Inflammation & Repair: Inflammation & Wound Healing Flashcards
What TXA2 do?
VasoC
Aggregation
What prosctacyclin do (PGI2)?
Decrease platelets aggregation
VasoD of endo cells
What does steroidal anti-inflammatory drugs do?
Eg.: cortisol
Inhibit phospholipase
Decrease synthesis of LTE and PG
LTE leukotrienes
PG prostaglandins
Adverse effect of NSAIDs = ?
Ulcers
What does NSAIDs (aspirin, ibuprofen) ?
Inhibit COX-1 and/or 2
Compensatory increase in LTE
Inhibition of COX = diminution of PG because COX is the enzymes used to metabolize PG
What are the chemotaxis protein in acute inflammation?
IL-1
IL-6
TNF
The activation of macrophage, mast cells and endothelial cells release which chemokines (2)?
IL-1
TNF
IL-1 also released via activation of INFLAMMASOME
What are the main fct of TNF and IL-1?
Local recruitment of leukocytes via expression of selectin/integrin
Increase prod of cytokines and eicosanoids (prod later PG and LTE) via activation of macrophage.
What is the fct of IL-1?
Increase proliferation of fibroblast in ECM and chemokines.
What is the fct of TNF?
Increase membrane permeability
In chronic inflammation, TNF and IL-1 may enter in circulation and create systemic effects. What are they (4)?
Fever
Drop in BP
Increase metabolic waist
« » synthesis of acute phase prot
- also stimulate by IL-6
« » leukocytes synthesis
But also
- Fever
- Leukocytosis
- Acute phase prot response
Which chemokines promote insuline resistance in skeletal muscle?
IL-1
TNF
Which chemokine promote formation of thrombus?
TNF
What are the chemical mediators of inflammation (8)?
Vasoactive amines
-serotonine, histamine
Plasma protease
-complement factors, coagulation factors
Kinin syst
-bradykinin
PG and LTE
Cytokines and chemokines
-IL-1, TNF, IL-6
Lysosomal enzymes & free radical
NO
Platelet activation factor (PAF)
Explain the systemic effect of inflammation called FEVER
IL-1 and TNF = pyrogen
Increase PG synthesis
Increase temperature set point in the thermoregulatory center (HYPOTHALAMUS)
Result in shivering and vasoC to generate heat and decrease heat lost
It increase the speed of migration of leukocytes and weaken microbes
Explain the systemic effect of inflammation called LEUCOCYTOSIS
Increased synthesis of
Macrophages
Monocytes
Lymphocytes
Increased maturation of developing leukocytes from bone marrow
Explain the systemic effect of inflammation called ACUTE PHASE PROTEIN RESPONSE
CRP monitored to dx chronic inflammation and risk of myocardial infarct in pt w/ atherosclerosis
Fibrinogen = blood clotting
Serum amyloid A (SAA); activate complement prot
SAA and CRP increase microbial elimination and opsonins
Lysosomal enzymes and free radical can activate what (2)?
Eg.: elastase, collagenase, cathepsin
Vasoactive complement prot
Bradikinin-like peptides
Lysosomal enzymes and free radicals can be inhibited by what?
a1-antitrypsin (elastase)
a2-macroglobulin
NO is released by what (2)?
Endothelial cells (vasoD)
Activated macrophages (kills microbes)
PAF is released by what type of cells(3)?
Platelets
Basophils
Neutrophils
What is the fct of PAF
Increase membrane permeability and vasoD (more puissant than histamine)
BronchoC
Increased synthesis of eicosanoid (PG LTE)
« » cytokines
« » leukocytes recruitment
« » leukocytes degranulation
« » oxidative burst
What are the characteristics of chronic inflammation (3)?
Infiltration of tissue by macrophage/lymphocyte
Tissue damage d/t ROS, lysosymes
Repair healing
Via fibrosis and angiogenesis
What are the major player macrophage in chronic inflammation?
M1 macrophage
In chronic inflammation macrophage initiate (2)
Fibrosis
Secrete inflammatory mediators (IFN-y)
Can activate lymphocytes which can activate more macrophages
What is a granuloma?
Aggregation of activated macrophages/lymphocytes
Give 3 examples of disease that present granuloma
TB
Bacteria resistent to macro
Foreign body
TB: Via chronic activation of macrophage by t-cells
High concentration of IL-1 triggers granuloma formation.
BACTERIA RESISTANT TO MACROPHAGES
-leuko aggregate & surround bacteria to protect the rest of the cells & prevent bacteria spreading.
AROUND A FOREIGN BODY
-splinters
Wich type of cell can fuse and become multinucleated cell in the case of GRANULOMA?
Macrophages
What are the type/patterns of inflammation (4)?
Serous
Fibrinous/membranous
Abscess
Ulcer
Describe a serous inflammation
Blister (cloque)
Minor edema of watery prot-poor liquid
EFFUSION liquid separating the epidermis from the dermis
Describe a fibrinous/membranous infla.
Where?
What can clean it up?
Severe edema
Fibrinogen exudate
(Deposit of fibrin on tissue)
Meninges
Lung pleura
Pericardium
Fibrinolysis
Scarring occur if cannot clean up all fibrin
Abscess
Cause
Pus
Excessive necrosis
Heavy tissue destruction under abscess = SCARRING
Ulcer
Where
Necrosis+infla
D/t ischemia+bacterial infection
GIT
What are the repair mechanisms of a tissue? 2
Regeneration healing by 1st intention
Scarring 2nd
Regeneration
Healing by 1st intention
Regenerative capacities 3
Examples
Cells replaced by the SAME TYPE
CELL PROLIFERATION
- Labile tissue (constant)
- Stable (in resp to injury/QUIESCENT)
- Permanent (low regenerative cap)
- Surface epithelial, GIT, hemapoethic cells of bone marrow
- Hepatocyte, liver kidney
- Neuron, cardiomyocytes, skeletal muscle cells
Scarring
2nd intention
Collagenase enzyme is secreted by which cell?
Give an example
What is is role
Complete regeneration impossible
Another type of cell
Macro
Matrix metalloproteinases
Digest connective tissue
Make place for replacement tissue
Then secrete angiogenetic/fibrigenic factors
=granulation tissue
=wound contraction(reorganize fibrous tissue)
Produce stable scar
In granulation tissue, fibroblast produce what?
ECM to stabilize the wound
In granulation tissue, fibroblast are recruited by what cytokine?
Give examples
Growth factor
(Also stimulate ECM deposition)
TGF-b
PDGF
FGF-2
Cytokines
Fibroblast can become what type of musle?
When does it happen during the granulation tissue formation?
Myofibriblast
Weak contractil properties
Last stage
Keloid
Does it decrease w/ age?
Excessive scarring for minor injuries
Excessive ECM/ fibrous tissue deposition
Yes
What are the factors affecting infla and repair?
Systemic
Local
Malnutrition
Db
Leukocytes defect
Glucocorticoids
Infection
Foreign bodies
Ischemia
Location of injury
