Chapter 2.5 Wound Healing

Question 1

At what point in inflammation is healing initiated?

Answer 1

healing is initiated when inflammation begins

combination of regeneration and repair (replace tissue with a scar; collagen and fibrosis)

Question 2

What is regeneration?

Answer 2

replacement of damaged tissue with native tissue

• dependent on regenerative capacity of tissue
• 3 types of tissues based on regenerative capacity

Question 3

What are some examples of labile tissues?

Answer 3

has SC constantly regenerating the tissue

(bowel, skin, RBC, WBC, platelets)

• small and large bowel (stem cells in mucosal crypts) …can regenerate after infection in GI tract or diarrhea
• skin (stem cells in basal layer) superficial layer of epithelium knocked out, SC/basal cells can regenerate that tissue constantly
• bone marrow (hematopoietic stem cells)

Question 4

Where are the stem cells in the labile tissues?

Answer 4

• small and large bowel (stem cells in mucosal crypts)
• skin (stem cells in basal layer…innermost layer of epi? dermis)
• bone marrow (hematopoietic stem cells)

Question 5

What is the marker of hematopoietic stem cells?

Answer 5

CD34

bone marrow stem cells are CD34+

Question 6

What is stem cell of alveoli of lung?

Answer 6

Type II pneumocytes

Question 7

Describe stable tissues.

Give two classic examples and provide a clinical example for each.

Answer 7

quiescent, but can reenter cell cycle

regeneration of liver by compensatory hyperplasia after partial resection
(each hepatocyte in liver can come out of quiesence and reenter cell cycle and divide and allow for regeneration of the liver)

proximal renal tubule of kidney (when patients undergo ATN=acute tubular necrosis, they get destruction of PT cells… can regenerate but takes time, so may have to place patient with ATN on dialysis to support them until kidney regenerates PT)

Question 8

What are the permanent tissues in the body?

Answer 8

lack significant regenerative potential

myocardium
skeletal muscle
neurons

(don’t have much SC capability so when damaged can’t regenerate)

Question 9

If permanent tissues are damaged, how do they heal?

Answer 9

with repair
repair replaced damaged tissue with fibrous scar

occurs when regenerative stem cells are lost or when tissue lacks regenerative capacity

(permanent tissues are myocardium, skeletal muscle, neurons)

Question 10

What is the end result of MI?

Answer 10

always a fibrous scar bc the heart does not have the ability to regenerate tissue

Question 11

If you get a deep cut why does a scar sometimes form instead of regenerative repair?

Answer 11

if basal cells are removed, get scar instead of replacement with skin

repair replaces damaged tissue with fibrous scar when tissue lacks regenerative capacity

Question 12

What is the initial phase of repair?

Answer 12

granulation tissue

Question 13

What three things does the initial phase of repair, granulation tissue, consist of?

Answer 13

fibroblasts (deposit type III collagen)

capillaries (provide nutrients)

myofibroblasts (contract wound)

Question 14

What is the difference between a granuloma and granulation tissue?

Describe the mechanism by which each is formed.

Answer 14

granuloma is a subtype of chronic inflammation: hallmark is epitheliod histiocyte, granuloma formed by IL-12 from macrophage converting CD4 T cell converting it to Th1 helper cell which secretes IFN gamma that gives macrophage an epitheliod appearance)

granulation tissue is the inital phase of repair when forming a scar (consists of fibroblasts, capillaries, and myofibroblasts)

Question 15

Eventually granulation tissue produces a scar. What distinguishes a scar from granulation tissue?

How does granulation tissue become a scar?

Answer 15

type III collagen is replaced with type I collagen (provides stability in final scar)
(type III prod. by fibroblasts)

collagenase removes type III collagen and requires ZINC as a cofactor.

Question 16

Describe the key features of the four types of collagen and where each is predominantly seen.

Answer 16

Type I collagen (seen in bone…bONE, tendons, skin, and most organs) key feature is its strong tensile strength, provides support

Type II collagen (seen in cartilage, carTWOlage)

Type III collagen (classic for its pliability, see it in blood vessels which need to stretch, in granulation tissue (needs to stretch to form scar), see in embryonic tissue/uterus bc baby growing and needs to stretch, keloids)

Type IV collagen (predominantly seen in basement membrane)

Question 17

What cofactor is requires in the reaction to convert granulation tissue to a scar?

Answer 17

zinc is the cofactor required

collagenase removes type III collagen

Question 18

What is the mechanism of regeneration and repair?

Answer 18

mediated by paracrine signaling via growth factors (factors secreted by macrophages will bind receptors and these interactions result in regeneration and repair)

interaction of factors with receptors results in gene expression and cellular growth

Question 19

Describe the following growth factors:

TGF alpha
TGF beta

Answer 19

TGF-alpha = epithelial and fibroblast growth factor

TGF-beta = important fibroblast growth factor; stimulates ECM synthesis, inhibits inflammation,

Question 20

Describe the following growth factor:

PDGF

Answer 20

platelet derived growth factor (platelets help seal blood vessel that has been damaged… if platelets activated they releaes PDGF which helps endothelium and smooth muscle regrow, and fibroblasts come in)

endothelium, smooth muscle, fibroblast growth factor, stimulates ECM protein synthesis

Question 21

Describe the following growth factor:

FGF

Answer 21

fibroblast growth factor

angiogenesis; skeletal development
ECM protein synthesis

Question 22

Describe the following growth factor:

VEGF

Answer 22

vascular endothelial growth factor

angiogenesis

Question 23

Cutaneous healing occurs via primary or secondary intention. Distinguish between the two.

Answer 23

primary - wouund edges brought together; minimal scar formation (big cut, suture two edges together…)

secondary - edges are not approximated/stitched together, granulation tissue fills in the defect
get BIG scar, granulation tissue will cause contraction of that wound

Question 24

Patient has large wound that has healed by secondary intention. Six weeks later the wound has reduced significantly in size. What mechanism?

Answer 24

myofibroblasts

(granulation tissue has three properties; capillaries, fibroblasts that lay down type IIl collagen, myofibroblasts (have contractile function)
…can contract wound and make it smaller

Question 25

What is the most common factor that may lead to delayed wound healing?

What are other causes? Describe the mechanism by which these causes delay wound healing.

Answer 25

wound, doesn’t heal in appropriate time

infection (most common cause) continued inflammation impairs healing of wound

zinc, copper, vitamin C deficiencies

other causes: foreign body (would induce chronic inflammation), ischemia (decreased blood supply to tissue) diabetes, malnutrition (don’t have building blocks to allow wound healing to occur

Question 26

Describe in detail the mechanism by which a Vitamin C deficiency could lead to wound healing.

Answer 26

-Vitamin C deficiency (when collagen produced by cell it is produced as separate alpha chains that wrap around each other and final result is pro-collagen, pro-collagen is secreted outside cell and is cross-linked outside the cell, before cross-linking can occur on pro-collagen you must hydroxylate the proline and lysine residues of pro-collagen)

collagen normal amino acid structure is Gly-x-y (x usually is proline or lysine, usually proline) y is proline or lysine that will be hydroxylated and OH added, Vitamin C is necessary to add that OH group. need OH group so when you cross link another collagen molecule, you do so by the OH groups, allows pro-collagen to be strengthened to the final collagen molecule

Question 27

Deficiencies of what substances may lead to delayed wound healing? Describe the mechanism.

Answer 27

zinc, copper, vitamin C

-Vitamin C deficiency (hydroxylation) (when collagen produced by cell it is produced as separate alpha chains taht wrap around each other and final result is pro-collagen, pro-collagen is secreted outside cell and is cross-linked outside the cell, before cross-linking can occur on pro-collagen you must hydroxylate the proline and lysine residues of pro-collagen)

copper deficiency (lysyl oxidase) enzyme that cross links lysine and hydroxylysine to form stable collagen, lysyl oxidase requires copper, if no copper can’t cross link collagen

zinc deficiency (granulation tissue contains type III collagen which needs to be converted to type I for scar formation, zinc is cofactor in order for this reaction by collagenase)

Question 28

What is dehiscence? In what clinical scenario is this most commonly seen?

Answer 28

rupture of wound, most commonly seen after abdominal surgery

Question 29

What is a hypertrophic scar? What type of collagen is predominant in this type of scar?

Answer 29

excess production of scar tissue that is localized to the wound

predominantly made of type I collagen

Question 30

What is a keloid? How does it differ from a hypertrophic scar?

Answer 30

keloid:
-excess production of scar tissue that is out of proportion to the wound
characterized by excess -type III collagen in the keloid

hypertrophic scar:

• excess production of scar tissue that is localized to the wound
• predominantly made of type I collagen

Question 31

What populations have a greater predisposition to keloid formation?

Answer 31

Genetic predisposition (more common in African Americans)

Question 32

Where are keloids commonly found clinically?

Answer 32

classically affects earlobes, face, and upper extremities