Thursday, March 19, 2009

Biochemistry, Toxicity

Biochemistry, Toxicity


When drinking alcohol, it diffuses to the blood easily because it is soluble in water and can enter the body with it. It enters the body from two ways.


  1. The stomach: only a small percentage of alcohol diffuses into the blood via the stomach. alcohol is irritant to the stomach, so it affects its lining and might cause vomiting.


  1. The small intestine: most of alcohol consumed enters the body through the small intestine.


Alcohol circulates in the blood. and since alcohol is considered a toxin to the body. the body needs to break it down. this process is done by the liver. so most of the alcohol consumed goes to the liver to be processed.


Effects on the liver:


The process of breaking down ethanol (alcohol) is to oxidize it to acetaldehyde with the help of alcohol dehydrogenase enzyme.


Acetaldehyde actually is 10-30 times more toxic than alcohol. also it is cocarcinogenic and mutagenic. Therefore, it has to be broken down.


The liver breaks it down acetic acid with the help of acetaldehyde dehydrogenase enzyme. In alcoholics, this process is slow due to the impaired function of liver from previous abuse.


Acetic acid as well is very toxic to the body, so the liver converts it to either [ CO2 + H2O ] or to fats depending on the energy needs.


this whole process will lead NAD+ to be converted to NADH. High NADH level will increase the glycerol 3-phosphate which will lead to an increase in the level of esterification of fatty acids. NADH inhibits the break down of fatty acids and help increase their synthesis.


Therefore, the liver needs NADH to be converted back to NAD+ . this can happen in the conversion of pyruvate to lactate (lactate dehydrogenase enzyme). so the liver will use the pyruvate in this process instead of using it in glyconeogenisis. Therefore, this will result in a decrease of the supply of glucose to tissues especially the brain. This is the reason for hangover (fatigue, weakness, mood disturbance, low attention and low concentration).


Effects on the Brain:


  1. indirectly: no nutrition supply as mentioned above.


  1. directly: alcohol itself is a depressant to the brain. It lowers the activity of the nervous system. the brain is divided to many region each responsible for some activities. those regions are connected by neurons. neurons communicate with each other via chemical and electrical signals. NTs (neurotransmitters) are responsible to convey the signal. Alcohol has effect on some NTs.


Most important NTs affected by alcohol:


  • Glutamate: it is a excitatory NT. Alcohol affects it by inhibiting it leading to inhibition of signals.


  • GABA: Inhibitory: Alcohol acts on the GABA receptors to facilitate their action leading to an enhanced inhibition.


  • Dopamine: it is for rewarding process. it leads to code the experience or memory of alcohol, drugs, sex, food, etc in the cortex of the brain. this can influence promote subsequent behavior such as further consumption of alcohol. Alcohol activates the secretion of Dopamine.


  • Serotonin: It is for rewarding process as well. It leads to mood compulsive disorders and aggression. It also is activated by alcohol.


Effects on the kidney:


Alcohol affects the function of the kidney. It impairs its ability to regulate the level of fluids by affecting the brain as mentioned above. It also induces the urine flow by:


  1. Affecting ADH which will inhibit the reabsorption of fluids leading to large volume of urine to be excreted.


  1. Affecting the level of pH in the body:
  • It will lower the level of phosphate due to hyperventilation during withdrawal from alcohol.
  • Alkalosis (low acidity) due to severe vomiting after binge drinking which causes loss of fluids, salts and stomach acid.

Wednesday, March 18, 2009

Hangover - EDITED



Hangover is characterized by the combination of unpleasant physical and mental symptoms that occur after a bout of heavy alcohol drinking. Physical symptoms of a hangover include fatigue, headache, increased sensitivity to light and sound, redness of the eyes, muscle aches, and thirst. Signs of increased sympathetic nervous system activity can accompany a hangover, including increased systolic blood pressure, rapid heartbeat (i.e., tachycardia), tremor, and sweating. Mental symptoms include dizziness; vertigo; and possible cognitive and mood disturbances, especially depression, anxiety, and irritability.

Symptoms of Hangover

Class of Symptoms

Type

Constitutional

Fatigue, weakness, and thirst

Pain

Headache and muscle aches

Gastrointestinal

Nausea, vomiting, and stomach pain

Sleep and biological rhythms

Decreased sleep, decreased REM(rapid eye movements), and increased slow-wave sleep

Sensory

Vertigo and sensitivity to light and sound

Cognitive

Decreased attention and concentration

Mood

Depression, anxiety, and irritability

Sympathetic hyperactivity

Tremor, sweating, and increased pulse and systolic blood pressure



The particular set of symptoms experienced and their intensity may vary from person to person and from occasion to occasion. Besides, it may depend on the type of alcoholic beverage consumed and the amount a person drinks. Typically, a hangover begins within several hours after the cessation of drinking, when a person's blood alcohol concentration (BAC) is falling. Symptoms usually peak about the time BAC is zero and may continue for up to 24 hours thereafter.

Overlap exists between hangover and the symptoms of mild alcohol withdrawal (AW), leading to the assertion that hangover is a manifestation of mild withdrawal. Hangovers, however, may occur after a single bout of drinking, whereas withdrawal occurs usually after multiple, repeated bouts. Other differences between hangover and AW include a shorter period of impairment (i.e., hours for hangover versus several days for withdrawal) and a lack of hallucinations and seizures in hangover. People experiencing a hangover feel ill and impaired. Although a hangover may impair task performance and thereby increase the risk of injury, equivocal data exist on whether hangover actually impairs complex mental tasks.

http://alcoholism.about.com/od/hangovers/a/causes.htm

http://biology.about.com/library/weekly/aa010104b.htm

http://en.wikipedia.org/wiki/Hangover

http://biology.about.com/library/weekly/aa010104a.htm

Clnical Features of Alcoholism (majorly edited)

What Is Alcohol Abuse?
•People whose use of alcohol has negative effects on any aspect of their lives, including health, relationships, work or school and money, are considered to have an alcohol problem
•Severity factors: type of alcohol you drink, how much you drink, and how long you have been drinking.
•Levels of alcohol use and abuse:
moderate drinking;
at-risk drinking;
alcohol abuse; and
alcohol dependence (alcoholism).

Moderate Drinking
•men: no more than two drinks per day
•women: no more than one drink per day (due to smaller amount of water in their bodies)
•over age 65: no more than one drink per day (besides smaller amount of water, have medical conditions that can be worsened by alcohol and take medicines that can have harmful effects when mixed with alcohol)
•A standard drink is considered to be:
12 ounces of beer or wine cooler;
5 ounces of wine; or
1.5 ounces of 80-proof distilled spirits
At-Risk Drinking
•drinking that poses a risk of developing problems:
men: more than 14 drinks per week or more than 4 drinks per sitting.
women: more than 7 drinks per week or more than 3 drinks per sitting.

Alcohol Abuse
•Involves one or more of the following problems within a one-year period:
Failure to carry out major responsibilities at work, school, or home;
Drinking in physically dangerous situations, such as while driving;
Legal problems related to using alcohol; and
Continued drinking despite ongoing problems in relationships with other people that are related to alcohol use.
Alcohol abuse does not involve physical dependence on alcohol. But if it is not treated, alcohol abuse can lead to alcohol dependence.

Alcohol Dependence
•"alcoholism”, chronic and potentially fatal disease in which a person is addicted to alcohol
•characterized by three or more of the following occurring in a one-year period:
Tolerance: increasing amounts of alcohol needed to get the same effect.
Withdrawal symptoms, such as shakiness, sweating, nausea, anxiety, and depression (symptoms of increased excitability of the central nervous system= delirium tremens or “DTs”)
Drinking larger amounts and for longer than you intended.
Inability to cut down or quit drinking.
Spending a lot of time getting and drinking alcohol or recovering from its effects.
Reducing or giving up important work or leisure activities.
Continued use despite the physical or emotional problems it causes to the drinker or other people.

Diagnosis of Alcoholism
•usually recognized by the friends and family of the drinker.
•C.A.G.E is usually practised clinically.
•Diagnostic tests used by docs:
Michigan Alcohol Screening Test (http://www.ncadd-sfv.org/symptoms/mast_test.html)
Alcohol Use Disorders Identification Test (http://www.testandcalc.com/etc/tests/audit.asp)
•However, a common symptom of alcoholism is denial!

Amnesic Episodes (Blackout)
- Long term memory creation is imparted.
- Similar to anterograde amnesia
- Believed to disrupt activity of the hippocampus
(part of the brain that is involved in the formation of memory)
- Not directly dependant on amount of alcohol consumed

http://pubs.niaaa.nih.gov/publications/arh27-2/186-196.htm


Liver Damage
(i) Fatty Liver
- build up of fat around liver
- appears within 3-7 days after excessive drinking

Signs and Symptoms
- usually none.
- sometimes an enlarged liver and tenderness in the

(i) Alcoholic Hepatitis

What is it?
Inflammation of the liver

Why does it happen? :
Consumption of alcohol causes the liver to break ethyl ethanol down to acetaldehyde (highly toxic)
Acetaldehyde triggers inflammation and destroys liver cells.

Symptoms
• Loss of appetite
• Nausea and vomiting, sometimes with blood
• Abdominal pain and tenderness
• Yellowing of the skin and whites of the eyes (jaundice)
• Fever
• Abdominal swelling due to fluid accumulation (ascites)
• Mental confusion
• Fatigue
• Dry mouth
• Unusual thirst

http://www.mayoclinic.com/health/alcoholic-hepatitis/DS00785/DSECTION=causes

Test and diagnosis
(a) full medical history, including drinking habits and a physical exam
(b) Blood tests. These check for high levels of certain liver-related enzymes
Eg. gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALAT).
(c) Ultrasound. the liver may be enlarged
and to rule out other problems such as gallstones or bile duct obstruction.
(d) Liver biopsy.
(http://www.patient.co.uk/showdoc/27000462/)

(iii) Cirrhosis
What it is:
irreversible replacement of a large amount of normal liver tissue with non-functioning scar tissue.
The scar tissue forms bands throughout the liver,
Destroys the liver's internal structure
impairs the liver's ability to regenerate itself or function.

Why does it happen?
Similar reason to alcoholic hepatitis

Symptoms
• weakness
• fatigue
• loss of appetite
• nausea
• vomiting
• weight loss
• abdominal pain and bloating when fluid accumulates in the abdomen (ascites)
http://www.merck.com/mmhe/sec10/ch135/ch135e.html
• itching

Test and Diagnosis
Similar to Alcoholic Hepatitis

http://www.merck.com/mmhe/sec10/ch136/ch136c.html

Cardiomyopathy
What is it?
Heart muscles weakens due to excessive alcohol intake

Causes
heart becomes enlarged
heart muscle thins
pump inefficiently,
leads to heart failure.

Symptoms
There are usually no symptoms until the disease is in an advanced stage. At that point, the symptoms occur due to heart failure and may include:
• Awakening during the night with shortness of breath)
• Breathing difficulty while lying down (orthopnea)
• Cough containing mucus, or pink, frothy material
• Decreased alertness or concentration
• Fatigue, weakness, faintness
• Irregular or rapid pulse
• Loss of appetite
• Sensation of feeling the heart beat (palpitations)
• Shortness of breath, especially with activity (dyspnea)

http://www.nlm.nih.gov/medlineplus/ency/article/000174.htm


Cognitive impairment
Damage to the brain occurs, especially the frontal lobe.
This results in :
-loss of memory, deterioration of personality and loss of intellectual ability. Interpersonal skills, attendance to usual interests and responsibilities may deteriorate and self-neglect may result.

Depression caused by a direct effect of alcohol on the brain and exacerbated by social problems that include unemployment, divorce and debt. There is an increased incidence of deliberate self-harm. The suicide rate is increased six fold in people who are dependent upon alcohol.

Anxiety. People often use alcohol to relieve symptoms of stress and anxiety. However, anxiety symptoms increase during periods of withdrawal, leading to a cycle of increased consumption.

Psychosis. Alcoholic hallucinosis is a rare condition that is not due to alcohol withdrawal. Auditory hallucinations, often derogatory, develop in an otherwise clear consciousness. The condition usually lasts for a few days, but can persist after several months of abstinence.

Hepatic Encelopathy

What is it?
deterioration of brain function that occurs because toxic substances normally removed by the liver build up in the blood and reach the brain

Causes
Usually due to alcoholic binging

Signs and symptoms
• decreased brain function
• subtle changes appear in logical thinking, personality, and behavior.
• Normal sleep patterns may be disturbed.
• Seem drowsy and confused
• movements and speech become sluggish
• Disorientation is common
• lose consciousness and lapse into a coma.

http://www.merck.com/mmhe/sec10/ch135/ch135f.html

Acute intoxication symptoms

•Alcohol increases the effect of the body's naturally occurring neurotransmitter GABA (gamma amino butyric acid), an inhibitory neurotransmitter reduces this signal flow in the brain. This explains how alcohol depresses both a person's mental and physical activities.
Resulting:
•Disinhibition of normal social functioning (excessive talking, showing off)
•Loss of memory
•Confusion
•Disorientation
•Movement not coordinated
•Progressive lethargy
•Coma
Ultimately the shutdown of the respiratory centers (death)

Atrial fibrillation(AF)

•irregular and often rapid heart rhythm (arrhythmia)
•electrical impulses running through the heart being delayed or disrupted
•develops when muscles in the heart's upper chambers contract too quickly, resulting in an ineffective, irregular heartbeat
•Irregularity can be continuous, or it can come and go
•the heart pumps blood less efficiently, allowing blood to pool within its chambers and increasing the risk of heart attack, stroke, and heart failure.
•However, moderate alcohol consumption is associated with a lower risk of cardiovascular disease than abstention or heavy drinking among older adults in observational studies (done in the US in 2007)
•development of AF after an episode of heavy alcohol intake is sometimes called "holiday heart syndrome."

Blood

•Alcohol excess can cause:
1)Anaemia due to deficiency of folic acid, resulting in fatigue.
Folic acid (Vitamin B9)- needed for the production of deoxyribonucleic acid (DNA) in all tissue cells and is a component of three of the four DNA bases -- thymine, adenine, and guanine -- (the fourth is cytosine).
In bone marrow, it is required for the normal production of the red blood cells and for RNA synthesis.
Alcohol abuse contributes to this type of anemia since alcohol interferes with folate metabolism in the liver, resulting in a profound depletion of folate stores.
2)A reduction in the white blood cells [leucopaenia] resulting in an increased susceptibility to infections.
Also caused by the shortage of vitamin B9.
3)A reduction in the platelet count [thrombocytopaenia] resulting in an increased tendency to bleeding and bruising.
Also caused by the shortage of vitamin B9.

Cerebellar degeneration
•The cerebellum sits in the lower portion of the skull, behind the brain stem. One of its main jobs is to smoothly coordinate movements.
•This disorder occurs more commonly among men. It is characterized by an unsteady gait, instability of the trunk, and poor coordination of the extremities. Additionally, difficulties with speech may occur. The disorder may progress over weeks or months.
•Alcoholic cerebellar degeneration is most likely due to nutritional deficiencies, such as the vitamin deficiencies seen in Wernicke-Korsakoff's syndrome.

Wernicke Korsakoff syndrome
•Wernicke-Korsakoff syndrome is a severe memory disorder usually associated with chronic excessive alcohol consumption, although the direct cause is a deficiency in the B vitamin thiamin.
•mental confusion, eye movement disorders, and ataxia (poor motor coordination)
•Thiamine helps produce energy needed to make neurons function properly. Insufficient thiamine can lead to damage or death of neurons.
•Thiamine deficiency damages regions of the brain, particularly the thalamus and the mammillary bodies.
•a syndrome of anterograde amnesia—an inability to form new memories—and confabulation in individuals with severe alcoholism or certain medical illnesses. (Confabulation refers to the practice of filling in gaps in memory by fabrication.)

Myopathy
•Breakdown of muscle tissue (myonecrosis), can come on suddenly during binge drinking or in the first days of alcohol withdrawal.
•The severe form - sudden onset of muscle pain, swelling, and weakness; a reddish tinge in the urine caused by myoglobin, a breakdown product of muscle excreted in the urine; and a rapid rise in muscle enzymes in the blood.
•Muscle atrophy occurs. The nerves of the extremities may also begin to break down, a condition known as alcoholic peripheral neuropathy.
•Proposed mechanisms:
Alcohol - metabolized in the liver, ethanol à acetate. Acetate is metabolized by skeletal muscle, and alcohol-related changes in liver function may affect skeletal muscle metabolism, decreasing the amount of blood sugar available to muscles during prolonged activity.
Because not enough sugar is available to supply needed energy, muscle protein may be broken down as an alternate energy source.
However, toxic effects on muscle may be a direct result of alcohol itself rather than of its breakdown products.

Alcoholic neuropathy
•decreased nerve functioning
•Otherwise known as primary axonal sensorimotor peripheral polyneuropathy
•May also be referred to as peripheral neuritis (Inflammation of a nerve accompanied by pain and sometimes loss of function), or if many nerves are involved, the terms polyneuropathy or polyneuritis may be used.
•May have tingling, numbness, unusual sensations, weakness, burning pain, impotence (in men), swallowing difficulty, speech impairment, loss of muscle function or feeling.
•However, it is unclear whether alcohol alone is responsible for the neuropathic symptoms, because chronic alcoholism is strongly associated with malnutrition.
•May also be the toxic effect of alcohol on nerve tissue
•Alcohol is very rich in energy, packing 7 calories per gram, thus causing euphoria, which depresses appetite, so that heavy drinkers tend to eat poorly and become malnourished.
•It is suspected that the B vitamins have a significant role. For example, thiamine (vitamin B1) deficiency, as it affects the CNS and PNS.

Pancreatitis
•acute pancreatitis - sudden inflammation of the pancreas. Can be mild or life threatening. However, the pancreas can usually return to normal function after the condition clears up. When patients suffer repeated attacks of acute pancreatitis, the pancreas gradually becomes scarred. This leads to the 2nd stage of pancreatitis.
•Chronic pancreatitis = 2nd stage. When the pancreas becomes inflamed, the digestive enzymes that it produces begin to attack its own tissues. Chronic pancreatitis always causes permanent damage to the pancreas. Over time, it is more difficult for the damaged pancreas to produce normal digestive enzymes and hormones.
•One theory is that excessive alcohol leads to protein plugs - precursors to small stones - that form in the pancreas and block parts of the pancreatic duct.
•Another theory is that alcohol directly injures pancreatic tissues.
•Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and non-oxidative pathways.

Alcohol Hangover-Clinical Effect

Alcohol Hangover : Unpleasant physical and mental symptoms like fatigue, headache, dizziness, muscle aches, and thirst after heavy alcohol drinking.

How alcohol contributes to a hangover :


1) Dehydration and electrolyte imbalance :

Fluid lost through :
  • vomitting
  • diarrhea
i) Alcohol inhibits the release of antideuretic hormone
ii)reduced levels of antideuretic hormone prevent the kidney from reabsorbing water
iii) increase urine production
iv) fluid loss
electrolyte imbalance:
  • Sweating - water evaporates from the body and release salts, eg. Sodium(Na+), Potassium(K+), Magnesium (Mg+), Calcium (Ca 2+), Chloride (Cl-)

2) Gastrointestinal Disturbances

i) alcohol increases the production of gastric acid, pancreatic and intestinal secretions

ii) Irritates ths stomach and intestines

iii) Inflammation of the stomach lining

iv) Cause upper abdominal pain, nausea and vomitting.

3) Low Blood Sugar (hypoglycemia - fatigue, weakness and mood disturbances {symptoms of hangover})

i) Too much intake of alcohol

ii) ethanol >>>>>> acetaldehyde (by enzyme alcohol dehydrogenase)

iii) acetaldehyde >>>>>acetic acid (by enzyme alcetaldehyde dehydrogenase)

iv) NAD+ >>>> NADH (reaction (ii) and (iii) cause this reaction to occur)

v) lactate + NAD+ >>><<<<> >>>>>pyruvate + NADH

pyruvate >>>>>>> glucose (glyconeogenesis)

v) more NADH, (reverse reaction) , more lactate which leads to lactic acidosis

vi) less pyruvate, less glucose formation and hence hypoglycemia

_____________________________

i) Prolonged alcohol consumption

ii) poor nutritional intake

iii) decrease glucose production

iv) glucose stored in liver in the form of glycogen is used

v) more glucose is lost

vi) hypoglycemia

Effect of Hangover :

Disruption of sleep and other biologucal rhythms :

The fatigue experienced during a hangover results from alcohol's distruptive effects on sleep. Alcohol induced sleep may be shorter duration and poorer quality because of rebound excitation after blood alcohol concentration fall.

Alcohol intoxication also interferes with the circadian nightime secretion of growth hormone, whici is important in bone growth and protein synthesis.

Alcohol induces the release of adrenocorticotropic hormone from the pituitary gland, which in turn stimulates the release of cortison, a hormone that plays a role in carbohydrate metabolism and stress response. Alcohol disrupt the normal circadian rise and fall or cortisol levels. Overall, alcohol's disruption of circadian induces a "jet lag" that is hypothesized to account for some of the deleterious effects of a hangover.

Link :

http://www.reactivehypoglycemia.net/alcohol-and-hypoglycemia.html

http://biology.about.com/library/weekly/aa010104a.htm

CAGE questionnaire

CAGE questionnaire
· The CAGE Questionnaire was developed in 1970 by Dr John A Ewing. It is a combination of 4 simple questions that can be used for the screening of patients for alcoholism.
· The questions focus on Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers. The acronym "CAGE" helps the physician to recall the questions.
· The 4 questions are "Have you ever:
(1) felt the need to cut down your drinking;
(2) felt annoyed by criticism of your drinking;
(3) had guilty feelings about drinking; and
(4) taken a morning eye opener?
· A positive response to the CAGE interview is not a diagnostic of alcoholism. A positive response should, however, alert the interviewer to the high likelihood of the presence of alcoholism.
· A total of two or more positive answers indicate a positive history of alcoholism.
· Studies have shown that many physicians miss the diagnosis of alcoholism.
· This questionnaire has to be completed as part of the patient’s medical history, so that the patient is not feel defensive.
· The questions refer to the whole life of the patient and not for this month or for the past year.
· It does not provide information about quantity, frequency, or pattern of drinking. These questions should be asked after the CAGE questions for the assessment to be valid.
· There are other tests such as the Michigan Alcohol Screening Test(MAST), which consists of 25 questions that inquire about drinking behaviour or adverse consequences of alcohol drinking. Another is the Alcohol Use Disorders Identification Test, which was designed to be sensitive to signs of hazardous and harmful drinking as well as alcohol dependence. However, but given the reluctance of busy primary care physicians to use the brief CAGE questions, the longer instruments are not likely to achieve broad acceptance
· One option adopted by some clinicians is to use the CAGE as a portable memorized instrument along with standard questions about quantity and frequency of drinking. The clinicians can then administer the Alcohol Use Disorders Identification Test or the Michigan Alcohol Screening Test, which can be self-administered for patients who require further investigation and possible referral to specialized treatment.
· The CAGE questions move the discussion toward the behavioural effects of the drinking rather than toward an isolated number of drinks per day.

References:

http://jama.ama-assn.org/cgi/content/full/300/17/2054

http://jama.ama-assn.org/cgi/data/300/17/2054/DC1/1

http://www.palliative.org/PC/ClinicalInfo/AssessmentTools/CAGE.PDF

Michigan Alcohol Screening Test (MAST) questions

http://www1.alcoholcme.com/?id=1776:8953

Alcohol Use Disorders Identification Test(AUDIT) questions

http://www.mentalneurologicalprimarycare.org/downloads/primary_care/11-2_audit_questionnaire.pdf

Nutritional Effect of Alcohol Consuming

Nutrition is a process that serves two purposes:
1. To provide energy
2. To maintain body structure and function

Alcohol -- High calories

· Alcohol contains about 9Kcal per gram. These calories do not provide any of the carbohydrates, protein, fat, vitamins or minerals needed to maintain our body functions.
· When large amount of alcohol are consumed, the body senses that its caloric needs have been met and therefore produces a decreased demand for other nutritional food.

How alcohol contribute to malnutrition?

· Alcohol interferes with the normal metabolisms such as absorption and storage of essential nutrients. Generally, it inhibits the breakdown of nutrients into usable molecules by decreasing the secretion of digestive enzymes from the pancreas.
· Alcohol impairs nutrient absorption—it damages the cells lining the stomach and intestines and disables transport of nutrients into blood.
· Nutritional deficiencies lead to further absorption problems. E.g. Folate deficiency alters the cells lining the small intestine which in turn impairs absorption of water and nutrients like glucose, sodium and additional folate.
Even if nutrients are digested and absorbed, alcohol can prevent them from being fully utilized by altering their transport, storage, and excretion. Decreased liver stores of vitamins such as vitamin A, and increased excretion of nutrients such as fat, indicate impaired utilization of nutrients by alcoholics.

Vitamins.

Vitamins are essential to maintaining growth and normal metabolism because they regulate many physiological processes.
· Chronic heavy drinking may cause deficiencies in many vitamins because of decreased food ingestion, impaired absorption, metabolism, and utilization.
E.g. alcohol inhibits fat absorption and thereby impairs absorption of the vitamins A, E, and D that are normally absorbed along with dietary fats. Vitamin A deficiency can be associated with night blindness, and vitamin D deficiency is associated with softening of the bones.
Vitamins A, C, D, E, K, and the B vitamins, also deficient in some alcoholics, are all involved in wound healing and cell maintenance. For example, since vitamin K is necessary for blood clotting, deficiencies of that vitamin can cause delayed clotting and result in excess bleeding. Deficiencies of other vitamins involved in brain function can cause severe neurological damage.

Minerals.

Deficiencies of minerals such as calcium, magnesium, iron, and zinc are common in alcoholics, although alcohol itself does not seem to affect the absorption of these minerals. Rather, deficiencies seem to occur secondary to other alcohol-related problems:
a. decreased calcium absorption due to fat malabsorption;
b. magnesium deficiency due to decreased intake, increased urinary excretion, vomiting, and diarrhea ;
c. iron deficiency related to gastrointestinal bleeding
d. zinc malabsorption or losses related to other nutrient deficiencies .
Mineral deficiencies can cause a variety of medical consequences from calcium-related bone disease to zinc-related night blindness and skin lesions.

For full text, please visit the following links:
http://alcoholism.about.com/cs/heal/a/aa990908.htm
http://alcoholism.about.com/cs/alerts/l/blnaa22.htm

Metabolism of alcohol and alex went on to ramble about biochem effects.

Metabolism of alcohol and NAD
Alcohol -> acetaldehyde -> acetate -> acetyl CoA -> goes into citric cycle.

2NADH is produced by the reduction. (Increase in NADH)
Most of the acetaldehyde is rapidly turned into acetate, but a small percentage escapes to the blood and produces effects elsewhere in the body. Acetaldehyde can damage cells, causes the hangover effects. In the liver, acetaldehyde disturbs the protein metabolism, resulting in protein accumulation and extra expansion of the liver.

Most of the acetaldehyde is rapidly turned into acetate, but a small percentage escapes to the blood and produces effects elsewhere in the body. Acetaldehyde can damage cells, thereby slowing down the rate at which the acetaldehyde is metabolized. In the liver, acetaldehyde disturbs the protein metabolism, resulting in protein accumulation and extra expansion of the liver.

Metabolism of alcohol by MEOS
MEOS (microsomal ethanol-oxidizing system)
- occurs only during heavy alcohol intake.
- produces free radicals (hydroxide and so on)
- these free radicals will cause damage to the vital components of cells.
- normally, antioxidants can counter effect these free radicals, but after MEOS, the amount of free radicals build up and upsets the balance.
- free radicals are made from oxygen atoms and this causes the amount of oxygen atoms in the blood to decrease. this leads to oxidative stress.


Lactate acidosis
As mentioned earlier, when excessive alcohol is introduced to the body, the alcohol is then metabolized to produce NADH and acetate.
lactate + NAD <-> pyruvate + NADH
This means that the amount of NADH in the body increases drastically. In turn, this will cause a shift and the amount of lactate and NAD increases. The increase in lactate acid will result in lactate acidosis.

Hypoxia
As mentioned earlier, the main pathway of alcohol metabolism, which involves ADH and ALDH, results in the generation of NADH. The NADH then is oxidized by a series of chemical reactions in the mitochondria (i.e., the mitochondrial electron transport system, or respiratory chain), eventually resulting in the transfer of electrons to molecular oxygen (O2), which then binds protons (H+) to generate water (H2O). To have enough oxygen available to accept the electrons, the hepatocytes must take up more oxygen than normal from the blood.

Liver
The liver is most commonly affected by alcohol-induced damage. The first stage of liver damage following chronic alcohol consumption is the appearance of fatty liver, which is followed by inflammation, apoptosis, fibrosis, and finally cirrhosis. The development of fatty liver is induced by the shift in the redox state of the hepatocytes that results from ethanol metabolism by ADH. This shift in the redox state favors the accumulation of fatty acids, rather than their oxidation. In addition to these metabolic effects, chronic ethanol consumption contributes to the development of fatty liver by influencing the activities of several proteins that help regulate fatty acid synthesis and oxidation

Neurodegeneration
Occurs because of the hypoglycemia. The proliferation of neural stem cells and the survival of neurons produced from the stem cells during alcohol exposure are decreased (Nixon and Crews 2002). The prefrontal cortex is involved in high-level cognitive and executive functions, such as planning complex cognitive behaviors, decisionmaking, and moderating correct social behavior.) have central roles in executive functions, such as decisionmaking.

Hypoglycemia
1) Lactate + NAD <-> pyruvate + NADH
2) Pyruvate <-> glucose

As mentioned earlier, when excessive alcohol is introduced to the body, the alcohol is then metabolized to produce NADH and acetate.
This means that the amount of NADH in the body increases drastically. In turn, this will cause a shift in the first equation to the left, and the amount of lactate and NAD increases.
This also means that the amount of pyruvate will decrease. When the amount of pyruvate decreases, the second reaction will then shift to the left as well, resulting in a decrease in blood glucose.
Alcohol-induced hypoglycemia occurs in the fasted state, when the diabetic's blood sugar levels are already low and the body depends on the production of new glucose molecules (i.e., gluconeogenesis) to maintain sufficient blood glucose levels. Gluconeogenesis, which occurs in the liver, requires certain compounds whose levels are regulated by a substance called reduced nicotinamide adenine dinucleotide (NADH). Alcohol metabolism in the liver generates excessive NADH levels and thus reduces the levels of the compounds needed for gluconeogenesis, thereby contributing to a further drop in blood sugar levels.

Hepatitis C
Hepatitis C is the inflammation of the liver caused by the hepatitis C virus. High alcohol intake causes the depression of the immune system, which in turn causes the susceptibility of the human to virus attacks. Another theory is that there is increased replication of HCV in the liver.

Hyperlipidemia
The increase in NADH also affects the ratio of NAD to NADH. NAD is needed to accept the hydrogen ions for the continuity of the citric cycle and the conversion of fatty acids to acetyl CoA. This results in a build up of acetyl CoA and fatty acids. The build up of fatty acids results in hyperlipidemia.
In people with hyperlipidemia, the levels of fat molecules in the blood - particularly molecules called triglycerides - are higher than normal. This condition can be associated with an increased risk of various health problems, the most serious of which is cardiovascular disease. Alcohol consumption may exacerbate hyperlipidemia, because the same metabolic alcohol effects that inhibit gluconeogenesis also inhibit fat metabolism. As a result, the production of certain molecules called very low density lipoprotein (VLDL) particles is increased.

Damage to the heart
Moderate drinking:
Reduced plaques leading to less risk of artherosclerosis.
Reduced blood clots.

Heavy drinking:
Heart muscle inflamed and thinning leading to cardiomyopathy.
Increased risk of arrhythmia (irregular heart beating)
Increased risk of hypertension (heart needs to pump faster to compensate for nutrient defiency, hypoxia, hypoglycemia.)



http://pubs.niaaa.nih.gov/publications/arh313/185-195.htm
http://www.nlm.nih.gov/medlineplus/ency/article/000174.htm
http://pubs.niaaa.nih.gov/publications/arh294/245-255.htm
http://health.howstuffworks.com/alcohol12.htm
http://www.enotalone.com/article/11222.html
http://findarticles.com/p/articles/mi_m0CXH/is_1_23/ai_57050109

Tuesday, March 17, 2009

Management of Alcoholism

MANAGEMENT OF ALCOHOLISM.

Should I cut down or completely stop ?

Stopping alcohol is usually the best if you have been alcohol dependant and also if you have a condition such as liver damage. The person has to be committed and determined to stop. Most importantly too is that the person should accept that they have a problem as some people may deny that they do have a problem. The next step is to seek help when necessary in order to curb it.
If you are not alcohol dependant but want to reduce your alcohol intake, here are a few tips:
• Consider drinking low alcohol beers, or at least do not drink 'strong' beers or lagers.
• Try pacing the rate of drinking. Perhaps alternate soft drinks with alcoholic drinks.
• Consider cutting back on types of social activity which involve drinking. Perhaps try different social activities where drinking is not a part. Perhaps reduce the number of days in the week where you go out to drink.
• Resist pressure from people who encourage you to drink more than you want to.

WITHDRAWAL
Alcohol withdrawal refers to symptoms that may occur when a person who has been drinking too much alcohol every day suddenly stops drinking alcohol.

Mild-to-moderate psychological symptoms:
• Jumpiness or nervousness
• Shakiness
• Anxiety
• Irritability or easy excitability
• Rapid emotional changes
• Depression
• Fatigue
• Difficulty thinking clearly
• Bad dreams



Mild-to-moderate physical symptoms:
• Headache -- general, pulsating
• Sweating -- especially the palms of the hands or the face
• Nausea and vomiting
• Loss of appetite
• Insomnia (sleeping difficulty)
• Pallor
• Rapid heart rate
• Eye pupils enlarged(dilated pupils)
• Clammy skin
• Tremor of the hands
• Involuntary, abnormal movements of the eyelids

Severe symptoms:
• Delirium tremens -- a state of confusion and visual hallucinations
• Agitation
• Fever
• Convulsions
• Black outs -- when the person forgets what happened during the drinking episode

Delirium tremens ('DTs')
• This is a more severe withdrawal reaction after stopping alcohol.
• It occurs in about 1 in 20 people who have alcohol withdrawal symptoms about 2-3 days after their last drink.
• Symptoms include: marked tremor (the shakes) and delirium (agitation, confusion, and seeing and hearing things that are not there) and convulsions.
• Complications can develop such as dehydration and other serious physical problems. It is fatal in some cases.







What Is Alcohol Rehab?

Alcohol rehab refers to the medical, psychotherapeutic, educational and social treatment processes required for alcoholism recovery.

Primary Elements of Rehab
• Alcohol Detox. This is the initial part of the recovery process. Detox involves stopping the consumption of alcohol and giving the body the time it needs to cleanse itself of the harmful toxins associated with wine, liquor or beer.
• Counseling. The core of any alcohol rehabilitation programs is counseling. During sessions with a counselor or therapist, the individual learns relapse prevention skills, receives education about alcoholism, and discovers the triggers that cause their unwanted behavior. Counseling in alcohol rehab takes two forms: individual and group sessions.
• Aftercare. When an individual "graduates" from alcohol rehab, they must then return to the outside world. This is not always as easy as it sounds, as individuals face a number of challenges when they return home after treatment, including:
o Temptation
o Stress and distraction.
o A lack of understanding.



Alcohol Rehab and Mental Health Issues

Many alcohol rehab programs have historically strictly provided alcohol rehab without attention to other mental issues. However, given the impact of addiction on other life issues, it is no surprise that mental health complications are very common among those who participate in alcohol rehab programs. In fact, more than 44% of alcoholics have mental health complications prior to the onset of alcohol dependence and many others develop mood-related complications, such as depression and dysthymia, after the onset of the addiction. The finest alcohol rehab centers incorporate mental health treatments in addition to alcohol rehab services in an effort to treat these co-occurring disorders.





Alcohol Rehab Process-Has 2 focal points:
i. Physical dependency(treatment involves managing alcohol withdrawal symptoms in a safe manner)
ii. Psychological dependency(treatment involves teaching the alcoholics new ways of interacting in an alcohol-free environment)

Alcohol Rehab Approaches

A. Detoxification

I. Getting rid of alcohol from the body while managing the withdrawal symptoms in a harmless atmosphere
II. Also a process by which heavy drinker’s system is brought back to normal after being used to having alcohol in the body on a frequent basis.
Precipitous withdrawal from long-term alcohol addiction without medical management can cause severe health problems and can also be fatal. Alcohol detoxification is not a treatment for alcoholism but it is the first step done in a rehab program under the supervision of a medical practitioner. After detoxification, other treatments must be undergone to deal with the underlying addiction that caused the alcohol use.

B. Behavioral Rehab such as Alcoholics Anonymous(AA), Motivation Enhancement Therapy and Cognitive Behavioral Therapy(CBT)

I. AA- it is a voluntary fellowship of people suffering from alcoholism who seek to become sober through mutual self-help by meeting in local, independent groups to share their experiences, strengths and aspirations with each other in the hope that they may solve their mutual problem and assist others in their quest to recover from alcohol dependence
II. Motivation Enhancement Therapy- encourages patient to develop a negative view of their abuse along with a desire to change their behavior
III. CBT- it’s a psychotherapeutic approach that aims to influence dysfunctional emotions, behaviors and cognitions through goal-oriented, systematic procedure





C. Therapeutic Medications-client/patient taking doctor prescribed medicine
Types of drugs:

I. Benzodiazepines- to treat alcohol withdrawal symptoms
There are two types: a) long lasting benzodiazepines(used in reducing tremor and agitation eg “Diazepam or Chordiazepoxide”)
b)short acting benzodiazepines(used in treatment of seizures eg “Lorazepam intravenously”)This drug can cause a physical dependence and a benzodiazepine addiction to develop and upon cessation of long term use a “benzodiazepine withdrawal syndrome” can occur. To avoid this take short courses at low doses.

II. Disulfiram(Antabuse)
• drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol
• it produces discomfort if present in the system when alcohol is consumed
• the drug elicits negative effects such as dizziness, vomiting, nausea if alcohol is ingested
• Antabuse has been proven to help prevent relapses and is effective mainly because it is such a strong deterrent

III. Naltrexone
• Minimizes both the craving for alcohol and the ‘high’ produced by its consumption

IV. Acamprosate
• Reduces the craving for alcohol in people who have stopped drinking
• Maybe prescribed to people after a successful detox to help them stay off alcohol

V. Vitamins
• Particularly vitamin B1 (Thiamine). Deficiency of it may cause Wernicke-Korsakoff Syndrome. Learn more about it here.
• Chronic alcohol consumption can result in thiamine deficiency by causing:
o Inadequate nutritional thiamine intake
o Decreased absorption of thiamine from the gastrointestinal tract
o Impaired thiamine utilization in the cells




D. Outpatient Alcohol Treatment and counseling
• There are various approaches that teach alcoholics how to become aware of the situational and psychological ‘hot button’ that trigger their drinking behavior
• Also they learn of different ways in which they can cope with circumstances that do not include the use of alcohol
• Individuals attend treatment during the day and return home (or to a sober living facility) in the evening.
• Better suited for individuals who are the head of household or have work and school that need to be attended.
• A good choice for individuals who have a non-life threatening form of alcohol addiction

E. Residential Alcohol Treatment Program and Inpatient Alcohol Rehabilitation
• Patient moves into a dorm and receives round the clock care. 24/7 care is better for more serious cases of alcohol addiction.
• It offers a supportive atmosphere and a structured environment in which the patient can begin to focus and learn how to restructure his/her life and develop new habits.
• Programs educate the family as well as alerting them to patterns that might have enabled the patient to take up drinking


In addition to these standard treatments, alcoholics are aided by alternative treatment such as acupuncture and hypnosis.


References

1.http://www.about-alcohol-rehab.com/
2. http://www.patient.co.uk/showdoc/40025148/
3. http://encyclopedia2.thefreedictionary.com/alcoholism
4. http://www.drug-rehabs.com/alcohol_rehab.htm
5. http://www.michaelshouse.com/alcohol-rehab/
6. http://www.patient.co.uk/showdoc/27000115/
7. http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/000764.htm

Monday, March 16, 2009

Summary of GE

Gastroenteritis is inflammation of the intestines by an infectious agent.

The predisposing factors are:
1) Nutritional status
2) Water quality
3) Food sanitary and sharing of food
4) Personal hygiene and environmental factors.

Causes:
1) Viruses (norovirus, rotavirus, adenovirus, astrovirus)
- Contact with contaminated object/surface
- Consuming contaminated food/water
- Contact with infected person

2) Bacteria (salmonella)
- Food not cooked properly
- Food washed in dirty water
- food not properly stored
- food handled by infected person

Symptoms
1) Nausea
2) Lethargy
3) Vomiting
4) Diarrhea

Signs to look out for:
1) Reduced skin rigidity
2) Sunken fontanels
3) Sunken eyeballs
4) Poor perfusion linking to pale skin

Differential diagnosis
1) Appendicitis
- Radiating pain from right side. Pain in GE is generalized and tenderness is not localized.
- Rebound tenderness.
- Rovsing’s sign.

2) Bowel obstruction
- GE is not associated with constipation.

3) Ulcerative Colitis
- GE is associated with vomiting where as this is not.

4) Pneumonia
- Cough is usually not present in GE.

Investigations
- Examination of stool for toxins
- Stool cultures for the organisms that cause the disease
- Microscopy for parasites and their ova and cysts.
- ELISA for virus

Fluid balance
- Disruption caused by excessive loss of water and reduced intake.
- Loss is caused by vomiting and diarrhea whereas intake is reduced due to lethargy.
- This leads to hypovolemia.

Body compensation
a) ADH
b) Thirst mechanism
- When there is a deficit of water with decreased volume and increased osmolarity , the thirst center in the hypothalamus is stimulated which prompts the individual to ingest fluid
c) Renin-Angiotensin-Aldosterone System
d) Sympathetic nervous system - system that is responsible for fight of flight response

Management
1) ORS (Oral rehydration salts)
- quickly replaces water and electrolyte loss. Should be taken in small frequent sips.
2) Fluids to take
- rehydration drinks or diluted fruit juices are okay.
3) Food should not be withheld but there should be no force feeding as well.
4) In case of severe dehydration, intravenous therapy is introduced.
5) Make sure infected person does not handle/share any food/towels
6) Regularly clean the infected person’s toilet
7) Stay home until free from vomiting/diarrhea for 48 hours.
8) Additional meals daily for 2 weeks to make up for nutritional loss.

Prevention
1) Wash hands frequently
2) Wash hands before preparing food/eating
3) Use disposable towels, not cloth as it can incubate the bacteria
4) Make sure food is thoroughly cooked.
5) Clean toilet regularly
6) In places with lack of sanitary, only drink bottled water

Management-Oral Rehydration Solution

Summary
  • ORS is absorbed in the intestines and can quickly replace the water and electrolytes lost through vomiting and diarrhea.
  • ORS is as effective as intravenous therapy in replacing loss fluids due to dehydration.
  • The United Nations Children’s Fund (UNICEF) recommends that each child drinks as much as possible but “at least a quarter to a half of a large cup of the ORS drink after each watery stool” for a child less than 2 years of age, and “at least a half to a whole large cup of the ORS drink after each watery stool” for a child more than 2 years of age.
  • Drinks high in sugar such as cola or undiluted juice should not be given to a child as it can cause osmotic worsening of diarrhoea and the low sodium content can lead to hyponatremia(abnormally low sodium concentration in blood).
  • ORS is usually given to children with mild to moderate dehydration. For children with severe dehydration, intravenous therapy is usually given.
    No/mild dehydration: ≤4% body weight loss
    Moderate 4–6% body weight loss
    Severe >7% body weight loss
  • The use of ORS is based on the principle of glucose facilitated sodium transport in the small intestine.
    The Na+/glucose transporter. This transmembrane protein allows sodium ions and glucose to enter the cell together. The sodium ions flow down their concentration gradient while the glucose molecules are pumped up theirs. Later the sodium is pumped back out of the cell by the Na+/K+ ATPase.
    The Na+/glucose transporter is used to actively transport glucose out of the intestine and also out of the kidney tubules and back into the blood
  • The preferred ORS are those that are hypotonic with an osmolarity between 200–250 mOsm/L
  • A child who is dehydrated as a result of diarrhoea can have a deficit of sodium up to 70-110 mmol/L .
    Thus, in the initial rehydration, a sodium concentration of 90 mmol/L in oral rehydration solution (ORS)would be suitable. However, in the maintenance phase, to replace continuing stool losses in which thesodium concentration is 50-60 mmol/L, an ORS containing 60 mmol/L of sodium would be safe and effective.
    Alternatively, to avoid the confusion of using two types of ORS, one can give ORS containing 90mmol/L sodium together with a normal intake of water and breast milk.

Links

1.
D’Alessandro, D.M. 2006, What is the New Oral Rehydration Salt Solution Made Up Of?, viewed 11 March 2009 from http://www.pediatriceducation.org/2006/12/18/

2.Gastroenteritis in Children 2006, Patient UK. Viewed on 11 March 2009 from http://www.patient.co.uk/showdoc/23068743/

3.
Burkhart, D.M. 1999, Management of Acute Gastroenteritis in Children, The American Academy of Family Physicians. Viewed on 10 March 2009 from http://www.aafp.org/afp/991201ap/2555.html

4. http://www.oley.org/documents/ORS%20Article%20-%20Dr.%20Kelly.pdf

5.
Rice Starch Low Sodium Oral Rehydration Solution (ORS) in Infantile Diarrhoea http://www.mma.org.my/Portals/0/MED%20J%20MALAYSIA%20VOL%2051%20NO%202%20JUNE%201995.pdf

Additional links for GE:

6. http://www.acadmed.org.my/cpg/AMMCOPdiarrhoeaCPG.pdf

7. http://www.racgp.org.au/afp/200504/200504webb.pdf