SIRS CIS Flashcards
What does SIRS stand for?
Systemic Inflammatory Response Syndrome
SIRS results from pathogenic over-stimulation of the immune response. If the pathogen is non-infectious in origin, what is the end result?
Shock
SIRS results from pathogenic over-stimulation of the immune response. If the pathogen is infectious in origin, what is the end result?
Sepsis and septic shock
Are the majority of cases of SIRS leading to shock infectious or non-infectious in origin?
Non-infectious
[infectious only accounts for about 43% of SIRS leading to shock]
When might you see an uptick in the percentage of septic shock cases?
Septic shock cases are infectious in origin, would see during epidemics of pathogens containing superantigens
Pancreatitis, trauma, burns, etc. are associated with what type of SIRS?
Non-infectious
When do symptoms appear during the phased inflammatory response exhibited by SIRS patients?
Symptoms appear during hyperinflammatory phase
What is the patient’s immune response called when they first respond to the hyperinflammatory phase of SIRS?
Compensatory anti-inflammatory response (CARS)
T/F: during the CARS period of a SIRS response, the patient is significantly immunosuppressed
True
The immune system will continue to rebound with hyperinflammatory reactions, leading to another compensatory response, each one becoming less severe until homeostasis is reached
At least 2 of a set of criteria are needed to make the SIRS diagnosis. What are the 4 criteria?
Body temp (above 38 or below 36)
Heart rate (greater than 90 bpm)
Respirations (greater than 20/min or PaCO2 less than 32 mm Hg)
WBC count (greater than 12x10^9/L or less than 4x10^9/L)
What criteria is needed for SIRS to be considered sepsis?
SIRS + infection
What criteria is needed for the diagnosis of SEVERE sepsis?
Sepsis associated with organ dysfunction, systemic hypoperfusion, or hypotension
What criteria is needed for the diagnosis of septic shock?
Sepsis with arterial hypotension despite adequate fluid replacement
What are some examples of initial insults to the system that may lead to SIRS?
Uncontrolled infection Major trauma Circulatory shock Tissue necrosis Apoptosis Anaphylaxis
Initial systemic insult is followed by a trigger in order to propagate toward a SIRS response. What are these triggers?
PAMPs or DAMPs
Which of the following is not a PAMP?
A. Lipopolysaccharide
B. Peptidoglycan
C. Uric acid
D. Lipotechoic acid
C. Uric acid
[uric acid, HMGB-1, heat-shock protein, and DNA are DAMPs]
What are the 3 categories of sensors and effector cells that respond to PAMPs and DAMPs that lead to SIRS?
Complex protein systems (complement, coagulation)
Vascular and tissue cells (endothelium, epithelium, adipose)
Blood and lymphatic cells (granulocytes, macrophages/monocytes, lymphocytes)
When SIRS impacts organ function, what effect might it have on the brain?
Confusion
When SIRS impacts organ function, what effect might it have on the lungs?
Respiratory distress
When SIRS impacts organ function, what effect might it have on the cardiovascular system?
Shock
When SIRS impacts organ function, what effect might it have on the kidney?
Oliguria/anuria
[severely diminished urine output]
When SIRS impacts organ function, what effect might it have on the liver?
Excretory failure
When SIRS impacts organ function, what effect might it have on the gut?
Loss of barrier function, ileus
[ileus = inability of the bowel to contract normally and move waste out of the body]
When SIRS impacts organ function, what effect might it have on microcirculation?
Capillary leak, edema, DIC
The ___________ is a signaling system for the detection of pathogens and stressors. It involves the assembly of a sensor (NLRP3) and adaptor (ASC) and an inactive caspase (caspase-1).
Inflammasome
What is the sensor involved in formation of the inflammasome?
NLRP-3
What does the inflammasome do with the inactive caspase, and what cytokines does it produce?
Activates the caspase, which in turn results in the expression of IL-1
Eventually results in production of both IL-1 and IL-18, which are potent inflammatory cytokines
How does the inflammasome contribute to the production of IL-1? (Specifically)
Innate immune signals coming from things like TLR stimulation in the nucleus result in transcription of Pro-IL-1-beta
The inflammasome produces active caspase-1, which acts on Pro-IL-1-beta to make it IL-1-beta which can then be secreted and cause acute inflammation
What are the innate acute phase cytokines that contribute to SIRS and Shock, and in what order are they produced?
TNF –> IL-1 –> IL-6
What anaphylotoxin is produced prior to the acute phase cytokines in SIRS and shock?
C5a
The innate acute phase cytokines stimulate the liver to produce what?
Yet more acute phase proteins, including CRP and C’
What does DIC stand for?
Disseminated intravascular coagulation
[responsible for inadequate blood flow and tissue perfusion]
What tissues are most susceptible to DIC?
Lungs, liver, and kidneys because they are highly vascularized with very small vessels
What complication of SIRS results in diffuse cerebral dysfunction caused by a systemic inflammatory response, and is the most frequent cause of delirium in critical illness due to tissue hypo-perfusion?
Sepsis Associated Encephalopathy
T/F: The MAJORITY of patients with severe systemic infections will experience fluctuating mental status changes, inattention, disorganized thinking, and loss of consciousness
True, about 70% of patients with severe systemic infections will experience these symptoms
What is ARDS?
Acute Respiratory Distress Syndrome
Results from vasodilation and edema in alveolar spaces followed by recruitment of phagocytes and deposition of microthrombi and fibrin
What is the two-hit theory associated with SIRS?
There is an initiating event followed by some recovery, then a second hit results in worsened condition
What are some of the “first hits” associated with SIRS?
Injury
Hypotension
Hypoxia
What are some examples of “second-hits” associated with SIRS?
Often iatrogenic in nature
Reperfusion of ischemic areas
Antimicrobial agents
Surgical procedures
What is the Jarisch-Herxheimer reaction?
Occurs when someone in a state of shock is given antibiotics for the pathogen which causes lysis and release of more PAMPs, resulting in temporary symptom relief followed by a worsened state of shock
Cellular and molecular elements of the CARS response include:
Lymphocyte dysfunction and _____________
Downregulation of _____/co-stimulatory receptors
________ deactivation
Cytokine production including _____ and ______
Apoptosis
HLA
Macrophage
IL-10; TGF-beta
What are some of the clinical elements of the CARS response?
Cutaneous anergy Hypothermia Leukopenia Susceptibility to infection Failure to clear infection
Shock may lead to immune exhaustion, what does this mean?
Depletion of mediators like cells and serum proteins leads to immunosuppressive state
Low expression of HLA class I and B7, poor APC function
Myeloid derived suppressor cells and IL-10
Are investigational strategies like anti-TNF polyclonal antibodies and activated protein C effective in the treatment of shock?
No, they were found to disrupt the physiological balance of cytokines and led to increased mortality risk
What is the only treatment that has found to be effective for SIRS?
Cytosorb, a hemodialysis filter that is able to filter out acute phase cytokines
Does IVIG work for SIRS or sepsis?
Only for sepsis
What is the most common clinical presentation of pneumonia among adults?
Pneumococcal pneumonia
What is the incubation period for pneumococcal pneumonia?
1-3 days - very short, become sick very quickly
Why is streptococcus pneumonia often considered to be “community-acquired”?
Because the majority of the population are carriers
How does the clinical presentation of streptococcus pneumoniae differ in children vs. adults?
Causes pneumococcal meningitis in children
Causes pneumonia in adults
What are some issues that affect SIRS patients after recovery?
Although there is a decreasing death rate for SIRS in the US, there is an increased risk of death in the year following recovery. There is also impaired physical and neurocognitive function, leading to an overall lower quality of life.
