Acute tissue injury and infection Flashcards
What are the outcomes of acute inflammation?
Resolution
Organisation (to scar, adhesion)
Dissemination (sepsis, shock, death)
Chronic inflammation (replaces, insidious, accompanies)
What are the stages of resolution?
(Elimination of cause essential) Danger signals wane Anti-inflammatory signals predominate Removal of exudate and debris Recovery of tissue architecture
How do danger signals wane?
Extravasation diminishes
Neutrophil apoptosis increases
Pro-inflammatory mediators are catabolised
How do anti-inflammatory signals predominate?
- Neutrophil apoptosis is a turning point= macrophage phagocytosis of apoptotic neutrophils (efferocytosis) triggers anti-inflammatory cytokine synthesis (IL-10, TGF beta)
- anti-inflammatory mediators
- neuroendocrine inhibitors= stress hormones (cortisol, catecholamines, vagus nerve effects- sympathetic inhibitors), anti-inflammatory cytokines attenuate sickness behaviours
Name anti-inflammatory mediators
Lipid resolvins and protectins
complement inhibitors
Receptor antagonists and decoy receptor fragments
Shed annexin A1 from apoptotic neutrophils inhibits further extravasation
Acute phase proteins
How is exudate and debris removed?
- Immunoresolvant lipid mediators= supress extravasation and cytokine release, stimulate macrophage clearance and efflux to lymph/ not circulatory system
- Macrophages clear debris= emigrate in lymph or die and themselves cleared/ default state is anti-inflammatory
- Vascular permeability normalises= excess interstitial fluid deported in lymph
How is the tissue architecture recovered?
Has to have ability to regenerate and damage sufficiently limited and short-lived
(lobar pneumonia)
What happens after resolution?
Trained immunity- epigenetic changes alter how some tissues and macrophages respond again to injury (weeks/ months)
How are scars formed?
Inflamed tissue and exudate replaced with granulation tissue which remains to form collagen scar rather than regenerative tissue repair
Extensive necrosis, leftover fibrin, poor regenerative capacity
What are the problems associated with sticky fibrin adhesions?
Bind surfaces together
Fibrinous exudate binds two serosal surfaces (bowels)- intestinal obstruction
Adhesion over a whole serosal surface (symphysis)- pericardium
When is sticky fibrin adhesions protective?
Omentum designed to wrap around inflamed intestine, protecting from rupture
What is sepsis?
Excessive disseminated inflammatory reaction to infection- 20% mortality, cytokine storm of host driven state
Hyperactivated inflammation but with suppression of the adaptive immune response
Depletes inflammatory resources so secondary infection kills you
What are the clinical grades of severity for sepsis?
Sepsis- life-threatening organ dysfunction caused by the dysregulated host response to infection
Septic shock- sepsis with high serum lactate (lactic acid necrosis due to anaerobic respiration of glycolysis) and refractory low blood pressure requiring vasopressors after fluid resuscitation
Why is inflammation dangerous?
Collateral damage, danger signalling imperfect
Hazard gradient- infection hazardous in sterile vital tissues/ blood compared to friendly microbes on epithelial surfaces (different level of response- heart more so than liver)
What are the checkpoints of inflammation?
- Extent of cell injury and resident macrophage density (cloaking)
- Soluble vs particle (multiple PAMP, phagocytic processing)
- Viability (bacterial/ viral nucleic acid)
- Virulence (system surveillance)
