1. Leukocyte recruitment to site of injury 2. Leukocyte Activation at the site of injury 3. Phagocytosis of particles

Acute Inflammation Flashcards by Kamille Aracan

is the local response of living mammalian tissues to injury from any agent which could be microbial, immunological, physical or chemical agents.

inflammation

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2 types of inflammation

Acute
Chronic

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[which type of inflammation]

due to early response by the body
short duration

acute inflammation

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[which type of inflammation]

occurs after delay
it is for longer duration
Characterized by response by chronic inflammatory cells.

Chronic inflammation

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Features of Acute inflammation

onset:
cellular infiltrate:
tissue injury, fibrosis:
local and systemic signs:

onset: fast
cellular infiltrate: many neutrophils
tissue injury, fibrosis: mild. self-limited
local and systemic signs: prominent

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Features of Chronic inflammation

onset:
cellular infiltrate:
tissue injury, fibrosis:
local and systemic signs:

onset: slow
cellular infiltrate: monocytes/macrophages & lymphocytes
tissue injury, fibrosis: severe and progressive
local and systemic signs: less prominent, subtle

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trigger stimuli for acute inflammation

infections
trauma
tissue necrosis
foreign bodies
immune (hypersensitivity reactions)

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Acute Inflammation Acute inflammation has 5 cardinal signs:

redness (rubor)
heat (calor)
swelling (tumor)
pain (dolor)
loss of function

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Mechanism of Inflammation

vasodilation
exudation - edema
emigration of cells
chemotaxis
phagocytosis

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Symptoms of:

increased blood flow

heat

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Symptoms of:

vasodilation
increased blood flow

redness

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Symptoms of:

extravasation of fluid (permeability)

swelling

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Symptoms of:

release of soluble chemical mediators
cellular influx (chemotaxis)

pain

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The two main events of the acute inflammation are:

Vascular events

Cellular events

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vascular events (7)

Initial transient vasoconstriction of arterioles.

Persistent progressive vasodilatation.

Elevation of the local hydrostatic pressure.

Increase in vascular permeability.

Transudation of fluid into the extracellular space.

Slowing or stasis of microcirculation.

Leucocytic margination.

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Increased permeability of vessels due to widened intercellular junctions and contraction of endothelial cells (Histamine, VEGF, Bradykinin)

VASODILATION

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Increased intravascular pressure causes an early ___ into interstitium.

transudate
(protein-poor filtrate of plasma)

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Causes of increased vascular permeability

Endothelial cell contraction → intercellular gaps in postcapillary venules

Endothelial injury
- Direct
- Leukocyte induced

Increased transcytosis of fluid

Leakage from new blood vessels

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Immediate sustained response - Occurs immediately and lasts until vessel repaired.

Direct Endothelial Injury

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Results of severe injuries (burns) or infections.

Direct Endothelial Injury

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Direct Endothelial Injury results in ___ by causing endothelial cell necrosis and detachment.

vascular leakage

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may also be damaged as a consequence of leukocyte accumulation along the vessel wall.

Endothelial cells

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Activated leukocytes release many toxic mediators that may cause ___

endothelial injury or detachment

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Cellular Events

Leukocyte recruitment to site of injury
Leukocyte Activation at the site of injury
Phagocytosis of particles

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Sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space.

Extravasation

Process of engulfment of solid particulate material by the leukocytes (neutrophils and monocytes)

Phagocytosis of particles

leukocytes assume peripheral portion of lumen

MARGINATION

leukocytes tumble slowly along the endothelium and adhere transiently, detach and bind again.

ROLLING AND ADHESION

Transmigration of leukocytes across the endothelium.

DIAPEDESIS

leukocyte migration towards the site of injury (locomotion oriented along a chemical gradient)

CHEMOTAXIS

Major role of: P-selectin

Rolling

Major role of: E-selectin

Rolling and Adhesion

Major role of: ICAM-1 (Integrin – β1)

Adhesion, Arrest & Transmigration

Major role of: VCAM-1 (Integrin – β2)

Adhesion

Major role of: PECAM-1 (CD-31)

Diapedesis

Chemical Mediators of Inflammation: Cell derived (Preformed)

Histamine Serotonin Lysosomal enzymes

Chemical Mediators of Inflammation: Cell derived (Newly synthesized)

Prostaglandins Leukotrienes Platelet activating factor Nitric Oxide Cytokines

Chemical Mediators of Inflammation: Plasma protein derived

Complement proteins Kinins Proteases activated during coagulation Factor XII

Chemical Mediators of Inflammation: Vasodilation

Prostaglandins Nitric oxide Histamine

Chemical Mediators of Inflammation: ↑ Vascular permeability

Vasoactive amines C3a, C5a Bradykinin Leukotrienes PAF Substance P VEGF

Chemical Mediators of Inflammation: Chemotaxis, Leukocyte activation

C5a LTB4 Chemokines IL-8 TNF Bacterial products

Chemical Mediators of Inflammation: Pain

Prostaglandins esp PGE2 Bradykinin Substance P

Chemical Mediators of Inflammation: Tissue damage

Neutrophils and macrophage lysosomal enzymes O2 metabolites Nitric oxide

Both exogenous and endogenous substances can be chemotactic for ___

leukocytes (Chemoattractants)

___ predominate in the inflammatory infiltrate during the first 6 -24 hrs

Neutrophils

Neutrophils are replaced by ___ in 24-48 hrs.

monocytes

Chemoattractants

Bacterial products, peptides with N-formylmethionine termini. Cytokines, especially those of the chemokine family, IL-8. Components of the complement system, particularly C5a. Products of the lipoxygenase pathway of arachidonic acid (AA) metabolism, particularly leukotriene B4 (LTB4)

defined as the process of engulfment of solid particulate material by the cells (cell- eating).

Phagocytosis

The cells performing Phagocytosis are called ___

phagocytes

Degranulation and the oxidative burst destroy the engulfed particle

Phagocytosis

2 main types of phagocytic cells

Polymorphonuclear neutrophils (PMNs) macrophages

Neutrophils and macrophages upon reaching the tissue spaces produce several proteolytic enzymes:

Lysozyme Protease Collagenase Elastase Lipase Proteinase Gelatinase Acid hydrolases *These enzymes degrade collagen and extracellular matrix.

Phagocytosis of the microbe by polymorphs and macrophages involves the following 3 steps:

1. Recognition and attachment – Opsonisation 2. Engulfment – Phagolysosome formation 3. Killing and degradation

Killing and degradation O2 dependent by:

O2 free radicals Lysosomal granules

Killing and degradation O2 independent by:

Lysozymal hydrolases Lacoferrin Major Basic Proteins Defensins Nitric Oxide

polymorphs after phagocytosis undergo

apoptotic cell death

most potent bactericidal system of neutrophils

Hydrogen peroxide-MPO-Halide system

Causes vasodilatation and venular endothelial cell contraction, Junctional widening

Histamine

Released by mast cells, basophils, platelets in response to injury (trauma, heat), immune reactions (IgE-mast cell)

Histamine

Vasodilatory effects similar to those of histamine

serotonin

Platelet dense - body granules; Release triggered by platelet aggregation

serotonin

Prostaglandins and leukotrienes are derived from arachidonic acid metabolism through:

Cyclo-oxygenase and lipoxygenase pathway

Arachidonic acid metabolism Cyclooxygenase pathway produces:

Thromboxane Prostacycline Prostaglandin

Aggregates platelets & causes vasoconstriction

Thromboxane

Inhibit platelets aggregation and dilates blood vessels.

Prostacycline

Increases vasodilation and increases vascular permeability.

Prostaglandin

chemical mediators (plasma derived)

complement kinins coagulation factors

Chemical Mediators (cell derived)

mast cell -histamine prostaglandins

specific mediators:

histamine serotonin

Leads to formation of bradykinin from cleavage of precursor (HMWK

Kinin system

Components C1-C9 present in inactive form - Activated via classic (C1) or alternative (C3) pathways to generate MAC (C5 – C9) that punch holes in microbe membranes

complement system

Polypeptide products of many cell types but mainly lymphocytes and macrophages that act on same cell autocrine, as a message to other cells paracrine effect or systemically endocrine effect .

cytokines

Increase endothelial cell adhesion molecule expression and activation and aggregation of PMNs.

cytokines

important cytokines in inflammation.

L-1 TNF-α and -β IFN-γ

- short-acting soluble free-radical gas. - - Produced by endothelial cells, macrophages, causes: - Vascular smooth muscle relaxation and vasodilatation - Kills microbes in activated macrophages

nitric oxide

Leak from PMNs and macrophages after demise, attempts at phagocytosis.

lysosomal components

Increased vascular permeability

Histamine Prostaglandin Leukotrienes Serotonin Bradykinin PAF (Platelet Activating Factor) NO (Nitric Oxide)

FACTORS DETERMINING VARIATION IN INFLAMMATORY RESPONSE

1) Factors involving the organisms -type of injury -virulence -dose 2) Factors involving the host -general health of host -immune state of host -leukopenia -local host factors

Accumulation of excessive clear watery fluid with a variable protein content.

serous inflammation

serous inflammation occurs in:

skin peritoneal, pleural and pericardial cavities

resulting from a burn or viral infection is a good example of the accumulation of a serous effusion either within or immediately beneath the epidermis of the skin

skin blister

Large amounts of fibrinogen pass the vessel wall, and fibrins are formed in the fluid exudate of extracellular spaces.

Fibrinous inflammation

fibrin is deposited on the pericardium.

Fibrinous pericarditis

The formation of purulent exudates or pus.

Suppurative (purulent) inflammation

Pus is made up of:

neutrophils necrotic cells edema fluid

a localized collection of purulent inflammation accompanied by liquefactive necrosis.

Abscess

FATE OF ACUTE INFLAMMATION

resolution repair suppuration chronic inflammation

Complete return to normal tissue following acute inflammation.

Resolution

Healing by regeneration in case of superficial tissue loss Healing by fibrosis in case of extensive tissue loss

repair

Persisting or recurrent acute inflammation leads to ___

chronic inflammation

EXAMPLES OF ACUTE INFLAMMATION

Acute appendicitis Acute meningitis Lobar pneumonia Acute pyelonephritis