GP_Ch2

Chapter 1: Introduction

Cells respond to stress in three main ways: adaptations, reversible injury, and cell death.
- Homeostasis: Cells maintain a steady state despite harmful agents.

Alterations that enable cells to cope with stress without damage.
- Example: Increased muscle mass due to increased workload.

Characterized by structural and functional abnormalities that can heal if the injurious agent is removed.
Examples of injurious agents leading to reversible injury:
- Infectious Pathogens: They produce toxins or stimulate immune responses, damaging infected cells.
- Hypoxia and Ischemia: Reduced oxygen (hypoxia) and blood supply (ischemia), depriving tissues of oxygen and essential nutrients.
- Toxins: Environmental and therapeutic agents harmful to cells.
- Environmental Insults: Physical trauma, radiation, nutritional imbalances.
- Genetic Abnormalities: Mutations impairing essential proteins or leading to DNA damage.
- Immunologic Reactions: Damage through inflammation caused by autoimmunity or allergens.
- Aging: A progressive form of cell injury.

Irreversible injury occurs when cells pass a point of no return, leading to death.
Characterized by:
1. Inability to restore mitochondrial function, oxidative phosphorylation, and ATP generation.
2. Altered membrane structure/function.
3. DNA damage and loss of chromatin integrity.

Necrosis vs Apoptosis:
- Necrosis: Accidental cell death due to severe injury with inflammation.
- Apoptosis: Regulated cell death, resulting in cellular dismantling without inflammation.
Necrosis is characterized by:
- Plasma membrane dissolution and leakage of cellular contents, causing local inflammation.
- Hallmarks include enzyme leakage and damage-associated molecular patterns (DAMPs) recognized by macrophages.

Necrosis causes include ischemia, microbial toxins, burns, and unusual enzyme leakage (e.g., pancreatitis).
Types of Necrosis:
- Coagulative Necrosis: Preserves architecture, often seen in ischemic injuries (e.g., heart, kidneys).
- Liquefactive Necrosis: Seen in bacterial infections and brain infarcts, resulting in pus formation.
- Gangrenous Necrosis: Pulmonary ischemia, can be dry (intact tissue) or wet (liquefied tissue).
- Caseous Necrosis: Typical of tuberculosis, looks cheesy microscopically.
- Fat Necrosis: From pancreatic lipase activity during acute pancreatitis, leading to chalky white areas.
- Fibrinoid Necrosis: Seen in immune reactions with antibody-antigen complexes deposition.

Apoptosis eliminates unneeded or damaged cells without inflammation.
Pathways of apoptosis:
- Mitochondrial (Intrinsic) Pathway: Activated by cellular stress; involves proteins BAX and BAK that lead to cytochrome c release and caspase activation.
- Death Receptor (Extrinsic) Pathway: Activated via TNF receptors and FAS, leading to caspase activation for targeted cell death.

Distinct morphologic features of apoptosis: nuclear pyknosis, cell shrinkage, and rapid clearance by phagocytes.
Other forms of cell death include necroptosis and pyroptosis:
- Necroptosis: Features of necrosis and apoptosis, regulated by kinases.
- Pyroptosis: Induced by bacterial toxins, causing local inflammation.
Autophagy: Cells digest inseparable organelles to recycle components for survival during nutrient deprivation.

The degree of cell injury varies with the type of agent and duration of exposure.
- Different cells have varying tolerances to ischemia.
Reactive Oxygen Species (ROS) can induce cellular damages such as lipid peroxidation and DNA breaks.
Injurious agents such as toxins directly or indirectly through metabolism can lead to cell injury (e.g., carbon tetrachloride).
Endoplasmic Reticulum Stress: Leads to apoptosis in the presence of misfolded proteins.

Cellular Adaptations: can be physiologic or pathologic.
- Hypertrophy: Cell size increase due to functional demand (e.g., weight lifting).
- Hyperplasia: Increase in cell number due to proliferation (e.g., hormonal responses).
- Atrophy: Decrease in cell size due to reduced stimuli (e.g., malnutrition).
- Metaplasia: Change from one cell type to another for survival in adverse conditions.
Abnormal Substance Accumulation: May cause injury or be harmless (e.g., steatosis in liver).

Calcification Types:
- Dystrophic Calcification: In normal serum calcium; seen in injured tissues (e.g., advanced atherosclerosis).
- Metastatic Calcification: In hypercalcemia conditions affecting various organs.
Excessive glycogen and amyloid deposits indicate metabolic or immune process disruptions, leading to potential organ dysfunction.