PHYSIOLOGICAL MECHANISM UNDERLYING ALCOHOL-INDUCED TISSUE INJURY

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Molina, PE1,2,3

1Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
2LSUHSC-NO Alcohol and Drug Abuse Center of Excellence, New Orleans, Louisiana, USA
3LSUHSC-NO Comprehensive Alcohol-HIV/AIDS Research Center, New Orleans, Louisiana, USA

Chronic heavy alcohol consumption, the most common and costly form of drug abuse, is a major contributing factor to many disease categories. The alcohol-attributable disease burden is closely related to the average volume of alcohol consumption with dose-dependent relationships between amount and duration of alcohol consumption and the incidence of diabetes mellitus, hypertension, cardiovascular disease, stroke, and pneumonia. The frequent occurrence of alcohol use disorders in the adult population, and the significant and widespread detrimental organ system effects highlight the importance of recognizing and further investigating the pathophysiological mechanisms underlying alcohol-induced tissue and organ injury. Alcohol can permeate to virtually all tissues in the body, resulting in alterations in significant multi-systemic pathophysiological consequences. Approximately 3.4% of global non-communicable disease-related burden of deaths, 5% of net years of life lost, and 2.4% of net disability-adjusted life years can be attributed to heavy alcohol consumption, with higher burden for cancer and liver cirrhosis. However, recognition of alcohol as an underlying causal factor in comorbid conditions remains a challenge in the clinical setting. This presentation will discuss salient alcohol effects on non-neural tissues derived from preclinical and clinical studies. Several pathophysiological mechanisms have been identified as causative factors in tissue and organ injury resulting from heavy alcohol consumption including: acetaldehyde generation and adduct formation, mitochondrial injury, cell membrane perturbations, immune modulation, and oxidative stress. Some of these mechanisms are the result of direct alcohol-induced cell perturbations; others are the consequence of tissue alcohol metabolism. Thus, a brief overview of salient aspects of alcohol metabolism and pharmacokinetics will precede the discussion on alcohol-induced organ injury. After providing an overview of some of the critical non-neuronal physiological systems impacted by alcohol abuse, their contribution to the pathophysiology underlying the most frequent comorbid conditions, and we highlight critical areas in need of further research.

Research supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health P60 AA09803 LSUHSC-NO Comprehensive Alcohol-HIV/AIDS Research Center.

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