Systemic inflammation
inflammatory response to blood-borne microbial molecules, tissue-derived enzymes and other proteins, & pro-inflammatory mediators
Systemic inflammatory response syndrome (SIRS)
tachypnea, tachycardia, fever/hypothermia, neutrophilia/neutropenia
Sepsis
a systemic inflammatory response triggered by microbial molecules
Endotoxemia
systemic inflammation triggered by gram-negative bacterial endotoxin (LPS)
Septic shock
sepsis + signs of hemodynamic shock
Sepsis pathogenesis
infection or mucosal damage allows microbes (usually bacteria) or microbial products to gain access to systemic circulation
- GI, respiratory, urogenital, umbilical, other mucosal surfaces
What is the most variable component of LPS?
O-specific antigen
What is the basic pathophysiology associated with sepsis?
Poor perfusion
- neutrophil & platelet aggregates
- thrombi-hypercoagulable (early)->later hypocoagulable with consumption of enough clotting factors
- hemodynamic shock
- altered/dysregulated peripheral vascular tone (red, warm extremities)
- poor CO
- increased vascular permeability
Tissue injury
- ischemia
- edema
- leukocyte products (reactive oxygen intermediates, degradative enzymes)
Ultimately lead to multi-organ dysfunction/failure
Two examples of non-septic SIRS
- immune-mediated disease
- severe trauma
Clinical signs of sepsis
- tachycardia, tacypnea
- hyper or hypothermia
- leukocytosis or leukopenia (left shift common)
- yperemic mucous membranes
- depression
- edema
- shock
- prolonced CRT
- poor peripheral pulses
- hypotension
- weak, trembling
- cool extremities
What are some lab findings that indicate systemic inflammation?
- high fibrinogen
- high WBC
- low mature PMN
- high bands
- low platelets
What are some lab findings with sepsis that indicate organ/metabolic failure?
- high BUN, creatinine
- high GGT, AST
- hyperglycemia (usu. adult) or hypoglycemia(usu. foals)
- hematuria, proteinuria
What are two contributing factors to high lactate?
- anaerobic metabolism due to poor perfusion
- cellular failure
What is an absolutely critical goal of therapy for sepsis?
INCREASE PERFUSION
- increase BP
- improve blood distribution
- reduce vascular leak syndrome
- address hypercoagulation
Fluid therapy for shock
Hypertonic (5% saline) or colloids followed by isotonic fluids(initial bolus and smaller boluses every 30 min if needed)
What treatment can help reduce endothelial permeability(vascular leak syndrome)
- hetastarch or plasma (plasma is expensive!)
What is a contraindication for Polymixin B administration?
High creatinine-drug is potentially nephrotoxic
When is Polymixin B useful for treatment of sepsis?
It will block LPS binding to LPS binding protein; not useful for other causes of sepsis
When should you use antibiotics in the treatment of sepsis?
- neutrophil count 1000 cells/uL or less
- septicemia is suspected or documented
- source of infection is found/documented
What are some treatment methods to prevent laminitis?
- circulatory support
- flunixin
- pentoxifylline
- J5 plasma
- careful exercise
- cryotherapy-ice feet if high risk
Describe how LPS induces CV shock
LPS binds LPS binding protein–>complex binds TLR and/or other receptors on macrophage–>triggers cascade–>production of pro-inflammatory mediators, toxic compounds inside cell, COX-2 upregulation–>PGE2 that is responsible for CV shock in septic patient
