Test 2- Wound Healing

Question 1

wound

Answer 1

injured tissue

Question 2

repair

Answer 2

replacement of injured tissue

Question 3

Healing begins…

Answer 3

Healing begins immediately after a wound develops

Question 4

Hemostasis

Answer 4

• Immediate

Vasospasm leads to relaxation

Platelets aggregate to exposed

collagen and a network of fibrin forms

• Reduces blood loss
• Binds edges of the wound

together

• Initiate angiogenesis (PDGF,

TGFβ)- growth factors are released, which are important for the proliferative phase

Question 5

Phases of wound healing

Answer 5

1. Hemostasis
2. Inflammation-“clean up”
3. Proliferation- 1 week in
4. Maturation- weeks in ;

Question 6

Inflammation

Answer 6

24-96 hours

Cardinal signs of inflammation seen

Some ECM components are chemotactic

Degradation–leukocytes“clean up” cell debris from the injury

Leukocytes secrete chemotactic

and growth factors leads to proliferation

phase

If excessive, can reduce healing

Question 7

Degradation

Answer 7

leukocytes“clean

up” cell debris from the injury

Leukocytes secrete chemotactic

and growth factorsproliferation

phase

If excessive, can reduce healing

Question 8

Proliferation

Answer 8

3-7 days, lasting up to 3-4 weeks

Regeneration of tissue:

- Endothelium (angiogenesis)

- Epithelium (epithelialization)

- Connective tissue (fibrosis)

Granulation tissue forms

Stem cells in a quiescent stage are

influenced by cytokines / growth factors

—Limited by proliferative potential of cell

types involved

Fibroblasts proliferate to fortify the

woundcollagen deposition

Decreases with age and disease

Question 9

Maturation

Answer 9

Begins 3-4 weeks after injury, after proliferation, can last years

Remodeling of granulation tissue, maturation of fibrosis, and wound contraction

Required for return of tensile strength

Re-establishment of cell interactions

Vascular regression

Question 10

Answer 10

Wound Healing by Primary Intention

Wounds with opposed edges

Question 11

Answer 11

Wound healing by Secondary Infection

Gaping wounds

Septic wounds

Foreign bodies

Wound with delayed healing process

Question 12

Primary vs secondary infection

Answer 12

• both have the same phases of wound healing

THE DIFFERENCE IS, the extent to which it has to be healed.

Primary can be healed in about 3-5 days.

Before secondary intention can occur, you have to have healthy granulation tissue, so it will take longer.

Scar will be much bigger in secondary intention and the tensile strength of the wound will be decreased.

Question 13

Note large amounts of granulation tissue and wound contraction in the healing by

Answer 13

secondary intention

Question 14

Degradation

Answer 14

Must remove junk before healing can occur

Things in the center of a wound:

– Dead cells

– Leukocytes

– Cytokines

– Serum/clotting proteins

– ECMsubstances

How leukocytes do it:

– Phagocytosisandlysosomaldegradation

– Degranulationandreleaseofdigestive enzymes

– Matrix metalloproteinases–very important for degrading the ECM

Must remove junk before healing can occur

Things in the center of a wound:

– Dead cells

– Leukocytes

– Cytokines

– Serum/clotting proteins

– ECMsubstances

How leukocytes do it:

– Phagocytosisandlysosomaldegradation

– Degranulationandreleaseofdigestive enzymes

– Matrixmetalloproteinases–very important for degrading the ECM

Question 15

Phase of Wound Healing

Answer 15

Degradation

Question 16

A tissues ability to return to normal depends on

Answer 16

A tissues ability to return to normal depends on:

Retention of ECM structural framework

Regenerative capacity of cells

Question 17

Regenerative capacity of cells

Answer 17

Regenerative capacity of cells

Labile/Continuously dividing cells

– Proliferate throughout life, replacing those cells that are destroyed

– Ex: epithelial cells of liver, kidney, lung, pancreas, skin, mucous membranes

Quiescent/Stable cells

– Low level of replication; undergo rapid division in response to stimuli

– Capable of reconstituting the tissue of origin

– Ex: smooth muscle, fibrocytes, vascular endothelial cells, chondrocytes, osteocytes

Permanent cell/Non-dividing cells

– Have left the cell cycle & cannot undergo mitotic division in postnatal life

– Ex: Neurons, cardiac & skeletal muscle

Question 18

Regeneration of Epithelium (Epithelialization)

Answer 18

Proliferate immediately at denuded surfaces

Must disassemble connections to the basement membrane and junctional complexes with neighboring cells

Must express surface receptors that bind ECM

Intact basement membrane greatly facilitates!

Regulated by contact inhibition

Question 19

Answer 19

Kidney from a calf with renal tubular necrosis and regeneration due to oak bud toxicosis

Question 20

Role of the extracellular matrix (ECM) in regeneration and repair.

Answer 20

Role of the extracellular matrix (ECM) in regeneration and repair.

Liver regeneration with restoration of normal tissue after injury requires an intact cellular matrix.

If the matrix is damaged the injury is repaired by fibrous tissue deposition and scar formation.

Question 21

Growth factors

Answer 21

Needed for cellular

– Proliferation
– Differentiation

EGF – bind receptors on epithelial cells thenactivates MAPK then induces G0 phase cell cycle

Question 22

Stem Cells

Answer 22

Stem Cells – important source for epithelial regeneration

Embryonic – pluripotent; isolated from blastocysts

Tissue stem cells- most in WOUND HEALING

– Not pluripotent; restricted lineage- specific differentiation capacity- depends on what tissue it is in

– Bone marrow(bone marrow, umbilical cord) – hematopoietic and mesenchymal cells- greater capacity-

– Skeletal muscle “satellite cells”

Question 23

Regeneration: Endothelium (Angiogenesis)

Answer 23

• Formation of new blood vessels from existing ones
• PDGF,FGF,VEGF-Abind GF-R’s on endothelial cells induce vascular formation by…

– Endothelial proliferation
– Recruitment of pericytes
– Deposition of ECM proteins

Question 24

Regeneration of Connective Tissue

Answer 24

Fibroplasia – migration & proliferation of fibroblasts

Fibrosis – scar formation by connective tissue remodeling

Factors that favor fibrosis:

– Severe and prolonged tissue injury

– Loss of tissue framework (basement membranes)

– Large amounts of exudate/inflammation

– Lack of renewable cell populations

Question 25

Fibrous connective tissue

Answer 25

– Dense accumulation of fibroblasts and collagen

– With time, the collagen becomes more densely packed

– Persists for years (life)

Question 26

Consequences of fibrosis

Answer 26

• Loss of functional parenchymal tissue
• Alteration of physical properties of tissue

Question 27

Granulation Tissue

Answer 27

• Distinctive arrangement of connective tissue fibers, fibroblasts, and blood vessels

– Fibroblasts and connective tissue grow parallel to wound surface

– Blood vessels arranged perpendicular to fibrosis

Fragile capillaries – bleeds easily

Granular surface

Can be excessive, a type of hypertrophic scar termed proud flesh

Question 28

Answer 28

Granulation Tissue

Question 29

Answer 29

When good granulation tissue goes bad…

“Proud flesh”
(aka exuberant granulation tissue)

Question 30

Wound contraction

Answer 30

A normal part of the maturation phase of wound healing

But can be bad when connective tissue contracts and place tension on surrounding tissues

May immobilize or deform the tissue (ex: burns)

Mediated by myofibroblasts

– Form within wounds in response to

TGF-β

– Increase with time and severity

Question 31

Conditions with Impaired Wound Healing

Answer 31

Tension on a tissue

Prolonged inflammation

– Local infection, foreign material

– Abundant necrotic tissue

Disorders in collagen synthesis

– Protein malnutrition

– Hyperadrenocorticism – antagonistic effect of steroids

– Inherited defects – osteogenesis imperfecta, Ehlers-Danlos syndrome

– Scurvy(vitaminCdeficiency)

Poor blood supply

– Diabetes mellitus – impaired angiogenesis

• Impaired ability of cellular regeneration

– Chemotherapy

– Old age

– Denervatedtissue

Question 32

What phase of wound healing is this, if there is necrosis and neutrophils?

Answer 32

early inflammation stages

Question 33

What stage of wound healing is this?

Answer 33

Proliferation.

You can see the hypertrophic epithelial cells toward the center of the picture.

Question 34

Angiogenesis process

Answer 34

1. proteolysis of ECM
2. Migration and chemotaxis
3. proliferation
4. lumen formation, maturation, and inhibition of growth
5. increased permeability through gaps and transcytosis

or

• *A** , Bone marrow. EPCs are mobilized from the bone marrow and may migrate to a site of injury. The homing mechanisms have not yet been defined. At these sites, EPCs differentiate and form a mature network by linking with existing vessels.
• *B,** Preexisting vessels (capillary growth). In angiogenesis from preexisting vessels, endothelial cells from these vessels become motile and proliferate to form capillary sprouts. Regardless of the initiating mechanism, vessel maturation (stabilization) involves the recruitment of pericytes and smooth muscle cells to from the periendothelial layer

Question 35

What is this?

Answer 35

Fibrous connective tissue

Question 36

Synthesis of ECM

Answer 36

– Collagen, elastin, fibronectin, laminin

– Growth factors induces fibroblasts to synthesize collagen

– Collagen = triple helices with lots of cross-linkage providing tensile strength

TGF-β

Produced by platelets & leukocytes

Is important for fibroblast migration & proliferation, and collagen/ECM protein synthesis

Question 37

Answer 37

Consequences of fibrosis

liver- nodular surface

Question 38

Answer 38

fibriotic liver stained with Thrichrome stain

Question 39

What is this?

Answer 39

Granulation tissue- VERY GOOD