1 pint beer = 2 units 1 glass sherry = 1 unit 1 glass wine = 1 unit (one 750ml bottle = 7-10 units) 1 bottle of 30 units

Transcription

1 Alcohol Abuse: Acute vs. : An overview Dr Carolyn Fedler Of all the drugs of abuse (DOA) category, alcohol is the most commonly abused. Alcohol abuse is a serious health issue with major socio-economic consequences. Any individual may be affected, although there are certain predisposing risk factors: family history of alcoholism, occupations such as businessmen (having long lunches, travel a lot etc), being single, and stress. The diagnosis of alcohol abuse is not straightforward since the patient s selfreporting of alcohol consumption is often unreliable, and they may well believe that it is not a problem. A high degree of clinical suspicion and collaboration with relatives/colleagues is therefore required. Recommended safe limits There is a wide variation in individual susceptibility to alcohol, however the following is considered to be safe: Weekly limit of 21 units (168g) for men, and 14 units (112g) for women 1 pint beer = 2 units 1 glass sherry = 1 unit 1 glass wine = 1 unit (one 750ml bottle = 7-10 units) 1 bottle of 30 units There are different types of drinkers: Social drinkers: not more than 2-3 units /day and do not get intoxicated. Binge drinkers: those who do not usually drink daily, but get intoxicated when attending an event/ party Heavy drinkers: regularly drink more than 6 units/day, without apparent immediate harm Problem drinkers: generally exceed the legal safe limits, and often experience personal and professional problems due to their drinking. Consumption of >50 units per week (400g) for men, and > 35 units (280g) for women is considered harmful. Alcohol dependence: compulsion to drink regardless of time of day; suffer withdrawal states if alcohol is reduced or stopped, and in whom drinking overrides other activities. They persist in using alcohol despite clear evidence of harm. Metabolism Alcohol (ethanol) is metabolized almost entirely by the liver, a small proportion is excreted by the lungs and kidneys unchanged. Ethanol is oxidized to

2 acetaldehyde, then to acetate by two main systems: the cytosolic alcohol dehydrogenase and the microsomal cytochrome P450 systems. The nicotinamide-adenine-dinucleotide (reduced form) (NADH) produced by these reactions result in a high NADH: NAD ratio, which is responsible for the biochemical effects of excessive alcohol consumption. Effects of alcohol abuse The physical health hazards associated with excessive alcohol consumption is well documented (Table 1), even though the mechanisms by which it exerts detrimental effects are not completely understood. Regular consumption of 7.5 units (60g)/day in men and 5 units (40g)/day in women is associated with increasing risk of any of the diseases, in addition to psychiatric, psychological and social problems. In pregnancy, it is associated with fetal alcohol syndrome. Table 1: effects of excessive alcohol consumption Organ or system Condition Effect Liver Fatty infiltration, alcoholic hepatitis, cirrhosis, liver failure Gastrointestinal Nervous system Cardiovascular Skeletal Acute Acute Withdrawal Oesphagitis, gastritis, Haematemesis, peptic ulceration, pancreatitis, diabetes mellitus, diarrhoea, malabsorption, weight loss, malnutrition Acute intoxication, euphoria, slurred speech, amnesia, disorientation, coma Dementia, Wernicke s encephalopathy, Korsakoff s psychosis, hallucinations, peripheral neuropathy Seizures, tremor (delirium tremens) Cardiomyopathy (beriberi) Myopathy

3 Blood Reproductive Anaemia, thrombocytopaenia Men: Impotence, testicular atrophy, gynaecomastia Women: menstrual irregularities, infertility The effects of alcohol excess falls under 2 categories: Acute alcohol poisoning; where effects are directly related to the blood level of ethanol at that time. Blood alcohol levels required to produce intoxication depend on a variety of factors which include: rate of intake (rapid vs. gradual), individual tolerance (increased by previous regular alcohol consumption), and whether drinking in isolation or in company. alcohol abuse caused by the metabolic effects of continued high ethanol concentrations. Many of the effects are either due to the toxic effects generated by acetaldehyde and/or failure of the liver s homeostatic and synthetic mechanisms. Indeed, one of the earliest signs of chronic alcohol abuse is hepatomegaly ( fatty liver, due to triglyceride accumulation as a result of increased synthesis from carbohydrates and reduce protein synthesis). Ethanol is a psychoactive drug that has a substantial energy value (7.1kcal/g). In the heavy drinker, alcohol represents + 50% of the total dietary energy intake. As a consequence, many normal nutrients are displaced in the diet, resulting in primary malnutrition. Alcohol also impairs the activation and utilization of nutrients, and secondary malnutrition may result from either malabsorption or maldigestion caused by gastrointestinal complications associated with alcoholism. The role of the laboratory in detecting alcohol abuse Laboratory tests are useful in helping to identify those drinking in excess, but cannot diagnose alcoholism definitively. Acute alcohol intoxication: measurement of alcohol levels in blood, urine and breath has a limited but important role. They do give objective evidence of recent drinking. A blood alcohol level might be helpful in the working environment or in car accidents if the patient appears intoxicated but is denying alcohol abuse.

4 The behavourial and clinical features of acute alcohol intoxication are summarized in Table 2: Blood alcohol concentration (g/100ml) Stage of Alcohol influence Subclinical Euphoria Excitement Confusion Stupor Coma Death Clinical effects Nearly normal behaviour Increased self confidence, talkative, some sensory-motor impairment, decreased attention, judgment and control, increased likelihood of accident Emotional instability, impaired memory, decreased reaction time, inco-ordination, impaired balance, drowsiness Disorientation, confusion, dizziness, exaggerated emotional states, staggering gait, slurred speech Inertia, decreased response to stimuli, unable to stand/walk, incontinence, vomiting, impaired consciousness, sleep or stupor Complete unconsciousness, coma, depressed reflexes, impairment of circulation and respiration, possible death Death from respiratory arrest For normal drivers the legal limit in South Africa is 0.05 g/100ml while for commercial drivers the limit is 0.02 g/100ml The short half-life of alcohol limits its use widely as a biomarker. As the blood alcohol level detects alcohol intake in the previous few hours it is not necessarily a good indicator of chronic excessive drinking. Proper collection, handling and storage of the blood alcohol specimen are essential. Blood is the specimen of choice, as alcohol present in the urine is usually labile. Measurement of alcohol levels in routine laboratories is essentially

5 a screening test. The laboratory worker should be familiar with the variety of methodologies employed and associated interferences that limit the use of routine alcohol assays. For more definitive testing for medico-legal purposes, specialized and sophisticated methodology such as gas chromatography is required. alcohol abuse can be difficult to detect especially if there are no overt objective clinical signs and overlying psychiatric problems. The patient s history (and if possible, collaborative history from a friend or relative) and examination can lead to high index of suspicion of alcohol abuse, and laboratory tests help to support the suspicion. The most widely used markers for alcohol abuse include: Gamma glutamyltransaminase (GGT): this enzyme is increased in the majority of chronic alcohol abusers. It is not increased in binge drinkers who don t drink consistently. Remember that it is not a specific test as it is increased in all forms of obstructive liver disease, and is induced by many drugs. The half life is days and levels usually returns to normal 4-5 weeks after stopping drinking, so it can be used as a marker of abstinence Mean cell volume (MCV): It can take a month of drinking >60g/day to raise MCV above its reference range. It takes several months of abstinence for it to return to normal, so it is not useful to monitor abstinence or relapse. Transaminases AST and ALT. In alcoholics, the AST and ALT values are almost never >2-4 times the upper reference limits. There is a high index of suspicion of alcohol abuse being the cause of liver disease when the AST:ALT ratio is >2. These markers are the most frequently used. Other tests that that may lend further evidence of excessive alcohol use are uric acid and triglycerides Carbohydrate deficient transferrin (CDT) is a potentially useful and specific marker. CDT appears to distinguish chronic heavy drinkers from light social drinkers. CDT is a desialylated form of transferrin whose levels increase after alcohol consumption of 50-80g per day for at least 3 weeks. During abstinence CDT normalizes after 15 days. If drinking resumes, the lower levels of alcohol intake can lead to a rapid re-elevation. CDT is of most use in monitoring patients for increase in alcohol consumption or confirming abstinence. It is not useful for screening for heavy alcohol consumption in the general population, especially in women, and cannot identify binge drinkers. Excessive alcohol consumption may lead to the following metabolic abnormalities:

6 Increased osmol gap and anion gap: the osmal gap is the difference between the measured osmolality and the calculated osmolality, and gives an estimation of the osmotically active particles in plasma (e.g. alcohol) other than electrolytes, glucose and urea. The high anion gap is due to lactate and ketone formation Hypoglycaemia: inadequate food intake is common in chronic alcoholics. In the absence of oral carbohydrates starvation (depletes the glycogen reserves), glucose production becomes dependant on gluconeogenesis. However, continued alcohol metabolism depletes the liver cytosol of NAD (increased NADH:NAD ratio), inhibiting gluconeogenesis, resulting in hypoglycaemia Impaired glucose intolerance and diabetes mellitus (DM): recurring acute pancreatitis as a result of alcohol induced damage. Eventually the pancreas may become so damaged that impaired insulin production will progress to secondary DM Hypertriglyceridaemia and raised HDL cholesterol: pathogenesis somewhat unclear, thought that due to TG and VLDL synthesis is induced due to increased NADH Lactic acidosis: accumulation of lactate (produced in the muscle and other organs, is usually transported to liver for conversion to glucose via Cori cycle) occurs due to low NAD concentration prevents the formation of lactate to pyruvate as the enzyme lactate dehydrogenase requires NAD Ketoacidosis: less common than lactic acidosis, reflects starvation. The low blood glucose results in decreased insulin, increased glucagons which results in increased lipolysis which releases free fatty acids which subsequently undergoes oxidation to form ketones Hypophosphataemia: decreased renal absorption consequent to reduced glomerular filtration rate due to dehydration and lactic acidosis Hypomagnesaemia: Decreased intake (nutrition, vomiting, and diarrhoea) and increased renal excretion. Severe magnesium deficiency can result in hypocalcaemia and hypokalaemia, both of which may occur in chronic alcoholics Hyperuricaemia: Common in alcoholics due to increased production and decreased renal excretion as a consequence of circulating lactate and ketones which diminish renal tubular urate secretion Abnormal liver enzymes: Alcohol is hepatotoxic, which can cause an increase in transaminases. Elevated GGT may reflect liver disease (supported by increased alkaline phosphatase) or enzyme induction High creatine kinase: due to alcoholic myopathy Hypoalbuminaemia: especially in cirrhosis, severe malnutrition Coagulation defects: the liver s synthetic capacity is impaired due to cirrhosis Fat soluble vitamin deficiencies (ADEK), thiamine deficiency: nutrient uptake is impaired, reduced dietary intake consequences may include bleeding tendencies, osteomalacia, cardiomyopathy

7 Alcohol abusers are at increased risk of damage from other substances such as smoking related diseases, and have reduced rates of metabolism of therapeutic drugs, and are more susceptible to poisoning with hepatotoxic substances. Furthermore, there is an increased incidence of upper GIT and respiratory tract cancers and alcoholic cirrhosis predisposes to hepatocellular carcinoma. (Note: Please refer to other articles on liver cirrhosis and liver function tests on liver disease/ liver failure and their laboratory features) Conclusion Alcohol abuse cannot be underestimated. It is a major contributor to morbidity and mortality, and every effort should be made to establish abuse by careful questioning of patients and relatives, thorough physical and psychological assessment and appropriate investigations. References: Teitz textbook of clinical chemistry and molecular diagnostics 4 th edition 2006 page Sharpe PC (2001) Biochemical detection and monitoring of alcohol abuse and abstinence. Annals of Clinical Biochemistry 38: Recommended reading (below are good reviews)