Injury and Repair - Introduction Flashcards
What are mechanisms of cell and tissue injury
- ischemia
- infection
- immune reactions
- genetic factors
- nutritional factors
- physical factors
- mechanical factors
- chemical factors
- psychosocial factors
What is ischemia?
- a lack of blood flow that is the underlying the minimus necessary to maintain cell homeostasis and metabolic function
What can cause ischemia?
- arteriosclerosis
- tourniquet
- blood clotting g
- anything that blocks blood flow or causes a blood vessel to be blocked o constricted
What are the effects from ischemia?
- loss of function of impaired function
- discoloration/palor
- loss of sensation
- cold
- can cause a slowing/death of tissue
What is an infection caused by
- bacteria, viruses and parasitic
what is primary injury vs secondary injury from infections
- primary injury: as a result from the bacteria and can cause cell death
- secondary injury: results of indirect effects of an infection such as inflammation
What is sepsis
- toxins that get into the blood and then take over the body
- releases endotoxins and cytokine, interleukin-1 and TNF (inflammatory markers)
how do viral infections kill cells?
- direct cytopathic effect where the virus targets a cell and causes destruction
- indirect cytopathic effect: causes a change in the cellular make up or internal changes
Immune reactions as a mechanism of cell death
- antibody attachment
- complement activation
- activation of the inflammatory cells
- innate immune system: saliva, flora in GI tract, mucus membranes, skin
Genetic factors as a mechanism of tissue injury and cell death
- alteration in structure of number of chromosomes
- single mutations of genes
- multiple gene mutation
Nutritional factors as a mechanism of cell death
- imbalances in essential nutrients can lead to cell injury of death
Physical factors as a mechanism of tissue injury and death
- trauma and physical agent
- extremes of physical agents such as temperature, radiation, and electricity, may damage cells
Mechanical factors as a mechanism of tissue injury and death
- such as muscle forces pulling on bone causes it to be built up (benefits of mechanical factors
- however some mechanical forces from bones for example can cause stress factors if it is too much force/too little/ or imbalanced
Chemical Factors as a mechanism of tissue injury and death
- toxic substances that can be ingested or we can be exposed to
- free radicals
Free radicals
- can be helpful or harmful
- oxidation can result in oxygen radicals and reactive oxygen
- modulation of free radials: antioxidants, NO, exercise
Psychosocial factors and how they affect tissue healing
- may influence an individual threshold values for tissue adaptation and injury
What are some cellular aging theories and explain
- free radical theory: changes in aging are a result of exposure to free radicals
- Telomere aging clock theory: the reduction of telomeres throughout the lifespan is though to be associated with aging
- epigenetic clock theory: changes based on many factors that affect gene expression
What are the types of cell injury
- reversible
- irreversible
irreversible cell injury
- Necrosis: internal cell death that is the result of a pathological reason
- Apoptosis: signaled/planned cell death
reversible cell injury
- stress to cells
- altered functional demand/reversible cell injury
- stress maintained
- possible adaptations
- atrophy, hypertrophy,hyperplasia, metaplasia, dysplasia
- removal of stressor
- return to normal cell
What are the components of tissue healing
- fibronectin
- proteoglycans and elastin
- collagen
- these molecules build structures for cartilage, ligaments, and tendons and depend on other factors
- what are the factors affecting tissue healing
- growth factors
- nutrition
- other factors: blood supply, sleep, infection/inflammation, stress, co morbidity
what are the phases of healing
- hemostasis and degeneration
- inflammation
- proliferation and migration
- remodeling and maturation
Hemostasis and degeneration:
- 1st you must stop the bleeding and form a hematoma
- possible necrosis
- beginning of inflammation response once the clot is formed
Inflammation- tissue healing stage
- begins once the clot is formed
- purpose is to rid the causative agent, remove dead cells, and start healing the tissue
- acute inflammation is good and chronic can be hazardous
- in this stage vasodilation and increased permeability of the blood vessels
- coordinated reaction f body tissues to cell injury and death
- ends with the removal of initiating agent
what are some cellular causes of inflammation
- microbes
- release of pro-inflammatory mediators from traumatic stimulation of nerves of mast cells
- traumatic bleeding
- cell death
What are clinical manifestations of inflammation
- redness, swelling, increased temperature
- pain
- decreased function of the affected site
What are some acute inflammation cellular infiltrate
- platelets
- neutrophils
- monocytes/macrophage
- fibrocytes/fibroblasts
- Endothelial cells
What are some chronic inflammation cellular infiltrate
- monocyte/macrophage
- lymphocytes
- plasma cells
- fibrocytes/fibroblasts
- endothelial cells
Acute Vs chronic inflammation: what happens to result in restitution of normal structure in acute inflammation
- injury
- injurious agent removed
- labile or stable cells or little necrosis
- restitution of normal structure and function
Acute vs chronic inflammation what happens to result in chronic inflammation
- injury
- acute inflammation
3a. injurious agent removed
3b.repeated episodes of acute inflammation
3c. injurious agent persists
4a. permanent cells or extensive necrosis
4b. chronic inflammation
4c. chronic inflammation 1 - organization
- scarring
Proliferation and Migration phase
- endothelial cells near edge begin to proliferate
- establish a vascular network
- neovascularization or angiogenesis: the endothelial cells bud out from vessels and form new capillary channels
- granulation tissue: health vascular tissue/type of new connective tissue
Remodeling and maturation phase
- scar tissue is reduced and remodeled, living tissue smoother and stronger and less dense
- the remodeling phase can take years as the skin first produces collagen fibers which are broken down and rearranged to withstand stress
- over time, scare tissue grows stronger, relaxes and then lightens
What are the zones of cartilage starting with the one attached to the bone
- calcified
- radial (best blood supply from the bone)
- transitional
- tangential (most injury as it is closer to where forces are applied)
- articular surface
What is hyaline cartilage made of
- 75% water
- chondrocytes
- type 2 collagen 20%
- glycoaminoglycans/proteoglycans 5%
- cartilage is neural, avascular, and lymphatic
What are the three areas of growing cartilage
- growth plate: epiphysis
- articular cartilage of joint surface
- apophyses (such as in stood Schlatter diease)
How can injury occur to cartilage
can occur in skeletally immature children and adolescents
- thought to be caused by hypertrophy and wearing of the hypertrophic zones of cartilage
What are the stages of bone healing
- hematoma
- granulation tissue formation
- callus formation
- bone remodeling
Bone healing: hematome
- immediately after fracture
- macrophages, neutrophils, and platelets release pro inflammatory cytokines such as TNF, bone morphogenetic proteins, platelet-derived growth factors, transforming growth factor, vascular endothelial growth factor and interleukins
Bone healing: granulation of tissue formation
- primary callus or fibrocartilaginous callus
- occurs within 2 weeks of fracture
- chondrogenesis
- fibrin-rich granulation tissue formation
- dependent on angiogenesis
Bone healing: callus formation
- endosteum and periosteum secrete fibroblast (over growth of bone)
- the cartilaginous soft call begins to undergo endochondral ossification and medullary callus further supports the bridging soft callus
Bone healing: bone remodeling
- coupled remodeling- balance between osteoclasts and osteoblasts activity
What is the ideal process of bone healing
- fracture reduction to restore the anatomy (closed = no surgery and open= surgery)
- fracture fixation to achieve absolute or relative stability
- [reservation of the blood supply to the bone and surrounding soft tissues
- early and safe mobilization
Factors that influence bone healing
- blood supply
- fracture characteristics
- infection
- age
- smoking
- comorbities
- medications
Subluxation
- comes out of the joint space but is not fully dislocated
- causes partial disruption
- commonly occurs in more mobile joints
dislocation
- complete disruption of anatomic relationships
- ligaments/tendons damaged
- congenital most common at the hip
What is the anatomy of a tendon
- contain collagen fibrils (type 1)
- tendons contain proteoglycan matrix
- fibroblasts that are arranged in parallel rows
What is the basic functions of tendons
- tendons carry tensile forces from muscle to bone
- they carry compressive forces when wrapped around a bone like a pulley
What is the blood supply in a tendon like
- vessels in perimysium (covering the tendon)
- supply from the periosteal insertion
- supply from surrounding tissue (muscle)
what is the anatomy of ligaments
- predominantly type 1 fibers
- similar to tendon with hierarchical structure
- collagen fibers are slightly less in volume fraction and organization
- fibroblasts
What is the basic function of a ligament
- when bones move they keep them in alignment
- resist some forces (the forces that muscle does not absorb)
What is the blood supply like in a ligament
- microvascularity from insertion sites
- nutrition for cell population: necessary for matrix synthesis and repair
- relies on bone and therefore the middle does not get as much blood supply
Ligament injury
- grade 1:
- grade 2:
- grade 3:
- grade 1: stretching and small tears
- grade 2: larger tear
- grade 3: complete tear
Ligament injury: repair phases and length
- acute inflammation lasts about 2-3 days
- proliferation or regenerative/repair phase (several weeks)
- tissue remodeling phase (months-years)
What occurs during each repair phase in a ligament injury
- inflammation: platelets, WBCs, histamines, cytokines etc come to the area to bring nutrients and blood flow
- Proliferation or regenerative phase: platelet-derived growth factor, transforming growth factor beta, vascular endothelial growth factor and fibroblast growth factor; fibroblast deposit collagen, proteoglycans, and other proteins and glycoproteins to the matrix
- Tissue remodeling phase: tissue synthesis and degradation
Tendon injury
- Tendon rupture, tendinosis, tendinopathy, tendinitis
Tendon rupture vs tendinpathy
- attached muscle is max contracted with oblique and quick external stress
- tendinopathy: overuse where tendon is repeated strained and then forms micro-tears
Spontaneous tendon rupture risk factors
- side effect of fluoroquinolone
- > 60 yrs
- heart, lung, kidney transplant
- h/o tendinopathy, Mg deficiency, PVD, RA, DM, or strenuous sports
Tendinosis vs tendinitis
- tendinosis: chronic, no inflammation
disorganized laying of collagen (failed healing process and thinner collagen fibers) , recovery 6-10 weeks - tendinitis: acute, inflammation, 6 days to 3 weeks recovery
tendon healing: controlled loading
- by cast immobilization = beneficial for tendon to bone healing (screwing tendons to bone)
- by passive motion= for flexor tendon healing
What is the basic way muscle reheal
- muscle degeneration, necrosis, hematoma, injured myofiber
- inflammation: neutrophils, macrophages
- muscle regeneration: SC proliferation, regenerated myofibers with centrally located myonuclei
- muscle remodeling: TGF-B1, Fibroblasts, and CT formation; revascularization maturation of regenerated myofibers
- extracellular matrix deposition, scar tissue formation; innervation of regenerated myofibers
Types of muscle injury
- muscle contusions from a force or smack
- lacerations
- strains
- degenerative disease
Muscle repair:
can it regenerate/what is needed for repair
- can regenerate but depends on extent of injury
- basement membrane/sarcolemma sheath
- satellite cells (adult muscle stem cells)
muscle repair phases
- degeneration/inflammation phase (1 couple days)
- regeneration phase (begins 4-5 days post injury; peaks at 2 weeks, complete by 4)
remodeling phase
strategies to improve repair of muscle
- factors: IGF, Platelet rich plasma (injection)
- Stem cells: more severe
- mechanics, stimulation: PROM, AAROM
Muscle strains
stretching or tearing of musculotendinous unit
Muscle strains types
- mild/1st degree
- stretching or minor tearing without loss of integrity
- minor swelling
- minimal loss of strength and movement - Moderate/2nd degree
- partial tear with loss of function
- pain, moderate disabilities, point tenderness, swelling, local hemorrhaging, abnormal motion - Severe/3rd degree
- extends across entire cross section of muscle
