Lec18 SIRS Flashcards
What is SIRS?
- systemic inflammatory response syndrome
- manifested by 2 or more of:
- — temp > 38 or < 36
- — HR > 90
- — RR > 20 or pCO2 < 32
- — WBC > 12K or < 4K or > 10% bands
What are blood pressure measures for SIRS definition?
BP not included in definition
What is the definition of sepsis?
SIRS and a high suspicion of or documented infection
What is the definition of severe sepsis?
sepsis associated with organ dysfunction or hypoperfusion
- lactic acidsosis from tissue hypoxia
- oliguria [not enough urine]
- alteration in mental status
What is definition of sepsis with shock?
when hypotension not responsive to IV fluid
What is definition of multi-organ system failure [MOSF]?
results from shock, under-perfusion and tissue damage from cytokines and endothelial injury
What are initial treatments for sepsis?
- fluids = mainstay treatment, give normal saline boluses
- antibiotics: start broadly and narrow when you get culture results [cefalosporin, vanco]
- give oxygen: O2 delivery is impaired in sepsis
What is the clinical pathophysiology of sepsis?
- impaired end organ function due to:
- injury to microvasculature [decreased vessel tone]
- decreased blood volume [leak of plasma into tissues, bleeding, coagulopathy]
- decreased O2 delivery [anemia, pulmonary edema, ventricular dysfunction]
What is the cellular pathophysiology of sepsis?
- initated by immune system - T cells, PMNs
- mediated by: cytokines, cell wall factors, coagulation cascade, complement
- results in immune dysregulation and tissue injury
What is the normal response to infection/insult?
- innate immune [T cells]
- adaptive immune [B cell]s
What are the physical barriers of the immune system?
- skin
- cornea
- mucus layers
what are the chemical barriers or the immune system?
- stomach acid
- fatty acids on skin
- lysozyme in tears
What are the active mech of immune system?
- immune cells
- intracellular [interferons, apoptosis]
- organismal [complement, phagocytosis]
How does innate immune recognize pathogens?
- toll like receptors recognize pathogen associated molecular patterns [PAMPS]
What are 3 examples of PAMPS?
LPS on gram-neg
lipotechoic acid on gram-pos
mannans on yeast
Which effector mech are activated as art of innate immune response?
- activation of complement
- activated NFkB
- initiation pro-inflammatory cytokines [IL1 and IL6] to recruit other cellular components
- activated adaptive immune response
- initiation anti-inflammatory mediators to limit host tissue injury [IL10, resolvins, protectins]
What are 3 hypotheses for sepsis:
- bacteria and products cause tissue injury and organ injury
- excessive host inflammatory response
- inadequate compensatory anti-inflammatory response causes dysregulated excessive pro-inflammatory response
What are the consequences of innate immune that lead to DIC [disseminated intravascular coagulopathy]?
- cytokines and antigens involved in immune response stimulate tissue factor release from blood vessel endothelium and activate coagulation cascade, suppress fibrinolysis
- get clot formation –> –> DIC
What is third spacing?
- get endothelial injury from inflammatory response
- endothelial injury causes plasma to leave vessel and go into interstitial space
- get edema, hypovolemia
What are mech of sepsis?
- failure of negative feedback [IL10] to regulate innate immune response
- high activity of inflammatory mediators –> leaky vessels, coagulation, direct/indirect tissue injury
- low systemic vascular resistance, hypotension
- oxygen delivery impairment
- coagulopathy/thrombosis
What two mediators cause decreases systemic vascular resisitance?
NO
TNF-alpha
What causes cellular dysoxia/oxygen delivery impairment in sepsis?
- have disordered lcal circulatory regulation
- causes cells to need to undergo anaerobic metabolism
- get metabolic acidsois
The 3 main types of disturbances in sepsis?
- micro-circulation [cell adhesion, vascular leak, DIC]
- macro-circulation [V/Q, systemic vasodilation, cardiac depression]
- inflammatory cascade [massive inflammation]
What causes some patients to get sicker than others
- co morbid illness or injury [chronic disease – liver disease or cancer]
- pathogen type and dose [pseudomonas aeruginosa particularly known to cause sepsis]
- genetic predisposition
