Lecture 2: Inflammation & Tissue Repair Flashcards
1
Q
What is an INJURY?
A
Impaired structure and function
Cells of tissues unable to carry out normal function
2
Q
Causes of injury:
A
Physical agents (burns, radiation) Metabolic processes (ischemic tissue) Biological processes (bacteria, viruses, parasites) Chemical agents (acids, gases)
3
Q
What is trauma?
A
Injury that results from physical force, not the actual force
4
Q
Physical trauma types
A
Macrotrauma & Microtrauma
5
Q
Macrotrauma
A
acute injury affecting multiple tissues
6
Q
Microtrauma
A
overuse injuries, like chronic repetition; low grade stress that doesn’t allow tissues to heal properly
7
Q
Secondary injury
A
May result from a trauma; an injury that may affect other tissues
8
Q
What factors affect the healing process?
A
Health of pt
Severity of injury
Site of injury
Acute vs chronic injury
9
Q
What is the PT goal in the Healing process?
A
Affect the healing process; how well the healing process occurs
Eliminate the cause of the injury
Promote regeneration of normal tissue
10
Q
Phases of Tissue Healing Continuum
A
Inflammation, Proliferation, and Maturation
11
Q
General Purpose of Inflammation Phase
A
prepares wound for healing
12
Q
General Purpose of Proliferation Phase
A
rebuilds damaged tissue & strengthen the wound
13
Q
General Purpose of Maturation Phase
A
modifies scar tissue into its mature form
14
Q
Goals of Inflammatory phases
A
Defend the body against foreign substances
To dispose of dead and dying tissue to allow for repair
15
Q
How can Inflammation phase be harmful?
A
it can become chronic or is directed at wrong tissue
16
Q
Cardinal Signs of the Inflammation Phase
A
Heat Redness Swelling Pain Loss of function
17
Q
Inflammatory phase events
A
Injury Ultrastructural changes Chemical mediation Hemodynamic/Vascular changes Metabolic changes Permeability changes Leukocyte migration Phagocytosis
18
Q
Vasoconstriction
A
Immediate response to stop bleeding
Lasts 5-10 min post-injury
19
Q
Vasodilation
A
Lasts about 1 hour post injury
Increased capillary permeability
Goal: to allow chemical mediators to get to site of injury
20
Q
Chemical Mediators
A
Histamine, Bradykinin, Hageman Factor, Prostaglandins, Complement System
21
Q
Histamine
A
released by mast cells, platelets, basophils
contributes to swelling & chemotaxis (attraction of leukocytes to dead tissue)
22
Q
Bradykinin
A
Biologically active peptides derived from plasma
↑ capillary permeability
23
Q
Hageman Factor
A
Coagulation
Plasma protein → plasmin kallikrein
Activates complement system
24
Q
Prostagladins
A
PGE1: ↑ vascular permeability
PGE2: attracts leukocytes & synergy with mediators
responsible for febrile states
25
Complement System
anaphylatoxins C3a, C4a, C5a
Induce mast cell and basophil degranulation → release histamine, further increase in vascular permeability
Main responsibility of complement system: increase permeability, stimulate phagocytosis, &
Chemotactic stimuli for leukocytes
26
Antihistamine
decreases histamine release to reduce inflammatory response
27
NSAIDs
Inhibit synthesis of prostaglandins, which can inhibit the inflammation phase
28
Role of Neutrophils
Short-lived leukocyte (7 hours) that is the first line of defense against bacteria via extravasation
29
Extravasation
Margination
Pavementing
Diapedesis
Emigration
30
Margination
Where the neutrophil move to the sides of capillaries
31
Pavementing
When the neutrophil is stuck to the side of the capillary vessel
32
Diapedesis
The neutrophil finds a gap in the capillary and squeezes through
33
Emigration
Neutrophils gets through capillary and is in perivascular space
34
Types of edema fluid
Transudate: thin, clear serum
Exudate: Cloudy, serum highly concentrated with protein WBCS, lipids cellular debris
Pus (Suppurative exudate): opaque, exudate highly concentrated in leukocytes, tissue debris, microorganisms; can result in abscess
35
Cells responsible for clot formation
Platelets
36
What do platelets do to form a clot?
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Bind to collagen, releasing fibrin→ stimulates clotting
Released PDGF (platelet derived growth factor)→ stimulates cell growth and division
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37
When does clot formation begin?
around 12 hours and completed by 48 hours
38
Macrophages
Most important cell in inflammatory phase
| Produce chemicals and enzymes → removal of tissue and bacteria
39
Immune Response Order
Macrophages → T-lymphocytes → B cells → Plasma cells → antibodies bind to antigens → Complement system
*Macrophages present foreign antigens to T lymphocytes to activate them which activate B cells, causing them to evolve into plasma cells, which make antibodies that specifically bind foreign antigens
40
Types of activation of the Complement system
Classical activation: antibody-antigen association
| Alternative activation: cellular or microbial substances
41
Inflammation Phase occurs during what days of injury healing process
Days 1-6
42
Proliferation Phase occurs during what days of injury healing process
Days 3-20
43
Goal of Proliferative Phase
Cover and strengthen the wound
44
Phases of Proliferation
Epithelialization
Collagen production
Wound contraction
Neovascularization
45
Epithelialization
Reestablishment of the epidermis (if injury is external)
Superficial vs deep wounds (superficial will occur faster)
Protective barrier
↓ fluid and electrolyte loss
↓ infection
Insufficient strength
46
Signs & Symptoms of Proliferation Phase
Scars are red and swollen (increased vascularity)
Tenderness to tension or pressure
decreasing signs & symptoms from inflammation phase
47
Collagen Production Stage
Fibroblasts make collagen and produce hyaluronic acid
Collagen: Connective tissue protein
provides increased strength (still poor overall) and facilitates movement of other cells
48
Granulation Tissue contents:
Newly formed capillaries
Fibroblasts/myofibroblasts
Collagen
*Decreases fibrin cloth and is mediated by chemotatic factors to increase fibroblast activity
49
Type III Collagen
thin, weak-structured collagen, inconsistent organization
50
Type I Collagen
mature and stronger than type III (replaces it ~day 12)
By day 21: collagen production maximal but strength ~20%
By 6 weeks: 80% of its long-term strength is present
51
Excessive Collagen production can lead to...
excessive scar tissue
52
Role of Hyaluronic Acid
Glycosaminoglycan (GAG) produced by fibroblasts
Draws H2O into area, inc amount of intracellular matrix and facilitates cellular migration
collagen + hyaluronic acid = scar architecture
53
Myofibroblasts
cells similar to fibroblasts that have contractile properties of smooth muscles
54
Wound Contraction
Pulls the edges of the injured sit together
| begins about day 5 and peaks about 2 weeks
55
“Picture frame” theory
the ring of myofibroblasts moves inward from the wound margin
linear wounds with one narrow dimension heal rapidly; square/rectangular wounds progress at moderate pace and circular wounds contract most slowly
56
Contractures
permanent shortening of scar tissue resulting in deformity
57
Wound healing categories:
Primary Intention
Secondary Intention
Delayed Primary Intention
58
Primary intention (primary union):
Sutures
| Minimal loss of tissue and minimal bacteria
59
Secondary intention (indirect union)
Significant loss of tissue or bacterial contamination
| Wound edges are not approximated
60
Delayed primary intension
Delayed approximation with sutures or skin grafts
61
Neovascularization
Angiogenesis
Supply O2 and nutrients to injured and healing tissue
Signaled by macrophages
Immobilization helps protect vessels
62
Angiogenesis
*growth of new blood vessels
New vascular network
Anastomosis of preexisting vessels
Coupling of vessels in injured area
63
Goals of Maturation Phase
Restore prior function of injured tissue
Long term process
Scar whiter in appearance (because less blood flow)
64
Time line for Maturation Phase
Day 9+
65
Maturation Phase Features
↓ fibroblasts, macrophages, myofibroblasts, and capillaries; ↓ water content
Collagen matures, vascularity decreases
Realignment/remodeling of collagen fibers
Rate of maturation and scar characteristics
66
Collagen Synthesis/Lysis
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Type 1 (bone, skin, tendon, scars)
Tensile strength ↑ faster than mass
Keloid/hypertrophic scar (too much scar tissue)
May last 12-24 months post injury
Redness= remodeling
Scars are inelastic
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67
Induction Theory
scar attempts to mimic the characteristics of tissue its healing
*Dense tissue has preferential status
68
Tension Theory
internal and external stresses placed on the injured area during maturation phase determine final tissue structure
* Phase of repair
* Nature of applied force
* Low-load, long duration stretch in correct phase for permanent changes to occur
69
Chronic Inflammation
Inflammatory response unable to eliminate cause of injury and restore normal function
Simultaneous progression of active inflammation, tissue destruction and healing
Macrophages accumulate, less stress or overuse keeps process going
70
Causes of chronic inflammation
Following acute inflammation due to persistence of injury or interference in healing process
Immune response or autoimmune disease
71
Acute inflammation phase
no longer than 2 weeks
72
Subacute inflammation phase
4 weeks +
73
chronic inflammation phase
months to years
74
cellular components in chronic inflammation
Lymphocytes, macrophages, monocytes, eosinophils
Increased fibroblast proliferation → collagen production → increased scar tissue and adhesion formation → loss of function
75
Local factors affecting healing process
Type, size, location
Infection
Vascular supply
76
External factors affecting healing process
Physical agents used to modify the healing process; thermal, mechanical, electromagnetic
Movement: immobilization vs CPM
77
Systemic factors affecting the healing process
Age
Disease
Medications
Nutrition
78
Cartilage healing
Lacks lymphatics, blood vessels, and nerves
Results in bad healing
Cartilage and subchondral tissue
79
Tendon healing
1st 3-4 days: inflammation; day 7-8: collagen synthesis, day 14: fibroblasts
Fibroplasia: intrinsic and extrinsic
Cell and collagen orientation
Synovial sheath injury may affect rehab by creating adhesions
Mobilization: active after 3 weeks
80
Ligament healing
Type, size of defect, amount of applied load
Intracapsular (less vascularity) < extracapsular/capsular
Stabilization vs early controlled loading
Mature repair still 30-50% weaker
81
Skeletal muscle healing
CANNOT proliferate
Satellite cells proliferate and differentiate to form new skeletal muscle cells
Myositis ossificans: calcified hematoma
82
Bone healing
Heals itself with like tissue
83
Primary vs secondary healing in Bone
Primary: bone has to be approximated with hardware
Secondary: bone is not displaced so it doesn’t need to be realigned
84
Stages in Bone healing
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Impaction
Induction
Inflammation
Soft Callus
Hard Callus
Remodeling
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85
Impaction
dissipation of energy from an insult; proportional to energy applied; inversely to volume of the bone: small fx: force is large or bone is small
86
Induction
osteogneic cells are activated
87
Soft callus
begins when pain and swelling decrease
88
Factors the impeded Healing
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Extent of injury
Edema
Hemorrhage
Poor vascularity
Separation of tissue
Muscle spasm
Atrophy
Corticosteroids
Keloids
Infection
Humidity, climate, oxygen tension
Health, age, nutrition
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