inflammation & repair 1,2

8/6/2019 Inflammation & Repair 1,2

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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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inflammation & repair 1,2

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