Inflammation and tissue healing

Question 1

What are the stages of inflammation and tissue healing? how long do they last? what happens during it?

Answer 1

1. Inflammatory Phase (lasts 6 – 10 days): prepares the wound for healing.
2. Proliferation Phase : (Day 3 on), Rebuilds & Strengthens the wound
3. Maturation Phase, A.K.A. Remodeling Phase: (Day 9 on), process that modifies tissue from weak- non-functional to strong-functional tissue.

Question 2

What occurs during the inflammation phase? (4 responses)

Answer 2

1. Vascular response
2. Hemostatic response
3. Cellular response
4. Immune response

Question 3

What is the cellular response in the early and late stage of inflammation?

Answer 3

• Early Inflammation (hours after injury) = neutrophils, basophils, and eosinophils (WBCs); Neutrophils are the first WBCs “seen” at the injured site because most WBCs in the plasma are neutrophils - Neutrophils use their phagocytic function to remove bacteria & debris from the site of injury
• late inflammation (24-48 hrs) = predominance of mononuclear monocytes and lymphocytes which peak 3-4 days post injury - predominate late phase bc they live longer than neutrophils
• monocytes convert to phagocytic macrophages

Question 4

What is the cellular response in that indicates the stage of healing?

Answer 4

• Re-epithelialization, fibroplasia in connective tissues, development of granulation tissues via capillary budding, wound contraction (proliferative)
• Collagen fibers taken up and reformed in a nonrandom orientation that increases tissue tensile strength – “a random to nonrandom change in the orientation of collagen fibers” (maturation/ remodeling)

Question 5

Arterial-venous capillary network gap so that larger molecules can enter the tissue and cause swelling. This leads to formation of edema

Answer 5

Micro-vessel permeability

Question 6

What are the physiological factors that change to cause local edema?

Answer 6

1. Increased capillary hydrostatic pressure - increases fluid flow out of the capillary
2. Decreased capillary oncotic pressure - Reduces fluid flow into the capillary from the interstitium
3. Increased fluid flow out of the capillary forming fluid in the tissue
4. Lymphatic obstructions

Question 7

What systemic conditions can cause edema in response?

Answer 7

1. CHF
2. Renal disease
3. Osmotic changes associated with severe burns

Question 8

When fluid is driven out of the vascular space or capillaries into the interstitial fluid, this is known as ______.
When fluid is driven into of the vascular space or capillaries from the interstitial space, this is known as ______.

Answer 8

Filtration; Reabsorption

Question 9

During the vascular response, what happens with leukocytes to that leads to increased permeability of the blood vessels? (leads to edema formation)

Answer 9

1. Blood flow initially slowes (caused by NE release for vasoconstriction at injured blood vessels, vasoconstriction dilation around injury) - causes seeding of leukocytes
2. Margination - L’s line the vessel wall
3. Diapedesis - L’s squeeze between the endothelial cells through the vessel walls
4. Emigration - L’s migrate from the blood vessel to the perivascular tissue
5. Chemoattractants are released from injured tissue that guides L’s to the injured tissue
6. Chemotaxis - L’s move toward source of injury in the interstitial space
7. Macrophages (L’s) clean up the injured tissue to prepare for healing)

Question 10

What are the starling forces that encourage filtration?

Answer 10

1. Increased capillary hydrostatic pressure (Pc) -Blood pressure against vessel walls, increases with increased blood flow through capillaries
2. Increased interstitial oncotic pressure (∏I) aka interstitial colloid osmotic pressure - The pressure that tends to increase diffusion of fluid from inside the vessels into the tissue by increasing the concentration of protein molecules in the tissue.

Question 11

What are the starling forces that encourage resorption?

Answer 11

1. Increased interstitial hydrostatic pressure (PI) - The pressure of fluid against the outside of the vessel wall; the more fluid the greater the pressure
2. Increased capillary oncotic pressure (∏C) aka plasma colloid osmotic pressure - The pressure that tends to increase diffusion of fluid from the tissue into the blood by increasing the concentration of protein molecules in the plasma

Question 12

What chemical mediators cause vasodilation?

Answer 12

1. Histamine
2. Substance P
3. Calcitonin gene-related peptide
4. Prostaglandins

Question 13

What chemical mediators cause increased vascular permeability?

Answer 13

1. Histamine
2. Bradykinin
3. Prostaglandins – Magnifies effect of histamine.
4. Hageman factor - clotting factor enzyme in blood
   - When these mediators are released, they cause the endothelial cells to constrict and widen the gap to allow leukocytes to move into tissue. Attracted to charges – when a cell is injured, it causes the outside of it to become more negative; the charge change causes in tact cells to shrink (contract)

Question 14

What chemical mediators chemotaxis?

Answer 14

Histamine

Question 15

What chemical mediator causes fever?

Answer 15

prostaglandins

Question 16

What chemical mediator causes pain?

Answer 16

Bradykinin

Question 17

How does cryotherapy influence the inflammatory response?

Answer 17

1. decreases vasodilation and chemical mediators
2. reduces metabolic demand of damaged tissue
3. diminishes physiologic functions (blood flow, inflammatory response and muscle activity)

Question 18

How does e-stim influence the vascular response?

Answer 18

• decreases micro vessel permeability of plasma proteins (albumin) by preventing the contracture of endothelial cells
• curbs edema during treatment

Question 19

What kind of e-stim influences the vascular response (edema)?

Answer 19

burst modulated monophonic pulsed current

- cathode (overall negative polarity) seems to have better results

Question 20

controls blood loss when vessels are damaged or ruptured and confines the inflammatory reaction to an area immediately surrounding the injury

Answer 20

hemostatic response of inflammation

Question 21

Contractures may occur in contractile or non contractile tissue due to immobilization or lack of use. What is believed to be the molecular basis that causes contractures?

Answer 21

• it allows anomalous cross-longs to form between collagen fibers; develops when itissue remain stationary because in the absence of normal stress and motion, fibers remain in contact with each other for prolonged periods and start to adhere at their points of interception; prevents normal alignment of collagen fibers when motion is attempted
• it causes fluid to be lost from fibrous connective tissue

Question 22

characterized by re-epithelialization, fibroplasia, granulation tissue via capillary budding, wound contraction; Involves both epithelial and connective tissues, and the formation of new
capillaries

Answer 22

Proliferative phase of tissue repair

Question 23

characterized by increased metabolism of randomly oriented collagen fibers which are replaced with collagen fibers oriented to
one and another in a nonrandom arrangement of increased tensile strength

Answer 23

Maturation (remodeling) phase

Question 24

Involves the migration of epithelial cells across the fund site (open wound in skin) until the open area is covered; when the cells stop migrating, they undergo mitosis, reforming layers of epithelial cells

Answer 24

re-epithelialization

- proliferative phase of epithelial tissue

Question 25

occurs when fibroblast cells migrate into the inflamed area along fibrin strands; The fibrin strands (fibrin lattice) were laid down by platelets (2 – 4 days post injury) during the Hemostatic response within the first 10 days; Within the first 2-4 days after the injury a weak scar begins to form as the fibroblasts secrete the protein collagen and mucopolysaccharides

Answer 25

Fibroplasia

• proliferative phase of connective tissue
• Fibroblast cell number peaks on about the 20th day post injury
• Scar tissue is a type of connective tissue that is primarily composed of Protein Collagen and Mucopolysaccharides which are secreted by the fibroblasts

Question 26

phase of tissue repair: Collagen fibers are “taken up” and “reformed” in an organized nonrandom orientation that increases tissue tensile strength; The Type III collagen fibers initially laid down by the fibroblasts are randomly oriented so that the connective tissue matrix is weak, i.e., collagen held together by weak hydrogen (ionic) bonds; Type III fibers are reabsorbed and replaced with new lengthened type I collagen fibers that are organized parallel to the applied force and held together by the stronger covalent bonds

Answer 26

maturation/ remodeling phase

• weak type III is replaced by stronger type I collagen
• starts on day 9 and continues for months to years

Question 27

What is the strength of type III collagen? When is it replaced by type I? When is the optimal time to load tissue?

Answer 27

• 15% of normal tissue
• replaced around 2 weeks
• ~6 weeks post injury - wound is 80% normal tissue strength; can load to increase strength

Question 28

Formation of new Blood Capillaries or Vessels; Parallels the increased appearance of the endothelial cells at the injury site; Spread over damaged tissue or wound at the same time as the formation of scar tissue.

Answer 28

Angiogenesis

• occurs during proliferative phase
• Formed from endothelial buds; the “buds” develop from intact capillaries. The intact capillary walls are made up of endothelial cells.

Question 29

• tissue that is red in appearance from the endothelial buds and developing scar tissue; a positive sign that the prognosis for full wound healing is good; indicates tissue has return of the blood supply needed for complete healing

Answer 29

Granulation tissue

Question 30

occurs at ~20 days post-injury; Myofibroblasts appear in the connective tissue during the formation the granulation tissue; Myofibroblasts cause wound contraction in the connective tissue

Answer 30

wound contraction

Question 31

fibroblasts that contain the contractile protein, actin, and have the ability to contract to pull the edges of the wound together.

Answer 31

myofibroblasts

Question 32

characterized by increased metabolism of randomly oriented collagen fibers which are replaced with collagen fibers oriented to one and another in a nonrandom arrangement of increased tensile strength. Overlaps with Proliferative phase - happens concurrently

Answer 32

maturation phase

Question 33

What are the 2 most important factors responsible for successful remodeling?

Answer 33

• want a mobile scar!
  1. Phases of repair process when the tissue is exposed to mechanical forces - forces applied during the remodeling phase of tissue healing for plastic changes (permanent) to occur
  2. The kind or nature of the forces applied to the tissue - Scars need low-load, long duration stretches applied that do not cause inflammation and result in discomfort only when the tissue is in a lengthened state past the point of resistance

Question 34

What are the signs of acute inflammation?

Answer 34

1. Redness
2. Warm
3. Edema
4. Pain before tissue resistance
5. Decreased function

Question 35

What is the effect of heat and stretching on extensibility of tissue?

Answer 35

Raises the temp of joint capsules and scar tissue b/c high collagen and low water content. This increases extensibility.

Question 36

When is heat indicated?

Answer 36

Subacute and chronic phases of tissue healing
- increases metabolism in the tissue in which heat is absorbed (increased oxygen absorption, increases demands for nutrients)
- Musle relaxes by decreasing muscle spindle activity and increasing GTO activity, allowing for further stretching of connective tissue without muscle guarding
- Pain relief through gate theory, decreasing nonmyelinated C-fiber activity, and inhibiting nociceptive signals in the spinal cord
- Increases capillary pressure and cell permeability promoting local swelling
Increases the extensibility of connective tissue