GIT Pathology

·         Ito cells are fat-containing lipocytes found within the space of Disse of the liver. They participate in the metabolism and storage of vitamin A and also secrete collagen in the normal and the fibrotic (cirrhotic) liver. In normal livers, types I and III collagens (interstitial types) are found in the portal areas and occasionally in the space of Disse or around central veins. In cirrhosis, types I and III collagens are deposited throughout the hepatic lobule.

·         Primary hemochromatosis is a genetic disorder of iron metabolism that is inherited as an autosomal recessive disorder. The classic clinical triad for this disease consists of micronodular pigment cirrhosis, diabetes mellitus, and skin pigmentation. The combination of diabetes and skin pigmentation is called bronze diabetes

Secondary hemochromatosis, also called systemic hemosiderosis, is most common in patients with hemolytic anemias, such as thalassemia. Excess iron may also be due to an excessive number of transfusions or to increased absorption of dietary iron.

In idiopathic (primary) hemochromatosis, iron accumulates in the cytoplasm of parenchymal cells, but in secondary hemochromatosis the iron is deposited in the mononuclear phagocytic system.

In both conditions the iron is deposited as hemosiderin, which stains an intense blue color with Prussian blue stain. Since the iron deposition does not usually occur in the parenchymal cells in secondary hemochromatosis, there usually is no organ dysfunction or injury.

·         Abnormal development of the biliary tract may lead to several abnormalities, including von Meyenburg's complex (small bile duct hamartomas near normal portal tracts) and Caroli's disease, which is characterized by segmental dilation of the larger intrahepatic bile ducts.

·         7 alpha hydroxylase is an enzyme involved in converting cholesterol to bile acids.

1 alpha-hydroxylase is involved in vitamin D synthesis,

 11 alpha-hydroxylase, 17 alpha-hydroxylase, and 21 alpha-hydroxylase are all enzymes found in the adrenal cortex. A deficiency of these enzymes is seen with congenital adrenal hyperplasia.

·         VIPomas produce Verner-Morrison syndrome, which is characterized by explosive, profuse diarrhea with hypokalemia and hypochlorhydria. This combination of symptoms is referred to as pancreatic cholera.

§  Gilbert’s syndrome-

·         mild elevation of indirect bilirubin without overt hemolysis, normal liver enzymes

·         nl PE → Patient is otherwise healthy

·         Glucoronyl tranferase is saturated creating a slight backup of bilirubin

·         Need to hydrate them.

·         all unconjugated bilirubin

§  Criggler-Najjar

·         Glucoronyl transferase deficiency

·         Type I

o   Autosomal recessive

o   complete deficiency

o   all unconjugated/indirect

·         Type II

o   partial deficiency

o   Half will be conjugated

·         Hypoglycemia and jaundice

§  Rotors syndrome

·         Active transport out of the liver for bilirubin diglucoronide is defective

·         No Black pigmented hepatocytes, GALLSTONES present

·         ­ conjugated bilirbin

o   Because sugar is used to conjugate bilirubin, always continue feeding with sugar even after hyperbilirubinemia develops.

·         Less severe than Dubin Johnson

§  Dubin-Johnson (AR)

·         Problem in the transport system out of the gallbladder

·         Will have black pigment in hepatocytes AND

·         GALLSTONES

·         In Children the most common causes of Cholecystectomy is Dubin-Johnson and hereditary.