,dhba,dc dsaufulunhiwuniaWOUND HEALING1, BASIC PA. Toll-like receptors (Tl.Rs)1. Present on cells of the innate immune system (e.g., macrophages and dendriticcells)2. Activated by pathogen-associated molecular patterns (PAMPs) that arecommonly shared by microbesi, CDI4 (a TLR) on macrophages recognizes I ipo polysaccharide (a PAMP) onthe outer membrane of gram-negative bacteria.3. TLR activation results in upregulation of NF-kB, a nuclear transcription factorthat activates immune response genes leading to production of multiple immunemediators.4. TLRs are also present on cells of adaptive immunity (e.g., lymphocytes) and,hence, play an important role in mediating chronic inflammation.B. Arachidonic acidasa dav d (AA) metabolites1. AA is released from the phospholipid cell membrane by phospholipase A, andthen acted upon by cyclooxygenaseRINCIPLESA. Healing is initiated when inflammation begins.B. Occurs via a combination of regeneration and repairII REGENERATIONA. Replacement of damaged tissue with native tissue; dependent on regenerativecapacity of tissueasB. Tissues are divid vaed into three types based on regenerative capacity: labile, stable, andpermanent.ava C. Labile tissuedsvs possess stem cells that continuously cycle to regenerate the tissue.1. Small and large a dbowel (stem cells in mucosal crypts, Fig. 2.5)2. Skin (stem cells in s vbasal layer. Fig. 2.6)3. Bone marrow (hematosdpoietic stem cells)D. Stable tissues are compr vised of cells that are quiescent {G_), but can reenter the cellcycle to regenerate tissue whs en necessary.1. Classic example is regenerasdtion of liver by compensatory hyperplasia afterpartial resection. Each hepatocytav e produces additional cells and then reentersquiescence.sE. Permanen t tissues lack significant regenerative potential (e.g., myocardium, skeletalmuscle, and naseurons).III. REPAIR aA. Replacemenss vat of damaged tissue with fibrous scarB. Occurs when reg vavsv sa va

sa vsav sdva asv aenerative stem cells are lost (e.g., deep skin cut) or when a tissueas vsad vadv sd