Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities

Alcohol misuse is a leading modifiable risk factor for disease burden across the lifespan. Alcohol-mediated end organ injury results from a combination of pathophysiological processes including oxidative stress, mitochondrial dysfunction, cell death, endoplasmic reticulum stress, extracellular matrix remodeling, and epigenomic adaptations. Alcohol's multi-systemic physiological impact causes direct cellular damage and impairs an individual's capacity to adapt or recover from additional health insults, thereby amplifying overall disease burden. While the impact of alcohol on liver and brain physiological mechanisms is the most studied, the adverse effects of alcohol extend to multiple other organ systems, and though frequently underappreciated, contribute to several comorbidities. This review focuses on alcohol-associated pathophysiological effects on the gastrointestinal, cardiovascular, immune systems, and energy metabolism that contribute to multiorgan injury and disease burden. Understanding the pathophysiological effects of alcohol on the different organ systems will significantly help inform therapeutic modalities to help reduce alcohol-associated comorbidities.