NURA 510: Advanced Pathophysiology Lecture Notes

NURA 510 Advanced Pathophysiology Spring 2024 Linda Wunder, PhD, CRNA, APRN, FAANA [email protected] Reading Assignment ˜ Chapter 2 : Altered Cellular and Tissue Biology: Environmental Agents  Cellular Adaptation ˜ Is the cell’s response to...

NURA 510 Advanced Pathophysiology Spring 2024 Linda Wunder, PhD, CRNA, APRN, FAANA [email protected] Reading Assignment ˜ Chapter 2 : Altered Cellular and Tissue Biology: Environmental Agents  Cellular Adaptation ˜ Is the cell’s response to escape and protect itself from injury. ˜ Adaptive changes in cells Ø Atrophy: Decrease in cell size Ø Hypertrophy: Increase in cell size Ø Hyperplasia: Increase in cell number Ø Metaplasia: Reversible replacement of one mature cell type by another less mature cell type Ø Dysplasia: Deranged cellular growth; is not a true cellular adaptation but rather an atypical hyperplasia Copyright © 2019, Elsevier Inc. All rights reserved. 3 Cellular Adaptation (Cont.) 4  Cellular Injury ˜ Leads to injury of tissues and organs, determining structural patterns of disease. ˜ Injured cells may recover (reversible injury) or die (irreversible injury). ˜ Causes cell stress. ˜ Is acute or chronic and reversible or irreversible. ˜ Can involve necrosis, apoptosis, accumulation, or pathologic calcification. 5  Cellular Injury (Cont.) ˜ Cellular injury can lead to cell death by: Ø Decreased ATP production Ø Failure of active transport mechanisms (sodium-potassium [Na+/K+] pump) Ø Cellular swelling Ø Detachment of ribosomes from endoplasmic reticulum Ø Cessation of protein synthesis Ø Mitochondrial swelling from calcium accumulation Ø Vacuolation Ø Leakage of digestive enzymes from lysosomes; autodigestion of intracellular structures Ø Lysis of the plasma membrane 6  Cellular Injury (Cont.) ˜ Causes Ø Lack of oxygen (hypoxia) Ø Free radicals Ø Toxic chemicals Ø Infectious agents Ø Physical and mechanical factors Ø Immunologic reactions Ø Genetic factors Ø Nutritional imbalances Ø Physical trauma 7  Cellular Injury (Cont.) ˜ Ischemia-Reperfusion Injury Ø Due to: Oxidative stress Radicals that cause membrane damage and mitochondrial calcium overload Mitochondrial permeability transition pore Ø Mechanism of injury in: Tissue transplantation Ischemic syndromes: myocardial, hepatic, intestinal, cerebral, renal, stroke 8  Cellular Injury (Cont.) ˜ Carbon monoxide (CO) Ø Is colorless and odorless. Ø Produces hypoxic injury. Directly reduces the oxygen-carrying capacity of blood, and promotes tissue hypoxia. CO’s affinity for hemoglobin is much greater than that of oxygen; it quickly binds with the hemoglobin, preventing oxygen molecules from doing so. 9  Cellular Injury (Cont.) ˜ Asphyxial injuries Ø Cause: Failure of cells to receive or use oxygen Ø Suffocation Ø Strangulation Hanging Ligature Manual Ø Chemical asphyxiants Ø Drowning 10  Cellular Injury (Cont.) ˜ Infectious injuries Ø Pathogenicity (virulence) of a microorganism Ø Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions 11  Cellular Injury (Cont.) ˜ Immunologic and inflammatory injuries Ø Phagocytic cells Ø Immune and inflammatory substances Histamine Antibodies Lymphokines Complement Proteases Ø Cause membrane alterations 12  Cellular Injury (Cont.) ˜ Temperature extremes and climate change Ø Hypothermic injury Slows cellular metabolic processes. Produces reactive oxygen species. Ø Hyperthermic injury Heat cramps, heat exhaustion, heat stroke Malignant hyperthermia, neuroleptic malignant syndrome Drug-induced hyperthermia Burns Overheating, sudden infant death syndrome 13  Cellular Injury (Cont.) ˜ Ionizing radiation Ø Any form of radiation capable of removing orbital electrons from atoms X-rays, gamma rays, alpha and beta particles Ø Mechanism of damage Early or late tissue reactions (deterministic) Stochastic (random effects) 14  Cellular Injury (Cont.) ˜ Ionizing radiation (cont.) Ø Bystander effects: Cells not in the directly radiated field are affected by the radiation; referred to as horizontal transmission Ø Genomic instability: Generations of cells derived from an irradiated progenitor cell appear normal, but time-lethal (i.e., irreversible) and nonlethal mutations appear; referred to as vertical transmission 15  Cellular Death ˜ Two types of cellular death: 1. Necrosis Includes inflammatory changes. Autolysis 2. Apoptosis No inflammatory changes Type I—programmed cell death Type II—autophagic cell death 16  Cellular Death: Necrosis ˜ Necrosis Ø Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis) 17 Cellular Death: Types of Necrosis (Cont.) ˜ Dry Gangrene 18  Cellular Death: Apoptosis ˜ Apoptosis Ø Is programmed cellular death. Ø ER stress results in apoptotic cell death. Ø Is the active process of cellular destruction. Ø Can occur normally or pathologically. Ø Dysregulated apoptosis is excessive or insufficient. can lead to cancer, autoimmune disorders, neurodegenerative diseases, and ischemic injury. 19  Cellular Death: Autophagy ˜ “Recycling center” ˜ Eats itself ˜ Self-destructive process ˜ Survival mechanism 20  Aging and Altered Cellular and Tissue Biology ˜ Aging is normal, inevitable, and universal. Ø Accumulation of damaged macromolecules ˜ Human life span is the time from birth to death. ˜ Maximal human life span is 80−100 years. ˜ Life expectancy is the average number of years of life remaining at a given age. ˜ Current generation may have a shorter life span than previous generations. 21  Aging and Altered Cellular and Tissue Biology (Cont.) ˜ Degenerative extracellular changes Ø Collagen binding and cross-linking Ø Increase in free radicals’ effects on cells Ø Structural alterations Ø Peripheral vascular disease and oxidative stress ˜ Cellular aging Ø Atrophy, decreased functioning, loss of cells Ø 4977 deletion or common deletion 22  Aging and Altered Cellular and Tissue Biology (Cont.) ˜ Tissue and systemic aging Ø Progressive stiffness and rigidity ˜ Frailty Ø Complex clinical syndrome Ø Involves oxidative stress, dysregulation of inflammatory cytokines and hormones, malnutrition, physical inactivity, and muscle apoptosis. 23  Somatic Death ˜ Is the death of the entire person. ˜ Does not involve an inflammatory response. ˜ Postmortem changes include: Ø Complete cessation of respirations and circulation Ø Algor mortis: Reduced temperature Ø Livor mortis: Purple skin discoloration Ø Rigor mortis: Muscle stiffening Ø Postmortem autolysis: Putrefactive changes associated with the release of enzymes and lytic dissolution 24