The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review

Abstract

Acute pancreatitis (AP), as a common cause of clinical acute abdomen, often leads to multi-organ damage. In the process of severe AP, the lungs and intestines are the most easily affected organs aside the pancreas. These organ damages occur in succession. Notably, lung and intestinal injuries are closely linked. Damage to ML, which transports immune cells, intestinal fluid, chyle, and toxic components (including toxins, trypsin, and activated cytokines to the systemic circulation in AP) may be connected to AP. This process can lead to the pathological changes of hyperosmotic edema of the lung, an increase in alveolar fluid level, destruction of the intestinal mucosal structure, and impairment of intestinal mucosal permeability. The underlying mechanisms of the correlation between lung and intestinal injuries are inflammatory response, oxidative stress, and endocrine hormone secretion disorders. The main signaling pathways of lung and intestinal injuries are TNF-α, HMGB1-mediated inflammation amplification effect of NF-κB signal pathway, Nrf2/ARE oxidative stress response signaling pathway, and IL-6-mediated JAK2/STAT3 signaling pathway. These pathways exert anti-inflammatory response and anti-oxidative stress, inhibit cell proliferation, and promote apoptosis. The interaction is consistent with the traditional Chinese medicine theory of the lung being connected with the large intestine (fei yu da chang xiang biao li in Chinese). This review sought to explore intersecting mechanisms of lung and intestinal injuries in AP to develop new treatment strategies.

Keywords: acute pancreatitis; endocrine disorders; inflammation response; intestinal injury; lung injury; oxidative stress.

FIGURE 1

The three main mechanisms of lung injury in acute pancreatitis (AP). This figure shows three most highlighted mechanisms in the studies of lung injury in AP, which include inflammatory response outbreak, oxidative stress damage, and endocrine disorders represented by matrix metalloproteinases (MMPs).

FIGURE 2

The signaling pathways of lung and intestinal injuries in acute pancreatitis (AP) in different environments and under certain physiological conditions. Several inflammatory activators, such as TNF-α, HMGB1, and proinflammatory factors, activate various intracellular signaling pathways – particularly NF-κB, STAT3, and ARE – by binding specific receptors, thereby releasing a range of inflammatory mediators and promoting each other, forming a vicious cycle.

FIGURE 3

The three main mechanisms of intestinal injury in acute pancreatitis (AP). The three most highlighted mechanisms of intestinal injury in AP are inflammatory response outbreak, oxidative stress damage, and endocrine disorders.