APPP 19 and 20: Inflammation / Tissue Repair and Wound Healing Flashcards
What is inflammation?
protective response to eliminate the cause of cell injury and to remove damaged products/cells
What are the 2 major functions of inflammation?
- stop the attack
- repair the damage
What are the triggers of inflammation? (4)
- infection (bacterial, fungal, toxin)
- injury, foreign bodies, trauma
- immunological (immune reactions, autoimmune conditions)
- chemical agents and radiation
What are the 3 types of inflammation?
- acute inflammation
- systemic inflammation (ie. septic shock)
- chronic inflammation (ie. allergy, autoimmune disease)
What is acute inflammation and what does it cause?
tissue injury caused by physical or chemical agent or pathogenic microorganism
- capillary widening → increased blood flow
- increased capillary permeability → release of fluid
- attraction of white blood cells → migration of white blood cells to injury
- systemic response → fever and proliferation of white blood cells
- these all result in heat, redness, tenderness, swelling, and pain
What are the stages of acute inflammation?
- recognition of danger
- vasodilation and increase vascular permeability
- chemotaxis
- systemic response
Stages of Acute Inflammation
- Recognition of Danger
- tissue resident immune cells (mast cells of macrophages) recognize damage signals through PRRs (such as toll-like receptors)
- recognize pathogen factors (PAMPs) and cells in stress (DNA, heat shock proteins)
- release stored chemicals – mast cells release histamine + NO, platelets release serotonin
- inflammatory response is initiated
Stages of Acute Inflammation
2a. Vasodilation
- earliest response mediated by histamine and nitric oxide (NO)
- dilation of blood vessels starts at arteriole → capillary → venule
- stasis occurs when enlarged vessels pack with cells – assists leukocyte migration along vessel endothelium (normally, blood flows too fast for directed leukocyte movement)
- increase blood flow to wound sites causes local tissue erythema (redness) and warmth, swelling, painfulness
Stages of Acute Inflammation
2b. Increase Vascular Permeability
- endothelial cells respond to histamine and cytokine release
- contraction and retraction of endothelial cells allow protein-rich exudate to cross into interstitial tissue
- results in reduced osmotic pressure in blood and increased osmotic pressure in interstitial space
- leakage of fluid out of blood vessels leads to edema
- when infection is present, edema can spread to nearby lymph channels and lymph nodes (lymphadenopathy)
- increase delivery of immune cells and mediators, and clotting factors
Stages of Acute Inflammation
- Recruitment of Immune Cells – Chemotaxis
What are the WBC migration steps? (3)
- rolling: loose, intermittent contact with endothelium
- adhesion: tight, constant contact with endothelium
- transmigration: WBCs cross endothelial layer through gaps created by contracted endothelial cells
Stages of Acute Inflammation
- Recruitment of Immune Cells – Chemotaxis
Leukocytes are recruited to the site of insult in different phases. What are these 2 phases?
6-24 hours post-injury:
- dominated by neutrophils
- first responders, fast arrival
- phagocytes, apoptosis after response
24-48 hours post-injury
- finds monocytes (→ macrophages, APC)
- finds lymphocytes (sometimes eosinophils)
Acute Inflammation Mediators
What are the 4 pre-formed mediators released by mast cell degranulation?
- histamine
- cytokines: TNF-a, IL-1, IL-6
- chemokines for neutrophils and eosinophils
- enzymes: tryptase, chymase, cathepsin
Acute Inflammation Mediators
What does histamine do?
- vasodilation, causing increased swelling or fluid in mucosa
in other tissues:
- bronchiole constriction = wheezing
- constriction of smooth muscles in intestine = cramps, diarrhea
Acute Inflammation Mediators
What do enzymes do?
responsible for changes in connective tissue matrix, tissue breakdown
Acute Inflammation Mediators
What are the 2 secondary mediators synthesized and secreted upon mast cell activation?
- eiconsanoids: leukotrienes, prostaglandins, and thromboxanes
- Th2 cytokines: Il-4, IL-5, IL-13, GM-CSF
Acute Inflammation Mediators
What do eiconsaoids do?
- slower reacting substances, but longer-lasting effects
- increase vascular permeability
- platelet aggregation
- bronchiole constriction
What are the 5 cardinal signs of inflammation and what are their mechanisms?
- redness (rubor) – increase blood flow
- heat (calor) – increase blood flow, exudation of fluid, release of inflammatory mediators
- swelling (tumor) – exudation of fluid
- pain (dolor) – release of chemical mediators, stretching of pain receptor and nerves by exudates
- loss of function (functio laesa) – pain, disruption of tissue structure
What are the 6 types of inflammatory exudate and their biological content?
- serous – cell-free plasma (ie. skin blisters, pericarditis)
- fibrinous – with increased fibrinogen for wound repair (ie. adhesions following surgery)
- mucinous – thick clear gel-like mucous provides physical barrier and aid targeting of infectious materials (ie. runny nose with common cold)
- purulent – thick, coloured pus containing WBCs (ie. abscesses, boils, cellulitis)
- sanguineous – fresh bleeding (ie. hematoma)
- mixed types – mixture of the above (ie. serosanguineous, mucopurulent)
Describe the steps of the inflammatory response.
- bacteria and other pathogens enter wound
- platelets form blood release blood-clotting proteins at wound site
- mast cells secrete factors that mediate dilation and constriction of blood vessels – delivery of blood, plasma, and cells to injured area increases
- neutrophils secrete factors that kill and degrade pathogens
- neutrophils and macrophages remove pathogens by phagocytosis
- macrophages secrete cytokines, which attract immune system cells to the site and activate cells involved in tissue repair
- inflammatory response continues until the foreign material is eliminated and the wound is repaired
Mast cells are the source of which mediators of inflammation?
histamine, others
Macrophages are the source of which mediators of inflammation?
cytokines, others
Endothelium is the source of which mediators of inflammation?
NO, cytokines, others
What plasma proteins are sources of mediators of inflammation?
- complement
- clotting factors and kininogens
What are the 4 outcomes of acute inflammation?
- resolution
- abscess formation
- fibrosis (scar) formation
- chronic inflammation
Outcomes of Acute Inflammation
Resolution
- damaging agent removed and damages repair
- organ regeneration and full function restored (normal function)