Developmental malformation in which the pancreas forms a ring around the duodenum.

Risk of duodenal obstruction

• Inflammation and hemorrhage ofthe pancreas
• Due to autodigestion of pancreatic parenchyma by pancreatic enzymes
• Premature activation of trypsin leads to activation of other pancreatic enzymes
• Results in liquefactive hemorrhagic necorsis of the pancreas and fat necrosis of the peripancreatic fat
• Most commonly due to alcohol and gallstones
• Other causes include trauma, hypercalcemia, hyperlipidemia, drugs, scorpion stings, umps, and ruptue of a posterior duodenal ulcer
• Clinical Features:
• Epigastric abdominal pain that radiates to the back
• Nausea and vomiting
• Periumbilical and flank hemorrhage- necrosis spreads into the periumbilical soft tissue and retroperitoneum 
• Elevated serum lipase and amylase: lipase is more specific for pancreatic damge
• Hypocalcemia: calcium is consumed during fat necrosis
• Complications:
• Shock: Due to peripancreatic hemorrhage and fluid sequestration
• Pancreatic Pseudocyst: Formed by fibrous tissue surrounding liquefactive necrosis and pancreatic enzymes
• Presents as an abdominal mass with persistently elevated serum amylase
• Rupture is associated with release of enzymes into the abdominal cavity and hemorrhage
• Pancreatic abscess: often due to E coli
• Presents with abdominal pain
• High Fever
• Persistently elevated amylase
• DIC and ARDS

• Fibrosis of pancreatic parenchyma most often secondary to actue pancreatitis
• MC due to alcohol in adults and CF in children
• Many cases are idiopathic
• Clinical Features:
• Epigastric abdominal pain that radiates to the back
• Pancreatic insufficiency- results in malabsorption with steatorrhea and fat soluble deficiencies
• Amylase and lipase are not useful serologic markers of chronic pancreatitis
• Dystrophic calification of pancreatic parenchyma on imaging contrast studies reveal a "chain of lakes" pattern due to dilation of pancreatic ducts
• Secondary to diabetes- late complication due to destruction of islets
• Increased risk for pancreatic carcinoma  

• Adenocarcinoma arising from the pancreatic ducts
• Most commonly seen in the elderly-avg age is 70
•  Major risk factors are smoking and chronic pancreatitis
• Epigastric abdominal pain
• Weight loss
• Obstructive jaundice with pale stools andPalpable gallbladder are associated with tumors that arise in the head of the pancreas
• MC location
• Secondary diabetes mellitus is assocaited with tumors that arise in the body or tail
• Pancreatitis
• Migratory thrombophlebitis (Trousseau sign): Presents as swelling, erythema, and tenderness in the extremities (seen in 10% of patients)
• Serum tumor marker is CA 19-9
• Surgical resection
• Very Poor prognosis: 1-year survival is < 10%

• Failure to form or early destruction of extrahepatic biliary tree
• Leads to biliary obstruction within the first 3 months of life
•  Presents with jaundice and progresses to cirrhosis

Cholelithiasis

Gallstones

• Solid round stones in the gallbladder
• Due to precipitation of cholesterol or bilirubin in bile
• Arises with supersaturation of cholesterol or bilirubin
• Arises with decreases phospholipids (lecithin) or bile acids
• Bile Acids normally increase solubility
• Arises with stasis
• Cholesterol stones are yellow and the most common type (90%) 
• Radiolucent (10% are radioopaque due to association with calcium)
• Risk factorse include: age (40s), estrogen (female gender, obesity, multiple pregnancies, and oral contraceptives), Native American ethnicity, Crohns disease, and cirrhosis
• Bilirubin Stones (pigmented) 
• Usually radioopaque
• Risk factors include extravascular hemolysis and biliary tract infection (E coli, Ascaris lumbrioides, Clonorchis sinensis)
• Ascaris lumbricoides: common roundworm that infects 25% of the worlds population, especially in areas with poor sanitation.  Fecal oral transmission.  Infects the biliary tract increasing the risk for gallstones
• Clonorchis sinensis: Endemic in China, Korea, and Vietnam. Called the Chinese liver fluke.  Infects the biliary tract increasing the risk for gallstones, cholangitis, and cholangiocarcinoma
• Gallstones are usually asymptomatic
• Complication include: biliary colic, acute and chronic cholecystitis, ascending cholangitis, gallstone ileus, and gallbladder cancer  

• Waxing and waning RUQ pain
• Due to the gallbladder contracting against a stone lodged in the cystic duct
• Symptoms are relieved if the stone passes
• Common bile duct obstruction may result in acute pancreatitis or obstructive jaundice  

• Acute inflammation of the gallbladder wall
• Impacted stone in the cystic duct results in dilation with pressure ischemia, bacterial overgrowth ( E coli) and inflammation
• Presents with RUQ pain, often radiating to the right scapula
• Fever
• Increased WBC count
• Nausea
• Vomiting
• Increased serum Alkaline phosphatse
• Risk of rupture if left untreated  

• Chronic inflammation of the gallbladder
• Due to chemical irritation from longstanding cholelithiasis with or without superimposed bouts of acute cholecystitis
• Characterized by herniation of gallbladder mucosa into the muscular wall  called Rokitansky-Aschoff sinus
• Presents with vague RUQ pain, especially after eating
• Porcelain gallbladder is a late complication
• Shrunken, hard gallbladder due to chronic inflammation, fibrosis, and dystrophic calcification
• Increased risk for carcinoma
• Treatment is cholecystectomy especially if porcelain gallbladder is present

• Bacterial infection of the bile ducts
• Usually due to ascending infection with enteric Gm (-) bacteria
• Presents as sepsis (high fever and chills), jaundice and abdominal pain
• Increased incidence with choledocholithiasis (stone in biliary duct)  

• Gallstone enters and obstructs the small bowel
• Due to cholecystitis with fistula formation between the gallbladder and small bowel 

• Adenocarcinoma arising from the glandular epithelium that lines the gallbladder wall
• Gallstones area major risk factor, especially when complicated by porcelain gallbladder
• Classically presents as cholecystitis in an elderly woman
• Poor prognosis  

• RBCs are consumed by macrophages of the reticuloendothelial system  
• Protoporphyrin (from heme) is converted to unconjugated bilirubin
• Albumin carries unconjugated bilirubin to the liver
• Uridine glucuronyl transferase in hepatocytes conjugates bilirubin
• Conjugated bilirubin is transferred to the bile canaliculi to form bile which is stored in the gallbladder
• Bile is released into the small bowel to aid in digestion
• Intestinal flora converts conjugated bilirubin to urobilinogen which makes the stool brown. 
• Urobilinogen is also partially reabsorbed into the blood and filtered by the kidney, making urine yellow  

Paravascular hemolysis

or

 Ineffective erythropoiesis

as a casue of Jaundice

• High Levels of unconjugated Bilirubin (UCB) overwhelm the conjugating ability of the liver
• Increased UCB on lab findings
• Dark urine due to increased urine urobilinogen
• UCB is not water soluble and this is absent from urine
• Increased risk for pigmented bilirubin gallstones

• Newborn liver has transiently low uridine glucuronyl transfease (UGT) activity
• Increased UCB on lab findings
• UCB is fat soluble and can deposit in the basal ganglia causing kernicterus leading to neurological deficits and death
• Treatment is phototherapy which makes UCB water soluble

• Midly low UGT activity
• AR
• Increased UCB
• Jaundice during stress (severe infections) otherwise not clinically significant  

• Absence of UGT
• Increased UCB on lab findings
• Kernicterus-UCB deposited in basal ganglia
• Usually fatal

• Deficiency of bilirubin canalicular transport protein
• AR
• Increased conjugated bilirubin
• Liver is dark
• Not clinically significant
• Rotor syndrome is similar to Dubin Johnson syndrome but lacks the liver discoloration  

Biliary Tract Obstruction

Obstructive Jaundice

• Associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and liver fluke
• Increased Conjugated bilirubin, increased urine urobilinogen, and increased alkaline phosphatase
• Dark Urine-due to increased uring urobilinogen
• Pale stool
• Pruritis due to increased plasma bile acid
• Hyprcholesterolemia with xanthomas
• Steatorrhea with malabsorption of fat souble vitamins 

• Inflammation disrupts hepatocytes and small bile ductules
• Increase in both conjugated and unconjugated bilirubin
• Dark urine due to increased urine bilirubin
• Urine urobilinogen is normal or decreased
• HAV: 
• Fecal oral transmission
• Acute hepatitis
• No Chronic state
• Anti-IgM marks current infection
• Anti-IgG is protective and indicated prior infection or immunization
• HEV:
• Acquired from contaminated water ot undercooked seafood
• Pregnant women
• Associated with fulfminant hepatits (liver failure with massive liver necrosis)
• HBV:
• Parenteral transmission (childbirth, unprotected intercourse, and IV drug use)
• Results in acute hepatitis 80% of cases
• HCV:
• Parenteral transmission
• Risk from transmission is almost nonexistant due to screening of the blood supply
• Chronic Disease in most cases
• HCV-RNA test confirms infection
• Decreased RNA levels indicate recovery
• Persistence indicates chronic disease
•  HDV:
• Dependeent on HBV for infection
• Superinfection upon existing HBV is more severe than coinfection with HBV

• Inflammation of the liver parenchyma
• Causes acute hepatitis which may progress to chronic hepatitis
• Acute hepatitis presents as jaundice (mixed CB and UCB) with dark urine (due to CB), fever, malaise, nausea, and elevated liver enzymes (ALT>AST)
•  Inflammation involves lobules of the liver and portal tracts and is characterized by apoptosis of hepatocytes
• Some cases may be asymptomatic with elevated liver enzymes
• Symptoms last < 6 months
• Chronic hepatitis is characterized by symptoms that last > 6 months
• Inflammation predominatly involves portal tract
• Risk of progression to cirrhosis

• End-stage liver damage characterized by disruption of the normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes
• Fibrosis is mediated by TGF-β from stellate cells which lie beneath the endothelial cells the line the sinusoid
•  Portal hypertension leads to:
• Ascites
• Congestive splenomegaly
• Portosystemic shunts- Esophageal varices, hemorrhoids, caput medusae (engorged paraumbilical veins)
• Hepatorenal syndrome-rapidly developing renal failure
• Decreased detoxification results in:
• Mental status change, asterixis, and eventual coma due to increased ammonia
• Gynecomastia
• Spider Angioma
• Palmar erythema
• Jaundice
• Decreased protein synthesis leads to:
• Hypoalbuminemia with edema
• Coagulopathy due to decreased synthesis of clotting factors

• Damage to hepatic parenchyma due to consumption of alcohol
• MCC of liver disease in West
• Fatty Liver is the accumulation of fat n hepatocytes
• Results in a heavy, greasy liver, resolves with abstinence
• Alcoholic hepatitis results from chemical injury to hepatocytes
• Seen with binge drinkning
• Acelaldehyde mediates damage
• Characterized by swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments)
• Necrosis
• Acute inflammation
• Presents with painful hepatomegaly and elevated liver enzymes (AST>ALT)
• May result in death
• Cirrhosis is a complication of long term, chronic alcohol0induced liver damage
• Occurs in 10-20% of alcoholics  

• Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol
• Associated with obesity
• Diagnosis of exclusion
• (ALT>AST) 

• Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage
• M>W
• If present in women not diagnoised until postmenopausal
• Tissue damage is mediated by generation of free radicals
• Due to AR defect in iron absorption (primary) or chronic transfusions (secondary)
• Primary hemochromatosis is due to mutations in the HFE gene, usually C282Y on chromosome 6
• Cysteine is replaced by tyrosine at amno acid 282
• Presents in late adulthood
• Classic triad:
•  Cirrhosis
• Secondary Diabetes mellitus
• Bronze skin
• Other findings are:
• Cardiac arrhythmias
• Gonadal dysfunction (due to testicular atrophy)
• Increased serum iron-used to follow therapy
• Increased % sat
• Increased ferritin
• Transferrin saturation is the best screening test: Values >45% indicate further testing is necessary
• Decreased TIBC
• Liver biopsy reveals accumulation of brown pigment in hepatocytes
• Prussan blue stain distinquishes iron (blue) from lipofuscian (brown pigment that is a by-product from the turn over of peroxidized lipids.  Commonly present in hepatocytes)
• Increased risk of cellular carcinoma
• Treatment is phlebotomy

• AR
• ATP7B gene
• Defective hepatocyte transport of copper into bile for excretion
• Defective incorporation of copper into ceruloplasmin (binding protein for copper in blood)
• Copper builds up in hepatocytes, leaks into serum, and deposits into tissues
• Copper mediated production of hydroxy free radicals which leads to tissue damage
• Onset of symptoms is 3-40 yrs old
• Cirrhosis
• Neurologic manifestation: behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in the putamen
• Copper deposits in the subthalamic nucleus produces hemiballismus
• Copper is toxic to the neurons in the cerebral cortex and produces dementia
• Kayser-Fleisher rings in the cornea
• Decreased total serum copper-due to decreased ceruloplasmin
• Decreased serum ceruloplasmin
• Increasd serum and urine free copper
• Increased risk for hepatocellular carcinoma
• Treatment is D-penicillamine (chelates copper)

• Autoimmune granulomatous destruction of intrahepatic bile ducts
• Classically arises in women of avg age 40
• Associated with other autoimmune disease
• Etiology is unknown
• Anti-mitochondrial antibody is present
• Presents with features of obstructive jaundice
• Cirrhosis is a late complication  

• Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
• Periductal fibrosis with an onion skin appearance
• Ininvolved regions are dilated resulting in a beaded apearance on contrast imaging
• Etiology is unknown but associated withulcerative colitis
• p-ANCA is often present
•  Presents with obstructive jaundice, cirrhosis is a late complication
• Increased risk for cholangiocarcinoma

• Fulminant liver faiure and encephalopathy in children with viral illness who take asprin
• Likely related to mitochondrial damage of hepatocyte
• Presents with hypoglycemia, elevated liver enzymes, and nausea with vomiting
• May progress to coma and death  

• Benign tumor of hepatocytes
• Associated wtih oral contraceptives: regresses with cessation of drug
• Risk of rupture and intraperitoneal bleeding, especially during pregnancy
• Tumors are subcapsular and grow with exposure to estrogen  

• Malignant tumor of hepatocytes
• Risk Factors include:
• Chronic hepatitis
• Cirrhosis
• Fatty liver disease
• Hemochromatosis
• Wilsons disease
• AIAT dificiency
• Anatoxins derived from Aspergillus (p53 mutations)
• Increased risk for Budd-Chiari syndrome
• Liver infarction secondary to hepatic vein obstruction
• Presents with painful hepatomegaly and ascites
• Tumors are often detected late because symptoms are masked by cirrhosis: poor prognosis
• Serum tumor marker is alpha-fetoprotein  

• More common than primary liver tumors
• MC sources include colon, pancreas, lung, and breast carcinoma
• Results in multiple nodules in the liver
• Clinically may be detected as hepatomegaly wiht a nodular free edge of the liver