Gin Lane 1751 - William Hogarth (1697-1764)
Source: Wikimedia Commons
Alcohol is absorbed from the gastrointestinal tract and distributed in the body in proportion to the amount of fluid in the tissues. Less than 10% is eliminated by the lungs and kidneys.
Pathways for metabolism
- alcohol dehydrogenase (to acetaldehyde)
- microsomal ethanol-oxidising system (cytochrome P450 to acetaldehyde; the main method for increased clearance in regular drinkers)
- catalase (to acetaldehyde)
Metabolism of acetaldehyde
- oxidised to acetate in the liver
- acetaldehyde toxicity is a function of glutathione depletion, oxidative stress, and lipid peroxidation
Alcohol metabolism and metabolic disturbances
- raised lactate: pyruvate ratio leads to lactic acidosis, and reduced urate clearance (leading in turn to secondary hyperuricemia)
- reduced carbohydrate metabolism and reduced gluconeogenesis from amino acids leads to hypoglycaemia
- reduced fat metabolism leads to fatty acid “trapping”, increased triglyceride synthesis, and reduced protein synthesis (leading to hepatocyte fat accumulation)
- reduced serotonin metabolism
- altered steroid metabolism
Alcohol is fully absorbed from the stomach within one to two hours with ingestion; a stomach alcohol concentration of equal to or greater than 500mg/dL corroborates recent drinking (Plueckhahn (1968)). Alcohol absorption is delayed with concurrent food consumption.
interpreting post mortem alcohol concentrations (Kugelberg and Jones 2007)
Interpreting alcohol toxicological analysis is difficult, and one must consider the condition (i.e. presence of decomposition) of the body, the post-mortem interval, the environmental conditions, and the nature of the biological specimen. There is post-mortem diffusion of alcohol from the stomach, and production of alcohol is possible during decomposition (with increasing post-mortem interval).
An example of difficulties in the interpretation of post-mortem alcohol concentrations is provided by Corry (1978), regarding the Moorgate tube train disaster, where there was a 4-day delay in retrieving the body of the tube train driver; apparently there was a difference of up to 80mg/dL in blood alcohol concentration measured from different body sites.
It is recommended that post-mortem blood samples are taken from a femoral vein (Druid and Holmgren 1997), with that sample being stored in a sodium fluoride preserved bottle/tube (fluoride is an enzyme inhibitor, particularly of fungal growth), with or without additional samples from urine and vitreous humour.
Alcohol analysis is performed using gas chromatography with flame ionisation (direct injectional head space), and a concentration of less than 10mg/dL can be considered to be negative. Less than 30mg/dL is of “debatable significance”.
Blood alcohol concentration can be converted into the amount absorbed and distributed in the body via the Widmark equation (but this usually results in an underestimate).
A fatal blood alcohol concentration depends on:
- drinking experience
- speed of drinking
- type of drink
- environmental temperature (i.e. hypothermia)
- the presence/absence of “positional asphyxia”
Alcohol toxicity is enhanced with the concurrent use of opiates, anti-depressants, and hypnotics (Koski 2003).
Alcohol elimination rates can be up to 20 to 30mg/dL per hour in heavy drinkers.
Deaths have been attributed to acute alcohol toxicity with a post-mortem blood alcohol concentration of 220 to 500mg/dL (mean 360mg/dL) by Jones and Holmgren (2003), but the post-mortem blood alcohol concentration should be interpreted alongside all the other post-mortem findings.
Baselt (2004) indicates that a non-fatal blood alcohol concentration of 780mg/dL has been recorded in the literature, and a concentration of 1130mg/dL has been recorded in a “failed suicide”.
Acute blood alcohol toxicity fatalities have been recorded (see Baselt 2004) with the following post-mortem concentrations:
- average blood alcohol concentrations 740mg/dL (range 420 – 1770mg/dL)
- average urine concentrations 620mg/dL (range 490 – 940mg/dL)
- urine alcohol versus blood alcohol concentrations
The urine to blood alcohol concentration ratio provides information regarding the status of alcohol absorption at the time of death (Jones and Holmgren 2003).
If the ratio is close to unity it implies that there is incomplete absorption of alcohol, such as where there has been recent alcohol consumption. In such circumstances, analysis of stomach contents might also show residual alcohol which has not yet been metabolised.
If the ratio is equal to, or greater than, 1.25 (i.e. 25% more alcohol in the urine), it is likely that there has been complete alcohol absorption with resulting excretion.
Moritz (1942) indicated that there was insignificant post-mortem alcohol diffusion from urine to blood.
The urine water content is approximately 99 – 100%, whereas the blood water content is closer to 80%.
For reference, one unit of alcohol is approximately equivalent to 10g of alcohol (i.e. half a pint of beer, a single measure of spirits, or a standard glass of table wine). The “average man” is able to metabolise 9g of alcohol per hour (range 7 – 16g per hour), whereas a “habituated drinker” is capable of metabolising up to 40mg/dL per hour.
A blood alcohol concentration of 80mg/dL is approximately equivalent to 107mg/dL in the urine, because of the difference in water content of those substrates.
vitreous humour alcohol analysis
There is thought to be a rapid entry of alcohol (apparently taking between 30 – 60 minutes to equilibrate), and there is very little difference between the eyes. Post-mortem synthesis of alcohol in vitreous humour is theoretically possible, because some glucose may be present in that substrate.
Estimating blood alcohol concentration from vitreous humour alcohol concentration is not advisable (vitreous humour alcohol to blood alcohol ratio = 1.2 to 1), but some authors have provided equations for doing just this; Gelbke (1978) states that the blood alcohol concentration can be calculated by multiplying the vitreous humour concentration x 0.81, whilst Jones and Holmgren (2001) states that the blood alcohol concentration can be calculated by dividing the vitreous humour alcohol concentration x 1.75.
Alcohol (and other drugs) is thought to be stable in vitreous humour at 40C in fluoride preserved collecting tubes/containers, and Zumwalt (1982) found very little bacteria within vitreous humour even in cases of bodies that were “moderately decomposed”.
Pounder and Kuroda (1998) claim that the use of vitreous humour to predict blood alcohol concentration is too variable to be of practical use.
post mortem decomposition and blood alcohol concentrations
Caution should be used when interpreting post-mortem blood alcohol concentrations in cases of decomposition, but Levine (1993) considers ante-mortem alcohol ingestion to be most likely where the post-mortem blood alcohol concentration is greater than 40mg/dL. There are, however, rare occasions when post-mortem decomposition results in spurious post-mortem blood alcohol concentrations being identified, including in the USS Iowa disaster explosion (reported by Mayes 1992), where a blood alcohol concentration of 190mg/dL was recorded, and concentrations of 150mg/dL were recorded in other aviation disasters. Other authors state that concentrations greater than 50mg/dL are rarely recorded as a consequence of post-mortem decomposition alone.
It is noted that post-mortem decomposition following submersion/drowning can result in elevated blood alcohol concentrations being measured, which may be a function of warm water immersion, although dilutional effects following prolonged immersion may also result in dilution of blood alcohol concentrations.
It should also be noted that microbes can also lower the post-mortem blood alcohol concentration. The main micro-organisms responsible for the post-mortem production of alcohol include Candida and E-coli.
Post-mortem redistribution is not thought to be an important phenomenon when interpreting post-mortem blood alcohol concentrations, as alcohol is unionised and rapidly absorbed and distributed evenly throughout body water.
post mortem extradural/ subdural haematoma alcohol analysis
Alcohol present in haematomas is not apparently metabolised as it would be in the general circulation (Pounder and Jones 1998), and alcohol can be analysed from the substrates, when peripheral blood cannot be sampled.
Haematomas can be successfully analysed by mixing the clot with water and then using gas chromatography (Senkowsky and Thompson 1990).
Eisele (1984) sounds a note of caution, however, and states that delayed subdural haemorrhage formation would give a negative result (presumably flowing metabolism and excretion), whilst levels in slowly forming haematomas in hospitalised individuals might actually be higher in the haematoma than that which would have been present at the time of injury. Post-injury alcohol metabolism is said to be variable, and alcohol diffusion rates may differ depending on the size of the haematoma, and the anatomical region in which it is found.
Toxicological analysis of subdural/extradural haematomas may therefore be more valuable for detecting pre-traumatic substance misuse where that substance has a short half life (of less than several hours).
alcohol withdrawal in art
source: Kerry Callen
(for this, and other, excellent spoof comic book covers, go to Kerry's blog)
alcohol in history - Prohibition (USA)
Prohibition - the 'noble experiment' - refers to the ban on manufacture, sale, and transportation of alcohol in the USA between 1920 and 1933.
When Prohibition was introduced, I hoped that it would be widely supported by public opinion and the day would soon come when the evil effects of alcohol would be recognized. I have slowly and reluctantly come to believe that this has not been the result. Instead, drinking has generally increased; the speakeasy has replaced the saloon; a vast army of lawbreakers has appeared; many of our best citizens have openly ignored Prohibition; respect for the law has been greatly lessened; and crime has increased to a level never seen before.
John D Rockefeller Jr 1932 (Letter on Prohibition - see Daniel Okrent, Great Fortune: The Epic of Rockefeller Center, New York: Viking Press, 2003. (pp.246/7) via Wikipedia )
pouring away alcohol seized during Prohibition (year unknown)
Alcoholics don’t eat, liver and musculature glycogen stores are depleted, and lipolysis is triggered, leading to the conversion of triglycerides to the fatty acids, which are then metabolised in the liver to the ketones. Lactate is increasingly produced during the oxidation of ethanol. The combination of ketoacidosis and hypoglycaemia (see below) may be augmented by vomiting.
augmented reality liver anatomy ipad app
alcohol and hypoglycaemia
Alcohol inhibits gluconeogenesis, leading to reduced blood sugar concentrations. Hypoglycaemia develops 6 to 36 hours following a heavy drinking session, especially in individuals who are undernourished, or who have not eaten within 24 hours.
Hypoglycaemia is a consequence of heavy alcohol consumption as first described by Brown and Harvey in 1941, and Gregory (2003) lists the symptoms as:
- emotional arousal
- increased heart rate
- normal pupils
- not agitated
- (may not smell of alcohol)
Marks and Medd (1964) listed the symptoms as:
- slurred speech
- decreased consciousness
- musculature rigidity
The co-existence of hypoglycaemia and metabolic acidosis is unusual in other causes of hypoglycaemia.
It is also possible that prolonged under-nutrition/sub-nutrition, hypovitaminosis, and reduced blood magnesium levels may also contribute to the symptoms seen in hypoglycaemia following alcohol consumption.
Individuals who develop such hypoglycaemia do not necessarily have to have pathological abnormalities on liver biopsies.
Hypoglycaemia following alcohol consumption is more frequently seen in a “hangover” than following an episode of near-“fasting”.
alcohol neuropathology (see Harper 1998)
Acute alcohol toxicity:
- petechial haemorrhages
- occasional large haemorrhage/infarct (e.g. with pre-existing hypertension/ atherosclerosis)
Chronic alcohol toxicity:
- cerebellar degeneration (superior vermis atrophy; crests of folia affected more than sulci (compared with hypoxia); Purkinje cell loss; granule cell loss; atrophic molecular layer; Bergmann gliosis; neuronal loss/gliosis in olivary nuclei)
- central pontine myelinolysis (demyelination in the basis pontis; hyponatraemia (e.g. in a setting of alcoholic liver damage, burns, inappropriate ADH secretion, psychogenic polydipsia, hyperemesis gravidarum, rapid correction of sodium levels in the blood); CPM leads to rapid confusion, weakness, dysarthria, hypotension, and is usually fatal within weeks; the naked-eye appearance of CPM is described as grey/soft/granular foci in the pons, extending into the middle cerebellar peduncles, and possibly the cerebellum, lateral geniculate nucleus, internal/external capsules, basal ganglia, thalami, and subcortical white matter. The microscopic appearance of CPM is described as the presence of active demyelination, reactive astrocytes/macrophages, fragmented axons (seen on palmgren staining), with preservations of neurones
- Wernicke’s encephalopathy (thiamine deficiency); acute manifestations are described as confusion, gaze palsy/ataxia, with or without Korsakoff psychosis (i.e. anterograde/retrograde amnesia and confabulation). Macroscopic appearance is said to be seen as petechiae, with a shrunken brown appearance in the mamillary bodies, hypothalamus, floor of the third ventricle, olivary nuclei and possibly the cortices. The microscopic appearance is of oedema, necrosis, reduced myelinated fibres, endothelial hyperplasia within capillaries, reactive astrocytes and/or petechiae (with preserved neurones) in the acute phase, leading to gliosis, spongiosis, macrophage deposition, and a reduction in the amount of neurones and myelinated fibres, with or without thalamic lesions in Korsakoff’s psychosis.
- Baselt RC. Disposition of toxic drugs and chemicals in man 7th Edition, Biomedical Publications, Foster City, California, USA 2004 [8th edition now available]
- Corry JE. Possible sources of ethanol ante- and post-mortem: its relationship to the biochemistry and microbiology of decomposition. Journal of Applied Bacteriology 1978; 44:1-56
- Druid H, Holmgren P. A compilation of fatal and control concentrations of drugs in post-mortem femoral blood. Journal of Forensic Sciences 1997; 42:79-87 [in Kugelberg and Jones 2007]
- Eisele JW, Reay DT, Bonnell HJ. Ethanol in sequestered hematomas: quantitative evaluation. American Journal of Clinical Pathology 1984; 81:352-355 [in Jones and Holmgren 2003]
- Gelbke HP, Lesch P, Spiegelhalder, Schmidt G. Postmortal alkoholkonzentrationen I. Die alkoholkonzentrationen im blut und in der glaskorperflussigkeit. Blutalkohol 1978; 15:1-10 [in Jones and Holmgren 2003]
- Gregory M. Alcohol-induced hypoglycaemia presenting as drug intoxication. Journal of Clinical Forensic Medicine 2003; 10:191-192
- Harper C. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? Journal of Neuropathology and Experimental Neurology 1998; 57:101-110
- Jones AW, Holmgren P. Uncertainty in estimating blood ethanol concentrations by analysis of vitreous humour. Journal of Clinical Pathology 2001; 54:699-702 [with discussion in Jones and Holmgren 2003]
- Jones AW, Holmgren P. Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism. Journal of Forensic Sciences 2003; 48:874-879 [95% of the distribution of ethanol concentrations in acute alcohol deaths was between 220-500 mg/dl; mean 360, range 74-680]
- Koski A, Ojanpera E, Vuori E. Interaction of alcohol and drugs in fatal poisonings. Human Experimental Toxicology 2003; 22:281-287 [in Kugelberg and Jones 2007]
- Kugelberg FC, Jones AW. Interpreting results of ethanol analysis in post-mortem specimens: a review of the literature. Forensic Science International 2007; 165:10-29
- Levine B, Smith ML, Smialek JE, Caplan YH. Interpretation of low post-mortem concentrations of ethanol. Journal of Forensic Sciences 1993; 38:663-667 [in O’Neil and Poklis 1996]
- Marks V, Medd WE. Alcohol-induced hypoglycaemia. British Journal of Psychiatry 1964; 110:228-232 [also referencing Brown and Harvey 1941]
- Mayes R, Levine B, Smith ML et al. Toxicologic findings in the USS Iowa disaster. Journal of Forensic Sciences 1992; 37:1352-1357 [in O’Neal and Poklis 1996]
- Moritz AR, Jetter WW. Antemortem and post-mortem diffusion of alcohol through the mucosa of the bladder. Archives of Pathology 1942; 33:939-948 [in Jones and Holmgren 2003]
- O’Neal CL, Poklis A. Postmortem production of ethanol and factors that influence interpretation: a critical review. American Journal of Forensic Medicine and Pathology 1996; 17:8-20
- Plueckhahn VD. The evaluation of autopsy blood alcohol levels. Medicine, Science, and The Law 1968; 8:168-176 [in Jones and Holmgren 2003]
- Pounder DJ, Kuroda N. Vitreous alcohol is of limited value in predicting blood alcohol. Forensic Science International 1994; 65:73-80 [in Jones and Holmgren 2003]
- Pounder DJ, Stevenson RJ, Taylor KK. Alcoholic ketoacidosis at autopsy. Journal of Forensic Sciences 1998; 43:812-816
- Pounder DJ, Jones AW. Measuring alcohol post-mortem. Chapter 5 In: Drug abuse handbook, Karch SB (Ed), CRC Press, Boca Raton, USA 1998 (pp. 356-374) [in Jones and Holmgren 2003][2nd edition now available]
- Senkowski CM, Thompson KA. The accuracy of blood alcohol analysis using headspace gas chromatography when performed on clotted samples. Journal of Forensic Sciences 1990; 35:176-180 [in Jones and Holmgren 2003]
- Zumwalt RE, Bost RO, Sunshine I. Evaluation of ethanol concentrations in decomposed bodies. Journal of Forensic Sciences 1982; 27:549-554 [in O’Neal and Poklis 1996]
liver anatomy ipad app
- interactive liver anatomy 3D model, with labelling capabilities and models of a 'fatty liver', and a cirrhotic liver