**2. Physiology**

Ethanol is absorbed in the stomach or small bowel. Approximately 25% is absorbed directly from the stomach into the bloodstream; the remainder is absorbed by the small bowel. Ethanol cannot be stored; 90% up to 98% of it is broken down in the liver by oxidation. The other 2% to10% is removed directly via urine, breathed out through the lungs or excreted in sweat. Ethanol reaches its peak-blood-concentration within one hour, particularly when ingested on an empty stomach.

Oxidation of ethanol takes place in two ways. Most of it is done by enzymes known as alcohol dehydrogenase (ADH), which produces acetaldehyde, and aldehyde dehydrogenase (ALDH), which transforms acetaldehyde into acetate, a non-toxic metabolite. In this process, hydrogen is transferred from nicotinamide adenine dinucleotide (NAD+) to become NADH (figure 1). Acetate is further metabolized through the citric-acid cycle and leaves the body as carbon dioxide and water. A small amount is processed via an alternative pathway, known as the 'microsomal ethanol-oxidizing system', using cytochrome P-450. In young people, this system is hardly used, as it is mainly activated in regular drinkers or when the level of alcohol is very high (1).

Fig. 1. Oxidation of Ethanol

Different subtypes of ALDH exist within the human body. Mitochondrial ALDH-2 has the biggest affinity with alcohol. About 50 per cent of East-Asian people have a genetic variation which causes their ALDH enzyme not to work very well, resulting in accumulation of toxic acetaldehyde.

The kinetics of alcohol has several metabolic consequences. Due to a changed NAD+/NADH ratio, which inhibits gluconeogenesis, the glucose metabolism can be affected. If existing glycogen deposits have been used, this might lead to hypoglycaemia. Young persons with low glycogen levels are particularly at risk. In other situations alcohol may favor, rather than inhibit, gluconeogenesis and may therefore cause hyperglycaemia (2).

In oxidation, several acid metabolites are being formed, such as lactate and hydroxyacid, which causes metabolic acidosis. In metabolic acidosis, renal potassium loss can cause hypokalaemia, which could be increased by vomiting. These metabolic alterations also favor liver damage. In practice, hypoglycaemia rarely occurs and acidosis is often mild (2) (see also Acute Care chapter).

Symptoms of alcohol intoxication usually appear at a blood alcohol concentration of 20-50

mg/dl (0.2-0.5%) (Table 3). However, interpersonal variability can be observed. Children have a smaller extracellular volume and could therefore experience symptoms at a lower blood concentration. Symptoms of alcohol use will be further discussed below.
