Week 7- Wound Heeling Flashcards
Name the 4 phases of wound healing
-haemostatsis
-inflammation
-proliferation
-remodelling
What is the function of inflammation
-limit spread of injury
-prevent further damage
-dilute or remove harmful agents e.g. bacteria, toxins etc
-removed damaged cells, tissues and debris ready for TISSUE REPAIR
-Name cardinal signs of inflammation
-swelling
-redness
-heat
-pain
-losss of function
What occurs in the vascular phase of inflammation
-capillary bed vasodilation (increased blood flow)
-capillary and venule have increased permeability (become leaky)
-tissue fluid from blood taken into connective tissue. Taken up by proteoglycans.
What stimulates the vascular response
Cytokinesis
How long does the vascular phase last
Secs-mins
How long till the cellular phase occurs
3-5days
When do mast cells burst, what do they release?
When tissue is damaged, release histamine, serotonin
When do platelets cells burst, what do they release?
Blood vessel damage. Release histamine, serotonin
Describe vascular phase (4)
1)Histamines cause vasodilation. Blood vessels widen, increasing blood flow (redness and heat) serotonin and prostoglandins prolong the duration
2) histamines stimulate endothelial cells to loose their tight junctions and blood vessels become-permeable (more leaky)
3) proteins and plasma move into the intracellular spaces by osmosis. Fluid moves into interstitial fluid/ taken up by proteoglycans and cause Odema (swelling)
4) pain receptors (nociceptors) are sensitised by bradykinin and prosteoglandins. Pressure from the swelling stimulates the pain receptors.
What is the function of neutrophil and macrophages
Undergo phagocytosis
How do neutrophil undergo their function
Use phagocytosis and chemical sprays (enzymes and free radicals) allow movement into tissue and break down damages tissue
-1-12hrs
Function of macrophages
Continue the clean up, remove old neutrophils, debris and bacteria.
Key to moving out of inflammation
-24-48hrs
How do phagocytes move into tissue
-margination
-rolling
-adhesion
-diapedesis/transmigration
-chemotaxis
Describe inflammation (5)
1) MARGINATION as blood flow becomes congested, phagocytes drop to the MARGINS
2)ROLLING/PAVEMENTING. week attraction and rolling along the endothelial cells.
3) ADHESION phagocyte attaches strongly to special attachment proteins
4) TRANSMIGRATION. Phagocyte squeezes through leaky membrane intointracellular space
5) CHEMOTAXIS. Cells move to area of damage following cytokine concentration gradient, cell debris etc
What do macrophages release, what does this stimulate?
-GROWTH FACTORS
-epithelial cells which have lost contact with each other in PROLIFERATION,are stimulated by gorwth factors (epidermal GF). They replicate and leap frog each other until they meet in the middle. They then make connections down a basement membrane.
Describe fibroblast growth factor in profliferation phase
-they migrate into the area from surrounding tissue and growth factors (fibroblast growth factor) stimulate them to replicate.
First they break down old extracellular matrix before making new ground substance (Proteoglycans ) and collagen (type 2)
Describe endothelial derived growth factor
-fibroblast and endothelial cell activity factors use up o2 (hypoxia) in the area
-endothelial cells from the surrounding blood vessels are stimulated by the hypoxia and grow due to growth factors (endothelial derived growth factor)
-new tissue made of fibroblast, proteoglycans,collagen type 2 and blood vessels is called GRANULATION TISSSUE
By the end of proliferation what has occurred?
-epithelial cells have recovered the site
-blood vessels have invaded and become organised
-fibroblasts have filled the wound with mostly type 3 and ground substance
-macrophages remain
Explain the role of Macrophages at the end of inflammation
Macrophages are pivotal in wound progression- they can release proinflammatory cytokines (chronic inflammation) or anti inflammatory cytokines and growth factors that progress the wound through REPAIR or RESOLUTION
After 12-24 hours the cellular phase of inflammation begins. Identify cells involved and describe their role in inflammation
NEUTROPHILLS- play major role in early phase (within 12 hours) bacterial clean up, plus further cytokine signalling
MACROPHAGES- play a later role (24 hrs) continue to clear bacteria plus cell debris/ damaged tisssue and dead neutrophils. Play major role in further cytokine signalling and controlling wound progression
Explain how these cells travel from blood to site of injury
Phagocytes move into tissue by MARGINATION- neutrophils and monocytes (immature macrophages) start to drop out of normal blood gathering towards the sides, ROLLING NEAUTROPHILS and MONOCYTES start to roll along the sides of the blood vessel wall, ADHESION,
- the endothelial cells in response to histamine make ‘Selectins’ which are hooks that attach to the neutrophils and monocytes and they attach DIAPEDDESIS
-neutrophils and monocytes squeeze through enlarged gaps ‘leaky’ and use CHEMOTAXIS, moving to the area of injury
List 2 phases of acute inflammation
Vascular
Cellular
State functions of vascular and cellular in acute inflammation
VASCULAR - to prevent further injury, dilute bacteria and their toxins, isolate the area to contain bacteria and preventing them from infecting other areas.
CELLULAR- remove bacteria, clean up tissue/ cellular damage and prepare for wound repair
What is the timescale of vascular and cellular
Vascular- seconds and lasts around 3-5 days
Cellular - neutrophils arrive within 24 hours (often by 12 hours) and lasts around 3-5 days
Describe what happens to epithelialcells in early proliferation
Loss of contact stimulates epithelial cells to replicate and this further stimulated by growth factors such as epidermal growth factor released by macrophages. The epithelial cells replicate and leapfrog over reach other, repeating the process until they meet in the middle. Contact inhibits any further replication and a basement membrane is formed
Describe the role of fibroblasts in early proliferation
Fibroblasts migrate into the wound from surrounding tissue and behind to replicate, stimulated by growth factors released by the M2 macrophage. They make ground substance (proteoglycans) and collagen type 3. This collagen is much weaker and less organised than normal type 1 and is easily broken
What is the name given for new blood vessel growth
Angiogenesis
Explain how blood vessels grow into the wound during early proliferation
Fibroblasts and epithelial tissue quickly use up local oxygen levels and if the blood supply has been lost in the injury then the area becomes hypoxia. M2 macrophages release growth factions (endothelial derived growth factor) that stimulate endothelial cells of blood vessels to replicate. They grow towards hypoxia areas
Granulation tissue is present at the end of late proliferation. List the compomermnys of granulation tissu and describe their organisation
Fibroblasts
Ground substance
Collagen type 3
Macrophages
New blood vessels
New epithelial tissue
Describe a myofibroblast and explain its function in early remodelling
Physical stress on new tissue stimulates the fibroblast to express/ make actin (smooth m,uncle actin). Myofibroblasts attatched to the collagen bundles and then contract to pull them inwards. This has the effect of reducing the size of the wound
Explain how the wound is mainly made up of collagen type 2, ground stance and a few fibroblasts by the end of remodelling
Fibroblasts and macrophages undergo apoptosis (cell death) and the new blood vessels are broken down. The remaining fibroblasts remodel the collagen under external stress which it is aligned to. The type 3 collagen is converted to type 1 collagen which is much stronger
