Wound Healing Terms

infectious agents

bacteria, fungi, viruses

immune reactions

allergies, autoimmune disorders

genetic factors

mutations such as down syndrome

ischemia

lack of blood supply that can result in hypoxia or anoxia

nutritional factors

imbalance of essential nutrients

physical factors

trauma; brain contusions

chemical factors

toxic substances (ex: heavy metals)

pathologies start with ______ to the cells

injuries

reversible cell injury

cell adapts and maintains homeostasis again

irreversible cell injury

leads to cell death (2 mechanisms for cell death, necrosis and apoptosis)

acute injury

cell is able to regain homeostasis and adapt post injury, temporary effects are cellular swelling and changes in ion concentration, normal cell structure and function return after removal of stressor

reversible cell injury (chronic)

stress to cell is maintained by cells can adapt to altered environment

apoptosis

programmed cell death

necrosis

active process of degradation of dead cells

primary wound healing

healing by “first intention” (like sutures, staples, etc.), minimal scarring, usually complete return to function

secondary wound healing

larger tissue loss, healing occurs from bottom of wound and up, larger scar

which side is primary healing and which is secondary

left is primary, right is secondary

4 phases of wound healing

hemostasis, inflammation, proliferation and migration, remodeling and maturation

steps of hemostasis

1. vascular spasm

2. platelet plug formation

3. coagulation

4. clot retraction and repair

5. fibrinolysis

vascular spasm (first step of hemostasis)

smooth muscle contracts causing vasoconstriction to reduce blood loss

platelet plug formation (second step of hemostasis)

platelets bind to collagen fibers, von willebrand factor acts like glue so that platelets actually stick, platelets release ADP and seratonin which calls more platelets over to come stick, platelets aggregate to form plug

coagulation (step 3 of hemostasis)

we form prothromin activator, prothrombin activator converts prothrombin into thrombin, thrombin converts fibrinogen into fibrin, fibrin makes a mesh by cross linking, this forms a clot

clot retraction and repair (step 4 of hemostasis)

platelet contraction pulls endothelial cells together to stabilize the clot, platelets secrete both platelet derived and vascular endothelial growth factors… these (1) repair collagen and connective tissue, and (2) regulates endothelial lining

fibrinolysis (step 5 of hemostasis)

plasminogen converts to plasmin, plasmin breaks fibrin mesh, clot is broken to prevent blood vessel occlusion

4 characteristics of inflammation

erythema (redness), heat, edema, pain

inflammation ends when _______

injurious agent is removed

acute inflammation

short and sudden onset of heat, erythema, edema, and pain

chronic inflammation

persists overtime/does resolve, lymphocytes and macrophages are present, increase in blood vessels, causes tissue restruction

2 pathways an injurious agent can be removed during inflammation

phagocytosis or complement proteins

first step of inflammation:

mast or dendritic cells degranulate to increase blood flow and move WBC to damaged aeras by releasing histamine, kinins, and prostaglandins

histamines

increase vascular permeability, activate neutrophils and macrophages

kinins

increase vascular permeability and promote chemotaxis

prostaglandins

increase vascular permeability, vasodilation, promote chemotaxis, induce pain

what do hisamines, kinins, and prostaglandins all have in common

they increase vascular permeability which causes smooth muscle relaxation which allows that increased blood flow in the first step of inflammation

increased blood flow in the first step of inflammation causes what symptoms

redness and heat

in inflammation after the histamines, kinins and prostaglandins cause smooth muscle relaxation, what do the endothelial cells do?

endothelial cells contract to create space and the p-selectins are activated

after smooth muscle relaxaion and p-selectin activation more WBCs are entering the damaged area, next we see what 3 things?

1. margination

2. diapedesis

3. chemotaxis

1. margination

slowing of WBCs in the blood vessel

2. diapedesis

WBCs squeeze through endothelial cell gaps

3. chemotaxis

WBCs move towards chemical (follow chemical gradient) where foreign invader is

in diapedesis WBCs are squeezing through the gaps created by the endothelial cells contracting to create space… what else happens at this step to cause what other symptoms of inflammation?

plasma can also squeeze through these gaps, this causes edema from the excess water and pain from this excess plasma rubbing up against nociceptors

step 1 of phagocytosis

WBCs from pseudopods are used to pull in bacteria

in phagocytosis what happens after the WBCs are used to pull in bacteria (aka what’s step 2)

macrophage engulfs bacteria to form a phagosome

in phagocytosis what comes after he creation of a phagosome (aka what is step 3)

phagosome and lysosome fuse together inside cell to form a phagolysosome

in phagocytosis what comes after the formation of the phagolysosome (aka what is step 4)

the lysosome digests the bacteria leaving only the antigens

what happens after the lysosome digests the bacteria in phagocytosis (aka what is the last step)

the macrophage spits out the antigens through exocytosis into the ec fluid

what is the tumor necrosis factor (TNF)

this is secreted by macrophages and mast cells and induces proinflammatory effects

what are interferons

these are produced by virus infected cells and interfere with DNA and RNA replication

what are cytokines

signalling proteins that help control inflammation in your body (ex: interleukins, interferons, tumor necrosis factor)

what is an interleukin

a specific cytonine that has a certain job in chemical messeging (ex: IL-4 and IL-5 have very important jobs in humoral immunity for stimulating proliferation and differentiation)

overall goal of proliferation and migration

generate and repair blood vessels and connective tissue

in proliferation and migration, what is step 1

fibroblasts arrive at wound site by following macrophages via growth factors (fibroblast proliferation)

in proliferation and migration, after fibroblasts arrive at wound site, what do they do (aka what is step 2)

fibroblasts repair connective tissue damage and make new collagen, elastin, and proteglycan molecules

how do the fibroblasts go about repairing the connective tissue in step 2 of proliferation and migration (we know they make new collagen, but more detail then that)

they produce granulation tissue made up of type III collagen, elastin, and protoglycan which fills the wound with enw tissue and protects it from further microbial invation. the way it restores the ECM is thorugh connecting the 2 sides of the wound back to each other via wound conraction. this produces the inital scar and if there are granulation formation errors then the scare ends up being fucked a little

wound contraction

actual contraction with the pulling of the edges of the wound towards the center hence making the wound smaller

note: myofibroblast is used to help accomplish this as it has contractile proteins to pull on the new collagen

what comes after the formation of granulation tissue and wound contraction (aka what is step 3 of proliferation and migration)

angiogenesis: the formation of new blood vessels while also supplying oxygen and nurients to currently healing tissue in preparation for remodeling

what comes after angiogenesis in proliferation and migration (aka last step of this phase)

re-epithelialization

• basal cells are laid down at the wound

• the basal cells on the magin undergo mitosis horizontally while the ones behind the margin grow vertically

what is the final part of wound contraction

the covering skin of the wound is stretch/thinned while the dermal thickness surrounding it is maintained

what are the 3 basic steps of remodeling and maturation

1. tissue contraction

2. tissue regeneration

3. tissue repair

goal of remodeling and maturation

scar tissue being reduced and remodeled; tissue becomes smoother, stronger, less red, and less dense

what is the first step of remodeling and maturation

more tissue contraction: newly formed ECM contracts and shortens but we still want to avoud excessive shortening (aka contracture)

what happens after tissue contraction in remodeling and maturation (aka what’s step 2)

tissue regeneration: replacement of dead cells with new cells to restore normal tissue structure and function (but this only occurs is the cells in question can undergo mitosis)

what happens after tissue regeneration in proliferation and migration (aka what is step 3)

tissue repair: we remove and replace the original tissue with fibrous connecive tissue. this starts with type III collagen getting replaced by type II and then eventually type I which is the strongest

Note: we will see some scarring here but we are trying to minimize it so it doesn’t interfere with organ funcction,,, so after the wound closes collagen degratation and resynthesis continues

wounds usually heal in ____ (amount of time)

4-6 weeks

a wound that lasts for _______ (amount of time) is considered a chronic non-healing wound

1-3 months

list the local factors that affect tissue healing

oxygenation and infection

why is oxygenation important for wound healing

it’s needed for cell metabolism since ATP is used in the healing process, also early wounds are hypoxic meaning they use up a lot of oxygen in the healing process from poliferation, migration, and re=epithelialization so if oxygen is not restored, healing becomes impaired

list the systemic factors that can affect wound healing

age and sex, obesity, medications, alcohol, smoking, nutiron, stress

obestiy can cause impaired wound healing because…

1. we have reduced blood flow to adipose tissue

2. skin fold harbor micro-organisms

3. skin-on-skin friction increases risk of ulceration

how can glucocorticoid steriods supress wound healing

they suppress proliferation phase, collagen synthesis, and increase risk of infection

how can chemotherapy impair wound healing

it’s designed to inhibit rapid cell divison and angiogenssis, it inhibits wound healing pathways, and weakens general immune function

why do smokers have delayed healing

micotine stimulates sympathetic nervous system which causes weaker vasoconctrucition and reduces oxygen supply to tissues; carbon monoxide in cigarrette smoke causes tissue hypoxia; hydrogen cyanide impairs cellular oxygen metabolism; and it impairs WBC migration