3.2-Inflammation

What is the principal effect of histamine in acute inflammation?

Increases vascular permeability and causes arteriolar dilation

Where is histamine stored and how is it released?

In mast cell granules; released by injury, IgE binding, C3a/C5a

What enzyme generates bradykinin and from what precursor?

Kallikrein; from high-molecular-weight kininogen

What are the effects of bradykinin?

Increases permeability, causes pain, vasodilation; involved in anaphylaxis

What does Substance P do in inflammation?

Promotes pain and vascular permeability; a neuropeptide from nerves/leukocytes

Which molecules are derived from arachidonic acid?

Prostaglandins, leukotrienes, and lipoxins

What enzyme forms prostaglandins and what are their effects?

COX-1/COX-2; cause fever, vasodilation, pain

What enzyme forms leukotrienes and what are their effects?

Lipoxygenase; cause bronchoconstriction and chemotaxis

What is the function of lipoxins?

Suppress inflammation by inhibiting neutrophil chemotaxis and adhesion

What drugs inhibit prostaglandin synthesis?

Aspirin and NSAIDs (COX inhibitors)

What drug is a 5-lipoxygenase inhibitor?

Zileuton

What drug is a leukotriene receptor antagonist?

Montelukast

What are the main producers of TNF-α?

Macrophages, dendritic cells, mast cells

What does TNF-α do to endothelial cells?

Upregulates E-selectin to promote leukocyte adhesion

What are systemic effects of TNF-α?

Fever, acute phase protein synthesis, cachexia

What cytokines mediate fever?

TNF-α and IL-1

What acute phase proteins are induced by inflammation?

CRP and fibrinogen

What is CRP and what does it do?

An opsonin that activates complement; marker of inflammation

What is the ESR and how is it affected by inflammation?

Erythrocyte sedimentation rate; increased by fibrinogen coating RBCs

What are the three complement activation pathways?

Classical, alternative, and lectin

What triggers the classical complement pathway?

Binding of C1 to antigen-antibody complexes (IgG or IgM)

What triggers the alternative pathway?

Microbial surfaces (e.g., endotoxin)

What triggers the lectin pathway?

Mannose-binding lectin binding to microbe carbohydrates

What enzyme is formed in all complement pathways?

C3 convertase

What does C3 convertase do?

Splits C3 into C3a and C3b

What are the functions of C3a and C5a?

Stimulate histamine release → anaphylaxis (vasodilation, permeability)

What is the role of C3b in immunity?

Opsonization and enhanced phagocytosis

What does the MAC complex do?

Causes lysis of cells, especially Neisseria bacteria

What is hereditary angioedema caused by?

C1 inhibitor deficiency → excessive complement activation

What is paroxysmal nocturnal hemoglobinuria (PNH) caused by?

Deficiency of DAF and CD59 → RBC lysis via complement

What is serous inflammation?

Exudation of cell-poor fluid (e.g., blister, effusions)

What is fibrinous inflammation and where is it seen?

Fibrin-rich exudate; seen in pericardium (→ friction rub)

What is purulent (suppurative) inflammation?

Pus formation with neutrophils and necrotic debris (e.g., abscess)

What is an ulcer?

Local tissue loss due to sloughing of inflamed necrotic tissue

What are the possible outcomes of acute inflammation?

Complete resolution, scarring/organization, or progression to chronic inflammation

What favors complete resolution in inflammation?

Limited injury, minimal tissue destruction, regenerative capacity

When does inflammation result in scarring (organization)?

Severe damage, non-regenerating tissue, persistent fibrin

What causes transition to chronic inflammation?

Persistent injurious stimuli or impaired healing

What are the cardinal signs of inflammation?

Rubor, calor, tumor, dolor, functio laesa

What mediators contribute to pain (dolor)?

Bradykinin, prostaglandins, substance P

What causes redness and heat in inflammation?

Vasodilation and increased blood flow

What causes swelling in inflammation?

Extravascular fluid accumulation (edema)

What causes loss of function in inflammation?

Tissue damage and pain