Both intra-and extrahepatic. Inflammation and fibrosis of bile ducts-->alternating structures and dilation with "beading" on ERCP. Associated with ulcerative colitis. Can lead to 2 degree biliary cirrhosis.

Charcot's Triad of cholangitis:

1. Jaundice

2. Fever

3. RUQ pain

Primary: Intrahepatic, autoimmune disorder; severe obstructive jaundice, steatorrhea, puruiritus, hypercholesterolemia (xanthoma). Increase alkaline phosphate, increasedd serum mitochondrial antibodies.

Secondary: Due to extrahepatic biliary obostruction, increase in pressure in intrahepatic ducts-->injury/fibrosis. Often complicated by ascending cholangitis (bacterial infection), bile stasis and "bile lakes." Increased alkaline phosphatase, increased conjugated bilirubin. 

Also called hepatoma. Most common first degree malignant tumor of the liver in adults. Increased incidence of hepatocellular carcinoma is associated with hep B and C, wilson's disease, hemochromatosis, alpha-antitrypsin deficiency, alcoholic cirrhosis and carcinogens (alfatoxin B1). Can present with tender hepatomegaly, ascites, polycythemia and hypoglycemia.

Hepatocellular carcinoma like renal is commonly spread by hematogenous dissemination. Elevated alpha fetoprotein. May lead to Budd-Chiari syndrome

Inadelquate hepatic copper excretion and fialure of copper to enter circulation as ceruloplasmin. Leads to copper accumulation, eespecially in the liver, brain, cornea, kidneys, joints. Also know as hepatolenticular degeneration. Wilson's disease characterized by:

Asterixis

Basal ganglia degeneration (parkinsonian symptoms)

1. Ceruloplasm decrease, 2. Cirrhosis, 3. Corneal deposits (Kayser-Fleischer rings), 4. Copper accumulation, 5. Carcinoma (hepatocellular), 6. Choreiform movements

Dementia

Treat with penicillamine. Autosomal-recessive inheritance.

Reye's Sysndrome

Form when solubilizing bile acids and lecithin are overwhelmes by increased cholesterol and/or bilirubin.

Three types of stones:

1. Cholesterol stonesn (radiolucent with 10-20% opaque due to calcifications)--associated with obesity, Crohn's disease, cystic fibrosis, advanced age, clofibrate, estrogens, multiparity, rapid weight loss and Native American origin.

2. Mixed stones (Radiolucent)--have both cholesterol and pigment components. Most common type.

3. Pigment stones (radiopaque)--seen in patietns with chronic RBC hemolysis, alcoholic cirrhosis, advanced age, biliary infection. 

Diagnose with ultrasoundd. Treat with cholecystectomy. 

Risk factors (4 Fs) 1. female 2. fat 3. fertile 4. forty

Caused bya ctivation of pancreatic enzymes-->autodigestion

Causes: Gallstones, Ethanol, Trauma Steroids, Mumps, Autoimmune disease, Scorpion sting, Hypercalcemia/Hyperlipidemia, Drugs (eg sulfa drugs). GET SMASHED

Clinical presentation: epigastric abdominal pain radiating to back: anorexia, nausea

Labs: elevated amylase, lipase (higher specfiicity). Can lead to DIC, ARDS, diffuse fat necrosis, hypocalcemia, pseudocyst formation, hemorrhage, and infection. Chronic calcifying pancreatitis is strongly associated with alcoholism. Chronic obstructive pancreatitis is strongly associated with gallstones. 

DDL can cause a fatal pancreatitis

Pancreatic adenocarcinoma

Prognosis averages 6 months or less, very aggressive, usually already metastasized at presentation; tumors more common in pancreatic head (obstructive juandice). Often presents with:

 1. Abdominal pain radiatingi to back

2. Weight loss (Due to malabsorption and anorexia)

3. Migratory thrombophlebitis (trousseau's syndrome)

4. Obstructive juadice with palpable gallbaladder (Courvoisier's sign)

1. cimetidine, 2. Ranitidine 3. Famotidine 4. Nizatidine

Mech: Reversible block of histamine H2 receptors-->decrease H+ secretion  by parietal cells. 

Clinical use: Peptic ulcer, gastritis, esophageal reflux

Toxicity: Cimetidien is potent inhibitor of P-450; also has antiandrogenic effect and decrease renal excretion of creatinine. .Other H2 blockers relatively free of these effects. 

1. Omeprazole 2. Lansoprazole

Mechanism: Irreversibly inhibit H+/K+ ATPase in stomach parietal cells

Clinical USe: Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome

Mechanism: Bind to ulcer base, providing physical protection, and allow HCO3 secretion to reestablish pH gradient in mucus layer.

Clinical use: Increse ulcer healing, traveler's diarrhea. 

Tripple therapy of H. pylori ulcers--metronidazole, bismuth, amoxicillin (or tetracycline).

Acute gastritis (erosive):

Disruption of mucosal barrier-inflammation. Can be caused by stress, NSAIDs, alcohol, uricemia, burns (CUrling's ulcer) and brain injury (Cushing's ulcer).

Chronic gastritis (nonerosive): 

Type A (fundal) Autoimmune disorder characterized by Autoantibodies to parietal cells, pernicious Anemia and Achlorhydria

Type B (antral) cuased by H. pylori infection (a Bug).

Both increase risk of gastric carcinoma

Misoprostol

Mechanism: A PGE1 analog. Increase production and secretion of gastric mucous barrier, decrease acid production.

Clinical use: Prevention of NSAID-induced peptic ulcers; maintenance of patent ductus arteriosus. Also used to induce labor.

Toxicity: Diarrhea, Contraindicated in women of childbearing potential (abortifacient). 

Pirenzepine, propantheline

Mechanism: Block M1 receptors on ECL cells (Decrease histamine secretion) and M3 receptors on parietal cells (Decrease H+ secretion).

Clinical use: Peptic ulcer

Toxicity: Bradycardia, dry nmouth, difficultyh focusing eyes.

Mechanism: A monoclonal antibody to TNF-alpha, proinflammatory cytokine.

Clinical use: Crohn's disease, rheumatoid arthritis

Toxicity: Respiratory infection, fever, hypotension

Mechanism: A combination of sulfapyridine (antibacterial) and mesalamine (anti-inflammatory). Activated by colonic bacteria

Clinical use: Ulcerative colitis, Crohn's disease

Toxicity: Malaise, nausea, sulfonamide toxicity, reversible oligospermia.

Infectious

May involve any portion of the GI tract, usually the terminal ileum and colon. 

Skips  lesions, rectal sparing.

Transmural inflammation. Cobblestone mucosa, creeping fat, bowel wall thickening ("string sign" on barium swallow x-ray), linear ulcers, fissures, fistulas.

Non caseating granulomas and lymphoid aggregates

Stictures, fistulas, perianal disease, malabsorption, nutritional depletion.

Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, uveitis, immunologic disorders. 

For Crohn's think of a fat grannny and old crone skipping down a cobblestone road away from the wreck (rectal sparing)

Autoimmune

Colitis=colon inflammation. Continuous lesions always with rectal involvement. Mucosal and submucosal inflammation only. Friable mucosal pseudopolyps wiht freely hanging mesentary. Crypt abscesses and ulcers, bleeding, no granulomas. Severe stenosis, toxic megacolon, colorectal carcinoma. Pyoderma gangrenosum, first degree sclerosing cholangitis.

Mechanism: 5HT3 antagonist. Powerful central-acting antiemetic.

Clinical use: Control vomiting postoperatively and in patient undergoing cancer chemotherapy.

Toxicity: Headache, constipation.

You willl not vomit with ONDANSestron so you can go ON DANCing

Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. Overuse can also cause the following problems:

1. Aluminum hydroxide-constipation and hypophosphatemia

2. Magnesium hydroxide--diarrhea

3. Calcium carbonate--hypercalcemia, rebound acid increase

All can cause hypokalemia

Aluminimum amount of feces

Mg=Must go to the bathroom

Mildly decreased UDP-glucoronyl transferase. Asymptomatic, but unconjugated bilirubin is elevated without overt hemolysis. Associated with stress.

Gilbert's has no clinical consequences.

Absent UDP-glucuronyl transferase. APresents early in life; patietns die wtihin a few years.

Findings: jaundice, kernicterus (bilirubin deposition in brain), increased unconjugated bilirubin. 

Treatment: plasmapheresis and phototherapy. 

Crigler-Najjar type I is a severe disease. Type II is less severe and responds to phenobarbital.

Conjugated hyperbilirubinemia due to defective liver excretion. Grossly black liver. Benign.

Rotor's syndrome is similar but even milder and does not cause black liver. 

Conjugated/unconjugated

Increased urine bilirurbin

Normal or decreased urine urobilinogen

Conjugated

Increased urine bilirubin

Decreased Urine urobilinogen

Unconjugated

Absent acholuria urine bilirubin

Increased urine urobilinogen

Deposition of hemosiderin (iron). Classic triad of micronodular cirrhosis, pancreatic fibrosis and skin pigmentation (bronze diabees). Results in CHF and increased risk of hepatocellular carcinoma. May be first degree (autosomal recessive) or second degree due to chronic transfusion therapy.

Increased ferritin, increased iron, decreased TIBC, increased transferrin saturation. 

Total body iron may reach 50g , enough to set off metal detectors. 

Treat with repeated phlebotomy, deferoxamine. 

Swollen and necrotic hepatocytes, neutrophil infiltration. Mallory bodies (intracytoplasmic eosinophilic inclusions), fatty change and sclerosis around central vein. SGOT (AST) to SGPT (ALT) ratio usually >1.5.

A Scotch and Tonic

AST elevated (>ALT) with alcoholic hepatitis. ALT>AST in viral hepatitis. 

Diffuse fibrosis of the liver

Nodular regeneration

Micronodular--nodules <3 mm, uniform size. due to metabolic insult (eg alcohol, hemochromatosis, wilson's disease). 

Macronodular--nodules>3 mm, varied size. Usually due to signfiicant liver injury leading to hepatic necrosis (postinfectious or drug induced hepatitis). Increased risk of heptocellular carcinoma

Protacaval shunt between splenic vein adn left renal vein my relieve portal hhypertension

Coma

Scleral icterus

Fetor hepaticus (breath smells like a freshly opened corpse) 

Spider nevi

Gyneomastia

Jaundice

LOoss of sexual hair

Liver "flap" =asterixis (Coarse hand tremor)

Bleeding tendency (Decreased prothrombin and clotting factors) 

Anemia

Annkle edema

Esophageal varicies

Hematemesis

Peptic uulcer

Melena

Splenomegaly

Caput medusae

Ascites

Hemorrhoids

3rd most common cancer. Risk factors--colorectal villous adenomas, chronic inflammatory bowel disease (sepecially ulcerative colitis), high fat and low fiber diets, increased age, familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer 9HNPCC), DCC gene deletion, personal and family history of colon cancer.

Peutz-Jeghers, a benign polyposis syndrome is not a risk factor. Screen patietns >50 yearsold with stool occult blood test, colonoscopy. Visualized on barium swallow x-ray as "apple core" lesion. CEA-nonspecific tumor marker.

Conggenital megacolon characterized by lack of enteric nervous plexus in segment (Auerbach's and Meissner's plexuses) on intestinal  biopsy. due to failure of neural crest cell migration. Presetns as chronic constipation early in life. Dilated portion of the colon proximal to the aganglionic segment, resulting in a "transition zone."

Risk increased wiht Down syndrome

All age groups; most common indication for emergent abdominal surgery in children. Initial diffuse periumbilical pain-->localized pain at McBurney's point. Nausea, fever, may peforate-->peritonitis.

Differential: diverticulitis (elderly), ectopic pregnancy (use B-hCG to rule out)

Blind pouch leading off alimentary tract, lined by muscosa, muscularis and serosa, that communicates wiht the lumen of the gut. Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed "false" in that they lack or have an attenuated muscularis externa. Most often in sigmoid colon.

"True" diverticulum--all three gut layers will outpouch.

"False" diverticulum or pseudodiverticulum--only mucosa and submucosa outpouch. Occurs especially where vasa recta perforate muscularis externa

Pain Greater with meals--weight loss.

H. pylori infection in 70%; chronic NSAID use also implicated. Due to decreased mucosal protection against gastric acid. 

Pain Decreases with meals--weight gain.

Almost 100% have H. pylori infection.

Due to increased gastric acid secretion or decreased mucosal protection. 

Hypertrophy of Brumnner's glands.

Tend to ahve clean "punched-out" margins unlike raised/irregular margins of carcinoma. P

otential complications: bleeding, penetration, perforation and obstruction (not intrinsically precancerous).

H. pylori incection can be treated with "tripple therapy " (1. metronidazole, 2. bismuth salicylate and either 3. amoxicillin or tetracycline) with or without a proton pump inhibitor.

Incidence of peptic ulcer disease is twice as great in smokers. 

Risk factors:

Alcohol

Barrett's esophagus

Cigarrettes 

Diverticuli (Zenker's diverticulum)

Esophageal web (eg Plummer-Vinson)/Esophagitis (due to reflux, irritants, infection)

Familial

Usually squamous cell carcinoma (Barrett's leads to adenocarcinoma)

Glandular (columnar epithelial)  metaplasia--replacement of nonkeratinized squamous epithelium with gastric (columnar) epithelium in teh distal esophagus. Due to chronic acid reflux.

BARRett's=Becomes Adenocarcioma, Results from Reflux. 

Viral hepatitis (ALT>AST)

Alcoholic hepatitis (AST>ALT)

Myocardial infarction (AST only)

Amylase

Lipase

Ceruloplasmin (Decreased)

ACute pancreatitis, mumps

Acute pancreatitis

Wilson's disease

Failure of relaxation of lower esophageal sphincter due to loss of myenteric (Auerbach's) plexus.

Causes progressive dysphagia. Barium swallow shows dilated esophagus with area of distal stenosis. Associated with increased risk of esophageal carcinoma. 

SEcond deggree achalasia may arise from Chagas' disease

Bird beak on barium swallow

A-chalasia=absence of relaxation.

Abdominal structures enter the thorax; may occur in infants as a result of defective development of pleuroperitoneal membrane. Most commonly a hiatal hernia in which stomach herniates upward through the esophageal hiatus of the diaphragm.

PRotrudes through inguinal (Hesselbach's) triangle. Direct hernia bulges directly through abdominal wall medial to inferior epigastric artery. Goes through external (superficial) inguinal ring only. Usulaly in older men.

MDs don't LIe

Medial to inferior epigastric artery=Direct hernia

Lateral to inferior epigastric artery=Indirect hernia

Inferior epigastric artery

Lateral border of rectus abdominis

Inguinal ligament

Composed of bile salts (bile acids conjugated to glycine or taurine to make them water soluble) phospholipids, cholesterol, bilirubin, water and ions.

Only significant mechanism for cholesterol excretion.

PRoduct of heme metabolism. Actively taken up by hepatocytes. Direct bilirubin-conjugated with glucoronic acid, water soluble. Indirect bilirubin--unconjugated, water insoluble.

Red blood cells (80%) heme catabolism in reticuloendothelial system

Bilirubin prpoduced from noonerythroid enzymes in liver (20%)

Renal excretion fo urobilirubin (4 mg/day)

Bacterial conversion to urobilinogen primarily in colon

some excretion as stercobilin in feces (gives stool dark color)