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Alcoholism Fatty Liver Liver Cirrhosisg6b1
Alcoholism Fatty Liver Liver Cirrhosisg6b1
Alcoholism Fatty Liver Liver Cirrhosisg6b1
BIOCHEMISTRY CONFERENCE
SECOND SEMESTER- SCHOOL YEAR 2015-2016
MEDICINE 1B-1 GROUP 6
REPORTERS:
Ching, Arkanel
Co, Marc Christian
Collado, Jodeeym
MEMBERS:
Clarito, Hermily Claire
Chuan, Lizette
Cipriano, Alvin
Objectives
At the end of the conference, the students should
be able to:
• Define Alcoholism.
• Discuss how the human body metabolized
alcohol.
• Enumerate the metabolites accumulated in
alcohol ingestion and the metabolic pathways
that are affected.
• Discuss causes of inebriation after alcohol
ingestion.
• Discuss the development of hypoglycemia.
• Discuss Wernicke-korsakoff encephalopathy.
Objectives
• Discuss the causes of fatty liver in chronic
alcoholism.
• Discuss the mechanisms involved in the production
of liver cirrhosis in chronic alcoholism.
• Enumerate the metabolic pathways are affected as
a result of liver damage in liver cirrhosis.
• Discuss the mechanisms involved in the
development of the clinical manifestations seen in
liver cirrhosis.
• Discuss the mechanisms behind the development
of hepatic coma in liver cirrhosis.
• Discuss the management of hepatic
encephalopathy.
Outline
I. Alcoholism VIII. Clinical Manifestation In Liver
i. Alcohol Cirrhosis
ii. Ethanol IX. Development of Hepatic Coma in
II. Alcohol Metabolism Liver Cirrhosis
i. Alcohol Dehydrogenase X. Management of Hepatic
Encephalopathy
ii. Catalase
iii. CYP2E1
iv. Acetaldehyde Dehydrogenase
III. Metabolites And Affected Pathway
IV. Alcohol Inebriation
V. Wernicke-korsakoff Encephalopathy
VI. Mechanisms Involve In Liver Cirrhosis
VII. Pathway Affected In Liver Cirrhosis
i. ADH Pathway
ii. Microsomal Ethanol Oxidizing
System
ALCOHOLISM
• (WHO) It refers to chronic continual drinking
or periodic consumption of alcohol which is
characterized by impaired control over
drinking, frequent episodes of intoxication
and pre-occupation with alcohol and the use
of alcohol despite adverse consequences.
ALCOHOLS
• A large group of organic compounds.
• Derived from hydrocarbons containing one or
more (-OH) group.
ETHANOL
• Also known as Ethyl alcohol.
• Molecular formula (C2H5OH).
• Main ingredient in alcoholic beverages.
– Beer
– Wines
– Spirits
ALCOHOL METABOLISM
(↑) Increase
NADH/NAD+
(↑) Increase
Lactate
(↓) Decrease
Glucose
HYPOGLYCEMIA
LIPOGENESIS
• The synthesis of Fatty Acid and their esterification
to glycerol to form Triacylglycerol.
• Impaired Fatty Acid oxidation and increased
lipogenesis is due to changes in NADH/NAD+
redox potential.
• Oxidation of ethanol by Alcohol Dehydrogenase
leads to excess production of NADH which
competes with reducing equivalents from other
substrate.
LIPOGENESIS
• It inhibits their oxidation and cause increased
esterification of Fatty Acid to form
Triacyglycerol resulting to Fatty Liver.
• Increased NADH/NAD+ ratios causes increased
Lactate/ Pyruvate resulting to
HYPERLACTICACEDEMIA.
ELECTRON TRANSPORT CHAIN
• Cytochrome P450- dependent Microsomal
Ethanol Oxidizing System (MEOS)
• This system increases activity in chronic
alcoholism.
• Many cytochrome P450 enzymes are induced
by substrate which give rise to tolerance.
• Ethanol can inhibit cytochrome P450 system.
• MEOS is utilized when ethanol is high.
INEBRIATION/ ACUTE INTOXICATION
• (WHO) A condition that follows the
administration of a psychoactive substances
and results in disturbances in the level of
consciousness, cognition, perception,
judgment, affect on behavior, or other
psychophysiological function.
Ref: http://awareawakealive.org/educate/blood-alcohol-content
INEBRIATION/ ACUTE INTOXICATION
(↑) Increase Alcohol
Intake
ALCOHOL
absorbed in stomach, most in small intestine
cannot be stored
small amount degraded in transit through the
gastric mucosa, but most is catabolized in the liver,
primarily by alcohol dehydrogenase (ADH) but also
by cytochrome P-450 2E1 (CYP2E1) and the
microsomal enzyme oxidation system (MEOS)
Alcohol produces toxin by product known to be acetaldehyde
that causes damage to the structure and function of
mitochondria in human body cells particularly the liver. Once
the liver become inflamed due to acetaldehyde the kupfer cell
will be activated because kupfer cell is responsible for
inflammation, then the kupfer cell will send signal to cytokines
that will activate the stellate cell. The stellate cell will now
produce fibrin scar that will replace the fluid space.
Pathways Affected by Liver Cirrhosis
• ADH pathway
• Microsomal Ethanol Oxidizing System
ADH pathway
converts alcohol to the toxic substance
acetaldehyde in a reaction that releases
hydrogen atoms
– Zinc
• Improve hyperammonemia by increasing the activity
of ornithine transcarbamylase, an enzyme in the
urea cycle. Increase in ureagenesis results in loss of
ammonia ions.
– L-carnithine
– Sodium benzoate, sodium phenylbutyrate
Most current therapies are designed to treat hyperammonemia that is a hallmark
of most cases in hepatic encephalopathy.
SUMMARY
• Alcoholism is chronic continual drinking of alcohol which is
characterized by impaired control over drinking.
• Alcohols are derived from hydrocarbons containing one or more (-
OH) group.
• Ethanol is main ingredient of alcoholic drinks.
• Alcohol metabolism takes place in Cytosol (Alcohol DH),
Microsomes (CYP2E1), Peroxisomes (Catalase), and Acetaldehyde
DH (Mitochondria).
• Wermicke’s encephalopathy is a paralysis of the muscles within or
surrounding the eyes.Inabilty to coordinate voluntary muscular
movements.
• Fatty liver is a accumulation of triaglycerides in hepatocytes.
• Liver cirrhosis is a replacement of liver tissue by fibrosis, scar tissue
and regenerative nodules.
References
Rodwell, V.M., Bender, D.A., Botham, K.M., Kennely, P.J., Weil., P.A. Haper’s Illustrated
Biochemistry 30th Ed. (2015). Mc graw Hill.
Zakari S. Overvie: How Is Alcohol Metabolize by the Body?. In Alcohol Research and
Health Vol. 29 No. 4. (2006) pp. 245-255.
Kumar, V. Abbas, A., Asster, J. Robbins and Cotran’s Pathologic Basis of Disease 9th
Ed.(2015) Elsevier.
www.who.int
www.emedicinehealth.com
http://awareawakealive.org/educate/blood-alcohol-content