2. Objectives
Define cirrhosis, list its causes, and understand its pathogens &
complications
Classify portal hypertension, know its causes and the pathogenesis of its
complications
Enlist causes and identify morphology of cholecystitis
Enlist causes and describe pathogenesis of Pancreatitis
3. Cirrhosis
A diffuse process characterized by fibrosis and conversion of liver
architecture into abnormal nodules (End-stage of chronic liver disease)
Three main characteristics are:
Bridging fibrous septae
P-P, P-C, C-C
Parenchymal nodules
Proliferating hepatocytes encircled by fibrosis, with diameters varying from
very small (<3 mm, micronodules) to large (several centimeters,
macronodules)
Disruption of lobular architecture of entire liver
4. Cirrhosis of Liver
ETIOLOGY
Alcoholic liver disease 60% to 70%
Viral hepatitis (HBV ,HCV) 10%
NASH
Biliary diseases 5% to 10%
Primary hemochromatosis 5%
Cryptogenic cirrhosis 10% to 15%
Cardiac cirrhosis in the setting of cardiac disease
5. Pathogenesis of Liver cirrhosis
Fibrosis: Stellate (Ito) cell in space of Disse
transformed by inflammatory mediator to
myofibroblasts -collagen producing cells
Parenchymal injury & consequent fibrosis: a diffuse process
Nodularity: reflects balance between regenerative activity and constrictive scarring
Vascular architecture: reorganized with formation of abnormal interconnections between
vascular inflow and hepatic vein outflow channels resulting in portal vein and arterial blood
partially by passes functional hepatocyte mass
8. Complications of Cirrhosis
1. Progressive Liver failure
2. Portal Hypertension
3. Development of Hepatocellular Carcinoma
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9. Portal Hypertension in Cirrhosis
Pathogenesis
Results from increased resistance to portal flow; at the level of the sinusoids
and compression of central veins by perivenular fibrosis and expanded
parenchymal nodules
Anastomoses between arterial and portal systems; in the fibrous bands also
contribute to portal hypertension by imposing arterial pressure on the
normally low-pressure portal venous system
An increase in portal venous blood flow; caused by arterial vasodilation in
the splanchnic circulation, resulting primarily from increased production of
nitric oxide (NO) in the vascular bed by bacterial DNA
10. Complications of Portal hypertension
Development of Portosystemic Shunt: Principal sites are;
Veins around and within the rectum (hemorrhoids)
Cardioesophageal junction (esophagogastric varices)
Retroperitoneum, and the falciform ligament of the liver
(involving periumbilical and abdominal wall collaterals-caput
medusae)
Splenomegaly;
Long-standing congestion may cause congestive
splenomegaly (1000 g or less)
Massive splenomegaly may secondarily induce a variety of
hematologic abnormalities attributable to hypersplenism
11. Acute Cholecystitis
Incidence: 4F’s(female, forty, fertile, fatty)
C/F: Acute right upper quadrant pain,
tenderness and fever
Etiology: Usually related to obstruction by
gallstones, 90% of the cases are precipitated
by obstruction of neck or cystic duct few are
caused by torsion of neck
Morphology: Edema of gall bladder wall with
hemorrhage and neutrophils infiltrate
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12. Chronic Cholecystitis
Incidence: peaks in 40's and 50's,
predominantly female
C/F: usually recurrent right upper quadrant
pain
Etiology: main cause gallstones
Morphology: chronic inflammatory cells
infiltrate in the wall
Rokitansky's-Aschoff sinuses present
Complications: Gangrene, perforation,
empyma, fistula formation and risk of
malignancy
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13. Acute Pancreatitis
Etiologic Factors includes:
1. Metabolic; Alcoholism, hyperlipoproteinemia, hypercalcemia, drugs (e.g.,
azathioprine)
2. Genetic; Mutations in the cationic trypsinogen (PRSS1) and trypsin
inhibitor (SPINK1) genes
3. Mechanical; Gallstones, trauma
4. Vascular; Shock, Atheroembolism
5. Infectious; Mumps, Coxsackievirus
Pathogenesis: Autodigestion of the pancreatic tissue by inappropriately
activated pancreatic enzymes
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14. Acute Pancreatitis
Gross; tan-yellow flecks of soft material within and
on the surface of pancreas due to fat necrosis
Microscopy; necrosis of pancreatic parenchyma,
acute inflammation, fat necrosis and destruction of
blood vessels leading to hemorrhage
(autodigestion)
Acute pancreatitis; a medical emergency , present
with sudden onset of an “acute abdominal pain,
abdominal guarding, and absence of bowel
sounds
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15. Chronic Pancreatitis
Irreversible parenchymal damage
resulting from long-standing
inflammation, fibrosis with destruction of
the exocrine and in its late stages, the
endocrine parenchyma
Microscopy; chronic inflammatory cells
in a fibrous stroma with a few islets of
Langerhans
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An increase in portal venous blood flow, caused by arterial vasodilation in the splanchnic circulation, resulting primarily from increased production of nitric oxide (NO) in the vascular bed by bacterial DNA which is absorbed from the gut, by passes the Kupffer cells due to intrahepatic shunting of blood from portal to systemic circulation
Clinically; chronic malabsorption and diabetes mellitus
