Cell Injury & Death

When apply stress to Cells it may:

  1. Adapt (via atrophy/hypertrophy/hyperplasia/metaplasia)

  2. Be injured (reversible or irreversible)

  3. Irreversible injury culminates in cell death (necrosis or apoptosis)


Adaptive Mechanisms:

  1. Atrophy: decrease in organ/tissue size due to decreased no./size of cells. Reasosn for atrophy- lack of endocrine stimulation, disuse, poor nutrition/blood supply, etc. Example: Alzheimer's

  2. Hypertrophy: increase in cell/tissue size. Can be physiological (e.g. uterus/pregnancy) or pathological (left ventricular hypertrophy due to Systemic Hypertension)

  3. Hyperplasia: increase in no. Of cells (e.g athlete's train at high altitude just before competitipn where there is low pO2 to trigger EPO production, EPOeisis & thus increase RBCs (“erythromycin hyperplasia”)

**Note: hypertrophy and hyperplasia can occur independently but usually co-occur.

  1. Metaplasia: one mature, differentiated cell type is replaced by another which is better suited to the adverse environment. Example: psuedostratified columnar epithelial cells of bronchus replaced by tough stratified squamous epithelial cells which can better withstand toxic chemicals from cig smoke.



Mechanisms of Cell Inujry

  1. Mitochondrial Dysfunction & Damage: ATP made via Ox. Phosphorylation in Mitochondria. Tissues w/ low glycolic activity (don’t break down glucose to release Energy ) depend on Ox. Phosphorylation for Energy. Mitochondrial damage = No Ox. Phosphorylation = No. ATP = Selective vulnerability of tissues w/low glycolytic activity (e.g. neurons, cardiac muscle)

  2. Ca2+ imbalances: cytosolic (in) Ca2+ levels are 10× lower than outside cell. Levels controlled by ATP- dependent pumps in mitochondria and ER. Ischaemia (low blood supply) and some toxins cause premature release of Ca2+ into cytosol. Excessive intracellular Ca2+ can cause cell injury by activating various enzymes (e.g. protease, phospholipases) that damage cell components.

  3. Oxidative Stress: R.O.S. produced due to chem/radiation injury, hypoxia, aging. Build up when production> cell's antioxidant defenses thus Oxidative STRESS. ****V. Reactive w/ nuclei acids, proteins, lipids so Dangerous

  4. Plasma Membrane Damage: most cell injury types compromise membrane's ability to maintain ionic balance between compartments ***especially affects mitochondria


*Key Organelles in Cell Damage/Death

  • Nucleus ( DNA damage response)

  • ribosomes (protein synthesis)

  • Mitochondria (ATP synthesis, apoptosis)

  • Plasma Membrane (barrier)

  • ER (protein folding, Ca2+ storage)

  • Lysosomes ( enzyme release and autophagy- digest/recycle cell contents for nutrients and energy in times of starvation)