How does sepsis produce emesis?

How Sepsis Produces Emesis

Sepsis produces emesis primarily through inflammatory cytokines (IL-1β and TNF) that directly trigger the chemoreceptor trigger zone and vagal afferent pathways, while simultaneously inducing gastrointestinal dysmotility and ileus through disruption of the enteric nervous system.

Primary Mechanisms of Sepsis-Induced Emesis

Inflammatory Cytokine-Mediated Pathways

The core mechanism involves direct action of pro-inflammatory mediators on emetic centers:

• Inflammatory cytokines IL-1β and TNF are released during the dysregulated host immune response to infection and directly stimulate nausea and vomiting centers in the brain 1
• These same cytokines trigger sickness-associated anorexia (SAA), which reduces energy intake and is accompanied by gastrointestinal symptoms including nausea and emesis 1
• The inflammatory mediators responsible for catabolic processes during infection simultaneously trigger SAA and associated gastrointestinal symptoms 1

Gastrointestinal Dysmotility and Ileus

Sepsis profoundly disrupts normal gastrointestinal function through multiple pathways:

• The gastrointestinal tract plays a pivotal role in sepsis pathogenesis through intestinal barrier dysfunction, bacterial translocation, and development of ileus 2
• Complex interplay within the gastrointestinal wall involves mast cells, residential macrophages, glial cells, neurons, and smooth muscle cells, all of which become dysregulated during sepsis 2
• This disruption involves intracellular signaling pathways, Toll-like receptors, and neuroactive substances including nitric oxide, prostaglandins, cytokines, and chemokines that impair normal motility 2
• The resulting gastrointestinal stasis and ileus contribute to nausea, vomiting, and inability to tolerate oral intake 2

Metabolic Dysregulation Contributing to Emesis

Hypoglycemia and Metabolic Disturbances

Later stages of sepsis involve metabolic changes that can trigger emesis:

• Lipopolysaccharide (LPS) and IL-1β induce hypoglycemia and reduce cerebrospinal fluid glucose, which can trigger nausea and vomiting 1
• In later stages of sepsis, hypoglycemia results from peripheral glucose usage and anorexia, correlating with poor outcomes and organ dysfunction 1
• These metabolic disturbances represent the body's attempt at metabolic adaptation but can produce significant gastrointestinal symptoms 1

Toxic Metabolite Accumulation

• Plasma triglycerides and free fatty acids can increase up to four-fold in septic patients, with toxic accumulation in organs causing damage 1
• Inflammation simultaneously down-regulates utilization of these fatty acids, leading to accumulation that interferes with mitochondrial function and can contribute to nausea 1

Neuronal and Autonomic Pathways

Vagal and Afferent Signaling

The nervous system plays a critical role in transmitting inflammatory signals:

• Multidirectional signaling between gastrointestinal wall components, spinal cord, and central nervous system impacts inflammation and its gastrointestinal consequences 2
• Afferent neuronal signaling from the inflamed gastrointestinal tract to the central nervous system triggers emetic responses 2
• The vagal anti-inflammatory pathway is disrupted in sepsis, contributing to both systemic inflammation and gastrointestinal symptoms 2

Clinical Implications

Recognition and Management Considerations

Understanding these mechanisms has practical implications:

• Emesis in septic patients reflects both central (cytokine-mediated) and peripheral (gastrointestinal dysmotility) mechanisms that occur simultaneously 1, 2
• The presence of significant nausea and vomiting may indicate progression of sepsis with metabolic dysregulation and gastrointestinal involvement 1
• Novel therapeutic strategies targeting inflammation and gastrointestinal motility, such as vagal pathway activation or ghrelin agonists, may address both the underlying sepsis and associated emesis 2

Common Pitfalls

• Failing to recognize that emesis in sepsis represents multi-organ involvement rather than isolated gastrointestinal pathology 2
• Overlooking the metabolic component (hypoglycemia, toxic metabolite accumulation) that contributes to nausea and vomiting 1
• Not appreciating that gastrointestinal symptoms may precede or accompany organ dysfunction in sepsis progression 1, 2