Inflammation and Repair, TBP Flashcards by Jonathan Paul Ladera

Protective response to rid the body of the cause of cell injury its resultant necrotic cells

Inflammation

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Process by which WBCs are drawn to the area where they are needed

Chemotaxis

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Acute vs chronic inflammation: Tissue repair coexists with tissue destruction

Chronic

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Acute inflammation: Stages (3)

1) Vasodilation (after a transient vasoconstriction)
2) Increased vascular permeability
3) Movement of WBCs from blood vessels into soft tissue at site of inflammation

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Acute inflammation: Purpose of vasodilation (2)

1) Increases hydrostatic pressure

2) Facilitates margination of leukocytes

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Acute inflammation: Mediators of increased vascular permeability (5)

1) Histamine
2) LTC4, D4, E4
3) Bradykinin
4) TNF
5) IL-1

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Acute inflammation: Purpose of increased vascular permeability

Increase protein levels in interstitial tissue

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Mechanisms of increase in vascular permeability (2)

1) Physiologic

2) Pathologic

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Mechanisms of increase in vascular permeability: Physiologic (2)

1) Endothelial contraction

2) Endothelial retraction

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Mechanisms of increase in vascular permeability: Referred to as immediate-transient response

Endothelial contraction

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Endothelial contraction: Mediators (3)

1) Histamine
2) Bradykinin
3) Leukotrienes

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Endothelial contraction: Vessels affected

Postcapillary venules

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Endothelial contraction: Time course

Immediate and short-lived (up to 30 minutes)

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Endothelial retraction: Mediators

1) TNF

2) IL-1

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Endothelial retraction: How

Structural rearrangement of cytoskeleton

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Endothelial retraction: Time course

4-6 hours hence referred to as delayed response, long-lived

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Direct endothelial injury: Mediators

Bacterial enzymes

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Direct endothelial injury: Vessels affected

All

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Direct endothelial injury: How

Endothelial cell necrosis

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Direct endothelial injury: Time course

Immediate hence referred to as immediate-sustained response

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Mechanisms of increase in vascular permeability: Due to UV, x-ray, and mild thermal injury

Delayed prolonged response

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Movement of WBCs from vessels to soft tissue: Steps

1) Rolling
2) Pavementing
3) Transmigration

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Movement of WBCs from vessels to soft tissue: Loose, intermittent contact of WBCs with endothelium, partially due to margination of WBCs from stasis of blood

Rolling

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Rolling: Mediator

1) Sialyl-Lewis X on WBCs

2) E-selectins on endothelial cells

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Movement of WBCs from vessels to soft tissue: Tight, constant contact of WBCs with endothelium

Pavementing

Pavementing: Mediators

1) LFA-1 and MAC-1 on WBCs | 2) ICAM-1 and VCAM-1 on endothelial cells

Movement of WBCs from vessels to soft tissue: WBCs crossing through endothelial layer

Transmigration

Transmigration: Mediators

CD31 or PECAM on both WBCs and endothelial cells

Chemotaxis: Exogenous mediators

Bacterial polysaccharides

Chemotaxis: Mechanism utilised by most endogenous mediators

Activation of G protein-activation of GTPases-Polymerization of actin

Opsonins: Recognized by Fc receptor on WBCs

IgG

Opsonins: REcognized bt C1q on leukocytes

Collectins

Methods of killing and/or degradation of foreign substances: Uses 2 O2 molecules to produce superoxide which is converted to H2O2

Reduced NADPH oxidase

Methods of killing and/or degradation of foreign substances: Converts H2O2 and halogen to HOCl causing halogenation or lipid peroxidation

Myeloperoxidase

Impaired inflammatory response: Loss of NADPH oxidase system

Chronic granulomatous disease

CGD: Components of NADPH oxidase system

1) Membrane | 2) Cytoplasmic

CGD: Forms

1) Autosomal recessive | 2) X-linked

CGD: Form that results in defective CYTOPLASMIC component

Autosomal recessive

CGD: Form that results in defective MEMBRANE component

X-linked

CGD: Effect of mutation

Inability to form H2O2

CGD: Particular organisms that cause infection

Catalase-producing

Impaired inflammatory response: Decreased cellular killing of bacteria due to reduced transfer of lysosomal enzymes to phagocytic vesicles

Chediak-Higashi syndrome

Chediak-Higashi: Autosomal vs X-linked

Autosomal recessive

Chediak-Higashi: Associated symptoms

1) Albinism 2) Nerve defects 3) Platelet disorders

Acute inflammation: Types (3)

1) Serous 2) Fibrinous 3) Purulent

Serous inflammation: Appearance

Watery fluid

Serous inflammation: Contents of fluid

Transudative

Serous inflammation: Seen in (2)

1) Viral infections | 2) Burns

Fibrinous inflammation: Appearance

Thick, finely particulate fluid

Fibrinous inflammation: Contents

Exudative

Fibrinous inflammation: Seen in

Uremic and post-MI pericarditis

Purulent inflammation: Appearance

Pus

Purulent inflammation: Contents

Neutrophils, protein, and necrotic cells

Purulent inflammation: Seen in

Bacterial and fungal infections

Light criteria, exudate: Fluid/serum protein ratio

>0.5

Light criteria, exudate: Fluid/serum LDH ratio

>0.6

Light criteria, exudate: Effusion LDH

Greater than 2/3 the upper limit of lab reference range

Outcome of acute inflammation: Inciting agent is removed and all damage done by inciting ager and inflammatory cells repaired

Resolution

1) Organ must be capable of regeneration | 2) Body must be capable of completely dealing with the inciting agent

Resolution

Resolution: Important for regeneration of epithelium

1) Intact basement membrane 2) Intact connective tissue scaffolding 3) Cells capable of cell division

Outcome of acute inflammation: Walled off collection of pus

Abscess

1) Body cannot rid itself of inciting agent | 2) Repair and scarring is more rapid in tissue around site of abscess

Abscess: Requirements for formation

Outcome of acute inflammation: Loss of mucosa

Erosion

Outcome of acute inflammation: Loss of mucosa and deeper tissues

Ulcer

Ulcer: Requirement

Body cannot rid itself of inciting agent

Ulcer: Layers (superficial to deep)

1) Fibrin 2) Neutrophils 3) Granulation tissue 4) Fibrosis

Ulcer: Most common location

GIT

Outcome of acute inflammation: Anomalous connection between 2 organs

Fistula

Fistula: Most common organs involved

Organs with a lumen

1) Inflammatory process involving FULL-THICKNESS of wall of organ, duct, or vessel 2) Wall adheres to an adjacent wall

Fistula: Requirements

Outcome of acute inflammation: T/F Acute inflammation can result in chronic inflammation

Outcome of acute inflammation: Replacement of lost parenchyma with disorganised CT (e.g. collagen)

Scar formation

1) Loss of tissue in an organ NOT CAPABLE of regeneration | 2) Loss of basement membrane or other framework required for successful regeneration

Scar formation: Requirements

Prolonged inflammation consisting of active inflammation and tissue destruction and repair, all occurring simultaneously

Chronic inflammation

Chronic inflammation: Cells involved

Macrophages and lymphocytes

Chronic inflammation: Products of activated macrophages that activate lymphocytes (2)

1) IL-1 | 2) TNF

Chronic inflammation: Product of activated lymphocytes that activates macrophages

IF-γ

Chronic inflammation: Collection of epithelia histiocytes

Granulomatous inflammation

Chronic inflammation: Morphology of granuloma

Activated macrophages (epithelia histiocytes) and multinucleate giant cells

Granulomatous inflammation: Causes

Mycobacteria, fungi, foreign materials, sarcoidosis, silica

Regeneration of parenchyma or replacement of damaged tissue with a scar

Repair

Healing vs regeneration: Complete replacement of damaged cells with no scar formation

Regeneration

Healing vs regeneration: Regeneration of cells combined with scarring and fibrosis

Healing

Tissues capable of regeneration (2)

1) Renewing tissues such as the GIT and skin | 2) Stable tissues such as the liver and kidney

Mediators of repair: Stimulates granulation tissue formation

EGF

Mediators of repair: Induces blood vessel formation

VEGF

Mediators of repair: Promotes migration and proliferation of FIBROBLASTS, smooth muscle cells, and monocytes

PDGF

Mediators of repair: Stimulates blood vessel formation and wound repair through macrophages, fibroblasts, and endothelial cell migration

FGF

Mediators of repair: Acts as growth inhibitor for epithelium

TGF-b

Components of healing

1) Induction of inflammatory process to deal with source of injury 2) Angiogenesis 3) Production of extracellular matrix 4) Tissue remodelling 5) Wound contracture 6) Increasing wound strength

T/F: Multinucleated giant cells are required for the formation of granuloma

1) Angiogenesis 2) Migration and proliferation of fibroblasts 3) Deposition of extracellular matrix 4) Maturation and reorganisation of fibrous tissue

Replacement of wound by scar

Tissue remodelling is a balance between

Extracellular matrix synthesis and degradation

Extracellular matrix is degraded by

Metalloproteinases

Timeframe of scarring: Begins

Within 24 hours of onset

Timeframe of scarring: Granulation tissue is formed

3-5 days

Timeframe of scarring: Collagen continues to be deposited and edema and inflammatory cells are almost entirely absent

Week 2

Timeframe of scarring: Inflammatory infiltrate absent and scar consists of collagen

1 month

Healing: Clean edges, close reapproximation of margins, minimal tissue disruption

Healing by first intention

Healing: Unclean edges, extensive tissue disruption, tissue necrosis

Healing by second intention

Wound contraction reduces wound size by

5-10%

Wound contraction occurs due to these cells

Myofibroblasts

Wound strength: 10% at

1 week

Unintentional reopening of wound due to pressure or torsion

Dehiscence

Hypertrophic scar vs keloid: Involve tissue beyond boundaries of wound

Keloid

Hypertrophic scar vs keloid: May undergo spontaneous resolution

Hypertrophic scar

Chemotaxis: Endogenous mediators (3)

1) C5a 2) LTB4 3) IL-8

Opsonins

1) IgG 2) C3b 3) Collectins

Opsonins: Recognized by CR 1,2,3 on leukocytes

C3b