Chapter Four - Tissue inflammation, healing and repair Flashcards
What is the main characteristic that a healthy tissue can do but an unhealthy tissue can’t?
Healthy tissue resists changes in their shape
Any tissue weakened by disease or trauma may not be able to adequately resist the application of force
What happens after tissue disuse?
TISSUE DISUSE
• Tissues adapt to decreased applied loads
• Active and passive tissues become weaker
• Less stress (load or force) to produce the same amount of strain (deformation)
Describe the basics of tendon breakdown. What happens to its physical properties? What is the definiton and the difference between acute and chronic tendon breakdown?
- Weaker, stiffer and less likely to deform (common patternt hat we see) (reduced toe region) due to vascular, cellular and collagen-related changes associated with age
- Acute: a known time and method of injury (partial tear to complete rupture)
- Chronic: unknown onset but involves repetitive loading to cause damage
Describe the basics of ligaments breakdown. What happens to its physical properties? What could an external load do to a ligament?
Insertion sites weaken with age, reducing strength and stiffness of tissue
Very sensitive to loading and loading history – without load rapid deterioration of biochemical and mechanical properties (reduced strength and stiffness)
When a ligament is taught for a particular joint position, an external load that results in any deformation of the tissue will exceed the elastic state and the ligament will fail
Ex: ACL tears - stops the tibia to sliding forward on the femur. ACL becomes very tight when you plant your foot on the ground, so if it gets hit at that same time (external load), we will see a tear (ex: soccer)
What is a quantitive way to describe the levels of tendon/ligament breakdown?
Describe the basics of cartilage breakdown. What happens when there’s a lack of cyclical loading? How can it affect other tissues, e.g. bones?
Disruption of synthesis and degradation in the ECM (softening)
Lack of cyclical loading (immobility, bed rest) deprives tissue stresses required for healthy function
• Decreased stress leads to changes in collagen (weaker bonds and unorganized structural changes)
Abnormal force transmission
Less water, increased stiffness, more force translated to other tissues (e.g., bone) and experiences earlier plastic zone
Describe the basics of bone breakdown. How can microtraumas, fractures, and osteogenesis (fragile bone) happend?
Cortical bone stays well within the elastic region of the load-deform curve (very little deformation)
Sustained, repetitive loads over time -> microtrauma (happens with a poor balance of activity and rest)
Abrupt, high loads -> fracture
Absent mechanical forces -> osteogenesis (fragile bone)
Give some examples of types of bone fractures.
Describe the basics of muscle breakdown. How can age, immobility and injury, individually affect muscles. Give three possible pain mechanisms.
Age: reduced cross sectional area (# and size of fibers), decreased ROM and power
Immobility: decreased force production (smaller fibers, impaired activation)
Injury: decreased force production (damaged sarcomeres, pain inhibition)
Possible pain mechanisms
• Reflex inhibition of motor units (to prevent further injury)• Central descending inhibition of injured muscles
• Decreased motivation (cognitive effective)
What are some of the most common causes of muscle breakdown (6)?
• Contusions and strains are the most common
- Inadequate muscle flexibility
- Inadequate strength or endurance
- Uncoordinated muscle contraction
- Insufficient warm up
- Poor rehab
There are two types of medications that we have seen in class. What are their name and how do they cause tissue damage?
Corticosteroids
Weakening of passive tissue with prolonged use Abnormal turnover of collagen fibers
Non-steroidal anti-inflammatory drugs (NSAIDs)
Interference with the healing process Resultant healed tissue potentially weaker than if no NSAIDs consumed
What is the importance of understanding the healing process?
- The clinician must recognize the signs and symptoms associated with different healing phases to be effective in incorporating the right treatment (e.g., exercise, modality) at the right time and in the right patient
- Understand the: physiological responses of the tissue to injury expected timing of each phase identification of something not right
Give the role(s) of parenchymal cells, endothelial cells and platelets.
- Parenchymal cell: carries out the function of a tissue or organ
- Endothelial cell: inner blood vessel, form new capillaries “angiogenesis”
- Platelet: an irregular, disc shaped element in the blood to assist with clotting
Give the roles of white blood cells in general, of mononuclear leukocytes (agranular) and polymorphonuclear leukocytes (granular). Which are the killer and the defender cells?
- White blood cells – involved in the inflammatory process and categorization depends on the type and age of injury, or if bacteria present
- Mononuclear Leukocytes (agranular): monocyte/macrophage, lymphocyte
- Polymorphonuclear Leukocytes (granular): eosinophil, basophil, neutrophil
What are fibroblasts? What are their functions in injury?
Flat shaped cells in the dermis of skin and structural tissues including ligaments and tendons
Function in injury:
Synthesize collagen for wound closure (forming scar)
ECM remodeling – degradation and production of collagen
Is the healing process made of clear steps of is it more of a continuum? Explain.
The healing process is a continuum
Not distinct phases
The healing process overlap one another
No definitive beginning or end points
How does homeostasis affect the inflammatory response during tissue healing?
- Within seconds, to stop blood loss
- Reflexive and transient vasoconstriction (decrease vessel size) -> allows the platelets to build up at the site of the injury, behind the vasoconstriction, and they start binding to the collagen, which generates a snowball effect to recruit more collagen
- Clot formation
- Adhesive platelets – to collagen molecules exposed by injury
- Plug formation – accumulated platelets
Which chemicals are released because of cell damage during the inflammatory phase, and what do they do? What are the two types of response that we can observe?
• Injury to the tissue results in damage to the cells -> release of chemicals
- E.g., bradykinin and histamine
- Releases with injury, triggering free nerve endings, ↑ pain
- Triggers the inflammatory response (2), until:• Stimulus is removed
- Inflammatory mediators are eliminated
Vascular Response
Cellular Response
What are the two characteristics of the cellular response during tissue injury? Describe the physiology of what happens and the two cell movements that we see in each characteristic.
a) WBCs (white blood cells) leave the vessels moving into the tissues (extravascular space)
• Triggered by chemical mediators supporting dilation and permeability
- Margination: leukocytes adhere to the endothelial cell well of vessel
- Diapedesis: squeezing between cells to leave the vessel
b) Seek and destroy foreign substances
- Chemotaxis: chemical gradient attracts leukocytes to injury site
- Phagocytosis: recognize foreign substance (e.g., bacteria), engulf, degrade
What is the fibroblastic phase (scar forming)? What is its timeframe? What are the two different possible pathways of scar forming? Which is the most common one? The fibroblastic phase depends on two things… what are they?
(scar forming)
Begins within hours to days post-injury
2 days to 6 weeks
Either a REGENERATIVE process to replace necrotic cells with new cells of the same type; OR a REPARATIVE (generally what we see, more common) process to replace necrotic cells with collagen and form scar tissue (type I and III collagen)
Dependent on:
• the extent of the injury (severe vs. mild)
• type of tissue (if its cells can divide or not)
Give a definition for angiogenesis. What causes it? What has to happend to lead to revascularization (4 steps)?
• Angiogenesis: lack of oxygen stimulates growth of endothelial capillary buds into the wound
The wound can then heal aerobically; increased oxygen delivery
Blood flow to deliver nutrients for tissue regeneration in the area
Vessels tend to be leaky so the tissue appears wet
- Proteolysis of basement membrane
- Migration and chemotaxis at the capillary tip
- Cell proliferation
- Increased permeability through gaps
What is the maturation phase? What is its timeframe? What happens to fibers? What is the apperance of the wound at this point?
Long-term process (3 week to multiple years)
Realignment collagen fibers (no new)
Increases in stress and strain to realign for maximum tension efficiency (more cross-linking bonds)
Fibers to orient themselves along stress line
Normal appearance and function but rarely as strong as the original tissue
What is the maturation remodeling phase? Use a graph to describe it.
What is the difference in cartilage healing between an injury that doesn’t reache the subchondral bone and one that does? Why?
Does not reach the subchondral bone (there is no vascular supply!): becomes necrotic, no healing
If the subchondral bone is reached: access to blood supply
• May resemble healthy tissue, but biochemically and mechanically differ
Fibrillation, fissures and degenerative changes occur
Describe the four stages of bone healing
