Alcohol Induced Liver Disease• When alcohol is used in “moderation, alcohol prolongs life;

reduces the risk of dementia and cardiovascular disorders; and, many would argue, contributes to the joy of living. Conversely, when consumed in excess, alcohol does nothing but diminish life in both quality and quantity (Lehne et al, 2015). Alcohol in and of itself is not the issue but the consumption of too much alcohol is the dangerous.

• 2 million people in US are affected

• 27,000 deaths each year

Alcohol Metabolism

Two major pathways (ADH and MEOS)

Alcohol absorption (stomach and intestine)

Etiology and Pathophysiology• Accumulation of fats in hepatocytes• Liver becomes yellow and enlarges• Not completely understood

Alcoholic Fatty Liver Disease

Manifestations• Usually without symptoms• Fatigue, weakness, discomfort to right upper abdomen• Liver enzymes may be elevated• May be reversible

Alcoholic HepatitisEtiology and Pathophysiology

• Excessive alcohol use• Inflammation and necrosis of liver cells

Manifestations• Jaundice, fever, pain, anorexia, tenderness, ascites, liver

failure and encephalopathy.

Alcoholic Cirrhosis

Etiology and Pathophysiology• Final result of repeated hepatocyte damage and

regeneration• Early cirrhotic liver vs. advanced cirrhosis• Portal hypertention, extrahepatic portosystemic

shunts and cholestasisManifestations

• Apetite loss, fatigue, weight gain, jaundice, edema, light colored stools, fever, confusion

Risk Factors

Prevention• Family Interventions for Youth (Parent Involvement)• College Binge Drinking (CBT and BMT)• Workplace drinking (EAP Services)• Military prevention (DUI Check and Community Based

Awareness)

Binge/Heavy drinking

Poor nutrition

Family history

Labs and Imaging • Lab values include complete blood cell count, liver enzymes,

renal function tests, electrolytes, and coagulation studies such as PT and international normalized ratio (INR)

• Alkaline phosphatase (ALP) • Albumin • Aspartate aminotransferase (AST) • Bilirubin • Alanine transaminase (ALT) • Gamma glutamyl transpeptidase (GGT)• Liver Biopsy• Chest X Ray, Ultrasound, MRI, CT Scan

Physical Examination

Laboratory Findings

Let’s Talk About Alcohol• The consumption of alcoholic beverage is an acceptable practice in most cultures.

However, alcohol is the most commonly abused drug in the United States. In most Western countries, it is the most utilized brain depressant and psychoactive drug of choice.

• When alcohol is used in “moderation, alcohol prolongs life; reduces the risk of dementia and cardiovascular disorders; and, many would argue, contributes to the joy of living. Conversely, when consumed in excess, alcohol does nothing but diminish life in both quality and quantity (Lehne et al, 2015). Alcohol in and of itself is not the issue but the consumption of too much alcohol is the issue.

• “The US National Institute on Alcohol Abuse and Alcoholism defines heavy drinking as consuming more than four drinks a day or 14 drinks a week for males, and consuming more than three drinks a day or seven drinks a week for females. It is estimated that one in four heavy drinkers have alcohol-related problems, such as dependence” (Wackernah, Minnick & Klapp, 2014).

Diagnosis of AlcoholismDSM-5

A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Alcohol is often taken in larger amounts or over a longer period than was intended.There is a persistent desire or unsuccessful efforts to cut down or control alcohol use

2. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.

3. Craving, or a strong desire or urge to use alcohol.4. Recurrent alcohol use resulting in a failure to fulfill major role obligations at work,

school, or home.5. Continued alcohol use despite having persistent or recurrent social or interpersonal

problems caused or exacerbated by the effects of alcohol.6. Important social, occupational, or recreational activities are given up or reduced

because of alcohol use.7. Recurrent alcohol use in situations in which it is physically hazardous.8. Alcohol use is continued despite knowledge of having a persistent or recurrent physical

or psychological problem that is likely to have been caused or exacerbated by alcohol.9. Tolerance and/or Withdrawal

What’s Happening in the Body (Pathophysiology)

• The chemical name for alcohol is ethanol. Alcohol can be broken down in three ways: alcohol dehydrogenase, cytrochrome P450, and catalase.

• The body processes and eliminates alcohol mainly by the pathway involving alcohol dehydrogenase (ADH). ADH is an enzyme that responsible for breaking apart the alcohol into other compounds (or metabolites), so that they are able be metabolized by the body. Some of these intermediate metabolites can have harmful effects on the body.

• ADH turns alcohol into acetaldehyde. Acetalyhyde is a toxic byproduct that is known as a tissue damage and cancer causing agent. Acetaldehyde is eventually oxidized to a another toxic compound called acetate by aldehyde dehydrogenase (ALDH).

• “This oxidation process involves an intermediate carrier of electrons, nicotinamide adenine dinucleotide (NAD+), which is reduced by two electrons to form NADH. As a result, alcohol oxidation generates a highly reduced cytosolic environment in liver cells (i.e., hepatocytes). In other words, these reactions leave the liver cells in a state that is particularly vulnerable to damage from the byproducts of ethanol metabolism, such as free radicals and acetaldehyde. Finally, acetate is oxidized to carbon dioxide and water mainly in tissues other than the liver.”

Continued

• Cytochrome P450 – metabolizes alcohol for heavy drinkers

• Catalase – metabolism in the brain

Alcohol Toxicity• Chronic alcohol abuse affects almost every organ system in the body:

• CNS – Wernicke syndrome and Korsakoff psychosis• Gastrointestinal - GERD, peptic ulcers, colitis• Cardiovascular - Hemorrhagic stroke, CAD, hypertension• Musculoskeletal - Progressive muscle weakness and wasting• Endocrine and reproductive - testicular atrophy and decreased sperm count

AND Alcohol becomes toxic when consuming more than one to two drinks per day. Alcohol toxicity can result in coma and possibly death. Alcohol Toxicity is caused

by:

• Metabolism of Alcohol: Liver, Tissues, Brain and GI• High Acetaldehyde Level: Toxic By Product

How Does Alcohol Affect the Brain?Alcoholism generally affects the brain in two ways:

1. Depresses the CNS2. Enhances the reward pathway • Alcohol interacts with three target proteins, “namely (1) receptors for gamma-aminobutyric

acid (GABA), (2) receptors for glutamate, and (3) the 5-HT3 subset of receptors for serotonin (5-hyddroxytrptamine, 5-HT). The depressant effects of alcohol result from binding with receptors for GABA (the principal inhibitory transmitter in the CNS) and receptors for glutamate (a major excitatory transmitter in the CNS” (Lehne, et al 438).

• The binding of alcohol with GABA causes depression of the CNS. The binding of alcohol with glutamate causes the blockage of “glutamate mediated” excitatory response and decreases CNS activity.

• The reward effects of alcohol are caused by alcohol binding with 5-HT3 receptors. When these receptors are activated, dopamine is released causing stimulation of the reward circuit pathway. When alcohol binds with the dopamine receptors, a serotonin mediated release of dopamine occurs, which intensifies the reward pathway (Lehne, 438).

Continued• “Whereas alcohol does not appear to selectively bind dopamine receptors,

its effects on dopamine release are likely mediated through interactions with other neurotransmitter systems, such as glutamate, GABA, corticotropin-releasing factor, and 5-HT, as well as through interactions with the endogenous opioid system (eg, endorphins, enkephalins)” (Wackernah, Minnick & Klapp, 2014).

• • “The depressant effects of alcohol are dose dependent. When dosage is low,

higher brain centers (cortical areas) are primarily affected. As dosage increases, more primitive brain areas (eg, medulla) become depressed) (Lehne, et al, 438).

• Cortical depression effects: thought, behavior, self restraint, inhibitions, motor function and sociability.

• CNS effects: decreased reflexes, consciousness, anesthesia

Withdrawal and Dependence

• Remember, GABA is excitatory and glutamate is inhibitory so “changing the balance between glutamate and GABA signaling establishes a state of hyperexcitability that is manifest upon cessation of drinking and that may contribute to the negative symptoms of alcohol withdrawal” (Wackernah, Minnick & Klapp, 2014).

• Repeated exposure to alcohol causes changes in several neurotransmitters, such as the down regulation of GABA (inhibitory) and the up-regulation of Glutamate (excitatory), leading to dependence.

Etiology and Risk Factors• The etiology and risk factors of alcoholism are quite complex and multifactorial.

Although it involves social, psychological and environmental factors, genetics is the most important determinant.

• 40 to 60 percent of cases involving alcohol dependence evidence genetic/familial link.

• The genetic differences in ADH and ALDH enzymes explains why some cultural groups/people have higher/lower incidences of alcohol related problems.

• “The type of ADH and ALDH an individual carries has been shown to influence how much he or she drinks, which in turn influences his or her risk for developing alcoholism (11). For example, high levels of acetaldehyde make drinking unpleasant, resulting in facial flushing, nausea, and a rapid heart beat. This “flushing” response can occur even when only moderate amounts of alcohol are consumed. Consequently, people who carry gene varieties for fast ADH or slow ALDH, which delay the processing of acetaldehyde in the body, may tend to drink less and are thus somewhat “protected” from alcoholism” (NIH).

Prevention of Alcoholism• Family Interventions for Youth: Parents who are actively involved in their

children’s lives are less likely to drink. The U.S. Preventative Services Task Force recommends screening and CBT for youth and children.

• College Binge Drinking: Cognitive behavioral or brief motivational interventions• Workplace drinking: Support programs through EAP services• Military prevention: “Military personnel ages 18 to 35 have rates of heavy

drinking about 60 percent higher than civilians in those age-groups.34 Recognizing these problems has led to efforts to reduce the availability of alcohol in communities with service bases. Such approaches include asking for identification checks, making sure alcohol retailers near a base do not serve minors, increasing the number and frequency of driving under the influence (DUI) checks, fostering community-based awareness, and supporting media campaigns to reduce drinking and promote alternative activities that do not include alcohol” (NIH).

Clinical Manifestations of Alcohol Abuse and Dependence

Abuse• Frequently neglecting responsibilities• Using alcohol in dangerous places/situations• Legal problems related to drinking• Marriage/relationship problems • Drinking to unload/de-stress

Dependence• Alcoholism encompasses most of the manifestations of alcohol abuse but

dependence is instrumental. Alcoholism involves: tolerance, withdrawal, loss of control, unsuccessful attempts to stop, neglecting family/activities, continued use despite negative consequences.

• Tremulousness, anxiety, increased heart rate and blood pressure, sweating, nausea, hyperreflexia, insomnia, increased hyperactivity.

History and Screening Tools• Evidence suggests that screening for risk levels of alcohol consumption

and brief intervention can be helpful and cost-effective11–14 and thus is recommended in both general practice and hospital settings. Screening at follow-up visits may also remind physicians to initiate or reinforce brief interventions because this leads to a reduction in the number of patients consuming harmful amounts of alcohol” (Fagan et al, 2013).

• CAGE questionnaire• How many times in the past year have you had 4 or more drinks a day

(women) or 5 or more drinks a day (men)? • In the case of acute alcohol toxicity that may occur binge drinking, the

nurse would assess for “injuries, trauma, diseases, and hypoglycemia” (Lewis et al, 159). Also, the nurse would make sure ABCs are satisfied until detoxification is completed.

History and Screening Tool• Many patients will be clinically evident with signs and symptoms

of liver disease, whereas others will be asymptomatic at the time of diagnosis. Although not a prerequisite for the development of ALD, screening for alcohol abuse and/or dependency may detect an at-risk population of patients. The Alcohol Use Disorders Identification Test (AUDIT) can identify risky alcohol use (score ≥8 for men up to age 60 or ≥4 for women, adolescents, or men over age 60) and alcohol dependence (score ≥20).1 Prior to complications of ALD, early ALD is clinically diagnosed in patients with a history of significant alcohol use combined with objective findings. Physical examination findings can be nonspecific, but most commonly hepatomegaly is present.

Labs and Imaging• Because no single lab marker definitively establishes alcohol as the etiology of liver disease, ALD is diagnosed on

the basis of a patient history of excessive alcohol consumption and evidence of liver disease supported by diagnostic study results. Key lab values include complete blood cell count, liver enzymes, renal function tests, electrolytes, and coagulation studies such as PT and international normalized ratio (INR).

• Liver Biopsy – sample of tissue from the liver for examiniation• Due to altered synthesis of coagulation proteins, a prolonged PT has been shown to correlate with the degree of

liver fibrosis.27A liver panel, including serum ALT, AST, GGT, INR, and albumin levels, can be used to evaluate changes in ALD. AST and ALT are liver enzymes released into the bloodstream from damaged hepatocytes. ALD is suspected when the ratio of AST to ALT is greater than 2:1, as was the case with Ms. J.1,3,28Diagnostic imaging is essential for diagnosing ALD and its complications.

• A chest X-ray can reveal pleural effusions and an abdominal ultrasound can help clinicians assess the patency of hepatic blood vessels and monitor for ascites. A contrast-enhanced computed tomography (CT) scan can show portal vein flow, thrombosis, and parenchymal distortion caused by cirrhosis.27 Ultrasonography, CT, and magnetic resonance imaging can all be used to assess steatosis.3,28The degree of liver disease can be evaluated with several assessment tools.

• The Child-Turcotte-Pugh (CTP) calculator (also called the Child-Pugh score) uses ascites, encephalopathy, total serum bilirubin, serum albumin, and PT or INR to grade the severity of cirrhosis.29,30 Considered more accurate than the CTP calculator, the Model for End-Stage Liver Disease (MELD) quantifies liver dysfunction based on serum bilirubin, INR, and serum creatinine levels.

Diagnostic Test and Labs• Alkaline phosphatase (ALP) is an enzyme found in liver biliary ducts and in bone. If ALP levels

are high, it could indicate a large bile duct obstruction.* Albumin is one of the proteins made by the liver. This chemical tends to be low in people who have some type of chronic liver condition. It can also be a sign of poor nutrition.* Aspartate aminotransferase (AST) is an enzyme that can be found in cells inside the liver. If the liver is damaged, there will be high levels of AST in the blood results. A large amount of this enzyme in the blood stream isn’t always indicative of liver problems, though. It is also produced when the heart or skeletal muscle is damaged.* Bilirubin is what gives a yellow color to bile. If it gets too high in the blood stream, it can be very noticeable. Jaundice causes people to develop a yellowish or orangish color on their skin and the whites of their eyes. A high level of bilirubin could indicate a blockage in the bile duct, or a disease process that is causing the red blood cells to be broken down too quickly.* Alanine transaminase (ALT) is an enzyme that is required to break down protein by speeding up chemical reactions. If the liver is inflamed, there will usually be high levels of ALT in the blood stream. This inflammation could be due to an injury or disease process.* Gamma glutamyl transpeptidase (GGT) is another enzyme associated with the liver. High levels of this can indicate cholestatic damage or alcohol toxicity.