Acute Inflammation: Vascular Dynamics, Mediators, and Cellular Mechanisms

Comprehensive practice flashcards defining key terminology, chemical mediators, vascular events, adhesion molecules, and bactericidal mechanisms in acute inflammation.

Inflammation

The reaction of living tissue to injury or infection, characterized clinically by the cardinal signs of heat, redness, swelling, and pain.

SHARP

A clinical acronym denoting the cardinal signs of acute inflammation: Swelling, Heat, Altered function (loss of function), Redness, and Pain.

Vasodilation

Active hyperemia resulting from the dilation of arterioles and capillaries, serving as the hallmark vascular change of acute inflammation.

Initial Vasoconstriction

An immediate, transient contraction of arterial smooth muscle lasting milliseconds to minutes following injury; plays a minor role in inflammation but is essential in coagulation.

Histamine

A preformed vasoactive amine stored in the granules of mast cells, basophils, and platelets that acts as the primary mediator in the immediate phase of vasodilation.

$H_1$ Receptor

A transmembrane histamine receptor located on the vascular endothelium that triggers endothelial cell contraction and intercellular gap formation upon binding free histamine.

Serotonin

A preformed vasoactive mediator primarily stored in platelets and enterochromaffin cells, released upon platelet aggregation and closely linked to the coagulation cascade.

Nitric Oxide ($\text{NO}$)

A soluble gas produced by nitric oxide synthase enzymes (eNOS in endothelium, iNOS in macrophages, nNOS in neurons) that mediates vascular smooth muscle relaxation and vasodilation.

Cyclooxygenase-1 ($\text{COX-1}$)

A constitutively expressed cyclooxygenase isoform that maintains constant, low-level prostaglandin production to perform physiological housekeeping functions (platelet regulation, renal perfusion, gastric cytoprotection).

Cyclooxygenase-2 ($\text{COX-2}$)

An inducible enzyme upregulated by inflammatory stimuli that produces high concentrations of prostaglandins responsible for inflammatory pain, heat, and swelling.

Prostaglandin $D_2$ ($\text{PGD}_2$)

A cyclooxygenase metabolite that relaxes vascular smooth muscle to cause vasodilation, while also inhibiting platelet aggregation and producing bronchoconstriction.

Prostaglandin $E_2$ ($\text{PGE}_2$)

A cyclooxygenase metabolite that enhances vascular permeability in postcapillary venules to cause edema, stimulates mast cells, heightens pain sensation, and causes vasodilation.

Prostacyclin ($\text{PGI}_2$)

An endothelial-derived prostaglandin that promotes vasodilation, inhibits platelet aggregation, and acts as a potent anticoagulant.

Thromboxane $A_2$ ($\text{TXA}_2$)

An eicosanoid that acts as a potent vasoconstrictor, promotes platelet aggregation (pro-thrombotic), and stimulates fibrinogen binding.

Leukotriene $B_4$ ($\text{LTB}_4$)

A 5-lipoxygenase metabolite produced from leukotriene $A_4$ ($\text{LTA}_4$) that acts as a potent chemoattractant and activator of functional neutrophil responses.

Cysteinyl Leukotrienes

Leukotrienes $\text{LTC}_4$, $\text{LTD}_4$, and $\text{LTE}_4$, which mediate intense vasoconstriction, bronchospasm, and increased vascular permeability.

Substance P

A vasoactive neuropeptide secreted by leukocytes and nerves that activates endothelial $\text{NK}_1$ receptors to promote hydrophilic channel formation, vascular permeability, and nitric oxide production.

Endothelial Gap Formation

An immediate, reversible, and short-lived ($15\text{ to }30\text{ minutes}$) widening of inter-endothelial junctions restricted to postcapillary venules, driven by endothelial cell contraction or cytoskeletal reorganization.

Transudate

A non-inflammatory, clear, watery ultrafiltrate of plasma characterized by low protein content ($<69{,}000\text{ Da}$) and few cells, resulting from elevated hydrostatic pressure or decreased colloid osmotic pressure.

Exudate

An inflammatory, cloudy, protein-rich extravascular fluid containing abundant leukocytes and cellular debris, caused by increased endothelial permeability or vascular damage.

Serous Exudate

An early inflammatory exudate composed of clear-to-turbid fluid with water, salts, albumin, and immunoglobulins that appears histologically as a homogenous, eosinophilic material.

Fibrinous Exudate

An inflammatory exudate rich in fibrin resulting from severe endothelial damage that allows fibrinogen ($500{,}000\text{ Da}$) to escape into tissues, forming friable, peelable yellow-white strands.

Suppurative (Purulent) Exudate

An exudate composed predominantly of degenerate and viable neutrophils and liquefied necrotic tissue debris, typically forming thick, yellow-white pus in response to bacterial infections.

Catarrhal Exudate

An inflammatory exudate characterized by copious, clear-to-cloudy mucus produced by submucosal glandular hypersecretion on inflamed mucosal surfaces.

Margination

The flow-dependent accumulation and lining up of circulating leukocytes along the peripheral endothelium of postcapillary venules, facilitated by hemoconcentration and reduced luminal negative charge.

Selectins

Transmembrane lectin-domain-containing glycoproteins ($\text{L-selectin}$, $\text{P-selectin}$, $\text{E-selectin}$) that mediate low-affinity, fast on/off tethering and rolling of leukocytes along endothelial surfaces.

L-Selectin ($\text{CD62L}$)

A selectin constitutively expressed on neutrophils, macrophages, and lymphocytes that binds endothelial sialylated glycoproteins, such as GlyCAM-1 and MadCAM-1.

P-Selectin ($\text{CD62P}$)

A selectin stored pre-formed within endothelial Weibel-Palade bodies and platelet granules that mobilizes to the luminal surface within minutes upon stimulation by histamine or thrombin.

E-Selectin ($\text{CD62E}$)

An endothelial adhesion receptor induced by de novo transcription in response to pro-inflammatory cytokines ($\text{IL-1}$, $\text{TNF}$) that binds leukocyte sialyl-Lewis X.

Integrins

Heterodimeric transmembrane leukocyte receptors (such as $\beta_2$ integrins $\text{CD11a/CD18}$) that undergo chemokine-induced conformational changes from a low- to high-affinity state to mediate firm adhesion to $\text{ICAM-1}$.

Focal Adhesion Kinase (FAK)

A cytoplasmic protein kinase linked to the intracellular tail of integrins that couples extracellular adhesion signals to cytoskeletal reorganization and leukocyte motility.

Diapedesis (Emigration)

The active transendothelial extravasation of leukocytes between adjacent endothelial cells and through the basement membrane, driven by homotypic interactions of $\text{PECAM-1}$ ($\text{CD31}$).

Chemotaxis

The unidirectional, receptor-mediated migration of leukocytes through extracellular matrix gradients toward chemical signaling molecules at the site of inflammation.

Opsonization

The coating of pathogenic particles by host-derived proteins ($\text{IgG}$ and $\text{C3b}$) to facilitate efficient recognition, binding, and ingestion by leukocyte surface receptors.

Respiratory Burst

A rapid surge in oxygen uptake by activated phagocytes leading to the enzymatic generation of reactive oxygen species ($\text{ROS}$) for pathogen eradication.

NADPH Oxidase

A membrane-bound multimeric enzyme complex that catalyzes the transfer of electrons from $\text{NADPH}$ to molecular oxygen, generating superoxide anions ($O_2^{\bullet-}$) during the respiratory burst.

Superoxide Anion ($O_2^{\bullet-}$)

The initial reactive oxygen free radical synthesized during phagocyte activation according to the reaction: $O_2 + \text{NADPH} \rightarrow 2\,O_2^{\bullet-} + \text{NADP}^+ + H^+$.

Hydroxyl Radical ($OH^\bullet$)

An intensely toxic, highly reactive oxygen radical formed from hydrogen peroxide in the presence of ferrous iron via the Fenton reaction ($H_2O_2 + Fe^{2+} \rightarrow OH^\bullet$).

Hypochlorite Anion ($OCl^-$ / $HOCl$)

A potent bactericidal oxidant formed in phagolysosomes when myeloperoxidase (MPO) converts hydrogen peroxide and chloride via the reaction: $H_2O_2 + Cl^- \rightarrow HOCl$.

Bactericidal Permeability-Increasing Protein (BPI)

An oxygen-independent antimicrobial granule protein that binds to and punches pores directly into Gram-negative bacterial membranes.

Lysozyme

A leukocyte granule enzyme that mediates oxygen-independent bacterial killing by enzymatically hydrolyzing the peptidoglycan wall of microbes.

Lactoferrin

An oxygen-independent antimicrobial protein stored in leukocyte granules that inhibits microbial division and growth by sequestering and chelating essential iron.