Liver, Gallbladder and Pancreatic Disease

The ability to regenerate. 25% of a liver can regenerate to full functional size in appropriate settings

• Jaundice (or icterus) is yellow-green pigmentation of the skin or sclerae caused by an increase in bilirubin!
• Excess bilirubin (breakdown product of erythrocytes) is over 2-3mg/dl.
• Etiology: overproduction, reduced hepatocyte uptake of bilirubin and obstruction of bile flow.
• Unconjugated: virtually insoluble (can't even urinate it out)
• Conjugated: soluble, nontoxic.

• 1. Overproduction of bilirubin caused by increased breakdown of RBC (e.g. intravascular hemolyis-hemolytic anemia).
• 2. Impaired uptake of bilirubin from blood secondary to liver disease (e.g. sepsis, drug toxicity)
• 3. Decreased conjugation of bilirubin in the hepatocyte (e.g. hepatitis, neonatal jaundice, Gilbert's syndrome)
• 4. Impaired secretion/excretion of biirubin either intrahepatic (e.g. Dubin-Johnson's Syndrome, recurrent jaundice of pregnancy) or extrahepatic (e.g. obstructive gallstones, carcinoma of head of pancreas).

• inflammation of the liver
• Many etiologies (drugs, autoimmune disease, infections, viral)
• Viral Hepatitis: This term is reserved fro infection by a group of hepatotropic viruses, hepatitis A, B C Delta, E and G

• Common, Self limiting infection, no carrier state or chronic disease. Acute severe sickness that resolves.
• RNA virus, transient viremia (not long term)
• Fecal or oral transmission
• incubation 15-45 days.

• Chronicity: 5-10% progress to chronic hepatitis, 90% are self-limiting infection.
• DNA virus
• Parental/sexual spread.
• Serology-remains in blood, chronic, cirrhosis.
• Incubation 30-180 days
• Some risk of malignancy (10%) become chronic hepatitis/cirrhosis.
• Vaccine to Hep B 95% antiHB antibody response

• Hep C is the worst type of Hepatitis!
• RNA virus: majority progress to chronic hepatitis.
• Incubation 7-8 weeks
• Transmission: Parental, sexual spread
• High risk of malignancy/progression to chronic hepatitis.
• Persistent infection + chronic hepatitis = hallmark feature of Hep C (85%) (BAD)
• No vaccine because of genomic instability/viral change

• Hep D: RNA virus, associated with Hep B
• Hep E: Rare in US. RNA virus, usually self-limited, waterborne, animal reservoirs.
• Hep G (not hepatotropic) No increase in serum aminotransferases, replicates in bone marrow and spleen.

• Chronic Hepatitis
• Fulminant Hepatic necrosis
• Carrier states (varies for each type of Hepatitis)
• Cirrhosis
• Hepatocellular cancer

• Acute hepatitis: diffuse liver injury with lobular disarray.
• Necrosis of random, isolated liver cells (Councilman bodies).
• Chronic Hepatitis: Portal tract inflammation with interface hepatitis.

• Resolution in 8 weeks (like type A and some type B)
• Symptoms: may be asymptomatic
• Histology: Panlobular disarray, inflammation, hepatocyte necrosis.
• Fulminant: massive necrosis.
• Can become chronic (Hep B and HEP C!)

Abnormal liver function for over 6 weeks.

Disorganized liver architecture, fibrosis (fibrotic bands), parenchymal nodules secondary to reorganized vascular architecture. Factors leading to hepatocyte death and inflammation.

• Fatty liver disease (main one 60-70%) caused by too much alcohol, obsesity, Diabeties, medications, toxins, nutritional deprivation)
• Postnecrotic cirrhosis (post viral)
• Biliary cirrhosis
• Hemochromatosis (excess iron)
• Wilson's disease (excess copper)
• Cirrhosis associated with alpha-1 anti-trypsin deficiency.
• Cryptogenic

• Nonspecific symptoms = weight loss, weakness
• Liver failure
• Portal hypertension: Ascites, collateral venous channels, splenomegaly.
• Neoplasm: Hepatocellular carcinoma

• hemochromatosis causes cirrhosis of the liver.
• Iron overload: build up of iron in liver, pancreas and heart.
• Genetics: homozygous recessive, chromosome 6.
• Tx: Phlebotomy: (draining the blood)
• Features: micronodular cirrhosis, diabetes mellitis, skin pigmentation.

• Causes cirrhosis
• it's the accumulation of Copper in the liver, brain, eyes.
• Autosomal recessive.
• Morphology: acute/chronic, steatosis, necrosis, cirrhosis.
• Tx: Chelation D-Penicillamine: selectively binds copper and removes it from organs.

• 1. Focal nodular hyperplasia (vascular, reactive non-neoplastic)
• 2. Bile duct adenomas
• 3. Liver cell adenomas/hepatoceullar adenoma (birth control pills, steroids).
• 4. Hemangioma: inappropriate blood vessel proliferation. Most common tumor in infants.

• 1. Hepatocellular carcinoma (HCC)
• 2. Cholangiocarcinoma (Bile duct carcinoma)
• 3. Hepatocholangiocarcinoma

• Benign
• Associated with oral contraceptives
• Presentation: acute abdomen, intra-abdominal bleed.
• Histology: bland hepatocytes and no bile ducts.

• Aflatoxin, cirrhosis, Hep B and HEP C
• elevated serum alpha-fetoprotein
• Histology: atypical hepatocytes, more than 2-3 cell plates.
• Poor prognosis: rapidly aggressive. Strong propensity for vascular invasion.
• Clinical history: upper abdominal pain, fatigue and weight loss, elevated serum alpha-fetoprotein from neoplastic cells.

• It is a variant of Hepatocellular carcinoma (HCC)
• Occurs in younger patients 20-40.
• Better prognosis
• Scirrhous tumor

Pancreas and Gallbladder (bile duct and pancreatic duct)

• Cholelithiasis are Gallstones.
• 80% silent.
• Association with inflamed gallbladder.
• 90% cholesterol stones, 10% pigment
• Complications: pain, inflammation, obstruction.

• Supersaturation of bile (bile has 3 constituents: cholesterol, bilirubin and lecithin).
• initiation of stone formation and growth.

• 1. Cholesterol stone etiology: increase in caucasians, age and females with high estrogen. Fat, fertile, forty, females = lots of gallstones. High calorie diet, obesity.
• 2. Pigment stones: Oriental more than occidental; rural more than urban. Chronic hemolysis, alcoholic cirrhosis, biliary infection, age.

• Obstruction of the common duct
• Biliary cholic (gall stones)
• Predisposition to cholecystitis

• Inflammation of the gallbladder
• Acute: 90% of cases secondary to impacted gallstone. Secondary gram negative infection. Severe pain, chemical, bacterial reflux-ischemai.
• Chronic: vague symptoms, stones 90%, fibrosis and inflammation.
• Pathology: enlarged gallbladder, red to purple color with acute inflammation in gallbladder wall.

• Diabetes: endocrine pancreas (insulin, glucagon)
• Pancreatitis: exocrine pancreas (digestive enzymes)

Inflammation of the pancreas. Sudden onset of abdominal pain associated with elevated serum pancreatic enzymes (amylase, lipase). Secondary inflammation and necrosis (parenchymal and fat necrosis) of the pancreas.

• Cholelithiasis (gall stones) and alcoholism are the two main ones.
• Also, trauma, drugs, septisemia, infection (mumps), metabolic: hypercalcemic and hyperlipic states.
• Idiopathic
• viral infections

• Progressive destruction of the pancreas, chronic relapsing pancreatitis is a better term.
• causes: alcoholism, biliary tract disease, familial hereditary, cystic fibrosis.
• Symptoms: Abdominal pain (with each relapse), sometimes no symptoms, pancreatic insufficiency, diabetes mellitus (late).

• reduced acini
• Chronic inflammation
• fibrosis
• Obstruction of ducts
• Spare islets

• Carcinoma of the pancreas affecting exocrine glands.
• Gross pathology: majority in head of pancreas.
• symptoms: obstruction, painless jaundice.
• histology: adenocarcinoma (glands)
• origin from ducts
• Very poor prognosis

• Endocrine tumors of the pancreas are ISLET CELL TUMORS.
• Insulinomas: more common, most often benign glucagonomas, somatostatinomas and VIPomas also seen.
• Clinical tiad (Insulinoma): attacks of hypoglycemia, acute confusion/stupor, relief with glucose administration/infusion.
• Some are malignant (metastases seen).