Robbins Basic Pathology - Tissue Repair

1. Tissue Repair

2. Tissue Repair
• Tissue repair = restoration of tissue architecture
and function after an injury
• Occurs in two ways:
– Regeneration of injured tissue
– Replacement by connective tissue (scarring)
• Usually, tissue repair involves both processes.
• Involves cell proliferation, and interaction between cells and
extracellular matrix.

3. Lots of cells proliferate during tissue repair:
injured tissue remnants
vascular endothelial cells
fibroblasts
We need to know about:
the cell cycle
the proliferative capacities of different tissues
stem cells
growth factors
the extracellular matrix

4. Regeneration and
Reparation
regeneration
◦ restoration of normal structure and function
◦ persistence of supportive „tissue skeleton“ necessary
◦ BM of epithelia
◦ reticulin frame in liver
reparation
◦ restoration of normal shape x function is impaired or lost
◦ parenchyma replaced by fibrous tissue

5. Tissue types
permanent
◦ nonproliferative in postnatal life
◦ neurons (?), cardiomyocytes (?)
stable
◦ regeneration as response to injury
◦ parenchyma – liver, pancreas, renal tubules
◦ mesenchymal cells, endothelium
labile
◦ continuous regeneration from stem cells (self-renewal)
◦ hematopoietic cells in bone marrow
◦ surface epithelia – skin, oral cavity, vagina, cervix
◦ duct epithelia – salivary glands, pancreas, biliary tract
◦ mucosas – GIT, uterus, fallopian tubes, urinary bladder

6. Stem
Cells Brain
I
)
CNS stem cells
Bone
Bone marrow
stromal cell
Fat cell
Cardiac muscle
Neuron
Glial cell

7. Epidermal stem cells located in the
bulge area of the hair follicle serve
as a stem cells for the hair follicle
and the epidermis.
Intestinal stem
cells are located
at the base of a
colon crypt, above
Stem-cell
niches in various tissues

8. Liver stem cells (known as oval
cells) are located in the canals
of Hering (thick arrow),
structures
ductules
that
(thi
n
connect
arrow)
bile
wit
hparenchymal
hepatocytes
Corneal stem cells are
located in the limbus region,
between the conjunctiva and
the cornea.

9. Growth Factors
• Very important in tissue repair.
• Actions:
• stimulate cell division and proliferation
• promote cell survival
• Huge list! Usually have “GF” in name:
• EGF
• TGF
• PDGF

10. Replacement of necrotic
tissue
resorption by macrophages
dissolution by enzymes
replacement by granulation tissue
◦uniform mechanism irrespective of inicial trigger
◦the same microscopic appearance
◦angiogenesis
◦migration and proliferation of fibroblasts
◦deposition of ECM
◦maturation and reorganization

11. Granulation tissue
new-formed connective tissue, apparent from 3rd day
thin-walled capillary vessels
fibroblasts
loose extracellular matrix
stimulation
◦PDGF, VEGF, FGF, TGF, TNF, EGF
inhibition
◦INFalfa, prostaglandins, angiostatins
control
◦cyclins, cyclin dependent kinases

12. Granulation tissue
pink soft granular appearance
richly vascularized
highly cellular
myxoid matrix
inflammatory cells
e.g. surface of wounds, bottom of ulcers

13. Granulation
tissue

14. first intention healing second intention healing

15. Angiogenesis
neovascularization
x vasculogenesis (embryonic process only)
highly complex phenomenon
angiogenic factors (FGF, VEGF)
antiangiogenic factors
healing, collateral circulation, tumors

16. Fibrosis and Remodeling
scar formation
fibroblasts
myofibroblasts
◦ spindle cells of both fibroblastic and smooth muscle phenotype
◦ production of collagen fibres
◦ wound contraction

17. Fibrosis and Remodeling
abundant collagen fibres bridging the defect
devoid of inflammatory cells
reepithelization of surface defect
◦from skin appendages and/or from periphery
secondary changes
◦calcification (dystrophic)
◦ossification (metaplastic)
remodeling
◦synthesis and degradation of ECM
◦metalloproteinases (MPs), tissue inhibitors of MPs

18. 6 hours 24 hours
2 days
1 week