• Full thickness defect of lip or alate
• Due to failure of facial prominences to fuse
• during early pregnancy, facial prominences (one from superior, two from the sides, and two from inferior) grow and fuse together to  form the face
• Clef lip and palate usually occur together
• isolated cleft lip or palate is less common

• painful, superficial ulceration of the oral mucosa
• Arises in relation to stress and resolves spon, but often recurs
• Char. by a grayish base surrounded by erythema

• Recurrent apthous ulcers, genital ulcers, and uveitis
• Due to immune complex vasculitis involving small vessels
• can be seen after viral infection, but etiology is unkown

• Vesicles involving oral mucosa that rupture, resulting in shallow, painful, red ulcers
• usually due to HSV-1
• primary infection occurs in childhood; lesions heal, but virus remains dormant in ganglia of the trigeminal nerve
• Stress and sunlight-->reactivation of the virus-->vesicles that often aris on the lips (cold sores)

• Malignant neoplasm of squamous cells lining the oral mucosa
• tobacco and alcohol are major risk factors
• floor of mouth is the most common location
• oral leukoplakia

1. Leukoplakia is a white plaque that cannot be scraped away; often represents squamous cell dysplasia
2. Leukoplakia is distinct from oral candidiasis (thrush) and hairy leukoplakia
3. Oral candidiasis is a white deposit on the tongue, which is easily scraped away, usually seen in immunocompromised states
4. Hairy leukoplakia is a white rough "hairy" patch that arises on the lateral tongue.  It is usually seen in immunocomporomise individuals (AIDS) and is due to EBV-induced squamous cell hyperplasia; not pre-malignant
5. Erythroplakia (red plaque) represents vascularized leukoplakia and is highly suggestive of squamous cell dysplasia
6. Erythroplakia and leukoplakia are often biopsied to rule out carcinoma

• exocrine glands that secrete saliva
• Divided into major (parotid, submandibular, and sublingual glands) and minor glands (hundreds of microscopic glands distributed throughout the oral mucosa)

• Infection resulting in bilateral inflamed parotid glands
• Orchitis, pancreatitis, and aseptic meningitis may also be present
• Serum amylase is increased b/c of salivary gland or pancreatic involvement
• ORchitis carries risk of sterility, especially in teenagers

• Inflammation of the salivary gland
• Most commonly due to an obstructing stone (sialolithiasis) leading to S. aureus infection; usually unilateral

• Benign tumor composed of stromal (Ex cartilage) and epithelial tissue; most common tumor of the salivary gland
• Usually arises in parotid; presents as a mobile, painless, circumscribed mass at the angle of the jaw
• High rate of recurrence, extension of small islands of tumor through tumor capsule often leads to incomplete resection
• Rarely may transform into carcinoma, which presents with signs of facial nerve damage (facial nerve runs through parotid gland)

• Benign cystic tumor w/ abundant lymphocytes and germinal centers (lymph node-like stroma); 2nd most common tumor of the salivary gland
• Almost always arises in the parotid

• Malignant tumor composed of mucinous and squamous cells; most common malignant tumor of the salivary gland
• Usually arises in the parotid; commonly involves the facial nerve

• Congenital defect resulting in a connection between the esophagus and trachea
• Most common variant consits of proximal esophageal atresia w/ the distal esophagus arising from the trachea
• Presents w/ vomiting, polyhydramnios, abdominal distension and aspiration

• Thin protrusion of esophageal mucosa, most often in the upper esophagus
• presents with dsyphagia for poorly chewed food
• increased risk for esophageal squamous cellcarcinoma
• Plummer-Vinson syndrome is char. by severe iron def. anemia, esophageal web, and beefy-red tongue due to atrophic glossitis

• Outpouching of pharyngeal mucosa through an acquired defect in the muscula wall (false diverticulum)
• Arises above the UE sphincter at the junction of the esophagus and pharynx
• Presents with dysphagia, obstruction and halitosis

• Longitudinal laceration of mucosa at the gastroesophageal (GE) junction
• Caused by severe vomiting, usually due to alcoholism or bulimia
• Presents with painful hematemesis
• Risk of Boerhaave syndrome- rupture of esophagus leading to air in the mediastinum and subcutaneous emphysema

• Dilated submucosal veins in the lower esophagus
• arise secondary to portal HTN
• Distal esophageal vein normally drains into the portal vein via the left gastric vein
•  In portal HTN, the left gastric vein backs up into the esophageal vein, resulting in dilation (varices).
• Asymptomatic, but risk of rupture exists
• Presents with pailess hematemesis
• Most common cause of death in cirrhosis

• Disordered esophageal motility with inability to relax the lower esophageal sphincer (LES)
• Due to damaged ganglion cells in the myenteric plexus
• Ganglion cells of myenteric plexus are located between the inner circular and outer longitudinal layers of the muscularis propria and are important for regulating bowel motility and relaxing the LES
• Damage to ganglion cells can be idiopathic or secondary to a known insult (ex Typanosoma cruzi infection in Chagas disease)
• Clinical features
• Dysphagia for solids and liquids
• Putrid breath
• High LES on esophageal manometry
• Bird beak sign on barium swallow study
• [image]
• Increased risk for esophageal squamous cell carcinoma

• Reflux of acid from the stomach due to reduced LES tone
• Risk factors include alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia
• Clinical Features
• Hearburn (mimics cardiac chest pain)
• Asthma (adult-onset) and cough
• Damage  to enamel of teeth
• Ulceration with stricture and Barrett esophagus are late complications

• Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells; seen in 10% of patients w/ GERD
• Response of lower esophageal stem cells to acidic stress
• May progress to dysplasia and adenocarcinoma

• Subclassified as adenocarcinoma or squamous cell carcinoma
•  
• Adenocarcinoma is a malignant proliferation of glands; most common type of esophageal carcinoma in the west
• Arises from preexisting Barrett esophagus; usually involves the lower 1/3 of the esophagus

• Squamous cell carcinoma is a malignant proliferation of squamous cells; most common esophageal cancer worldwide
• Usually arises in upper or middle 1/3 of the esophagus
• mjr risks

1. alcohol and tobacco (most common causes)
2. very hot tea
3. Achalasia
4. Esophageal Web
5. Esophageal injury

Esophageal Carcinoma presents late- poor prognosis

• Symptoms include progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis
• Squamous cell carcinoma may additionally present with hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement)
• Location of lymph node spread depends on the level of the esophagus that is involved

1. Upper 1/3-->cervical lymph nodes
2. Middle 1/3-->mediastinal or tracheobronchial nodes
3. Lower 1/3 celiac and gastric nodes

• Congenital malformation of the anterior abdominal wall leading to exposure of abdominal contents

• Persistent herniation of bowel into umbilical cord
• due to failure of herniated intestines to return to the body cavity during development
• Contents are covered by peritoneum and amnion of the umbilical cord

• Congenital hypertrophy of pyloric smooth muscle;more common in males
• classically presents two weeks after birth as

1. projectile nonbilious vomiting
2. Visible peristalsis
3. Olive-like mass in the abdomen
4. Treatment is myotomy

• Acidic damage to the stomach mucosa
• due to imbalance between mucosal defenses and acidic environment
• defenses include mucin layer produced by foveolar cells, bicarbonate secretion by surface epithelium, and normal blood supply (provides nutrients and picks up leaked acid)

Risk Factors

1. Severe Burn (Curling Ulcer) Hypovolemia leads to decreased blood supply
2. NSAIDS (decreased PGE2)
3. Heavy alcohol consumption
4. Chemotherapy
5. Increased intracranial pressure (cushing ulcer) increased stimulation of vagus nerve leads to increased acid production
6. Shock-multiple (stress) ulcers may be seen in ICU patients
7. Acid damage results in superficial inflammation, erosion (loss of superficial epithelium), or ulcer (loss of mucosal layer)

• Chronic inflammation of stomach mucosa
• Divided into two types based on underlying etiology: chronic autoimmune gastritis and chronic H pylori gastritis

• Due to autoimmune destruction of gastric parietal cells, which are located in teh stomach body and fundus
• associated w/ antibodies against parietal cells and /or intrinsic factor; useful for diagnosis, but pathogenesis is mediated by T cells (type IV hypersensitivity)

• Clinical Features

1. Atrophy of mucosa with intestinal metaplasia
2. Achlorhydria w/ increased gastrin levels and antral G-cell hyperplasia
3. Megaloblastic (pernicious) anemia b/c of lack of intrinsic factor
4. increased risk for gastric adenocarcinoma (intestinal type)

• due to H. pylori-induced acute and chronic inflammation; most common form of gastritis (90%)
• H pylori ureases and proteases along w/ inflammation weaken mucosal defenses; antrum is the most common site
• Presents with epigastric abdominal pain; increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type), and MALT lymphoma
• Treatment involves triple therapy
• Resolves gastritis/ulcer and reverses intestinal metaplasia
• Negative urea breath test and lack of stool antigen confirm eradication of H. pylori

• Solitary ulcer involving proximal duodenum (90%) or distal stomach (10%)
• differential diagnosis of ulcers includes carcinoma
• duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare)
• Gastric ulcers can be caused by gastric carcinoma (intestinal subtype)
• benign peptic ulcers are usually small <3cm, sharply demarcated (punched-out), and surrounded by radiating folds of mucosa
• malignant ulcers are large and irregular with heaped up margins
• biopsy is required for definitive diagnosis

• almost always due to H. pylori >95%; rarely, may be due to ZE syndrome
• Presents with epigastric pain that improves with meals
• Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands
• May rupture leading to bleeding from the gastroduodenal artery (Anterior ulcer) or acute pancreatitis (posterior ulcer)

• usually due to H pyloris (75%)
• other causes NSAIDS and bile reflux
• Presents w/ epigastric pain that worsens with meals
• ulcer is usually located on the lesser curvature of the antrum
• rupture carries risk of bleeding from left gastric artery

• Malignant proliferation of surface epithelial cells (adenocarcinoma)
• subclassified into intestinal and diffuse types

• Intestinal type (more common) presents as a large, irregular ulcer with heaped up margins; most commonly involves the lesser curvature of the antrum (similar to gastric ulcer)
• risk factors include intestinal metaplasia (ex. due to H. pylori and autoimmune gastritis), nitrosamines in smoked food (Japan), and blood type A

• Diffuse type is characterized by signet ring cells that diffusely infiltrate the gastric wall; desmoplasia results in thickening of stomach wall (lnitis plastica)
• Not associated with H. pylori, intestinal metaplasia or nitrosamines
• Gastric carcinoma presents late with weight loss, abdominal pain, anemia, and early satiety; rarely presents as acanthosis nigricans or Leser-Trelat sign
• spread to lymph nodes can involve the left supraclavicular node (Virchow node)
• Distant metastasis most commonly involves liver; other sties include

1. periumbilical region (sister Mary Josephy nodule); seen with intestinal type
2. Bilateral oaries (krukenbeer tumor) seen with diffuse type

• Congenital failure of duodenum to canalize; asociated with Down syndrome
• clinical features:
• polyhydramnios
• Distension of stomach and bloind loop of duodenum "double bubble sign"
• Bilious vomiting

• Outpouching of all 3 layers of the bowel wall (true diverticulum)
• arises due to failure of the vitelline duct to involute
• Rule of 2s
• seen in 2% of the poulation (most common congenital anomaly of the GI tract)
• 2 inches long and located in the small bowel wi 2 feet of the ileocecal valve
• can present during the first 2 years of life with bleeding (due to heterotopic gastric mucosa), volvulus, intussusception, or obstrucion (mimics appendicitis); however most cases are asymptomatic

• Twisting of bowel along its mesentery
• Results in obstruction and disruption of the blood supply with infarction
• most common locations are sigmoid colon (elderly) and cecum (young adults)

• Telescoping of proximal segment of bowel forward into distal segment
• Telescoped segment is pulled forward by peristalsis, resulting in obstruction and disruption of blood supply with infarction
• Associated with leading edge (focus of traction)
• In children, the most common cause is lymphoid hyperplasia (ex due to rotavirus)l usually arises in the terminal ileum, leading to intussusception into the cecum
• In adults, the most common cause is tumor

• Small bowel is highly susceptible to ischemic injury
• transmural infarction occurs with thrombosis/embolism of the superior mesenteric artery or thrombosis of the mesenteric vein
• mucosal infarction occurs with marked hypotension
• Clinical features include abdominal pain, bloody diarrhea, and decreased bowel sounds

• Decreased function of the lactase enzyeme found in the brush border of enterocytes
• Lactase normally breaks down lactose into glucose and galactse
• presents with abdominal distension and diarrhea upon consumption of milk products; undigested lactose is osmotically active
• deficiency may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood); temporary def. is seen after small bowel infection (lactase is highly susceptible to injury.)

• Immune mediated damage of small bowel villi due to gluten exposure; associated w/ HLA-DQ2 and DQ8
• gluten is present in wheat and grains; it's most pathogenic component is gliadin
• Once absorbed, gliadin is deamidated by tissue transglutaminase (tTG)
• Deamidated gliadin is presented by APC via MHC class II
• helper T cells mediate tissue damage
• clinical

1. Children classically present w/ abdominal distension, diarrhea, and failure to thrive
2. adults classically present w/ chronic diarrhea dn bloating
3. small, herpes-like vesicles may arise on skin (dermatitis herpetiformis) Due to IgA depostion at the tips of dermal papillae; resolves with gluten-free diet

Lab findings:

• IgA abs against endomysium, tTG, or gliadin; IgG abs are also present and are useful for diagnosis in individuals w/ IgA def. (increased incidence of IgA def. is seen in Celiac disease)
• Duodenal biopsy reveals flattening of villi, hyperplasia of crypts, and increased intraepithelial lymphocytes.  Damage is most prom. in the duodenuml jejunum and ileum are less involved

Symptoms resolve w/ gluten free diet

• Small bowel carcinoma and T-cell lymphoma are late complications that present as refractory disease despite good dietary control

• Dmg to small bowel villi due to an unknown organism resulting in malabsorption
• sim. to celiac disease, except
• Occurs ub Trioucak reguibs (ex Caribbean)
• Arises after infectious diarrhea and responds to antibiotics
• Damage is most prominent in jejunum and ileum (secondary vitamin B12 or folate def. may ensue); dueodenum is less commonly involved

• Systemic Tissue damage char. by macrophages loaded w/ Tropheryma whippeli organismsl partially destroyed organisms are present in macrophage lysosomes (positive for PAS)
• Classic site of involvement is the small bowel lamina propria
• macrophages compress lacteals
• chylomicrons cannot be transferred from enterocytes to lymphatics
• results in fat malabsorption and steatorrhea
• other common sites of involvement include synovium of joints (arthritis), cardiac valves, lymph nodes, and CNS)

• Autosomal recessive def. of apolipoprotein B-48 and B-100
• Clinical features
• Malabsorption-due to def. chylomicron formation (req. B-48)
• Absent plasma VLDL and LDL (require B-100)

Carcinoid tumor

• Malignant proliferation of neuroendocrine cells; low grade malignancy
• Tumor cells contain neurosecretory granules that are positive for chromogranin
• can arise anywhere along the gut; small bowel is the most common site
• grows as submucosal polyp-like nodule
• often secretes serotonin
• Serotonin is released into the portal circulation and metabolized by liver monamine oxidase (MAO) into 5-HIAA
• 5-HIAA is excreted in the urine
• Metastasis of carcinoid tumor to the liver allows serotonin to bypass liver metabolism
• Serotonin is released into the hepatic vein and leaks into systemic circulation via hepato-systemic shunts, resultin in carcinoid syndrome and carcinoid heart disease
• Carcinoid syndrome is characterized by bronchospash, diarrhea, and flushing of skin; symptoms can be triggered by alcohol or emotional stress, which stimlulate serotonin release from the tumor
• Carcinoid hear disease is char. by right-sided valvular fibrosis (increased collagen) leading to tricuspid regurgitation and pulmonary valve stenosis; left-sided valvular lesions are not seen due to presence of monoamine oxidase (metabolizes serotonin in the lung)

• Acute inflammation of the appendix; most common cause of acute abdomen
• Related to obstruction of the appendix by lymphoid hyperplasia (kids) or a fecalith (adults)
• Clinical features:
• Periumbilical pain, fever, and nausea; pain eventually localizes to right lower quadrant (McBurney point)
• Rupture results in peritonitis that presents with guarding and rebound tenderness
• Periappendiceal abcess is a common complication

• Chronic relapsin inflammation of bowel
• Possibly due to abnormal immune response to enteric flora
• classically presents in young women (teens to 30s) as recurrent bouts of bloody diarrhea and abdominal pain
• more prevalent in the West particularly in Caucasians and Eastern Euopean Jews
• Diagnosis of exclusion; symptoms mimic other causes of bowel inflammation (ex infection)
• subclassified as ulcerative colitis or Chron disease

• Defective relaxation and peristalsis of rectum and distal sigmoid colon
• associated with Down Syndrome
• Due to congenital failure of ganglion cells (neural crest-derived ) to descend into myenteric and submucosal plexus
• Myenteric (Auerbach) plexus is located btw the inner circular and outer longitudinal muscle layers of the muscularis propria and regulates motility
• Submucosal (Meissner) plexus is located in the submucosa and regulates blood flow secretions, and absorption

Clinical features are based on obstruction

• Failure to pass meconium
• Empty rectal vault on digital rectal exam
• Massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture
• Rectal suction biopsy reveals lack of ganglion cells
• Treatment involves resection of teh involved bowel; ganglion cells are present in teh bowel proximal to teh diseased segment

• Outpouching of mucosa and submucosa through the muscularis propria (false diverticulum)
• Related to wall stress
• asociated w/ constipation, straiing, and low-fiber diet; commonly seen in older adults (risk increases with age)
• Arise where the vasa recta traverse the muscularis propria (weak point in colonic wall); sigmoid colon is the most common location
• usually asymptomatic complications include:
• rectal bleeding hematochezia
• diverticultis-due to obstructing fecal material; presents with appendicitis-like symptoms in the left lower quadrant
• Fistula-inflamed diverticulum ruptures and attaches toa a local structure.  Colovesicular fistular presents with air (or stool ) in urine

• Acquired malformation of mucosal and submucosal capillary beds
• usually arises in the cecum adn right colon due to high wall tension
• Rupture classically presents as hematochezia an an older adult

• Autosomal dominant disorder resulting in thin-walled blood vessels, especially in the mouth and GI tract
• rupture presents as bleeding
• [image]

• Ischemic damage to the colon, usually at the splenic flexure (watershed area of superior mesenteric artery (SMA))
• Atherosclerosis of SMA is the most common cause
• Presents with postprandial pain and weight loss; infarction results in pain and bloody diarrhea

• Relapsing abdominal pain with bloating, flatulence, and change in bowel habits (diarrhead or constipation) that improves with defecation; classically seen in middle-aged females
• related to distrubed intestinal motility; no identifiable pathologic changes
• increased dietary fiber may improve symptoms

• Raised protrusions of colonic mucosa
• Most common types are hyperplastic and adenomatous polyps
• Hyperplastic polysp are due to hyperplasia of glands; classically show a serrated appearance on microscopy
• most common type of poly; usually arise in the left colon (rectosigmoid)
• benign, with no malignant potential
• Adenomatous polyps are due to neoplastic proliferation of glands; 2nd most common type of colonic polyp
• Benign, but premalignant; may progress to adenocarcinoma via the adenoma-carcinoma sequence
• Adenoma-carcinoma sequence descrbes the molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma
• APC (adenomatous polyposis coli gene) mutations (sporadic or germline) increase risk for formation of polyp
• K-ras mutation leads to formation of polyp
• p53 mutation and increased expression of COX allow for progression to carcinoma; aspirin impedes progression from adenoma to carcinoma
• Screening for polyps is performed by colonoscopy and testing for ecal occult blood. Polyps are usually clinically silent, but canbelled
• Goal is to remove adenomatous polyps before progression to carcinoma
• On colonoscopy, hyperplastic and adenomatous polyps look identical.  Hence all polyps are removed and examined microscopically
• Greatest risk for progression from adenoma to carcinoma is related to size >2 cm, sessile growth, and villous histology

• Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps
• Due to inherited APC mutation (chromosome 5); increases propensity to develop adenomatous polyps throughout colon and rectum
• Colon and rectum are removed prophylactically; otherwise, almost all patients develop carcinoma by 40 years of age

• FAP with fibromatosis and osteomas
• Fibromatosis is a non-neoplastic proliferation of fibroblasts; arises in retroperitoneum (desmoid) and locally destroys tissue
• Osteoma is a benign tumor of bone that usually arises in the skull
• Turcot syndrome is FAP with CNS tumors (medulloblastoma and glial tumors)

• Sporadic hamartomatous (benign) polyp that arises in children (<5 years)
• usually presents as a solitary rectal polyp that prolapses and bleeds
• Juvenile polyposis is characterized by multiple juvenile polyps in the stomach and colon; large numbers of juvenile polyps increase the risk of progression to carcinoma

• Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin; autosomal dominant disorder
• Increased risk for colorectal, breast, and gynecologic cancer

• Carcinoma arising from colonic or rectal mucosa; 3rd most common site of cancer and 3rd most common cause of cancer-related death
• Peak incidence is 60-70 years of age
• Most commonly arises from adenoma-carcinoma sequence; a second important molecular pathway is microsatellite instability (MSI)
• Microsatellites are repeating sequences of noncoding DNA; integrity of sequnce (stability) is maintained during cell division
• Instability indicates defective DNA copy mechanisms (ex DNA mismatch repair enzymes)
• Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due to inherited mutations in DNA mismatch repair enzymes
• Increased risk for colorectal, ovarian, and endometrial carcinoma
• Colorectal carcinoma arises de novo (not from adenomatous polyps) at a relatively early age; usually right-sided
• Screening for colorectal carcinoma occurs via endoscopy and fecal occult blood testing; begins at 50 years of age
• Goal is to remove adenomatous polyps before carcinoma develops and to detect cancer early before clinical symptoms arise
• Carcinoma can develop anywhere along entire length of colon
• Left-sided carcinoma usually grows as a napkin-ring lesion; presents with decreased stool caliber, left lower quadrant pain, and blood streaked stool
• Right-sided carcinoma usually grows as a raised lesion; presents with iron def. anemia (occult bleeding) and vague pain.  An older adult with iron def. anemia has colorectal carcinoma until proven otherwise
• Colonic carcinoma is associated with an increased risk for streptococcus bovis endocarditis
• Staging
• T-depth of invasion; tumors limited to the mucosa generally do not spread due to lack of lymphatics to the mucosa
• N- spread to regional lymph nodes
• M-Distant spread: most commonly involves the liver
• CEA is a serum tumor marker that is useful for assessing treatment response and detecting recurrence; not useful for screening