Lipid abnormality in

alcoholism and fatty liver

Liver cirrhosis
Auen Joy Egar* l Marella Coleen Espiritu
Bea Clarissa Esteves l Martina Faderugao*
GROUP 9 1-C1
 Topic outline
FIRST PART
•Ethanol
•Metabolism of Ethanol
•Effects of alcohol metabolites in
the affected metabolic pathways
•Hypoglycemia
•Blood Alcohol Concentration
•Causes of inebriation after
alcohol ingestion
SECOND PART
● Wernicke-Korsakoff
Encephalopathy
● Pathophysiology of fatty liver
secondary to chronic
alcoholism
● Case correlation
● Management of fatty liver
● Role of disulfiram (Antabuse) in
chronic alcoholism
● Acetaldehyde Syndrome
•type of alcohol produced by E
fermentation of grains, fruits, or
other sources of sugar T
•clear, colorless liquid rapidly
absorbed from the gastrointestinal
H
tract and distributed throughout A
the body
•has a depressive effect on the N
central nervous system and
because of its psychoactive effects,
O
it is considered a drug
L
 ABSORPTION
•Ethyl alcohol taken in via
ingestion
•Absorbed in the stomach
(approx. 20%) and the small
intestine (approx. 80%)
•Result in increased blood
alcohol
concentrations(BAC)
> 90% - completely oxidized to acetic acid (liver)
10% - Excreted (sweat, urine, or given off in one’s breath)
Because glycerol, pyruvate and oxaloacetate cannot
be converted to glucose via gluconeogenesis, the
liver is unable to synthesize and release glucose in
circulation. All these factors are responsible for low
glucose levels in blood:

HYPOGLYCEMIA
 Blood Alcohol Concentration (BAC)

percent of alcohol (ethanol) in a person's blood stream. A BAC of

.10% means that an individual's blood supply contains one part
INEBRIATION
AFTER
ALCOHOL
INGESTION
Gamma-aminobutyric acid (GABA) Glutamate receptors
● Major excitatory
● Major inhibitory neurotransmitter in the
neurotransmitter in the brain.
brain ● Alcohol acts to inhibit
● Alcohol acts primarily at (N-methyl-D’aspartate)
the GABA receptor to of glutamate receptors
facilitate its action, thus thus diminishing the
in essence creating excitatory actions of
enhanced inhibition glutamate.
 ACETALDEHYDE
•more toxic than ethanol
•has been shown to increase the
risk of developing cirrhosis of the
liver, multiple forms of cancer,
and alcoholism
•accumulates in the blood and
makes the person feel sick- facial
flushing, headaches, nausea,
vomiting, and a rapid heart rate.
Wernicke- korsakoff encephalopathy
➢ Cause by Vitamin B1 or Thiamine
Deficiency
➢ Wernicke’s encephalopathy -
Acute, reversible stage
➢ Korsakoff Syndrome – Chronic ,
irreversible
 Thiamine
➢ Thiamine is stores in the liver
➢ Absorbed in the duodenum then
➢ Moves throughout the body
➢ It is involved in numerous cellular
Thiamine Phosphate
processes ➢ Assist in Glucose metabolism
➢ Helps metabolize lipids and carbohydrates
➢ Maintain normal amino acid &
neurotransmitter levels
➢ Helps with propagation of a neural
impulse
Wernicke’s encephalopathy
➢ Ophthalmoplegia – weakness or
paralysis of eye muscles
➢ Ataxia or unsteady gait
➢ Changes in mental state –
confusion, apathy , difficulty
concentrating
Korsakoff syndrome
➢ Targets the limbic system
➢ Severe memory impairment
● Anterograde amnesia
● Retrograde amnesia
➢ Confabulation
 Thiamine deficiency
➢ Major cause is alcohol abuse
➢ Other causes
● inadequate intake -> malnutrition &
anorexia
● Malabsorption -> Stomach cancer & IBD
Alcohol
1. Interferes with the conversion of
thiamine to active form
2. Prevents absorption -> decrease gene
expression for thiamine transporter 1
3. Chronic alcohol abuse -> cirrhosis ,
interferes with storage of thiamine
Fatty liver disease
1) Non- Alcoholic Liver Disease
➢ Revolves mainly around the family
history of an individual
➢ An individual whose family has a
history of obesity, diabetes, and high
cholesterol may develop NAFLD without
the aid of alcohol consumption
➢ Other causes: Starvation, Rapid weight loss,
Diabetes Mellitus (DM), Insulin resistance, High
Blood pressure
 Fatty liver disease
2) Alcoholic liver disease
➢ Large heavy, greasy tender
➢ Other symptoms not yet present
➢ Acetaldehyde can bind to macromolecules
enzymes , membranes and all sorts of other
compounds inside the cell.
➢ When they bind to some of this, they effectively
inhibit that molecule and when that happen,
they form acetaldehyde adducts
➢ then the immune system recognize these new
ROS – hydrogen peroxide , hydroxyl radical, superoxide
compounds as foreign and starts sending anion react with different components of that
neutrophils to clean it hepatocyte like proteins and even DNA and this process
can cause serious damage to the cells
➢ Destruction of an hepatocytes by
neutrophilic infiltration as the cells
become inflamed and damaged patients
have now developed alcoholic hepatitis
and we start to know to change on
Histology and notice these bundles of
proteins called Mallory bodies
➢ Neutrophilic leukocytosis
➢ As cells become damaged in die off
scar tissue starts to form around the
central veins deliver known as
perivenular fibrosis
➢ Enzymes leak out:
-↑ ALT -↑ ↑ AST
-↑ ALP -GGT
➢ Thrombocytopenia
➢ Hypoglycemia
 Management: fatty liver
Non-alcoholic
Alcoholic
➢ Goal: Reverse factors that contribute to
➢ Stopping alcohol insulin resistance
➢ Corticosteroid suppress ➢ Healthy diet
immune function ➢ Active lifestyle
➢ Medications that control blood glucose

The most effective treatment is a combination of individual and group therapy
Motivational Interviewing
➢ used to understand why
an individual wants to
stop using alcohol
➢ Specific barriers to
treatment
Management: alcoholism
Cognitive- Behavioral Therapy
➢ Can help an individual
learn about withdrawal
➢ Discuss thoughts feelings
& behaviors that lead to
alcohol use
➢ Create a plan to
navigate triggers
Peer support program
➢ Use group discussions to
hep individuals commit
to ending alcohol use
➢ Hold one another
accountable
 Management: alcoholism
medications:
Naltrexone Acamprosate Disulfiram
-Alpha mu-opiod receptor -Administered immediately -Inhibits the enzyme
antagonist following acute withdrawal Acetaldehyde dehydrogenase
-Blocks euphoric effects of -Reestablishes some GABA and -Leads to buildup of
alcohol glutamate pathways acetaldehyde
-Blocks feelings of -Causes hangover immediately
intoxication after consumption of alcohol
-Helps reduce heavy drinking
 DISULFIRAM Acetaldehyde syndrome
➢ More commonly known as the Asian Flush
Syndrome
➢ Overactive alcohol dehydrogenase; acetaldehyde
is broken down faster than what is deemed to be
normal causing what is called as a "buzz"
sensation
➢ ALDH2 is inactive which means that the
Ø Causes a buildup of such in our
acetaldehyde broken down in the liver cannot be
blood vessels rendering it to dilate synthesized as fast as it was degraded
and eventually turn our faces into a ➢ Acetaldehyde is more toxic than alcohol and a
reddish shade known carcinogenic agent
Signs of Asian flush syndrome ➢ trigger inflammation in the upper
Ø Facial blushing gastrointestinal tract, cause DNA damage, and
Ø Rapid heartbeat
increase one’s risk for gastrointestinal
Ø Nausea
Ø Headaches diseases, namely oesophageal and stomach
cancers as well as peptic ulcers
 CASE:
A 36-year-old woman was found to have serum concentrations of triglyceride 73.0
mmol/L (6388mg/dL) and cholesterol 13 mmol/L (503mg/dL). After some initial
prevarication she admitted to drinking three bottles of vodka and six bottles of wine
per week. When she continued alcohol, her triglyceride concentration decreased to 2
mmol/L (175mg/dL) and her cholesterol concentration decreased by 5.0 mmol/L
(193mg/dL). Three years later, the woman presented again with an enlarged liver and
return of the lipid abnormality. Lipid biopsy indicated alcoholic liver disease with
steatosis ( infiltration of the liver cells with fat)
Hepatocellular steatosis is caused by alcohol through several
mechanisms.
➢ First, oxidation of ethanol by alcohol dehydrogenase leads to
excess production of NADH and this inhibits their oxidation and
causes increased esterification of FAs to form TAGs
➢ Second, ethanol impairs the assembly and secretion of
lipoproteins. The net effect is to cause the accumulation of
intracellular lipids.
As liver injury aggravates, hyperlipidemia wanes and liver steatosis is
exaggerated. The changes in serum lipids may be a sensitive
indicator of the progression of liver damage in the alcoholic.
Oxidation of ethanol requires conversion of
nicotinamide adenine dinucleotide (NAD) to the
reduced form NADH. Because NAD is required for
the oxidation of fat, its depletion inhibits fatty
acid oxidation, thus causing accumulation of
fat within the hepatocytes (steatosis). Some of
the excess NADH may be reoxidized in the
conversion of pyruvate to lactate.
Accumulation of fat in the hepatocytes may
occur within days of alcohol ingestion; with
abstinence from alcohol, the normal redox state
is restored, the lipid is mobilized, and steatosis
resolves.