Binge Drinking's Effects on the Body

Abstract

Studies have focused on the effects of chronic alcohol consumption and the mechanisms of tissue injury underlying alcoholic hepatitis and cirrhosis, with less focus on the pathophysiological consequences of binge alcohol consumption. Alcohol binge drinking prevalence continues to rise, particularly among individuals ages 18 to 24. However, it is also frequent in individuals ages 65 and older. High blood alcohol levels achieved with this pattern of alcohol consumption are of particular concern, as alcohol can permeate to virtually all tissues in the body, resulting in significant alterations in organ function, which leads to multisystemic pathophysiological consequences. In addition to the pattern, amount, and frequency of alcohol consumption, additional factors, including the type of alcoholic beverage, may contribute differentially to the risk for alcohol-induced tissue injury. Preclinical and translational research strategies are needed to enhance our understanding of the effects of binge alcohol drinking, particularly for individuals with a history of chronic alcohol consumption. Identification of underlying pathophysiological processes responsible for tissue and organ injury can lead to development of preventive or therapeutic interventions to reduce the health care burden associated with binge alcohol drinking.

Figure 1

Mechanisms of alcohol-induced tissue injury. Alcohol contributes to tissue injury directly and indirectly through mechanisms including oxidative stress, inflammation, acetaldehyde adduct formation, barrier integrity disruption, decreased anabolic signaling, enhanced catabolic processes (particularly through the ubiquitin proteasome pathway), profibrotic changes, mitochondrial dysfunction and injury, and cell membrane perturbations. Note: mTORC1, mammalian target of rapamycin complex 1; mTORC2, mammalian target of rapamycin complex 2; ROS, reactive oxygen species. Source: Molina PE, Gardner JD, Souza-Smith FM, et al. Alcohol abuse: Critical pathophysiological processes and contribution to disease burden. Physiology. 2014;29(3)203–215.

Figure 2

Tissue alcohol metabolism contributes to tissue and organ injury through altered redox potential, generation of ROS, and generation of metabolites, such as acetaldehyde, that form DNA and protein adducts. Alcohol (ethanol) is metabolized to acetaldehyde primarily by ADH in the cytosol and CYP2E1 in the endoplasmic reticulum. Acetaldehyde is converted to acetate in the mitochondria by the enzyme ALDH. Acetaldehyde can form adducts with DNA and proteins that can produce injury through activation of immune responses. During the oxidative process, both ADH and ALDH reactions reduce NAD+ to NADH, shifting the cellular redox ratio. In addition, the cytochrome P450 enzymes, particularly CYP2E1, contribute to the oxidation of alcohol to acetaldehyde, particularly at increasing alcohol concentrations, as well as following their induction by chronic alcohol misuse. The pathway of alcohol oxidation results in the production of large amounts of ROS, including H₂O₂, and is thought to be an important mechanism contributing to alcoholic liver injury. ROS are eliminated by antioxidants like GSH under normal conditions. Alcohol depletes cellular GSH stores, thereby exacerbating ROS-mediated injury. ROS can interact with lipids, producing lipid peroxidation, which leads to formation of reactive molecules such as MDA and HNE, which can then form protein adducts. Note: Acetyl-CoA, acetyl coenzyme A; ADH, alcohol dehydrogenase; ALDH, acetaldehyde dehydrogenase type 2; CYP2E1, cytochrome P450 2E1; GSH, glutathione; H₂O, water; H₂O₂, hydrogen peroxide; HNE, 4-hydroxy-2-nonenal; MDA, malondialdehyde; NAD+, nicotinamide adenine dinucleotide (oxidized); NADH, nicotinamide adenine dinucleotide (reduced); NADP, nicotinamide adenine dinucleotide phosphate (oxidized); NADPH, nicotinamide adenine dinucleotide phosphate (reduced); O₂, oxygen; ROS, reactive oxygen species. Source: Molina PE, Gardner JD, Souza-Smith FM, et al. Alcohol abuse: Critical pathophysiological processes and contribution to disease burden. Physiology. 2014;29(3)203–215.

Figure 3

The systemic effects of chronic binge alcohol consumption and the principal organ systems affected.

Figure 4

Factors that contribute to disease processes associated with binge alcohol drinking. For individuals who drink alcohol, factors such as type of alcohol, pattern of consumption, duration of alcohol misuse, and the age and diet of the drinker contribute to the incidence and severity of tissue injury. Another factor, polypharmacy, particularly affects the older adult population, as multiple medications increase the potential for toxicity during an alcohol binge. Similarly, pre-existing comorbid conditions may predispose binge drinkers to accelerated tissue injury. Finally, genetic predisposition and environmental toxins are likely to be determining factors that affect the incidence and severity of tissue and organ injury.