For Medical students

1. ALCOHOL
METABOLISM
A little progress in each day
adds up to big results.
“Stop waiting for tomorrow
Start now”
Have a nice day to all
By
Dr. Santhosh Kumar N
Associate Professor of Biochemistry
PRIMS, Warangal

2. • About 5% of all deaths in India are due to liver diseases cause by alcohol
• Absorption of alcohol starts from stomach & complete absorbed by intestine
• Only 1% of the alcohol is excreted through the lungs or urine
• Major fraction of the alcohol is oxidized in the liver
• Alcohol metabolism is slower & even small quantity of alcohol may produce symptoms of
intoxication

3. Alcohol’s effects from parson to person, depending on variety of factors
• How much you drink
• How often you drink
• Your age
• Your health status
• Your family history

4. • Increased blood alcohol concentration (BAC)- NIAAA (National Institute on Alcohol
Abuse & Alcoholism)
Short term effect
• Feelings of relaxation or drowsiness
• A sense of giddiness
• Slurred speech
• Dehydration –related effect : Nausea & vomiting, Headache
• Change in mood (affect your judgment & behavior)
• Contribute to more far –reaching effects- accidents & injuries)
• Reduced inhibitions
• Impulsive behavior
• Changes in hearing, vision, & perception
• Loss of coordination
• Trouble focusing
• Loss of consciousness

5. • Long term effects
• Persistent changes in mood- anxiety & irritability
• Insomnia
• Weakened immune system (develop pneumonia & tuberculosis)
• Changes in sexual functions
• Changes in appetite & weight
• Muscle weakness, cramping, eventually atrophy
• Problems with memory & concentration- Difficulty focusing on tasks
• Increased tension &disturb family relationships
• Death
Dr. Santhosh Kumar/Associate Professor /PRIMS

6. Ethanol Alters Energy Metabolism in Liver
• The activity of alcohol dehydrogenase is more than aldehyde dehydrogenase.
• EtOH consumption leads to accumulation of NADH
Cytoplasmic Mitochandrial
microsome
Acetyl coA

7. Biochemical Alterations
in
Alcoholism

8. High levels of acetaldehyde in the blood
Facial flushing (red & hot or strong emotion),
palpitations, nausea, & general hangover
symptoms occurs.
alcohol flush reaction or oriental flushing
syndrome

9. ↑↑sed conc. of NADH/NAD+ ratio
↑sed lactate levels
↓
Inhibits the transtubular
transport of uric acid
↓
concomitant ↓se in urinary uric
acid excretion
↓
Hyperuricemia →Gout
lactic acidosis
↓
Muscle weakness,
abnormal heartbeat,
difficulty in breathing,
nausea, vomiting,
kussmaul breathing &
generalized weakness
Pyruvate → Lactate
↓sed pyruvate levels
↓
inadequate formation of
oxaloacetate
↓
depression of
gluconeogenesis
↓
Hypoglycemia

10. Oxaloacetate
Malate
Inadequate availability of oxaloacetate
suppression of TCA cycle.
So Acetyl CoA is accumulated
↓
Stimulates Ketone bodies -Acidosis &
FA & TAG & synthesis in liver
&
Inhibits fatty acid oxidation
↓
Fat is accumulated in liver
↓
Fatty liver / steatosis
↓sed pyruvate & high NADH
level causes
followed by replacement by fibrous tissue - Cirrhosis
When liver functions are reduced - hepatic coma

11. Alcoholism & liver (FATTY LIVER)
 Fatty liver disease (steatosis) is a condition caused by having too much fat
deposited in the liver.
 Major risk factors include obesity and type 2 diabetes associated with
excessive alcohol consumption.
Symptoms occur, fatigue, weight loss and abdominal pain.
Dr. Santhosh Kumar/Associate Professor /PRIMS

13. Excessive alcohol consumption
Blocks conversion of ammonia into urea
Blood ammonia conc rises
Producing neurological effects
COMA & DEATH

14. Alcohol
Targeted amino groups, sulfhydryl
groups, nucleotides & phospholipids
↓
↑ses Hydroxyethyl radicals (ROS)
mitochondrial damage and
apoptosis
causes CNS depression
(by inhibiting excitatory receptors
(N-methyl aspartate receptors) &
by inhibitory neurotransmitter
(GABA) receptors)
leads

15. Alcoholism and Nervous System
In chronic alcoholics
• The brain ventricles are enlarged, neurons are lost, neuro-degenerative changes set
in the memory is affected.
• Combined thiamine deficiency leads to Wernick's disease.
• Aldehyde inhibits PLP; hence neuritis (inflammation of nerve or peripheral nervous
system)

16. Laboratory Findings in Chronic Alcoholism
• Increase in serum levels of GGT & ALT
• Alcohol abuse – GGT, AST & AST/ALT ratio (>2.0) &
» Decrease in aldehyde dehydrogenase activity (in liver cells and
RBCs) is the best markers.
• Desialylated transferrin level in blood is a highly sensitive marker for
chronic alcohol abuse.
• Fatty acid ethyl esters synthase activity is ↑ed in alcoholics

17. Metabolism of Methyl alcohol or Methanol
• Cheap & potent adulteration used in manufacture of illicit liquors.
• Rapidly absorbed from all routes of exposure (dermal, inhalation & oral)
• Easily crosses all membranes
• Uniformly distributed to organs & tissues
• Lethal dose is less than 30ml
Dr. Santhosh Kumar/Associate Professor /PRIMS

18. THF
Formyl-tetra hydrofolate
CO2+ H2O

19. toxic to optic nerve causing
visual disturbances, ocular
changes consisting of retinal
edema, blurring of the disc
margins & optic atrophy &
CNS depression
Inhibits mitochondrial
cytochrome -c oxidase,
causing cellular hypoxia
(histotoxic hypoxia ) &
metabolic acidosis
Methanol Toxicity
Vomiting &Abdominal pain,
Death may occur

20. Investigations:
 Measuring plasma methanol conc.
 ABG analysis and
 Complete ophthalmic evaluation
Treatment for methyl alcohol toxicity:
– Preferred antidote is fomepizole & ethanol
– Sodium bicarbonate for metabolic acidosis, &
– Haemodialysis to remove methanol & formate from the blood.

21. • Ethanol being a structural analogue of methanol
• Acts as a competitively inhibitor of ADH, thus blocking the metabolism of methanol, thereby
prevents formaldehyde toxicity

22. Thank You
for success