S3M1 Pathology Conran Inflammation And Repair 6

Front 1

There are four general components of repair by fibrosis, what are they?

Back 1

-Formation of new blood vessels (angiogenesis)
-Migration and proliferation of fibroblasts
-Deposition of ECM
-Maturation and reorganization of fibrous tissue

Front 2

Repair begins within _____ hours?

Back 2

24 hours

Front 3

Repair by Fibrosis causes emigration of fibroblasts and endothelial cell proliferation. By 2-5 days, what tissue is present?

Back 3

At 3-5 days, granulation tissue is apparent,

Front 4

Appearance of granulation tissue is characterized by:

Back 4

-Proliferation of fibroblasts
-macrophages
-myofibroblasts with contractile actin

Front 5

Histologically compare Granulation tissue to a healed (scarred) myocardial infarction.

Back 5

Granulation tissue has myofibroblasts with pinkish type 3 collagen.

A healed scare will be avascular, with dense CT (dense fibrosis)

Front 6

Blood vessels are assembed by what two processes?

Back 6

1.) Vasculogenesis: assembed from angioblasts during embryonic development

2.) angiogenesis:
-preexisting vessels send out sprouts to make new vessels

Front 7

The four general steps in new capillary vessel development are :
1.) proteolytic degradation of parent vessell BM
2.) Endothelial cell migration toward an angiogenic stimulus.

What are the last two steps?

Back 7

3.) Proliferation of endothelial cells behind leading edge

4.) Maturation of endothelial cells; including recruitment of pericytes and smooth muscle cells for support.

Front 8

New vessels are leaky due to incomplete interendothelial junctions. The most important factors that induce angiogenesis are:

Back 8

1.) basic fibroblast growth factor (bFGF)

2.) Vascular endothelial growth factor (VEGF)

Front 9

What do angiogenic factors like bFGF and VEGF cause?

Back 9

-proliferation
-endothelial cells to secrete proteinases to degrade BM
-endothelial cell migration
-direct vascular tube formation

Front 10

Regarding angiogenesis, structural ECM proteins regulate ______________ while nonstructural ECM proteins ______________.

Back 10

structural ECM proteins regulate vessel sprouting via integrins

Nonstructural ECM proteins:
-destabilize cell-ECM interactions and also facilitate cell migration via thrombospondin and tenascin C

Front 11

Angiogenesis starts with little capillary buds with no lumen. Describe the growth of a BV.

Back 11

Capillary "bud-cells" begin migrating outwards and proximal cells b/g dividing. Eventually, migrating cells form arcades with other migrating cells in the middle and the bud acquires a lumen. Finally, smooth muscle comes along and adheres to the outside.

Front 12

Fibrosis (scar formation) builds on what type of tissue?

Back 12

builds on granulation tissue framework of new vessels and loose ECM.

Front 13

What are the two steps of fibrosis?

Back 13

1.) emigration and proliferation of fibroblasts into site of injury.

2.) deposition of ECM by these cells

Front 14

Recruitment and stimulation of fibroblasts are driven by what three Growth factors?

Back 14

1.) Platelet derived growth factor (PDGF)
2.) bFGF
3.) TGF-B

Front 15

During scar formation these cells are important because they elaborate growth factors and other medaiators that induce fibroblast proliferation.

Back 15

Mononuclear cells (specifically Macrophages)

No neutrophils because the wound is clean by now.

Front 16

Collagen synthesis is critical to development of strength in would healing. What makes collagen and when?

Back 16

Fibroblasts begin making collagen early (3-5 days) and continues for weeks.

Front 17

Collagen synthesis is induced by what 3 molecules?

Back 17

1.) Growth factors (PDGF, bFGF, and TGF-B)
2.) cytokines (IL-1)
3.) tumor necrosis factor (TNF)

Front 18

Granulations tissue is used as a scaffold to make a scar which is composed of what materials?

Back 18

Inactive fibroblasts and collagen

Front 19

Bacterial produces or other immune complexes activate macrophages to secrete _______ and ________. These initiate fever, endothelial cell effects, fibroblasts proliferation and other cytokine secretion.

Back 19

IL-1/TNF

Front 20

Degradation of collagens and other ECM components occurs by metalloproteinases. There are three important classes:

Back 20

1.)interstitial collagenases
cleave fibrillar col I, II, III

2.) gelatinases (type IV) collagenases) that degrade amorphous col and fibronectin.

3.) stromelysins:
-variety of ECM such as
proteoglycans, laminin, fibronectin or amorphous collagen.

Front 21

Degradation of scar or "scar remodeling" is mainly controlled by what enzyme class?

Back 21

Metalloproteinases

Front 22

Activated collagenases (metalloproteinases) can be rapidly inhibited by:

Back 22

Tissue inhibitors of metalloproteinases (TIMPs)

These prevent the collagenases from overchewing collagen

Front 23

Metalloproteinases are made by fibroblasts, macrophages and neutrophils and are regulated by:

Back 23

-growth factors
-cytokines
-phagocytosis

Inhibited by TGF-B
inhibited by steroids

Front 24

Since metalloproteinases are inactive, they must first be activated by:

Back 24

-chemicals (HOCl. radical)
-Proteases(plasmin)

Front 25

Healing by first intention or primary union is healing of clean uninfected incision that causes only focal disruption of BM. What type of generation is occuring?

Back 25

Epithelial regerneration predominates over fibrosis.

Front 26

Within 24 hours of first intention healing, what is happening?

Back 26

-neutrophils at incision margin migrating toward the fibrin clot.
-Basal cells at incision margin exhibit an increase in mitotic activity.

Front 27

Within 48 hours of first intention healing, what is happening?

Back 27

Epithelial cells proliferate and deposit basement membrane components and cells meet in midline beneath the scab in a thin but continuous epithelial layer.

Front 28

Day 3 of first intention healing, what is happening?

Back 28

-Macrophages replaced neutrophils
-Granulation tissue invades incision space
-collagen fibers are evident at incision margins
-Fibers are vertically oriented and do not bridge incision
-epithelia thickens and epidermal covering layer.

Front 29

Day 5 of first intention healing, what is happening?

Back 29

-Neovascularization stops
-collagen increases and bridges incision
-epidermis recovers its normal thickness
-surface keratinization

Front 30

During the second week of healing by first intention, collagen continues to accumulate and you have increase fibroblasts. What three things are diminished?

Back 30

WBC's, edema and vascularity

Front 31

What is blanching?

Back 31

Increasing collagen deposition and regression of blood vessels; Mature scar.

Front 32

At what time during the healing by first intention is a scar
1.)devoid of WBCs and covered by epidermis
2.)dermal appendages destroyed by incision are lost*
3.) Tensile strength of the wound increases with time

Back 32

End of the first month

Front 33

Not a questions!!

Back 33

Not a question

Front 34

This is a type of wound healing caused by cell or tissue loss, infarction, inflammatory ulceration, abscess or large wounds.

Back 34

Second Intention

Front 35

healing by second intention is more complex because parenchymal cells alone cannot heal; how is healing done?

Back 35

Healing is by regeneration and fibrosis;

There is more granulation tissue but bulk of wound is fibrosis

Front 36

Second intention healing differs from First intention healing in several ways:
1.)Non-opposed wound margins
2.) Large tissue defects have a more necrotic debris, exudate and fibrin
what is 3 and 4?

Back 36

3.) More granulation tissue
4.)Myofibroblasts-->wound contraction within 6 weeks

Front 37

What is the single most important cause of delay in healing?

Back 37

Infection

Glucocorticoids can also delay wound healing b/c of anti-inflammatory effects

Front 38

What are the facts that interfere with repair:
1.) Infection
2.)Nutrition
3.) Glucocorticoids (steroids)
what other 3 things?

Back 38

4.) Mechanical
5.)Poor perfusion
6.) Foreign bodies

Front 39

What are keloids?

Back 39

-accumulation of collagen
-hereditary in blacks and asians

Front 40

Exuberant granulation (proud flesh) is:

Back 40

Excessive granulation tissue
-abnormal cell growth and ECM production
-hinders re-epithelialization
-Cautery or surgical resection is necessary for restoration of epithelial continuity.