Cellular Responses to Stress

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Cellular Adaptations - Shape Shifters

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

AdaptationDefinitionMechanism HighlightsExamples
Hypertrophy↑ cell size↑ protein synthesis, ↑ organellesCardiac muscle (LVH in hypertension), skeletal muscle (exercise)
Hyperplasia↑ cell numberGrowth factor-driven proliferation of mature/stem cellsBenign Prostatic Hyperplasia (BPH), endometrial hyperplasia, calluses
Atrophy↓ cell size/number (due to loss of cell substance)↓ protein synthesis, ↑ protein degradation (ubiquitin-proteasome)Disuse atrophy, denervation atrophy, senile atrophy, ↓ blood supply
MetaplasiaReversible change: one adult cell type to anotherReprogramming of stem cells, altered differentiation pathwayBarrett's esophagus (squamous to columnar), squamous metaplasia in bronchi

⭐ 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:

FeatureNecrosisApoptosis
NaturePathologic; acute injuryProgrammed (physiologic/pathologic)
Cell SizeSwelling (oncosis)Shrinkage
NucleusPyknosis, karyorrhexis, karyolysisChromatin condensation, fragmentation
Plasma MembraneDisrupted, contents leakIntact, blebbing; PS flip
Cellular ContentsEnzymatic digestion, uncontrolled releasePackaged into apoptotic bodies
InflammationSignificantAbsent; bodies phagocytosed
ATPDepletedRequired (energy-dependent)
DNA BreakdownRandom, diffuseInternucleosomal cleavage (laddering)
Key MediatorsLysosomal enzymes, ROS, $Ca^{2+}## Necrosis vs. Apoptosis - Deathly Duo

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).

Practice Questions: Cellular Responses to Stress

Test your understanding with these related questions

What is the approximate time at which the quantity of ATP within ischemic cardiac myocytes is reduced to 10% of the original?

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Flashcards: Cellular Responses to Stress

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The movement of calcium from the cytosol to the extracellular space takes place by _____ active transport

TAP TO REVEAL ANSWER

The movement of calcium from the cytosol to the extracellular space takes place by _____ active transport

primary and secondary (primary/secondary)

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