Module 3 Pathology Robbins Ch3 Tissue Repair

Front 1

Granulation tissue, histologis characteristics

Back 1

Proliferation of fibroblasts and angiogenesis in a loose ECM.

Progressively accumulation of CT matrix and resluting in a scar.

Front 2

Four sequential processes of repair by CT tissue deposition

Back 2

1. angiogenesis
2. migration and proliferation of fibroblasts
3. deposition of ECM (scar formation)
4. maturation and reorganization of the fibrous tissue (remodeling)

Front 3

Blood vessels are assembled by two processes

Back 3

1. vasculogenesis: primitive vascular network from angioblast during embryonic development
2. angiogenesis / neovascularization: preexisting vessels send out capillary sprouts to produce new vessles

Front 4

Two forms of angiogenesis

Back 4

A. Angiogenesis form EPCs (endothelial precursor cells) form the bone marrow
B. Angiogenesis from preexisting vessels

Front 5

Main steps in angiogenesis from vessels

Back 5

1. vasodilation (NO, VEGF)
2. migration of endothelial cells
3. proliferation of endothelial cells
4. inhibition of endothelial cell prolif and remodeling into capillary tubes
5. reqruitment of periendothelial cells (pericytes, SMC)

Front 6

REGENERATION

Back 6

- Replacement of lost structures
- Is dependent on the type of normal turnover the original tissue has
- Can be differentiated from “compensatory” growth

Front 7

HEALING (repair)

Back 7

-Needs a wound, inflammatory process, or necrosis
- Many disease appearances anatomically are the result of “healing” such as atherosclerosis
- Often ends with a scar
- Fibrosis, as one of the 3 possible outcomes of inflammation, follows “healing”
- Requires a connective tissue “scaffold”
- Fibrosis occurs in proportion to the damage of the ECM

Front 8

Continously dividing tissue

Back 8

= Lable tissues
Hematopoetic SC, surface epithelial cells

Front 9

Stable tissues

Back 9

Cells are quiescent (G0). Capable of proliferating in response to injury. Parenchymal cells of most solid tissues (liver, kidney, pancreas). Endothelial cells, fibroblasts, SMC.

Front 10

Permanent tissues

Back 10

Terminally differentiated and nonproliferative in postnatal life. Neurons, cardiac muscle cells. Injury is irreversible and results in a scar.

Front 11

Characterisitic properties of SC

Back 11

Self renewal, asymmetric replication.

Front 12

Growth Factors

Back 12

Polypeptides
Cytokines
Functions:
LOCOMOTION
CONTRACTILITY
DIFFERENTIATION
ANGIOGENESIS

Front 13

Different Growth Factors

Back 13

Epidermal
Transforming (alpha, beta)
Hepatocyte
Vascular Endothelial
Platelet Derived
Fibroblast
Keratinocyte
Cytokines (TNF, IL-1, Interferons)

Front 14

Epidermal GF (EGF)

Back 14

Made in platelets, macrophages
Present in saliva, milk, urine, plasma
Acts on keratinocytes to migrate, divide
Acts on fibroblasts to produce “granulation” tissue

Front 15

Transformin GF-alfa

Back 15

Made in macrophages, T-cells, keratinocytes
Similar to EGF, also effect on hepatocytes

Front 16

Hepatocyte GF

Back 16

Made in “mesenchymal” cells
Proliferation of epithelium, endothelium, hepatocytes
Effect on cell “motility”

Front 17

Vascular endothelial GF (VEGF)

Back 17

Made in mesenchymal cells
Triggered by HYPOXIA
Increases vascular permeability
Mitogenic for endothelial cells
KEY substance in promoting “granulation” tissue

Front 18

Platelet derived GF (PDGF)

Back 18

Made in platelets, but also MANY other cell types
Chemotactic for MANY cells
Mitogen for fibroblasts
Angiogenesis
Another KEY player in granulation tissue

Front 19

Fibroblast GF (FGF)

Back 19

Made in MANY cells
Chemotactic and mitogenic, for fibroblasts and keratinocytes
Re-epithelialization
Angiogenesis, wound contraction
Hematopoesis
Cardiac/Skeletal (striated) muscle

Front 20

Transforming GF-beta

Back 20

Made in MANY CELLS
Chemotactic for PMNs and MANY other types of cells
Inhibits epithelial cells
Fibrogenic
Anti-Inflammatory

Front 21

Keratinocyte GF

Back 21

Made in fibroblasts
Stimulates keratinocytes:
Migration
Proliferation
Differentiation

Front 22

Insuline-like GF

Back 22

Made in macrophages, fibroblasts
Stimulates:
- Sulfated proteoglycans
- Collagen
- Keratinocyte migration
- Fibroblast proliferation
Action similar to GH (Pituitary Growth Hormone)

Front 23

TNF

Back 23

Made in macrophages, mast cells, T-cells
Activates macrophages
KEY influence on other cytokines

Front 24

Interleukins

Back 24

Made in macrophages, mast cells, T-cells, but also MANY other cells
MANY functions:
- Chemotaxis
- Angiogenesis
- REGULATION of other cytokines

Front 25

Interferon

Back 25

Made by lymphocytes, fibroblasts
Activates MACROPHAGES
Inhibits FIBROBLASTS
REGULATES other cytokines

Front 26

Collgen type I, II, III, IV

Back 26

Collagen One - bONE (main component of bone)

Collagen Two - carTWOlage (main component of cartilage)

Collagen Three - reTHREEculate (main component of reticular fibers)

Collagen Four - FLOOR - forms the basement membrane

Front 27

Functions of ECM

Back 27

Maintain cell differentiation
“Scaffolding”
Establish microenvironment
Storage of GF’s

Front 28

Genetic collagene disorders

Back 28

I: OSTEOGENESIS IMPERFECTA, E-D
II: ACHONDROGENESIS TYPE II
III: VASCULAR EHLERS-DANLOS
V: CLASSICAL E-D
IX: STICKLER SYNDROME
IV: ALPORT SYNDROME
VI: BETHLEM MYOPATHY
VII: DYSTROPHIC EPIDERMOLYSIS BULLOS.
IX: EPIPHYSEAL DYSPLASIAS
XVII GEN. EPIDERMOLYSYS BULLOSA
XV, XVIII KNOBLOCH SYNDROME

Front 29

Healing by first intention

Back 29

Wound is small, clean, like a surgical incision.
24h: neutrophils, fibrin clots. Epithelial cells migrate and proliferate along dermis.
Day3: macrophages, granulation tissue
Day5: neovascularization reaches it's peak, collagen fibers bridge the incision
2w: continued collagen accumulation and fibroblast proliferation

Front 30

Healing by second intention

Back 30

Larger wound, abscess formation or ulceration.
Intense inflammatory reaction, abundant granulation tissue, contraction by myofibroblasts.

Front 31

Keloid

Back 31

Excessive production of ECM (collagen). Genetic predisposal, more in blacks