alcohol and alcoholism

Alcohol and Alcoholism

Moderator DR POONAM GUPTA (MD)

ANIL KUMAR G

Introduction • Alcohol (beverage ethanol ) distributes

throughout the body , affecting almost all systems and altering nearly every neurochemical process in the brain.

• Low doses of alcohol have some health benefit.• The intake of more than three standard drinks per

day on a regular basis enhances the risk for cancer and vascular disease, and alcohol use disorders decrease the life span about 10 years.

1.HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.

Epidemiology • Worldwide, an estimated 2.3 million people die

from alcohol related causes.• 3.7% of all deaths, of this 6.1% among men and 1.1

% among women• WHO estimated 2 billion people worldwide

consume & 76.3 million with disorder arising out of harmful use.

• In India around 20-30 % of adult males and around 5 % adult females use alcohol.

PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

PHARMACOLOGY AND NUTRITIONAL IMPACT OF ETHANOL • Blood levels of ethanol are expressed as mg or gm of ethanol per dL (e.g., 100

mg/dL = 0.10 g/dL)• With values of 0.02 g/dL resulting from the ingestion of one typical drink. In

round figures, 340 mL (12 oz) of beer, 115 mL (4 oz) of nonfortified wine, and 43 mL (1.5 oz) (a shot) of 80-proof beverage such as whisky, gin, or vodka

• Each contain 10–15 g of ethanol and represent a standard drink• 0.5 L (1 pint) of 80-proof beverage contains 160 g (about 16 standard drinks), and

750 mL of wine contains 60 g of ethanol. One unit = 10 gm of alcohol

One oz = 30ml

Proof =2*%ethanol by volume

One drink = 44ml of whiskey(80%proof), 3- 5oz wine or 12 oz beer.

BAC –blood alcohol conc.

0.1%BAC =100 mg alcohol in 100ml blood. . HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no

3456-3552

Absorption GIT ,20% in stomach, rest in small intestine

80%-90% absorption within 30-60mins.

Absorption also depends on other factors

Females attain higher blood alcohol level.

BAC decreases by 15-25 mg /100ml/ hr.

Inhalation –pulmonary vascular bed.

PHARMACOLOGY

C2H5OH

Colorless, odourless liquid

M.Wt - 46

1gm ethyl alcohol – 7.1 kcal energy .HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.

METABOLISM

• Alcohol supplies calories (a drink contains 300 kJ, or 70–100 kcal), these are devoid of nutrients such as minerals, proteins, and vitamins. In addition, alcohol can also interfere with absorption of vitamins in the small intestine and decreases their storage in the liver with modest effects on folate (folacin or folic acid), pyridoxine (B6), thiamine (B1), nicotinic acid (niacin, B3), and vitamin A.

• A heavy ethanol load in a fasting, healthy individual is likely to produce transient hypoglycemia within 6–36 h, secondary to the acute actions of ethanol on gluconeogenesis. This can result in temporary abnormal glucose tolerance tests.

• HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552

Alcoholics may have thiamine deficiency because of the following:

• Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.

• Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.

• Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.

• Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.

• Ethanol per se inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).

Butterworth RF, Gaudreau C, Vincelette J et al. (1991). "Thiamine deficiency and wernicke's encephalopathy in AIDS". Metab Brain Dis 6 (4): 207–12.

• The other most prominent actions relate to boosting GABA activity, especially in GABAA receptors.

• Enhancement of this complex chloride channel system contributes to anticonvulsant, sleep-inducing, antianxiety, and muscle relaxation effects of all GABA-boosting drugs.

• Continued use of this drug increases density of GABAA receptors, while alcohol withdrawal states are characterized by decreases in GABA-related activity.

• Ability of acute alcohol to inhibit postsynaptic N-methyl-d-aspartate (NMDA) excitatory glutamate receptors, while chronic drinking and desistance are associated with an upregulation of these excitatory receptor subunits.

• Relationships between greater GABA and diminished NMDA receptor activity during acute intoxication and diminished GABA with enhanced NMDA actions during alcohol withdrawal explain much of intoxication and withdrawal phenomena.

HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.

• Drinking alcohol acutely increases dopamine levels in the brain, changes in dopamine pathways are also linked to increases in "stress hormones," including cortisol and adrenocorticotropic hormone (ACTH) during intoxication and decreases in these hormones during withdrawal.

• Such alterations are likely to contribute to both feelings of reward during intoxication and depression during falling blood alcohol concentrations.

• Alcohol-induced changes in opioid receptors, with acute alcohol also causing release of beta endorphins.

HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.

Pathophysiology

GABA ↑. Glutamate ↓.

↑NADH/NAD ratio.

↑ketogenesis.

↓gluconeogenesis

↑glycogenolysis

Fluid & electrolyte imbalance.

Behavioral Effects and Tolerance • "Legal intoxication" with alcohol in most states requires a blood

alcohol concentration of 0.08 g/dL, while levels of 0.04 or even lower are cited in other countries. In INDIA 0.15g/dL.

• Effects of Blood Alcohol Levels in the Absence of Tolerance.Blood level g/dL Usual EffectLess then 0.03 Not noticeable0.03-0.05 Selective impairment

0.05-0.10 Slight impairment

0.10-0.15 Under the influence

0.15-0.20 Drunk

0.20-.30 Very drunk

0.30-0.35 Stupor to coma

Over 0.35 Comatose to death

ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514

Selective impairment: (0.03-0.05gm/dL) increase in reaction time; impairment of complex skills such as flying an aircraft or driving a motor vehicle. Detectable only on detailed examination

Slight impairment: (0.05-0.10gm/dL) flushed face; dilated pupils; euphoria; loss of restraint

Under the influence: (0.10-0.15gm/dL) flushed face; dilated pupils; euphoria; loss of restraint ; test errors; stagger on sudden turning.

Drunk: (0.15-0.20gm/dL) flushed face; dilated sluggish/inactive pupils; clouding of intellect; incoordination of thought, speech and action; staggering gait with reeling and lurching while making sudden turns.

Very drunk:(0.20-.30gm/dL) flushed or pale face; pupil inactive, contracted or dilated; mental confusion; marked incoordination of thought, speech and action; staggering gait with reeling and lurching while making sudden turns , vomiting amnesia.

.PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

Repeated use of alcohol contributes to acquired tolerance, at least three types of compensatory mechanisms.

(1) After 1–2 weeks of daily drinking, metabolic or pharmacokinetic tolerance can be seen, with up to 30% increase in the rate of hepatic ethanol metabolism.

(2) Cellular or pharmacodynamic tolerance develops through neurochemical changes that maintain relatively normal physiologic functioning despite the presence of alcohol. Subsequent decreases in blood levels contribute to symptoms of withdrawal.

(3) Individuals learn to adapt their behavior so that they can function better than expected under influence of the drug (learned or behavioral tolerance).1.HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.

Different alcohol poisonings.

Acute ethanol intoxication

Acute methanol poisoning.

Acute ethylene glycol poisoning.

Acute isopropyl alcohol poisoning

Acute ethyl poisoning • Ethyl alcohol depresses central nervous system irregularly

in descending order from cortex to medulla.• 1. Stage of excitement: (0.03-0.10%) feeling of well being and

pleasure resulting from inhibition of higher centres. Drinker converses well , laughs and smiles readly or becomes angry easily. He may disclose secrets.

• 2. Stage of incoordination: (0.10-0.30%) incoordination of thought, speech, and action, which manifest as impaired judgement, confusion, slurred speech, and staggering gait. May become morose , euphoric or irritable depending on his inherent emotions. Nausea and vomiting are common. Pupils dilated. Offences committed in this stage. Impaired judgment may lead to accidents, sexual excesses, violence and crime.

.PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION , chapter 18 mental health- alcoholism and drug dependence no 774.

• 3.Stage of narcosis: pt passes into deep sleep and responds only to strong stimuli. Pulse is rapid, temperature subnormal, breathing Sertorius, & pupils may contracted. Macewans sign seen. If this stage lasts for more then 12hrs, death ensues from paralysis of cardiac or respiratory center or later from effects of pulmonary edema.

• Recovery occurs with acute depression and gastrointestinal irritation which continue for 24hrs or longer. Headache is also present as an hang over effect and is due to cerebral edema. Hang-over means a temporary state of indisposition usually following recovery from drunkenness.

3.PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

• Fatal dose : depend on age and habits of the pt and the strength of liquor taken. Death usually occurs from large quantity taken in short time. Concentration of 0.35gm/dL & above of alcohol in blood is generally sufficient to cause death.

• Fatal period: usually 12 to 24 hrs though death may be delayed for 5 to 6 days.

• Cause of death : depression of respiratory center. May be lethal at relatively lower blood levels when combined with other CNS depressants such as barbiturates, carbon monoxide, or morphine, & in presence of some natural disease of heart or lungs.


Associated acute problems Alcoholic ketoacidosis. Alcoholic hypoglycemia. Fluid & electrolyte imbalance. Wernicke’s encephalopathy Acute effects on heart. Acute GI effects. Acute alcoholic myopathy. Trauma Associated other substance poisoning.

2.ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

Alcoholic ketoacidosis: High anion gap acidosis Normal or low glucose level Chronic alcoholics Binge drinking wks before symptoms Dehydration, starvation due to vomiting ,gastritis

Altered mental status Kussumal breathing Ketotic breath Lab finding high anion gap acidosis ↑beta hydroxybutyrate : acetoacetate ↓insulin level Exclude other causes of ↑A;G acidosis.ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

• Alcohol poor food intake dehydration ↓ ↓ ↓ Acetaldehyde glycogenolysis ↑counter regulatory ↓ hormonesAcetate ↓ ↓ ↓↑NADH/NAD ↑glucagon ratio ↓insulin ↓• ↓gluconeogenesis

ketogenesis

Chronic alcoholic found unresponsive Symptoms neuroglycopenic →confusion,fatigue,seizure, loss of consciousness→death autonomic responses → palpitation ,tremor , sweating Signs pallor ,diaphoresis tachycardia,raised systolic B.P transient focal neurological signs


Alcoholic hypoglycemia

Water and electrolytes disorders Immediate ↑ in urine volume followed by ↑ADH. Hydration also depends on -diet, nonalcoholic fluids, type of drinks -vomiting, diarrhea, infection Water intoxication & hyponatremia in severe chronic

alcoholics→seizure & altered sensorium Central pontine mylenolysis

• Other electrolytes abnormalities Hypomagnesemia Hypophosphatemia Hpokalemia Hypocalcemia3.PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

Wernicke-korsakoff’s syndrome As high as 12.5% in alcoholics. Major reversible cause of death. If untreated 10-20% mortality rate. Thiamine deficiency is the root cause. Magnesium deficiency in thiamin resistant cases. Clinical features global confusion ocular abnormalities ataxia

.Neurology in Clinical Practice e-dition, 5th Edition Bradley, Daroff, Fenichel & Jankovic; chapter 61 Deficiency Diseases of the Nervous System no 1650-1654.

Acute effect on heart Direct negative inotropic effect & vasodilation. PR & QT prolongation Both supraventricular & ventricular arrhythmia. “holiday heart syndrome” Various degree of heart block.

Acute alcoholic myopathy Acute muscle necrosis mainly in binge drinkers Alcoholism is the most common cause of rhabdomyolysis Raised CKMM, myoglobinuria, Acute tubular necrosis→↑urea ,creatinine

ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

Acute gastrointestinal effect

Acute gastritis & esophagitis.

Epigastric distress and gastrointestinal bleeding.

Mallory-weiss tear.

Acute hepatitis & pancreatitis.


Differential diagnosis in acutely intoxicated patient.

Toxic Metabolic Infectious diseases Neurologic Miscellaneous Trauma

Management Airway Breathing Circulation Intubate if poor gag reflex Finger stick glucose , iv dextrose Thiamin 100 mg im/ iv stat. iv dextrose magnesium

.ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

. 2 mg naloxone Exclude other causes of intoxication ABG Osmolar gap. 2Na+ + BUN/2.8 + Glu/18 + Eth/4.6 Serum electrolytes Anion gap. Correct other electrolyte abnormalities Phenytoin CT scanESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no

497-514.

Blood alcohol conc (BAC)

Enhanced elimination evacuation after 1 hr little benefit activated charcoal. fructose haemodialysis metadoxine (300-900mg iv) (VIBOLIV, ALCOLIV)


(pyridoxine–pyrrolidone carboxylate)

Methanol poisoning CH3OH(wood alcohol)

Solvent ,antifreeze, paint remover.

Epidemics of methanol toxicity.

Poisoning mainly by ingestion Clinical effects Inebriated but lack of euphoria. 1-72 hrs of latent period. Fatal dose 60-240 ml. Vertigo ,nausea, vomiting, diarrhea, abdominal

pain,dyspnea,agitation.

Blurred vision, photophobia, ↓ visual acuityBradycardia, blindness, seizures, coma


Physical examination constricted visual field, fixed & dilated pupils, retinal edema & hyperemia of disc resp apnea , opisthotonus & seizure in pts dying of Methanol intoxication Lab finding high anion gap acidosis (correlates with mortality) high osmolar gap

serum methanol> 20 mg/dl symptoms > 50 mg/ dl serious > 100 mg/ dl ocular signsESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

Specific treatment aggressive tt of acidosis ethanol achieve BAC of 100- 150mg

/100ml loading 0.8gm/ kg of 5 – 10%

ethanol followed by 130mg/kg/hr. oral loading if no iv preparation if dialysis,250-350 mg/kg/hr. ethanol indications methanol >20

mg/100ml,symptomatic acidosis, need for HD. ingestion >o.4ml/kg

Folic acid 30 mg iv every 4 hrly Leucovorin 1-2mg/kg iv 4-methyl pyrazole(fomepizole ) 15-20

mg/kg iv Haemodialysis not haemoperfusion Haemodialysis indications: methanol>20-50mg/100ml acidosis not responsive to

bicarbonate formate levels > 20 mg/100ml visual impairment renal impairement Dialysis till methanol

level≈0mg/100ml and acidosis clears.


Alcoholism (Alcohol Abuse or Dependence)

• Alcohol dependence is defined in DSM-IV as repeated alcohol-related difficulties in at least three of seven areas of functioning that cluster together over a 12-month period. Two of these seven items, tolerance and withdrawal, may have special importance as they are associated with a more severe clinical course.

• Alcohol abuse is defined as repetitive problems with alcohol in any one of four life areas—social, interpersonal, legal, and occupational—or repeated use in hazardous situations such as driving while intoxicated in an individual who is not alcohol dependent. About 50% of those with alcohol abuse continue to have alcohol problems 2–5 years later, but only 10% of these patients—including adolescents—go on to develop alcohol dependence.

• The lifetime risk for alcohol dependence in most Western countries is about 10–15% for men and 5–8% for women.

1.HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552

Current risk terms Abstinence : no alcohol use

Moderate drinking :

Men: no more than 2 standard drinks per drinking d

Women: no more than 1 std drink per drinking d

Elder persons(>65y): no more than 1 std drink per drinking d

Risky or hazardous drinking :

Men : More than 4 std drink per drinking d/ More than 14 std drink per drinks per wk

Women : More than 3 std drink per drinking d/ More than 7 std drink per drinks per wk

Elder persons(>65y): More than 3 std drink per drinking d/ More than 7 std drink per drinks per wk

.CONNS CURRENT THERAPY BOPE KELERMAN 2013, SECTION 16 PSYCHIATRIC DISORDERS- ALCOHOLISM no 921-927.

Three types of chronic alcohol abuse seen1. regular daily excessive drinking2.regular heavy drinking on weekends only3.long periods of sobriety interspersed with binges that last days, weeks, months.

Familial influence1. a family history of alcoholism , son of an alcoholic father2. family history of teetotalism (i.e, avoidance of alcohol under any circumstance)3. an alcoholic spouse

.NMS PSYCHIATRY 5th edition JOUHUA T. THORNHILL 4, chapter 5 substance related disorder chapter 7 no 158-159

Screening

• Alcohol Use Disorders Identification Test (AUDIT)

• CAGE questionnaire• TWEAK questionnaire• CRAFFT questionnaire• S-MAST-G questionnaire


Screening

• Add all scores to obtain a total > 8 for men or > 4 for women indicates a higher risk of alcohol use disorder

• Alcohol Use Disorders Identification Test (AUDIT)

CAGE questionnaire


• Two or more points indicate possible alcohol problem.CONNS CURRENT THERAPY BOPE KELERMAN 2013, SECTION 16 PSYCHIATRIC DISORDERS- ALCOHOLISM no 921-927.

CRAFFT questionnaire

One yes response indicates need for further assessment; two yes responses indicates risk of alcohol use disorder .CONNS CURRENT THERAPY BOPE KELERMAN 2013, SECTION 16 PSYCHIATRIC DISORDERS- ALCOHOLISM no 921-927.

The Short MAST-GERIATRIC VERSION (SMAST-G)

Please answer Yes or No to the following questions: Yes No 1. When talking with others, do you ever underestimate how much you drink? 2. After a few drinks, have you sometimes not eaten or been able to skip a meal

because you didn’t feel hungry?

3. Does having a few drinks help decrease your shakiness or tremors? 4. Does alcohol sometimes make it hard for you to remember parts of the day or

night?

5. Do you usually take a drink to calm your nerves? 6. Do you drink to take your mind off your problems? 7. Have you ever increased your drinking after experiencing a loss in your life? 8. Has a doctor or nurse ever said they were worried or concerned about your

drinking?

9. Have you ever made rules to manage your drinking? 10. When you feel lonely, does having a drink help?

SCORING: Score 1 point for each ‘yes’ answer and then total the responses 2+ points = are indicative of an alcohol problem


DIAGNOSIS

Diagnosis of alcohol use problems • Alcohol abuse (> 1 in last year )• Alcohol has caused or contributed to repeated: failure to

fulfil obligation at home, school, or work.;arrests or other legal problems; physical fights; driving ,swimming.

• Alcohol dependence (>3 in the last 12 mnth): development of physical tolerence,;binging episodes; reduced time in other pleasurable activities; drinking persists despite physical or psychological problems.

• Alcohol withdrawal (> 2 within hours to days after lowered blood alcohol levels ): autonomic hyperactivity; hand tremor; insomnia; anxiety; seisures;hallicinations; nausea vomiting

Intervention • Assess: screen patients with AUDIT or with CAGE or CRAFFT or S-

MAST-G questionnaires as appropriate and compute average drinks per week.

• Advise: give feed back in the form of concern, direct conclusions, and recommendations

• Agree: when the patient concurs that a change in drinking would be beneficial, agree on a specific goal to cut down to a particular daily and weekly limits for low risk drinking or to stop drinking. Agreement should be recorded and a copy given to the pt both as a reminder and motivator for behavioural change.

• Assist : work with the pt to formulate concrete steps to implement the drinking reduction plan, how to avoid high risk drinking situation , keep a record of alcohol intake.

• Arrange: set up follow up support and counseling visits or refer pts meeting dependence criteria for specifically treatment. Seek medical treatment if withdrawal symptoms occur. .CONNS CURRENT THERAPY BOPE KELERMAN 2013, SECTION 16 PSYCHIATRIC DISORDERS- ALCOHOLISM no 921-927.

Treatment

• Pharmacological therapy: • Benzodiazepines – diazepam 10-20mg(valium) &

chlordiazepoxide 50-100mg(librium) CIWA-Ar score less then 8.

• Long acting barbiturates , phenobarbital (120mg loading followed by 60mg 6hrly) for CIWA-Ar score of 10 or more.

• Thiamine 100mg/day for 3 days counter act thiamine deficiencies


• Asssessment of motivation : pt who is willing to consider abstaining completely for 1 month has at least some motivation to give up.

Medication management:

• Disulfiram(antabuse) – works by inhibiting the metabolism of alcohol, causing build up of acetaldehyde, a noxious substance .( 125-500mg/day).

• Naltrexone : reduction of craving of alcohol, (vivitrol long acting I.M, once monthly 300mg reduces non compliance)

• Acamprosate(campral): taurine analogue works on GABA and glutamate neurotransmission, reduce relapse to drinking, two 333mg tab 3 times daily who have ceased alcohol at least 5days.

• Topiramite (topamax): titrated over 5wks between 50mg and 300mg daily.


Involvement of family: • A family intervention in which all family members confront

the patients drinking, help the patient to deal with denial.• Refusal by spouse to remain with the pt unless he or she

stops drinking

Alcoholics anonymous (AA): highly useful treatment group and found most effective treatment model.

Behaviour therapy : punishing drinking (e.g disulfirum) and rewarding sobriety (e.g. by paying the pt for abstinence)

On going emotional support by primary physician.


Long term effects of alcohol

Alcohol liver disease • Risk factors:• Drinking pattern- >80gm of alcohol / day• Sex- women• Genetics – HLAB8 , hep B & C acts as co factor • Nutrition- alcohol increases daily requirement of

cholin, folic acid, protein deficiency promotes the toxic of alcohol

.SLEISENGER AND FORDTRANS 9th edition gastrointestinal and liver disease Vol2 Section IX – Liver;CHAPTER 84 – Alcoholic Liver Disease no 1394.

• Mechanism of liver injury 1. direct toxic effect of alcohol 2. acetaldehyde: binds with phospholipids, amino residues, & sulphydryl groups and thus becomes reactive and toxic; binds to tubulin and impairs the microtubules of cytoskeleton.OTHER MECHANISM 1. Changes in intracellular redox potential2. Mitochondrial swelling3. Liver cell water protein retention4. Hypermetabolic state5. Increased liver fat6. Immunological liver damage 7. Fibrosis8. Cytokine mediated injury.


Morphological change • Fatty liver: presence of more than 5gm of fat/ 100gm of liver tissue. Lab featuresa. Hyperbilirubinemia b. AST/ALT > 2 in 80% ( due to pyridoxine deficiency)c. ALP elevated in the absence of cholestasisd. GGT/ALP ratio 5 or higher in 50% cases e. GGT blood levels > 30U & Carbohydrate Deficient Transferrin > 20U ( specificity and sensitivity > 70 % ) f. Other blood increased MCV > 91 and sr uric acid > 7mg/dl


Alcohol hepatitis: • c/f: anorexia, nausea, weakness, icterus, weight loss or fever.• Morphological change : liver cell damage, neutrophilic infiltration,

pericellular & perivenular fibrosis, mallory hyaline or mallory body.• Physical signs: hepatomegaly(95%), hepatic tenderness (50-60%), signs of

portal htn (40-70%) jaundice, fever, upper GI bleeding (30%) & evidence of hepatic encephalopathy.

• Lab features: bilirubin increase , AST & ALT elevated, PT prolonged.

Hepatic cirrhosis: • Morphological change : micronodular type. • c/f: asymptomatic 10-20%, commonly presents with complications and

stigmata of CLD • Lab features: transaminases incresed, hypoalbuminaemia , PT prolonged.• Prognosis : Discriminant function = 4.6 *increased PT (sec) + sr bilirubin

(mg)


Treatment • Dicremination factor > 32 can be tried with steroids

prednisone 40mg/day for four weeks and then taper or pentoxyphylline.

• Abstinence from alcohol• Dietary supplementation • Avoid precipitating factors( infection)• Treatment of withdrawal syndrome • Treatment of complications ( ascites, SBP, hepatorenal

syndrome, hepatic encephalopathy, upper GI bleed)• hepatic transplantation in selected cases


Fetal alcohol syndrome(FAS) Any unborn child, male or female of any race might be affected by the alcohol that a mother consumes while she is pregnant.

FAS in 1 to 2 births / 1,000 in U.S each year.

Drunkenness

• Is a condition produced in a person, who as taken alcohol in a quantity sufficient to cause him to lose control of his faculties to such an extent, that he is unable to execute safely, the occupation in which he was engaged at the particular time.

• Model scheme of medical examination: suggested by special committee of British Medical Association “the drinking driver” 1965.2.ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS

DEPRESSANTS no 497-514.

1. Exclusion of injuries and pathological state: head injury, metabolic disorder, neurological condition, drugs, pre-existing psychological disorder.

2. History: relevant events obtained from accused person while observing him. The amount and time of liquor taken should be noted.3. General behaviour: state of dress, speech, self control.4. Memory and mental alertness: memory of recent events, calculations5. Hand writing: time taken, repetition or omission of words , ability to read his own hand writing, sign his name.6. Pulse: rapid and usually bounding.7. Temperature: surface temp is usually raised.8. skin: moist, dry, flushed or pale9. Mouth: smell of breath10. Eyes: general, visual acuity, intrinsic muscles (pupils ) ,extrinsic muscle (nystagmus) .ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

11. Ears: gross impairment of hearing 12. Gait: manner of walking, reaction time to direction to turn, manner of turning 13. Stance. Romberg's sign 14. Muscular coordination: placing finger to nose, placing finger to finger, picking medium sized objects from the floor. 15. Reflexes: knee and ankle delayed or sluggish. Planter reflex may be extensor or flexor 16. Pulmonary, cardiovascular and git systems : presence or absence of disease 17. Tests: nerve conduction speed, pupillary reflex time ..ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS

DEPRESSANTS no 497-514.

• 18. Lab invest :

Blood: preserved in 100mg sodium fluoride and 30 mg potassium oxalate for 10ml.Widmark: evolved a formula which takes into account the size and sex of person and the type of alcohol liquor consumed, a=prc

a-weight of alcohol(gm) in body; p-body weight (in kg); c- concentration of alcohol on blood (mg/kg); r- is constant (0.6 for men, 0.5 for women) 1. kozelka and hine test is macro method 2. cavett test is a micro method. ( in a test tube 1ml of unknown solution+ one drop sulphuric acid + one ml of acetic acid, heat gently for one min, strong fruity odour is positive..ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

Sample Relative concentration of alcohol at equilibrium

Whole blood 1

Plasma/serum 1.12 to 1.2

alveoli 0.0021

Spinal fluid 1.1 to 1.27

brain 0.8

vitreous 1.3

Urine 1.3

Liver 0.8

• Breath: alcohol absorbs radiation in infrared region of spectrum and that the amount of infrared light absorbed by vapour is proportional to concentration of alcohol in that vapour.

60-100ml of breath is received in dry balloon and analysed by drunkometer, drunkotester, intoximeter, alcometer. The end portion of a prolonged forced expiration gives correct results. Alcohol in deep lung air is dependent on that of arterial blood (2100-2300 of alveolar blood contains same amount of alcohol in 1ml of blood)


Urine: in order to compare the urine and blood, a ratio of 1.3:1.0 is usually accepted when urine and blood are in equilibrium. Disadvantages: 1.time lag before equilibrium between blood and urine reached; max concentration reached 20-25 min later than in blood.

Vitreous: not change after death due to putrefaction, at equilibrium , for every unit of alcohol in blood , there are 1.2 units in vitreous.ESSENTIALS OF FORENSIC MEDICINE K S NARARYAN REDDY 28TH EDITION ; chapter 30 CNS DEPRESSANTS no 497-514.

References1.HARRISONS PRINCIPLES OF INTERNAL MEDICINE 18th edition vol 2; chapter 392 alcohol and alcoholism no 3456-3552.



4.CONNS CURRENT THERAPY BOPE KELERMAN 2013, SECTION 16 PSYCHIATRIC DISORDERS- ALCOHOLISM no 921-927.

5.SLEISENGER AND FORDTRANS 9th edition gastrointestinal and liver disease Vol2 Section IX – Liver;CHAPTER 84 – Alcoholic Liver Disease no 1394.

6.Neurology in Clinical Practice e-dition, 5th Edition Bradley, Daroff, Fenichel & Jankovic; chapter 61 Deficiency Diseases of the Nervous System no 1650-1654.

7.PARIKHS TEXT BOOK OF MEDICAL JURISPRUDENCE FORENSIC MEDICINE AND TOXICOLOGY, 6TH EDITIOIN PART 5 CLINICAL AND FORENSIC TOXICOLOGY SECTION 10, CHAPTER 50 INEBRIANT POISONS 10.14-10.34.

8.NMS PSYCHIATRY 5th edition JOUHUA T. THORNHILL 4, chapter 5 substance related disorder chapter 7 no 158-159

• Next seminar – ANAND

Thank you

Ethylene glycol poisoning Colourless, odourless ,nonvolatile,water

soluble.

Paints,polishes, cosmetics,antifreeze.

Viscous & sweet –poorman’s substitute for alcohol.

Minimal lethal dose 1-1.5ml/kg.

Peak level 1-4 hr.

• Clinical effects

Stage 1– inebriated without odour of alcohol. (1-12hrs) other CNS symptoms.

Stage 2-- CVS changes (12-24 hrs)

Stage3-- ARF (24-72 hrs)

Lab finding: oxalate crystals in urine. hypocalcemia ↑A: G acidosis tt mainly on history & clinical

symptoms.

Specific treatment: ethanol pyridoxine thiamine magnesium 4-methyl pyrazole(antidote) HD


Isopropyl alcohol poisoning 2-propanol,isopropanol.

Clear, volatile ,bitter taste,aromatic odour

Solvent, & disinfectant.

2nd to ethanol as most commonly ingested alcohol.

Twice potent than ethanol as CNS depressant.

Toxic dose--- 1ml/kg of 70 % solution.

Lethal dose---2-4ml/kg.

80% absorbed from GIT in 30 mins.

Dermal absorption & inhalation.

.PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

Diagnosis inebriated with –ve or low

ethanol. elevated osmolar gap ketosis without acidosis >50mg/dl

toxic,200-400mg/dl lethal.

Treatment: GI evacuation. dialysis if 3-4 ml /kg of 70%

solution blood level

>400mg/dl unrespnsive

hypotension renal failure,coma.

.

PARKS TEXTBOOK OF PREVENTIVE AND SOCIAL MEDICINE ; 21 EDITION ,CHAPTER 18 mental health- alcoholism and drug dependence no 774.

alcohol and alcoholism

Health & Medicine