Alcohol

George F. Koob , ... Michel Le Moal , in Drugs, Addiction, and the Brain, 2014

Blood alcohol levels are measured in gram%. The degree of intoxication throughout the United States is measured by a blood alcohol level, and the legal limit is 0.08   gram%. For example, 0.08grams alcohol/100ml = 0.08gram% = 17mM. Generally, for a male who weighs 150   lbs, 4   ounces of spirits (100 proof = 50% alcohol), four glasses of wine, or four beers will result in a blood alcohol level of approximately 0.10   gram%. For a female who weighs 150   lbs, these same amounts of alcohol will result in a blood alcohol level of 0.12   gram%. The difference in blood alcohol levels in males and females has been attributed to differences in the distribution of body fat, with more fat per kilogram (thus less water) for females, and lower gastric levels of the alcohol-metabolizing enzyme alcohol dehydrogenase in females.

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Alcohol a double-edged sword

Amitava Dasgupta , in Alcohol, Drugs, Genes and the Clinical Laboratory, 2017

Physiological effects of various blood alcohol levels

Blood alcohol depends on many factors including number of drinks, gender (females show higher blood alcohol than males for consuming same amounts of alcohol when body weights are comparable), and body weight. Moreover, peak blood alcohol level is lower if alcohol is consumed with food and if alcohol is sipped instead of consumed rapidly. The presence of food not only reduces blood alcohol level but also stimulates its elimination through the liver. Alcohol is first metabolized to acetaldehyde by the enzyme alcohol dehydrogenase and then by aldehyde dehydrogenase into acetate. Acetate finally breaks down into carbon dioxide and water. For higher alcohol consumption, liver CYP2E1 plays a role in alcohol metabolism.

Substantial research has established that the effect of alcohol on the human depends on the blood alcohol concentration. At a very low blood alcohol level people usually feel relaxation and mild euphoria and some loss of inhibition or shyness. However, at blood alcohol levels that exceed the legal limit for driving in United States, significant impairment of motor skills may occur. At a blood alcohol level of 0.3% and higher, complete loss of consciousness may occur and a blood alcohol level of 0.5% and higher may even cause death (Table 1.2). Drinking excessive alcohol in one occasion may cause alcohol poisoning which if not treated promptly may be fatal. Celik et al. reported that postmortem blood alcohol levels ranged from 136 to 608   mg/dL in 39 individuals who died due to alcohol overdose. Most of those deceased were male [5]. The mechanism of death from alcohol poisoning is usually attributed to paralysis of respiratory and circulatory centers in the brain causing asphyxiation.

Table 1.2. Physiological effects of various blood alcohol levels

Blood alcohol level Physiological effect
0.01–0.04% (10–40   mg/dL) Mild euphoria, relaxation, and increased social interactions.
0.05–0.07% (50–70   mg/dL) Euphoria with loss of inhibition making a person more friendly and talkative. Some impairments of motor skills may take place in some individuals, and as a result, in some countries, e.g., Germany, the legal limit of driving is 0.05%.
0.08% (80   mg/dL) Legal limit of driving in United States. Some impairment of driving skills may be present in some individuals.
0.08–0.12% (80–120   mg/dL) Moderate impairment to significant impairment of driving skills depending on drinking habits. Emotional swings and depression may be observed in some individuals.
0.12–0.15% (120–150   mg/dL) Motor function, speech, and judgement are all severely affected at this height of blood alcohol. Staggering, and slurred speech, may be observed. Severe impairment of driving skills.
0.15–0.2% (150–200   mg/dL) This is the blood alcohol level where a person appears drunk and may have severe visual impairment.
0.2–0.3% (200–300   mg/dL) Vomiting, incontinence, symptoms of alcohol intoxication.
0.3–0.4% (300–400   mg/dL) Signs of severe alcohol intoxication and a person may not be able to move without the help of another person. Stupor, blackout, and total loss of consciousness may also happen.
0.4–0.5% (400–500   mg/dL) Potentially fatal and a person may be comatose.
Above 0.5% (500   mg/dL) Highly dangerous/fatal blood alcohol level.

Impairment of motor skills may occur at blood alcohol levels lower than 0.08%. Phillips and Brewer commented that accident severity increases when the driver is merely "buzzed" compared to sober drivers because buzzed drivers are significantly more likely to speed, and the greater the blood alcohol, the greater the speed as well as the severity of the accident. Moreover, a buzzed driver may not put the seatbelt on properly. Usually alcohol-related traffic accidents are more likely to take place on weekends, in the months of June–August, and from 8   pm to 4   am [6].

Falleti et al. demonstrated that cognitive impairment associated with 0.05% blood alcohol is similar to staying awake for 24   h [7]. Moreover, many industrialized countries such as Austria, France, Germany, and Italy have set legal limit of driving at 0.05%. Although the legal limit of driving in Canada is 0.08%, in some Canadian provinces, 0.05% blood alcohol is considered as the "warning range" limit at which officers may suspend a driver's license for 1–7 days. The National Transportation Safety Board in 2014 recommended lowering the legal limit of driving in the United States to 0.05%, but it is not adopted as the law. Scientific research has shown that even at 0.05% blood alcohol virtually all drivers are impaired regarding at least some driving practices [8]. For avoiding driving while intoxicated in United States, consumption of alcohol with food is highly recommended. For men, up to 2 standard drinks consumed with food in a 2   h period (1 drink per hour) and for women up to 1 drink with food consumed in a 2   h period should produce blood alcohol levels below 0.08%.

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Methods for Determining Blood Alcohol Concentration: Current and Retrospective

Kate B Carey , John T P Hustad , in Comprehensive Handbook of Alcohol Related Pathology, 2005

Overview of methods

BAC measurements can be obtained from living or deceased subjects, from a variety of body fluid or tissue specimens (Caplan, 1996). The standard is direct blood alcohol measurement because it best represents the effects of alcohol on the brain and can be obtained from a living person. In addition to body fluids (blood, urine, saliva, sweat), BAC can also be derived from breath samples and it can also be estimated under controlled conditions.

One source of confusion in the literature is the methods of expressing BAC. BACs can be expressed in two formats: (a) weight by volume (w/v) or (b) weight by weight (w/w). In the more common w/v format, BAC is calculated using grams or milligrams of alcohol in a given volume of blood (usually 100 ml or its equivalent, 1 dl). Thus, BAC in grams per deciliter is equivalent to grams per 100 ml, and can be expressed as grams percent (0.10%) or milligrams percent (100 mg%). See Table 2 for two BACs expressed in common units found in the research literature.

Table 2. BAC expressed in common units found in the research literature

W/v W/w Breath analysis
0.10% 0.10 g/100 ml 0.10 g/dl 100 mg/dl 1 g/l 0.095% 0.10 g/210 l breath
0.08% 0.08 g/100 ml 0.08 g/dl 80 mg/dl 0.8 g/l 0.076% 0.08 g/210 l breath

Note: W/w = w/v ÷ 1.055 (i.e., specific gravity of blood).

In the following sections we will present an overview of common methodologies associated with blood, breath, urine, saliva, and transdermal analysis. We also discuss methods of retrospective reconstruction using formulas for deriving BACs. For each method, we will present the primary advantages and disadvantages of the approach.

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The Clinical Biochemistry of Alcohol

S.B. Rosalki , in Scientific Foundations of Biochemistry in Clinical Practice (Second Edition), 1994

Accident and Emergency Departments.

Blood alcohol concentrations have been measured in patients attending accident and casualty departments with head and other injuries; some 50% were found to have raised values, usually in the region of 100–300 mg/dL (22–65 mmol/L). Similarly, 40% of patients attending an accident and emergency service during the evening hours had positive breath-alcohol readings, one-third of these corresponding to a blood alcohol greater than 80 mg/dL (17 mmol/L). 49

Alcohol measurements in accident and emergency departments may grossly underestimate the frequency of chronic alcohol abuse. In patients attending such a department, randomly screened by questionnaire for problem drinking, measurement of breath alcohol showed a diagnostic sensitivity of only 22%. 50 Almost 80% of positive breath tests were thought to represent casual drinking only.

Up to one-third of drivers involved in road traffic accidents and with blood alcohol concentrations exceeding 80 mg/dL (11 mmol/L) have been found to show additional biochemical changes suggestive of chronic alcohol abuse.

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Alcohol Withdrawal Seizures

PROSPER N'GOUEMO , MICHAEL A. ROGAWSKI , in Models of Seizures and Epilepsy, 2006

Blood Sampling and Measurement of Blood Alcohol Concentrations

Blood alcohol concentrations are typically measured during intoxication, at the onset of withdrawal symptoms, and during the fully developed withdrawal syndrome. Blood samples are usually collected from the tail vein in mice or by intracardiac sampling in deeply anesthetized rats using large-bore (21-gauge) needles to prevent hemolysis. Blood samples are stored in tubes containing heparin or the anticoagulant potassium oxalate and sodium fluoride (Becton Dickinson Vacutainer Systems, Rutherford, NJ). Blood ethyl alcohol concentrations are measured using gas chromatography (Brown and Long, 1988) or determined in the plasma using the alcohol dehydrogenase method, which requires a spectrophotometer to measure the absorbance at 340 nm (Pointe Scientific, Canton, MI).

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Toxicology/Alcohol

A. Stowell , in Encyclopedia of Forensic Sciences (Second Edition), 2013

Abstract

Although blood alcohol concentrations are most commonly used to assess the degree of alcohol intoxication, blood is not always available for analysis, and it may be in poor condition, especially in postmortem investigations. Therefore, analysis of alcohol in other body fluids is common in forensic laboratories. The alcohol concentration in a body tissue or fluid is generally proportional to the water content of that tissue or fluid. For example, if the water content of a body tissue is 10% higher than that of blood, the tissue's alcohol content should be 10% higher than that of blood. This is the basis for estimating blood alcohol concentrations from alcohol concentrations in other body fluids and tissues. Knowledge of the alcohol content of oral fluid, sweat, and tears can be used to make reliable estimates of coexisting blood alcohol concentrations. However, such estimates are more complicated when dealing with body fluids existing in isolated compartments where there is slow or very little exchange of alcohol between blood and the isolated fluid, for example, bile, eye fluid, and urine. Nevertheless, in postmortem investigations, knowledge of the alcohol content of any one of these and other fluids can often be used to estimate the minimum blood alcohol concentration existing some time before death.

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The Effects of Alcohol on the Human Nervous System

Kathleen T. Brady , in The Effects of Drug Abuse on the Human Nervous System, 2014

2.2 Acute Intoxication

As blood alcohol levels increase in humans, the impact of alcohol on cognitive abilities, psychomotor performance, and vital physiologic functions increases (Naranjo and Bremner, 1993, Table 2).

Table 2. Clinical Manifestations of Blood Alcohol Concentration

Blood Alcohol Level mg% Clinical Manifestations
20–99 Loss of muscular coordination
Changes in mood, personality, and behavior
100–99 Neurologic impairment with prolonged reaction time, ataxia, incoordination, and mental impairment
200–299 Very obvious intoxication, except in those with marked tolerance nausea, vomiting, marl-zed ataxia
300–399 Hypothermia, severe dysarthria, amnesia, Stage 1 anesthesia
400–799 Onset of alcoholic coma, with precise level depending on degree of tolerance
Progressive obtundation, decreases in respiration, blood pressure and body temperature
Urinary incontinence or retention, reflexes markedly decreased or absent
600–800 Often fatal because of loss of airway protective reflexes from airway obstruction by flaccid tongue, from pulmonary aspiration of gastric contents, or from respiratory arrest from profound central nervous system obstruction

Source: Reproduced with permission (Mayo-Smith, 2009)

With chronic use, tolerance to the effects of alcohol develops, so the functional impact of a specific amount of alcohol is dependent on a number of factors including degree of tolerance, rate of intake, body weight, percentage of fat and gender.

Alcohol intoxication initially impacts the frontal lobe region of the brain, causing disinhibition, impaired judgment, and cognitive and problem-solving difficulties. At blood alcohol concentrations between 20   mg% and 99   mg%, along with increasing mood and behavioral changes, the effects of alcohol on the cerebellum can cause motor-coordination problems. With blood alcohol levels of 100–199   mg%, there is neurologic impairment with prolonged reaction time, ataxia, and incoordination. Blood alcohol levels of 200–399   mg% are associated with nausea, vomiting, marked ataxia and hypothermia. Between 400   mg% and 799   mg% blood alcohol level, the onset of alcohol coma can occur. Serum levels of alcohol between 600   mg% and 800   mg% are often fatal. Progressive obtundation develops with decreases in blood pressure, respiration, and body temperature. Death may be caused by the loss of protective airway reflexes, aspiration of gastric contents or respiratory/cardiac arrest through depressant effects of alcohol on the medulla oblongata and the pons (Table 2, and Mayo-Smith, 2009).

Severely intoxicated individuals may require admission to the hospital for management in specialized units with close monitoring and respiratory support. In individuals with coma, alternative causes must always be investigated, such as head injury, other drug use, hypoglycemia, or meningitis.

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Death from Alcohol Poisoning

JA Crampton , K Berry , in Comprehensive Handbook of Alcohol Related Pathology, 2005

Aspiration of Gastric Contents

Blood alcohol levels greater than 250 mg/dl produces profound effects on the respiratory centre in the brain causing respiratory paralysis, and also on the glottic reflex, increasing the likelihood of aspiration of gastric contents. Many deaths that occur from acute alcohol poisoning are associated with aspiration of gastric content, subsequent asphyxia and death.

Classically, the aspiration of gastric content causes an acute chemical pneumonitis. This is characterized by acute inflammation of the major airways and the lungs in response to direct contact with the noxious material. Aspiration of acidic contents, such as gastric content, is associated with immediate injury to the trachea, bronchi and alveoli. On direct vision at bronchoscopy, diffuse bronchial erythema is seen. The degree of injury is directly related to the pH of the gastric content, with low pH materials having the most profound effects. The resultant process is that of acute lung injury, with release of proinflammatory cytokines and inflammatory cell infiltration. The acute inflammatory process plays an important role in the sequelae of aspiration pneumonia. Sequelae primarily involve hypoxaemia that can be life-threatening (Johnson and Hirsch, 2003). There are many factors that play a role in the formation of hypoxaemia and are shown in Table 4.

Table 4. Factors contributing to hypoxaemia in aspiration pneumonitis

Re.ex bronchospasm

Decreased surfactant activity

Atelectasis

Subsequent ventilation–perfusion mismatch

Intrapulmonary shunting

Direct alveolar damage

Note: Sequence of events as a result from aspiration of gastric contents after acute alcoholic intoxication.

In people who have suffered acute alcohol poisoning, the primary event that will lead to their death will be hypoxaemia.

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Biochemical Mechanisms of Fatty Liver and Bioactive Foods

R. Sharma , in Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease, 2013

3 Diagnosis of Fatty Liver Disease

3.1 Elevated Liver Enzymes

Serum ADH, serum transaminases aspartate transaminase [AST] and ALT are major indicators of alcohol-induced injury. Author established hepatocyte and Kupffer cell enzymes participating in liver injury and drug metabolism at different points in cell as shown in Figure 41.2. In fatty liver, diffused liver injury was shown associated with elevated liver tissue metabolite contents, serum metabolites and nuclear magnetic resonance (NMR) relaxation data with visible changes in liver magnetic resonance imaging (MRI) scan (see Figure 41.4; Table 41.1).

Figure 41.4. Focal hepatic steatosis is shown by different imaging modalities including US (a), CT (b), in phase MRI (c), out phase MRI (d), T 2wt MRI (e), T 2FS MRI (f), T 1Grad MRI (g), and out of phase susceptibility MRI (h).

 Source: http://radiopaedia.org/articles/focal_fat_infiltration.

Table 41.1. Comparative NMR Biochemical Correlation Analysis of Liver with Diffused Injury by Different Methods Using NMR Relaxation Times, In Vitro NMR Spectroscopy, In Vivo MR Spectroscopy, Tissue Metabolites, and Serum Enzyme Levels

Method Normal liver Diffused liver injury
In vitro pulsed NMR
T 1 ms
T 2 ms
448   ±   20   ms
88   ±   7   ms
939   ±   11   ms
144   ±   9   ms
In vitro NMR spectroscopy
  Phosphocreatine/creatine
  Phosphorylcholine
  Taurine
0.48   mM
7.2   mM
5.75   mM
1.06   mM
61.3   mM
23   mM
In vivo NMR spectroscopy
  Glutamine
  Aspartate
36.1   mM
6.27   mM
35.2   mM
2.7   mM
Biochemical tissue metabolites
  Phospholipids
  Triglycerides
113.8   ±   3.9   mg%
89.7   ±   4.8   mg%
168.9   ±   5.6   mg%
139.9   ±   3.6   mg%
Biochemical serum levels a
  Serum glutamate pyruvate transaminase
  Alkaline phosphatase
  Bilirubin
18.5   ±   1.9 IU
39.5   ±   7.8 IU
1.5   ±   0.2   mg%
140.9   ±   15.4 IU
239.9   ±   23.4 IU
4.2   ±   0.6   mg%
a
IU is defined as μ moles substrate used per minute per mg enzyme protein.

Source: Sharma, R., 1995. PhD (MRI) dissertation thesis submitted at Indian Institute of Technology, New Delhi.

3.2 Imaging of Fatty Infiltration

Liver imaging is emerging as theradiagnostic tool to image liver tissue changes with localization of cellular or molecular lesions or infiltration. MRI is choice of microimaging of soft tissues. Due to soft tissue of liver and active metabolism in hepatocytes, sequential changes in liver acini offer a window to assess metabolic changes and fatty infiltration as shown in Figure 41.2.

3.3 Focal Hepatic Steatosis

Focal hepatic steatosis (focal fat infiltration of the liver) is common and seen in a number of clinical settings, essentially the same as those that contribute to diffuse hepatic steatosis:

•

Diabetes mellitus

•

Obesity

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Alcohol abuse

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Exogenous steroids

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Drugs (amiodarone, methotrexate, chemotherapy)

•

IV hyperalimentation

In general treatment of the underlying condition will reverse the findings.

3.4 Location

A characteristic location for focal fatty change is the medial segment of the left lobe of the liver (segment IV) either anterior to the porta hepatis or adjacent to the falciform ligament. This distribution is the same as that seen in focal fatty sparing and is thought to relate to variations in vascular supply. This also would account for focal fatty change/sparing sometimes seen related to vascular lesions.

3.5 Radiographic Features

3.5.1 Ultrasound

Ultrasound features only become apparent when the amount of fat reaches 15–20%. Features include the following:

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Increased hepatic echogenicity

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Hyperattenuation of the beam

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Mild or absent positive mass effect

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Geographic borders

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No distortion of vessels

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Inability to visualize the portal vein walls (as the parenchyma is as bright as the wall)

3.5.2 Computed tomography
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Decreased attenuation (noncontrast computed tomography (CT))

○

normal liver 50 57 HU

○

decreases by 1.6 HU per mg of fat in each gram of liver

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Decreased attenuation (postcontrast CT)

○

liver and spleen should normally be similar on delayed (70   s) scans

○

earlier scans are unreliable as the spleen enhances earlier than the liver (systemic supply rather than portal)

3.5.3 Magnetic resonance imaging

MRI is the imaging modality of choice in any case where the diagnosis is felt to be less than certain:

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Increased T1 signal

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Signal dropout in out of phase imaging

•

Ability to quantify fat fraction

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Alcohol: Absorption, Metabolism, and Physiological Effects

R. Rajendram , ... V. Preedy , in Encyclopedia of Human Nutrition (Third Edition), 2013

Effects of Food on Blood Ethanol Concentration

The peak BEC is reduced when alcohol is consumed with or after food. Food delays gastric emptying into the duodenum. This attenuates the sharp early rise in BEC seen when alcohol is taken on an empty stomach. Food also increases elimination of ethanol from the blood. The area under the BEC/time curve (AUC) is reduced (Figure 4). The contributions of various nutrients to these effects have been studied, but small, often conflicting, differences have been found. It appears that the caloric value of the meal is more important than the precise balance of nutrients.

Figure 4. Blood ethanol concentration curve after oral dosing of ethanol. A subject ingested 0.8   g   kg−1 ethanol over 30 minutes either after an overnight fast or after breakfast. The peak blood ethanol concentration and the area under the curve are reduced if ethanol is consumed with food.

In animal studies ethanol is often administered with other nutrients in liquid diets. The AUC is less when alcohol is given in a liquid diet than with the same dose of ethanol in water. The different blood ethanol profile in these models may affect the expression of pathology.

However, food increases splanchnic blood flow, which maintains the ethanol diffusion gradient in the small intestine. Food-induced impairment of gastric emptying may be partially offset by faster absorption of ethanol in the duodenum.

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