Path_3.txt

• the tissue works to eliminate the offending agent
• contain the damage
• prepare surviving cells for replication

• combination of regeneration on fibrosis (scarring)
• heart and brain are not able to regenerate so they scar
• Extensive exudate with fibrin will cause scarring

• tissue growth that replaces lost structures
• must have intact connective tissue scaffold

• cell proliferation
• differentation
• apoptosis

• physiologic;hormaonal
• pathologic; injury, cell death
• signals may inhibit or stimulate
• can recruit cell into the cell cycle

• G1, presynthesis
• S DNA synthesis
• G2 Premitotic
• M mitosis
• G0 resting state

• cells proliferate throughout life replacing dead cells
• surface epithelium, the intestinal tract, bone marrow

low level replication but still capable of dividing in response to stimuli; liver, kidney, fibroblasts, smooth muscle, endothelial cells

neurons, skeletal muscle, cardiac muscle

• prolonged self renewal capacity
• asymetric replication

embryonic stem cells

• located in niches
• restricted differentiation capability
• liniage specific

• canals of Hering; junction of hepatocyte and bile duct
• only differentiate if direct hepatocyte proliferation is not possible

VEGF-2

• Source; platelets, macrophages, saliva, urine , milk, plasma
• Function; stimulates keritinocytes and fibroblasts to proliferate

• source; macrophages, T cells,
• function; stimulates replication of hepatocytes, and epithelial cells

• source; mesechymal cells
• function; stimulates epithelial, endothelial, and hepatocyte proliferation
• stimulates mobility

• source; mesenchymal cells
• function; increase vascular permeability, endothelial cell proliferation

• source; platelets, macrophages, smooth muscle, endothelial cells
• chemotactic; PMNs, macrophages, fibroblasts, smooth muscle cells,
• activation of all cells
• mitogenic for fibroblasts, endothelial cells, smooth muscle
• stimulates production of, proteases, fibronectin,
• angiogenisis and would contraction
• inhibits platelet aggrigation
• regulates integrin expression
• alpha granuals

• source; macrophages, mast cells, t cells, endothelial cells,
• chemotactic for fibroblasts
• mitogenic for fibroblasts and keritocytes
• wound contraction
• angiogenesis
• centrally involved in would repair
• form resivoirs of inactive factors

• source; platelets, t cells, macrophages, smooth muscle, fibroblasts
• chemotactic ; macrophages, neutrophils, lymphocytes, fibroblasts,
• stops proteasis; tissue inhibitor of proteases
• down regulates intigrins
• anti-inflammatory effect
• promotes fibrosis by stimulation chemotaxis

• fibroblasts
• stimulates keratinocyte migration, differentation, and proliferation

source; macrophages, fibroblasts

• macrophages, mast cells, lymphocytes
• activates macrophages, regulates the cytokines

• macrophages, mast cells, lymphocytes
• many functions

• lymphocytes, fibroblasts
• activates macrophages,
• inhibits fibroblast proliferation and synthesis of MMPs

• most growth factors
• Ras
• PI3
• phospholipase C
• activated Ras binds to Raf and then activates a MAP kinase
• PLC leads to IP3 and DAG, increased cytosol calcium

• cytokines
• stats are transcription factors

• glucogon, epi, chemokines, ACTH
• generates cAMP

• diffuse directly into membrane
• intranuclear trascription factors

cell cycle inhibitor gene

• the rapid response time needed by the cell does not permit for new synthesis, it rather relys on post transcriptional modification that allows migration into the necleus
• modification; dimerization, phosphorilation, release of inhibitors

• CDKs; protein kinases become active after binding cyclin
• each step needs different kinases
• CDKs are regulated by catabolism or inhibitors
• p53 works by expressing cyclin inhibitor, this stops the cell cycle until the damage is corrected or can induce apoptosis

the restore functional capacity, not reconstruct original anatomy

the other kidney will hypertrophy to make up for the lost one

• skin and bone; type 1
• cartilage; type 2
• basment membrane; type 4
• elastin type 3
• formed as individual alpha chain, form a triple helix

fibrilin 1

collogen v

collogen III

collegen I

• catillage
• any grooming disorder
• arachnidactyl

• immunoglobins
• cadherins; calcium dependent
• intigrins, cell-cell adhesion as well as cell to to ECM
• selectins

cadherins and intigrins

• lots of adhesion
• in hemidesmosoms

laminin

osteonectin

• bind large amounts of water and GAGs
• give turner and resists compression

a fibroproliferative response that pathces rather then restores

ECM depositing at a site of injury

• inflammatory response to eliminate stimulus and remove injured tissue
• proliferation and migration of parechymal and connective tissue
• angiogenisis; new blood vessels
• synthesis of ECM proteins
• tissue remodeling
• wound contraction
• granulomas are a hallmark of healing

PDGF, FGF, TGF-B

PDGF, EGF, FGF, TGF-B, IL-1

PDGF, EGF, FGF, TNF

VEGF, FGF

TGF-B, PDGF

PDGF, FGF, EGF, TNF, TGF-b inhibits

vasulogenesis

angiogenesis

• NO dialates preexisting vessel
• VEGF induces increased permeability
• metalloprotinases degrade BM
• plasminogen activator disrupts cell cell interaction
• ECs migrate to angiogenic stimulus
• EC mature into capillary tubes
• periendothelial cells are recruited

• VEGF and the angiopoetins
• VEGFR2; tyrosine kinase receptor

PDGF

TGF-B

• Fibroblast migration and proliferation
• ECM deposition and scar formation
• Tissue remdeling

zinc

degrade amorphous collagen

tissue inhibitor metalloproteinases

• epidermal appendages do not regenerate
• induction of inflammation
• granulation tissue formation, type III collagen
• ECM deposit and remodeling with wound contraction

• opposed edges, clean surgical cut
• 0 hours; incision is filled with blood
• 3-24 hours; meutrophils infiltrate
• day 3; macrophages replace neutrophil;s
• day 5; granuloma fills incision space, neovasculation
• week 2; inflammation and edema are done
• month 2; scar is now connective tissue devoid of inflammation covered by epidermis. strength will continue to accrue

• greater inflammation response
• more scaring
• thinner epidermis
• thicker granuloma
• most significantly wound healing is characterized by contraction; myofibriblassts

• 1 week 10%
• within 3 months 70-80%

keloid

too much contractor in the healing process from inflammation

inhibit collegen synthesis