Alcohol abuse - systemic effects

Abuse vs. Dependence

Abuse: during 12 months, at least 1 of following:

    • Failure at social obligations due to drug use

    • Legal problems due to drug use

    • Use even in hazardous situations

    • Use despite having social problems

Dependence: during 12 months, at least 3 of the following:

    • Tolerance, increased amounts needed

    • Withdrawal

    • Need to use more

    • Cannot cut down or control use

    • Much time spent obtaining the drug

    • Social activities relinquished as direct result of drug use

    • Persistence of use despite being aware of harmful effects

Effects of Alcohol

CNS:

    • Acute: CNS depression, amnesia, fragmented sleep.

    • Chronic: Wernicke's and Korsakoff's syndromes (thiamine def), cerebellar deg, alcoholic dementia, peripheral neuropathy.

      • Cerebellar atrophy 2° to alcohol abuse tends to be more prominent in the anterior-superior vermis and paravermal zones, corresponding to the anterior lobe of the cerebellum.

        • Central truncal and gait ataxia is prominent feature, with lesser involvement of the upper limbs, and only rarely oculomotor symptoms of cerebellar dysarthria.

Thiamine deficiency causes the Wernicke-Korsakoff syndrome and is an important cause a peripheral neuropathy. Thiamine is mostly seen in chronic alcoholics. It is second only to traumatic lesions as the cause of pathological alterations in the brains of alcoholics.

Wernicke encephalopathy is characterized by fairly rapid onset of confusion, paralysis of extraocular muscles (particularly the lateral rectus), and ataxia. The syndrome may progress to coma and death if untreated but responds well to the administration of thiamine in the early stages. If not treated promptly, a permanent memory deficits known as Korsakoff psychosis the result. Korsakoff psychosis is characterized by an inability to either form new memories for retrieval ones, often accompanied by confabulation.

Thiamine deficiency has also been implicated in the development of atrophy of the superior vermis often seen in alcoholics, termed alcoholic cerebellar degeneration. In the peripheral nervous system, thiamine deficiency causes a peripheral axonal neuropathy.

Morphology: mamillary bodies of the hypothalamus, the dorsal medial areas of the thalamus, and the gray matter around the cerebral aqueduct, the last correlating with the eye movement abnormalities noted clinically. The earliest changes capillary endothelial proliferation associated with abnormal vascular permeability.

CVS:

    • Acute: negative inotropic, peripheral vasodilation.

    • Chronic: HTN, CM, increased HDL chol?

Pulmonary

    • Aspiration pneumonia is common

    • Increased susceptibility to gram-negative infections and tuberculosis

    • Recurrent bronchitis, asthma, chronic obstructive pulmonary disease

GI:

    • Acute: Esophageal and gastric inflammation, acute pancreatitis

    • Chronic: Mallory-Weiss tear, esophageal varices, portal HTN, chronic pancreatitis

Liver:

    • Acute: liver gluconeogenesis

    • Alcohol-induced hepatitis, cirrhosis

    • Fats accumulate in liver cells, leading to “fatty liver”

    • Risk of hepatocellular carcinoma 10 times higher than for general public.

Hematopoietic system:

    • Acute: macrocytosis

    • Chronic: thrombocytopenia, hypersplenism, decreased platelet aggregation

      • Splenic: alcohol use can lead to an enlarged spleen and sequestering of blood cells

Genitourinary system:

    • Acute: ED

    • Chronic: testicular atrophy, amenorrhea, ovarian atrophy, increased risk of abortion, fetal-alcohol synd.

Central nervous system and neurologic complications

    • “Blackouts”; fragmented sleep, with deep sleep deficiency

    • Wernicke’s and Korsakoff’s syndromes

    • Dementing illness: Marchiafava-Bignami disease, alcohol-induced persisting dementia, pellagrous encephalopathy (pellagra = dementia, diarrhea, dermatitis)

    • Cerebellar degeneration, peripheral neuropathy, decreased sensation of pain

Dermatologic: rosacea, spider angiomas, telangiectases, palmar erythema, seborrheic dermatitis

Endocrine

    • Intoxication can lead to hypoglycemia

    • Chronic alcohol use can lead to diabetes mellitus

    • In males: testicular atrophy, gynecomastia (from increase in estrogen production), decreased erectile capability, increased or decreased sex drive

    • In females: increased estrogen production, amenorrhea, decreased sex drive, infertility, spontaneous abortions, increase in male secondary sexual characteristics

Malnutrition

    • Poor absorption leading to multiple deficiencies: Vitamins A, C, D, and E, also niacin, pyridoxine, riboflavin, and thiamine

    • To prevent Wernicke’s encephalopathy, must administer thiamine before any intravenous administration of glucose-containing fluids

    • Hypomagnesemia and hypoalbuminemia common

Musculoskeletal

    • “Alcoholic myopathy” (painful, swollen muscles with increased creatinine phosphokinase level, also muscle weakness is common

    • Alterations of calcium metabolism can lead to increased risk of bone fractures, and especially osteonecrosis of femoral head

Oncologic: increased risk of cancers of head and neck (mouth, tongue, larynx), esophagus, stomach, liver, pancreas, breast.

Oral: periodontal disease, parotid gland enlargement.

Renal

    • Renal failure from hypertensive or diabetic effects on kidneys or from direct toxic effects of alcohol

    • Decreased uric acid excretion, which can lead to gout

Smoking:

    • ASK

    • ADVISE

    • ASSESS

    • ASSIST

    • ARRANGE

BAL: 43 mmol/L (0.2 g/dL) in nonhabituated patients is generally enough to cause impaired mental activity. >65 mmol/L (0.3 g/dL) is associated with stupor. Development of tolerance may allows the chronic alcoholic to remain awake at levels of >87 mmol/L (0.4 g/dL)

Alcohol intoxication: blood levels of 0.3 to 0.5% lead to respiratory depression, coma, death in non-dependent persons.

Testing:

Direct biomarker of alcohol testing: Preferred testing method. BAL. Urine Ethyl glucuronide, Ethyl sulfate in urine (last upto 5 days);

Phosphatidylethanol is a alcohol biomarker that is formed by the action of phospholipase D on ethanol. PEth160/181 and PEth 160/182. Half life 3-5 days. 2-4 weeks in window of detection. Serial monitoring of PEth may be useful to check for alcohol abstinence. Not affected by renal failure but advanced liver disease can have falsely elevated PEth concentrations. It should always be interpreted in the context of patient's clinical and behavioral history.

FFPET - Overview: Phosphatidylethanol (PEth), whole blood

<10 ng/mL: abstinent. Not detected

10-19 ng/mL: abstinent or light alcohol consumption (2 drinks/day for several days/week)

20-200 ng/mL: moderate alcohol consumption (4 drinks/day for several days/week)

>200 ng/mL: Heavy alcohol consumption or chronic alcohol consumption. (For men, consuming more than 4 drinks on any day or more than 15 drinks per week For women, consuming more than 3 drinks on any day or more than 8 drinks per week),

Indirect alcohol biomarkers look at the effect of alcohol on body chemistry: GGT, ALT, MCV

Approach: Order GGT, ALT, MCV, urine ethyl glucuronide, BAL, PEth.

Problem drinking:

Drinking in Moderation: According to the "Dietary Guidelines for Americans 2020-2025,” U.S. Department of Health and Human Services and U.S. Department of Agriculture, adults of legal drinking age can choose not to drink or to drink in moderation by limiting intake to 2 drinks or less in a day for men and 1 drink or less in a day for women, when alcohol is consumed. Drinking less is better for health than drinking more.

Binge Drinking:

  • NIAAA defines binge drinking as a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08 percent - or 0.08 grams of alcohol per deciliter - or higher. For a typical adult, this pattern corresponds to consuming 5 or more drinks (male), or 4 or more drinks (female), in about 2 hours.

  • The Substance Abuse and Mental Health Services Administration (SAMHSA), which conducts the annual National Survey on Drug Use and Health (NSDUH), defines binge drinking as 5 or more alcoholic drinks for males or 4 or more alcoholic drinks for females on the same occasion (i.e., at the same time or within a couple of hours of each other) on at least 1 day in the past month.

Heavy Alcohol Use:

    • NIAAA defines heavy drinking as follows: For men, consuming more than 4 drinks on any day or more than 15 drinks per week For women, consuming more than 3 drinks on any day or more than 8 drinks per week

    • SAMHSA defines heavy alcohol use as binge drinking on 5 or more days in the past month.

If you can smell alcohol on the person’s breath, the likely level is greater than 0.125%

CAGE:

C—Have you ever felt you should cut down on your drinking?

A—Have people annoyed you by criticizing your drinking?

G—Have you ever felt bad or guilty about your drinking?

E—Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangoverr?

Two of four answered positively: 70%-80% indicative of alcohol dependence

Four of four answered positively: 100% indicative of alcohol dependence

HALT Questions:

Do you usually drink to get High?

Do you drink Alone?

Do you ever find yourself Looking forward to drinking?

Have you noticed that you are becoming Tolerant to alcohol?

BUMP Questions:

Have you ever had Blackouts?

Have you ever used alcohol in an Unplanned way (drank more than intended or continued to drink after having enough)?

Do you ever drink for Medicinal reasons (to control anxiety, depression, or the shakes?

Do you find yourself Protecting your supply of alcohol (hoarding, buying extra)?

Epidemiology

    • 90% of U.S. population have had a drink

    • 60% to 70% are current drinker

    • Lifetime prevalence of alcohol abuse: women, 5% to 10%; men, 10% to 20%

    • Lifetime prevalence of alcohol dependence: women, 3% to 5%; men, 13%

    • Up to 20% of primary care patients have their alcoholism go unnoticed

    • Life expectancy can be decreased by up to 10 years from use of alcohol

    • Alcohol is involved in more than 25% of those who die because of motor vehicle accidents (in some studies, up to 55%), drowning, suicide, homicide, or those who have suffered from abuse, assaults, or rape.

    • High rates of alcohol-use problems in whites more than in African Americans

    • Higher prevalence in Native Americans

    • Lesser prevalence in Asian Americans and Jews

    • Age at onset of alcohol abuse in about 17 years and for dependence, about 22 years

Metabolism

    • 90% of alcohol is metabolized by oxidation in the liver, 10% is excreted unchanged in the urine, sweat, air (thus the Breathalyzer test is useful)

  • Alcohol dehydrogenase breaks down alcohol to acetaldehyde, then aldehyde dehydrogenase breaks down acetaldehyde to acetic acid.