Alcohol's Trip Through The Body

27.4.07

Beer
1. MOUTH: usual ingestion route.
2. STOMACH: little absorption/breakdown here. Most emptied to small intestine.
3. SMALL INTESTINE: uptake into bloodstream.
4. BLOODSTREAM: carries the alcohol.
5. LIVER: oxidises alcohol into water, carbon dioxide and energy at 0.015%/hour.

Alcohol - access to body
• Ingestion.
-Slowly absorbed from stomach.
-Rapidly absorbed from small intestine.
• Other routes of entry:
-Skin.
-Nasal passages/lungs.
-Other epithelia??

How to measure alcohol consumption?
• Units/grams.
• 1 unit = 8g of alcohol.

"Safe limit" for alcohol?
• In healthy male, no more than 28u/week.
• In healthy female, no more than 21u/week.

Ethanol
• Provides "empty" calories - no nutritional benefit.
• 7 cal/g - almost as high as fat in calorific content.
• Water-soluble - does not enter fat.
• Size and body build affect uptake.

Absorption of alcohol
• Rate-dependent on alcohol type and concentration.
• Peaks 1 hour after consumption.
• Faster with carbonated alcohol.
• Greater with empty stomach.
• Increased by drugs enhancing gastric emptying and those drugs that inhibit gastric alcohol dehydrogenase.
• Retarded by food, especially carbohydrate (as much as 75% compared to an empty stomach).

Distribution of absorbed alcohol
• Distribution throughout water in body.
• Most tissues exposed to same concentration of alcohol as blood.
• Liver has higher exposure due to portal system.

Elimination of absorbed alcohol
• 2-5% excreted unchanged in urine, sweat, faeces, milk or breath.
• 95% metabolised by liver.

Alcohol breakdown in liver
• ADH and ALDH2 metabolise ethanol consumed.

ADH ALDH
• Ethanol Acetaldehyde Acetate.
• ADH variants found in most tissues, but highest in liver.

Alcohol metabolism
• 1st step: oxidation of ethanol to acetaldehyde, catalysed by ADH containing NAD+.
• Conversion of acetaldehyde into acetate by ADLH also results in generation of NADH.
• NADH = Hydrogen-transfer chemical enabling oxidative phosphorylation to take place.

ADH
• Up to 50% Japanese people lack ADH.
• Inheritance of high activity ADHb2 enzyme, encoded by ADH2*2 gene, and inactive ALDH202 gene product conclusively associated with decreased risk of alcoholism.

Alcohol metabolism has powerful effects on cellular energy production pathways
• Drinking alcohol warms people up - rapid NADH production from alcohol dramatically increases energy availability and body temperature.

Excess NADH can block other normal metabolic pathways
1. Convert pyruvic acid to lactic acid.
-Hepatic gluconeogenesis inhibited.
-Glucose production decreased.
-Risk of hypoglycaemia.
-Overproduction of lactic acid blocks uric acid excretion by kidneys. Acidosis.
2. Inhibits lipogenesis.
-Accumulated fatty acid converted into ketones and lipids.
-Heavy drinkers ketotic and overweight.
3. Makes excess ATP.
-Inhibits fat oxidation and citric acid cycle.
-Accumulated fatty acids/acetyl coA → ketones and lipids.
-Excess fat in liver and blood.

Metabolism of alcohol faster in heavy drinkers
• Normal metabolism increased, generating high blood concentrations of acetate.
• Microsomal ethanol oxidising system.

Alcohol damages GI tract
• Causes inflammation of tongue, stomach, pancreas, liver and intestines.
• Breakdown products lead to fat deposition, fibrosis and scarring of liver.
• Impairs digestion of food and absorption into blood etc.

Alcoholic hepatitis
• Inflammation induces accumulation of extracellular matrix) collagen - liver fibrosis.
• Scar tissue forms.

Therefore, cirrhosis
• Growth of connective tissue destroys liver cells.

Signs
• Jaundice.
• Fluid in belly.
• Haematemesis.
• Confusion.
• Spider naevi.
• Gynaecomastia.

Oesophageal varices
• Abnormal dilatation of vein due to increase in portal vein pressure.
• Can cause life-threatening bleed.

Alcohol intoxication
• Elation, euphoria, stimulation of pleasure and reward centres in brain.
• Altered behaviour, personality, aggression etc.
• Sedation - mild anaesthetic.

Blood alcohol and brain
• Cerebral impairment at 0.1%.
• Damage of information exchange between cerebellar cortex and cerebrum, at 0.15-0.35%.
• Medulla function depressed - can occur at levels as low as 0.30%.

Alcohol on the brain
• Increased dopamine release to cause euphoria.
• Inhibits glutamate receptor function - when blocked, results in cognitive impairment and amnesia.
• Potentiates GABA receptor function - site of action of sedation and anaesthesia.
• Increased release of 5-HT (serotonin), causing one to become sleepy.

Physiological changes accompanying alcohol consumption
• Sweating, flushing, bruising.
-Body can suffer from heat loss and hypothermia.
• Tachycardia and increase in blood pressure.
• Kidneys secrete more urine.

Alcohol and sex
• Decreased sexual performance.
• Loss of libido.
• Can lead to impotence/less sperm.
• Atrophy of testicles.
• Decreased vaginal lubrication.
• Poor decision increase risk of STDs.
• Menstrual abnormalities.
• Alcohol during pregnancy causes complication for fetus.
• Breast cancer risk factor for females who engage in even moderate drinking.