Cellular Responses to Stress

Cellular Adaptations - Shape Shifters

Cells adapt to stress by altering size, number, or phenotype. These are reversible changes.

⭐ Barrett's esophagus (intestinal metaplasia in the distal esophagus due to chronic GERD) significantly ↑ risk of esophageal adenocarcinoma.

Cell Injury Mechanisms - Damage Control

• Cellular response to stress, if overwhelmed, leads to injury. Key players:

  • Mitochondria: ATP depletion (↓5-10% of normal → irreversible), ROS ($O_2^{\cdot-}$, $H_2O_2$, $\cdot OH$) production.
  • Calcium homeostasis: ↑ cytosolic $Ca^{2+}$ activates damaging enzymes (phospholipases, proteases, endonucleases, ATPases).
  • Membrane integrity: Damage to plasma & organellar membranes is crucial.
  • DNA & protein damage: Misfolded proteins, DNA damage.

• Reversible Injury: Cellular swelling, fatty change, plasma membrane blebbing, loss of microvilli, mitochondrial swelling, ER dilation, ribosome detachment, nuclear chromatin clumping.

• Irreversible Injury: Severe mitochondrial damage (vacuolization), profound membrane damage (plasma, lysosomal), nuclear changes (pyknosis → karyorrhexis → karyolysis).

  • Point of no return: Irreversible mitochondrial dysfunction, critical membrane damage.

⭐ Plasma membrane damage is a critical event in irreversible cell injury, leading to enzyme leakage (e.g., troponins, CK-MB) and $Ca^{2+}$ influx.

• Free radical injury: Lipid peroxidation, protein modification, DNA damage. Neutralized by antioxidants (e.g., SOD, catalase, glutathione peroxidase).

Necrosis vs. Apoptosis - Deathly Duo

Key Differences:

Key Differences:

influx | Caspases (initiator & executioner) |* Necrosis: Uncontrolled "cell homicide" from severe injury (e.g., ischemia). Pathologic, causes inflammation. - Types: Coagulative, Liquefactive, Caseous, Fat, Fibrinoid, Gangrenous. (📌 Mnemonic: Can Lazy Cats Feel Good Frequently?)

• Apoptosis: Regulated "cell suicide." Physiologic (embryogenesis) or pathologic (DNA damage). No inflammation.
  • Forms apoptotic bodies, phagocytosed. Key enzymes: Caspases.

⭐ Caspases (Cysteine-dependent Aspartate-directed proteases) are the central executioners of apoptosis. Initiator caspases (e.g., -8, -9) activate executioner caspases (e.g., -3, -6, -7).

Apoptosis Pathways:

Subcellular Responses & Accumulations - Inner Workings

• Autophagy: Lysosomal degradation of damaged organelles; cellular housekeeping.

• Endoplasmic Reticulum (ER) Stress: Misfolded proteins accumulate, triggering Unfolded Protein Response (UPR).

  • UPR: ↑chaperones, ↓protein synthesis, or apoptosis if severe.

• Heat Shock Proteins (HSPs): Molecular chaperones; protect against stress, aid protein folding.

• Intracellular Accumulations:

  • Lipids: Steatosis (e.g., fatty liver).
  • Proteins: E.g., Russell bodies (plasma cells), Mallory bodies (liver).
  • Glycogen: Glycogenoses; visible as clear vacuoles.
  • Pigments:
    • Lipofuscin:

High‑Yield Points - ⚡ Biggest Takeaways

• Key cellular adaptations: hypertrophy, hyperplasia, atrophy, metaplasia.
• Reversible injury signs: cellular swelling (hydropic change), fatty change.
• Irreversible injury: critical membrane damage, massive Ca²⁺ influx, mitochondrial failure.
• Necrosis causes inflammation; apoptosis is programmed, non-inflammatory cell death.
• Heat Shock Proteins (HSPs) are crucial for protein folding and stress protection.
• Oxidative stress (↑ROS) damages cells; countered by antioxidants.
• ER stress activates the unfolded protein response (UPR).