Integumentary Injury and Repair

rapid, coordinated response to injury/infection/disease to...
1. maintain/restore homeostasis
2. fairly non-specific
3. multiple systems (ex- immune, clotting)

normal, necessary step in promoting recovery
1. typically successful in isolating and destroying injurious factors and debris
2. consequences of this must often be addressed

1. vascular response
-- see cardinal signs
--goal to stop bleeding (vessel changes; platelet and coagulation cascade)
-- prepare for recovery (vessel changes; fluid dynamics)

2. cellular response
-- clear debris
-- fight invaders as needed
-- chief characteristic: mvt of WBC's to injury (margination and emigration; chemotaxis (cytokines, cellular debris, complement)

1. see initial vasoconstriction, then vasodilation
2. increased capillary permeability
3. hemostasis/coagulation:
-- platelet activation
-- cascade to form fibrin (clot to stop bleeding; form scaffold for later collagen deposition; pathway for monocytes and fibroblasts)
-- activated platelets release various cytokines and growth factors (PDGF, TGFB)

1. neutrophils (PMN's)
2. Monocytes/Macrophages
3. Clean Debris (phagocytes and MMP's-- breaking down collagen)
4. kill bacteria
5. O2- more necessary for anti-bacterial actions
6. Chemotaxis (pro-inflammatory cytokines, cell debris, hypoxia/lactate)
7. Galvanotaxis (current of injury)- skin surface normally negative vs. inside; allows current flow with injury (impeded in dry wounds)

1. wound "short circuits" system, allowing current to flow into wound (weak current to system)
2. currents are highest at wound edges
3. initial reversal of polarity, gradual return to baseline voltage (restarting system for healing)
-- regenerating species show much greater and more rapid reversal of injury polarity

1. overlaps with inflammatory phase (may start within as little as 48 hrs)
2. rapid cell division and growth (in a healthy system)

1. angiogenesis (new blood vessels, carrying O2 and nutrients)
2. granulation (production of granulation (intermediate) tissue
3. contraction
4. re-epithelialization (new superficial skin layer)

1. requires endothelial cells
2. local tissue and WBC growth factors
-- initial hypoxia (stimulating O2, etc. flow to area)
-- inflammatory cytokines, growth factors, etc.
-- stimulates capillary "buds" (see red dots in tissue)
-- these factors are not good to have after initial response
3. leads to new capillary beds (providing nutrients and cells, removes waste, relieves edema)

1. highly vascular connective tissue
2. composition: macrophages, fibroblasts, new vessels, immature collagen and ECM
3. provides framework for cellular migration
4. also see chemotaxis from cytokines, etc.

1. fills wound defect
2. temporary
3. high in fibronectin and hyaluronic acid
4. will be replaced by scar tissue or replacement tissue

1. main component for contraction to occur
2. derived from fibroblasts
3. TGFB stimulates production of CTGF which makes myofibroblasts
4. have contractile apparatus similar to smooth muscle
5. produce large amounts of collagen and other ECM proteins
6. normally transient

1. main players are myofibroblasts
2. shape of wound affects rate of closure (larger and/or rounder wounds are more difficult to close)-- may need to temp. splint for closure
3. limited by dermal compliance (no proliferation; thin dermis will be remodeled to normal thickness)
4. chronic wounds are prone to recurrance

1. occurs at margins of wound, across granulation tissue
2. highly metabolic process (requiring O2)
3. full epithelial coverage completes proliferation
4. will start occurring before wound is filled
5. insulin may have a role in progression (making it not function properly--reduced proliferation and differentiation of of keratinocytes

1. assoc. with closing of wounds (clearly goals often relate to wound size)
2. different tissue types can be used for appropriate goals

ex.- wound will contain at least __% of granulation tissue

1. remodeling and strengthening of connective tissue
2. collagen synthesis still high after contraction (type III eventually becomes type I)
3. alignment and reorientation (induction vs. tension theory)
4. phase may take years

lysis=anaerobic
synthesis=aerobic

which is why for tissue synthesis you wat to make sure there is sufficient blood, O2, etc. to wound

1. Hypertrophic
2. Keloid
3. Contracture
4. Dehiscence
5. also see pain from mvt., pressing onto other tissues, etc.

1. excessive collagen synthesis
2. remain in convfines of wound margins

1. excessive collagen synthesis
2. progress outside initial wound margins
3. ethnic (pigmentation) and genetic (hereditary) predisposition

1. shortening of scar tissue resulting in deformity or loss of ROM
2. often assoc. with hypertrophic scars and keloids

1. separation of wound margins

1. platelets
2. macrophages
3. keratinocytes
4. fibroblasts
5. endothelial cells

1. PDGF- chemotactic for neutrophils
2. TGFB- directs collagen matrix expression in late phase of wound repair

1. PDGF- chemotactic for neutrophils
2. TNF-alpha- induces MMP transcription; Proinflammatory; stim. nitric oxide synthesis
3. IL-1- proinflammatory; stimulates NO synthesis; amplifies inflammatory response through increased synthesis of IL-1 and IL-6
4. IL-6- proinflammatory
5. G-CSF- proinflammatory
6. GM-CSF- necrotic ECM degradation

1. IL-6- stimulate keratinocytes; induce keratinocyte proliferation
2. VEGF- potent stimulus for angiogenesis

1. KGF-2- enable cellular migration the ECM; directs epithelialization
2. IL-1- proinflammatory; amplifies inflammatory response through increased IL-1 and IL-6 synthesis
3. TGFB- directs collagen matrix exession; upregulates tissue inhibitors of MMP's

1. VEGF- potent stimulus for angiogenesis; upregulated in presence of NO

1. hemostasis
2. inflammation response
3. degradation
4. proliferation/epithelialization
5. remodeling- scar formation

autologous PRP- person's own plasma taken and injected into site of wound to promote quicker tissue healing

This most likely won't have a great effect on chronic wounds because the person may already have trouble generating the needed blood factors (PDGF, EGF, VEGF, TGFB) to increase healing

manufactured factors may be more successful

non-replicating microbes

1. replicating microbes without host response
2. only in dead skin, slough, etc.

1. replicating microbes invade viable tissue
2. general rule- 10^5/g of tissue (varies with virulence, host)

1. maintains inflammatory phase (signs of inflammation, prominent necrotic tissue, usually some drainage with variable appearance)
2. increased metabolic demand
3. tissue necrosis (microbes produce endotoxins, etc.)
4. risk of abcess

1. number of microbes (bioburden)
2. Virulance (how toxic, # of microbes or amt of toxin that is lethal)
3. host resistance (ex- HIV- harder to fight off infection)

1. universal precautions
2. standard precautions
3. hand washing
4. follow directions
5. sterile technique (set up and maintain sterile field, keep dry)
6. clean technique (no sterile field or gloves; includes WP, US, stim electrodes)

1. packing wound (deep/tunneling wounds)
2. large wounds
3. Burns
4. immunosuppression

1. pts are taking immunosuppressents to void transplant rejection
2. pts also underwent surgery
3. going to have impaired inflammatory response (not showing cardinal signs; may have fever, etc. instead)

1. signs and symptoms of inflammation out of proportion to expectations
---ex. extensive, poorly-defined periwound erythema (possibly streaking); extensive elevation of temperature
2. not sufficient for diagnosis of infection (but sufficient for suspicion)
3. infection associated with increased amount, viscosity, and purulence of drainage
4. increased foul odors (after cleansing)

1. swabbing
2. fluid aspiration (usually for abcess; pretty risky)
3. tissue biopsy (golden standard)
4. microbiology lab (gram stain, etc.)

1. bone or bone marrow infection
2. staph aureus (esp MRSA) most common mechanism

1. often tricky, infection can be occult
2. poor healing causes suspicion
3. bone sx/aspiration
4. imaging
5. if you can see or touch bone, assume osteomyelitis, unless proven otherwise

1. need different tests than bacteria (Gomori-Wheatley, Acridine Orange)
2. may worsen with antibiotic therapy or anti-inflammatories (ex-ringworm)
-- d/t decreased bacteria competition
-- steroid as an anti-inflammatory inhibiting immune response

1. antibiotics (topical, systemic- oral, intravenous)
2. antiseptics (rubbing alcohol, iodine, etc.)
3. debridement
4. possibly modalities (polarities, types of stim.)

1. more specific the better (aerobes vs. anaerobes)
2. avoid broad-spectrum drugs
3. presence of resistant strains of fungi (MRSA, VRE)
-- more common, but not more resistant
4. lots of topical agents (silver common addititive)-- better to use over intravenous if lack of blood flow to wound

1. broadly anti-microbial
2. ex- bleach, Acetic Acid, H2O2, povidone-iodine (Betadine)
3. also generally cytotoxic (more harm than good- kills microbes along with healthy, healing tissue and immune cells)
4. more useful in short-term applications

1. necrotic tissue is a breeding ground for microbes
2. lowers wound oxygenation
3. occupies host cells that try to clean up necrotic tissue
4. blocks granulation and epithelialization

1. bacteriocidal/bacterostatic modalities
2. UV light (sterilizing)
3. electrical stim.

1. cathodal pulsed, Hi-volt or DC
2. contraindicated with osteomyelitis-- won't heal infection, promotes closure over site

1. relatively hydrophilic (free-floating)
2. minimal glycocalyx (coatings--shield)
3. susceptible to antibacterial agent such as antibiotics
4. most knowledge of antibiotic activity based on planktonic bacteria
5. sadly most bacteria doen't live this way (live in biofilms)

1. interacting communities of microorganisms bound to solid surface (occur at a given pop. density--quorum)
2. coatings (glycocalyx) can make them less vulnerable (enhance drug resistance; may even turn body's own defenses against it---ex-fibrin)
3. may work synergistically to optimize replication (anaerobes working with aerobes; both have different resistances of different organisms)

Dental plaque: mainly streptococci

1. debridement- frequent and aggressive
2. selective biocides (silver, Iodosorb, Hydrofera Blue)
3. antibiofilm agents (lactoferrin,Xylitol, etc.)
4. antibiotics