Cellular Damage and Cell Death Overview

Cellular Damage and Cell Death

• Cell damage can result from various factors, including oxygen deprivation, chemicals, drugs, infections, immune reactions, genetic abnormalities, and nutritional imbalances.
• Reversible cell injury involves early functional and structural alterations, which are correctable if the damaging stimulus is removed. This includes generalized cell swelling due to water influx (failure of the Na+/K+ pump) and fatty changes (accumulation of lipids, particularly in the liver).
• Irreversible cell injury leads to cell death, either through necrosis or apoptosis. Necrosis is characterized by cell swelling, membrane rupture, and release of intracellular enzymes. Apoptosis is a programmed cell death process where the cell fragments and is removed by phagocytosis.

Point of No Return

• The point of no return for cellular damage depends on the cell's ability to adapt, the type and duration of the insult, and the involvement of organelles.
• Irreversible injury affects the membranes, cytoskeleton, and DNA, leading to misfolding of proteins and disrupted functions.

Mitochondrial Dysfunction

• The electron transport chain, not always directly linked to ATP production, can be disrupted by thermogenin/uncoupling protein-1 (UCP-1) and can generate heat.
• Proliferative cells utilize glycolysis for respiration instead of oxidative phosphorylation, using intermediates to create lipids, proteins, and nucleotides, supporting rapid growth.
• Mitochondrial problems play critical roles in apoptosis and necrosis, both types of cell death.

DNA Damage

• Damage to nuclear DNA activates p53, an onco-suppressor gene, which triggers DNA repair pathways.
• If repair is impossible, the p53 pathway might initiate apoptosis to eliminate the damaged cell.
• ROS (reactive oxygen species) damage DNA and other cellular components, including proteins and lipids. They can result from radiation, toxins, and other environmental factors.

Oxidative Stress and ROS

• ROS, produced during cellular processes, can damage proteins, lipids, and DNA.
• Oxidative stress is increased during ischemia and reperfusion events when blood flow is restored.
• Phagocytosis utilizes ROS to eliminate pathogens.
• Cell injury can result from ROS overproduction as occurs in ischemia-reperfusion injury.

Phagocytosis

• Phagocytic cells like macrophages and neutrophils utilize ROS, in part, for destroying pathogens and debris.

Chronic Granulomatous Disease

• This is an immune deficiency that affects the ability of phagocytic cells to kill ingested pathogens, producing chronic inflammation due to compromised pathogen elimination.

Pathologic Effects of Free Radicals

• Lipid peroxidation damages cell membranes.
• Oxidative modifications alter protein structure and function.
• DNA damage leads to mutations.
• Unfolded protein response (UPR) can lead to protein misfolding and cell stress.

Cellular Aging

• Aging involves accumulating damage (free radicals, DNA damage, inability to divide, protein modifications) leading to reduced function.
• Replicative senescence describes the limited capacity for cell division.
• Telomeres, short DNA sequences at the end of chromosomes, shorten with each replication and signal cell cycle arrest for normal cells.
• Genetic conditions can prematurely accelerate some aging signs.

Apoptosis

• Apoptosis is normal cell death with no inflammation.
• It allows the body to remove unneeded or damaged cells.
• Mitochondria and caspases are critical components in its execution involving the formation of apoptosome.

This quiz explores the concepts of cellular damage and cell death, including reversible and irreversible injuries. Learn about various factors that cause cell damage and the differences between necrosis and apoptosis. Understand the mechanisms and implications of cellular injury in the body.