L5 Healing

• Aberrations of Inflammation and Repair

  • Inadequate scar formation
  • Wound dehiscence: rupture
  • Ulceration: inadequate vascularisation
  • Hypertrophic scar: keloid
  • Wound contracture

  
• Ulceration


  Aberrations of Inflammation and Repair
• Keloid


  Aberrations of Inflammation and Repair
• Excess collagen deposition in the skin

  Aberrations of Inflammation and Repair
• Contractures


  Aberrations of Inflammation and Repair
• Skin Wounds


  Healing by Fibrosis and Scarring

  
• Myocardial infarct (24 hours)


  • Early myocardial fibre necrosis and the beginnings of the acute inflammatory response

  
• Myocardial infarction (3 days)

  • Necrotic fibres, and a predominantly mononuclear (macrophage) inflammatory cell infiltrate

  
• Myocardial infarction (5 days old)


  • Immature granulation tissue with thin walled new vessels and plump fibroblasts, with little collagen as yet

  
• Maturing granulation tissue


  • Less obvious new vessels, and fibroblasts laying down intercellular collagen
• Old myocardial infarction


  • Repaired by dense collagenous scar

  
• Structure of a long bone

  • Compact bone: concentric bony layers contain lacunae containing osteocytes, fed by blood vessels in Haversian and Volkmann's canals

  
• Cortical bone


  • Periosteum, Osteocyte nucleus, Osteocyte lacuna, Osteoblasts, Connective tissue with blood vessels

  
• Fracture Healing


  1. Inflammatory phase

  2. Reparative phase

  3. Remodeling phase
• Fracture Healing: Inflammatory Phase

  1. 1-2 days: Tearing of periosteum and adjacent soft tissues leads to extensive haemorrhage and clot formation, Necrosis of bone fragments

  2. 2-5 days: Acute inflammatory response with fluid and cellular exudate and beginnings of granulation tissue
• Fracture Healing: Reparative Phase

  7 days: Osteoblasts grow from stem cells in granulation tissue, ECM synthesised by osteoblasts encourages mineralisation, Cartilage often also forms initially, gradually replaced by bone, Bone appears - woven (disorganised structure), Granulation tissue containing bone or cartilage: callus
• Callus


  • Newly formed woven bone rimmed by active osteoblasts, sitting in granulation tissue composed of thin-walled vessels and fibroblasts

  
• Fracture Healing: Inflammatory Phase

  Next few weeks: Blood clot (and bone fragments) cleared by phagocytosis, Building and organisation of callus by action of osteoclasts and osteoblasts, Fractured bone ends joined by callus
• Fracture Healing: Remodelling


  Reorganisation of woven bone to lamellar bone, again by balanced action of osteoclasts and osteoblasts, In response to mechanical stress, Problems: Non-union or fibrous union resulting from delayed healing - infection, excessive movement, poor blood supply

  
• Healing by scarring


  Replacement of damaged cells by connective tissue
• Granulation tissue


  New, proliferating thin walled vessels, loose ECM and plumb fibroblasts that are synthesizing collagen

  
• The initially loose and fragile granulation tissue gradually gains strength as the collagen content increases
• Scar remodelling occurs over months, but original strength is not regained
• Healing objectives


  • Describe healing of skin wounds and fractures and list common causes for impaired healing of skin wounds and fractures
  • Describe healing of cerebral infarcts and recognize and describe cerebral infarcts that are days, weeks and years old
  • Describe and recognise the "wave of healing by repair" as seen in the healing of a myocardial infarct
  • Describe healing of myocardial infarcts and recognize and describe the features of myocardial infarcts that are days, weeks and months old
  • Describe the conditions under which the liver heals by regeneration and when the liver heals by repair

  
• The cell's ability to regenerate- labile, stable cells, presence of ECM scaffold vs scar/fibrosis

  
• Macrophages setting the stage for healing- cytokines and growth factors
• Granulation tissue: angiogenesis, fibroblasts, ECM
• Skin healing: primary vs secondary intention

  
• Primary (first) intention healing

  Well approximated wound edges, leads to regeneration of epithelium with minimal scarring in the dermis

  
• Secondary intention healing


  Large deficit in epithelium, limited epithelial regeneration with significant scarring, wound contraction (~10%) by modified fibroblasts called myofibroblasts

  
• Regeneration


  1. Labile & stable cells

  2. Parenchymal tissue (restore function)

  3. Connective tissue (restore strength)

  4. Inflammatory response

  5. Messenger release

  6. Migration & Proliferation (parenchymal & connective tissue)
• Repair


  1. VEGF & FGF

  2. FGF, TGF-β

  3. Angiogenesis

  4. Fibroblast deposition of ECM (collagen, etc)

  5. Scar remodeling

  6. TGF-β, PDGF

  7. FGF, VEGF

  8. Fibrosis

  9. Granulation tissue
• Factors that may complicate healing

  • Local factors: Wound infection -↑necrosis, Foreign bodies e.g. bone, Mechanical factors –torsion, pressure, Poor perfusion e.g. PVD, ↓venous drainage, (diabetes), Wound location -pleura
  • Systemic factors: Age, Pre-existing or concomitant disease e.g. diabetes, Medications e.g. steroids ↓TGFβ, Nutrition deficiency in proteins & Vit. C

  
• Healing outcomes


  • Healed skin wound (by primary intention) is 70%- 80% original strength at 3 months (dermal appendages lost)
  • Inadequate healing: deficient venous or arterial blood flow e.g. ulcers, wound dehiscence: the reopening of a wound, many causes (infection, strain, poor blood flow)
  • Fibrosis describes the deposition of collagenous scar tissue in organs from chronic inflammation or after myocardial infarction
  • Organisation: another form of fibrosis if an exudate is incorporated upon resolution/ repair

  
• Excessive scar formation


  • Hypertrophic scar: excessive scar tissue but within the bounds of the original wound. Usually resulting from deep trauma or burns
  • Keloid: Scar tissue grows beyond the original bounds of wound, predisposition in some individuals, more common in African Americans

  
• Contractures


  Excessive wound contraction leading to deformity particularly on palms, soles, thorax
• Adhesions


  Bands of scar tissue that join two surfaces e.g. pleural adhesions, post abdominal surgery
• Normal liver - the work horse of the body
• Detoxification of blood, Bile production, Storage of glycogen, Processing fats, Making protein, And more!
• Paracetamol overdose can lead to centrilobular necrosis of the liver