Endotoxins are lipopolysaccharides (LPS) located in the outer membrane of Gram-negative bacteria. Unlike exotoxins, they are not actively secreted, but are released during bacterial lysis or as blebs from living bacteria.
Structure of Endotoxin (LPS)
| Component | Function / Feature |
|---|---|
| O-antigen | Variable polysaccharide → immune evasion |
| Core polysaccharide | Structural component connecting O-antigen to lipid A |
| Lipid A | Toxic component responsible for major systemic effects |
Special note: Neisseria species have lipooligosaccharide (LOS) instead of full LPS.
Key Features
- Heat stability: Extremely heat-stable (can withstand autoclaving).
- Source: Released by cell lysis or outer membrane blebs.
- Target: Activates innate immune responses.
Mechanism of Action
Endotoxin exerts its effects through three main pathways:
- Macrophage activation (via TLR4/CD14)
- Cytokine release: TNF-α, IL-1, IL-6 → fever, hypotension, shock
- Complement activation
- Produces C3a, C5a → histamine release → edema, hypotension
- Neutrophil chemotaxis → inflammation
- Tissue factor activation
- Activates coagulation cascade → DIC
Clinical Manifestations (Mnemonic: ENDOTOXIN)
| Letter | Effect |
|---|---|
| E | Edema |
| N | Nitric oxide → vasodilation → hypotension |
| D | DIC / Death |
| O | Outer membrane LPS |
| T | TNF-α → fever, hypotension |
| O | O-antigen + core polysaccharide + lipid A |
| X | eXtremely heat stable |
| I | IL-1 and IL-6 → fever |
| N | Neutrophil chemotaxis → inflammation |
Summary: Endotoxin → macrophage & complement activation + tissue factor → fever, hypotension, DIC, shock.
Learning Objective (USMLE Step 1): Understand the structure, mechanism, and systemic effects of endotoxins (LPS) from Gram-negative bacteria, and differentiate them from exotoxins in terms of secretion, heat stability, and clinical manifestations.
Activity: Click the part of the LPS Toxic component responsible for major systemic effects.
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