Wound Healing and Cell Death

Wound Healing 1

• Wound healing is a complex process in the human body
• It involves the coordination of various cell types for haemostasis, inflammation, proliferation, and remodelling.
• Cell injury can be reversible or irreversible.
• Irreversible cell injury leads to different types of cell death depending on the nature and severity of the insult.
• Two major types of cell death are apoptosis and necrosis.
• Necroptosis and pyroptosis are also mechanisms of unusual cell death.
• Autophagy is a cellular adaptation to nutrient deprivation. During autophagy, cells digest their organelles for energy and substrates.
• Autophagy leads to apoptosis if the stress is too great.
• Homeostasis, is a state of stable internal environment maintained by cells

Cell Injury and Cell Death

• The intracellular environment of cells is highly regulated to maintain homeostasis.
• Cell injury can be caused by hypoxia/ischemia, toxins, infectious agents, immune reactions, genetic abnormalities, nutritional imbalances, physical agents, and aging.
• Cells encounter physiological stress (like increased workload) or injurious conditions (like nutrient deprivation).
• Cells can adapt to these stresses to maintain their viability and function.

Types of Cell Injury and Cell Death

• Cell injury can be reversible or irreversible, depending on the insult's nature and severity.
• Injured cells die through different mechanisms.
• Necrosis is always a sign of pathological cell damage; it's not a normal process.
• Apoptosis occurs in both healthy and diseased tissues. This is a programmed cell death for normal cell turnover and tissue homeostasis.
• Necroptosis and pyroptosis are unusual forms of cell death, characterized by inflammation.
• Autophagy is a cellular adaptation to nutrient deprivation; severe stress can lead to cell death through apoptosis.

Apoptosis and Necrosis

• Apoptosis : Cells shrink, condense chromatin, form apoptotic bodies, and are engulfed by phagocytes. No inflammation. Normal cell turnover/removal.
• Necrosis: Cells swell, lose membrane integrity, DNA breaks down, and cause inflammation. Pathological cellular damage results

Pyroptosis and Necroptosis

• Pyroptosis involves caspase-1 activation and inflammatory responses.
• Necroptosis is driven by RIPK1 and RIPK3 triggering cell death and inflammation.

Autophagy

• Autophagy is a cellular process where cells recycle their organelles when there's a nutrient shortage,
• This process involves the formation of autophagic vacuoles which fuse with lysosomes to break down cell components, providing new substrates.
• If the stress is excessive, this process can lead to apoptosis.

Cellular Response During Wound Healing

• Wound healing is a complex process involving spatial and temporal changes in the synchronisation of different cells
• Stages include haemostasis, inflammation, proliferation and remodelling.

Summary

• Cell injury can be reversible or irreversible.
• Irreversible injury results in apoptosis, necrosis, pyroptosis, and necroptosis.
• Autophagy functions to allow cells to recycle their own components when there is a lack of nutrients.
• Wound healing involves multiple cell types in four key steps (haemostasis, inflammation, proliferation and remodelling) that work together in a coordinated manner.