Sepsis Inflammation Impact on Organ Dysfunction
SUMMARY:
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The immune system in sepsis consists of both pro-inflammatory and anti-inflammatory responses.
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These responses can produce multiple various organ sepsis. derangements in patients with sepsis.
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The role these organ system derangements play in sepsis and secondary infections should not be overlooked.
REVIEW:
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The typical immune response is release of localized inflammatory and anti-inflammatory agents leading to repair, returning the system to normal homeostasis.
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Sepsis is currently defined as a “dysregulated host response to infection”.
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Sepsis may have a pro-inflammatory response leading to tissue damage and an anti-inflammatory response making the patient susceptible to secondary infections.
- An unbalanced host response is seen with sepsis with elevated protective mechanisms lead to persistent host cell release and injury.
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Numerous immune mechanisms activated with sepsis as a protective mechanism ultimately become detrimental both with excessive inflammation and immune suppression.
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The initial phase of sepsis releases high levels of pro-inflammatory cytokines and proteases.
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With ongoing sepsis, neutrophils are released from the bone marrow.
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- Neutrophils are the mainstay of the cytokine system.
- Neutrophils impair chemotaxis and induce endothelial damage.
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Additional factors contributing to the hyperinflammatory and immunosuppressive phase of sepsis include:
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- Complement products
- Coagulation factors
- Vascular endothelium
- Lymphocytes
- Gut bacteria
- With sepsis being a multi-faceted disease, various organ systems can be impacted and may play a role in the sepsis process separate from the common occurrence of acute kidney injury.
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- GI
- The GI microbiome plays a key role in maintaining health
- Once a disequilibrium occurs, pathogenic bacteria predominate
- The epithelial barrier is breached
- This source of infection can be a major source of secondary episodes of infection.
- GI
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- Liver
- Biliary and Portal system defend against infecting bacteria.
- Pathogens may decrease bacterial clearance, interfere with release of cytokines during sepsis, and disrupt detoxification.
- Acute liver injury may occur along with cholestasis
- Liver
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- Lungs
- 50% of sepsis patients develop ARDS with increased mortality
- Gut associated microbes found in lungs of sepsis patient
- Lungs
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- Bone Marrow
- Widespread suppression of immunologic cell production
- Bone Marrow
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- Spleen
- Largest immune organ, with various infection fighting sub-populations suppressed
- CNS
- CNS modulates the immune response and release of cytokines, which can be disrupted with sepsis.
- Maintaining adequate CNS function is essential to control the immune balance
- Spleen
CONCLUSIONS:
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The adverse effects of sepsis on the immune system account for more than 80% of sepsis-related mortality.
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Better understanding of the molecular mechanisms of sepsis induced immune cell death is needed.
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The interplay between organ function and the dysregulated hyperinflammation associated with sepsis is complex and should not be overlooked.
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Erkan Hassan is the Co-Founder & Chief Clinical Officer of Sepsis Program Optimization where he designs & oversees the implementation of solutions to optimize sepsis programs.
To discuss your organization’s Barriers of Effective Sepsis Care, contact Erkan by phone (844) 4SEPSIS (844-473-7747), email (erkan@spo.icu), or video chat.