HEPATOBILIARY SYSTEM

LIVER: CIRRHOSIS

This is the liver of a 60-year-man who died from acute liver failure.

1.    What are the morphological features of this specimen?
 
The organ shown here is the liver. The prominent features are multiple (nearly) spherical nodules of varying sizes (from 0.5 to 3cm in diameter) scattered throughout the liver parenchyma, compressing the intervening parenchyma. The liver capsule is intact. There are no signs of fatty change or presence of other space-occupying lesion in the liver. The nodules are not bile-stained. This specimen is a cirrhoticc liver.

2.    What are the likely histological features?
 
In cirrhosis, the normal architecture of the liver is diffusely replaced by nodules of regenerated liver cells, separated by bands of collagenous fibrosis. It has three characteristics, namely long-standing destruction of liver cells, associated chronic inflammation that stimulates fibrosis, and regeneration of hepatocytes to cause nodules. Bridging fibrous septa in the form of delicate bands and broad scars replace multiple adjacent lobules.

3.    What is the pathogenesis of this condition?
 
The central pathogenetic process is progressive fibrosis. It is thought that growth factors and growth factors produced as part of inflammatory responses, as well as toxins such as alcohol stimulate mesenchymal cells in the liver to proliferate and differentiate into collagen-secreting fibroblasts. The mesenchymal cells involved are the fat-storing cells of Ito, located in the space of Disse.

4.    What are the common causes?
 
a.    Common: alcoholic liver disease, chronic hepatitis caused by hepatitis B and C.
c.    Uncommon: autoimmune chronic hepatitis, primary biliary cirrhosis, primary hemochromatosis, Wilson disease, a-antitrypsin deficiency, cystic fibrosis.

5.    What could precipitate acute liver failure in this patient and what problems can it cause?
 
Acute liver failure, which develops when there has been damage to the majority of hepatocytes such that liver function is critically impaired, is seen in three main clinical situations:
 
a.    Following severe hepatocyte damage, e.g. as a consequence of extensive liver necrosis or metabolic damage.
b.    Following severe systemic shock as part of a multi-organ failure along with ARDS and acute renal failure.
c.    As an acute decline in otherwise stable chronic liver disease.
 
The main precipitating factors are alcohol binge, development of intercurrent infection, gastrointestinal bleed, portal vein thrombosis, and development of carcinoma of the liver.
 
Acute liver failure causes 5 chief problems:
 
a.    Hypoglycaemia.
b.    Hepatic encephalopathy.
c.    Hemorrhage.
d.    Ascites.
e.    Infection.
f.     Renal failure secondary to hepatorenal syndrome.

6.    What are the long-term complications of this condition?
 
The main consequences of cirrhosis are:
 
a.    Reduced hepatocyte function: decreased synthesis of proteins, failure of detoxification.
b.    Disturbance of blood flow through the liver due to compression by regenerating nodules and fibrosis, arterio-venous anastomosis, causing portal hypertension with all its attendant complications such as ascites, esophageal varices and hepatic encephalopathy.
c.    Reduced immune competence and increased susceptibility to infection.
d.    Increased risk of development of hepatocellular carcinoma.

7.    Related the pathology to the clinical signs that can be seen in this patient.
 
a.    Portal hypertension: varices, splenomegaly and caput medusae.
b.    Petechiae and ecchymoses: failure to synthesize clotting factors.
c.    Impaired metabolism of endogenous estrogens: testicular atrophy, spider nevi and gynecomastia.
d.    Low serum albumin: ascites and edema.
e.    Conjugated hyperbilirubinaemia due to hepatic failure to secrete bile: jaundice, scratch marks and pruritus.

8.    What are the biochemical abnormalities?
 
a.    Alkaline phosphatase: may be greatly elevated if the cause is biliary obstruction.
b.    AST and ALT: transaminase levels are elevated, proportional to the activity of liver cell destruction.
c.    Bilirubin: elevated levels, which may be very high in cases caused by biliary obstruction.
d.    Serum albumin: low, as a result of failure of synthesis.
e.    Prothrombin time: prolonged because of failure of synthesis of coagulation factors. 

LIVER: FATTY CHANGE

1.    What are the morphological features of this specimen?
 
The organ shown here is the liver. The liver is enlarged, orange and greasy. The capsule is smooth and intact. There are no signs of fibrosis or presence of any space-occupying lesions. 

2.    What are the likely causes?
 
Fatty change is a common response of the liver to diverse adverse stimuli. 
 
The main causes are:
 
a.    Metabolic stress: hypoxia, kwashiorkor, diabetes mellitus.
b.    Toxins: alcohol.
c.    Reye's syndrome: causes extensive microvesicular fatty change.
d.    Fatty liver of pregnancy.

3.    What is the pathogenesis of this condition?
 
a.    Excessive entry of free fatty acids into the liver, e.g. starvation, corticosteroid therapy.
b.    Enhanced fatty acid synthesis.
c.    Decreased fatty acid oxidation.
d.    Increased esterification of fatty acids to triglycerides, e.g. alcohol.
e.    Decreased apoprotein synthesis in carbon tetrachloride poisoning.
f.    Impaired lipoprotein secretion from the liver, e.g. alcohol.

4.    What are the main functions of the liver?
 
a.    Carbohydrate metabolism: the liver is a storage site for glycogen and is a main source of plasma glucose.
b.    Fat metabolism: the liver is central in the processing of dietary fats to lipoproteins.
c.    Protein metabolism: the liver is a major site of protein synthesis, particularly for plasma proteins such as albumin, coagulation factors, binding proteins for iron and copper, and certain acute-phase proteins.
d.    Bile synthesis: the liver secretes bile containing bilirubin, cholesterol, electrolytes, and bile salts.
e.    Storage: the liver stores glycogen, iron, copper and fat-soluble vitamins.
f.    Detoxification: the liver detoxifies many metabolites, particularly nitrogenous compounds, hormones and drugs. 

LIVER: CHRONIC VENOUS CONGESTION

1.    What are the morphological features of this specimen?
 
The organ shown here is the liver. The liver has a congested mottled 'nutmeg appearance' with alternating pale and dark areas. 

2.    What are the likely histological features?
 
The centrilobular sinusoids are dilated by blood, and the centrilobular hepatocytes are atrophic.

3.    What is the pathogenesis of this condition?
 
Right-sided cardiac failure causes a back-pressure in the systemic venous system, which is transmitted back down the hepatic vein to the central veins, causing mild increase in hepatic size. This is particularly seen in tricuspid valve incompetence, when the liver is pulsatile.

CHOLECYSTITIS

The patient is a 55-year-old lady who complains of a sudden onset of fever, jaundice and pain radiating to the shoulders. She has been having intermittent colicky pain in the right iliac fossa and indigestion for the past 3 months. An open surgery was performed for her.
 
1.    Compare and contrast the two specimens shown.
 
The organ shown is the gallbladder. No gallstones are seen.
 
a.    Left: The gallbladder is enlarged, edematous, tense and dark in color. There is a purulent exudate on the surface. These are features consistent with that of acute cholecystitis.
b.    Right: The gallbladder is shrunken. The wall is thickened 2 - 3 times the normal size due to fibrosis. These are features consistent with that of chronic cholecystitis.

2.    What is the pathogenesis of this condition?
 
Most cases are associated with gallstones and there is often obstruction of the cystic duct by a stone. Inflammation is precipitated by the chemical effects of concentrated bile in the gallbladder with gallbladder dysmotility, distention and ischaemia.
 
In the severely ill patient, cholecystitis is the direct result of ischaemia of gallbladder or sepsis.

3.    What complications can it lead to?
 
a.    Bacterial superinfection with cholangitis and sepsis.
b.    Gallbladder perforaiton or rupture.
c.    Enteric fistula formation.
d.    Aggravation of pre-existing illness. 

4.    What investigations would you do to confirm the diagnosis and what are the expected findings?
 
a.    FBC: increased WCC and acute-phase reactants are indicative of an active infection.
b.    Liver function test: ALP and bilirubin levels are raised.
c.    Ultrasound: may detect presence of gallstones.
d.    ERCP: to confirm presence of stones in the common bile duct is it is dilated on ultrasound.

5.    What operation is likely to be done and what are its possible complications?
 
Open cholecystectomy involves opening the abdomen through an oblique subcostal or transverse or paramedian incision. The cystic artery and duct are ligated and the gallbladder is peeled away from the liver.
 
The complications of this procedure are:
 
a.    Wound hematoma and sepsis.
b.    Collection of bile, blood or pus in the subhepatic space forming a subhepatic abscess.
c.    Leakage of bile leading to peritonitis.
d.    Bile duct stricture from accident ligature of one of the main ducts.
e.    Cholangitis: bleeding into the biliary tree.
f.     Pancreatitis.   

6.    What is your post-op management of this patient?
 
a.    After exploration of common bile duct, a T-tube is usually left in the bile duct draining freely to the exterior.
b.    A T-tube cholangiogram is performed 8 - 10 days and if there are no retained stones, the tube may be pulled out. 

7.    What other alternatives are there besides this type of surgery?
 
a.    Laparoscopic cholecystectomy.
b.    ERCP.

CARCINOMA OF HEAD OF PANCREAS

1.    Describe the morphological features of this specimen.
 
The organ shown is the head of pancreas at the ampulla of vater at the duodenum. There is a large white fleshy mass surrounding and compressing the ampulla of vater. Part of it has ulcerated into the duodenum. The features are consistent with that of carcinoma of head of pancreas.

2.    What are its clinical manifestations?
 
a.    Weight loss, anorexia and chronic persistent epigastric pain radiating to the back.
b.    Obstructive jaundice with painless palpable dilatation of the gallbladder (Courvoisier's sign).
c.    Migratory thrombophlebitis, in which there is development of multiple thrombosis in superficial and deep leg veins (Trousseau's syndrome).

3.    How does it spread?
 
a.    Local: causing obstructive jaundice, or invasion of the duodenum. 
b.    Lymphatic: spreading to adjacent lymph nodes.
c.    Hematogenous: spreading to the liver.

4.    What are the risk factors associated with this condition?
 
a.    Smoking.
b.    Alcohol consumption.
c.    Diabetes melllitus

ACUTE HEMORRHAGIC PANCREATITIS

1.    Describe the morphological features of this specimen.
 
The organ shown is the pancreas. It appears edematous, soft, and flabby. Its appearance is dark with a variegated pattern of blue-black hemorrhages and gray-white necrotic softening with foci of yellow-white chalky fat necrosis. 

2.    What is the pathogenesis?
 
The pancreas secretes 22 enzymes including proteases, elastases and phospholipases secreted as proenzymes requiring activation by trypsin in the duodenum and amylase and lipase which are secreted in their active form.
 
Damage to the pancreatic acini and ducts by inflammatory mediators and toxins lead to the release of these enzymes which cause tissue proteolysis, lipolysis and hemorrhage.
 
The mechanisms for activation of pancreatic enzymes are:
 
a.    Pancreatic duct obstruction by gallstones, with impaction in the ampulla of Vater and pancreatic duct obstruction. An enzyme-rich interstitial fluid accumulates, and resident tissue leukocytes release proinflammatory cytokines, promoting local inflammation and edema.
b.    Primary acinar cell injury: damage by viruses, drugs, trauma, and the ischemia of shock.
c.    Defective intracellular transport of proenzymes: acinar cell digestive enzymes are misdirected toward lysosomes rather than toward secretion; lysosomal hydrolysis of the proenzymes promotes local release of activated enzymes.
d.    Alcohol promote acinar cell injury by misdirected intracellular transport of proenzymes and promotes the deposition of inspissated protein plugs within the pancreatic ducts, leading to local obstruction and inflammation. 

3.    What are the pancreatic alterations seen histologically?
 
a.    Leakage of vasculature to cause edema.
b.    Necrosis of regional fat by lipolytic enzymes.
c.    An acute inflammatory reaction.
d.    Proteolytic destruction of the pancreatic substance.
e.    Destruction of blood vessels with subsequent interstitial hemorrhage. 

4.    What are the etiologic factors associated with this condition?
 
a.    Metabolic: alcoholism, hyperlipoproteinaemia, hypercalcemia.
b.    Mechanical: gallstones, traumatic injury, ERCP.
c.    Vascular: shock, atheroembolism.
d.    Infectious: mumps, coxsackievirus, mycoplasma pneumoniae.

5.    What are the likely laboratory findings?
 
a.    FBC: neutrophil leukocytosis.
b.    Serum amylase: greatly elevated.
c.    Serum albumin: falls in severe disease, due to loss in acute inflammatory exudate.
d.    Serum calcium: falls due to complexing with necrotic fat.
e.    Blood sugar: hyperglyacemia due to loss of pancreatic islet cells.
f.    Alkaline phosphatase: mild elevation from edema and obstruction of lower end of bile duct.
g.    Bilirubin: mild elevation. 

6.    What are the causes of death?
 
Death occurs from shock, acute respiratory distress snydrome and acute renal failure. 

7.    What are the usual sequelae of this condition?
 
a.    Chronic pancreatitis.
b.    Pancreatic abscess.
c.    Pancreatic pseudocyst.