CHRONIC

ALCOHOLISM
AND FATTY
LIVER
Group 1 C
CLEOFE, DATINGUINOO, DE RAMOS, DEL ROSARIO
 Learning Objectives
● Discuss the metabolism of alcohol (ethanol)
● Discuss the blood alcohol level and the associated
effects on the body.
● Discuss the effects of alcohol metabolites on the
different biochemical pathways
● Explain the pathophysiology of fatty liver due to
alcohol ingestion.
● Discuss the possible causes of fatty liver.
● Explain the mechanism of action of Disulfiram
(Antabuse) in the management of chronic
alcoholism
 01
What causes
inebriation after
alcohol ingestion?
 INEBRIATION
Syn. Drunkenness, Intoxication
A physiologic state (that may also include
psychological alterations of consciousness)
induced by the ingestion of ethanol (alcohol)
Affects the central nervous system (CNS)
● GABA receptor
● NMDA receptor
● Dopamine
The degree to which the CNS has impaired
function is directly proportional to the blood
alcohol concentration.
 Neurotransmitter gamma-aminobutyric acid
(GABA-A) receptors

Produce a depressant effect

Anxiolytic, anticonvulsant, hypnotic and sedative actions
Alcohol binds to GABA receptors, potentiating its effect.
Allows more Cl- ions into the post-synaptic neuron
Glutamate receptor Dopamine

Alcohol inhibits NMDA May inhibit dopamine lysis

receptor
Dopamine affects:
stimulates the cortex,
hippocampus and nucleus behavior and cognition

accumbens, which are voluntary movement

responsible for thinking and motivation
pleasure seeking.
 02
Metabolism
of alcohol
 Oxidation of
ethanol by alcohol dehydrogenase
 03
What metabolites accumulate in
excessive alcohol ingestion?
 METABOLITES ACCUMULATED IN EXCESSIVE
ALCOHOL INGESTION

Acetate and
Acetaldehyde acetyl coA

NADH Malate
 METABOLITES ACCUMULATED IN EXCESSIVE
ALCOHOL INGESTION

● acetaldehyde- major toxic metabolite

-Some researchers believe that acetaldehyde may be
responsible for some of the behavioral and physiological effects
previously attributed to alcohol

● acetate - It is hypothesized that upon chronic alcohol intake

the brain starts using acetate rather than glucose as a
source of energy.
● NADH - The increase in NADH due to alcohol metabolism
prevents pyruvate conversion to glucose by lowering the
concentration of pyruvate.
● MALATE- malate cannot be coverted to oxaloacetate in
alcoholism.
AFFECTED PATHWAYS AND THE METABOLITES
ACCUMULATED

● Gluconeogenesis
● Fatty acid oxidation pathway
● TCA cycle
● Glycolysis (Lactic acidosis)
 AFFECTED PATHWAYS AND THE METABOLITES
ACCUMULATED
● Gluconeogenesis -The increase in NADH due to alcohol
metabolism prevents pyruvate conversion to glucose by lowering
the concentration of pyruvate, which in turn decreases the pyruvate
carboxylase reaction, one of the rate limiting steps of
gluconeogenesis.
● Fatty acid oxidation pathway -Chronic alcohol consumption,
decreases fatty acid oxidation by interfering with citric acid cycle
activity.
● TCA cycle - inhibit the citric acid cycle function and reduce ATP
levels.
● Glycolysis (Lactic acidosis) - Acetaldehyde's stimulatory effect
appears to be due to its ability to accelerate glycolysis via its effect
on the cellular redox balance.
DRINK
MODERATELY!
INUMAN
LANG,
WALANG
IYAKAN
 04
Wernicke-Korsakoff
encephalopathy
What is the pathophysiology of this condition in
relation to chronic alcohol intake?
Wernicke encephalopathy is an acute
neurological condition characterized by
a clinical triad of ophthalmoplegia,
ataxia, and confusion. This disease is
caused by thiamine deficiency, which
primarily affects the peripheral and central
nervous systems.
Wernicke syndrome is considered the acute
phase of WKS and if left untreated,
transitions to the chronic irreversible
Korsakoff syndrome.
What is the pathophysiology of this condition in relation to
chronic alcohol intake?
 05
FATTY LIVER
CAUSES OF FATTY LIVER

● GENETICS

● DIET

● INSULIN RESISTANCE
PATHOPHYSIOLOGY OF FATTY LIVER
DUE TO CHRONIC ALCOHOLISM
Management
1. Abstinence
2. Therapy
3. Medication
4. Lifestyle Changes
5. Transplant