"With ordinary talent and
extraordinary perseverance, all
things are attainable."
- Thomas E. Buxton
"Achievement is connected
with action, not in genes..…!”
- Conrad Hilton
Alcoholic liver disease
•
•
Excessive alcohol consumption is the
leading cause of liver disease.
Alcoholic liver disease comprises of
three main stages
1. Hepatic steatosis
2. Alcoholic hepatitis
3. Cirrhosis
Hepatic steatosis
• Pathogenesis :
• Fatty change is an acute, reversible manifestation of
ethanol ingestion.
• Ethanol causes
– Increased fatty acid synthesis by causing catabolism of fat in the
peripheral tissues
– Acetaldehyde which is metabolite of ethanol converts NAD+ to
NADH. An excess NADH stimulates lipid biosynthesis.
– Oxidation of fatty acid by mitochondria is decreased
– Acetaldehyde impairs the function of microtubules, resulting in
decreased transport of lipoproteins from liver
• Collectively these metabolic consequences produce fatty
liver.
• Pathology:
• Gross:
– The liver becomes yellow, greasy and is
enlarged (up to 4 to 6 kg)
– The increase in weight is because of
accumulation of fat, protein and water
Alcoholic Fatty Liver
• Microscopy:
• Following even moderate intake of alcohol,
small (microvesicular) lipid droplets
accumulates in the liver
• With chronic intake of alcohol, more lipid
accumulates, creating a large
macrovesicular globules, compressing the
nucleus the periphery.
Steatosis in Alcoholism
Alcoholic Fatty Liver
• Clinical features of alcoholic steatosis
– Hepatomegaly
– Mild elevation of serum bilirubin, alkaline
phasphatase and gamma GT
Alcoholic hepatitis
•
Is characterized by
1.
2.
3.
4.
Hepatocyte swelling and necrosis
Mallory bodies
Neutrophilic inflammatory response
Perivenular fibrosis
• Hepatocyte swelling and necrosis:
– Single or scattered foci of cells undergo
swelling (ballooning degeneration) and
necrosis
• Mallory bodies:
– Scattered hepatocytes accumulate cytokeratin
intermediate filaments and other proteins
– Visible as eosinophilic cytoplasmic inclusions
in degenerating hepatocytes
• Neutrophilic reaction:
– Neutrophils accumulate around the
degenerating hepatocytes, particularly those
having Mallory bodies.
– Lymphocytes and macrophages also enter
portal tracts and spill into parenchyma
• Fibrosis :
– Commonly seen in the form of sinusoidal and
perivenular fibrosis
– Occasionaly periportal fibrosis may
predominate
– Fibrosis mainly occurs because of the
activation of sinusoidal stellate cells and
portal tract fibroblasts
• Clinical features:
– Malaise, anorexia, weight loss, upper
abdominal discomfort, tender hepatomegaly.
– Laboratory findings:
• Hyperbilirubinemia
• Elevated ALP,GGT, moderate elevation of AST
• Neutrophilic leucocytosis
• Alcoholic cirrhosis:
– The final and irreversible form of alcoholic
liver disease
– Usually evolves slowly
– Gross:
• Initially the liver is yellow-tan, fatty and enlarged.
• Later it is transformed into brown, shrunken,
nonfatty organ with multiple nodules.
• Sometimes nodularity becomes very prominent
with scattred lager nodules creating a “hobnail”
appearance on the surface of liver
Normal Liver
Cirrhosis
Micronodular cirrhosis:
Alcoholic Cirrhosis
• Microscopy:
– Initially fibrous septae are very delicate and
extend through sinusoids from central to
portal regions as well as from portal tract to
portal tract.
– As the fibrous septae dissect and surround
nodules, the liver becomes more fibrotic,
loses fat, and shrinks in size. (Laennec
cirrhosis)
– Bile stasis may be seen.
Normal Liver Histology
Cirrhosis
Fibrosis
Regenerating Nodule
Liver Biopsy – Cirrhosis
Cirrhosis in Alcoholism
• Clinical features:
–
–
–
–
Features are similar to other forms of cirrhosis.
Malaise, weakness, weight loss, loss of appetite
Jaundice, ascites, and peripheral edema
Features of portal hypertension
• Laboratory findings:
– Hyperbilirubinemia, elevated serum
aminotransferase, alkaline phasphatase,
hypoproteinemia and anaemia
Alcoholic Liver Damage
Liver abscesses
Introduction
• Liver abscesses can result from bacterial infection
(pyogenic abscess) or from Entamoeba histolytica.
• Pyogenic abscesses have a high mortality rate of
40%.
• Liver abscesses generally result from spread of infection
from :
 the digestive tract via the portal vein,
 from biliary disease or
 by direct extension from an adjacent infection.
• Risk factors include:




Biliary disease
Trauma
Diabetes
Malignancy.
Aetiology of liver abscess
• Enteric Gram-negative bacilli (aerobes
and anaerobes) are frequently cultured.
• Many of the causative organisms originate
in the gastrointestinal tract:
Escherichia coli
Klebsiella pneumoniae
Bacteroides spp.
Enterococcus spp.
Anaerobic Streptococcus spp.
Streptococcus ‘milleri’ group.
Diagnosis of liver abscess
Signs and symptoms include:
Fever
Anorexia
Nausea
Weight loss
Weakness
Upper right quadrant pain
Jaundice is rare until a late stage of the
infection.
Laboratory diagnosis
• Diagnostic investigations include:
• Culture of aspirated material (under ultrasound
guidance) is the most useful diagnostic test
• With the advent of modern systems and improved
media, particularly for the recovery of anaerobic
organisms, blood culture is often helpful.
• Imaging
– CT is the most useful imaging technique, with
ultrasound effective for lesions more than a couple of
centimetres in diameter.
Amoebic liver abscess
• Amebiasis is a disease caused by a onecelled parasite called Entamoeba
histolytica .
• Mode of transmission: feco-oral with
ingestion of amoebic cysts.
Symptoms of amoebic liver abscess
•
•
•
•
•
•
•
•
•
Pain
Enlarged liver with maximal tenderness over abscess
Intermittent fever (38-39°C)
Night sweats
Weight loss
Nausea
Vomiting
Cough
Dyspnoea
Symptoms of amebiasis
• The symptoms often are quite mild and can
include loose stools, stomach pain, and stomach
cramping.
• Amebic dysentery is a severe form of amebiasis
associated with stomach pain, bloody stools, and
fever.
• Rarely, E. histolytica invades the liver and forms
an abscess.
• Even less commonly, it spreads to other parts of
the body, such as the lungs or brain.
Pathogenesis & pathology :
• Amoebic liver abscess is always preceded
by intestinal colonisation of the protozoan.
• Trophozoites invade veins to reach the liver
through the portal system.
• Inoculation of amoebae into the liver results
in acute inflammation & necrosis of
hepatocytes.
• The necrotic contents of the liver “abscess”
are described as “anchovy-sauce” OR
“chocolate-paste”.
Trophozoites of entamoeba
histolytica:
• The liver parenchyma is replaced by
necrotic tissue surrounded by a thin rim of
congested hepatic tissue, having a
“shaggy” appearance due to fibrin.
Complications of amoebic liver
abscess(ALA):
• ALA has a high mortality rate when
associated with other-organ involvement.
• The abscess can rupture into :
– the pleural space,
– lung,
– peritoneal cavity,
– pericardial cavity and
– the sub-phrenic space forming amoebic
abscesses in these sites.
‘Time’ is the best kept
secret of the rich..!
– Jim Rohn