Wound Healing Flashcards
Recruitment of Quiescent Cells into the Cell Cycle (Most Important)
Quiescent cells (also called stable cells) are cells that are normally not dividing but have the ability to re-enter the cell cycle and start dividing when needed.
When there is tissue damage, growth factors (like PDGF, TGF-β, and EGF) signal these cells to leave their resting state (G0 phase) and enter the proliferation phase (G1, S, G2, M phases) to produce new cells.
This is the main mechanism by which tissues regenerate and repair.
Shortening of Cell-Cycle Time (Less Important)
Cells go through different phases in the cell cycle (G1 → S → G2 → M), and under certain conditions, the time it takes to complete one cycle can be reduced.
While this can increase the speed of cell division, it is less important than recruiting more cells to enter the cycle in the first place.
Why is Recruitment More Important?
Even if a cell divides faster, the total number of dividing cells is still limited. However, if more quiescent cells are activated and start dividing, the tissue can regenerate much more effectively.
Proliferative Capacity of Cells:
Cells in the body have different abilities to divide and regenerate. They are categorized into three groups:
Labile Cells (Constantly Dividing)
These cells continuously divide and replace old or damaged cells.
Found in tissues that experience frequent wear and tear.
Examples:
Gut epithelium (lining of the intestines, which constantly renews itself).
Bone marrow stem cells (produce blood cells continuously).
Stable Cells (Can Divide When Needed)
These cells are normally quiescent (in the G0 phase of the cell cycle) but can start dividing if needed (e.g., after injury).
They help in wound healing and organ regeneration.
Examples:
Fibroblasts (produce collagen in wound healing).
Endothelial cells (form new blood vessels).
Hepatocytes (liver cells can regenerate after damage).
Permanent Cells (Rarely or Never Divide)
These cells have lost their ability to divide, so if they are damaged, they cannot regenerate and are replaced by scar tissue.
Examples:
CNS neurons (brain and spinal cord cells—damage leads to permanent loss, e.g., stroke).
Cardiac myocytes (heart muscle cells—damage, like in a heart attack, leads to scar formation instead of new muscle).
Why is this Important?
Labile cells heal quickly (e.g., skin wounds heal fast).
Stable cells can regenerate if needed (e.g., liver can recover from partial damage).
Permanent cells do not regenerate, leading to permanent damage and scarring in the brain and heart.
healing by first intention vs. healing by second intention,
Healing by First Intention (Primary Intention)
Happens when wound edges are close together (e.g., a surgical incision that is sutured).
Minimal scarring because the wound heals with little tissue loss.
Healing is faster with fewer complications.
Process:
The wound is closed (e.g., with stitches).
Minimal granulation tissue forms.
The wound heals with a thin scar.
2. Healing by Second Intention (Secondary Intention)
Happens when wound edges are far apart (e.g., open wounds, burns, ulcers).
More granulation tissue forms to fill the gap.
Healing is slower and results in a larger scar.
Higher risk of infection.
Process:
The wound remains open.
Granulation tissue (new connective tissue and blood vessels) fills the wound.
The wound contracts and eventually forms a thicker scar.
healing by first intention (primary intention).
Key Steps (from the images):
Immediate Response (Minutes to Hours)
Haemostasis: Platelets and fibrin form a clot to stop bleeding.
Inflammation: Neutrophils arrive to kill bacteria and clear debris.
First Few Days (1–3 days)
Macrophages arrive and remove dead cells.
Fibroblasts migrate in and start producing collagen.
Early Healing (7–10 days)
Scar tissue starts forming.
Blood supply improves, and the wound is mostly closed.
Long-Term Healing (1 month–2 years)
Collagen remodeling: The scar matures and strengthens.
The scar can take up to 2 years to fully mature, though most healing happens in a few months.
Healing by Second Intention (Secondary Intention)
This happens when the wound edges cannot be brought together (e.g., larger open wounds, ulcers, burns).
More tissue loss → more granulation tissue → larger scar.
Healing is slower and has a higher risk of infection.
Key Differences in Second Intention Healing:
Wound remains open → No sutures, so healing must occur from the bottom up.
More inflammation → More neutrophils and macrophages are needed to clear debris.
Granulation tissue fills the gap → Fibroblasts produce more collagen to bridge the wound.
Wound contracts over time with the help of myofibroblasts.
Healing takes longer and results in a larger, irregular scar.
What is Epithelialization?
Epithelialization is the process where new epithelial (skin) cells cover the wound.
It is essential for closing the wound and restoring the skin barrier.
Key Steps in Epithelialization (Slide 1)
Cells at the wound edge flatten → This allows them to migrate.
De-differentiation → Cells temporarily lose their specialized function to become more mobile.
Pseudopod formation → Cells extend out to move across the wound.
Migration across the wound → Cells use integrin receptors to attach to the extracellular matrix and crawl across the wound.
Cell division at the margins → New cells multiply to form a full layer of skin.
Wound closure → In surgical wounds, this happens in 24-48 hours.`
What Can Delay
Epithelialization? (Slide 2)
Epithelialization can be slowed down by several factors:
Bacteria → Causes infection and prolongs inflammation.
Protein exudate from leaky capillaries → Creates a fluid barrier that slows cell migration.
Necrotic debris → Dead tissue must be removed for new cells to grow.
If epithelialization is delayed, inflammation lasts longer, increasing the risk of chronic wounds.
How to Promote Faster Healing?
Keeping the wound clean and moist helps epithelial cells migrate more effectively.
What Happens in the Remodelling Phase?
This phase strengthens and reshapes the wound to restore normal tissue function.
Wound Contraction
Fibroblasts transform into myofibroblasts, which pull the wound edges together.
This is stimulated by TGF-β (Transforming Growth Factor-beta) and PDGF (Platelet-Derived Growth Factor).
Collagen Remodeling
Collagen synthesis and degradation are regulated by metalloproteinases (enzymes produced by macrophages, endothelial cells, and fibroblasts).
The initial collagen (type III) is replaced with stronger type I collagen, increasing wound strength.
Scar Formation & Strength
The wound gains 20% of its final strength by 3 weeks.
The final scar is only about 70% as strong as normal skin (it never fully regains original strength).
Re-epithelialization
The epidermis (skin layer) regrows over the wound, covering it completely.
Organization of the new tissue continues to improve function.
