Intracellular Accumulations and Cellular Aging

Study Notes

Result from metabolic disturbances leading to abnormal material buildup within cells.
Can occur due to excessive intake, defective transport, or defective catabolism.
Triglycerides: Accumulate in cells during conditions like fatty liver.
Cholesterol: Accumulates in macrophages and smooth muscle cells of vessel walls in atherosclerosis.
Proteins: Immunoglobulins accumulate in plasma cells during immune responses.
Glycogen: Accumulates in liver and muscle in glycogen storage diseases.
Pigments:
- Exogenous:
  - Carbon (anthracosis)
  - Lipofuscin (aging pigment)
  - Iron (in hemosiderosis)
- Endogenous:
  - Lipofuscin (aging pigment) is found in liver and other cells.
  - Iron (in hemosiderosis) is found in liver and other cells.

Refers to the morphological and functional changes that occur in cells due to their prolonged lifespan
Several contributing factors:
- Accumulating genetic cellular damage.
- Reduced ability to repair damaged DNA.
- Reduced capacity to divide (senescence).
- Defective protein homeostasis.
- Effect of high caloric intake.
Morphological changes:
- Abnormal shaped nuclei, mitochondria, Golgi apparatus.
- Decreased endoplasmic reticulum, ribosomes.
- Accumulation of cytoplasmic lipofuscin pigment (aging pigment).
Examples:
- Lipofuscin in neurons
- Lipofuscin in Cardiac Muscle
Autophagy:
- Main mechanism of cellular aging.
- Involves engulfing cell organelles into cytoplasmic vacuoles, which fuse with lysosomes for digestion.
- Also occurs in cancers.

Cells adapt to stress to maintain homeostasis.
Hypertrophy:
- Increased cell size and organ size.
- Occurs in response to increased workload or growth.
- Example: Hypertrophy of smooth muscle cells of the uterus during pregnancy.
Hyperplasia:
- Increased cell numbers.
- Driven by hormonal and growth factor stimulation.
- Occurs in tissues with dividing cells or tissue stem cells.
- Example: Hormonal hyperplasia of the female breast during puberty.
Atrophy:
- Decreased cell size and organ size.
- Results from decreased nutrient and blood supply or disuse.
- Mechanism involves decreased synthesis of cellular proteins and organelles and increased breakdown.
- Example: Senile brain atrophy.
Metaplasia:
- Replacement of one differentiated cell type by another differentiated cell type of the same category (e.g., epithelium to another epithelium).
- Often occurs in response to chronic irritation.
- Allows cells to better resist the stress.
- Example: Squamous metaplasia of respiratory epithelium in cigarette smokers.

Includes:
- Cellular swelling (cloudy swelling; hydropic degeneration): Intracellular accumulation of water. Example: Kidney tubules lining epithelium.
- Fatty change: Intracellular accumulation of fat. Example: Hepatocytes.
Morphology:
- Cell swelling.
- Cell membrane blebs.
- Mitochondrial swelling.
- Swelling of the endoplasmic reticulum.
Cells maintain their shape and can return to normal after injury.

Necrosis:
- Death of a group of cells or tissues.
- Morphology:
  - Dead cells and tissue become more eosinophilic.
  - Nuclear dissolution.
  - Breakdown of plasma membrane and organelle membranes forming myelin figures.
  - Enzymatic digestion of cellular contents.
  - Surrounding inflammation.
Apoptosis:
- Programmed single-cell death.
- Removes unwanted or genetically damaged cells.
- Mechanism:
  - Activation of cellular enzymes called 'caspases'.
  - Cell fragmentation into apoptotic bodies (nuclear fragments + cytoplasm).
  - Engulfment of fragmented cells by phagocytes.
- Pathways:
  - Intrinsic pathway: triggered by stress or DNA damage.
  - Extrinsic pathway: triggered by death receptors on cell surface.