inflammation & repair 1,2
TRANSCRIPT
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HISTORY
Egyptian papyrus - 3000 B.C.
Celsus (Roman in 1st century A.D.)
-1st
physician scientist to describe
inflammation
Rubor - Tumor - Calor - Dolor (Latin)
redness - swelling - heat - pain
Virchow added functio laesa later
INFLAMMATION AND REPAIR
DEFINITION
1. Reaction of vascularized tissues to local injury
2. Series of changes which take place in living
tissue following injury
3. Local reaction of the body to injury
4. Reaction of irritated and damaged tissues which
still retain viability
Inflammation
Protective response intended to eliminate
the initial cause of cell injury and thenecrotic cells and tissues arising from the
injury.
Inflammation is intimately associated with
the repair process which includes
parenchymal cell regeneration and scarring.
TWO TYPES OF INFLAMMATION
Acute Chronic
minutes to days ( cut off is
3 days)
weeks to years
Characterized by fluid and
protein
PMNs or
Polymorphonuclears
Lymphocytes and
macrophages together
with basophils,
eosinophils and
plasma cells
Mononuclear Cells-
predominant
population
Exudate SG > 1.020
The immediate and early
response to an injurious
agent
Inflammation of
prolonged duration
(weeks or months) in
which active
inflammation, tissue
destruction, and
attempts at repair are
proceeding
simultaneously
EXUDATES are the things which come out of the vesseland are more cellular because of PMN contents.
TRANSUDATEShave SG of 1.012
Exudate is a result of the ff:
o vascular permeability
high protein & cell debris
SG > 1.020
Transudate is a result of the ff:
normal vascular permeability
hydrostatic pres.p plasma ultrafiltrate
low protein (mostly albumin)
SG < 1.012
*Transudates are less cellular and protein
contents are lower.
Edema is a condition where the fluid comes out and
accumulates in the interstitial vessel.
Subject: PathologyTopic: Inflammation and Repair 1 & 2Lecturer: Dr. CruzDate of Lecture: 06/21/2011Transcriptionist: Jobell, Ceej, Maika,JaimeeEditor: PinayPages: 15
SY
2011-2012
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CAUSES OF INFLAMMATION
1. Physical Agents: Heat, Trauma, irradiation
2. Chemical Agents: Organic and Inorganic
3. Microbial Infections: most important cause of
inflammation
4. Hypersensitivity Reactions: allergy
5. Necrosis of Tissues: product of inflammation
- can also cause inflammation
MAJOR COMPONENTS OF ACUTE INFLAMMATORY
RESPONSE
1. Alterations in vascular caliber
2. Structural changes in microvasculature thisare vascular changes
3. Emigration of leucocytes or Accumulation in
focus of injury this are cellular events
exudate or transudate ; interstitium or
cavity
In any local injury there will be:
Transient vasoconstriction- 1st event tohappen
Vasodilatation- can bring about Endothelialpermeability
Endothelial permeability Extravasation of PMNs caused by
increased permeability
Five classic local signs of acute inflammation
Heat Calor vasodilatation
Redness Rubor
vasodilatation
Swelling Tumor vascular
permeability
Pain Dolor mediator
release/PMNs
Loss of
function
Functio laesa loss of
function
y Tumor happens when there isextravasation of fluid as well as formed
elements form the blood vessel,
accumulates in one area and produces a
swelling.
y Dolor- vasodilation and presence of cellswithin the area can impede nerve cells
and then cause pressure and pain. More
blood to the area can also bring pain.
This is the basic mechanism for
migraine headaches.
Vascular changes are the ff:(you need to know this)
Transient vasoconstriction Vasodilation Exudation of protein rich fluid Blood stasis Margination
Emigration/Transmigration
In Vascular changes
Protein exits vessels :
q intravascular osmotic pressure
o intravascular hydrostatic pressure
*Osmotic pressure and hydrostatic pressure are the
two pressures maintaining fluid in the vessel.
Endothelial gaps at intercellular junctions:
* immediate transient response
* histamine, bradykinin, leukotrienes,
substance P
* In Endothelial gaps at intercellular junctions, there
is definitely vascular permeability bec the fluid
within the vessel comes out.
*This picture is the course within the blood vessel
with osmotic and hydrostatic pressure. Proteins
inside the vessel maintain oncotic pressure. The
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blood flow, on the other hand, produces hydrostatic
pressure.
Vascular permeability
Vasodilation increased blood flow*Vasodilation will produce vascular
permeability.
Increased intravascular hydrostatic pressure Transudate - ultrafiltrate blood plasma
(contains little protein)
*Again, this is very transient and
just gets the process started.
Exudate - (protein-rich with PMNs and isusually the end point)
*Exudate is the characteristic fluid
of acute inflammation and hallmark
of acute inflammatory process.
Intravascular osmotic pressure decreases Osmotic pressure of interstitial fluid
increases
*Osmotic pressure is a pressure
which retains fluid in a vessel. While
hydrostatic pressure pushes the
fluid outside the vessel.
Outflow of water and ions - edema*This is the schema. Osmotic pressure and oncotic
pressure are in the venular side and hydrostatic
pressure is in the arteriolar side.
How do endothelial cells become permeable?
There are 5 mechanisms:
Endothelial cell contraction
*Capillaries have gaps but do not permit
fluid to come out of the vessel. Most of the
capillaries are lined by 2 endothelial cells
forming circumference. When there is
endothelial cell contraction, there is an
increase in gap so fluid comes out.
Junctional retraction Direct endothelial injury (immediate
sustained response)
Leukocyte-dependent endothelial injury Increased transcytosis of fluid
*Before injured areas are regenerated,
it has to be leaky at first.
Direct endothelial injury (immediate sustainedresponse)
Endothelial cell necrosis and detachment Result of severe injury or burn Occurs immediately and lasts until vessel
repaired
Leukocyte-dependent endothelial injury
Occurs at sites of leukocyte accumulation*In inflammation, leukocytes are stimulated
bec of bacterial toxin or necrotic debris. So
the presence of leukocytes can induce
Leukocyte-dependent endothelial injury in
the area. Inflammation is double bladed, it
can protect but cannot recognize what is
normal and what is not normal.
Due to leukocyte activation which releasesproteolytic enzymes and toxic oxygen
*If the enzymes from the leukocytes are
released, it can destroy everything in the
area as well as the vessels.
Leukocyte Cellular Events
Margination and Rolling Adhesion and Transmigration Migration into interstitial tissue
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*The normal blood flow is laminar, which is parallel
in the course of flow. This flow will maintain the
cellular elements at the middle (thats normal ). In
the event of transudation, there is decrease in fluid
so the cell will go to the sides. The process of the
cells touching the endothelium is a source of injury
bec the endothelial cells are very fragile.Slowing of
blood flow will result to stasis.
*STASIS is brought about by cells touching the
endothelial cells. The fluid comes out of the vessel.
Decrease in fluid will result to hemoconcentration.
In lesser fluid, the cells will again touch the
endothelium.
BINDING OF COMPLEMENTARY ADHESION
MOLECULES ON THE LEUKOCYTE AND
ENDOTHELIAL SURFACES
redistribution of adhesionmolecules to surface
induction of adhesion molecules onendothelium
*Some of the adhesion molecules are redistribted in
the surface of the endothelial cells as well as the
WBCs. In the pocess of injury, there is chemical
gradient produced. This gradient is recognized by
the WBCs as foreign and attracts them to go to that
area. The process of which an agent attracts the
WBCs is calledCHEMOTAXIS.
CHEMOTAXIS: locomotion oriented along a
chemical gradient
Biomolecules
Margination
Normal flow - RBCs and WBCs flow in thecenter of the vessel
A cell poorplasma is flowing adjacent toendothelium
As blood flow slows, WBCs collect along theendothelium Margination
Endothelial Activation
The underlying stimulus causes release ofmediators which activate the endothelium
causing selectins and other mediators to be
moved quickly to the surface. (Expose
receptors for other cells)
Selectins CAMS / Integrins
Weak and transient
binding
Integrins upregulated and
activated for increased
affinity to CAMS
Results in rolling and
margination
Results in firm adhesion
and transmigration
Results in rolling
Also known as:
Sialyl-Lewis X PSL-1 &
ESL-1)
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Selectins
Selectins bind selected sugars Selected + Lectins (sugars) =
Selectins
Some selectins are present on endothelialcells (E-Selectin)
Some selectins are present on leukocytes(L-Selectin)
Some selectins are present on platelets (P-Selectin)
Weak & transient binding Results in rolling
*In selectin, there are points of attachment but they
are weak. Once attached can e attached, so it rolls.
Rolling
Selectins transiently bind to receptors PMNs bounce or roll along Rolling(causes
further injury)
Adhesion
Mediated by integrins ICAM-1 and VCAM-1
*Different from rolling. There are also platelet
cellular adhesion molecules. Integrins present binds
firmly to the receptors and so they become
attached.
From slide 32-60, Inflammation and Repair
Adhesion mediated by integrins,
ICAM-1 (intercellular adhesion molecules) and;
VCAM-1 (vascular cellular adhesion molecules)
PECAM-1 (platelet cellular adhesion molecules)
These integrins bind firmly to the receptors and
become attached. PECAM-1 also produces enzymes
that will degrade the cell together with the
basement membrane.
Transmigration mediated/assisted by PECAM-1
and ICAM-1; diapedesis (refers to the crawling
movement the cell when it attaches to the
endothelium, enzymes are released, cell &
basement membrane are degraded, and the entire
big bulk can slowly pass through the gaps present in
the endothelium); cell goes out from intravascular
space to the extravascular space
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Chemotaxis - movement toward the site of injury
along a chemical gradient; attracting WBCs
intravascularly to go out
Chemotactic factors include:
- Complement components (20 serumproteins)
- Arachadonic acid (AA) metabolites- Soluble bacterial products- Chemokines, cytokines(released by
WBCs)
Phagocytosis and Degranulation
- Cleaning up the area; when somethingis wrong, the macrophages eat them up
- Phagocytosis (engulf and destroy);enzymes they produce are more
potent, aimed towards stopping the
inflammation process- Degranulation (occur within) and the
oxidative burst destroy the engulfed
particle
- Recognition & attachment -Opsoninscoat target and bind to leukocytes
- Engulfment- Killing/degradation or degranulation
Mechanisms:
O2 dep: Reactive O2 species in lysosomes & EC
O2 indep: Bactericidal permeability agents,
lysozyme, MBP, lactoferrin
Leukocyte-induced tissue injury
- Lysosomal enzymes are released intothe extracellular space during
phagocytosis causing cell injury and
matrix degradation
- Activated leukocytes release reactiveoxygen species and products of
arachidonic acid metabolism which can
injure tissue and endothelial cells
- These events underlie many humandiseases (e.g. Rheumatoid arthritis)
Leukocyte adhesion deficiency 1 (LAD-1)
- Recurrent bacterial infections- Inflammatory lesions lack neutrophil
infiltrate
- High numbers of neutrophils in thecirculation
- Neutrophils from patients can roll butdo not stick
- B-chain of CD11/CD18 integrin- Transfuse patients with normal
neutrophils and they can emigrate
- Mechanism:o Absence of integrins on
neutrophils
o Mutation in n-terminal regionof the integrin F chain inhibits
proper integrin assembly
o Normal function is restoredfollowing transfection of
patient cells with cDNA for F
chain
Chediak-Higashi Syndrome
- Defect in chemotaxis and lysosomaldegranulation into phagosomes
Chronic Granulomatous Disease
- Defect in NADPH oxidase system- Marked decrease in ability to kill
microorganisms
Chemical mediators of inflammation
- Plasma-derivedo Circulating precursors (kinase,
complement system)
o Have to be activated- Cell-derived
o Sequestered intracellularsubstances
o Synthesized de novo- Most mediators bind to receptors on
cell surface but some have direct
enzymatic or toxic activity
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- Mediators are tightly regulated in orderto control inflammation as well
Plasma Mediator Systems Interaction, check and
balance among these systems
1. Kinin
2. Clotting
3. Complement
4. Fibrinolytic
see last page for bigger picture
Kinin cascade
- Leads to formation of bradykinin- Bradykinin causes
o Increased vascular permeabilityo Arteriolar dilatationo Smooth muscle contraction
- Bradykinin is short lived (kininases)- Vascular actions similar to histamine
Complement system
- Role in immunity (C5-9 complex)o Membrane Attack Complex
(MAC C5-9)
o Punches a hole in themembrane
- Role in inflammation (c3a and c5a)o Vascular effects
Increase vascularpermeability and
vasodilation
Similar to histamineo Activates lipoxygenase pathway
of arachidonic acid metabolism(c5a)
o Leukocyte activation, adhesionand chemotaxis (c5a)
o Phagocytosis c3b acts as opsonin and
promotes phagocytosis
by cells bearing
receptors for c3b
Inflammatory Mediators from Complement
Anaphylatoxins:
- C3a, C5a, & C4a trigger mast cells torelease histamine and cause
vasodilatation
- C5a also activates the lipoxygenasesystem in PMNs and monocytes p
release of inflammatory mediators
Leukocyte activation, adhesion, & chemotaxis:
- C5a activates leukocytes, promotesleukocyte binding to endothelium via
integrins and is chemotactic for PMNs,
monos, eos, & basos
Phagocytosis
- C3b and C3bi are opsoninsControl:
- Convertases are destabilized by "decayaccelerating factor" (DAF)
- Inability to express DAF causesparoxysmal nocturnal hemoglobinuria
- C1 inhibitor (C1INH) deficiency causeshereditary angioneurotic edema
Vasoactive amines
- Histamineo Found in mast cells, basophils
and platelets
o Released in response to stimulio Promotes arteriolar dilation and
venular endothelial contraction
results in widening ofinter-endothelial cell
junctions with
increased vascular
permeability
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- Serotonin (in platelets)o Vasoactive effects similar to
histamine
o Found in plateletso Released when platelets
aggregate
Bradykinin: Potent biomolecule
1. Vasodilatation2. Increased vascular permeability
3. Contraction of smooth muscle
4. Pain on injection
5. Short life, kininase degrades
Factor XII activated by:
1. Plasmin
2. Kallikrein
3. Collagen & basement membrane
4. Activated platelets5. Co-factor = HMWK
Vascular Permeability:
- Bradykinin
- Fibrionopeptides
- Fibrin Split Prod.
- Factor Xa
- Leukotrienes
Arachidonic Acid (AA)
y Where is it located?o AA is a component of cell
membrane phospholipids
y The breakdown of AA into its metabolitesproduces a variety of biologic effects
Arachidonic acid metabolites
y Metabolites of AA - short-range hormonesy AA metabolites act locally at site of
generation
y Rapidly decay or are destroyedArachidonic Acid
y AA is released from the cell membrane byphospholipases(solution of the lipids) which
have themselves been activated by various
stimuli and/or inflammatory mediators
y AA metabolism occurs via two majorpathways named for the enzymes that
initiate the reactions; lipoxygenase and
cyclooxygenase
AA metabolites (eicosanoids)
y Cyclooxygenases synthesizeo Prostaglandinso Thromboxanes
y Lipoxygenases synthesizeo Leukotrienes- most importanto Lipoxins
see last page for bigger picture
*Prostaglandin G2 (PGG2) and Prostaglandin H 2
(PGH2 ) will be metabolize to produce prostacyclin.
*Prostacyclin produces vasodilation and inhibits
platelet aggregation
*Thromboxane produces vasoconstriction and also
promotes platelet aggregation.
*PGD2 PGE2 PGF2 causes vasodilation and edema.
Arachidonic Acid Pathways
y Lipoxygenaseo 5-HETE- hydroeicosatetraenoic acids
y Chemotaxiso 5-HPETE- hydroperoxyeicosatetraenoic
acids
y Leukotriene generationo Leukotrienes
y Vasoconstricitony Bronchospasm
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y Increased vascularpermeability
o 5-HETE, 5-HPETE*, Leukotrienesy Spasm (Vaso, Broncho)
y Cyclooxygenaseo Prostaglandins
y Vasodilatationy Increased vascular permeability
o Prostacycliny Vasodilatationy Inhibits platlelet aggregation
o Thromboxane A2y Vasoconstrictiony Promotes platlelet aggregation
o Prostaglandins - EDEMAo Prostacyclin vs TXA2
y Vasodilatation vs.Vasoconstriction
y Platelet aggregationInhibits vs. promotes
Arachidonic Acid Metabolites
y Participate in every aspect of acuteinflammation
y Effective Anti-inflammatory agents act on AApathways
o Aspirin and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) not use
anymore but acts on Cyclooxygenase
pathway
o Steroids act, in part, by inhibitingPhospholipase A2
Can also counteract metabolic pathwayPlatelet-Activating Factor (PAF)
y Another phospholipid-derived mediatorreleased by phospholipases
y Induces aggregation of plateletsy Causes vasoconstriction and
bronchoconstriction
y 100 to 1,000 times more potent thanhistamine in inducing vasodilation and
vascular permeability
y Enhances leukocyte adhesion, chemotaxis,degranulation and the oxidative burst
necessary for killing of bacteria and
destruction of necrotic debris.y It does everything!
Cytokines
y Polypeptides that are secreted by cellsy Act to regulate cell behaviorsy Autocrine, paracrine or endocrine effectsy These biological response modifiers are
being actively investigated for therapeutic
use in controlling the inflammatory
response
y Control mechanism-production of cytokinesLymphocyte function
1. Macrophages make IL-1 & TNF-E
2. T-cells make TNF-F (lymphotoxin)
3. Can be autocrine, paracrine, endocrine
4. IL-1, TNF, IL-6 -> acute phase responses ininflammation, fever, (appetite, slow wave sleep,
circ. pmn, ACTH, corticosteroids produce
during acute phase response of inflammation)
5.TNF notable for role in septic shock and
maintenance of body mass (cachexia in cancer from
TNF-E)
Inflammatory Cells & Their Chemokines
Target Cell Important Chemokines
Neutrophils IL-8, GroE, F, K, others
Monocytes MIP-1E, MIP-1F, MCP-
1,2,3
Eosinophils Eotaxin
Lymphocytes Lymphotaxin
Basophils IL-8, MIP-1E, MCP-1,3,
RANTES
Nitric Oxide
y NO is a soluble free radical gasy Made by nitric oxide synthetase (NOS) in
endothelium (eNOS), macrophages (iNOS),
and specific neurons in the brain (nNOS)y Broad range of functions and effects that
are short range
o Vasodilatation by relaxing smoothmuscle.
o platelet aggregationo Inhibits mast cellso Regulates leukocyte recruitment
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y Is also a control mechanismOutcomes of Acute Inflammation
y Resolution- if inflammation ensuesnormally or bring back to its normal cell
y Fibrosis- too much tissue are destroyed andtissue are replaced by fibroblast
y Abscess formation- excessive leukocytesactivation and the leukocyte accumulates inthe area
y Progression to chronic inflammation- youcannot destroy the bacteria, it will lead to
progression to chronic inflammation
Above: abcess
Above: some of the effects ofinflammation
a. blister
b. necrosis
c. vessel within a heart in rheumatic fever--aschoff
bodies
d. Ulceration
ulcer-totally no epithelium together with someareas in subepithelial area
Chronic inflammation
y Difficult to definey Interplay of several events: degeneration,
fibrosis and healing process and
superimpose acute inflammation.
y Inflammation of prolonged duration inwhich active inflammation, tissue injury and
the healing proceed simultaneouslyy Occurs in:
o Persistent infections - AFB, fungi,Treponemes
Low toxicity Delayed hypersensitivity Granulomatous
inflammation
o Prolonged exposure potentiallytoxic agents
Silica- cannot be degraded,no enzyme
Toxic plasma lipids(superoxide)
atherosclerosis
o Autoimmunity - RA, lupusChronic inflammation is characterized by:
y Infiltration with mononuclear cells(macrophages, lymphocytes & plasma cells)
y Tissue destructiony Repair involving angiogenesis and fibrosis-
granulation tissue
y Macrophage is the prima donna of chronicinflammation
Macrophage
-prominent role due the large repertoire of products
it can produce when activated
Key macrophage events
1. Recruitment from circulation
2. Local Proliferation
3. Immobilization
Macrophages immobilized in area,
especially in granulomatous inflammation
4. Differentiation (microglia, kupffer, alveolar
macrophage, osteoclasts) in events that there is an
injury present in that particular tissue.
Note that the activated macrophage releasesproducts that are similar to those released by PMNs
Some of the products of macrophages are not being
produced by neutrophils. The action of
macrophages is more modified.
Granulomatous Inflammation
y Subset of chronic inflammation
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y Aggregations of activated, modified(epitheliod) appearance
y Granuloma focal collection ofgranulomatous inflammation
o Central caseation necrosis,epitheloid cell, langhans type of
giant cell and rim of lymphocytes.
y Bacteriao Tuberculosiso Leprosy
y Parasiteso Schistosomiasis
y Fungio Histoplasmosiso Blastomycosis
y Metal/Dusto Berylliosiso Silicosis
y Foreign bodyo Splintero Sutureo Graft material
y SarcoidosisChronic Granulomatous Inflammation
-Distinctive aggregation of chronic
inflammatory reaction in which the predominant
cell type is an activated macrophage (EPITHELOID
CELL).
GRANULOMA :
-Microscopic aggregation of macrophages
transformed into EPITHELOID CELLS surrounded by
a collar of mononuclear cells
Above: activated macrophage
Types of Granuloma
1. Foreign body granuloma - cannot be
dissolved, multinucleated giant cells which is
aggregates of nucleus
2. Immune granuloma
Histologic Features
1. epitheloid cell
2. giant cells (Langhans type)
3. inflammatory cells and fibroblasts
4. central caseation necrosis
Above: caseation necrosis, lymphocytes, and some
epitheloid cell
Above: several langhans giant type cell, caseation
necrosis, lymphocyte at the left corner. Typical
ganuloma
Repair Regeneration of injured tissue by
parenchymal cells of the same type.
Basically, you replace a worn out tissue of
the same type or another type (regenerate).
Replacement by connective tissue. Fibrosis. Starts as early as 24 hours Granulation tissue at 3 - 5 days Four Components:
Angiogenesis: new blood vesselformation
Migration and proliferation offibroblasts
Deposition of extracellular matrix(ECM): supposed to be controlled.
(evident in Keloids)
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Remodeling (Maturation &organization of fibrous tissue).
Brought about by certain enzymes.
Angiogenesis + migration and proliferation of
fibroblasts combined is called GRANULATION
TISSUE.
Proliferative Potential Labile cells - continuously dividing
Epidermis, mucosal epithelium, GI
tract epithelium etc
Stable cells - low level of replicationHepatocytes, renal tubular
epithelium, pancreatic acini
Permanent cells - never divideNerve cells, cardiac myocytes,
skeletal muscle
Cell cyclePhosphorylation as the key point. But the discussion
will be focused on the G2 phase and mitosis -cell
proliferation and division for reparative
mecahanisms.
Cyclic Dependent Kinase 1 by itself, is inactive. For
this to stimulate the cells to divide, it should bind
with Cyclin B (control mechanism).
Hence, if this is not attached, the cell will not
proceed from G2 to mitosis.
Components of the process
of fibrosis
Angiogenesis - New vessels budding fromold
Fibrosis, consisting of emigration andproliferation of fibroblasts and deposition
of ECM
Scar remodeling, tightly regulated byproteases and protease inhibitors
Components of fibrosis
1. Formation of new bld vessels*
2. Migration and proliferation of fibroblasts.*3. Deposition of ECM4. Maturation and organization of fibrous
tissue.
*granulation tissue
More collagen, fibrosis & fibroblast= more blue
stain.
Tissue Remodeling
Balance of deposition vs. degradation Zn-dependent matrix metalloproteinases
Interstitial collagenases acts on type I, II, III collagen
Gelatinase acts on type IVcollagen & fibronectin
Stromelysins acts on variety ofECM
Membrane-bound matrixmetalloproteinases (MBMM)
Tissue inhibitors ofmetalloproteinase (TIMP)
Scar remodeling is regulated by metalloproteinases
and their inhibitors.
In this picture, collagenases are actually the
metalloproteinases. While the TIMP are the
inhibitors that will stop the cell remodeling or
deposition of the ECM.
If the remodelling is not stopped, there are harmful
effects of inflammation:
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Fibrinous pericarditis:
In this case, we have an autoimmune response in
rheumatic heart disease.
Liver cirrhosis:
Alcohol induced fibrosis. Nodules are separated by
marked fibrosis.
Wound healing
Is a complex but orderly phenomenon
number of processes:
Induction of acute inflammatory responseby an initial injury
Regeneration of parenchymal cells Migration and proliferation of both
parenchymal and connective tissue cells.
Best exemplified by fibroblasts.
Synthesis of ECM proteins (collagens). Remodeling of connective tissue and
parenchymal components to restore tissue
function
Remodeling of connective tissue to achievewound strength
We divide wound healing by:
1. primary intention (primary union);2. secondary intention
Healing by first/primary intention :
Clean, uninfected, surgical incision with sutures.
Events:
1. Blood clot forms2. < 24 hours PMNs appear3. 24-48 hrs cut edges of epidermis thicken
and forms basal cell hyperplasia, and
epithelium migrates
for union.
4. By day 3 PMNs replaced by macrophages.Granulation tissue invades & collagen at
margins.
5. Incision filled with granulation tissue.Maximal neovascularization & collagen
bridges gap. Epidermis covers & is mature.
6. One week After suture removal woundstrength only 10% (compared with
unwounded skin)
7. Second week Continued collagendeposition and fibroblast proliferation.
PMNs gone.
8. First month Scar with cellular connectivetissue and no inflammatory cells.
Regressed vascular channels.
9. Third month 70-80% of maximumstrength.
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Healing by second intention:
Larger injury, abscess, infarction.Process is similar but results in much larger scar
and then primary union
Large tissue defect to fill commondenominator
Differs from primary union in several ways: More fibrin, more debris more
intense inflammation. Hence, you
will destroy more tissue.
More granulation tissue is formed Wound contraction aided by
myofibroblasts . *you can only find
wound contraction second
intention.
Factors that influence healing
Nutrition - vitamin C (collagen formation). Metabolic status diabetes hinders Circulatory status- dehydration Hormones too much
steroids/glucocorticoids inhibit
Infection Mechanical stress Foreign bodies Size, locations and type of the wound
Whether a wound heals by primary or secondary
union is determined by the nature of the wound,
rather than by the healing process itself.
TERMINOLOGIES:
RESTITUTION : attainment of pre-existing tissue
architecture after inflammation
RESOLUTION : the inflammatory response has
successfully dealt with the injury with little or no
damage
ORGANIZATION : inflammatory response causes
excessive exudation or tissue death and when local
conditions are unfavorable for removal of debris
REGENERATION : replacement of dead cells by new
cells of the same type.
Summary:
____________End of Transcription_________
Youre light must shine before men so that they
may see goodness in your acts and give praise to
your heavenly Father.
-Matthew 5:16
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