Inflammation and Tissue Repair Flashcards
Modalities/Interventions:
- Modify = ? (what )
- Reduce = ? (what )
- Improve = ? (what )
Inflammation and Tissue Repair
Modalities/Interventions:
- Modify healing process
- Reduce adverse effects such as prolonged inflamma
- Improve function and achievement of goals
What are the cardinal signs of inflammation?
(5)
Inflammation and Tissue Repair
(1) Heat
- Calor
- Caused by increased vascularity
(2 ) Redness
- Rubor
- Caused by increased vascularity
(3) Swelling
- Tumor
- Caused by blockage of lymphatic drainage
- Leaking of proteins, fluids that manage inflammation
(4) Pain
- Dolor
- Caused by physical pressure of chemicalirritation
(5) Loss of Function
- Caused by pain and swelling
Describe three phases of tissue inflammation and repair (healing) and their relative time frames
Inflammation and Tissue Repair
Mediators & Response:
- Histamine = ?
- Factor XII/Hagemen factor = ?
- Bradykinin = ?
- Prostaglandins = ?
- Complement fractions = ?
Inflammation and Tissue Repair
Mediators & Response:
(a) Histamine =
- Causes vasodilation, attracts WBCs to site
(b) Factor XII/ Hagemen factor =
- Activates coagulation, causes vasoconstriction
(c) Bradykinin =
- Increase permeability, pain response
(d) Prostaglandins =
- Increase permeability, attracts WBCs to site, NSAID inhibit synthesis of prostaglandins
(e) Complement fractions =
- Increase permeability, chemotaxis
Goals of inflammatory response = ?
Inflammation and Tissue Repair
Goals of Inflammatory Response:
- Eliminate pathological or physical insult
- Replace tissue
- Promote regeneration of normal tissue structure
- Restoration of function
Common Causes of Inflammation = ?
Inflammation and Tissue Repair
Common Causes of Inflammation:
- Pathogens (germs) like bacteria, viruses or fungi
- External injuries like scrapes or foreign objects
- Effects of chemicals or radiation
What’s the difference between..
- Tendonitis = ?
- Tendinosis = ?
- Tendinopathy = ?
Inflammation and Tissue Repair
(a) Tendonitis:
- An active inflammation in the tendon most likely from an acuteinjury sprain/strain or significant overuse.
(b) Tendinosis:
- A chronic tendon change due to failed healing or repetitivetrauma increase of immature type III collagen fibersvs they typical mature type I fibers dominate in healthytendon tissue.
- The collagen fibers are no longer aligned andfail to link together.
- No inflammatory markers/factors arepresent.
- Brown and dull vs normal tendons which are whiteandshiny.
(c) Tendinopathy:
- Tendinosis without specific etiology.
What are the five cardinal signs of inflammation = ?
Inflammation and Tissue Repair
Five cardinal signs of inflammation:
(1) Heat:
- Calor
- Caused by increased vascularity
(2) Redness:
- Rubor
- Caused by increased vascularity
(3) Swelling:
- Tumor
- Caused by blockage of lymphatic drainage
- Leaking of proteins, fluids that manage inflammation
(4) Pain:
- Dolor
- Caused by physical pressure of chemicalirritation
(5) Loss of function:
- Caused by pain and swelling
What modalities/interventions do you think of…
- Inflammation phase = ?
- Proliferation phase = ?
- Maturation phase = ?
Inflammation and Tissue Repair
(a) Inflammation phase:
- Immediate protective response
- Attempts to destroy, dilute, or isolate cells/agents at fault
- Cryotherapy (game ready, ice bath, cold packs) and laser therapy designed to treat this stage
(b) Proliferation phase:
- Rebuilds damage structure
- Strengthens the wound
- Thermal Ultrasound is example of PT modality at this stage
(c) Maturation phase:
- Modifies the scar tissue into its mature form
- Scar tissue release, traction are example of PT modality designed to treat this stage.
Discussion:
(1) Differentiate between tendonitis, tendinosis, tendinopathy= ?
(2) What is the purpose of inflammation = ?
(3) What are the five cardinal signs of inflammation = ?
(4) What are the three stages of inflammation and repair = ?
(5) Why can modalities be important in the healing process = ?
Inflammation and Tissue Repair
Discussion:
(1) Differentiate between tendonitis, tendinosis, tendinopathy:
(2) What is the purpose of inflammation:
(3) What are the 5 cardinal signs of inflammation:
(4) What are the 3 stages of inflammation and repair:
(5) Why can modalities be important in the healing process:
Inflammatory Phase (Days 1-6):
- What happens = ?
Inflammation and Tissue Repair
(#1) Inflammatory Phase (Days 1-6):
- Pathological or Physical Insult
- Inflammation Phase
- Vasoconstriction
- Vasodilation
- Clot Formation
- Phagocytosis
Inflammatory Phase (Days 1-6):
Vascular Response:
- What two things happen right away = ?
Inflammation and Tissue Repair
Inflammatory Phase (Days 1-6):
(-) Vascular Response:
- Trauma or injury may cause hemorrhage, fluid loss, cell injury, exposure to foreign material, including bacteria.
- Two things happen right away: vasoconstriction then vasodilation .
- Extravasation - Migration of neutrophils to injured area
(-) Hemostatic Response:
- Immediately controls blood loss
- Platelets bind to exposed collagen
- Releases fibrin
- Stimulates clotting
(-) Cellular Response: Cells released =
- Erythrocytes (RBCs): Primarily oxygen transport to area.
- Platelets: Clotting (Hemostatic Response)
- Leukocytes (WBCs): Help to clear the injured site of debris and microorganisms.
(-) Immune Response:
- Antibodies: Bind foreign antigens, inhibits their function.
- Antibody release activates one of the complement system pathways (Membrane Attack Complex (MAC))
Vascular Response
- Vasoconstriction, response is mediated by = ?
- Vasodilation, results in = ?
Inflammation and Tissue Repair
(a.1) Trauma or injury may cause:
- Hemorrhage, fluid loss, cell injury, exposure to foreign material, including bacteria
- Two things happen right away: vasoconstriction then vasodilation
(a.2) Vasoconstriction
- Immediate constriction of blood vessels to minimize blood loss
- 5-10 minutes
- Response is mediated by norepinephrine (neurotransmitter)
(a.3) Vasodilation:
- Increases cellular permeability
- Initiated by mediators
- Lasts up to 1 hour after tissue damage
Vascular Response
- What happens = ?
- Describe the sequence of events = ?
Inflammation and Tissue Repair
Vascular Response
(a) What happens?
- Neutrophils are initial WBC to site of injury
(b) Sequence of Events (Extravasation) = Migration of neutrophils to injured area
- Margination – neutrophils line the margins of the vessels
- Pavementing– cells accumulate and lay down in layers
- Diapedesis – neutrophils squeeze through the vessel walls
- Emigration – in response to chemo-attractant, the white blood cells move to the perivascular tissues
Vascular Response
- Transudate = ?
- Exudate = ?
- Pus = ?
- Abscess = ?
Inflammation and Tissue Repair
Vascular Response
(-) Edema to Swelling
(-) Accumulation of excess fluid in extravascular space and interstitial tissues
(-) Results from
- Increased capillary hydrostatic pressure
- Increased interstitial osmotic pressure
- Increased permeability
- Overwhelmed lymphatic system
(-) Fluid Release
- Transudate - light, watery as there’s minimal cells and protein
- Exudate - thicker, cloudy with increased debris and lipids
- Pus - WBC, digestion products, exudate, bacteria if infection is present
- Abscess - collection of pus in a tissue, organ
During the hemostatic response, how is blood loss controlled = ?
Inflammation and Tissue Repair
Hemostatic Response: Immediately controls blood loss
(a) Platelets bind to exposed collagen
- Releases fibrin
- Stimulates clotting
(b) Platelets release a regulatory protein, platelet-derived growth factor (PDGF) that is chemotactic and mitogenic.
(c) Platelets have a role in hemostasis and contribute to fibrin deposition, fibroplasia, and angiogenesis.
Hemostatic Response
Fibrin and fibronectin form cross-links with collagen to create fibrin lattice that provides a temporary = ?
Inflammation and Tissue Repair
Hemostatic Response:
(a) Fibrin and fibronectin form cross-links with collagen to create fibrin lattice
- Provides temporary plug in blood and lymph vessels – limit local hemorrhage and fluid drainage.
- Seals off damaged vessels and confines inflammatory reaction
- Fibrin lattice
- Only source of tensile strength
- Do not reopen until later in the healing process
Cellular Response
Leukocytes cells released = ?
Inflammation and Tissue Repair
Cellular Response:
(a) Leukocytes (WBCs)Cells released:
(I) Erythrocytes (RBCs):
- Primarily oxygen transport to area
- Hematoma - Accumulation of blood in tissue or organ
- Hemarthrosis - bloody fluid in joint
(II) Platelets
- Clotting (Hemostatic Response)
- Helpto clear the injured site of debris andmicroorganisms
- Migrateinto injury site within hours
- Supply antibodies to mediate immune response
What role does Polymorphonucleocytes and Mononuclear cells play in the cellular response = ?
Inflammation and Tissue Repair
Cellular Response - Leukocytes:
Polymorphonucleocytes (PMNs)
(1) Neutrophils:
- Early stages, rid site of bacteria and debris
- Phagocytosis
- Release chemotaxis agents to bring other WBC
(2) Basophils
- Release histamine, increase permeability
(3) Eosinophils
- Help with phagocytosis
Mononuclear cells
(1) Monocytesto Macrophages
- Essential for wound healing
- Assist with phagocytosis
- Release byproducts that assist with healing and signal for more help if needed
- Attract fibroblasts
- More effective when O2 present
Immune Response
What do antibodies do = ?
Inflammation and Tissue Repair
Immune Response:
(a) Antibodies
- Bind foreign antigens
- Inhibits their function
- Easier to ingest through phagocytosis
(b) Antibody release activates one of the complement system pathways
- Membrane Attack Complex (MAC)
- Increased vascular permeability
- Increased phagocytosis
- Chemotactic stimuli for leukocytes
Summary of Inflammatory Phase = ?
Inflammation and Tissue Repair
(I) Days: 1-6
(II) Vascular Response
- Vasoconstriction slows blood flow
- Vasodilation increases blood flow
- Increased permeability allows for extravasation
(III) Hemostatic Response
- Clotting and fibrin lattice
(IV) Cellular Response
- WBC response to injury
- Phagocytosis
(V) Immune Response
- Activates complement systems
- Vascular permeability
- Stimulates phagocytosis
- Chemotactic stimuli for leukocytes
Proliferative Phase (Days 3-20)
Inflammation and Tissue Repair
Proliferative Phase (Days 3-20):
(1) Proliferation = Phase involves the rapid growth and reproduction of cells to replace those lost during injury.
- It includes the migration of cells such as fibroblasts, endothelial cells, and epithelial cells to the wound site.
(2) Epitheliazation = Process of forming new epithelial tissue over the wound surface.
- Epithelial cells migrate from the wound edges and multiply to cover the wound, forming a protective barrier against pathogens and fluid loss.
(3) Fibroplasia/Collagen production = Formation of fibrous tissue by fibroblasts, leading to the production and deposition of collagen.
- Collagen provides structural support and strength to the wound, helping to restore its integrity.
(4) Wound contracture = Gradual shrinking and tightening of the wound edges, mediated by myofibroblasts, which pull the edges of the wound together.
- Wound contracture reduces the size of the wound and helps in wound closure.
(5) Neovascularization = Also known as angiogenesis, this process involves the formation of new blood vessels from existing ones.
- Neovascularization is crucial for delivering oxygen and nutrients to the healing wound and removing waste products, facilitating tissue repair and regeneration.
“Re-establishment of the epidermis” = ?
Inflammation and Tissue Repair
Epithelialization:
(a) “Reestablishment of the epidermis”
(b) Covering the surface of the wound and closing the defect
- Uninjured epithelial cells migrate over the injured area pulling intact epidermis over wound edge.
- Not strong enough for demands of tissue?
- Wound too deep?
- This stage will occur after collagen production and neovascularization
Main structural protien in the extracellular space for various connective tissues = ?
Inflammation and Tissue Repair
Collagen: Greek root word for glue
- Main structuralproteinin theextracellular spacefor variousconnective tissuesin animal bodies.
- The most abundant protein in mammals,making up from 25-35% of the whole-body protein content.
2 major roles in wound healing
- Provides increased strength
- Facilitates movement of other cells
- Endothelial cells
- Macrophages
Steps in collagen production = ?
Inflammation and Tissue Repair
Collagen Production:
(a) Also known as Fibroplasia
- Takes place in connective tissue
- Migrate in response to chemotactic influences
- Need oxygen, ascorbic acid, other cofactors (zinc, iron, manganese, copper)
(b) Steps =
- Fibroblasts synthesize procollagen
- Cleavage by collagenase to form tropocollagen
- Tropocollagen chains coil together to form collagen microfibrils
- Collagen filaments
- Crosslinking to increase tensile strength
Contraction begins (?) days after injury.
Inflammation and Tissue Repair
Wound Contraction:
(a) Contraction begins 5 days after injury, peaks at 2 weeks
(b) Myofibroblasts attach to the margins of intact skin and pull the entire epithelial layer inward
- Possess contractile properties of smooth muscle
(c) “ Picture frame theory ” – ring of myofibroblasts moves inward from wound margin
(d) Different from epithelialization
- Epithelialization : covers the wound surface
- Wound Contraction : pulls the edges together
Wound Contraction
- Primary intention = ?
- Secondary intention = ?
Inflammation and Tissue Repair
Wound Contraction:
(a) Healing by primary intention (primary union)
- When the initial injury causes minimal tissue loss and minimal bacterial contamination, the wound can be closed with sutures
- Thus, heals without wound contraction
(b) Healing by secondary intention (indirect union)
- When the initial injury causes loss of tissue or bacterial contamination, the wound must first undergo the process of wound contraction
Wound Contraction
- Linear wounds = ?
- Square or rectangular wounds = ?
- Circular wounds = ?
- Uncontrolled wound contraction = ?
Inflammation and Tissue Repair
Wound Contraction:
(a) Linear wounds
- With one narrow dimension contract rapidly
(b) Square or rectangular wounds
- With no edges close to each other, progress at a moderate pace
(c) Circular wounds
- Contract slowest
(d) Uncontrolled wound contraction
- Possible contracture formation
What happens during neovascularization = ?
Inflammation and Tissue Repair
Neovascularization:
(a) Development of a new blood supply – the result of angiogenesis
(b) Macrophages may be responsible for signaling neovascularization to start through the release of growth factors
(c) Vessels in wound periphery develop small buds
(d) Eventually capillary loops cease to function and retract –resulting in whitish appearance of scar
(e) Exercise and mobility can increase blood supply and angiogenesis.
Summary of Proliferative Phase = ?
Inflammation and Tissue Repair
Summary of Proliferative Phase (Days: 3-20):
(I) Epithelialization
- Covers wound
(II) Collagen production
- Improves tensile strength of wound
(III) Wound Contracture
- Primary or secondary intention
- Pulls edges together
(IV) Neovascularization
- New blood supply to area
3 Maturation Phase (Day 9 on…)
Inflammation and Tissue Repair
#3 Maturation Phase (Day 9 on…):
- Maturation Phase =
- Collagen synthesis/lysis balance →
- Collagen Fiber orientation →
- Healed orientation →
- Healed injury
Maturation Phase
Goal = ?
Inflammation and Tissue Repair
Maturation Phase:
Goal = Restoration of prior tissue function
Key Takeaways:
- Leukocytes begin to decrease due to reduced inflammatory response
- Water content declinesdue to reduced inflammatory response
- Collagen matures
What determines the rate of maturation and the final characteristics of the scar?
- Fiber orientation
- Balance of collagen synthesis and lysis
- Can last > 1 year
Collagen Types:
- Type I = ?
- Type II = ?
- Type III = ?
Inflammation and Tissue Repair
Collagen Types:
(a) 27 types of collagen have been identified
- Type I found in bone, skin, tendon and is predominant in mature scars
- Type II is the major collagen in cartilage
- Type III is found in skin, GI tract, uterus, and blood vessels
(b) Keloid scars
- Result of excessive collagen deposition caused by inhibition of lysis.
- Production is greater than rate of lysis
- Extend beyond original boundaries
- Hypertrophic Scars
- Raised, in margins of wound
Orientation of Collagen Fibers
- Induction Theory = ?
- Tension Theory = ?
Inflammation and Tissue Repair
Orientation of Collagen Fibers:
(a) Induction Theory:
- Scar attempts to mimic the characteristics of the tissue it is healing
- - Dense tissue = dense, highly cross-linked tissue
- - Pliable tissues = loose, less cross-linked
- Early movement is beneficial
(b) Tension Theory:
- Internal and external stresses placed during maturation phase determine final tissue structure.
- Length and mobility of area can be modified by application of stress during appropriate phase of healing.
- Scars need low-load, long-duration stretching during appropriate phases for permanent change to occur
What are the potential outcomes of the acute Inflammatory processes = ?
Inflammation and Tissue Repair
Potential outcomes of Acute Inflammatory processes =
- Replacement of the injured tissue with like tissue
- Healing by scar formation
- Formation of an abscess
- Progression to chronic inflammation
Chronic Inflammation
- Two types = ?
- Results = ?
Inflammation and Tissue Repair
Chronic Inflammation:
(a) Simultaneous progression of active inflammation, tissue destruction, and healing
(b) Inflammation timelines
- Normal Acute inflammatory process: no more than 2 weeks
- Subacute: more than 4 weeks
- Chronic Inflammation: months to years
(c) Two types
- Follows acute inflammation – due to continued presence of injurious agent (i.e. continued microtrauma)
- Due to immune response (i.e. implant or suture) or the result of autoimmune disease (i.e. RA)
(d) Results
(1) Continued leukocyte activity =
- Signifies the prolonged presence and function of white blood cells at the site of tissue injury or infection, indicating ongoing immune response and tissue repair processes.
(2) Increased fibroblast proliferation =
- A heightened rate of growth and division of fibroblast cells, which are responsible for producing collagen and other extracellular matrix components essential for wound healing and tissue repair processes.
(3) Collagen production
(4) Loss of function
Factors that Affect the Healing Process
- Local factors = ?
- External factors = ?
- Systemic factors = ?
Inflammation and Tissue Repair
Factors that Affect the Healing Process:
(a) Local factors
- Type, size, location of injury
- Infection
- Vascular supply
(b) External forces – the application of physical agents
Movement/excessive pressure
- Retained foreign body
- Temperature deviation
- Topical medications
- Electromagnetic energy
(c) Systemic Factors
- Age
- Disease or infection
- Medications
- Nutrition
- Metabolic status
- Hormones
- Temperature/Fever
- Oxygen
NSAIDS & Steroids
Patients that take NSAIDs after any workout are actually impairing = ?
Inflammation and Tissue Repair
NSAIDS and Steroids:
- Patients that take NSAIDs after any workout are actually impairing their own collagen repair/regeneration.
- They have high rates of gastric ulcerations and gastric bleeds.
- Corticosteroids (Steroid dose packs, dexamethasone, etc.) are our most powerful anti-inflammatory agents but they will also impair healing.
- When corticosteroids are taken for long periods of time for RA, autoimmune condition will impair the immune system and cause osteoporosis.
Steroids or NSAIDS?
KNOW YOUR SCOPE = ?
Inflammation and Tissue Repair
REMINDER – KNOW YOUR SCOPE
- PT does not prescribe any medications
- Good to know when asked by patients to educate
- Refer to PCP for specific medication questions
Healing Properties of MSK Tissues
Why does cartilage have a limited ability to heal = ?
Inflammation and Tissue Repair
Healing Properties of Specific Musculoskeletal Tissues -Cartilage:
(a) Limited ability to heal
- no lymphatics, blood vessels, or nerves
(b) Injury to cartilage alone
- No clot formation, no recruitment of neutrophils or macrophages
(c) Injury to articular cartilage and subchondral bone
- EX : Complex knee ACL injuries, Osteochondritis Dissecans
- Vascularization of subchondral bone allows formation of fibrin-fibronectin gel
- Inflammatory cells, formation of granulation tissue
- Granulation tissue - chondrocytes after 2 weeks - normal appearing cartilage after 2 months
Healing Properties MSK Tissues
What does the repair potential of tendon depend on = ?
Inflammation and Tissue Repair
Healing Properties of Specific Musculoskeletal Tissues -Tendons and ligaments:
(-) Inflammation during first 72 hours
(-) Collagen synthesis within week 1
(-) What is the repair potential of tendon?
- Depends on the type of tendon, tension of tendon
- Damage to tendon sheath
- Vascular supply
- Duration of immobilization
Ligament
Healing influenced by = ?
Inflammation and Tissue Repair
Ligament - Healing influenced by:
- Type of ligament
- Size of defect
- Amount of loading applied
- Early controlled loading promotes healing
- Injuries to capsular & extracapsular ligaments generally have adequate repair response (i.e. MCL)
- Injuries to intracapsular ligaments often DO NOT (i.e. ACL)
Tendon/Ligaments - Clinical Pearl = ?
Inflammation and Tissue Repair
Tendon/Ligaments - Clinical Pearl:
Healing Properties MSK Tissues
TRUE or FALSE:
- Muscle cells cannot proliferate = ?
Inflammation and Tissue Repair
Healing Properties of Specific Musculoskeletal Tissues -Skeletal Muscle:
(-) Injury by blunt trauma, violent contraction or excessive stretch, muscle wasting diseases.
(-) Muscle cells CANNOT proliferate
(-) Stem cells can differentiate to form new skeletal muscle
Notes:
- Documented in biopsy specimens from patients with muscular dystrophy and polymyositis.
- Skeletal muscle regeneration in humans after trauma has not been documented.
- Myositis ossificans may develop after a severe contusion
Healing Properties of MSK Tissues - Bone
Four histologically distinct stages = ?
Inflammation and Tissue Repair
Healing Properties of Specific Musculoskeletal Tissues - Bone:
(-) Two mechanisms of healing
- Primary Healing = Occurs with rigid internal fixation
- Secondary Healing = Occurs without fixation
(-) Four histologically distinct stages
(1) Inflammation = Begins shortly after impact, lasts until some fibrous union at the site.
(2) Soft callus = Marked by increased vascularity and cell proliferation, fibrous and cartilaginous tissue, pain and swelling subside
(3) Hard callus = Starts with stick, hard callus and ends when new bone unites with the fragments, 3 weeks to 4 months
(4) Remodeling = Fibrous bone is converted to lamellar bone, may take several months to several years to complete
