alcohol and its types, the tests associated with it and the clinical conditions arising from it

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ALCOHOL METABOLISM

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Page 1: Alcohol and its types, the tests associated with it and the clinical conditions arising from it

ALCOHOL METABOLISM

Page 2: Alcohol and its types, the tests associated with it and the clinical conditions arising from it

CONTENTS

ETHANOL • METABOLISM• ACTIONS• ABSTINANCE• EFFECTS ON ORGANS• TERATOGENICITYMETHANOLISOPROPANOL

ESTIMATION• BLOOD ALCOHOL• BREATH ALCOHOL• SALIVARY ALCOHOL• URINARY ALCOHOL• POSTMORTEM ALCOHOL

ALCOHOLIC LIVER DISEASE

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ETHANOL

• WEAKLY CHARGED MOLECULE• MOVES EASILY THROUGH CELL MEMBRANES• RAPIDLY EQUILIBRATING BETWEEN BLOOD AND TISSUES

IN BEVERAGES IN ADDITION TO ALCOHOL• LOW MOLECULAR WT ALCOHOLS(METHANOL ,BUTANOL)• ALDEHYDES• ESTERS• HISTAMINE

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• PHENOLS • TANNINS• IRON,• LEAD• COBALT• ADVERSE CONSEQUENCES WITH HEAVY DRINKING

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ABSORPTION

RATE INCREASED BY• RAPID GASTRIC EMPTYING• ABSENCE OF PROTEINS FATS AND CARBOHYDRATES• ABSENCE OF CONGENERS• CARBONATION(EG. CHAMPAGNE)

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EXCRETION

• LUNGS, URINE AND SWEAT (SMALL AMOUNTS)

• LIVER (GREATER PART)

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ALCOHOL

• SUPPLIES CALORIES • DEVOID OF MINERALS, PROTEINS AND VITAMINS• INTERFERES WITH VITAMIN ABSORPTION FROM

INTESTINE• DECREASES THEIR STORAGE IN THE LIVER• MODEST EFFECT ON FOLATE, VIT B6, THIAMINE, NIACIN

AND VIT A

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Mitochondrion

Ethanol

Acetaldehyde

Acetate

CytosolER

ADHNAD+

NADH

AlDHNAD+

NADH

MEOS

NADP+

NADPHO2

P450

Extra-hepatic tissue

Disulfiram

CELLULAR PROCESSING

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Glc

Malate MDHNADHNADH

Malate

PEPCK

G6PGK

F6P

F16BPPFK

PEP

PyrPK

NADHMalate

Suc

Fum

PDHAcetyl CoA

Cit

ICitMitochondrion

Cytosol

NADH

NADH

PC

OAA

MDHNAD+

OAAMDHNAD+

αKG

IDHNAD+

Lactate LDHNAD+

S CoAαKGDHNAD+

G6Pase

F16BPase

NADH

FAβ-OxNADH

PATHWAY PERTURBATIONS

NADH

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HYPOGLYCEMIA AND ALCOHOL INTOXICATION

VULNERABLE INDIVIDUALS• FASTED• PROLONGED STRENUOUS EXERCISE• USING INSULIN-HYPOGLYCEMIA OCCURING MANY HOURS

AFTER ALCOHOL CONSUMPTION

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ALCOHOL KETOACIDOSIS• POOR DIET• RECURRENT VOMITING• MISDIAGNOSED AS DIABETIC KETOSIS• INCREASE IN KETONES• MILD INCREASE IN BLOOD GLUCOSE• LARGE ANION GAP• MILD TO MODERATE INCREASE IN SERUM LACTATE• Β-HYDROXYBUTYRATE/LACTATE RATIO BETWEEN 2:1 AND 9:1 (NORMAL

1:1).

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MEOS PATHWAY• P450-DEPENDENT MICROSOMAL ETHANOL OXIDIZING SYSTEM• INVOLVING NADPH AND O2• INCREASES IN ACTIVITY IN CHRONIC ALCOHOLISM• GENERATES ACETALDEHYDE AND SUBSEQUENTLY ACETATE• WHILE OXIDIZING BIOSYNTHETIC REDUCING POWER, NADPH, TO NADP+. • BECAUSE IT USES OXYGEN, THIS PATHWAY GENERATES FREE RADICALS THAT

DAMAGE TISSUES. • MOREOVER, BECAUSE THE SYSTEM CONSUMES NADPH, THE ANTIOXIDANT

GLUTATHIONE CANNOT BE REGENERATED EXACERBATING THE OXIDATIVE STRESS.

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• BELOW 100 MG/DL (22 MMOL/L), THE MEOS SYSTEM, (HIGH KM FOR ALCOHOL), CONTRIBUTES LITTLE.

• WHEN LARGE AMOUNTS OF ETHANOL ARE CONSUMED, THE ADH SYSTEM BECOMES SATURATED OWING TO DEPLETION OF NAD+.

• ABOVE 100 MG/DL, THERE IS INCREASED CONTRIBUTION FROM THE MEOS SYSTEM, WHICH DOES NOT RELY UPON NAD+

• DURING CHRONIC ALCOHOL CONSUMPTION, MEOS ACTIVITY INCREASES.

• CHRONIC ALCOHOL CONSUMPTION RESULTS ALSO IN THE INCREASED CLEARANCE OF OTHER DRUGS ELIMINATED BY THE MEOS SYSTEM.

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• LIVER MITOCHONDRIA CAN CONVERT ACETATE INTO ACETYL COA IN A REACTION REQUIRING ATP.

• ENZYME IS THE THIOKINASE THAT NORMALLY ACTIVATES SHORT-CHAIN FATTY ACIDS.

• HOWEVER, FURTHER PROCESSING OF THE ACETYL COA BY THE CITRIC ACID CYCLE IS BLOCKED, BECAUSE NADH INHIBITS

• ISOCITRATE DEHYDROGENASE AND A-KETOGLUTARATE DEHYDROGENASE

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CONSEQUENCES OF ACETYL COA ACCUMULATION

• ↑KETONE BODIES FORMATION, EXACERBATING THE ACIDIC CONDITION ALREADY RESULTING FROM THE HIGH LACTATE CONCENTRATION.

• THE PROCESSING OF THE ACETATE IN THE LIVER BECOMES INEFFICIENT, LEADING TO A BUILDUP OF ACETALDEHYDE.

• THIS VERY REACTIVE COMPOUND FORMS COVALENT BONDS WITH MANY IMPORTANT FUNCTIONAL GROUPS IN PROTEINS, IMPAIRING PROTEIN FUNCTION.

• IF ETHANOL IS CONSISTENTLY CONSUMED AT HIGH LEVELS, THE ACETALDEHYDE CAN SIGNIFICANTLY DAMAGE THE LIVER, EVENTUALLY LEADING TO CELL DEATH

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↑NADH

• INHIBITS FATTY ACID OXIDATION• ↑FATTY ACID SYNTHESIS• INCREASED ESTERIFICATION OF FATTY ACIDS IN TRIACYLGLYCEROL• INCREASED LIPOGENESIS • ↑ CHOLESTEROL SYNTHESIS FROM ACETYL-COA, • ↑ LIPID PEROXIDATION• CITRIC ACID CYCLE IS BLOCKED• INHIBITS ISOCITRATE DEHYDROGENASE AND A-KETOGLUTARATE DEHYDROGENASE• HYPERLACTIC ACIDEMIA• DECREASES EXCRETION OF URIC ACID-GOUT

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ETHANOL

• CNS ACTIONS OF ETHANOL PRONOUNCED DURING ABSORPTIVE PHASE THAN ELIMINATION PHASE- PHENOMINON OF ACUTE TOLERANCE

• SYNERGISTIC ACTION WITH CNS DEPRESSIVE DRUGS• DEATHS OCCURRED

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MECHANISM OF CNS DEPRESSION

• ENHANCEMENT OF MAJOR INHIBITORY NEURONS

• IMPAIRMENT OF EXCITATORY NEURONS

• INHIBITORY NEURONAL SYSTEM-GABA

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GABA binds to post synaptic receptor

subtype GABAA

This complex opens

Inward flux of Cl-

Membrane hyper

polarization

Decreased electrical response

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GABA MEDIATED INHIBITORY RESPONSE ENHANCED BY • ETHANOL• BARBITURATES• BENZODIAZEPINES• MOST GENERAL ANAESTHETIC AGENTS

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• CNS EXCITATORY RESPONSE MEDIATED BY GLUTAMATE

• ETHANOL INHIBITS THE EXCITATORY RESPONSE MEDIATED BY CA ION GATED GLUTAMATE RECEPTOR SUBTYPE N-METHYL D ASPARTATE(NMDA)RECEPTOR

• ↑ THE ACTIVITY OF PHENYLETHANOLAMINE N METHYLTRANSFERASE

NOREPENEPHRINE EPENEPHRINE

PNMT

• EPINEPHRINE IN TURN ACTIVATES PRESYNAPTIC Α2 RECEPTORS WHICH INHIBITS RELEASE OF NOREPINEPHRINE

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PHYSICAL ABSTINANCE SYNDROME

• ABRUBT WITHDRAWL-PHYSICAL ABSTINANCE SYNDROME• CNS EXCITATION• ANXIETY, IRRITABILITY• INSOMNIA• MUSCLE TREMOR AND CRAMPS• SEIZURES• HALLUCINATIONS• ↑TEMPERATURE, BP, HEART RATE

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DELIRIUM TREMENS• INTENSE ACUTE WITHDRAWL• DELIRIUM- MENTAL CONFUSION, AGITATION AND

FLUCTUATING LEVELS OF CONSCIOUSNESS• TREMENS- ↑ PULSE, BP AND RESPIRATION• CONCOMITANT MEDICAL DISORDERS

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EFFECTS OF ETHANOL ON ORGAN SYSTEMS

NERVOUS SYSTEM• BLACKOUT, AN EPISODE OF TEMPORARY ANTEROGRADE

AMNESIA• DISTURBED SLEEP• DISTURBING DREAMS• SNORING• EXACERBATES SLEEP APNOEA• IMPAIRED JUDGEMENT AND COORDINATION

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CHRONIC ALCOHOLISM• PERIPHERAL NEUROPATHY• CEREBELLAR DEGENERATION OR ATROPHY-PROGRESSIVE UNSTEADY

STANCE AND GAIT OFTEN ACCOMPANIED BY MILD NYSTAGMUS

WERNICKE’S (OPHTHALMOPARESIS, ATAXIA, AND ENCEPHALOPATHY)KORSAKOFF ’S (RETROGRADE AND ANTEROGRADE AMNESIA)• THIAMINE DEFICIENCY• TRANSKETOLASE DEFICIENCY

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PSYCHIATRIC PROBLEMS• IMPULSIVITY AND DISINHIBITION• PREEXISTING SCHIZOPHRENIA OR MANIC DEPRESSIVE

DISEASE • ANXIETY DISORDERS SUCH AS PANIC DISORDER.• INTENSE SADNESS LASTING FOR DAYS TO WEEKS IN THE

MIDST OF HEAVY DRINKING• AUDITORY HALLUCINATIONS

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GASTROINTESTINAL SYSTEM

ESOPHAGUS AND STOMACH• EPIGASTRIC DISTRESS AND GASTROINTESTINAL BLEEDING• MALLORY-WEISS LESION

PANCREAS AND LIVER• ACUTE PANCREATITIS• ALCOHOL-INDUCED HEPATITIS, PERIVENULAR SCLEROSIS, AND

CIRRHOSIS

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• (A) ABDOMINAL X RAY OF A PATIENT WITH ALCOHOLIC PANCREATITIS. NOTE THE SPECKLED CALCIFICATION (I.E., CALCIUM DEPOSITS) WITHIN THE PANCREAS (MARKED BY ARROWS).

• (B) ABDOMINAL X RAY FROM A SUBJECT WITHOUT PANCREATITIS.

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CANCER • BREAST CANCER• ORAL AND ESOPHAGEAL CANCERS• RECTAL CANCERS

HAEMATOPOETIC SYSTEM• INCREASE IN (MCV)• ACCOMPANIED BY FOLIC ACID DEFICIENCY-HYPERSEGMENTED NEUTROPHILS,

RETICULOCYTOPENIA• MILD THROMBOCYTOPENIA• CHRONIC HEAVY DRINKING-DECREASED PRODUCTION OF WBCS

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CARDIOVASCULAR SYSTEM

• MILD TO MODERATE HTN• CORONARY ARTERY DISEASE• CARDIOMYOPATHY• UNEXPLAINED ARRHYTHMIAS TO HEART FAILURE“HOLIDAY HEART.”• ATRIAL OR VENTRICULAR ARRHYTHMIAS, ESPECIALLY PAROXYSMAL

TACHYCARDIA, CAN ALSO OCCUR AFTER A DRINKING BINGE IN INDIVIDUALS SHOWING NO OTHER EVIDENCE OF HEART

• OBSERVED TRANSIENTLY IN THE MAJORITY OF ALCOHOLICS ENTERING TREATMENT.

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GENITOURINARY SYSTEM CHANGES AND SEXUAL

FUNCTIONINGMEN • MODEST DOSES-INCREASE SEXUAL DRIVECHRONIC ALCOHOLISM-• IRREVERSIBLE TESTICULAR ATROPHY• SHRINKAGE OF THE SEMINIFEROUS TUBULES, • DECREASES IN EJACULATE VOLUME,• LOWER SPERM COUNT

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WOMEN • AMENORRHEA, A DECREASE IN OVARIAN SIZE, • ABSENCE OF CORPORA LUTEA WITH

ASSOCIATED INFERTILITY, • INCREASED RISK OF SPONTANEOUS

ABORTION.

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BONE

• CHANGES IN CALCIUM METABOLISM• LOWER BONE DENSITY• DECREASED GROWTH IN THE EPIPHYSIS• ↑RISK OF FRACTURES• OSTEONECROSIS OF FEMORAL HEAD

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OTHER EFFECTS• ALCOHOLIC MYOPATHY• ↑CORTISOL• ↑ VASOPRESSIN AT RISING BLOOD ALCOHOL CONC• ↓ VASOPRESSIN AT FALLING BLOOD ALCOHOL CONC• MODEST ↓ IN T4• MARKED ↓ IN T3

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FETAL ALCOHOL SYNDROME• HEAVY DRINKING DURING PREGNANCY• PLACENTAL TRANSFER OF ETHANOL AND ACETYLDEHYDE

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ACUTE ALCOHOL INTOXICATION

• CORTISOL RELEASE• ↑PLASMA CATECHOLAMINES• SHARP REDUCTION IN PLASMA TESTOSTERONE• ↑ PLASMA LH

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CHRONIC ALCOHOLISM

• ↑GGT

• CARBOHYDRATE DEFICIENT TRANSFERRIN

• ABNORMAL PITUITORY, ADRENOCORTICAL AND MEDULLARY FUNCTION

• DESIALYLATION OF PROTEINS

• ↑MCV

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METHANOL

• CONSTITUENT OF ANTIFREEZE AND WINDOW CLEANING FLUIDS AND CANNED FUEL

• INTENSIONAL CONSUMPTION-ETHANOL SUBSTITUTE• ACCIDENTALLY-ILLEGAL WHISKY• ACCIDENTAL –CHILDREN• CNS EFFECTS LESS SEVERE THAN ETHANOL• LIVER ADH

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FORMIC ACID• SERIOUS ACIDOSIS• OPTIC NEUROPATHY• BLINDNESS • DEATH

• FORMATE IS TOXIC BECAUSE IT INHIBITS MITOCHONDRIAL CYTOCHROME C OXIDASE, CAUSING THE SYMPTOMS OF HYPOXIA AT THE CELLULAR LEVEL, AND ALSO CAUSING METABOLIC ACIDOSIS

• SERUM FORMATE CORRELATE WITH ACIDOSIS AND SEVERITY OF CNS AND OCULAR TOXICITY THAN DO SERUM METHNOL CONC

• ETHANOL IS SOMETIMES DENATURED (ADULTERATED), AND THUS MADE UNDRINKABLE, BY THE ADDITION OF METHANOL. THE RESULT IS KNOWN AS METHYLATED SPIRIT

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TREATMENT OF METHANOL INTOXICATION

• ETHANOL• FOMEPIZOLE TO INHIBIT METHANOL METABOLISM• SODIUM BICARBONATE THERAPY FOR METABOLIC

ACIDOSIS• FOLATE-ENHANCE FOLATE MEDIATED METABOLISM OF

FORMATE• HAEMODIALYSIS- CLEARANCE OF METHANOL AND

FORMATE

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ANALYSIS

• HEAD SPACE GAS CHROMATOGRAPHY-METHOD OF CHOICE FOR METHANOL ESTIMATION

• ENZYMATIC ASSAY• BASED ON FORMATE DEHYDROGENASE

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ISOPROPANOL • 70% AQUEOUS SOLUTION- RUBBING ALCOHOL• TWICE THE CNS DEPRESSANT ACTION AS ETHANOL• NOT AS TOXIC AS METHANOL• SHORT HALF LIFE-6HOURS• RAPIDLY METABOLISED BY ADH TO ACETONE WHICH IS

ELIMINATED MORE SLOWLY(T1/2 17 TO27 HRS)• ALVEOLAR AIR AND URINE• ACETONE CONC EXCEEDS ISOPROPANOL IN ELIMINATION

PHASE

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ISOPROPANOL • ACETONE-CNS DEPRESSANT ACTIVITY SAME LIKE ETHANOL• LONGER HALF LIFE-PROLONGS THE CNS EFFECTS

SEVERE INTOXICATION-• COMA OR DEATH• TREATMENT- HAEMODIALYSIS• ETHANOL NOT INDICATED

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ISOPROPANOL -ESTIMATION

• HEAD SPACE GAS CHROMATOGRAPHY• NMR SPECTROMETRY

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BLOOD ALCOHOL

• SERUM, PLASMA OR WHOLE BLOOD• SITE CLEANSED WITH ALCOHOL FREE DISINFECTANT LIKE

BENZALKONIUM CHLORIDE• SERUM: WHOLE BLOOD ETHANOL RATIO IS 1.14• SPECIMENS WELL CAPPED• BLOOD PROPERLY SEALED-14 DAYS AT ROOM TEMP• 4 DEG WITH OR WITHOUT PRESERVATIVE• LONGER STORAGE-SODIUM FLUORIDE PRESERVATIVE• NON STERILE POST MORTEM SPECIMENS-SODIUM FLUORIDE

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ESTIMATION • ENZYMATIC ANALYSIS USING ALCOHOL

DEHYDROGENASE• ETHANOL TO ACETALDEHYDE• AMOUNT OF NADH FORMED AT 340NM• ADH RELATIVELY SPECIFIC TO ETHANOL• INTERFERENCE 7% -ISOPROPANOL, 3 % METHANOL

AND 4 % ETHYLENE GLYCOL• SPECTROPHOTOMETERS OR AUTOMATED ANALYSERS• SERUM COMMONLY• URINE OR SALIVA• WHOLE BLOOD-PRECIPITATION STEP- AVOID

HAEMOGLOBIN INTERFERENCE

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BREATH ALCOHOL• POINT OF CARE• PRINCIPLE-ALCOHOL IN CAPILLARY ALVEOLAR BLOOD RAPIDLY

EQUILIBRATES WITH ALVEOLAR AIR IN A RATIO 2100:1(BLOOD:BREATH)

• BREATH ALCOHOL G/210L=G/DL IN WHOLE BLOOD• BLOOD:BREATH=2100:1• WAITING PERIOD-15 MIN• VERY RECENT DRINKING, ALCOHOL CONTAINING MOUTHWASH OR

VOMITING ALCOHOL RICH GASTRIC JUICE

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BREATH ALCOHOL

• ACTIVE ALCOHOL ABSORPTION-30-120 MIN• ARTERIAL BLOOD ALCOHOL>PERIPHERAL VENOUS

BLOOD• BREATH ALCOHOL>VENOUS BLOOD BECAUSE END

EXPIRATORY AIR EQUILLIBRATES WITH PULMONARY ARTERIAL BLOOD

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US DEPARTMENT OF TRANSPORTATION

• BREATH ALCOHOL• 0.02-0.04G/210L-NO DUTIES FOR 8HRS• 0.04G/210L-SUSPENDED FROM DUTY UNTIL EVALUATION

BY SUBSTANCE ABUSE PROFESSIONALS

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BREATH ALCOHOL MEASUREMENT

• INFRA RED ABSORPTION SPECTROMETRY(MOST COMMON)

• DICHROMATE SULFURIC ACID OXIDATION REDUCTION• GC(FLAME IONIZATIONOR THERMAL CONDUCTIVITY

DETECTION• ELECTROCHEMICAL OXIDATION• METAL OXIDE SEMICONDUCTOR SENSORS

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SALIVA ALCOHOL

• EASY• NONINVASIVE• ETHANOL DISTRIBUTION BETWEEN BLOOD AND SALIVA BY

PASSIVE DIFFUSION• 9%HIGHER THAN WHOLE BLOOD• SIMILAR TO SERUM ALCOHOL• CONCENTRATION TIMES SAME IN BLOOD, BREATH AND

SALIVA

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QED SALIVA ALCOHOL TEST

• ETHANOL IN SALIVA• ADH REACTION COUPLED WITH DIAPHORASE MEDIATED COLOUR

INDICATOR REACTION• RESULTS IN AGREEMENT WITH VENOUS BLOOD OR BLOOD• ON SITE USE• EMERGENCY DEPT, WORKPLACE, ROADSIDE• APPROVED BY DOT FOR ALCOHOL SCREENING• DESIGNED FOR SALIVA• ACCURATE MEASUREMENT OF SERUM ETHANOL AS WELL

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QED TESTUSING THE COTTON SWAB INCLUDED, ACTIVELY SWAB AROUND THE CHEEKS, GUMS, AND TONGUE FOR 30-60 SECONDS OR UNTIL THE COTTON SWAB IS COMPLETELY SATURATED WITH SALIVA

PLACE THE TEST DEVICE ON A FLAT SURFACE. GENTLY TWIST THE SWAB WITH THE COLLECTED SALIVA SAMPLE INTO THE ENTRY

PORT AND APPLY STEADY PRESSURE TO ACTIVATE THE CAPILLARY

ACTIONUNTIL THE PINK FLUID PASSES THE QA SPOT™ LOCATED AT THE TOP OF THE TEST DEVICE.

READ THE TEST RESULTS. ALLOW THE TEST DEVICE TO DEVELOP FOR TWO MINUTES. A DISTINCT PURPLE BAR WILL FORM WITHIN THE MARKED SCALE REGION. THE HIGHEST POINT OF THE PURPLE BAR REPRESENTS THE LEVEL OF ALCOHOL EXPRESSED AS EITHER A PERCENTAGE (.0X%) OR MILLIGRAMS (ML/DL) CONCENTRATION.

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• U.S. DEPARTMENT OF TRANSPORTATION (DOT)

• ALCOHOL TESTING FORM

• (THE INSTRUCTIONS FOR COMPLETING THIS FORM ARE ON THE BACK OF COPY 3)

• STEP 1: TO BE COMPLETED BY ALCOHOL TECHNICIAN

• A: EMPLOYEE NAME______________________________________________________________________________________

• (PRINT) (FIRST, M.I., LAST)

• B: SSN OR EMPLOYEE ID NO. _____________________________________________________________________________

• C: EMPLOYER NAME _____________________________________________________________________________

• STREET CITY, ST ZIP _____________________________________________________________________________

• DER NAME AND

• TELEPHONE NO. ___________________________________________________(_____)____________________

• DER NAME DER PHONE NUMBER

• D: REASON FOR TEST: . RANDOM . REASONABLE SUSP . POST-ACCIDENT .RETURN TO DUTY . FOLLOW-UP . PRE-EMPLOYMENT

• STEP 2: TO BE COMPLETED BY EMPLOYEE

• I CERTIFY THAT I AM ABOUT TO SUBMIT TO ALCOHOL TESTING REQUIRED BY US DEPARTMENT OF TRANSPORTATION REGULATIONS AND THAT THE

• IDENTIFYING INFORMATION PROVIDED ON THE FORM IS TRUE AND CORRECT.

• ___________________________________________________________________ _____________/____/_____

• SIGNATURE OF EMPLOYEE DATE MONTH DAY YEAR

• STEP 3: TO BE COMPLETED BY ALCOHOL TECHNICIAN

• (IF THE TECHNICIAN CONDUCTING THE SCREENING TEST IS NOT THE SAME TECHNICIAN WHO WILL BE CONDUCTING THE CONFIRMATION TEST,

• EACH TECHNICIAN MUST COMPLETE THEIR OWN FORM.) I CERTIFY THAT I HAVE CONDUCTED ALCOHOL TESTING ON THE ABOVE NAMED

• INDIVIDUAL IN ACCORDANCE WITH THE PROCEDURES ESTABLISHED IN THE US DEPARTMENT OF TRANSPORTATION REGULATION, 49 CFR PART

• 40, THAT I AM QUALIFIED TO OPERATE THE TESTING DEVICE(S) IDENTIFIED, AND THAT THE RESULTS ARE AS RECORDED.

• TECHNICIAN: . BAT . STT DEVICE: . SALIVA . BREATH* 15-MINUTE WAIT: . YES . NO

• SCREENING TEST: (FOR BREATH DEVICE* WRITE IN THE SPACE BELOW ONLY IF THE TESTING DEVICE IS NOT DESIGNED TO PRINT.)

• _____ __________________ ________________________________ _____________ ____________ _________

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• TEST # TESTING DEVICE NAME DEVICE SERIAL # OR LOT # & EXP DATE ACTIVATION TIME READING TIME RESULT

• CONFIRMATION TEST: RESULTS MUST BE AFFIXED TO EACH COPY OF THIS FORM OR PRINTED DIRECTLY ONTO THE FORM.

• REMARKS:• __________________________________________________________________________________________• ALCOHOL TECHNICIAN’S COMPANY COMPANY STREET ADDRESS• _______________________________________________

_______________________________(_____)_________________• (PRINT) ALCOHOL TECHNICIAN’S NAME (FIRST, M.I., LAST) COMPANY CITY, STATE, ZIP

PHONE NUMBER• _______________________________________________ __________/____/________• SIGNATURE OF ALCOHOL TECHNICIAN DATE MONTH DAY YEAR• STEP 4: TO BE COMPLETED BY EMPLOYEE IF TEST RESULT IS 0.02 OR HIGHER• I CERTIFY THAT I HAVE SUBMITTED TO THE ALCOHOL TEST, THE RESULTS OF WHICH

ARE ACCURATELY RECORDED ON THIS FORM. I UNDERSTAND• THAT I MUST NOT DRIVE, PERFORM SAFETY-SENSITIVE DUTIES, OR OPERATE HEAVY

EQUIPMENT BECAUSE THE RESULTS ARE 0.02 OR GREATER.• ______________________________________________________________________ _____________/_____/____• SIGNATURE OF EMPLOYEE DATE MONTH DAY YEAR• OMB NO. 2105-0529

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ONSITE ALCOHOL TEST CARD DEVICE

• SALIVA OR URINE• SAME REACTION• POSITIVE RESPONSE FOR ETHANOL CONCENTRATION

GREATER THAN 0.02G/DL• ALSO APPROVED BY DOT

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THIRD DEVICE

• PLASTIC TEST STRIP• DOT APPROVED• ADH DIAPHORASE COUPLED INDICATOR

COLOUR BAR• IF 0.02G/DL OR GREATER

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COLLECTION DIFFICULT

• FLOW OF SALIVA UNDER CONTROL OF PARASYMPATHETIC NERVOUS SYSTEM

• ANTICHOLINERGIC SYMPTOMS• DRY MOUTH ASS WITH TCA OVERDOSE• SALIVARY FLOW MAY BE IMPAIRED IN SOME ALCOHOLICS

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URINE ALCOHOL

• ALTERNATIVE TO SALIVA• LESS INVASIVE THAN BLOOD• POST ABSORPTIVE PHASE-CONCENTRATION 1.3 TIMES BLOOD• DISCOURAGED BY SOME AS THIS RATIO IS HIGHLY VARIABLE• REPRESENTS AN AVERAGE OF BLOOD ALCOHOL• EMPTYING THE BLADDER, COLLECTING URINE AFTER 20 TO 30 MIN• PREVIOUS 8 HRS• NOT APPROVED BY DOT

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POSTMORTEM ALCOHOL

• POSTMORTEM BLOOD• VITREOUS HUMOR• MUSCLE

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ALCOHOLIC LIVER DISEASE

RISK FACTORS1.DURATION AND MAGNITUDE OF ETHANOL

INGESTION• THRESHOLD 40G/DAY IN MEN AND 10G/DAY IN WOMEN• RISK DOSE-80G/DAY(200ML OF WHISKY OR EQUIVALENT)• DAILY DRINKING RISKIER

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2. GENDER-WOMEN• GREATER LIKELYHOOD OF PROGRESSION TO CIRRHOSIS• WOMEN HAVE REDUCED ACTIVITIES OF ADH

3. HEPATITIS B OR C• INCREASE THE SEVERITY IN PATIENTS WHO DRINK HEAVILY

4.GENETIC FACTORS• INHERITED PREDISPOSITION TO ALCOHOLISM

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5. NUTRITIONAL STATUS• PROTEIN CALORIE MALNUTRITION• POOR INTAKE• ABNORMAL NUTRIENT METABOLISM• OBESITY MAY BE A RISK FACTOR

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PATHOLOGY

• IMMUNOLOGICAL COMPONENT• MODIFICATION OF LIVER PROTEINS BY ETHANOL

METABOLITES

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LIVER DAMAGE FROM EXCESSIVE ETHANOL CONSUMPTION OCCURS IN THREE STAGES.

1. FATTY LIVER. 1. GOOD PROGNOSIS2. STEATOSIS DISAPPEARS AFTER 3 MONTHS OF ABSTINANCE

2. ALCOHOLIC HEPATITISWORSE PROGNOSIS

3. CIRRHOSIS • THE CIRRHOTIC LIVER IS UNABLE TO CONVERT AMMONIA INTO UREA,• AMMONIA IS TOXIC TO THE NERVOUS SYSTEM AND CAN CAUSE COMA

AND DEATH.

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ACUTE ALCOHOLIC HEPATITIS

• ACUTE FEBRILE ILLNESS• LEUCOCYTOSIS• ↑ACUTE PHASE PROTEINS• AST>2 TIMES ALT• CHOLESTATIC FORM WITH ↑ ALP>3 TIMES MAY BE SEEN-

HIGHER MORTALITY• ↑BILIRUBIN, ↓ALBUMIN AND PT-POOR PROGNOSIS

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GENETIC COMPONENT

• BOTH ALCOHOLISM AND SUSCEPTIBILITY TO THE DEVELOPMENT OF CIRRHOSIS

• VARIATION IN ALCOHOL INTAKE-GENETIC• GENETIC POLYMORPHISM OF THE (MEOS) MICROSOMAL ETHANOL

OXIDISING SYSTEM AND ADH• 50% ASIANS HAVE ABSENT ADH-FLUSH REACTION TO ALCOHOL THAT

INHIBITS DRINKING• HETEROZYGOTES OF ACETALDEHYDE DEHYDROGENASE(AADH)-

IMPAIRED CLEARANCE OF ACETALDEHYDE-PUTATIVE TOXIN-LIVER INJURY

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FATTY LIVER• ACCUMULATION OF FATTY ACIDS IN THE LIVER• ENDOGENOUS SYNTHESIS• NO IMPAIRMENT OF HEPATIC SYNTHESIS OF PROTEIN

AFTER ETHANOL INGESTION

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FATTY LIVER

• ↑ACETYL COA- ↑ FATTY ACID SYNTHESIS• ACETALDEHYDE-PRIMARY TOXIN

• CAUSES GENERATION OF FREE RADICALS• DEPLETION OF ANTI-OXIDANTS, LIKE GLUTATHIONE

• INJURY TO LIVER CELLS• INDUCTION OF COLLAGEN SYNTHESIS- FIBROSIS AND

CIRRHOSIS

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78

Alcohol and the Liver

Normal Liver Fatty Liver Cirrhotic Liver

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BIOCHEMICAL MARKERS

AMINO TRANSFERASES• AMINO TRANSFERASE ACTIVITIES RARELY EXCEED

300U/L-ACUTE ALCOHOLIC HEPATITIS• MUCH LOWER IN CHRONIC LIVER DISEASE• ALCOHOL DEPLETES THE VIT B6 DEPENDENT PYRIDOXAL

5 PHOSPHATE-PRECURSOR OF AMINO TRANSFERASE• AST:ALT>2

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BIOCHEMICAL MARKERS

• ↑APPEARANCE OF MITOCHONDRIAL AST(MAST)• NOT SOLE CAUSE• DAMAGE TO OTHER TISSUES WHICH RELEASE AST BUT NOT ALT, CONFINED TO

LIVER

ALP ELEVATED 2 TO 4 FOLD

GGT• GGT-SCREENING TEST• GGT-INDUCIBLE ENZYME ELEVATED BY MANY DRUGS AND DISEASES

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BIOCHEMICAL MARKERS

• CLINICAL SENSITIVITY FOR ALCOHOL CONSUMPTION SATISFACTORY

• NOT SPECIFIC FOR CHRONIC ALCOHOL ABUSE

ETHYL ESTERS OF FATTY ACIDS

COVALENT PROTEIN ADDUCTS-• ETHANOL METABOLISM AND LIPID PEROXIDATION

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BIOCHEMICAL MARKERS

• ALCOHOL INTERFERES WITH GLYCOCONJUGATION REACTIONS -ACETALDEHYDE INHIBITION OF GLYCOTRANSFERASES

ISOFORMS OF TRANSFERRIN• CHRONIC ABUSE-CARBOHYDRATE DEFICIENT(CDT)

ISOFORMS(HYPOSIALYL AND ASIALYLTRANSFERRIN)• CDT AND GGT-INCREASES THE ACCURACY OF DETECTING

PROLEM DRINKERS

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↑MEAN ERYTHROCYTE CORPUSCULAR VOLUME• DYSFUNCTIONAL PRODUCTION OF RED CELLS• MORE SPECIFIC THAN GGT

• PT PROLONGED• DECREASED ALBUMIN

SERUM LEVELS OF PROCOLLAGEN TYPE III• CORRELATE WITH COLLAGEN SYSTHESIS• DISEASE SEVERITY

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NON SPECIFIC LAB ABNORMALITIES• HYPERURICEMIA• HYPERLACTICACIDEMIA• HYPERTRYGLYCERIDEMIA• HYPOGLYCEMIA • HYPERGLYCEMIA• HYPOPHOSPHATEMIA• HYPOMAGNESEMIA• MACROCYTOSIS

Liver biopsy • Disease

severity• Prognosis• Rule out treatable

diseases like chronic hepatitis

and hemochromatosi

s

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ACUTE ALCOHOLIC HEPATITIS

DISCRIMIANT FUNCTION• [4.6X(PT-CONTROLPT)]+PLASMA BILIRUBIN(MG/DL)] VALUE >32• HIGH MORTALITY RATE

MODEL FOR END STAGE LIVER DISEASE(MELD)SCORE>11• SIMILAR SENSITIVITY• BETTER SPECIFICITY

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86

Summary

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