Ch. 6 Regeneration And Repair

Front 1

T/F When inflammation causes widespread cellular death (necrosis), the nature of the subsequent healing is different depending on the type of tissue.

Back 1

True

Front 2

What are the tissues that can regenerate?

Back 2

Smooth Muscle and Liver

Front 3

What are the tissues that can not regenerate?

Back 3

Brain and Heart/Skeletal Muscle

Front 4

T/F Tissue destruction is followed by a period of healing.

Back 4

True

Front 5

The most favorable outcome of healing is resolution, or this: complete return to normal structure and function

Back 5

Regeneration

Front 6

What is full resolution?

Back 6

Regeneration

Front 7

When is resolution possible?

Back 7

The damage is minor
– No complications occur
– The destroyed tissue can regenerate

Front 8

What is possible only in tissue that is capable of proliferation of the remaining cells?

Back 8

Regeneration

Front 9

Which cells can regenerate?

Back 9

Liver, skin, and smooth muscle cells can regenerate
– Nerves and muscles (skeletal and heart) cannot regenerate

Front 10

When resolution is not possible, what takes place instead?

Back 10

Repair

Front 11

When does repair take place?

Back 11

The damage is extensive
– Infection results in abscess or granuloma formation
– The destroyed tissue cannot regenerate

Front 12

What is when the replacement of destroyed tissue with scar tissue

Back 12

Repair

Front 13

What is scar tissue composed of?

Back 13

collagen

Front 14

What produces collagen?

Back 14

fibroblasts (connective tissue cells)

Front 15

During repair, what proliferate and increase collagen synthesis?

Back 15

fibroblasts

Front 16

What fills the lesion and restores tensile strength (the tissue’s resistance to being torn apart) but cannot carry out the physiologic function of the tissue?

Back 16

Scar tissue

Front 17

T/F If you have a scar, resolution did not happen. It has just been repaired.

Back 17

True

Front 18

Regeneration and repair begin during this, with phagocytes cleaning up the lesion (debridement)

Back 18

Inflammation

Front 19

is the process by which phagocytes clean up debris

Back 19

Debridement

Front 20

occurs when the enzymes of phagocytes dissolving the fibrin clots (scabs)

Back 20

Debridement

Front 21

protein involved in blood clotting
– Forms a "mesh" (plug or clot) over a wound site (in conjunction with platelets)

Back 21

Fibrin

Front 22

T/F A Scab is a dried up fibrin clot.

Back 22

True

Front 23

When does the following occur: The exudate, toxic products and other inflammation substances are drained away
– Both vascular dilation and vascular permeability are reversed

Back 23

After Debridement

Front 24

When does the following occur: The wound fills with inflammatory exudate and fibrin clot
• The exudate includes neutrophils, macrophages, red blood cells, fibrin, dead cells
(bacteria and host)
• Debridement

Back 24

Filling in the wound (fibrin clot), Step 1 of repair

Front 25

When does the following occur: • Epithelial cells proliferate and cover the wound
• Formation of new blood vessels

Back 25

Covering or sealing the wound, Step 2 of repair

Front 26

Which step of repair is Shrinking the wound (contraction)?

Back 26

Step 3

Front 27

What stage is Forming scar tissue (collagen formation)?

Back 27

Stage 4 of repair

Front 28

How many types of wounds are there?

Back 28

Two

Front 29

This type of healing occurs in wounds that heal under conditions of minimal
tissue loss (small wounds, clean incisions- as opposed to blunt force- like
stabbing yourself with a screwdriver)
– Paper cut
– Sutured surgical wound

Back 29

Primary Intention Wounds

Front 30

Primary Intention Wounds heals predominantly by the 1st step (filling- in the wound) because:

Back 30

There is minimal tissue loss and
– Joining of the wound edges requires very little sealing and shrinkage

Front 31

Occurs in open wounds such as pressure sores (decubitus ulcer)
• The healing requires a lot more tissue replacement
• Thus, all stages of healing takes longer: Surgical wounds exhibit all phases of resolution and repair, thus they are a useful model of healing

Back 31

Wounds that heal by Secondary Intention

Front 32

Which step is the inflammatory phase and always happens?

Back 32

Step 1

Front 33

Regardless of the type of intention the initial step of wound healing begins with what?

Back 33

Acute Inflammation

Front 34

This initial step, the inflammatory stage includes:

Back 34

Filling in the wound and Debridement of the wound

Front 35

What process is the following: The wound is initially sealed off by a scab (a blood clot) containing:
• Fibrin (protein mesh) and
• Trapped cells (WBC, RBC, platelets)
– Sealing help unite the wound edges
– For healing to continue, the fibrin clot (scab) must be dissolved (by enzymes) so that it can be replaced by either normal tissue or scar tissue

Back 35

Process 1 of Step 1: Filling in the Wound

Front 36

What process is the following: Debridement is followed by either regeneration or repair
– Macrophages clear away debris and dead cells from the dissolving clot

Back 36

Process 2 of Step 1: Debridement of the wound

Front 37

After the initial step and regardless of the type of intention, resolution and repair occur in two overlapping phases

Back 37

Reconstructive and Maturation

Front 38

Begins 3-4 days after injury and continues up to SEVERAL weeks

Back 38

Reconstructive Phase

Front 39

Consists of filling-in and sealing of the wound

Back 39

Reconstructive Phase

Front 40

Characterized by collagen synthesis & epithelialization
• Collagen synthesis
– Macrophages secrete fibroblast-activating factor, which stimulates fibroblasts to enter the lesion site
– Fibroblasts synthesize and secrete collagen
• Collagen forms scar tissue
• Collagen is the most abundant protein in the body (present in all connective tissue, skin, bones, teeth, blood vessels)
• The scar tissue matures over a period of several months, increasing its strength and ability to resist stress

Back 40

Reconstructive Phase

Front 41

Macrophages secrete other mediators that promote healing by stimulating what?

Back 41

Angiogenesis and Epithelialization

Front 42

formation of new blood vessels
• Vascular endothelial cells form capillary buds grow into the lesion

Back 42

Angiogenesis

Front 43

epithelial cells growth): to form granulation tissue and seal the wound

Back 43

epithelialization

Front 44

Epithelial cells migrate under the scab (clot) and secrete enzymes that break down the scab
– They stop proliferating when they make contact with cells from all sides of the wound
– They remain active and undergo differentiation to form the various layers of the skin
– is faster if the wound is kept moist thus preventing fibrin clot from becoming a scab
(wound treatment with dressing)

Back 44

epithelialization

Front 45

is formed due to both angiogenesis and epithelialization

Back 45

Granulation Tissue

Front 46

grows inward from the healthy connective tissue surrounding the wound

Back 46

Granulation Tissue

Front 47

It is filled with new capillaries and gives the wound a red, granular appearance

Back 47

Granulation Tissue

Front 48

The processes of shrinking of the wound (wound contraction) and collagen deposition continue during the maturation phase
• It is hard to tell where one stage stopped and the next stage begins

Back 48

Granulation Tissue

Front 49

Which step is the maturation phase?

Back 49

Step 3

Front 50

Begins several weeks after injury, continues up to 2 years

Back 50

Maturation Phase

Front 51

Consists of:
1. Wound contraction (shrinkage)
2. Remodeling of the scar

Back 51

Maturation Phase

Front 52

What is the following: Inward movement of the wound’s edge
– Necessary for closure of all wounds, especially those that heal
by secondary intention
– Contraction is noticeable 6-12 days after injury and may amount
to 0.5 mm/day of inward movement
– The cells responsible for wound contraction are myofibroblasts
• Myofibroblasts have features of both smooth muscle cells and fibroblasts
• They possess structures that extend from their plasma membrane,
connect neighboring cells, and pull on them to cause wound contraction

Back 52

Wound contraction (shrinkage)

Front 53

What is the following: Capillaries disappear, leaving an avascular scar
– Excess collagen is removed
– Within 2-3 weeks after maturation begins, the scar tissue gains about 2/3 of its eventual maximum strength
– At best, at the end of healing, repaired tissue regains 80% of its original tensile strength
• Remodeling is characterized by removal of excess collagen and decreasing capillaries

Back 53

Remodeling of the scar

Front 54

the the force separating the wound
– Load applied per unit of cross-section area (kg/cm2)

Back 54

Tensile Load

Front 55

is the resistance of the tissue
– Collagen increases this

Back 55

Tensile Strength

Front 56

Skin achieves its peak of what by about 60 days post injury

Back 56

Tensile Strength

Front 57

T/F Scar tissue strength is 70-80% of normal.

Back 57

True

Front 58

T/F Clinically we are not concerned with breaking strength as that is the force required to bring a wound apart

Back 58

False - we are concerned.

Front 59

How many types of tissue heal differently during the maturation phase?

Back 59

Three

Front 60

Which kinds of cells can perform complete regeneration?

Back 60

epithelial, hepatic, and bone marrow cells can perform complete regeneration (compensatory hyperplasia)

Front 61

Which kinds of cells can form repair?

Back 61

Fibrous connective tissue such as tendons and ligaments can only form repair, but the scar tissue is very similar to the original tissue (collagen fibers)

Front 62

Which kinds of cells can heal without replacement?

Back 62

Heart and skeletal muscles as well as nerve cells heal without replacement; A scar or fibrous tissue fills the damaged area
This scar tissue doesn’t look anything like the original- so you can see it very clearly

Front 63

What kind of healing is the following: Healing requires increased metabolic needs
• Blood supply to the site of the lesion must remain increased for continued oxygen, glucose and protein supply
• Thus, ischemia and poor nutrition interfere with wound healing
• All components of healing require energy and protein synthesis

Back 63

Dysfunctional

Front 64

What conditions might cause dysfunctional healing?

Back 64

Anti-inflammatory steroids, Decreased blood supply, nutritional deficiency, and diabetes mellitus

Front 65

What is the following: • Drugs: anti-inflammatory steroids:
– Prevent macrophages from migrating to the injury site thus inhibit the release of mediators from macrophages, further inhibiting :
• Angiogenesis and epithelialization
• Fibroblast migration into the wound, causing decreased scar tissue formation

Back 65

Drugs causing dysfunctional healing

Front 66

What is the following: it can be due to many things- some of them are:
ischemia, vasoconstriction, hypovolemia- remember, it’s a decrease in blood
volume) or decreased oxygen in the blood (hypoxemia)
• Hypovolemia and vasoconstriction:
– The response to hypovolemia is vasoconstriction
– Vasodilatation is required to bring the inflammatory cells and oxygen to the site of injury

Back 66

Decreased blood supply causing dysfunctional healing

Front 67

What is the following: Optimal nutrition is important during all phases of healing
because metabolic needs are increased
• ATP is needed for chemotaxis, phagocytosis, and protein synthesis
– Protein is absolutely necessary for proper healing (all mediators,
cells, and cell components are made from protein)
– Other nutrients are also important as well

Back 67

Nutritional Deficiency causing dysfunctional healing

Front 68

What is the following: – Persons with diabetes heal poorly, mostly due to infection
– They are at risk for ischemic wounds because of compromised oxygen delivery
• They tend to have small-vessel-diseases that impair their microcirculation
• Their hemoglobin is glycoslylated so it has an increased affinity for oxygen and does not readily release it in the tissue
– Ischemic tissue is susceptible to infection (sepsis)

Back 68

Diabetes Mellitus causing dyfunctional healing

Front 69

What is the following: These conditions may mostly result in insufficient repair during all phases of wound healing
• Infection: wound sepsis
– Infection prolongs inflammation by increasing exudation, fibrin formation, and pus
– Infection prevents complete healing because the pus and fibrin inhibit formation of granulation tissue
– Infection promotes excessive scar formation
• Wound sepsis is treated by:
– Debridement of necrotic tissue (surgery or dressings)
– Wound irrigation
– Antibiotics
Surgical Debridement

Back 69

Infections causing dysfunctional healing

Front 70

What is the following: • Older people are at risk for impaired wound healing due to:
– Chronic illness (diabetes, cardiovascular disease)
– Medications (such as anti-inflammatory steroids)
– Diminished immune functions (increase infections)
• Older people are at risk for sustaining more wounds due to:
– Impaired sensation, balance, and mobility
– Decreased subcutaneous fat Less protection
– Less elastic collagen fibers Less protection
– Atrophied epidermis Less protection

Back 70

Aging causing dysfunctional healing

Front 71

T/F Dysfunctional healing may not occur during any phase of wound-healing.

Back 71

False - it may occur at any phase.

Front 72

Dysfunctional healing may involve:

Back 72

Insufficient repair & Excessive repair

Front 73

What is the following: Continued bleeding during acute inflammation may result in:
• A clot (due to hemorrhage)
– Serves as a mechanical barrier to oxygen
– Increases the amount of space that the granulation tissue must fill
• Accumulation of blood cells prolongs the process of debridement
– Accumulated blood is an excellent culture medium for bacteria and promotes infection

Back 73

Insufficient repair during the inflammatory phase

Front 74

What is the following: Due to excessive amounts of fibrin
– Fibrin has to be reabsorbed or it forms adhesions
– Adhesions are scar tissue that adheres (binds) to surrounding tissues and organs
– When adhesions shrink they distort the affected organ
• Pleural (lung covering) and pericardial (heart covering) tissue may bind to the underlying organs
• Organs may bind together in the abdominal cavity

Back 74

Excessive Repair during the inflammatory phase

Front 75

Dysfunctional healing during the reconstructive phase includes what?

Back 75

Impaired epithelialization or impaired wound contraction

Front 76

What is the following: – Epithelialization is suppressed by:
• Anti-inflammatory steroids
• Hypoxemia
• Ionizing radiation
• Zinc deficiency
– Wound care to promote epithelialization:
1. Dressing
– The ideal dressing absorbs some drainage without being incorporated into the clot or granulation tissue
– Dressings that debrid healthy epithelial cells along with necrotic tissue prolong epithelialization because epithelial cells must migrate across the wound for healing to complete
2. Solutions used to clean and irrigate the cells
– Should not kill the new, fragile epithelial cells
– Normal saline is the best solution (hydrogen peroxide and iodine are too strong)

Back 76

Impaired Epithelialization during the reconstructive phase

Front 77

What is the following: Excessive contraction results in a deformity called contracture, which pulls on the underlying tissue causing dysfunction
– Burns are especially susceptible to contracture development
– To prevent contractures therapists use proper positioning and range-of-motion exercises and doctors may perform surgery

Back 77

Impaired Contraction during the reconstructive phase

Front 78

What is the following: A potential complication in wounds that are sutured is when wound pulls apart at the suture line
– This usually occurs 5-12 days after suturing, when collagen synthesis is at its peak
– It may be due to sepsis or excessive tensile stress

Back 78

Wound disruption during the reconstructive phase

Front 79

What is the following: May occur in the reconstructive phase and/or in the maturation phase
– May be either insufficient production or over-production of collagen

Back 79

Dysfunctional collagen production

Front 80

What is the following:
-Predominantly due to nutritional factors
• Protein, iron, oxygen, calcium, copper and more nutrients are needed for collagen synthesis
• Ascorbic acid (vitamin C) is one of the cofactors required for collagen formation by fibroblasts
– Lack of vitamin C causes scurvy, a disease in which capillary walls break down due to the loss of collagen (the glue that holds
together connective tissue)
– The symptoms of scurvy include internal hemorrhages weakness, joint pain, skin lesions, and loose teeth

Back 80

Impaired Collagen Production

Front 81

What is the following: Hypertrophic scars are:
• Raised scars
• Remain within the original boundaries of the wound
• They tend to regress over time
– Keloid scars are:
• Raised scars
• Extend beyond the original boundaries of the wound, invading the surrounding tissue
• Likely to recur after surgical removal
• Have a familial tendency with greater incidence in blacks than in whites

Back 81

Excessive Collagen Production