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.

Naringenin protects against acute pancreatitis-associated intestinal injury by inhibiting NLRP3 inflammasome activation via AhR signaling

“…Intestinal injury is secondary to severe acute pancreatitis and results in aggravation of the systemic inflammatory response, which accounts for the high mortality of AP (He et al, 2017). Liu et al (2022) reported that inflammatory response outbreaks, oxidative stress damage, and endocrine disorders are the three main mechanisms of intestinal injury in AP. The development and prognosis of intestinal damage in AP are significantly influenced by the inflammatory response (Ge et al, 2020).…”

Hydrogen Sulfide: A Gaseous Mediator and Its Key Role in Programmed Cell Death, Oxidative Stress, Inflammation and Pulmonary Disease

“…The incidence of acute pancreatitis keeps increasing worldwide and the global morbidity and mortality are still very high [ 82 ]. The lungs are one of the most easily affected organs aside from the pancreas during the onset, development and progression of acute pancreatitis [ 83 ]. As H 2 S imbalance has been implicated in acute pancreatitis, the actions played by H 2 S in acute pancreatitis-induced ALI are becoming increasingly clear [ 24 , 28 ].…”

Hemorheological and Microcirculatory Relations of Acute Pancreatitis

“…The central events are the release of proinflammatory mediators (cytokines, vasoactive substances, free oxygen radicals) and the deterioration of microcirculation, and the activation of leukocytes and their rolling and infiltration into the tissue. These mediators are produced in the pancreas in the initial period of pancreatitis but later in the liver, lungs, and spleen as well [ 3 , 5 , 9 , 18 , 19 , 20 , 21 ].…”

“…The mechanism for this secondary and systemic proinflammatory cytokines release is unknown, but the injury of the bowel mucosa barrier and the unknown factors involving the mesenteric lymph duct may play a role in the generalized deterioration of microcirculation and SIRS [ 21 , 28 , 29 ]. The development of microcirculatory disturbances seems to be one of the most important factors in the progression of necrotizing pancreatitis.…”