• architecture
• regen. of cells
• absence of factors that can impede healing
  • persistance of causative agent
  • poor blood supply
  • defects in leukocytes
  • protein deficiency, malnutrition
  • vitamin C deficiency, leads to inh. of collagen syn.
  • suppressed immune response or steroids

1. use same as neutrophils
2. monocytes become macrophages once enter tissue
   1. recruited
   2. resident

• pathogens bind endotoxin (LPS) and toll like receptors (TLR's)
• cytokines- IFN gamma (Th1 path)
• chemotaxin mediated
• Ag-Ab mediated
• products of necrotic cells (ex: uric acid)
• free radicals and oxidative struess

• lysosomal enzymes and oxygen metabolites
• cytokines
  • TNF α
  • IL-1
  • IL-6
• chemokines
  • IL 8
  • MCP 1
• arachodonic acid metabolites- PG's, leukotrienes
• plasminogen activators

1. remove of debris and edema
   • lytic action of neutrophil proteases
   • reabsorption of edema via lymphaitcs
   • macrophage phagocytosis remove cell and tissue debris
2. regeneration of native cells
   • activated macrophages produce growth factors that stimulate prolif. of native cells (ex: EGF, HGF, TGF alpha)
   • architecture of remaining tissue must be able to support recovery
     • give structure
     • tissue resources must be sufficient to allow recovery of native cells
3. organization- prolif. of CT to form provisional "granulation tissue" of three major cell types
   • activated macrophages (via TGF β) induce prolif. of endothelial cells and fibroblast
   • endothelial cells prolif. in response to GF's mainly produced by macrophages (ex: VEGF, FGF, TGF beta) to develop new arterioles (angiogenesis)
   • fibroblasts0 proliferate in response to FGF, TGF beta to increase collagen
4. replacement with fibrosis-scar
   • macrophages reorganize fibrovascular granulation tissue to adapt to lines of stress
   • fibroblasts/myofibroblasts contract to close wound and syn. collagen to create strength within scar (wound shrinks)
   • mature scar- few cells, little vascular support

1. EPC from marrow enter site of injury and differentiate
2. endothelial buds grow from pre-existin capillaries
3. neovascularization

• accum. of activated mcarophages
• prolif. of fibroblasts with a fibrin matrix
• fine collagen strands
• new capillaries- neovascularity, angiogenesis
  • EPC (endothelial progenitors) from marrow enter site of injury and differentiate
  • endothelial buds grow from pre-existing capillaries
  • neovascularization

• prolif. fibroblasts
• differentiation to myofibroblasts
• circulating fibrocytes

Stim. via TGF beta, FGF, PDGF (also stimulate fibroblast motility, collagen and fibronectin syn.)

• fibrosis- scar
  • dense collage sclerosis
  • few cells
  • vascular regression

Requires metallopretinases produced by macrophages and fibroblasts regulated by TGFbeta induced inhibitors.

• requires repair (need fill with granulation tissue before epithelium can cover)
• I can't approximate the edges of the wound
• healing starts from bottom, then comes from the sides
• once large wound filled by granulation tissue and covered by epithelium, it undergo revision and contraction until heatlhy stable state is reached
• defect bridged by unspecialized CT (repair)

• edges of wound can be approximated to one another
• healing by primary union
• minimal scar

• during wound repair, there is an excessive collagen matrix(increase TGF beta) 
  • increase in irregular collagen bundles
  • tendency to recur despite excission
  • excessive raised scar
  • dense collagen in irregular bundles
  • lack of skin appendage in area of scar (as in any dermal scar)
  • rises above the skin

• 7-10 days
  • if i take the sutures out too early, you dehis the wound (reopen wound)
  • gives enough time so there is enough collagen in place
  • but if we leave it in too long, the collagen can prolif. to the point where the sutures are embedded in the collagen

• prolonged active inflam (greater than 2-3 weeks)
• concurrent healing and repair
• adaptive immune mediated component includes macrophages, lymphocytes, some plasma cells
  • NO neutrophils
• macrophages are KEY effector cells
• infiltrate of lymphocytes/macrophages

• granulation tissue filling alveolar septae
• large lympocyte infiltrate

• acute- nonspecific
• chronic- immune mediated

• acute- abrupt, well defined
• chronic- vague

acute- prominant

chronic- subdued

• simple
  • formless mononuclear cell infiltrate lymphocytes
• granulomatous
  • nodular macrophage aggregates/cluster w/ rim of peripheral lymphocytes

• cluster of modified epitheliod macrophages
  • prominant (elongated, vesicular) nuclei
  • generous pink cytoplasm (epitheloid)
  • decreased mobility
  • decrease phagocytosis
  • increase cytokine production (ex: TNF alpha)
• peripheral rim of lymphocytes
  • T lympocytes (IFN gamma produced by and causes differentiation of Th1 cells)

• foreign body
  • nonspecific response
  • randomly clustered nuclei
• Langhan's
  • immune mediated response
  • ring of nuclei at cell periphery

Multinucleated macrophages

• TB  (low pathogenicity, strong immune response)
• inorganic dusts (indigestable foreign particulate matter)
• fungi (neutrophils, macrophages cant eradicate)
• sarcoidosis (immune mediated disease)

caseous necrosis (pink amorphus granular degree material surrounded by macrophages)

(TB- caseous necrosis w/granuloma)

• granulomas in draining lymph node
• peripheral granuloma = Ghons focus (cheesy white look to it)

Ghon complex= granulomas in periphery and node

• inner zone of caseous necrosis
• next layer out is macrophages
• next layer out is lymphocyts
• outside you will see fibroblasts and fibrosis

• inflam.
• CT prolif.
• probably fibrosis

Could see mixed infiltrate that has neutrophils, lymphocytes, and macrophages

• resolution with complete healing (no necrosis, changes are reversible such as bee sting)
• organization and repair- replace exudate and dead tissue with CT
• spread of inflammation- local defenses overwhelmed
• persistance of chronic inflam.- exudative cdhanges with healing

• loss of organ cell function
• irreversible accum. of collagen that distorts functional architecture
  • ex: liver cirrhosis, portal HTN
• persistant regen. of surviving cells favors those adapted to abnormal microenvironments and those with mutations, leading to cancer
  • ex: hep C can lead to hepatocellular carcinoma

• acute- prominent vascular effects and exudate
• chronic- mild tissue effects

• acute- exudate is neutrophils
• chronic- exudate is lymphocytes, macrophages

• acute- CT prolif. occurs as inflam. subsides
• chronic- CT prolif. is concurrent with on going inflammation