Tissue Injury and Repair

Question 1

The ____ ____ to infection and injury begins the process of repair.

Answer 1

Inflammatory response

Question 2

Two main repair processes:
1. _____:restoration of normal cells
2. ____/____: deposition of connective tissue
Ultimate repair is usually a combination of both.

Answer 2

Regeneration
Scarring/fibrosis

Question 3

Regeneration:
1. ____ of differentiated cells that survive injury
2. Tissue ____ ____ produce new differentiated cells

Answer 3

Proliferation
Stem cells

Question 4

Regeneration is generally limited to some components of most tissue and requires ____ ____ ____.

Answer 4

Intact supporting structures

Question 5

Scarring/fibrosis:
The injured area is ____ with connective (fibrous) tissue. Occurs when either cells of injured tissue are not capable of ____ or ____ ____ are too severely damaged.

Answer 5

Patched
Regeneration
Supporting structures

Question 6

Scarring/fibrosis does not replace normal function of the tissue because the injured cells are replaced by ___ ___, which provides ____ but not function.

Answer 6

Connective
Structure

Question 7

A tissue’s ability to repair depends on ____ capacity and ___ ___. There are three classes of tissue in this regard:

Answer 7

Proliferation
Stem cells

Labile tissue, stable tissue, permanent tissue

Question 8

____ tissue is constantly dividing. ____ tissue is quiescent but not able to divid if needed. ____ tissue is not able to divid.

Answer 8

Labile
Stable
Permanent

Question 9

Labile tissue is constantly turning over by stem cells and proliferation of mature cells.
Examples of Labile tissue and cells:

Answer 9

Lungs: type II pneumocytes, skin (basal cells), GI tract (Crypt cells), hematopoietic cells (CD34+ cells)

Question 10

Picture of Labile tissue:

Answer 10

Question 11

Stable tissue is made of ____ cells (G0). Capable of proliferating when tissue is injured or lost.
Examples:

Answer 11

Quiescent

Solid tissues such as liver, kidney, pancreas
Connective tissues such as endothelium, smooth muscle, and fibroblasts

Question 12

Picture of stable tissue:

Answer 12

Question 13

Permanent tissue cells are terminally differentiated and can’t ____. Repair is almost entirely ____.
Examples:

Answer 13

Proliferate
Fibrosis

Most neurons, cardiac and skeletal muscle.

Question 14

Picture of permanent tissue repair:

Answer 14

Question 15

Regeneration is driven by ___ ___ that are derived from activated ____ at the site of injury. Also derived from platelets, epithelial cells, Stromal cells, sequestered pool in extracellular matrix.

Answer 15

Growth factors
Macrophages

Question 16

Regeneration depends on the integrity of the ____ ____. Some growth factors are present bound to the ___ ___ and therefore disruption of the ___ ___ could result in growth factor expression.

Answer 16

Extracellular matrix
Extracellular matrix
Extracellular matrix

Question 17

Three phases of scarring/fibrosis:
1. _____: day 1 to 3. Cellular mediators involved are platelets, neutrophils, and macrophages. There is acute inflammatory response with macrophages clearing debris.

Answer 17

Inflammatory

Question 18

Picture of inflammatory response:

Answer 18

Question 19

Three phases of fibrosis:
2. _____: day 3 to weeks. Fibroblasts, myofibroblasts, endothelial cells, epithelial cells, and macrophages. They establish _____ ___, angiogenesis, epithelial cell proliferation, and type III collagen deposition

Answer 19

Proliferation
Granulation tissue

Question 20

Picture of granulation tissue:

Answer 20

Question 21

______ is stimulated by VEGF. It stimulates both migration and proliferation of endothelial cells. Promotes vasodilation by stimulating the production of ___ ___. Contributes to the formation of vascular lumen

Answer 21

Angiogenesis
Nitric oxide

Question 22

Three phases of fibrosis:
3. _____: weeks to months. ____ are the cellular mediators. They replace type III collagen deposition with type I collagen. _____ contract to bring the wound edges together and add strength.

Answer 22

Remodeling
Fibroblasts
Macrophages

Question 23

____ collagen provided a temporary structure in the injured area. ___ collagen is laid down in an orderly fashion facilitated by ____ and ___.

Answer 23

Type III
Type I
Fibroblasts
Macrophages

Question 24

After it’s deposition, the connective tissue in the scar counties to be modified and remodeled by ____ _____.

Answer 24

Matrix metalloproteinases (MMP)

Question 25

Diagram of tissue repair:

Answer 25

Question 26

Regulation of regeneration and repair: _____ M1 and M2 activation. M1: M2:

Answer 26

Macrophage Clears offending agents and dead tissue Provides growth factors causing proliferation of various cells

Question 27

M2: Macrophages secrete cytokines that stimulates _____ to proliferate and deposited connective tissue ECM.

Answer 27

Fibroblasts

Question 28

M1 and M2 activation of macrophages is ___ ___. Macrophages are initially classically activated (M1), but are gradually replaced by alternatively activated type (M2).

Answer 28

Temporally regulated

Question 29

___ is the most important cytokine in fibrosis. It is produced by most cells in granulation tissue including M2 macrophages.

Answer 29

TGF-beta

Question 30

TGF-beta stimulates fibroblast ___ and ___. It increases synthesis of ___ and ___. It decreases degradation of ECM by inhibiting ___ ____. It also has anti-inflammatory properties

Answer 30

Migration Proliferation Collagen Fibronectin Matrix metalloproteinases (MMPs)

Question 31

____ limits and terminates the inflammatory response.

Answer 31

TGF-beta

Question 32

Table of growth factors:

Answer 32

Question 33

Wound strength: At week one, the wound is at about ____ strength of normal skin. Gradually, more ___ and less ___ ___ increases the strength

Answer 33

10% Collagen Granulation tissue

Question 34

Wound strength: After 2 moths, maximum strength is achieved, still only ___ of original tissue strength

Answer 34

75%

Question 35

Complications of tissue repair: ___ ___: clinical factors can impede the repair process ___ ___: hypertrophic scars and keloid. Contractures

Answer 35

Chronic wounds Excessive scarring

Question 36

Delayed wound healing occurs in ____, causing prolonged inflammation and ongoing injury.

Answer 36

Infection

Question 37

____ results in delayed wound healing due to poor perfusion and neuropathy leading to mechanical factors

Answer 37

Diabetes

Question 38

___ ___ contributes to delayed wound healing. Vitamin C and protein deficiency both result in impaired ___ synthesis. Zinc deficiency inhibits replacement of ____ collagen to ___ collagen.

Answer 38

Nutritional deficiencies Collagen Type III Type I

Question 39

____/____: can contribute to delayed wound healing. They reduce inflammation but also inhibit fibrosis (this can be good or bad).

Answer 39

Medications/steroids

Question 40

___ ___ can contribute to delayed wound healing. Healing wounds are weaker than native tissue and can be pulled apart

Answer 40

Mechanical stress

Question 41

____: is poor perfusion that can contribute to delayed wound healing. Lack of nutrients needed for repair.

Answer 41

Ischemia

Question 42

___ ___ can lead to delayed wound healing by serving as continued stimuli for chronic inflammation and ongoing injury

Answer 42

Foreign material

Question 43

____ is rupture of a wound, most common after abdominal surgery

Answer 43

Dehiscence

Question 44

____ ___ is excess production of scar tissue that is localized to the wound

Answer 44

Hypertrophic scar

Question 45

____ is excess production of scar tissue that is out of proportion to the wound. Characterized by excess ____ collagen. It classically affects earlobes, face, and upper extremities.

Answer 45

Keloid Type III

Question 46

Pictures of hypertrophic scar: It is limited to boundaries of original wound.

Answer 46

Question 47

Picture of keloids:

Answer 47

Question 48

Microscopy of keloid scarring: Contains keloidal collagen that are disorganized

Answer 48

Question 49

Scar ____ is an exaggeration of normal contraction of the wound during healing. Prone to developing in the palms, soles, and anterior aspect of the thorax

Answer 49

Contracture

Question 50

____ ___: a sutured surgical incision with tightly apposed edges ___ ___: a wide open wound due to more inflammation and more granulation tissue

Answer 50

First intention Second intention

Question 51

____ ____ plays a major role in ultimate wound closure.

Answer 51

Myofibroblastic contraction

Question 52

Cutaneous wound healing picture :

Answer 52

Question 53

Macrophages largely replace neutrophils by day 3. Granulation tissue starts to develop.

Answer 53

Question 54

Day 5: _____ aided by ___ and granulation tissue peaks. Fibroblasts begin to lay down type III collagen

Answer 54

Neovascularization VEGF

Question 55

Two weeks: type I collagen replaces Type III and greatly increases cellularity and blood vessels decrease

Answer 55

Question 56

1 month: cellularity markedly diminished and scar contracts via action of ____.

Answer 56

Myofibroblasts