Gastrointestinal pathology

-Generally benign; often in parotid gland

• -Pleomorphic adenoma (most common tumor; painless, movable mass, benign with high rate of recurrence)
• -stromal (e.g. cartilage) and epithelial tissue
• -most commonly in the parotid
• -rarely may transform into CA

• -Warthin's tumor (benign, heterotropic salivary gland tissue trapped in a LN, surrounded by lymphatic tissue)
• -Always in the parotid

• -Mucoepidermoid carcinoma (most common malignant)
• -mucinous and squamous cells
• -parotid; commonly involves CNVII

• Inflammation of salivary gland
• most commonly due to obstructing stone: sialolithiasis leading to S. aureus infection
• Usually unilateral

• Infection with mumps virus results in bilateral inflamed parotid glands.
• -as well as orchitis, pancreatitis, and aseptic meningitis

Full thickness defect of lip or palate

Cause: failure of facial prominences to fuse (five)

Usually occur together; isolated occurrences are less common

• aka Canker sore
• Painful, superficial ulcer of the oral mucosa
• Related to stress, resolve spontaneously

• Triad:
• 1. Recurrent aphthous ulcers
• 2. Genital ulcers
• 3. Uveitis

• Etiology: unknown
• -due to immune complex vasculitis involving small vessels

• aka cold sores
• Vesicles involving oral mucosa that rupture → shallow, painful, red ulcers
• Usually due to HSV-1
• Virus remains dormant in ganglia of trigeminal nerve; come out after stress, sunlight

Risk factors: smoking, alcohol

• Presentation:
• -floor of the mouth is most common

• Pathophysiology:
• 1. Leukoplakia: white plaque that cannot be scrapped away (unlike candidiasis) that often represents squamous cell dysplasia
• 2. Erythroplakia (red plaque) represent vascularized leukoplakia (highly suggestive of squamous cell dysplasia)

aka globus hystericus and globus pharyngis

• -feeling of having a 'lump' in on'es throat without clinical or radiographic evidence
• -often triggered by strong emotion; benign

• -Achalasia = absence of relaxation
• -Failure of relaxation of LES due to loss of myenteric (Auerbach's) plexus.

• -high opening pressure and uncoordinated peristalsis → progressive dysphagia to solid and liquids
• -Barium swallow shows dilated esophagus with an area of distal stenosis
• 
• -("bird's beak")

-Increased risk of esophageal CA

• -Secondary achalasia may arise from Chagas' disease (infection with Trypanosoma cruzi)
• -Scleroderma (CREST syndrome) is associated with esophageal dysmotility involveing low pressure proximal to LES

• Sx:
• -Dysphagia for solids and liquids
• -Putrid breath
• -High LES pressure
• -"Bird'beak" sign on barium swallow study
• -increase risk for esophageal Squamous cell CA

• Gastroesophageal reflux disease (GERD)
• Esophageal varices
• Esophagitis
• Mallory-Weiss syndrome
• Boehaave syndrome
• Esophageal strictures
• Plummer-Vinson syndrome
• Zenker diverticulum
• Esophageal carcinoma

• Presentation:
• -heartburn
• -asthma (adult-onset) and cough
• -regurgitation upon lying down
• -damage to enamel of teeth
• -nocturnal cough and dyspnea
• -ulceration with strictures and Barrett's esophagus (late complications)

• Pathophysiology:
• -reduced LES tone

• Risk factors:
• -alcohol
• -tobacco
• -obesity
• -fat-rich diet
• -caffeine
• -hiatal hernias

-Dilated submucosal veins in the lower esophagus

• -Painless bleeding of submucosal veins in lower 1/3 of esophagus
• -Painless hematemesis

• Etiology: arise secondary to portal hypertension
• -**Most common cause of death in cirrhosis (bleeding + coagulopathy)

• Associated with reflux, infection:
• -HSV-1: punched out culcers;
• -CMV: linear ulcers;
• -Candida: white pseudomembrane

or chemical ingestion

• Congenital defect resulting in connection between esophagus and trachea
• 

• Presentation:
• -Vomiting
• -Polyhydramnios
• -Abdominal distension
• -Aspiration

• Mucocal (Longitudinal) lacerations at the GE junction due to severe vomiting
• -leads to painful hematemesis

Found in alcoholics and bulimics

Risk of Boerhaave syndrome: rupture of esophagus leading to air in mediastinum and subcutaneous emphysema

Outpouching of pharyngeal mucosa through an acquired defect in the muscular wall (false diverticulum)

-Arises above the UES at the junction of the esophagus and pharynx

• Presentation: dysphagia, obstruction, halitosis
• -often asymptomatic

• -Transmural esophageal rupture due to violet retching;
• -leads to air in the mediastinum → subcutaneous emphysema

"Been-heaving Syndrome"

Associated with lye ingestion and acid reflux

Thin protrusion of esophageal mucosa, most often upper esophagus

• Presentation:
• -dysphagea for poorly chewed food

• -increased risk for esophageal squamous cell carcinoma
• -Plummer-Vinson syndrome**

• Triad of:
• 1. Dysphagia (due to esophageal webs)
• 2. Glossitis - beefy-red tongue due to atrophic glossitis
• 3. Iron deficiency anemia

• Gradual metaplasia in the distal esophagus:
• -replacement of nonkeratinized (stratified) squamous epithelium → intestinal (columnar) epithelium with goblet cells

• Etiology:
• 1. Chronic acid reflux (GERD)
• -10% of patients with GERD
• -Associated with esophagitis, esophageal ulcers, and increased risk of esophageal adenocarcinomas
• 

• Presentation: progressive dysphagia (first solids, then liquids) and weight loss; pain, hematemesis
• -Poor prognosis; present late

• Risk factors:
• 1. Squamous cell carcinoma (upper 2/3rds of esophagus)
• -Alcohol/Achalasia
• -Cigarettes
• -esophageal web
• -esophageal injury (lye ingestion)
• -Very hot tea

• 2. Adenocarcinoma (lower 1/3 of esophagus)
• -Barrett's esophagus/GERD
• -Esophageal web/Esophagitis
• -Diverticular (e.g. Zenker's)

*The esophagus is a SAC on A BED

• Worldwide: SCC > adenocarcinoma
• US: adenocarcinoma > SCC

• LN spread:
• -Upper 1/3 → cervical nodes
• -Middle 1/3 → mediastinal or tracheobronchial nodes
• -Lower 1/3 → celiac and gastric nodes

• -Tropical sprue
• -Whipple's disease
• -Celiac sprue
• -Disaccharidase deficiency
• -Abetalipoproteinemia
• -Pancreatic insufficiency

These Will Cause Devistating Absorption Problems

• Sx:
• -diarrhea
• -steatorrhea
• -weight loss
• -weakness

• Probably infectious; responds to Abx
• Similar to celiac sprue, but can affect entire small bowel

• Infection with Tropheryma whippelii (gram positive)
• -PAS+ foamy macrophages in intestinal lamina propria, mesenteric nodes

• Presentation:
• -diarrhea, steatorrhea, weight loss, weakness
• -Arthralgias, cardiac and neurologic symptoms are common
• -Most often occurs in older men

• Foamy Whipped cream in a CAN:
• -Foamy (PAS+) macrophages
• -Cardiac symptoms
• -Arthralgias
• -Neurologic symptoms

• Autoimmune-mediated intolerance of gliadin (gluten) in wheat and other grains → steatorrhea
• Proximal small bowel primarily (↓ mucosal absorption that primarily affects jejunum)

Epidemiology: European descent

• Findings:
• -antibodies to gliadin
• -antibodies to tTG (tissue transglutaminase)
• -blunting of villi
• -Lymphocytes in the lamina propria
• 
• -(blunting of villi and crypt hyperplasia)

• Association: Dermatitis herpetiformis
• -Moderately increased risk of malignancy (T-cell lymphoma)

Most common lactase deficiency → milk intolerance

• Presentation:
• -Nl appearing villi
• -Osmotic diarrhea

-since lactase is located at tips of intestinal villi, self-limited lactase deficiency can occur following injury (i.e. viral diarrhea)

• Lactose tolerance test: positive for lactase deficiency if:
• 1. Administration of lactose produces sx, and
• 2. Glucose rises <20mg/dL

• ↓ synthesis of apo B:
• → inability to generate chylomicrons → ↓ secretion of cholesterol, VLDL into bloodstream → fata accumulation in enterocytes

-presents in early childhood (with malabsorption and neurologic manifestations)

• Etiology:
• -Cystic fibrosis
• -obstructing cancer
• chronic pancreatitis

Causes malabsorption of fat and fat-soluble vitamins (vitamins A, D, E, K)

↑ neutral fat in stool

• Gastritis (acute and chronic)
• Gastroschisis
• Omphalocele
• Pyloric stenosis
• Peptic ulcer disease
• Gastric carcinoma

• Acute gastritis (erosive)
• Chronic gastritis (non-erosive)
• -Type A (fundus/body)
• -Type B (antrum)

Disruption of mucosal barrier → inflammation, damage to stomach mucosa

• Causes:
• -stress
• -NSAIDs (↓PGE2 → ↓gastric mucosa protection)
• -Alcohol
• -Uremia
• -Burns (Curling's ulcer: ↓plasma volume → sloughing of gastric mucosa)
• -Brain injury causing increased intracranial pressure (Cushing's ulcer: ↑ vagal stimulation →↑ ACh →↑H+ production)
• -Chemotherapy

• *Burned by the Curling iron.
• *Always Cushion the brain

• Type A (fundus/body)
• -Autoimmune disorder characterized by: Autoantibodies to parietal cells, pernicious Anemia, and Achlorhydria (low acid production) with increased gastrin levels and antral G-cell hyperplasia
• -Type IV hypersensitivity (T cell mediated disease)
• -Increased risk for gastric adenocarcinoma (intestinal type)

AB pairing - pernicious Anemia affects gastric Body

• Type B (antrum)
• -most common type; caused by H. pylori infection
• -abdominal pain, increased risk for gastric adenocarcinoma
• -↑ risk of MALT lymphoma

*H. pylori Bacterium affects Antrum

• Congenital malformation of anterior abdominal wall
• →exposure of abdominal contents
• 

Persistent herniation of bowel into umbilical cord

• -Failure of intestines to return to the body cavity during development
• -Contents covered by peritoneum and amnion of the umbilical cord

• -Gastric hypertrophy with protein loss
• -Parietal cell atrophy
• -↑ mucous cells
• -Precancerous
• -Rugae of stomach are so hypertrophied that they look like brain gyri

• Congenital hypertrophy of pyloric smooth muscle
• ♂ > ♀

• Presentation: two weeks after birth
• 1. projectile nonbilious vomiting
• 2. Visible peristalsis
• 3. Olive-like mass in the abdomen (on physical exam)

Tx: myotomy

Solitary mucosal ulcer involving:

• 1. Proximal duodenum (90%)
• -of which, >95% is due to H. pylori
• -rarely due to ZE syndrome
• Presentation:
• -pain that improves with meals
• -hypertrophy of Brunner glands
• -rupture may lead to bleeding from the gastroduodenal artery
• -Anterior ulcer more common
• -almost never malignant

• 2. Distal stomach (10%)
• -Usually H. pylori (75%); other causes include NSAIDs and bile reflux (decreased mucosal protection)
• Presenation:
• -Pain that worsens with meals
• -Rupture caries risk of bleeding from Left gastric artery
• -Can be caused by gastric CA (intestinal subtype)
• -Benign: punched-out, <3cm, 
• -Malignant: large, irregular, heaped up margins

• Tx: triple therapy
• 1. PPI
• 2. Clarithromycin
• 3. Amoxicillin

• Complications:
• -Hemorrhage --Gastric, duodenal (posterior > anterior)
• -Perforation -- Duodenal (anterior > posterior)

• Adenocarcinoma most common
• -early aggressive local spread and node/liver mets
• -association with dietary nitrosamines (smoked foods), achlorhydria (low acid production), chronic gastritis, type A blood
• -Often presense with acanthosis nigricans

• Intestinal type: more common
• -large, irregular ulcer with heaped up margins
• -resembles colonic adenocarcinoma
• -most commonly involves lesser curvature of the antrum (similar to gastric ulcer)
• -Risk factors: intestinal metaplasia due to H. pylori and autoimmune gastritis, nitrosamines in smoked food

• Diffuse type:
• -signet ring cells that diffusely infiltrate the gastric wall
• -grossly thickened and leathery (linitis plastica)
• 

Virchow's node: involvement of left supraclavicular node by mets from stomach

• Krukenberg's tumor: bilateral mets to ovaries
• -Abundant mucus, signet ring cells

Sister Mary Joseph's nodule: subcutaneous periumbilical metastasis

• Hemorrhage:
• -Gastric, duodenal (posterior > anterior)
• -Rupture gastric ulcer on the lesser curvature of the stomach → bleeding from left gastric artery
• -Posterior wall of duodenum → bleeding from gastroduodenal artery)

• Perforations:
• -Duodenal (anterior > posterior)

• Full-thickness inflammation with knife-like fissures (transmural)
• Location: anywhere; skip lesions; terminal ileum, skips the rectum
• Sx: RLQ pain, non-bloody diarrhea
• Inflammation: lymphooid aggregates with granulomas
• Gross appearance: Cobblestone mucosa, creeping fat, strictures
• Complications: Malabsorption, fistula formation, carcinoma, calcium oxalate nephrolithiasis, strictures
• Association: Ankylosing spondylitis, migratory polyarthritis, erythema nodosum, uveitis, 
• Smoking: increases risk
• Tx: corticosteroids, azathioprine, methotrexate, infliximab, adalimumab

• Mucosal and submucosal ulcers
• Location: begins in rectum and extends proximally up to the cecum (at most); continuous
• Sx: LLQ pain, bloody diarrhea
• Inflammation: Crypt abscesses with neutrophils
• Gross appearance: Friable pseudopolyps; loss of houastra ("lead pipe" sign on imaging)
• Complications: toxic megacolon and carcinoma; carcinoma
• Associations: Primary sclerosing cholangitis and p-ANCA
• Smoking: protective!
• Tx: ASA preparations (sulfasalazine), 6-mercaptopurine, infliximab, colectomy

• Recurrent abdominal pain associated with ≥ 2 of the following:
• -Pain improves with defecation
• -Change in stool frequency
• -Change in appearance of stool

• No structural abnormalities
• Most common in  middle-aged women
• Chronic symptoms
• Presentation: diarrhea, constipation, alternating sx

• Acute inflammation of the appendix due to obstruction by fecalith (adults) or lymphoid hyperplasia (children)
• Initial diffuse periumbilical pain, migrates to McBurney's point
• Presentation: nausea, fever
• Complication: perforation → peritonitis
• Differential: diverticulitis (elderly), ectopic pregnancy (check β-hCG)
• Tx: appendectomy

• Blind pouch protruding from the alimentary tract that communicates with the lumen of the gut
• Most are "false" (esophagus, stomach, duodenum, colon) and are acquired
• Most often in sigmoid colon

• only mucosa and submucosa outpouch
• lack the muscularis externa
• Occurs especially where vasa recta perforate muscularis externa

• All 3 gut wall layers outpouch
• e.g., Meckel's diverticulum

• Many false diverticula
• Common (50% of all people > 60 years)
• Cause: ↑ intraluminal pressure and focal weakness in colonic wall
• Associated with low-fiber diets
• Most often in sigmoid colon
• Presentation: asymptomatic, or associated with vague discomfort
• Common cause of hematochezia (fresh blood passed through anus)
• Complications: diverticulitis, fistulas

• Inflammation of diverticula
• Classic presentation: LLQ pain, fever, leukocytosis
• Labs: stool occult blood is common; +/- hematochezia
• Complication: perforate → peritonitis, abscess formation, bowel stenosis; colovesical fistula (fistula with bladder) →pneumaturia (passage of air or gas in the urine)
• Tx: antibiotics

• False diverticulum
• Herniation of mucosal tissue at Killian's triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor
• Presentation: halitosis, dysphagia, obstruction

• True diverticulum
• Persistence of the vitelline duct
• May contain ectopic acid-secreting gastric mucosa and/or pancreatic tissue
• *Most common congenital anomaly of the GI tract
• Complication/presentation: melena, RLQ pain, intussusception, volvulus, or obstruction near terminal ileum
• Differentiate: omphalomesenteric cyst (cystic dilation of vitelline duct)
• Dx: pertechnetate study for ectopic uptake

• 2 inches long
• 2 feet from the ileocecal valve
• 2% of population
• Presents within the first 2 years of life
• May have 2 types of peithelia (gastric/pancreatic)

• Telescoping of 1 bowel segment into distal segment
• Commonly at the ileocecal junction
• "Current jelly" stools
• Complication: compromise blood supply (abdominal emergency)
• Unusual in adults: think intraluminal mass or tumor
• Most occur in children (idiopathic)

• Twisting of portion of bowel around its mesentery
• Complication: obstruction and infarction
• Common at cecum and sigmoid colon, where there is redundant mesentery
• Usually in elderly

Congenital megacolon: lack of ganglion cells/enteric nervous plexus (Auerbach's and Meissner's plexus)

• Cause:
• failure of neural crest cell migration

• Presentation:
• -chronic constipation early in life
• -Dilated portion of colon proximal to the aganglionic segment ("transition zone")
• -Involves rectum
• -Usually fail to pass mechonium

**Think of Hirschsprung's as a giant spring that has sprung in the colon

↑ risk with Down syndrome

• Dx: rectal suction biopsy
• Tx: resection

• Causes early bilious vomiting with proximal stomach distention ("double-bubble" on X-ray)
• Failure of recanalization of small bowel
• Associated with down syndrome

• In Cystic fibrosis:
• meconium plug obstructs intestine
• prevents stool passage at birth

• Necrosis of intestinal mucosa and possible perforation
• Colon is usually involved; can involve entire GI tract
• Neonate: more common in preemies (↓ immunity)

• Reduction in intestinal blood flow causes ischemia (pain out of proportion with physical findings)
• Pain after eating → weight loss
• Commonly occurs at splenic flexure and distal colon
• Typically affects elderly

• Fibrous band of scar tissue
• Commonly forms after surgery
• Most common cause of small bowel obstruction
• Can have well-demarcated necrotic zones

• Tortuous dilation of vessels → hematochezia
• Most often found in cecum, terminal ileum, ascending colon
• More common in older patients
• Confirmed by angiography

• Masses protruding into gut lumen → sawtooth appearance
• 90% are non-neoplastic
• Often rectosigmoid
• Can be tubular or villous

• Tubular adenoma
• Smaller, more rounded, more likely to be benign

• Villous adenoma
• Long, finger-like projections

• Precancerous - precursor to colorectal cancer
• Malignant risk is associated with ↑ size, villous histology, ↑ epithelial dysplasia
• **More villous → more likely to be malignant (villous = villainous)
• Polyp symptoms - often asymptomatic, lower GI bleed, partial obstruction, secretory diarrhea

Most common non-neoplastic polyp in colon (>50% found in rectosigmoid colon)

• Mostly sporadic lesions in children <5 years of age
• If single, no malignant potential
• Jvenile polyposis syndrome: multiple juvenile polyps in GI tract; ↑ risk of adenocarcinoma

• Single polyps are not malignant
• Peutz-Jeghers syndrome:
• -Autosomal dominant syndrome featuring multiple nonmalignant hamartomas throughout GI tract
• -Hyperpigmented mouth, lips, hands, genetalia
• -Associated with ↑ risk of CRC and other visceral malignancies

• Epidemiology:
• -3rd most common cancer
• -3rd most deadly in US
• -Most pts >50 years of age
• -25% have a family history

• Risk factors:
• -Genetics
• -IBD
• -tobacco use
• -large villous adenomas
• -juvenile polyposis syndrome
• -Peutz-Jeghers syndrome

• Familial adenomatous polyposis (FAP):
• -Autosomal dominant
• -mutation of APC gene on chrom 5q
• -2-hit hypothesis
• -100% progression to CRC
• -Thousands of polyps; pancolonic; always involves rectum

• Gardner's syndrome:
• -FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium

• Turcot's syndrome:
• -FAP + malingant CNS tumor
• **Turcot = Turban

• Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome):
• -Autosomal dominant mutation of DNA mismatch repair genes
• -80% progress to CRC
• -Proximal colon is always involved

• Rectosigmoid > ascending > descending
• Ascending: exophytic mass, iron deficiency, anemia, weight loss
• Descending: infiltrating mass, partial obstruction, colicky pain, hematochezia
• Rarely presents as Streptococcus bovis bacteremia

• Iron deficiency anemia in males (especially >50 years of age) and postmenopausal females raises suspicion
• Screen patients > 50 years of age with colonoscopy or stool occult blood test
• "Apple core" lesion seen on barium enema x-ray
• 
• CEA tumor marker; good for monitoring recurrence not useful for screening

• 1. Microsatalite instability pathway (15%)
• -DNA mismatch repair gene mutations → sporadic and HNPCC syndrome
• -Mutations accumulate, but no defined morphologic correlates

• 2. APC/β-catenin (chromosomal instability) pathway) (85%):
• 
• **Order of gene events - AK-53

• Tumor of neuroendocrine cells
• Constitute 50% of small bowel tumors; most common malignancy in the small intestine
• Most common sites: appendix, ileum, rectum
• "Dense core bodies" seen on EM
• Often produce 5-HT, which can lead to carcinoid syndrome

• Presentation:
• -wheezing
• -right-sided heart murmurs
• -diarrhea
• -flushing

• Tumor location:
• -Tumor confined to GI system, no carcinoid syndrome is observed, since liver metabolizes 5-HT
• -If tumor or metastases (usually to liver) exists outside GI system, carcinoid syndrome is observed

• Tx:
• -resection
• -octreotide
• -somatostatin

• Diffuse fibrosis and nodular regeneration destroys normal architecture of liver
• Increased risk for hepatocellular carcinoma
• Etiologies: alcohol (60-70%), viral hepatitis, biliary disease, hemochromatosis

• Gut: Esophageal varicies
• Butt: hemroids 
• Caput: Caput medusae

• Esophageal varices → hematemesis
• Peptic ulcer → melena
• Splenomegaly
• Caput medusae, ascites
• Portal hypertensive gastropathy
• Hemorrhoids

• Coma
• Scleral icterus
• Fetor hepaticus (breath smells musty)
• Spider nevi
• Gynecomastia
• Jaundice
• Testicular atrophy
• Liver "flap" - asterixis (coarse hand tremor)
• Bleeding tendency (↓ clotting factors, ↑ prothrombin time)
• Anemia
• Ankle edema

• Aminotransferases (AST and ALT):
• -Viral hepatitis (ALT > AST)
• -Alcoholic hepatitis (AST > ALT)

• Alkaline phosphatase (ALP):
• -Obstructive liver disease (hepatocellular carcinoma)
• -bone disease
• -bile duct disease

• γ-glutamyl transpeptidase (GGT):
• -↑ in various liver and biliary diseases like ALP, but not in bone disease

Amylase: Acute pancreatitis, mumps

Lipase: Acute pancreatitis

Ceruloplasmin: ↓ in Wilson's disease

• Rare, often fatal childhood hepatoencephalopathy
• Findings:
• -mitochondrial abnormalities
• -fatty liver (microvesicular fatty change)
• -hypoglycemia
• -vomiting
• -hepatomegaly
• -coma

Associated with viral infection (especially VZV and influenza B) that has been treated with aspirin

• Mechanism:
• -Aspirin metabolites ↓ β-oxidation by reversible inhibition of mitochondrial enzyme

**Avoid aspirin in children, except those with Kawasaki's disease

• Hepatic steatosis (fatty liver disease)
• Alcoholic hepatitis
• Alcoholic cirrhosis

• Short-term change with moderate alcohol intake
• Macrovesicular fatty change that may be reversible with alcohol cessation
• 

• Requires sustained, long-term consumption
• Swollen and necrotic hepatocytes with neutrophilic infiltration
• Mallory bodies (intracytoplasmic eosinophilic inclusions) are present
• AST > ALT (ratio usually >1.5)

• Final, irreversible form
• Micronodular, irregularly shrunken liver with "hobnail" appearance
• Sclerosis around central vein (zone III)
• Has manifestations of chronic liver disease (e.g., jaundice, hypoalbuminemia)

• Most common 1° malignant tumor of the liver in adults
• Risks: hepatitis B and C, Wilson's disease, hemochromatosis, α₁-antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (e.g., aflatoxin from Aspergillus)
• Findings: jaundice, tender, hepatomegaly, ascites, polycythemia, and hypoglycemia
• -Commonly spread by hematogenous dissemination
• -↑ α-fetoprotein
• -*May lead to Budd-Chiari syndrome

• Cavernous hemangioma:
• -Common, benign liver tumor
• -Typically occur at age 30-50 years
• -Biopsy contraindicated because of risk of hemorrhage

• Hepatic adenoma:
• -Benign liver tumor
• -often related to oral contraceptive or steroid use
• -can regress spontaneously
• -risk of rupture in pregnancy

• Angiosarcoma:
• -Malignant tumor of endothelial origin
• -Associated with exposure to arsenic, polyvinyl chloride

• Due to backup of blood into liver
• Commonly caused by right-sided heart failure and Budd-Chiari syndrome
• The liver appears mottled like a nutmeg
• Persistence: centrilobular congestion and necrosis can result in cardiac cirrhosis

• Occlusion of IVC or hepatic veins with centrilobular congestion and necrosis, leading to congestive liver disease (hepatomegaly, ascites, abdominal pain, and eventual liver failure)
• May develop varices and have visible abdominal and back veins
• Absence of JVD
• Associated with hypercoagulable state, polycythemia vera, pregnancy, and hepatocellular carcinoma

• -Misfolded gene product:
• -Protein aggregates in hepatocellular ER → cirrhosis with PAS + globules in liver
• -Lungs: lack of functioning enzymes → ↓ elastic tissue → panacinar emphysema
• -Codominant trait

Yellow skin and/or sclerae resulting from elevated bilirubin

• Caused by:
• -Direct hepatocellular injury
• -Obstruction to bile flow
• -Hemolysis

• Hyperbilirubinemia: direct/indirect
• ↑ Urine bilirubin
• Normal or ↓ urine urobilinogen

• Hyperbilirubinemia: direct
• ↑ Urine bilirubin
• ↓ urine urobilinogen

• Hyperbilirubinemia: indirect
•  Absent (acholuria) urine bilirubin
• ↑ urine urobilinogen

• At birth, immature UDP-glucuronyl transferase → unconjugated hyperbilirubinemia → jaundice/kernicterus
• Treatment: phototherapy (converts UCB to water-soluble form)

• Gilbert's syndrome
• Criger-Najjar syndrome, type I
• Dubin-Johnson syndrome

• Mildly ↓ UDP-glycuronyl transferase or ↓ bilirubin uptake
• Asymptomatic
• Elevated unconjugated bilirubin without overt hemolysis
• Bilirubin increases with fasting and stress
• *No clinical consequences

• Absent UDP-glucuronyl transferase
• Presents early in life; pts die within a few years
• Findings: jaundice, kernicterus (bilirubin deposition in brain), ↑ unconjugated bilirubin
• Treatment: plasmapheresis and phototherapy
• *Type II is less severe and responds to phenobarbital, which ↑ liver enzyme synthesis

• Conjugated hyperbilirubinemia due to defective liver excretion
• Grossly black liver
• Benign
• Rotor's syndrome: same; mild, no black liver

• 1. Gilberts = problem with bilirubin uptake → unconjugated bilirubinemia
• 2. Crigler-Najjar = problem with bilirubin conjugation → unconjugated bilirubinemia
• 3. Dubin-Johnson = problem with excretion of conjugated bilirubin → conjugated bilirubinemia

• -Inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmin
• -Leads to copper accumulation, especially in liver, brain, cornea, kidneys, and joints

• Characterized by: **Copper is Hella BAD"
• -Ceruloplasmin ↓, Cirrhosis, Corneal deposits (Kayser-Fleischer rings), Copper accumulation, Carcinoma (hepatocellular)
• 

• -Hemolytic anemia
• -Basal ganglia degeneration (parkinsonian symptoms)
• -Asterixis
• -Dementia, Dyskinesia, Dysarthria

• Treatment:
• -Penicillamine

• -Autosomal-recessive inheritance (chromosomal 13)
• -Copper is normally excreted into bile by hepatocyte copper transporting ATPase (ATP7B gene)

• Hemosiderosis is the deposition of hemosiderin (iron)
• Hemochromatosis is the disease caused by this deposition - *Can Cause Deposits

• Triad:
• -micronodular Cirrhosis
• -Diabetes mellitus
• -Bronze skin pigmentation ("Bronze" diabetes)

• -Results in CHF
• -testicular atrophy in males
• -↑ risk of hepatocellular carcinoma

• 1°: Autosomal recessive - C282Y or H63D mutation on HFE gene. 
• -Associated with HLA-A3

2°: chronic transfussion therapy (e.g., β-thalassemia major)

• Labs:
• ↑ ferritin, ↑ iron, ↓ TIBC → ↑ transferrin saturation

• Treatment:
• - repeated phlebotomy
• - deferasirox
• - deferoxamine

• Pathophysiology:
• -Autoimmune reaction → lymphocytic infiltrate + granulomas

• Presentation:
• -Pruritus
• -Jaundice
• -Dark urine
• -light stools
• -hepatosplenomegaly

• Labs:
• -↑ conjugated bilirubin
• -↑ cholesterol
• -↑ alkaline phosphate

• Additional information:
• -↑ serum mitochondrial antibodies, including IgM
• -Associated with other autoimmune conditions (e.g., CREST, RA, celiac disease)

• Pathophysiology/pathology:
• -Extrahepatic biliary obstruction (gallstone, biliary stricutre, chronic pancreatitis, carcinoma of the pancreatic head)
• → ↑ pressure in intrahepatic ducts → injury/fibrosis and bile stasis

• Presentation: same
• -Pruritus
• -Jaundice
• -Dark urine
• -light stools
• -hepatosplenomegaly

• Labs:
• -↑ conjugated bilirubin
• -↑ cholesterol
• -↑ alkaline phosphate

• Additional information:
• -Complicated by ascending cholangitis

• Pathophysiology/pathology:
• -Unknown cause of concentric "onion skin" bile duct fibrosis → alternating strictures and dilation with "beading" of intra- and extrahepatic bile ducts on ERCP

• Presentation:
• -Pruritus
• -Jaundice
• -Dark urine
• -light stools
• -hepatosplenomegaly

• Labs:
• -↑ conjugated bilirubin
• -↑ cholesterol
• -↑ alkaline phosphate

• Additional information:
• -Hypergammaglobulinemia (IgM)
• -Associated with ulcerative colitis
• -Can lead to 2° biliary cirrhosis

• Risk factors:
• ↑ cholesterol and/or bilirubin
• ↓ bile salts
• gallbladder stasis
• 

• Dx:
• -ultrasound
• -radionuclide biliary scan (HIDA)

• Tx:
• -Cholecystectomy

• Female
• Fat
• Fertile (estrogen)
• Forty

• 80% of stones
• Radiolucent with 10-20% opaque due to calcifications
• Associated with: obesity, Crohn's disease, cystic fibrosis, advanced age, clofibrate, estrogens, multiparity, rapid weight loss, Native Americans

• Radiopaque
• Seen in pts with chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infection
• Black: hemolysis
• Brown: infection

• Cholecystitis
• Ascending cholangitis
• Acute pancreatitis
• Bile stasis
• Biliary colic: neurohormonal activation (e.g., by CCK after a fatty meal) triggers contraction of the gallbladder, forcing stone into cystic duct
• -Presentation: +/- pain (e.g. diabetics)
• Fistula between gallbladder and small intestine, leading to air in the biliary tree
• -obstruction of the ileocecal valve, air can be seen in biliary tree on imaging

• Jaundice
• Fever
• RUQ pain (positive Murphy's sign: inspiration arrest on deep RUQ palpation due to pain)

• Inflammation of gallbladder
• Usually from gallstones
• rarely ischemia or infectious (CMV)
• ↑ alkaline phosphatase if bile duct becomes involved (e.g., ascending cholangitis)

Autodigestion of pancreas by premature activation of pancreatic enzymes

• Causes: **GET SMASHED
• Gallstones
• Ethanol
• Trauma
• Steroids
• Mumps
• Autoimmune disease
• Scorpion sting
• Hypercalcemia/Hyperglyceridemia (>1000)
• ERCP
• Drugs (e.g., sulfa drugs)

• Presentation:
• -epigastric abdominal pain radiating to back
• -Anorexia
• -Nausea

• Labs:
• -elevated amylase, lipase (higher specificity)

• Complications:
• -DIC
• -ARDS
• -Diffuse fat necrosis
• -hypocalcemia (Ca2+ collects in pancreatic calcium soap deposits)
• -Pseudocyst formation
• -Hemorrhage
• -infection
• -multiorgan failure
• -pancreatic pseudocysts (lined by granulation tissue, not epithelium; can rupture and hemorrhage)

• Chronic inflammation, atrophy, calcification of the pancreas
• Causes: alcohol abuse and idiopathic
• Complication: lead to pancreatic insufficiency → steatorrhea, fat-soluble vitamin deficieency, diabetes mellitus, and ↑ risk of pancreatic adenocarcinoma
• Amylase and lipase are less elevated (compared to levels in acute pancreatitis)

• Prognosis: ≤6 months
• Arises from pancreatic ducts; usually metastisized at presentation
• More common in pancreatic head (→ obstructive  jaundice)
• Associated with CA-19-9 tumor marker (also CEA, less specific)

• Tobacco use (but not EtOH)
• Chronic pancreatitis (especially > 20 years)
• Age > 50 years
• Jewish and African-American males

• Presentation:
• -Abdominal pain radiating to back
• -Weight loss (due to malabsorption and anorexia)
• -Migratory thrombophlebitis: redness and tenderness on palpation of extremities (Trousseau's syndrome)
• -Obstructive jaundice with palpable, nontender gallbladder (Courvoisier's sign)

• Treatment:
• -Whipple procedure
• -Chemotherapy
• -Radiation therapy