Inflammation / Wound Healing Flashcards
Metabolism of arachidonic acid via the COX pathway generates an unstable endoperoxide PGG2, which is converted to _________, the precursor of all prostaglandins and thromboxanes, with the release of toxic oxygen free radicals.
PGH2
Metabolism of arachidonic acid via the COX pathway generates an unstable endoperoxide ________, which is converted to PGH2, the precursor of all prostaglandins and thromboxanes, with the release of toxic oxygen free radicals.
PGG2
Various enzymes act on PGH2 to produce _______________, __________, __________ and ________________.
- PGI2 (prostacyclin)
- thromboxane A2
- PGD2
- PGE2
PGE2 (what is it, 3 things it does)
- Considered to be the predominant eicosanoid (lipid-based signaling molecule) associated with inflammatory conditions.
- Associated with vasodilation, increased vascular permeability, and edema.
- Decreases the nociceptive threshold, thereby enhancing the pain response to other stimuli.
Fill in the blank: The branch of an artery is __________ than the parent artery from which it arises. However, if one artery branches into two arteries concurrently, as in the terminal aorta at the level of the iliacs, the combined area of the branching vessels is generally __________ than that of the parent vessel
smaller
greater
What is directly proportional to the degree of tissue damage?
Temperature and duration of exposure
At what temperature range does failure of the cell membrane sodium pump occur?
40°C to 44°C (104°F to 111°F)
What type of burn occurs if the skin temperature reaches 60°C (140°F) for 1 second?
Epidermal necrosis (partial-thickness burn)
Skin temperatures above _______ result in full-thickness burns in less than 1 second.
70°C (158°F)
What is the tissue effects from a burst of laser energy?
Laser beam —> vaporization, carbonization, coagulation, hyperthermia
Zones of injury after a burn
Zone of coagulation
Zone of stasis
Zone of hyperemia
What is the inner area of burn wounds called?
zone of coagulation (also called the zone of necrosis or zone of destruction)
This area contains no viable tissue.
What is the middle area of burn wounds referred to as?
zone of stasis
It is named for its reduced perfusion. Further insult leads to necrosis. Effective therapy can restore perfusion and maintain viability.
What is the outer area of burn wounds called?
zone of hyperemia
This is the primary area of the inflammatory response to the burn. Tissues are viable and can heal if no further injury is sustained.
What are the primary sources of chemokines in burn wounds?
Damaged tissue and inflammatory cells
These sources initiate the inflammatory response.
Which four substances are involved in the inflammatory response in burn wounds?
- Endotoxin
- Prostaglandin E2
- Histamine
- Activated complement
These substances play critical roles in the inflammatory process.
What acts as a potent vasodilator in burns?
Nitric oxide
Nitric oxide plays a crucial role in increasing blood flow during burns.
Nitric oxide act as a potent vasodilator in burns indirectly by stimulation of release of what type of vasodilatory cytokines?
substance P
These cytokines help to further promote vasodilation.
Nitric oxide act as a potent vasodilator directly in burns on what?
vascular smooth muscle
Vascular smooth muscle contraction and relaxation are critical for regulating blood flow.
What is a primary reason burn wounds heal slowly?
Lower concentrations of wound healing cytokines compared to surgical wounds
This affects the overall healing process and recovery time.
What percentage of normal levels of fibroblast growth factor-2 (FGF-2) is found in wound fluid from burns?
Less than 5%
FGF-2 is crucial for wound healing and tissue repair.
What type of activity is absent in burn wound fluid that is present in normal surgical wounds?
Capillary endothelial chemotactic and proliferative activity
This activity is important for angiogenesis and wound healing.
What percentage of collagen in unwounded dermis is Type I?
80%
Type I collagen is the most abundant collagen type in the skin.
What percentage of collagen in unwounded dermis is Type III?
20%
Type III collagen is often found in early wound healing.
What type of collagen predominates in early wound healing (2-3 weeks)?
Type III collagen
Type III collagen is produced by young fibroblasts and is found in early granulation tissue.
What type of collagen predominates in late wound healing (after 2-3 weeks)?
Type I collagen
What is the composition of collagen in scar formation (12 to 18 months)?
Only 10% Type III collagen
The majority of collagen in scars is Type I.
What is the strength of scar tissue compared to the original tissue?
Approximately 70 to 80%
Scar tissue is generally weaker than the original tissue.
Types of Topical Hemostatic Agents (3)
- Mechanical hemostatic agents
- Active hemostatic agents
- Hemostatic sealants
Name Mechanical Hemostaic Agents.
These agents absorb blood to provide a mechanical barrier or tamponade to prevent further bleeding; they also create a matrix for clot formation and stabilization. Essentially, they rely on the normal functioning of the patient’s own hemostatic mechanisms. Some products may be combined with procoagulants to improve clot formation (in which case, they are both mechanical and active).
Gelatin Mechanism of Action
- Swells w/ blood, providing matrix for fibrin strand formation
- Does NOT actively promote PLT aggregation
- Resorbs by granulomatous inflammation & fibroblast replacement of sponge
Mechanical Hemostatic Agent
Collagens Mechanism of Action
- Mechanical action and enhances PLT aggregation → Clot formation
- Absorbed by fibroblast remodeling in 8-10 weeks (potentially more tissue reaction)
- Better but more expensive than gelatins
Mechanical Hemostatic Agent
Oxidized Cellulose Mechanism of Action
- Appears to form dense gelatinous clot independent of pathway, acidic properties
- Mechhanism of hemostasis is not fully understood
Mechanical Hemostatic Agent
Polysaccharide spheres +/- Oxidized Cellulose Mechanism of Action
- Hydrophilic → dehydrate solid components → stimulation of PLT responses and providing mechanical barrier→ EXPANDS
Mechanical Hemostatic Agent
Bone Wax Mechanism of Action
- Formulation of beeswax with paraffin, isopropyl palmitate or both
- Mechanical blocking of the surface to allow clotting
Mechanical Hemostatic Agent
Name Active Hemostatic Agents.
These agents actively stimulate the normal processes of hemostasis or improve hemostasis in circumstances in which the patient is failing, such as in thrombocytopenia. They sometimes are used in combination with mechanical agents (e.g., gelatin with thrombin).
Thrombin Hemostatic Agent Mechanism of Action (4)
- Factor II (AKA thrombin) available in three different forms: bovine, human, and recombinant
- Utilizes the normal clotting cascade mechanisms to convernt fibrinogen to fibrin and create a clot
- Concern for antibody development (do not repeat use)
- Can be combined with gelatin or fibrinogen but NOT cellulose (inactivated in acidic environment)
Active Hemostatic Agent
Alginate Hemostatic Agent Mechanism of Action (3)
- Seaweed derived protein may be combined with calcium or sodium ions
- Contact with saline/body fluid -> calcium ion released -> activates clotting cascade
- NOT suitable for intravacitary use due to foreign body reaction
Active Hemostatic Agent
Name Hemostatic Sealants
Hemostatic sealants are products created for sealing of vascular or dural defects without utilizing endogenous hemostatic mechanisms at all-a biologic equivalent of glue.
Hemostatic Sealants Mechanism of Action
- Fibrin combination sealants work completely independently of the patient’s clotting ability or even vessel damage, providing both thrombin and fibrinogen to the surgical site
- Derived from pooled human plasma
- Synthetic sealants polyethylene glycol or albumin seals tissue independent of clotting mechanisms
- Safety concern of swelling (up to 400% with Coseal and up to 50% with Duraseal)
Canine Skin Layers
A. Epidermis
B. Dermis.
C-D. Hypodermis (sometimes including cutaneous trunci muscle depending on location)
The blood vessels are present in three layers, represented in cross-section: subcutaneous or subdermal plexus, cutaneous plexus, and subpapillary plexus. The subpapillary plexus is composed of small capillaries that nourish the epidermis. Hair follicles are present at different depths in the dermis and in the upper part of the hypodermis.
What are the three layers of blood vessels present in the skin?
- Subcutaneous or subdermal plexus
- Cutaneous plexus
- Subpapillary plexus
These layers are represented in cross-section.
The subpapillary plexus are composed of small capillaries that provide nourishment ot what layer?
Composed of small capillaries that nourish the epidermis
The subpapillary plexus is crucial for epidermal health.
At what depths are hair follicles found?
Dermis and in the upper part of the hypodermis
Hair follicles vary in depth, affecting their interaction with surrounding tissues.
Fill in the blank: The subpapillary plexus is composed of _______ that nourish the epidermis.
small capillaries
These capillaries are essential for providing nutrients to the epidermal layer.
What is the deepest vascular network in the skin?
Subdermal plexus
Located at the boundary between the dermis and the hypodermis (subcutaneous tissue)
Which plexus is located within the deeper layers of the dermis?
Cutaneous plexus
It branches off from the subdermal plexus to supply blood to deeper structures like hair follicles and sweat glands
What is the most superficial plexus in the skin?
Subpapillary plexus
Found just beneath the dermal papillae, it supplies blood directly to the epidermis
The subdermal plexus is located at the boundary between the dermis and the _______.
hypodermis
The cutaneous plexus supplies blood to which structures in the skin?
- Hair follicles
- Sweat glands
True or False: The subpapillary plexus is deeper than the cutaneous plexus.
False. The subdermal plexus is.
What is the order of the vascular networks from deepest to most superficial?
- Subdermal plexus
- Cutaneous plexus
- Subpapillary plexus
Tumor Necrosis Factor alpha is a pro- or anti-inflammatory?
Pro-inflammatory
A major source of Tumor Necrosis Factor alpha is ___ ___.
Activated macrophages
Tumor Necrosis Factor alpha interacts with which two receptors?
TNFR1 & TNFR2 receptors
Found on numerous cell
True or False : Tumor Necrosis Factor alpha peaks quickly.
True
Tumor Necrosis Factor alpha initiates the production of:
- proinflammatory cytokines
- reactive oxygen intermediates
- chemotaxins
- endothelial adhesion molecules
Faclities recruitment of cells ar site of inflammation
Tumor Necrosis Factor alpha activates :
- Natural killer cells
- Proliferation of cytotoxic T-cells
- T-cell apoptosis
What is Misoprostol?
Synthetic analogue of prostaglandin E1 (PGE1)
Misoprostol is used in various medical applications, including gastrointestinal protection.
What are the two main cytoprotective agent functions of Misoprostol?
- Acid-INHIBITORY
- Mucosal-PROTECTIVE properties
These functions help protect the stomach lining and reduce acid secretion.
What are the three functions that Misoprostol increases?
- Bicarbonate secretion
- Mucus production
- Mucosal blood flow
These functions contribute to its protective effects on the gastrointestinal tract.
How does Misoprostol affect gastric acid secretion?
Decreases intracellular cAMP -> decreased H+/K+-ATPase pump activity -> decreased gastric acid secretion
This mechanism helps in reducing acidity in the stomach.
What is the half-life of Misoprostol?
Short half-life of 30 minutes
Due to its short half-life, Misoprostol is often administered multiple times a day.
How often should Misoprostol be administered due to its half-life?
3 to 4 times a day
Frequent dosing is necessary to maintain its therapeutic effects.
What is Cyclooxygenase - 1 also known as?
Housekeeping isoform
Which cells produce Cyclooxygenase - 1?
- GI cells
- PLT
- Endothelial cells
- Renal cells
True or False : COX is expressed in most tissues and is primarily responsible for producing prostaglandins that maintain normal physiological functions (homeostatsis) like protecting the stomach lining and regulating kidney function
Cyclooxygenase
True
What is Cyclooxygenase - 2 (COX2) characterized by?
Rapidly inducible and tightly regulated
Which cytokines stimulate the expression of Cyclooxygenase - 2 (COX2)?
- TNF and IL
Where is Cyclooxygenase - 2 (COX2) expressed?
kidney and brain
What effect does Cyclooxygenase - 2 mediate in damaged or inflamed gastrointestinal mucosa?
Cytoprotective effect
What are the three main effects caused by Cyclooxygenase - 2?
- inflammation
- pain
- fever
Fascia has ______ tensile strength than skin at 7 days post injury.
higher
Fascia equals skin tensile strength at 21 days post injury.
The strength of IRA decreases significantly within the first ______.
48 hours
Specific decreases: esophageal 37%, gastroduodenal 64%, SI 70%, and colon 72%.
High collagenase activity occurs on days ______ to ______, leading to decreased strength.
0-3
This time frame is critical for understanding tissue healing dynamics.
Bladder mucosa reepithelializes in ______ days.
2-4
This process is essential for restoring bladder integrity.
Bladder mucosa regains 100% of its unwounded strength in ______ days.
21
This indicates the timeframe for full recovery of bladder tissue.
Breaking strength at 7 days significantly less in dogs or cats?
cats
Granulation tissue forms earlier in dog or cats?
dogs (4.5 days)
cats 6.3 days
Contraction & epithelialization faster in dogs or cats?
dogs
Loose skin located on trunk & neck heals primarily by epithelialization or contraction?
contraction
Tighter skin located on extremities heals primarily epithelialization or contraction?
epithelialization
In dogs, superior healing has been shown to occur in males or females?
females (Androgens negatively impact wound healing & susceptibility to wound infection)
What is the characteristic of wound edges in primary wound closure?
Wound edges are apposed (minimal gap)
This indicates that the edges of the wound are closely aligned, facilitating healing.
In which type of wounds is primary closure indicated?
Clean, sharply incised wounds with minimal trauma & contamination
This type of closure is optimal for wounds that have not been exposed to significant bacteria or foreign material.
What is the time frame for wounds to be seen for primary closure?
Wounds seen within hours of injury
Timely treatment is crucial for the success of primary wound closure.
Any wound that can be completely excised can be converted to primary closure. True or False?
True
This means that if a wound can be entirely removed, it can be closed immediately.
What is the time frame for delayed primary wound closure?
3 to 5 days after wounding but BEFORE granulation tissue formation
This method allows for appositional closure of the wound during this period.
Delayed primary wound closure is indicated for which types of wounds?
Mildly contaminated, minimally traumatized wounds
This type of closure is suitable for wounds that do not have significant contamination or trauma.
What are the benefits of delayed primary wound closure?
Reduction of microbial contamination & maximization of tissue health before closure
These benefits help promote better healing outcomes.
What is Secondary Wound Closure also known as?
Third Intention Healing
What is the time frame for appositional closure of a wound in Secondary Wound Closure?
> 3-5 days after wounding with granulation tissue formation in wound bed
What type of wounds is Secondary Wound Closure indicated for?
Severely contaminated, traumatized wounds
What does Secondary Wound Closure allow for in terms of wound management?
Ongoing open wound management
What are the goals of ongoing open wound management in Secondary Wound Closure?
Ensure reduction of microbial contamination, treatment of infection (if present), and improvement in tissue health
What does the granulation bed provide in Secondary Wound Closure?
Microbial-resistant, vascular substrate
What is the mechanical action of gelatins in clot formation??
Swells with blood, providing matrix for fibrin strand formation
Gelatins do not actively promote platelet aggregation.
How do gelatins resorb in the body?
By granulomatous inflammation and fibroblast replacement of sponge
What is the mechanical action of collagens in clot formation?
Enhances platelet aggregation leading to clot formation
How long does it take for collagens to be absorbed?
8-10 weeks, potentially more tissue reaction
Which has a better performance, collagens or gelatins?
Collagens but more expensive
What unique property does oxidized cellulose have?
Forms dense gelatinous clot independent of pathway due to acidic properties
What is the effect of polysaccharide spheres on platelet responses?
Hydrophilic, dehydrates solid components, stimulates platelet responses, and provides a mechanical barrier
By what percentage do polysaccharide spheres expand?
500%
What is the primary function of bone wax in clotting?
Mechanical blocking of the surface to allow clotting
What is bone wax primarily composed of?
Beeswax with paraffin or Ostene
