Sepsis Inflammation Impact on Organ Dysfunction

SUMMARY:

• The immune system in sepsis consists of both pro-inflammatory and anti-inflammatory responses.
• These responses can produce multiple various organ sepsis. derangements in patients with sepsis.
• The role these organ system derangements play in sepsis and secondary infections should not be overlooked.

REVIEW:

• The typical immune response is release of localized inflammatory and anti-inflammatory agents leading to repair, returning the system to normal homeostasis.
• Sepsis is currently defined as a “dysregulated host response to infection”.
• 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.
• Numerous immune mechanisms activated with sepsis as a protective mechanism ultimately become detrimental both with excessive inflammation and immune suppression.
• The initial phase of sepsis releases high levels of pro-inflammatory cytokines and proteases.
• With ongoing sepsis, neutrophils are released from the bone marrow.
• -- Neutrophils are the mainstay of the cytokine system.
• -- Neutrophils impair chemotaxis and induce endothelial damage.
• Additional factors contributing to the hyperinflammatory and immunosuppressive phase of sepsis include:
• -- 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.
• -- 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.
• -- 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
• -- Lungs
• ---- 50% of sepsis patients develop ARDS with increased mortality
• ---- Gut associated microbes found in lungs of sepsis patients
• -- Bone Marrow
• ---- Widespread suppression of immunologic cell production
• -- 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

CONCLUSIONS:

• The adverse effects of sepsis on the immune system account for more than 80% of sepsis-related mortality.
• Better understanding of the molecular mechanisms of sepsis induced immune cell death is needed.
• The interplay between organ function and the dysregulated hyperinflammation associated with sepsis is complex and should not be overlooked.

Erkan Hassan, Pharm.D., FCCM is a transformational healthcare leader with extensive experience developing innovative solutions to improve clinical outcomes, enhance provider experience and increase revenue.

You can reach Erkan at [email protected]