EFFECTS OF
ALCOHOL
S. Yogesh
2023 batch
OBJECTIVES:
Digestion and absorption of alcohol
Metabolism
Toxic effects from metabolism of ethanol
Adverse effects of alcohol
1. Acute alcoholism
2. Chronic alcoholism
Effects of alcohol in human population
DIGESTION AND
ABSORPTION
After consumption, alcohol is absorbed unaltered in stomach and small
intestine.
It distributes throughout the body in direct proportion to blood level
APPLICATION:
Law enforcement agencies-breath test
METABOLISM:
Rate of metabolism affects the blood alcohol level.
So, chronic alcoholics develop tolerance to alcohol as they have higher rate of
metabolism than others..
Most of ethanol in blood is converted to acetaldehyde by three enzyme systems.
1. Alcohol dehydrogenase – cytosol of hepatocytes
2. Cytochrome P-450 isoenzymes – microsomal ethanol oxidase
system
3. Catalase – peroxisomes
Alcohol dehydrogenase is main enzymes of alcohol metabolism
Cyt P450 acts at higher blood level of alcohol
Catalase responsible for only 5% of metabolism.
METABOLISM:
MICROSOMAL ETHANOL
OXIDIZING SYSTEM
At higher blood levels of alcohol, cytochrome P-450 enzyme system come
into play.
Common form involved is CYP2E1 isoform in smooth endoplasmic
reticulum.
Induction of P-450 enzymes by alcohol cause increased susceptibility of
drugs like Acetaminophen, cocaine, anaesthetics, carcinogenesis and
industrial solvents.
Alcohol at higher concentration competes with other substrates of these
enzymes potentiating the effect of drugs by decreasing catabolism.
TOXIC EFFECTS FROM
METABOLISM OF ALCOHOL:
Acetaldehyde responsible for acute effects of alcohol.
The efficiency of alcohol metabolism varies among population due to
genetic variants.
50% asians have very low ALDH activity due to substitution of lysine for
glutamine at 487 residue.
Normal allele – ALDH2*1
Inactive variant – ALDH2*2 – dominant negative activity.
Heterozygous inactive variant cause reduced enzyme activity.
Homozygous one cause intolerance to alcohol causing nausea, flushing,
tachycardia and hyperventilation
TOXIC EFFECTS FROM
ETHANOL METABOLISM:
Alcohol oxidation, by alcohol dehydrogenase cause reduced NAD.
Deficiency of NAD leads to:
1. Fatty liver due to impaired fatty acid oxidation
2. Lactic acidosis due to increase in NADH/NAD ratio
ROS generation, Metabolism of ethanol in liver by CYP2E1 produce ROS,
causing lipid peroxidation of hepatocyte membrane.
Alcohol provokes release of endotoxins(LPS) from intestinal flora, that
stimulates production of TNF and other cytokines from macrophages and
kupffer cells.
ADVERSE EFFECTS OF
ETHANOL:
Acute alcoholism exerts it’s effects mainly on CNS, but it may induce
hepatic and gastric changes.
These effects are reversible if alcohol consumption stopped
Chronic alcoholism affects not only liver and stomach, but also all other
organs and tissues as well.
ACUTE ALCOHOLISM:
Hepatic steatosis – intake of alcohol cause multiple fat droplets
accumulate in cytoplasm of hepatocytes.
Acute gastritis and ulceration
CNS depression – affecting subcortical structures like high brain stem
reticular formation that modulate cortical activity leading disordered
cortical, motor and intellectual behaviour.
Respiratory arrest – at higher blood alcohol level cortical neurons and
lower medullary centres are depressed
CHRONIC ALCOHOLISM:
Liver : alcoholic hepatitis and cirrhosis. Cirrhosis associated with portal
hypertension and increased risk of hepatocellular carcinoma.
GIT: Massive bleeding due to gastritis, ulceration, oesophageal varices –
fatal.
CNS: peripheral neuropathies and wernicke korsakoff syndrome, atropy,
degeneration of neurological structures.
CVS: dilated congestive cardiomyopathy, hypertension. Liver injury results
in decreased HDL levels.
Pancreas: acute and chronic pancreatitis
Malnutrition: empty calories but causes B vitamins deficiency.
CHRONIC ALCOHOLISM:
Fetus: fetal alcohol syndrome – microcephaly, growth and mental
retardation, facial abnormalities. Consumption during first trimester is
harmful.
Carcinogenesis: Increased incidence of cancer of oral cavity, esophagus,
liver. Acetaldehyde is main agent associated with alcohol induced laryngeal
and esophageal cancer. Acetaldehyde-DNA adducts were observed in
tumors.
People with ALDH2*2 have high risk of developing esophageal cancer.
But alcohol may be protective against coronary heart disease.
It increases HDL levels, inhibits platelet aggregation, lower fibrinogen levels.
DEATH TOLL DUE TO
ALCOHOL:
Alcohol abuse disorder (AUD) is chronic relapsing brain disease
characterized by impaired ability to stop or control alcohol use that leads to
consequences.
3.3 million deaths were reported due to alcohol worldwide annually.
Of these 50% due to drunken driving and alcohol related homicides and
suicides
“ Despite all attention given to illicit drugs such as cocaine and
opiates, alcohol abuse is far more widespread hazard and claims
more lives”.
THANK YOU.
