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• Study notes for NURA 510 Advanced Pathophysiology Spring 2024

Cellular Adaptation

• Cells respond to escape and protect against injury through adaptation.
• Adaptive changes in cells include atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia.
• Atrophy is the decrease in cell size.
• Hypertrophy is the increase in cell size.
• Hyperplasia is the increase in cell number.
• Metaplasia is the reversible replacement of one mature cell type by another less mature cell type.
• Dysplasia is deranged cellular growth and atypical hyperplasia and isn't a true cellular adaptation.

Cellular Injury

• Leads to injury of tissues and organs, determining patterns of disease.
• Injured cells can recover, which is reversible injury, or die, which is irreversible injury.
• Cellular injury causes cell stress and can be acute or chronic and either reversible or irreversible.
• Cellular injury can result in necrosis, apoptosis, accumulation, or pathologic calcification.
• Cell death can occur if there's decreased ATP production, failure of active transport mechanisms, or cellular swelling.
• Detachment of ribosomes, cessation of protein synthesis, mitochondrial swelling from calcium accumulation are other results of cell injury.
• Vacuolation, leakage of digestive enzymes, and lysis of the plasma membrane are results of cell injury.
• Cellular injury causes include hypoxia, free radicals, toxic chemicals, infectious agents, physical and mechanical factors, and immunologic reactions.
• Genetic factors, nutritional imbalances, and trauma can cause cellular injury.

Ischemia-Reperfusion Injury

• Caused by oxidative stress, radicals that cause membrance damage and excess mitochondrial calcium.
• It can also be caused by a Mitochondrial permeability transition pore
• Mechanism of injury occurs in tissue transplantation and ischemic syndromes like strokes and myocardial, hepatic, and intestinal, cerebral and renal conditions.

Carbon Monoxide (CO)

• Colorless and odorless gas that produces hypoxic injury
• Directly reduces the oxygen-carrying capacity in the blood and promotes tissue hypoxia
• CO's affinity for hemoglobin is much greater than oxygen's; it quickly binds with the hemoglobin, which prevents oxygen molecules from binding.

Asphyxial Injuries

• Caused by the failure of cells to receive or use oxygen.
• Includes suffocation, strangulation, chemical asphyxiants, and drowning.
• Strangulation can occur by hanging, ligature, or manually.

Infectious Injuries

• Pathogenicity is the virulence (disease-producing potential) of a microorganism.
• Disease-producing potentials include invasion and destruction, toxin production, or production of hypersensitivity reactions.

Immunologic And Inflammatory Injuries

• Involves phagocytic cells, immune and inflammatory substances, and cause membrane alterations.
• Immune and inflammatory substances include histamine, antibodies, lymphokines, complement, and proteases.

Temperature Extremes and Climate Change

• Hypothermic injury slows cellular metabolic processes and produces reactive oxygen species.
• Hyperthermic injuries include heat cramps, heat exhaustion, heat stroke, malignant hyperthermia, neuroleptic malignant syndrome, drug-induced hyperthermia, burns, overheating, and sudden infant death syndrome.

Ionizing Radiation

• Is any form of radiation capable of removing orbital electrons from atoms, such as X-rays, gamma rays, alpha, and beta particles.
• Mechanisms of damage include early or late tissue reactions (deterministic) and stochastic (random effects).
• Bystander effects occur when cells not directly radiated are affected by radiation, referred to as horizontal transmission.
• Genomic instability refers to the fact that generations of cells from irradiated cells appear normal, but time-lethal and nonlethal mutations appear; known as vertical transmission.

Cellular Death

• Two types of cellular death are necrosis and apoptosis.
• Necrosis includes inflammatory changes and autolysis.
• Apoptosis has no inflammatory changes and can be Type I (programmed cell death) or Type II (autophagic cell death).

Necrosis

• Sum of cellular changes after local cell death, and includes the process of cellular autodigestion (autolysis)

Apoptosis

• Programmed cellular death, during ER stress is apoptosis
• Is the active process of cellular destruction, and can occur normally or pathologically.
• Dysregulated apoptosis can be either excessive or insufficient, and lead to cancer, autoimmune disorders, neurodegenerative diseases, and ischemic injury.

Autophagy

• Functions as a "recycling center," eats itself, is a self-destructive process and a survival mechanism.

Aging and Altered Cellular and Tissue Biology

• Aging is normal, inevitable, universal, and includes accumulation of damaged macromolecules.
• Human life span is the time from birth to death, and the maximal human life span is 80-100 years.
• Life expectancy is the average number of years of life remaining at a given age given a current generation may have a shorter life span than previous generations. Degenerative extracellular changes
• This includes collagen binding and cross-linking.
• Increase in free radicals' effects on cells
• Structural alterations
• Peripheral vascular disease and oxidative stress
• Cellular aging is atrophy, decreased functioning, loss of cells 4977 deletion or common deletion

Tissue And Systemic Aging

• This includes progressive stiffness and rigidity
• Frailty is a complex clinical syndrome that involves oxidative stress, dysregulation of inflammatory cytokines and hormones, malnutrition, physical inactivity, and muscle apoptosis.

Somatic Death

• Is the death of the entire person
• Doesn't involve an inflammatory response.
• Postmortem changes include complete cessation of respirations and circulation.
• Algor mortis is reduced temperature.
• Livor mortis is purple skin discoloration.
• Rigor mortis is muscle stiffening.
• Postmortem autolysis is putrefactive changes associated with the release of enzymes and lytic dissolution.