Chronic Alcohol

Consumption
AND IT'S CLINICAL CONSEQUENCES

Pathology Assignment
Ammar Malik
Roll no. 057
Excessive alcohol consumption is a major cause of liver disease in
most western countries

→ There are three forms of alcohol induced liver injury

1) Steatosis or fatty change

2) Alcoholic steato-hepatitis

3) Fibrosis
 E T H A N O L M E TA B O L I S M
Ethanol is metabolised in two steps.

1) First step

•Ethanol is catabolised to acetaldehyde in liver by three pathways

•In Smooth endoplasmic reticulum via microsomal p450 oxidases where only part of
ethanol is metabolised

•In Peroxisomes minor pathway via catalase such as H₂O ₂.

•In cytosol by major rate limiting pathway of Alcohol dehydrogenase (Major pathway) into
Acetaldehyde

2) Second step

•ALDH acts as coenzyme and converts acetaldehyde to acetate

•Most of the acetate is finally oxidised to carbon dioxide and water or converted to fatty
ands NAD is reduced to NADH resulting in increased NADH:NAD ratio
R I S K FA C T O R S F O R
ALCOHOLIC LIVER DISEASE

1) Drinking patterns :
Chronic and excessive consumption of alcohol
invariably leads to fatty liver in >90% of chronic
alcoholics. Daily imbibing of 60-80g of ethanol for at
least 10 years is likely to result in alcoholic cirrhosis.

2) Gender :
Women have increased susceptibility to develop
alcoholic liver disease with much less alcohol intake
(20-40 g/day). This could be because estrogen inleases
gut permalulity to endotoxins
R I S K FA C T O R S F O R A L C O H O L I C L I V E R D I S E A S E

3) Malnutrition :
Absolute or relative malnutrition of proteins and vitamins along with chronic alcohol ingestion
leads to alcoholic liver disease. Calories derived from alcohol may displace other nutrients
leading to malnutrition and deficiency of vitamins in alcoholics.

4) Ethnic & genetic factors :

ALDH 2 a variant of aldehyde dehydrogenase found in 50% of Asians has a very low enzyme
activity. They are unable to oxidize acetaldehyde properly and are intolerant of alcohol

5) Comorbid conditions :
Concurrent infection with HBV & HCV is an important risk factor for progression of alcoholic
liver disease
 PAT H O G E N E S I S
1) Direct Hepatotoxicity by Ethanol :
Ethanol is directly toxic to mitochondria, microtubules and membrane
of hepatocytes

2) Hepatotoxicity by ethanol metabolites : Acetaldehyde is

responsible for hepatotoxic effects by -

•Production of protein aldehyde adducts which are extremely toxic and

can cause Cytoskeletal and membrane damage and bring about
hepatocellular necrosis.

•Formation of Malon-di-aldehyde-acetaldehyde (MAA) adducts

which produce autoantibodies and initiate autoimmune response

3) Oxidative stress :
Oxidation of ethanol by cytochrome P450 leads to generation of free
Ingoude
Company
radicals which causes oxidative damage.
 PAT H O G E N E S I S

4) Immunological mechanism :
Cell mediated immunity is impaired in alcoholic liver disease.
Ethanol causes direct immunologic attack on hepatocytes

5) Inflammation :
Chronic ethanol ingestion is injurious to intestinal cells which
releases inflammatory mediators which produces inflammatory
reaction

6) Fibrogenesis :
Main event facilitating hepatic fibrogenesis is activation of stellate
cells by various stimuli
PAT H O G E N E S I S

7) Increased redox ratio :

Marked increase in the NADH:NAD redox ratio in hepatocytes results in increased redox
ratio of lactate pyruvate leading to lactic acidosis

8) Retentions of liver cell water & proteins : Alcohol is inhibitory to secretion of newly
synthesized proteins by liver leading to their retention causing swelling of hepatocytes

9) Hypoxia :
Chronic ingestion of alcohol results in increased oxygen demend by liver resulting in
hypoxic state which causes hepatocellular damage

10) Increased liver fat :

In chronic alcoholism, there is rise in amount of fat available to the liver
MACROSCOPIC AND
M I C R O S C O P I C F E AT U R E S

1) Alcoholic Steatosis (Fatty liver):

Grossly the liver is enlarged, yellow
greasy and firm with a smooth and
glistening capsule
Microscopically, the features consist
of initial microvesicular droplets of
fat followed by macrovesicular large
droplets of fat dispersing the nucleus
to periphery
 M O R P H O L O G I C A N D M I C R O S C O P I C F E AT U R E S
2) Alcoholic Hepatitis
Histologic features of Alcoholic Hepatitis
1) Hepatocellular necrosis : 2) Mallory Bodies :
Small clusters of hepatocytes especially Eosinophilic, intracytoplasmic
in the Centrilobular area undergo inclusions seen in perinuclear location
ballooning degeneration & necrosis within swollen & ballooned hepatocytes.
Mallory bodies are highly suggestive of
but not specific for alcoholic hapatitis
3) Inflammatory response :
The areas of hepatocellular necrosis and
regions of mallory bodies are associated
with an inflammatory infiltrate chiefly
consisting of polymorphs and some
scattered mononuclear cells
4) Fibrosis :
Most cases of alcoholic hepatitis are
accompanied by Pericellular and
perivenular fibrosis producing web like
appearance.
MORPHOLOGIC AND
M I C R O S C O P I C F E AT U R E S

3) Alcoholic cirrhosis

Grossly alcoholic cirrhosis classically

begins as micronodular cirrhosis
(nodules <3mm diameter) Eventually
liver shrinks becomes non fatty having
macronodular cirrhosis (nodules > 3mm
diameter) resembling post-necrotic
cirrhosis.
MORPHOLOGIC AND
M I C R O S C O P I C F E AT U R E S

1) Nodular Pattern :
Normal lobular architecture is effaced in which
central veins are hard to find and is replaced
with nodule formation

2) Fibrous septa :

As the fibrous scarring increases with time

the fibrous septa become dense and more
confluent
MORPHOLOGIC AND
M I C R O S C O P I C F E AT U R E S

3) Hepatic Parenchyma :
The hepatocytes of surviving Parenchyma undergo slow
proliferation forming regenerative nodules having disorganized
masses of hepatocytes. The hepatic parenchyma shows
extensive fatty change early but as fibrous septa becomes more
thick the amount of fat in hepatocytes is reduced Thus there is
inverse relationship between amount of fat & amount of fibrous
scarring

4) Necrosis, inflammation and bile duct Proliferation :

The fibrous septa usually contain sparse infiltrate of
mononuclear cells with some bile duct proliferation. Bile stasis
and increased cytoplasmic haemosiderin deposits due to
enhanced iron absorption in alcoholic cirrhosis are some other
noticeable findings
C L I N I C A L F E AT U R E S

1) Elevated transaminases , increase in SGOT (AST) is more than that of SGOT

(ALT)
2) Rise in serum gamma glutamyl transpeptidase
3) Elevation in serum alkaline phosphatase
4) Hyperbilirubinaemia
5) Hypoproteinaemia with reversal of A:G ratio
6) Prolonged prothrombin time and partial thromboplastin time
7) Anaemia
8) Neutrophilic leucocytosis. in alcoholic hepatitis and in secondary infections
9) Malaise, anorexia and weight loss
10) Hepatic steatosis causes Hepatomegaly
 Thank you!

Ammar Malik
Roll number - 057
enrollment no. - 211936102057