Medicine, Surgery, and Anesthesia Flashcards
Define Regeneration.
When restitution occurs through tissue that is structurally and functionally indistinguishable from native tissue
Define Repair.
if tissue integrity is reestablished primarily through the formation of scar tissue
What 2 organs are more likely to regenerate than repair?
Bone and liver.
Define labile cells.
Divide throughout their life span
Examples of labile cells
keratinocytes of the epidermis and epithelial cells of the oral mucosa
Define stable cells
Low rate of duplication but can undergo rapid proliferation in response to injury
Examples of stable cells
Fibroblasts and pluripotent mesenchymal cells that differentiate into osteoblasts and osteoclasts
Define permanent cells
Specialized nerve cells that do not divide in postnatal life
What is a fibrous scar normal for
Skin wounds, but abnormal for bone since bone is stable and skin is labile
Healing by first intention
Closed primarily with no dehiscence, minimal scar formation
Healing by second intention
Complicated wound healing resulting in protracted filling of defect with granulation and connective tissue.
Healing by secondary intention is common with which injuries
Avulsion, local infection, inadequate closure of wound
Healing by third intention
Staged procedure that allows secondary healing with delayed primary closure. Wound debrided and allowed to granulate and heal by secondary intention for 5-7 days then wound is sutured by first intention.
Inflammatory phase of healing.
Presages reparative response and lasts 3-5 days
Steps of inflammatory phase BEFORE hemoatasis
- Vasoconstriction of injured vasculature to stop healing
- Tissue trauma activated Hageman factor to initiate complement, plasminogen, kinin, and clotting
- Thrombocytes aggregate by injury site and exposed endothelium to form primaruy platelet plug within fibrin matrix
- Clot has cytokines and GF that activate platelete degrandulation
- Plateletes release IL, TGF B, PDGF, and VEGF
Steps of Inflammatory phase AFTER hemostasis
- Vasodilation mediated by histamine, prostaglandins, kinins, leukotrines to allow plasma, leukocytes, to pass through (diapedesis) to populate extravascular space
- Clinical manifestation of swelling, redness, heat, and pain
- Cytokines recruit neutrophils that are predominant
- Neutrophilas migrate through clotand release proteases and cytokines to cleanse wound debris. Activated by opsonic Ab leaking from wound.
- Neutrophils release IL-1a and IL-1b to lengthen inflammatory response and go away in 24-72 hours
- Monocytes come in and secrete collagenases and elastase to break down injured debris
- Monocytes GF and cytokines to allow early wound healing and tissue remodeling by proteolytic enzymes
What factors help with angiogenesis and fibroplasia
Thrombospondin-1 and IL-1b
Define proliferative phase
Day 3-Week 3. Forms granulation tissue with inflammatory cells, fibroblasts, and vasculature in loose matrix with local microcirculation for oxygen for regenerating tissues
What causes angiogenesis
Wound hypoxia, VEGF, FGF-2, TG-B
What causes scaffolding of collagen in granulation tissue
Fibroblasts make ECM, and Type III immature collagen
Reepithelization in mucosa vs skin
The process of reepithelializa- tion progresses more rapidly in oral mucosal wounds in contrast to skin. In a mucosal wound, the epithelial cells migrate directly onto the moist exposed surface of the fibrin clot instead of under the dry exudate (scab) of the dermis.
How does reepitheliazation stop and finish
Reepithelialization is facilitated by underlying contractile connective tissue, which shrinks in size to draw the wound margins toward one another. Wound contraction is driven by a subset of the fibroblasts that transform into myofibroblasts and generate strong contractile forces. The extent of wound contraction depends on the depth of the wound and its location. In some extraoral instances, the forces of wound contracture are capable of deforming osseous structures.
How does tensile strength of scar tissue change
The fibroblasts start to disappear and the collagen Type III deposited during the granulation phase is gradually replaced by stronger Type I collagen. Correspondingly, the tensile strength of the scar tissue gradually increases and eventually approaches about 80% of the original strength.
Neuropraxia
mildest form of nerve injury and is a tran- sient interruption of nerve conduction without loss of axonal continuity. The continuity of the epineural sheath and the axons is maintained and morphologic alterations are minor. Recovery of the functional deficit is spontaneous and usually complete within 3–4 weeks.
Axonotmesis
If there is a physical disruption of one or more axons without injury to stromal tissue, the injury is described as axonotmesis. Here, the individual axons are severed but the investing Schwann cells and connective tissue elements remain intact. The nature and extent of the ensuing sensory or motor deficit relates to the number and type of injured axons. Morphologic changes are manifest as degeneration of the axoplasm and associ- ated structures distal to the site of injury and partly proximal to the injury. Recovery of the functional deficit depends on the degree of the damage.
Neurotmesis
Complete transection of the nerve trunk is referred to as neurotmesis and spontaneous recovery from this type of injury is rare. Histologically, changes of degen- eration are evident in all axons adjacent to the site of injury [11]. Shortly after nerve severance, the investing Schwann cells begin to undergo a series of cellular changes called Wallerian degeneration.
Wallerian degeneration
The degenera- tion is evident in all axons of the distal nerve segment and in a few nodes of the proximal segment. Within 78 h, injured axons start breaking up and are phagocy- tosed by adjacent Schwann cells and by macrophages that migrate to zone of injury. Bungers band will attempt regeneration.
Bungers band
Once the axonal debris has been cleared, Schwann cell outgrowths attempt to connect the proximal stump with the distal nerve stump. Surviving Schwann cells proliferate to form a band (Büngner’s band) that will accept regener- ating axonal sprouts from the proximal stump. The pro- liferating Schwann cells also promote nerve regeneration by secreting numerous neurotrophic factors that coordi- nate cellular repair as well as cell adhesion molecules that direct axonal growth.
Neuroma
In the absence of surgical realignment or approximation of the nerve stumps, pro- liferating Schwann cells and outgrowing axonal sprouts may align within the randomly organized fibrin clot to form a disorganized mass termed neuroma.
Rate of regeneration of peripheral nerves
it is generally considered to approximate 1 mm/day. The regeneration phase lasts up to 3 months and ends on contact with the end-organ by a thin myelinated axon. In the concluding maturation phase, both the diameter and performance of the regenerating nerve fiber increase.
Indirect healing
Left alone, fractured bone is capable of restoring itself spontaneously through sequential tissue formation and differentiation
Steps if indirect healing
Necrotic material at the fracture site provokes an immediate and intense acute inflammatory response which attracts the polymorphonuclear leukocytes and subsequently, mac- rophages to the fracture site. The organizing hematoma serves as a fibrin scaffold over which reparative cells can migrate and perform their function. Invading inflamma- tory cells and the succeeding pluripotent mesenchymal cells begin to rapidly produce a soft fracture callus that fills up interfragmentary gaps. Comprised of fibrous tis- sue, cartilage, and young immature fiber bone, the soft and compliant callus acts as a biologic splint by binding the severed bone segments and damping interfragmen- tary motion. An orderly progression of tissue differen- tiation and maturation eventually leads to fracture consolidation and restoration of bone continuity.
Direct healing
An abbreviated callus-free bone healing
Steps of direct healing
The displaced bone segments are surgi- cally manipulated into an acceptable alignment and rigidly stabilized through the use of internal fixation devices. The resulting anatomic reduction is usually a combination of small interfragmentary gaps separated by contact areas. Ingrowth of mesenchymal cells and blood vessels starts shortly thereafter, and activated osteoblasts start depositing osteoid on the surface of the fragment ends. In contact zones where the fracture ends are closely apposed, the fracture line is filled concentri- cally by lamellar bone. Larger gaps are filled through a succession of fibrous tissue, fibrocartilage, and woven bone. In the absence of any microinstability at the frac- ture site, direct healing takes place without any callus formation.
Basic multicellular unit (BMU)
Functional sculpting and remodeling of the prim- itive bone tissue is carried out by a temporary team of juxtaposed osteoclasts and osteoblasts
Where do osteoblasts develop from
pluripotent mesenchymal stem cells
Where do osteoclasts develop from
monocyte/macrophage lin- eage
When do osteoids begin to mineralize
6 μm thick
How long is remodelling phase
Osteoclasts reaching the end of their lifespan of 2 weeks die and are removed by phagocytes. The majority (up to 65%) of the remodeling osteoblasts also die within 3 months and the remainder are entombed inside the mineralized matrix as osteocytes.
How does functional loading affect remodelling
The “grain” of the new bone tissue starts paralleling local compression and ten- sion strains. Consequently, the shape and strength of the reparative bone tissue changes to accommodate greater functional loading. Tissue-level strains produced by functional loading play an important role in the remod- eling of the regenerate bone.
Low vs high tissue strain
Whereas low levels of tis- sue strain (~2000 microstrains) are considered physiologic and necessary for cell differentiation and callus remodeling, high strain levels (>2000 microstrains) begin to adversely affect osteoblastic differentiation and bone matrix formation
What if there is excess interfragmentary motion for an instable fracture
bone regenerates primarily through endochondral ossification or the formation of a carti- laginous callus that is gradually replaced by new bone.
How does bone heal across a stabilized fracture
occurs primarily through intramembranous ossification
What factors determine mechanical milieu of a healing fracture
- fracture configuration
- the exactness of fracture reduction
- the stability afforded by the selected bone stabilization approach
- the degree and nature of microstrains provoked by function
What if fracture fixation is incapable of stabilizing the fracture
the interfragmentary microinstabil- ity provokes osteoclastic resorption of the fracture surfaces and results in a widening of the fracture gap. Although bone union may be ultimately achieved through secondary healing by callus production and endochondral ossification, the healing is protracted.
Manifestations of excessive microstrains
Fibrous healing and nonunions
Describe healing of dental implant
Following the seating of an endosseous implant, a blood clot forms in the interstices between the implant grooves and the osseous bed. The clot is rap- idly infiltrated by granulocytes and macrophages. Eventually, fibroblastic progenitor cells migrate into the provisional matrix, allowing formation of succedent granulation tissue. The granulation tissue is vascularized by endothelial cell migration and the cells in the granu- lation tissue begin to differentiate into osteoblasts and create bone [15]. The bone formation starts within a few days after dental implant placement and most of the bone–implant contact is achieved by 3 months.
How do occlusal forces effect dental implant
Depending on the mechanical stress caused by occlusal forces, notable bone remodeling around the dental implant can persist for at least 1 year. Mechanical load- ing by occlusal forces can stimulate peri-implant bone but excessive micromotion can compromise osseointe- gration and lead to implant failure
By what intention do extraction wounds heal by
Secondary intention
Steps of healing of extraction wounds
Organization of the clot begins within the first 24–48 h, with engorgement and dilation of blood vessels within the periodontal ligament rem- nants, followed by leukocytic migration and formation of a fibrin layer. In the first week, the clot forms a tem- porary scaffold upon which inflammatory cells migrate. Epithelium at the wound periphery grows over the sur- face of the organizing clot. Osteoclasts accumulate along the alveolar bone crest and set the stage for active crestal resorption. Angiogenesis proceeds in the rem- nants of the periodontal ligaments. In the second week, the clot continues to get organized through fibroplasia and new blood vessels begin to penetrate toward the center of the clot. Trabeculae of osteoid slowly extend into the clot from the alveolus, and osteoclastic resorp- tion of the cortical margin of the alveolar socket is more distinct. By the third week, the extraction socket is filled with granulation tissue and poorly calcified bone forms at the wound perimeter. The surface of the wound is completely reepithelialized with minimal or no scar formation.
How long is bone remodeling after extraction
Active bone remodeling by deposition and resorp- tion continues for several more weeks. Reorganization and maturation of the alveolar site may continue up to 1 year after the extraction, but most of the dimensional changes evident clinically take place in the first 3 months [18]. The rate of bone makeover is extremely variable between individuals with complete remodeling of the precursor woven bone into lamellar bone and bone mar- row taking from several months to years
Etiology of local alveolar osteitis
Occasionally, the blood clot fails to form or may dis- integrate, causing a localized alveolar osteitis. When this happens, the healing is delayed considerably and the socket fills gradually. In the absence of a healthy granu- lation tissue matrix, the apposition of regenerate bone to the remaining alveolar bone takes place at a much slower rate. Compared to a normal socket, the infected socket remains open or partially covered with hyper- plastic epithelium for extended periods.
Full thickness skin graft
A full-thickness graft is composed of epidermis and the entire dermis
Split thickness skin graft
split-thickness graft is com- posed of the epidermis and varying amounts of dermis. Depending on the amount of underlying dermis included, split-thickness grafts are described as thin, intermediate, or thick
Nutritional support of free skin graft
Following grafting, nutri- tional support for a free skin graft is initially provided by plasma that exudes from the dilated capillaries of the host bed.
How is graft fixed to host-bed?
A fibrin clot forms at the graft–host interface, fixing the graft to the host bed. Host leukocytes infiltrate into the graft through the lower layers of the graft.
What does graft survival depend on
Graft survival depends on the ingrowth of blood vessels from the host into the graft (neovascularization) and direct anastomoses between the graft and the host vasculature (inosculation). Endothelial capillary buds from the host site invade the graft, reaching the dermoepidermal junc- tion by 48 h. Concomitantly, vascular connections are established between host and graft vessels. However, only a few of the ingrowing capillaries succeed in devel- oping a functional anastomosis.
How do we know that a graft took vascularly?
The formation of vas- cular connections between the recipient bed and transplant is signaled by the pink appearance of the graft, which appears between the third and fifth day postgrafting. Fibroblasts from the recipient bed begin to invade the layer of fibrin and leukocytes by the fourth day after transplantation. The fibrin clot is slowly resorbed and organized as fibroblastic infiltration con- tinues. By the ninth day, the new blood vessels and fibro- blasts have achieved a firm union, anchoring the deep layers of the graft to the host bed.
Re-innervation of the skin graft occurs by nerve fibers entering the graft through its base and sides. The fibers follow the vacated neurilemmal cell sheaths to reconstruct the innervation pattern of the donor skin. Recovery of sensation usually begins within 2 months after transplantation. Grafts rarely attain the sensory qualities of normal skin, because the extent of re- innervation depends on how accessible the neurilemmal sheaths are to the entering nerve fibers. The clinical per- formance of the grafts depends on their relative thick- ness. As split-thickness grafts are thinner than full-thickness grafts, they are more susceptible to trauma and undergo considerable contraction; however, they have greater survival rates clinically. Full-thickness skin grafts do not “take” as well and are slow to revascular- ize. However, full-thickness grafts are less susceptible to trauma and undergo minimal shrinkage.
1.5 Wound Healing Complications
Healing in the orofacial region is often considered a natural and uneventful process and seldom intrudes into the surgeon’s consciousness. However, this changes when complications arise and hamper the wound heal- ing continuum. Most wound healing complications are evident in the early postsurgical period but some may manifest much later. The two problems most commonly encountered in the orofacial region are wound infection and dehiscence; proliferative healing is less typical.
1.5.1 Wound Infection
Infections complicating surgical outcomes usually result from gross bacterial contamination of susceptible wounds. All wounds are intrinsically contaminated by bacteria; however, this must be distinguished from true wound infection where the bacterial burden of replicat- ing microorganisms actually impairs healing [22, 23]. Experimental studies have demonstrated that, regardless of the type of infecting microorganism, wound infection occurs when there are more than 1 × 105 organisms per gram of tissue [24]. Beyond relative numbers, the patho- genicity of the infecting microorganisms as well as host response factors also determines whether wound healing is impaired.
The continual presence of a bacterial infection stim- ulates the host immune defenses leading to the produc- tion of inflammatory mediators, such as prostaglandins and thromboxane. Neutrophils migrating into the wound release cytotoxic enzymes and free oxygen radi- cals. Thrombosis and vasoconstrictive metabolites cause
Reinnervation of skin graft
Re-innervation of the skin graft occurs by nerve fibers entering the graft through its base and sides. The fibers follow the vacated neurilemmal cell sheaths to reconstruct the innervation pattern of the donor skin. Recovery of sensation usually begins within 2 months after transplantation. Grafts rarely attain the sensory qualities of normal skin, because the extent of re- innervation depends on how accessible the neurilemmal sheaths are to the entering nerve fibers. The clinical per- formance of the grafts depends on their relative thick- ness.
Split thickness vs full thickness grafts
As split-thickness grafts are thinner than full-thickness grafts, they are more susceptible to trauma and undergo considerable contraction; however, they have greater survival rates clinically. Full-thickness skin grafts do not “take” as well and are slow to revascular- ize. However, full-thickness grafts are less susceptible to trauma and undergo minimal shrinkage.
When does wound infection happen.
the bacterial burden of replicat- ing microorganisms actually impairs healing [22, 23]. Experimental studies have demonstrated that, regardless of the type of infecting microorganism, wound infection occurs when there are more than 1 × 105 organisms per gram of tissue
How does wound infection happen
The continual presence of a bacterial infection stim- ulates the host immune defenses leading to the produc- tion of inflammatory mediators, such as prostaglandins and thromboxane. Neutrophils migrating into the wound release cytotoxic enzymes and free oxygen radi- cals. Thrombosis and vasoconstrictive metabolites cause wound hypoxia, leading to enhanced bacterial prolifera- tion and continued tissue damage. Bacteria destroyed by host defense mechanisms provoke varying degrees of inflammation by releasing neutrophil proteases and endotoxins. Newly formed cells and their collagen matrix are vulnerable to these breakdown products of wound infection, and the resulting cell and collagen lysis contribute to impaired healing.
Clinical manifestion of wound infection
Clinical manifestations of wound infection include the classic signs and symp- toms of local infection: erythema, warmth, swelling, pain, and accompanying odor and pus.
What reduces risk of wound infection
The most important factor in minimizing the risk of infection is meticulous surgical technique, including thorough debridement, adequate hemostasis, and elimination of any dead space. Careful technique must be augmented by proper postoperative care, with an emphasis on keeping the wound site clean and pro- tecting it from trauma.
When does wound dehiscece happen
Partial or total separation of the wound margins may manifest within the first week after surgery.
What causes wound dehisence
Most instances of wound dehiscence result from tissue failure rather than improper suturing techniques.
What to do if wound dehisced
The dehisced wound may be closed again or left to heal by secondary intention, depending upon the location, extent of the disruption, and the surgeon’s assessment of the clinical situation.
Two forms of hyper proliferative healing
Hypertrophic scars and keloids
What defines hyper proliferative healing
Excessive scarring, persistent inflammation, and overproduction of ECM (such as glycosaminoglycans and collagen Type I.
Hypertrophic scars
- Arise shortly after injury
- Cicumscribed within boundaries of wound
- Eventually receed
Keloids
- Manifefst months after injury
- Grow beyond wound edges
- Rarely subsides
Common places for keloids to form
Face, ear lobes, and anterior chest
Etiology of hyperproliferative scarring
Altered apoptotic behaivior. Ordinarily, apoptosis or programmed cell death is responsible for the removal of inflammatory cells as healing proceeds and for the maturation of granulation tissue into scar. Dysregulation in apoptosis results in excessive scarring, inflammation, and an overproduction of extracellu- lar matrix components. Both keloids and hypertrophic scars demonstrate sustained elevation of growth factors including TGF-β, platelet-derived growth factor, IL-1, and IGF-I [25]. The growth factors, in turn, increase the numbers of local fibroblasts and prompt exces- sive production of collagen and extracellular matrix. Additionally, proliferative scar tissue exhibits increased numbers of neoangiogenesis-promoting vasoactive mediators as well as histamine-secreting mast cells capa- ble of stimulating fibrous tissue growth.
How to reat hyperproliferative scarring
Although there is no effective therapy for keloids, the more common methods for preventing or treating these lesions focus on inhibiting protein synthesis. These agents, primar- ily corticosteroids, are injected into the scar to decrease fibroblast proliferation, decrease angiogenesis, and inhibit collagen synthesis and extracellular matrix pro- tein synthesis.
Planning surgical incisiom
Properly planned, the surgical incision is just long enough to allow optimum exposure and adequate operating space. The incision should be made with one clean consistent stroke of evenly applied pressure.
Dissection to minimize trauma
Sharp tissue dissection and carefully placed retractors further minimize tissue injury.
Sutures to minimize tissue trauma
Sutures are useful for holding the severed tissues in apposition until the wound has healed enough. However, sutures should be used judiciously as they can add to the risk of infection and are capable of strangulating the tis- sues if applied too tightly.
Risks of hematoma under wound
The collection of blood or serum at the wound site provides an ideal medium for the growth of microorganisms that cause infection. Additionally, hematomas can result in necrosis of over- lying flaps.
How to eliminate deadspace in wound
Postoperatively, the surgeon may insert a drain or apply a pressure dress- ing to help eliminate dead space in the wound.
Necrotic burden of a hematoma
Devitalized tissue and foreign bodies in a healing wound act as a haven for bacteria and shield them from the body’s defenses. The dead cells and cellular debris of necrotic tissue have been shown to reduce host immune defenses and encourage active infection. A necrotic bur- den allowed to persist in the wound can prolong the inflammatory response, mechanically obstruct the pro- cess of wound healing, and impede reepithelialization.
Debridement of wound importance
Dirt and tar located in traumatic wounds not only jeop- ardize healing but may result in a “tattoo” deformity. By removing dead and devitalized tissue, and any foreign material from a wound, debridement helps reduce the number of microbes, toxins, and other substances that inhibit healing.
How does oxygen help tissue perfusion
Oxygen is necessary for hydroxylation of proline and lysine, the polymerization and cross- linking of procollagen strands, collagen transport, fibro- blast and endothelial cell replication, effective leukocyte killing, angiogenesis.
Relative hypoxia in region of injury
Relative hypoxia in the region of injury is useful to the extent that it stimulates a fibro- blastic response and helps mobilize other cellular ele- ments of repair
How does low oxygen levels affect wounds
However, very low oxygen levels act together with the lactic acid produced by infecting bac- teria to lower tissue pH and contribute to tissue break- down. Cell lysis follows, with releases of proteases and glycosidases and subsequent digestion of extracellular matrix. Impaired local circulation also hinders the deliv- ery of nutrients, oxygen, and antibodies to the wound. Neutrophils are affected because they require a minimal level of oxygen tension to exert their bactericidal effect. Delayed movement of neutrophils, opsonins, and the other mediators of inflammation to the wound site fur- ther diminishes the effectiveness of the phagocytic defense system and allows colonizing bacteria to prolif- erate. Collagen synthesis is dependent on oxygen deliv- ery to the site, which in turn affects wound tensile strength. Most healing problems associated with diabe- tes mellitus, irradiation, small vessel atherosclerosis, chronic infection, and altered cardiopulmonary status can be attributed to local tissue ischemia.
Causes of tissue hypoxia in wounds
Tissue rendered ischemic by rough han- dling, or desiccated by cautery or prolonged air drying, tends to be poorly perfused and susceptible to infection. Similarly, tissue ischemia produced by tight or improp- erly placed sutures, poorly designed flaps, hypovolemia, anemia, and peripheral vascular disease all adversely affect wound healing. Smoking is a common contribu- tor to decreased tissue oxygenation
How does smoking effect tissue hypoxia
The peripheral vasoconstriction produced by smoking a cigarette can last up to an hour; thus, a pack-a-day smoker remains tissue hypoxic for the most of each day. Smoking also increases carboxyhemoglobin, increases platelet aggre- gation, increases blood viscosity, decreases collagen deposition, and decreases prostacyclin formation, all of which negatively affect wound healing.
How to optimize smokers for wound healing
Patient optimi- zation, in the case of smokers, may require that the patient abstain from smoking for a minimum of 1 week before and after surgical procedures. Another way of improving tissue oxygenation is the use of systemic hyperbaric oxygen (HBO) therapy to induce the growth of new blood vessels and facilitate increased flow of oxy- genated blood to the wound.
How diabetes effects wound healing
Studies have demonstrated that the higher incidence of wound infection associated with diabetes has less to do with the patient having diabetes and more to do with hyperglycemia [32]. Simply put, a patient with well-controlled diabetes may not be at a greater risk for wound healing problems than a nondiabetic patient.
How does tissue hyperglycemia effect wound healing
Tissue hyperglycemia impacts every aspect of wound healing by adversely affecting the immune system including neutrophil and lymphocyte function, chemo- taxis, and phagocytosis [33]. Uncontrolled blood glu- cose hinders red blood cell permeability and impairs blood flow through the critical small vessels at the wound surface. The hemoglobin release of oxygen is impaired, resulting in oxygen and nutrient deficiency in the healing wound.
How to assess immunocmopromise
An important assessment parameter is total lymphocyte count. A mild deficit is a lymphocytic level between 1200 and 1800, and levels below 800 are considered severe total lymphocyte deficits.
What can cause a debilitated immune system
Patients with debilitated immune response include human immu- nodeficiency virus (HIV)-infected patients in advanced disease stages, patients on immunosuppressive therapy, and those taking high-dose steroids for extended periods.
What CD4 count of HIV causes poor wound outcome
Studies indicate that HIV-infected patients with CD4 counts of less than 50 cells/mm3 are at significant risk of poor wound outcome
Effect of newer immunosuppresive drugs on wound healing
Although newer immuno- suppressive drugs, such as cyclosporine, have no appar- ent effect on wound healing, other medications can retard the healing process, both in rate and quality, by altering the inflammatory reaction and the cell metabolism.
Effect of prednisone on wound healing
The use of steroids, such as prednisone, is a typical example of how suppression of the innate inflammatory process also increases wound healing complications. Exogenous corticosteroids diminish prolyl hydroxylase and lysyl oxidase activity, depressing fibroplasias, colla- gen formation, and neovascularity. Fibroblasts reach the site in a delayed fashion and wound strength is decreased by as much as 30%. Epithelialization and wound con- traction are also impaired.
How to attenuate effects of glucocorticosteroids on wound healing
The inhibitory effects of glu- cocorticosteroids can be attenuated to some extent by vitamin A given concurrently.
How do antineoplastic agents effect cells
Most antineoplastic agents exert their cytotoxic effect by interfering with DNA or RNA production. The reduction in protein synthesis or cell division reveals itself as impaired proliferation of fibroblasts and colla- gen formation.
What is attendant neutropenia
Attendant neutropenia also predisposes to wound infection by prolonging the inflammatory phase of wound healing.
How soon do pathologic collateral of radiation happen
The pathologic processes of radiation injury start right away; however, the clinical and histologic features may not become apparent for weeks, months, or even years after treatment
Radiation effects which kinds of cells
Early acute changes are observed within a few weeks of treatment and primarily involve cells with a high turnover rate.
What mediates inflammatory reponse of radiation injury
The inflammatory response is largely mediated by cytokines activated by the radiation injury. Overall, the response has the features of wound healing; waves of cytokines are produced in an attempt to heal the radia- tion injury. The cytokines lead to an adaptive response in the surrounding tissue, cause cellular infiltration, and promote collagen deposition.
How does radiation effect vasculature
Damage to local vascula- ture is exacerbated by leukocyte adhesion to endothelial cells and the formation of thrombi that block the vascu- lar lumen, further depriving the cells that depend on the vessels.
Late effects of radiation
The late effects of radiation are permanent and directly related to higher doses. Collagen hyalinizes and the tis- sues become increasingly fibrotic and hypoxic due to obliterative vasculitis, and the tissue susceptibility to infection increases correspondingly. Once these changes occur, they are irreversible and do not change with time.
Common complications of surgery with irradiated tissue
Wound dehiscence is common and the wound heals slowly or incompletely. Even minor trauma may result in ulceration and coloni- zation by opportunistic bacteria. If the patient cannot mount an effective inflammatory response, progressive necrosis of the tissues may follow.
How to surgically intervene with an irradiated site
Healing can be achieved only by excising all nonvital tissue and cover- ing the bed with a well-vascularized graft. Due to the relative hypoxia at the irradiated site, tissue with intact blood supply needs to be brought in to provide both oxygen and cells necessary for inflammation and heal- ing.Theprogressiveobliterationofbloodvesselsmakes bone particularly vulnerable. Following trauma or disin- tegration of the soft tissue cover due to inflammatory reaction, healing does not occur because irradiated mar- row cannot form granulation tissue. In such instances, the avascular bone needs to be removed down to the healthy portion to allow healing to proceed.
Los tissue oxygen tension
Concept that low tissue oxygen tension, typically a partial pressure of oxygen (PO2) of 5–20 mm Hg, leads to anaerobic cellular metab- olism, increase in tissue lactate, and a decrease in pH, all of which inhibit wound healing
HBO regimen
BO therapy requires that the patient recline in a hyperbaric chamber and breath 100% oxygen at 2.0–2.4 atmospheres for 1–2 h. The HBO therapy is repeated daily for 3–10 weeks.
How does HBO work
HBO increases the quantity of dissolved oxygen and the driving pressure for oxygen diffusion into the tissue. Correspondingly, the oxygen diffusion distance is increased threefold to fourfold, and wound PO2 ulti- mately reaches 800–1100 mm Hg. The therapy stimu- lates the growth of fibroblasts and vascular endothelial cells, increases tissue vascularization, enhances the kill- ing ability of leukocytes, and is lethal for anaerobic bac- teria.
Examples of diseases that HBO can help with
Clinical studies suggest that HBO therapy can be an effective adjunct in the management of diabetic wounds [39]. Animal studies indicate that HBO therapy could be beneficial in the treatment of osteomyelitis ansoft tissue infection
Adverse effects of HBO
Adverse effects of HBO therapy are barotraumas of the ear, seizure, and pulmo- nary oxygen toxicity. However, in the absence of con- trolled scientific studies with well-defined end points, HBO therapy remains a controversial aspect of surgical practice
Why does healing slow down with age
The decline in healing response results from the gradual reduction of tissue metabolism as one ages, which may itself be a manifestation of decreased circulatory efficiency. The major components of the healing response in aging skin or mucosa are defi- cient or damaged with progressive injuries [43]. As a result, free oxidative radicals continue to accumulate and are harmful to the dermal enzymes responsible for the integrity of the dermal or mucosal composition. In addition, the regional vascular support may be subjected to extrinsic deterioration and systemic disease decom- pensation, resulting in poor perfusion capability. However, in the absence of compromising systemic con- ditions, differences in healing as a function of age seem to be small.
How does wound healing change in malnourished patients
In malnourished patients, fibroplasia is delayed, angio- genesis decreased, and wound healing and remodeling prolonged.
Which amino acids critical for healing
Amino acids are critical for wound healing with methionine, histidine, and arginine playing important roles. Methionine appears to be the key amino acid in wound healing. It is metabolized to cysteine, which plays a vital role in the inflammatory, proliferative, and remodeling phases of wound healing.
Albumin levels and healing
Nutritional deficiencies severe enough to lower serum albumin to <2 g/dL are associ- ated with a prolonged inflammatory phase, decreased fibroplasia, and impaired neovascularization, collagen synthesis, and wound remodeling.
Serum prealbulmin vs serum albumin
Serum prealbumin is commonly used as an assess- ment parameter for protein [45, 46]. Contrary to serum albumin, which has a very long half-life of about 20 days, prealbumin has a shorter half-life of only 2 days. As such, it provides a more rapid assessment ability. Normal serum prealbumin is about 22.5 mg/dL, a level below 17 mg/dL is considered a mild deficit, and a severe defi-cit would be below 11 mg/dL. As part of the periopera- tive optimization process, malnourished patients may be provided with solutions that have been supplemented with amino acids such as glutamine to promote improved mucosal structure and function and to enhance whole- body nitrogen kinetics.
Vitamin A and wound healing.
Vitamin A stimulates fibro- plasia, collagen cross-linking, and epithelialization and will restimulate these processes in the steroid-retarded wound.
Vitamin C and wound helaing
Vitamin C deficiency impairs collagen synthesis by fibroblasts, because it is an important cofactor, along with α-ketoglutarate and ferrous iron, in the hydroxyl- ation process of proline and lysine. Healing wounds appear to be more sensitive to ascorbate deficiency than uninjured tissue. Increased rates of collagen turnover persist for a long time, and healed wounds may rupture when the individual becomes scorbutic. Local antibacte- rial defenses are also impaired because ascorbic acid is also necessary for neutrophil superoxide production.
B complex and wound healing
The B-complex vitamins and cobalt are essential cofac- tors in antibody formation, white blood cell function, and bacterial resistance.
Copper and wound healing
Copper is essential for covalent cross-linking of collagen
Calcium and wound healing
calcium is required for the normal function of granulocyte col- lagenase and other collagenases at the wound milieu.
Zinc and wound healing
Zinc deficiency retards both fibroplasia and reepithelialization; cells migrate normally but do not undergo mitosis [48]. Numerous enzymes are zinc dependent, particularly DNA polymerase and reverse transcriptase. On the other hand, exceeding the zinc lev- els can exert a distinctly harmful effect on healing by inhibiting macrophage migration and interfering with collagen cross-linking.
Applying exogenous PDGF to wound
Becaplermin (recombinant human platelet-derived growth factor-BB [rhPDGF]; Regranex, 0.01% gel; Ortho-McNeil Pharmaceutical Inc., Raritan, New Jersey) was one of the first US Food and Drug Administration-approved recombinant growth factor products introduced to promote growth of soft tissue granulation tissue in treating cutaneous wounds. The recombinant PDGF increases fibroblast replication and induces fibroblasts to produce collagenase, which is important for connective tissue remodeling. In addition, rhPDGF increases the production of other connective tissue matrix components including glycosaminogly- cans and proteoglycans. Notwithstanding its clinical efficacy, becaplermin has not found broad application due to its high costs
Applying exogenous FGF to wound
Within the fibroblast growth factor family (FGF), some members including FGF-2, FGF-7, and FGF-10 are essential to wound healing.
Applying exogenous KGF
The recombinant human keratinocyte growth factor 2 (KGF-2) enhanced both the formation of gran- ulation tissue in rabbits and wound closure of the human meshed skin graft explanted on athymic nude rats
Applying exogenous NGF
Nerve growth factor (NGF), synthesized by Schwann cells distal to the site of injury, aids in the survival and development of sen- sory nerves. This finding has led some investigators to suggest that exogenous NGF application may assist in peripheral nerve regeneration following injury
Applying exogenous BMP
Of the multiple osteoinductive cytokines, the bone morphogenetic proteins (BMPs) belonging to the TGF-β superfamily have received the greatest attention [58, 59]. These cytokines stimulate chondrocyte and osteoblast proliferation, promote the osteoblastic differentiation of mesenchymal stem cells, and increase production of extracellular matrix. Advances in recombinant DNA techniques now allow the production of these biomole- cules in quantities large enough for routine clinical appli- cations. In particular, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-7 have been studied extensively for their ability to induce undif- ferentiated mesenchymal cells to differentiate into osteo- blasts (osteoinduction).
Gene therapy of adenovirus-hBMP-2 cDNA
Mesenchymal cells transfected with adenovirus-hBMP-2 cDNA have been shown to be capable of forming bone when injected intramuscularly in the thighs of rodents [67, 68]. Similarly bone marrow cells transfected ex vivo with hBMP-2 cDNA have been shown to heal femoral defects [69]. Using osteoprogeni- tor cells for the expression of bone-promoting osteo- genic factors enables the cells to not only produce bone growth promoting factors but also to respond, differen- tiate, and participate in the bone formation process.
What is the gold standard for replacing dermal mucosal surfaces
autologous grafts remain the standard for replacing der- mal mucosal surfaces
Types of human skin substitutes
Available human skin substitutes are grouped into three majortypesandserveasexcellentalternativestoauto- grafts. The first type consists of grafts of cultured epi- dermal cells with no dermal components. The second type has only dermal components. The third type con- sists of a bilayer of both dermal and epidermal elements.
Examples of bioengineered skin substitute
Apligraf®, an allogeneic living epidermal and dermal skin derived from cultured neonatal foreskin. This bio- engineered, full-thickness skin product consists of a liv- ing permanent bilayer skin graft with active cellular and growth factor components. It does not elicit an immune response because its Langerhans cells have been extracted. Currently, Apligraf® is FDA approved for covering venous and diabetic foot ulcers. The chief effect of most skin replacements is to promote wound healing by stimulating the recipient host to produce a variety of wound healing cytokines. The use of cultured skin to cover wounds is particularly attractive inasmuch as the living cells already know how to produce growth factors at the right time and in the right amounts.
Noninvasive cardiac testing
stress test using specific exercise protocol with age- related heart rate requirement and real-time ECG monitoring. The sensitivity of the stress test is low depending in part on how many vessels are stenosed.
More sensitive cardiac testing
exercise echocardiography, dobutamine stress echocardiogra- phy, and dipyridamole thallium stress testing.
If cardiac high risk, what last test should they undergo
coronary angiography
Define myocardial work
Myocardial work is primarily determined by four factors related to myocardial oxygen demand: heart rate, preload, afterload, and contractility
What is heart rate influenced by
Heart rate is influ- enced by a number of factors including oxygen demand, physical activity, and hormonal and neurogenic mecha- nisms.
What is pre load
Preload represents all factors that contribute to passive ventricular wall stress at the end of diastole. It approximates the end-diastolic ventricular pressure. Volume status significantly influences preload.
How to accurately measure preload
An accu- rate determination of preload requires a central line to measure central venous pressure or pulmonary capillary wedge pressure.
Define afterload
Afterload represents all factors that con- tribute to the ventricular wall stress during systole. The total peripheral resistance has the most influence on afterload, although intrathoracic pressure may also influence afterload as is the case with mechanical venti- lation.
What is contractility
Contractility refers to the ability of the myocar- dium to contract.
Patients with acute coronary syndrome
Should not undergo noncardiac surgery
Chest X ray shows
Cardiomegaly, pulmonary edema, pleural effusion
ECG shows
Left ventricular hypertropher, ST segment changes, inverted T waves, Q waves, and arrhythmias
Transthoracic Dopper Echo shows
Wall motion abnormalities, ejection fraction, and chamber pressures
Stress test shows
functional cardiac ischemia
Perfusion nuclear imaging shows
Cardiac perfusion at rest and with function
What symptomatic disorders may CAD lead to
Stable angina or an acute coronary syndrome
What is stable angina
Presents with precordial pain radiating to left arm, neck a nd jaw on exertion. Relieved by rest or by sublingual nitroglycerin
Examples of ACS
ACSs include unstable angina, non-ST-elevated MI, and ST-elevated MI. Symptoms are similar to stable angina but occur with less exertion than is usual, or at rest, and do not abate with further rest. The history surrounding the onset of chest pain has a diagnostic sensitivity of 90% when the symptoms are classic. An ECG may show ST segment depression or inverted T waves indicating ischemia. ST segment elevation indicates frank MI. The treatment of any patient suspected of having ACS begins with the correct diagnosis.
How to diagnose ACS
A 12-lead ECG (ST elevation, inverted T waves, Q waves) and Cardiac enzymes (CK-MB [MB isoenzyme of cre- atine kinase], troponins
Treatment for ACS or MI
The initial treatment for suspected ACS or MI has tradi- tionally been morphine, oxygen, nitrates, and aspirin (MONA). Current evidence supports the use of aspirin which has been shown to reduce mortality. Morphine remains the drug of choice for pain but it has not been shown to reduce mortality. Nitrates should be used in the presence of persistent ischemia, heart failure, and hypertension but it has not been shown to reduce mortality. Oxygen should be used when oxygen satura- tion is less than 90% on room air as it has been shown to increase the infarct size [7]. The advent of anti-platelet drugs, fibrinolytics, and percutaneous coronary angio- plasty (PCA) has reduced the mortality from MI to 3%.
How to reduce cardiac events including MI in perioperative period
The use of perioperative beta blockers has been shown to reduce the likelihood of cardiac events includ- ing MI. Patients with a recent MI may be at risk for re- infarction following the initial infarct.
How long after MI to operate
Patients with a recent MI may be at risk for re- infarction following the initial infarct. The ACC recommends waiting a minimum period of 6 weeks after an MI before proceeding with elective surgery [8]. Furthermore, the longer the time period from the MI to the elective surgery, the greater the risk reduction.
DAPT are given to PCA
Patients who have had PCA and are typically treated with dual anti-platelet therapy (DAPT). This typically involves the use of aspirin and a glycoprotein IIb/IIIa inhibitor (e.g., abciximab or eptifibatide) or an ADP antagonist (e.g., clopidogrel, etc.). It is recommended that in the event that a patient requires noncardiac sur- gery, the aspirin should be continued. The glycoprotein IIb/IIIa inhibitor or ADP antagonist should be contin- ued for a minimum period of 14 days, 30 days, and 3 months for balloon angioplasty, bare metal stents, and drug eluting stents, respectively
What is CHF
CHF is a result of inadequate cardiac output.
When is CHF a contraindication to surgery
Compensated CHF is considered an intermediate clini- cal predictor, whereas decompensated CHF is consid- ered a major clinical predictor within the ACC/AHA algorithm and a contraindication to elective surgery.
Causes of CHF
Causes of CHF include MI, valvular heart disease, HTN, anemia, pulmonary embolism (PE), cardiomyopathy, thyrotoxicosis, and endocarditis.
Left CHF
Left-sided failure presents with exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, cardiomegaly, rales, and a third heart sound (S3) gallop.
Right CHF
Right-sided heart failure results in elevated jugular venous pressure, peripheral edema (especially lower extremities), and atrial fibrilla- tion (AF).
How to diagnose CHF
The diagnosis is best made with a transtho- racic echocardiogram, although the measurement of brain natriuretic peptide (BNP) can be used to help diagnose and monitor CHF progression. Posteroanterior and lateral chest radiography will often reveal cardio- megaly and may show pulmonary edema and plural effusions if decompensated.
