Alcoholism And Its Effects

 ALCOHOLISM 

ALCOHOLISM: A chronic (for long period /lifelong) disease characterized by uncontrolled drinking and preoccupation with ALCOHOL.

Alcohol when taken orally reaches the stomach and assimilates into the blood. It takes 20 minutes for ingested alcohol to metabolize when taken orally. There will be a race between the stomach and the liver. As the alcohol gets absorbed into the blood easily (as it does not require any kind of digestion before absorption) it reaches liver and liver metabolize alcohol as it is toxic to our body. If the amount of alcohol intake is increased the load on the liver for metabolizing alcohol increases. This results in an imbalance in the body. If a person takes alcohol as an injection directly through a vein it leads to alcohol poisoning and the person might die immediately. In this case, alcohol does not reach the liver in small amounts as it was happening in the above case. Entire alcohol injected rushes towards the liver and might result in alcohol poisoning. Apart from this when you take alcohol as an injection the bacteria and other toxic chemicals present in alcohol might also enter into your body. But when taken orally all of the bacteria are killed and harmful chemicals are not absorbed by our intestine. There is a lower risk of facing the abovementioned problems.

 LET’S START WITH THE INGESTION OF ALCOHOL 

• While ingesting the alcohol the alcohol comes in contact with the glottis and gastrointestinal tract. 
• After the alcohol enters your bloodstream and participates in several metabolic reactions.

 In Gastrointestinal Tract:

1.  As alcohol travels through the digestive pathway some of the alcohol is absorbed by the cells lining the gastrointestinal tract.
2. These cells metabolize some amounts of alcohol (which can be a precursor for cancer of the gastrointestinal tract). 
3. In the stomach alcohol (even dilute [optimum of 10%]) stimulates gastric glands to produce more quantity of gastric juice. 
4. As a result, you may experience acidity and inflammation in the gastrointestinal tract, Gastritis. This can also lead to carcinoma (cancer) of the gastrointestinal tract or peptic ulcers. 
5. In the case of acute alcohol consumption, causes inflammation of the oesophagus and stomach. 
6.  In most cases, chronic consumption of alcohol leads to vomiting. >
• In case of violent vomiting, longitudinal tearing of the mucosal lining of gastrointestinal junction (the region where the oesophagus joins with the stomach). It is also known as Mallory-Weiss Syndrome. This tearing becomes easier due to the acidic condition created by alcohol in the stomach. 
7. Alcohol ingestion impairs glottis reflexes. Due to irregular opening and closing of glottis the oropharyngeal bacteria enter the respiratory tract and may cause Pneumonia, lung abscess and sleep apnea(a condition in which breathing repeatedly stops and starts).

 After It Enters Bloodstream 

1. The main organ in which alcohol is metabolized, Liver. A little amount of alcohol is metabolized in Pancreas and brain (also in cells lining the gastrointestinal tract). 
2. Alcohol metabolism takes place in the liver. 
3. A fetus does not develop a liver in the early stages of development and the liver is not functional, alcohol metabolism takes place differently. 
• Alcohol reaches the fetus through the placenta of the mother. 
• Coming to the fetus, alcohol is metabolized by the enzyme Cytochrome P4502E1(belongs to cytochrome enzyme family, found in intermembrane space of mitochondria in healthy cells) into acetaldehyde. This process is very slow and leads to the accumulation of alcohol in the fetus. As alcohol is metabolized acetaldehyde is formed. 
• As acetaldehyde is unstable it forms free radicals. 
• These free radicals can damage neural crest embryonic cells(ectodermal in origin, the precursor for melanocytes, craniofacial cartilage and bone, smooth muscles, peripheral and enteric neurons and glia) 
• It can cause severe birth defects. 
• Alcohol metabolism in the presence of cytochrome P2E1 leads to the formation of highly reactive oxygen-containing molecules – Reactive Oxygen Species [ROS] and superoxide radicals. 
• These byproducts react with proteins and DNA. In some cases, DNA is damaged. 
• These byproducts react with other substrates to form carcinogens. 
• Superoxide radicals induce oxidation of polyunsaturated fatty acids which can damage the cell membrane and thus cell. The byproducts formed in this reaction are toxic aldehyde products like 4-hydroxynoneal(HNE)[A highly toxic and most abundant stable end product of lipid peroxidation, has been implicated in the tissue damage, dysfunction, injury associated with ageing and other pathological states such as cancer, Alzheimer, diabetes, cardiovascular and inflammatory complications] 
• In adults (or teenagers), the majority of the ingested alcohol is metabolized by the liver and a little amount of alcohol is metabolized by the pancreas and brain. 
• Alcohol metabolism occurs in the presence of 2 major enzymes. They are Alcohol Dehydrogenase (ADH1B [class1, beta polypeptide]) and Aldehyde Dehydrogenase (ALDH2). 
• The efficiency of ADH and ALDH changes from person to person as it depends on the genetic material of the person. In essence, there are wide varieties of ADH and ALDH found in people around the globe. 
• The gene coding for ADH is located on the locus of chromosome 4. 
• The gene coding for ALDH is located on the locus of chromosome 12. 
• Alcohol metabolism also depends on the liver size and body mass. 
• The variety of the enzyme not only depends on the genetic factors but also on the surrounding environmental conditions. 

Ethnic Differences: 

• Effective ADH variant ADH1B*2 is commonly found in Chinese, Japanese and Korean and another variant ADH1B*3 is found in 15-25% of African Americans. o Higuchi and his colleagues found that as alcohol consumption increased in japan between 1979 and 1992, the per cent of Japanese alcoholics who carried the protective ADH1B*2 gene version increased from 2.5 to 13 per cent. 
• Effective ALDH variants are ALDH1A1*2 and ALDH1A1*3. These were found by Spence and his colleagues. 
• More ethnic native Americans die due to alcohol-related causes, but there is no difference in enzyme patterns and the rate of alcohol metabolism.[this shows a piece of evidence that environmental factors do influence a person consuming alcohol.]

Consequences of possessing different variants of ADH and ALDH: 

• A person with an effective ADH variant and a slow ALDH variant metabolize alcohol to acetaldehyde at a faster rate and acetaldehyde to acetic acid at a relatively slow rate. This leads to the accumulation of acetaldehyde in the blood. As we have discussed earlier that acetaldehyde is toxic and may cause cancer, these people are more vulnerable to the diseases and disorders caused by alcohol consumption. 
• Ironically these people cannot consume more amount of alcohol as they experience the behaviour and physiological changes quickly after consuming a little amount of alcohol and this makes alcohol unpleasant for them and thereby protects the person from alcoholism. 
• A person with less efficient ADH and more efficient ALDH is more prone to alcoholism and is vulnerable to the ill effects of alcohol in the body. As ALDH is more effective the person does not get drunk easily as acetaldehyde is metabolized quickly and efficiently. As ADH is less efficient this leads to the accumulation of alcohol and alcohol poisoning. 
• As alcohol accumulates in the body it reaches the brain (it can cross the blood-brain barrier as it can lipophilic). Here alcohol is metabolized by catalase and cytochrome P450 to acetaldehyde. The role of ADH in alcohol metabolism in the brain is not known. 
• Alcohol suppresses the functioning of mitochondria and reduces insulin production. It affects carbohydrates and fat metabolism. This leads to the accumulation of fat in the body. As fat is stored in the liver the person develops an alcoholic fatty liver. 
• Alcohol interacts with fatty acids to form Fatty Acid Ethyl Ester [FAEE] which cause irreversible damage to the liver and pancreas. 
• Alcohol increases the sensitivity of the brain towards aroma and food. This leads to increased consumption of food and the accumulation of fats and leads to obesity. 
• A person with efficient ADH and ALDH is prone to alcoholism as they can metabolize loads of alcohol. Although the process is quick and efficient, the concentration of byproducts (radicals) formed increases and the risk of cancer goes to peak levels. 
• Alcohol reacts with ADH in adults (and CytochromeP450 in fetuses whose mothers consume alcohol in large amounts) or Catalase to form acetaldehyde. 
• Acetaldehyde reacts with ALDH to form acetic acid. 
• Acetic acid reacts with either Acyl CoA synthetase or Acetyl CoA synthetase to form Acetyl CoA. 
• Acetyl CoA enters the Citric Acid cycle and forms carbon dioxide and water. 

ACETALDEHYDE – THE CULPRIT: 

• Most of the researchers believe that all the ill effects caused by alcohol consumption are due to Acetaldehyde. 
• Acetaldehyde is a highly unstable compound and forms free radicals. 
• International Agency for Research on Cancer [IARC] suggests acetaldehyde to classify as a carcinogen. 
• These formed free radicals are quenched (removed/extinguished) by antioxidants like thiamine (vitamin B1) and vitamin C. Thus a person who consumes large amounts of alcohol can suffer from these vitamin deficiency disorders. 
• Some of the ill effects caused by acetaldehyde are: 
• It can damage embryonic neural crest cells. 
• It can inhibit the growth of neural cells and the differentiation of stem cells into neurons. 
• Some researchers believe that the behavioural and psychological effects of alcohol are due to Acetaldehyde. 
• It is carcinogenic (formed free radicals react with DNA and proteins to form cancer). 
• It can cause facial flushing when taken in moderate amounts. 
• It results in a rapid heartbeat. 
• It can cause nausea. 
• Acetaldehyde also interferes with the copying of DNA and proteins and the process in which DNA is repaired. 

EFFECTS ON VITAL ORGANS: 

• LIVER: 
• As fats are stored in the liver, due to decreased metabolism of fats in the body (as mentioned above) a person develops a fatty liver. In this case, the liver gets enlarged, yellow, greasy and firm. 
• Alcoholic fatty liver develops Alcoholic Cirrhosis (liver tissue is damaged). 
• Hepatocytes become pale, swollen and contain a dense mass called Mallory’s body. These hepatocytes are surrounded by polymorphonuclear leucocytes. This condition is known as Alcoholic hepatitis. 
• Accumulated fat can block the bile duct and cause jaundice, abdominal pain and hepatomegaly (enlarged liver). This condition is known as Cholestasis [chole=bile, stasis=standing still]. 

• Nervous Tissue: 
• Axons are inflamed and cause Neuritis. 
•  Affects: 
• will power, judgement power, self-control 
• control on emotions 
• moral sense 
• The cerebellum is affected and leads to loss of muscle coordination, difficulty in learning, incoherent speech and the person might become a staggering gait (a person who has difficulty in walking). 

• Heart : 
• Due to the deposition of alcoholic fat on the walls of blood vessels, blood pressure increases (hypertension) and can lead to a heart attack if coronary arteries are affected. 

• Kidneys: 
• The secretion of vasopressin/Anti Diuretic Hormone reduces. This results in the excretion of large amounts of water and leads to dehydration. 
• Alcoholic myopathy (painful and swollen muscles) occurs in muscles. 
• Hormonal changes include increased release of Cortisol and decreased release of vasopressin, triiodothyronine and thyroxin. 
• Cancer can develop in the regions of the Liver, Brain, upper Respiratory tract, colon, rectum and breast. 

GLOSSARY: 

• Carcinogen: Cancer-causing agents like radioactive nuclide, radiation, etc.(Damage genome and interrupt in cell metabolism) 

• Blood-Brain Barrier: a selectively permeable layer of cells that protect the brain from solutes circulating in the bloodstream. 

• Alcoholism: A chronic (for long period /lifelong) disease characterized by uncontrolled drinking and preoccupation with ALCOHOL.

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