance - Oxygen tension falls  disrupts oxidative phosphorylation  decreased ATP o ↓ Na+ /K+ ATPase  increased intracellular Na+  swelling o ↓ ATP-dependent Ca++ pumps  increased cytosolic Ca++ o Depletion of glycogen from altered metabolism o Decreased pH from lactic acid accumulation o Decreased protein synthesis from ribosome detachment from RER - End result – cytoskeletal disruption with loss of microvilli, bleb formation, etc
- Excess cytoplasmic Ca++  denatures proteins, poisons mitochondria, inhibits cellular enzymes o Therefore, membrane damage and Ca++ homeostasis is critical o Injured membranes allow intracellular components to enter the serum and can be measured - Free radical injury (acetaminophen – Tylenol overdose) o Lipid peroxidation – damage to cellular and organellar membranes o Protein crosslinking/fragmentation from oxidative modification of amino acids and proteins o DNA damage from free radical reaction with thymine - Types o Chemical o Inflammation/microbial killing o Irradiation o Oxygen o Age-related - Free Radical Derivations o Superoxide – O2 ● - – produced by cellular oxidases o H2O2 – produced by superoxide mutase or catalase o OH● - – produced by ionizing radiation, H2O2 and O2 ● - , and fenton reaction
- Morphological changes follow functional changes o Reversible injury  Light microscope – cell swelling, fatty change  Ultrastructural changes – cell membrane alterations, swelling and small deposits of mitochondria, RER and attached ribosome swelling o Irreversible injury  Light microscope  Loss of RNA (which is basophilic) – increased cytoplasmic eosinophilia (pink colour)  Cytoplasmic vacuolization  Nuclear chromatin clumping  Ultrastructural  Membrane breakage  Large amorphous densities in mitochondria  Nuclear changes  Pyknosis – nuclear shrinkage, increased basophilia (blue colour)  Karyorrhexis – fragmentation of pyknotic nucleus  Karyolysis – fading of basophilia of chromatin - Types of Cell Death o Apoptosis – usually regulated, may be pathogenic, has a role in embryogenesis o Necrosis – always pathologic, many causes - Apoptosis o Programmed cell death in embryogenesis o Hormone dependent involution of adult organs (thymus) o Cell deletion in proliferative populations o Cell death in tumors o Cell injury in some viral diseases (hepatitis) - Necrosis o Causes  Coagulative (most common)  Cells basic outlines are preserved  Homogenous, glassy eosinophilic appearance due to loss of cytoplasmic RNA (basophilic) and glycogen (granular)  Nucleus may show any of pyknosis, karyorrhexis, or karyolysis  Liquefactive – most often in CNS and abscess – usually from enzymatic dissolution of necrotic cells (usually due to release of proteolytic enzymes from neutrophils)