Inflammation and Tissue Repair Flashcards

Question

Steps in collagen production = **?** ## Footnote *Inflammation and Tissue Repair*

Answer 1

**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

Answer 2

**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

Answer 3

**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

Answer 4

**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

Answer 5

**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 .

Answer 6

**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

Answer 7

**#3 Maturation Phase** (Day 9 on…): * Maturation Phase = * Collagen synthesis/lysis balance → * Collagen Fiber orientation → * Healed orientation → * Healed injury

Answer 8

**Maturation Phase**: **Goal** = Restoration of prior tissue function **Key Takeaways**: * Leukocytes begin to decrease due to reduced inflammatory response * Water content declines due 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

Answer 9

**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

Answer 10

**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

Answer 11

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

Answer 12

**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**

Answer 13

**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

Answer 14

**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.

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

**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)

Answer 19

**Tendon/Ligaments** - Clinical Pearl:

Answer 20

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

Answer 21

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

Answer 22

**Terms to Know**: (a) **Vasoconstriction**: * Narrowing of blood vessels, which reduces blood flow to a particular area. * Vasoconstriction can help to reduce inflammation and swelling in skin conditions like eczema and psoriasis, where excessive blood flow to the skin contributes to symptoms. (b) **Vasodilation**: * Widening of blood vessels, leading to increased blood flow to an area. * Vasodilation can occur in response to inflammation or injury, resulting in redness, warmth, and swelling. (c) **Neutrophils**: * Type of white blood cell that plays a key role in the body's immune response. * They are among the first responders to sites of infection or inflammation, where they help to combat pathogens and clear away debris. * Neutrophils are involved in the inflammatory process (d) **Macrophages**: * Type of white blood cell involved in the immune response. * They play a role in phagocytosis, the process of engulfing and digesting foreign particles, dead cells, and debris. (e) **Phagocytosis**: * The process by which cells, such as neutrophils and macrophages, engulf and digest foreign particles, bacteria, and damaged cells. * Phagocytosis is essential for clearing away debris and pathogens, contributing to the body's defense against infection and promoting tissue repair. (f) **Edema**: * Swelling caused by the accumulation of fluid in tissues. (g) **Collagen**: * A structural protein found in the skin, tendons, ligaments, and other connective tissues. * It provides strength and support to the skin, helping to maintain its structure and elasticity. (h) **Fibroblasts/Fibrin**: * Cells found in connective tissue that produce collagen, as well as other proteins and fibers that make up the extracellular matrix. * Fibrin is a fibrous protein involved in blood clot formation and wound healing. (i) **Extravasation**: * Extravasation refers to the leakage of fluid, cells, or proteins from blood vessels into surrounding tissues. * It can occur as a result of inflammation, injury, or underlying vascular problems. (j) **Platelets**: * Also known as thrombocytes, are small cell fragments found in the blood that play a crucial role in blood clotting (hemostasis) and wound healing. * When blood vessels are damaged, platelets adhere to the site of injury, aggregate together, and release various substances that help initiate the clotting process to stop bleeding. (k) **Chemotaxis**: * The process by which cells, such as white blood cells (leukocytes) and immune cells, move in response to chemical signals or gradients in their environment. (l) **Primary Intention**: * A type of wound healing process where the wound edges are closely approximated and held together with sutures, staples, or adhesive strips. * This results in minimal tissue loss and a narrower wound gap. (m) **Secondary Intention**: * A type of wound healing process where the wound is left open to heal naturally without surgical closure. * This occurs when the wound edges cannot be easily approximated due to tissue loss, contamination, or infection. * Secondary intention healing involves the formation of granulation tissue, contraction of the wound edges, and epithelialization to gradually fill in the wound gap and restore tissue integrity.