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
Alcohol absorption
(stomach and
intestine)

Two major pathways

(ADH and MEOS)

Alcoholic Fatty Liver Disease

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

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

Alcoholic Hepatitis
Etiology 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 cholestasis
Manifestations
Apetite loss, fatigue, weight gain, jaundice,
edema, light colored stools, fever, confusion

Risk Factors
Family history
Poor nutrition
Binge/Heavy drinking

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)

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

Lets 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 Alcoholism
DSM-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

Whats 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 CNS
2. Enhances the reward pathway

. Alcohol interacts with three target proteins, namely (1) receptors for gammaaminobutyric 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
childrens 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 agegroups.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 costeffective1114 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 isnt 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.