2. Alcohol is not only an intoxicant but also a
nutrient.
Excess intake of alcohol produces most serious
health concerns all over the world.
Alcohol consumption in excess is associated
especially with liver disorders (more than 20-
30g/day).
3. At low doses alcohol have some beneficial
effects-
1. Decrease rate of myocardial infarction
2. Decreases stroke and formation of
gallstones.
3. vascular disorders
4. alzehimers disease
4. Average drink of alcohol represents11-15g.
Energy yielding
A drink contains 300kcal or70-100kcal,it is devoid
of nutrients such as minerals, proteins and
vitamins.
5. Ethanol is readily absorbed from the intestine by
passive diffusion.
A small of percentage of ethanol enters
mucousmembraneof mouth ,oesophagus &
stomach in small amouts(0-5%)where it is
metabolised.The remaing enters the blood.Of this
(85-98%)is metabolised in liver.
6. The rate of absorption is increased by rapid
gastric emptying in absence of proteins, fats
and carbohydrate.
Alcohol can also interfere with absorption of
vitamins in small intestine and decrease their
storage in liver.
2%(at low blood alcohol con)&10%(high blood
alcohol) of ethanol is excreated directly through
lungs, sweat, or urine but greater part is
metabolised to acetaldehyde.
7. Ethanol is both lipid soluble and water soluble
Ethanol is dietary fuel that is metbolised to
acetate in the liver with generation of NADH.
The major route of Ethanol metabolism in liver
is through liver alcohol dehydrogenase it
oxidises ethanol to acetaldehyde with
reduction of NAD+
to NADH.
8. The acetaldehyde exits toxic effects in the liver,
blood and other tissues.
90% of acetaldehyde that is generated is
metabolised to acetate in the liver. The enzyme
involved is mitochondrial acetaldehyde
dehydrogenase.
It oxidises acetaldehyde to acetate with
generation of NADH.
Acetate has no toxic affects, and may be
activated to acetyl Coa in liver ( Where it can
enter TCA cycle or pathway of fatty acid
synthesis
9. Most of the acetate generated enters the
blood and it is activated to acetyl COA in
skeletal muscles and other tissues.
Acetate is generally considered nontoxic and is
normal constituent of the diet.
10.
11. 10 to 20% ingested Ethanol is oxidised through
MEOS.
Which also oxidises Ethanol to acetaldehyde.
The microsomal enzyme involved is Cyt P450
It uses NADPH and molecule O2 forming water
and acetaldehyde.
This route accounts only for moderate drinkers.
12.
13.
14. Oxidation Of Ethanol In Liver Alters NAD+
/NADPH
Ratio
Changes in fatty acid metabolism
The high NADH / NAD+
Generated inhibits fatty
acid oxidation and fatty acids accumulate in liver.
These fatty acids are re-esterified into triacyl
glycerol by fatty acyl COA transferase by combing
with glycerol 3phospate.
15. The triacyl glycerol are incorporated in to VLDL it
accumulate in liver & enter blood causing
Hyperlipidemia.
The sources of fatty acids can be dietary fat fatty
acids synthesized in liver, or fatty acids released
from adipose tissues stores.
Adipose tissue lipolysis increase after ethanol
consumption, because of release of epinephrine.
16. Alcohol-induced ketoacidosis.
Fatty acids that are oxidized are converted to
acetyl COA and subsequent to ketone bodies.
The high NADH – NAD+
ratio shifts oxaloacetate in
the TCA cycle to malate .
So availability of OAA is too low for citrate
synthesis.
Thus acetyl COA enters pathway for ketone bodies
synthesis instead of TCA cycle.
17. Lactic Acidosis Hyperuricemia, and Hypoglycemia
The high NADH level favours conversion of
pyruvate to lactate leading to lactic acidosis.
The elevation of blood lactate decrease excretion
of uric acid by kidney resulting in gout increased
degradation of purines may also lead to
Hyperuricemia
The Increased NADH / NAD+
can cause
hypoglycemia in fasting individual and dependent
on gluconeogenesis to maintain blood glucose.
18. Alanine & lactate are gluconeogenic Precursors
that enter gluconeogenesis as pyruvate so high
NADH/ NAD+
ratio convert pyruvate to lactate &
cannot enter gluconeogenesis.
A part from this consumption of ethanol with meal
lead to hyperglycemia because high NADH / NAD+
inhibit glycolysis at glyceraldehyde 3 P
dehydrogenase.
19. Acetaldehyde reacts with sulfhydryl groups of
various groups of enzymes reducing their activity it
also causes tachycardia, hypotension, headache &
nausea.
It also causes CNS depression by inhibiting
exitatory receptors (N methyl aspartate receptors).
20.
21. In chronic alcoholics there will be considerable
risk of nutritional defeciencies.
But the neurological hematological symptoms
are associated with thiamine, pyridoxine and
folate deficiencies.
Folate deficience leads to Megaloblastic
Erythropoiesis . Alcohol interfers with folate
absorption.
Pryidoxine deficiency leads to sideroblastic
anemia.
22. Some alcoholics also develop a peripheral
neuropatty due to impaired activation and
increased degradation of pyridoxine.
Acetaldehyde displaces PLP from its carrier
protein in plasma PLP degraded to inactive
compound & excreted.
Chronic ethanol consumption causes
redistribution of vit A stores in the body it
increases mobilization & catabolism of liver vit A
to inactive metabolites by hepatic cyt P450
system
23. Deficiency of thiamine leads to disorder
WERNICKE-KORSAKOFF syndrome
symptoms:
• mental disturbances
• ataxia
• un coordinated eye movements
• congestive heart failure.
24. Defect in 25 hydroxylation step in liver & increased
rate of metabolism of Vit D to inactive products by
activated cyt P450 leads to decreased bone density &
cause Osteoporosis.
A port from vitamins they will also have decreased
serum levels of Zn, Ca, Mg, due to poor dietary intake
& increased urinary loss.
Iron deficiency anemia is very rare unless thre is gastro
intestinal bleeding or chronic infections because
alcoholic beverages contain high iron levels & it
enhance iron absorption.
25. Currently, 67% of the population 18 years of age
or older drink alcohol & suffer from serious
health consequences.
More than 14 million Americans meet criteria for
alcohol abuse and dependence, corresponding
to a prevalence of 7.4%. This is highe r inmen
(11%) than in women (4%).
Alcohol abuse causes 2,00,000 deaths annually.
40% of deaths from cirrhosis are attributed to
alcohol – induced liver disease.
26. Acute Alcoholic Hepatitis
It is potentially reversible form of liver injury.
Alcoholic hepatitis can produce fever liver
tenderness and Jaundice.
The hepatocytes of liver are accumulated by
fat causing necrosis & cell injury.
In acute hepatitis,bilirubin& urobilinogen are
readily detectable in urine by DIP-STICK
technique.
27. The metabolites formed during Ethanol
oxidation are toxic to hepatocytes.
This toxicity is mediated by glutathione
depletion, mitochondrial injury, altered
metabolism of methionine & cytokines release
from kupffer cell.
There is hepatocellular necrosis & fibrosis
around central vein due to hypoxia.
28.
29. Chronic Alcoholic Hepatitis
Irreversible liver damage or alcoholic cirrhosis.
It is characterized by hard shrunken liver with
formation of micronodules, & Surrounded by
dense bound of Collagen.
The three dlistinctive form of liver diseases are
1. Hepatic steatosis
2. Alcoholic hepatitis
3. Alcoholic Cirrhosis
30. 1. Hepatic Steatosis ( Fatty Liver)
Even moderate intake of alcohol lipid
droplets accumulates in hepatocytes.
In chronic intake of alcohol there will be
clear macro vesicular globules and displaces
the nucleus to periphery.
The fatty liver in chronic alcoholism is large
soft, organ which is yellow and gresy.
Fibrous tissue develops around terminal
heapatic vein.
Clinical features:
1. Mild elevation of serum bilirubin,ALP.
31. Single or group of cells undergo swelling &
necrosis.
The swelling is due to accumulation of fat, water,
and Proteins.
In some cases there is cholestasis in surviving
hepatocytes & mild deposition of iron in
hepatocytes & kupffer cells.
32. Clinical features:
1. Hyper bilirubinemia
2. Elevated ALP
Mallory bodies;
Tangled skeins of cyto keratin intermediate
dilaments and other Proteins visible as
Eosinophilic cytoplasmic inclusions.
They are also seen in primarybiliary cirrhosis,
wilson disease, and hepato cellular tumours.
33. Neutrophilic reaction:
Neutrophils permeate the lobule and accmulate
around degenerating hepatocytes.
Lymphocytes and Macrophages also enter
portal tracts and spill in to parenchyma.
34. Fibrosis:
Activation of sinusoidal stellate cells and
portal tract fibroblasts, give rise to fibrosis.
It splits the parenchyma apart.
The steatotic hepatocytes are also present &
they are interspersed with inflammatory cells
& activated stellate cells.
The Microscopic structure of liver is mottled
red with bile stained areas. It often contains
visible nodules.
35. 3. Alcoholic Cirrhosis;
It is final & irreversible form of alcoholic liver
disease.
The cirrhotic liver is yellow tan fatty, and
enlarged.
The fibrous septae are delicate & Extend
through sinusoids from central to portal
regions.
The Entrapped parenchymal hepatocytes
form micronodules and give Hobnail
appearance.
36. Clinical features:
1. Impaired synthesis of albumin
2. Elevated serum amino transferase
3. Hyper bilirubinemia
4. Elevated serum ALP
5. hypoproteinemia
37.
38. Ethanol and Cancer:
Use of alcoholic beverages is associated
with an increased incidence of cancer of
oral cavity, pharynx, oesophagus,liver&
breast.
Ethanol is not a direct carcinogen the metabolite
acetaldehyde act as tumor promoter.
It inhibits detoxification of chemical carcinogens such
as nitrosamines which
are associated with tumors of upper GI tract.
39. Two other chemicals methanol & ethylalcohol
are ingested and metabolized by ADH.
methanol
formaldehyde,formicacid.
results:1 metabolic acidosis
2 dizziness
3 vomiting
4 blurred vision
5 respiratory depression.
