Cell Injury Mechanisms

• Cell injury can be reversible or irreversible.
• An injury occurs when cells cannot adapt to stress.
• Reversible injuries occur when the stress is small or short enough in duration for the cell to restore homeostasis.
• Irreversible injuries result in cell death (necrosis) due to stress that is larger in magnitude or longer in duration.
• Intracellular proteins denature when cell injury is irreversible.
• Irreversible cell injury causes damage to the cell nucleus and autolysis.
• The cell swells, ruptures releasing its contents into extracellular fluid, and is picked up into the body's circulation.
• Lysosomal enzymes released by the damaged cell can harm surrounding healthy cells.
• Irreversible cell injury is synonymous with cell death.
• Reversible cell injury begins with an increase in intracellular ions when a cell is exposed to certain agents.
• Influx of ions causes interstitial fluids from the extracellular space to merge into the cytosol and cell organs.
• The cell volume increases during cell injury.
• The cell membrane begins to bleb during cell injury.
• Organelles swell when a cell is injured.
• Ischemia means blood flow is insufficient or absent, resulting in hypoxia or anoxia, thus a cause for cell injury.
• Causes of ischemia include circulatory, metabolism, inadequate respiratory transport, and inadequate cardiovascular transport.
• Cells swell and their function is compromised due to loss of aerobic metabolism and reduced ATP synthesis.
• Intracellular accumulation of ions and fluids impacts cell function.
• Infections are causes of cell injury, including bacterial, viral, immune reactions (hypersensitivities/autoimmune disorders).
• Bacteria can penetrate the body and invade the host structures.
• The body's first defense line includes the skin or mucosal membranes.
• An inflammatory response occurs when bacteria have invaded, resulting in cell injury/death.
• Bacteria produce endotoxins that induce the synthesis of cytokines like tumor necrosis factor and interleukins, which are responsible for the systemic manifestations of sepsis.
• Exotoxins damage the host cells directly or disrupt normal processes.
• Viral infections have a direct or indirect effect depending on whether they are RNA or DNA viruses.
• RNA viruses have cytopathic effects on the cell, while DNA viruses signal the cell to be destroyed.
• Chemical factors that cause cell injury include carbon monoxide, ammonia, heavy metals (mercury/aluminum), alkylating agents, and free radicals.
• Carbon monoxide and ammonia are the cause of injuries and death.
• Free radical formation, an unstable byproduct of oxidation, destroys cell membranes and is associated with cancer, atherosclerosis, Alzheimer's, and Parkinson's.
• Physical factors that cause cell injury include blunt trauma, temperature extremes (hypothermia/hyperthermia), radiation, and electricity.
• Mechanical factors depend on characteristics of the load and the tissue tolerance and can lead to damage.
• Nutritional causes of cell injury include Vitamin B12 deficiency (neuropathy), calcium deficiency (poor bone quality), and protein malnutrition (weight loss, edema).
• Psychosocial factors such as fear, tension, anxiety, depression and isolation can impact activity and participation levels, influencing thresholds for tissue adaptation and injury.
• Clinical manifestations of inflammation include redness, swelling, increased temperature, pain, and decreased function.
• Acute inflammation typically subsides when the agent is resolved, and structure/function remains intact.
• Examples of acute inflammation are blisters, cuts, and scratches; it can also be linked to pathologies (atherosclerosis, diabetes, and obesity).
• Local signs and symptoms of inflammation are known as cardinal signs.
• Rubor (redness) comes from vasodilation due to increased blood flow from histamine and prostaglandins.
• Increased vascular permeability causes protein and cellular components to seep out of vessels into the injured area, creating exudate and edema with Rubor.
• Calor is heat due to the increased blood flow from the body's core, creating palpable heat on the surface of the tissue
• Tumor is swelling due to the capillary fluid shift mechanism, increasing permeability and causing protein and water movement from circulation into interstitial spaces.
• Dolor is pain with two classifications: mechanical (swelling/edema causes pressure) and biochemical (inflammatory mediators irritate nerve endings).
• Examples of biochemical pain mediators include substance P, ions, prostaglandins, and bradykinin.
• Necrosis is the end point of a pathological and irreversible process.
• Apoptosis is programmed, genetically mediated cell death without activation or trigger, where cells shrink, are recycled, or absorbed by phagocytes.
• Necrotic tissue can be yellow, soft, granular with a cheesy appearance due to released lipids, due to Mycobacterium tuberculosis.
• Lipases breaking down lipids can combine with calcium, magnesium, and sodium ions to create soaps via saponification.
• Necrotic tissue may contain opaque and chalk-like substances.

Cellular Adaptations After Injury

• Adaptations can occur within cells, tissues, and organs.
• Adaptations occur when injury is not immediately lethal/chronic.
• Adaptations enable cells to function in an altered environment and avoid injury.
• Adaptation is cellular response to stress/demand that helps to function.
• Atrophy is a reduction in cell or tissue/organ size, for example: bone loss, muscle wasting, and aging-related brain cell loss.
• Hypertrophy is the increased size of the cell tissue or organ.
• Hyperplasia is an increase in the number of cells, like the thickening of the endometrium during the menstrual cycle or callus formation under mechanical pressure.
• Metaplasia is a change in cell morphology or conversion of one cell type to another due to persistent stimulus, exemplified by the replacement of ciliated pseudostratified columnar cells with stratified squamous epithelial cells in the respiratory system of a chronic smoker.
• Dysplasia occurs when sublethal stress remains over time, altering cell morphology/histology, increasing cell number, and losing histological organization.
• Dysplasia is considered preneoplastic or pre-cancerous.
• In acute inflammation, exudation of fluid and plasma proteins and migration of leukocytes (primarily neutrophils) characterize tissue response.
• Causes and mechanisms of acute inflammation include: infection, immune reaction, foreign bodies, and noxious substances.
• In chronic inflammation, the inflammation persists causing repeated acute cases.
• Lymphocytes and macrophages are the predominant cells involved in chronic inflammation.
• Fluid seeps into the affected area due vascular reaction in chronic inflammation.
• The region experiences proliferation of blood vessels with lymphocytes and macrophages invading the region.
• Effusion generally refers to the escape of fluid which encompasses both transudate and exudate.
• Transudate occurs with intact capillary vessels, imbalances and is not associated with inflammation, so fluid moves from the blood vessel to the tissues
• Transudate contains few plasma proteins or leukocytes and is described as clear fluid.
• Primary reasons for transudate are an increase in hydrostatic pressure or a decrease in colloidal osmotic pressure which resists fluid reabsorption.
• Transudate can be seen in right-sided congestive heart failure (fluid accumulation in extremities) and left-sided CHF (pulmonary edema).
• Exudate has higher protein and leukocyte content and is the result of inflammation.
• Vasodilation and increased vascular permeability mean the fluid will be higher in plasma proteins and leukocytes
• Inflammatory exudates are described based on color, viscosity, odor, amount, and type of cells present: sanguineous, serous, serosanguinous, catarrhal, and purulent.
• Sanguineous exudate is bloody drainage, e.g., a hematoma.
• Serous exudate is thin, clear, watery fluid with plasma proteins and immunoglobulins, common in early inflammatory responses, e.g., a fluid-filled blister.
• Serosanguinous exudate is blood-tinged serous fluid.
• Cattarhal exudate is a thin, clear, mucus-like liquid seen within mucous membranes, e.g., with an upper respiratory infection.
• Purulent exudate is viscous, cloudy, pussy, filled with leukocytes/debris, e.g., abscesses, which can evolve into further complications.
• Systemic inflammation involves the entire body and is called septicemia, caused by bacteria, viruses, or toxins in the blood (blood poisoning/sepsis).
• Septicemia is often confused with bacteremia (presence of bacteria in blood).
• Individuals with septicemia report malaise, nausea, appetite loss, and fatigue and require medical intervention as a medical emergency.
• Systemic inflammation causes fever, chills, sweats, and discomfort, leading to decreased blood pressure and rapid breathing (above 22rpm).
• A cascade effect from damage triggers releases of leukocytes and cytokines, mediating fever, tumor necrosis factor, and interleukin-1.
• Temperature is increased by stimulating the hypothalamus to upregulate.
• Temperatures above 108°F can cause brain damage.

Role of PT and Tissue Healing

• Physical therapists address pathologies from the perspective of movement and well-being.
• Apply the International Classification Framework (ICF) model for a comprehensive perspective.
• Diseases or conditions effects the individual's functional abilities (activities) and impact on functional outcomes (participation).
• The role of PT is to understand the precautions / contraindications, pathophysiology and right the right interventions.
• PTs factor in disease process and its effect on goals / treatment plans.

Bone Injury and Healing

• A bone fracture is a significant bone injury, and the initial phase is hematoma formation (inflammatory).
• The physician decides on the appropriate treatment (surgery or non-surgical) based on injury severity / involvement.
• Percutaneous pinning is minimally using Kirschner wires to pin fractures.
• Pins are driven transcutaneously thru bone cortex, across reduced fracture and into opposing cortex, stabilizes common fractures (phalanges, metacarpals, distal radius, proximal humerus, metatarsals).
• Percutaneous Pinning disadvantage: pins breaking or bending, provides no stability.
• External Fixation maintains the bone's alignment/traction, no confinement to hospital bed.
• Threaded traction pins are inserted into the bone proximally / distally to fracture site, manual reduced, fixed with carbon fiber bars outside skin across the fracture site.
• Using fine wires in a circular fixator is the least damaging to medullary blood supply.
• Stability can be provided for endosteal healing without external callus.
• Open Reduction and Internal Fixation reduces anatomically and absolutely stabilized as many fracture fragments as possible.
• Rigidly internally fixing fractures produces no periosteal callus and heals by combining endosteal callus / primary cortical union.
• Locking plates are fixation devices with screw holes, screw threads to plate/ function as a fixed-angle scaffold.
• Intramedullary Nailing provides relative stability that’s locked proximally/distally, tight fixation at the fracture
• Fixation with Intramedullary Nailing can have rotational/angular instability.
• The intramedullary nail blocks endosteal healing but enough movement results in triggering periosteal callus.
• Mobilization post femoral / tibial rodding = advances vs prolonged traction.
• Splints/ fracture that lie along extremity surfaces are made of prefabricated material/plaster secured with bandage.
• Splints/ fracture aim to immobilize/passively correct stable fractures, temporarily.
• Casting is rigid circumferential support which incorporates holes and three-point fixation.
• Casting more effectively immobilizes fracture fragments, maintains the reduction of ankle, tibia, pediatric forearm, distal.
• Skeletal/Buck's traction is applied manually using pulleys that overcome shortening force of muscles across the fracture site.
• Surgical reduction along with internal fixation has reduced usage of Skeletal / Buck's traction.
• Continuous immobilization of skeletal muscle causes consequences, include: cartilage degeneration, decreasing mechanical properties in ligaments, decreased bone density, and muscle atrophy.
• Immobilization of a joint results in arthritic changes and causes atrophic changes in articular cartilage by reducing matrix proteoglycans/ softening cartilage.
• The superficial zone contains the most reduction of the matrix proteoglycan.
• Following immobilization, CTs' vulnerability rises.
• Osteogenesis is stimulated by mechanical forces on bone; lack of these forces inhibits osteogenesis and inhibits bone density.
• Muscle atrophy (imbalance between protein synthesis and degradation) can occur from immobilization.
• General muscle atrophy typically occurs in one-joint muscles , while two-joint muscles are “less” immobilized by typical immobilization methods and are less prone to atrophy.
• Muscle atrophy happens a lot in type I fibers; decline in Type I fibers will increase proportion of Type IIa fibers.

Periarticular Tissues Injury and Healing

• The joints of the skeletal system have three supportive structures ligaments, joint capsules, and tendons.
• Structures stabilize the joint.
• They provide motion biomechanics.
• Ligaments / joint capsules offer mechanical stability that prevents motion.
• To transmit tensile loads, tendons join from muscle/bone, causing joint motion; tendons and tendons/ligaments consist of type 1 regular collagen
• Joints help to protect against tensile loads in a parallel alignment.
• Composed of type 1 dense irregular collagen joint capsule in multiple direction to resist loads.
• In connective tissue and a decrease in synovium, joint capsule injury causes laxity to joint.
• Joint fluid is given, with adds to stabilize joints.
• Injury can leads to the joint capsule / fluid container causing the joint stability to alter causing instability in the joint.
• Joint capsule needs to maintain vascular supply for healing / capsular healing, and joint regaining stability through immobility.
• Maintain dynamic stability of the joint, with appropriate mobilization for treating joint injuries.
• Managing joint, along with effusion/loading, requires the key and the amount function to the original injury/stability to be maintained by limiting scar tissue formation.
• Viscoeleastic load should be placed to maintain tissue health and death on the proper amount of stress.
• Load deformation happens by tissue and an example in a stress curve with (force) load on tissue being cross sectioned to find figure.
• The strain is calculated by dividing the length by the original length.
• Collagen fibers are crimped in toe region of the length until little force appears upon strain.
• The ligament resists through linearity for deformation with molecules and friction on the stiffness of tissue.
• The likelihood of injury with 6-10% of physical deformation for strain is reduced.
• Deformations appear as fibrils fail for regularity during the curve within tissue.
• Direct and Indirect insertion occur for ligament attachment when the Femoral/Medial Ligament is inserted.
• Ligament attachments lead bone integration by progressive stiffening/stress control.
• Ligament attachments leads bone integration by Sharpey's fiber transitions and fibroblast transition.
• Ligament injuries are classified under a three-grade range:
  • Grade I tears have pain and collagen torn, yet no laxity.
  • Grade II are torn to have increased pain the the laxity presents.
  • Grade III are complete with little pain however all the ligaments still appear with laxity.
• Healing of the ligament can be based on the amount cyclical mobility leads scar proliferation controlled.
• The scar collagen/types leads tissue from injury and a decrease in the GAG's.
• Proper stress amounts are important and controlled by a certified PT.
• Prominent loading must orient with ligament ends in contact in for progressive loads with the ligament and is protected.
• Surgery will involve stabilizing injuries in ligamentous.
• Some ligaments will heal faster than others.
• It becomes important for them to be monitored during the healing phase. If not they may heal inferior in relation and have 40 weeks until back to baseline.
• ACL intra-articular injuries are will have synovial fluid that results in enzymes that delay fibrin clot from occurring.
• A surgery will be performed depending on the performance of the athlete with the injuries ligament.
• Extra-articular ligament like collateral ligaments are able to heal will management and will depend on degree of the injury.
• The fiber-tape acts as to help and is a collagen coated help for augmenting the medial ulnar ligament.
• Ligament can be strengthened.
• With regenerative therepies are innovative materials by the orthobiologics field developed to treat ligaments surgically now than the initial treatment.
• Rehab for fibers is now better compared to surgery due to the strength tape can provide during the process.
• Tissue healing timelines should still be thought out for best results.
• Stresses should be minimized and bracing will occur based on a therapy schedule.
• Ligaments Extra-articular Heal through: events overlapping a sequential cascade
  • Inflammation: retraction of retraction and form hematoma causes mediators of chemistry and vasodilation of ligaments on end.
  • Repair: type III collagen
  • Proliferation: The neurovascularizations can be stimulated as stress responds with Type I replace III.
  • Permeability, as well as pain can come as well.
  • Trauma sites is brought by mobilization histamine, bradykinins, and prostaglandins.
  • Initiation (PMNs and lymphocytes) in the acute inflammatory phase becomes phagocytes (Monocytes/Macrophages).

Periarticular tissues Immobilization, healing and safe load bearing

• Clear mechanisms indicate, ligament that complexes have loads and load Hx,
• Deprivation of load =immbolization of joints will cause properties by net and a rapid loss In strength.
• State cells will lead imbalances, building/ catabolic with the matrix loss to tissue.
• Quality with the injury in the cells indicates for decreased bone and the resorb.
• Power with ligaments has been indicated through time due to the strength and mobilization.
• Six to Nine has been shown to be complex to see slight weakening and be mobilized for normal complexes.
• This means joint should be less joint and still perform for stiffening of the joint.
• Stiffening can be the result of deterioration of the amount to joint in fact that less stiff mobility can occur easier through time.
  • cartilage and muscle shortening occurs.
  • Capsular development in decreasing with the amount of water and compliance of decreased results.
  • Exercise mobilizations leads scars in the ligaments unlike immobile areas .
• Influence of ligament scars with movement is great and if not the forces with tissues may not have healing to better health.