Exam 1 Flashcards
What are dental caries caused by
Focal demineralization of tooth structure (enamel and dentin) by acidic metabolites of fermenting sugars that are produced by bacteria
What is the significance of fluoride with teeth
It is incorporated into crystalline structure of enamel, forming fluoropatite, which contributes to the resistance to degreaton by bacterial acids
What are the features of dental plaque
Sticky, colorless, biofilm that collects btw and on the surface of teeth; contains bacteria, salivary proteins, and desquamated epithelial cells; if not removed, becomes mineralized to form calculus (tartar)
What age group is gingivitis most prevalent in
Adolescence
What is periodontitis
Inflammatory process that affects supporting structure of teeth (periodontal ligaments) alveolar bone, and cementum; can lead to destruction of ligament (loosens and loss of teeth)
What is periodontal dz associated with
Shift in types and proportions of bacteria along the gingiva; *faculative gram + bacteria usually colonize oral mucosa, but in periodontitis, anaerobic and microaerophilic gram - colonize it
Which bacteria are associated with periodontitis
Aggregatibater (actinobacillus) actinomycetemcomitans, porphyromonas gingivalis, and prevontella intermedia
What diseases can periodotitis be a component of
AIDS, leukemia, Crohn dz, DM, downs, sarcoidosis, and syndromes associated w/ defects in neutrophils (chediak-higashi, agranulocytosis, and cyclic neutropenia); *can also be the origin of systemic dz such as endocarditis and pulm/brain abscesses
What are aphthous ulcers
Canker sores; common, recurrent, superficial oral mucosal ulceration of unknown etiology; most common in first 2 decades; associated with immuno disorders; single or multi, shallow, hyperemic ulceration covered by thin exudate (first mononuclear, but w/ secondary bacterial infection results in neutrophilic) and rimmed by erythema; resolve in 7-10 days unless immmunocompromised
What is an irritation fibroma
Aka traumatic fibroma and focal fibrous hyperplasia; fibrous proliferative lesion; submucosal exophitic smooth nodular mass of fibrous connective tissue that occurs on buccal mucosa along bite or gingiva line; reactive proliferation cause by repetitive trauma; surgical excision
What is a pyogenic granuloma
Type of fibrous proliferative lesion; found typically in children, young adults, and pregnant women (pregnancy tumor), ulcerated and red to purple in color; growth can be rapid; histo: vascular proliferation or organizing granulation tissue; can regress, mature into dense fibrous masses, or develop into peripheral ossifying fibroma; can be hemorrhagic; needs surgical excision
What is a peripheral ossifying fibroma
Common gingival growth that is reactive in nature rather than neoplastic; can develop from pyogenic granuloma or de novo from cells of the periodontal ligament; red, ulcerated, nodular; peak incidence in young and teenage females* ***recurrence rate of 15-20% so need to excise down to periosteum
What is a peripheral giant cell granuloma
*uncommon lesion of oral cavity (usually gingiva); reactive/inflammatory response; not neoplastic; covered by intact gingival mucosa, but can be ulcerated; histo: aggregation of multinucleate, foreign-body like giant cells separated by fibroangiomatous stroma; not encapsulated but easily excised; should be diff from neutral giant cell tumors within the jaw and “brown tumors” seen in hyperparathyroidism (histo is similar)
When do primary infections of HSV 1 usually occur
Btw 2-4 y/o; often asymptomatic; in 10-20% of cases, can present as acute hermetic gingivostomatitis w/ abrupt onset of vesicles and ulceration of oral mucosa (gingiva); accompanied by LAD, fewer, anorexia and irritability
What is the morphology of HSV-1 vesicles
Can be few mm or large bullae; at first filled w/ clear serous fluid, but rapidly rupture to yield painful, red-rimmed, shallow ulceration; histo: intra and intercellular edema (acantholysis), creating clefts that can become transformed into macroscopic vesicles; individual epidermal cells in margins of vesicle develop eosinophilia intranuclear viral inclusions or can fuse to produce giant cells (multinucleate polykaryons) *demonstrated by Tzanck test; clears in 3-4 wks
What is viral reactivation of HSV-1 called
Recurrent hermetic stomatitis; occurs at the site of primary inoculation or in adjacent mucosa associated w/ the same ganglion
What other viral infections can involve the oral cavity and head and neck region
Herpes zoster, EBV (mono, nasopharyngeal carcinoma, lymphoma), CMV, enterovirus (herpangina, hand-foot-mouth dz, acute lymphonodular pharyngitis) and rubeola (measles)
What is the most common fungal infection of the oral cavity
Candida albicans (normal flora in 50% of people)
What are the forms of oral candidiasis
Pseudomembranous (most common - thrush), erythematous, and hyperplastic
What are the characteristics of the pseudomembraneous type of oral candidiasis
Superficial, gray to white inflammatory membrane composed of matted organisms enmeshed in fibrinosuppurative exudate that can be scraped off to reveled underlying erythematous base; remains superficial unless immunocompromised
What infectious diseases can cause oral manifestations
- scarlet fever: raspberry (fiery red tongue) or strawberry tongue (white coated w/hyperemic papillae)
- Measles: spotty enathema in oral cavity often precedes skin rash; ulceration in buccal mucosa (koplik spots)
- mono: pharyngitis and tonsillitis can cause gray white membrane; palatal petechiae
- diphtheria: dirty white, fibrinosuppurative membrane over tonsils
- HIV: candida and kaposi sarcoma; hairy leukoplakia
What dermatologic conditions can have oral manifestations
Lichen planus, pemphigus, bullous pemphigoid, erythema multiforme
What hematologist disorders can cause oral manifestations.
Pancytopenia (oral infections), leukemia (oral lesions), monocytic leukemia (leukemic infiltration and enlargement of gingiva w/ periodontitis)
What diseases can cause melanotic pigmentation
Addison’s, hemochromatosis, fibrous dysplasia of bone (Albright syndrome), peutz-jaghers syndrome (GI polyposis)
What oral manifestation can rendu-osler-Weber syndrome cause
AD; multiple congenital aneurysmal telangiectasias beneath mucosal surfaces of oral cavity and lips
Which fungi can cause deep fungal infections in the oral cavity, head and neck
Histo, blasts, coccidioidomycosis, cryptococcosis, zygomycosis and aspergillosis
What is hairy leukoplakia
Oral lesion on lateral border of the tongue caused by EBV; white confluent patches of fluffy hyperkeratotic thickening; cannot be scraped off; histo: hyperparakeratosis and acanthus is w/ balloon cells in upper spinous layer; stains can show RNA transcripts of EBV; can have superimposed candida infection on top
What is leukoplakia
White patch or plaque that cannot be scraped off and cannot be characterized as any other dz; reserved for oral cavity; can be premalignant so until proven otherwise, considered precancerous
What is erythroplakia
Less common and more ominous than leukoplakia; red, velvety, rodeo area in oral cavity that remains level or depressed in relation to surrounding mucosa; epithelium is atypical and risk of malignant transformation is higher
What are speckled leukoerythroplakia
Intermediate forms btw leukoplakia and erythroplakia
What population are leukoplakia and erythroplakia most commonly seen in
Age 40-70; males; use of tobacco is common antecedent
What is the histo of erythroplakia
Severe dysplasia, carcinoma in situ, or minimally invasive carcinoma
What is the most common cancer of the head and neck
Squamous cell carcinoma; 2nd is adenocarcinoma of salivary gland
What are the causes of squamous cell carcinoma of the head and neck
- tobacco and alcohol abusers
- actinic radiation (sunlight) - lower lip
- younger than 40, if not infected w/ HPV, unknown
What is the survival rate dependent on for squamous cell carcinoma of the head and neck
-early stage of smoking and alcohol is about 80%
-HPV positive better prognosis than HPV negative
Development of multiple tumors decreases survival; secondary tumors are increased prevalence than any other malignancy *field cancerization or can be intraepithlial Mets
Which mutations are commonly involved in SCC
P53, p63, NOTCH 1; overexpress p16
Where can SCC occur in the oral cavity
Ventral surface of tongue, floor of mouth, lower lip, soft palate, gingiva; early stages: raised, firm, pearly plaques or irregular roughened areas of mucosal thickening; dyplastic lesions may or may not develop to full thickness dysplasia before invading (in cervical cancer, usually develops before invasion); can be well diff keratinizing or anaplastic tumors -> not related to behavior; met to cervical LN or mediastinal LN, lungs, liver, and bones
What are odontogenic cysts
Derived from remnants of odontogenic epithelium present in jaw; epithelial lined cysts;classified as either inflammatory or developmental
What are dentigerous cysts
Originates around crown of unerupted tooth; result of fluid accumulation btw developing tooth and dental follicle; associated w/ impacted wisdom teeth; histo: lined by stratified squamous epithelium; complete removal is curative
What are odontogenic keratatocysts (OKC)
Aka keratocystic odontogenic tumor; *aggressive; most common btw 10-40 yo males in posterior mandible; unilocular or multilocular; histo: keratinized stratified squamous epithelium w/ basal cell layer; needs complete removal; high rate of recurrence for incomplete removal; most are solitary lesions
What should you test for if someone has multiple OKCs
Nevoid basal cell carcinoma syndrome (gorlin syndrome); associated w/ mutations in PTCH (tumor suppressor) on chrom 9q22
What is a peripheral cyst
Inflammatory; common - found on apex of teeth; develop as a result of pulpitis (inflammation of teeth); complete removal
What are odontogenic tumors
Group of lesions w/ diverse histo appearances and clinical behavior; some are true neoplasms and other are hamartomas; derived from odontogenic epithelium, ectomesenchyme or both
What are the two most common odontogenic tumors
- ameloblastoma: arises from odontogenic epithelium and shows NO ectomesenchymal differentiation; commonly cystic, slow growing, and locally invasive but has indolent course in most cases; tx: resection
- odontoma: most common type*; arises from epithelium but shows extensive depositions of enamel and dentin; hamartomas rather than true neoplasms; cured by local excision
What are the inflammatory odontogenic cysts
Perioapical, residual, paradental
What are the developmental odontogenic cysts
Dentigerous, odontogenic keratocyst, gingival cyst of newborn and adult, eruption cyst, lateral periodontal, glandular odontogenic, calcifying epithelial odontogenic (gorlin)
What are the benign and malignant tumors of odontogenic epithelium
- Benign: ameloblastoma, calcifying epithelial odontogenic tumor (pindborg), squamous odontogenic tumor, adenomatoid odontogenic
- Malignant: ameloblastic carcinoma, malignant ameloblastoma, clear cell odontogenic carcinoma, ghost cell odontogenic carcinoma, primary intraosseous squamous cell carcinoma
What are the tumors of odontogenic ectomesenchyme
Odontogenic fibroma and my soma, cementoblastoma
What are the benign and malignant tumors of odontogenic epithelium and ectomesenchyme
Benign: ameloblastic fibroma, ameloblastic fibro-odontoma, adenomatoid odontogenic tumor, odontoameloblastoma, complex odontoma, compound odontoma, calcifying cystic odontogenic tumor, denitogenic ghost cell tumor
Malignant: ameloblastic fibrosarcoma
What drugs is xerostomia commonly a side effect of
Anticholinergic, antidepressant, antipsychotic, diuretic, anti-HTN, sedative, m relaxant, analgesic, and antihistamine
How can xerostomia present
Dry mucosa or atrophy or papillae of the tongue, with fissuring and ulceration
What are complications of xerostomia
Dental caries, candidiasis, difficultly swallowing and speaking
What is sialadenitis
Inflammation induced by trauma, viral or bacterial infection or autoimmune dz; mucoceles- most common type of inflamm salivary gland lesion; most common form of viral sialadenitis is pumps
What are mucocele
Most common lesion of salivary glands; results from either blockage or rupture of salivary gland duct w/ leakage of saliva into surrounding connective tissue; most often found on lower lip and are result of trauma; most common in toddlers, young adults and elderly; present as fluctuate swellings that have blue translucent hue; lesion can change in size (w/ eating); histo:; pseudocysts lined by granulation tissue - cystic spaces filled w/ mucin nad macrophages; excision of cyst and minor salivary gland needed
What is ranula
Epithelial lined cysts that arise when the duct of the sublingual gland has been damaged; can become so large it develops into plunging ranula which is cyst that has dissected through connective tissue, connecting the two bellies of the mylohyoid m
What is nonspecific bacterial sialadenitis
Most often involves major salivary glands (submandibular); common; secondary to ducal obstruction produced by stones (sialolithiasis); common offenders are S aureus and Strep. Viridans; can be obstructed by impacted food Debris as well; decreased salivary production can be underlying cause as well (ppl on phenothiazines) or dehydration (leads to bacterial suppurations parotitis in elderly w/ recent hx of thoracic or ab surgery); unilateral involvement of single gland
What are the most common benign tumors of the salivary gland
Pleomorphic adenoma (mixed), warthin tumor, oncocytoma, basal cell adenoma, canalicular adenoma, Ductal papilloma
What are the most common malignant tumors of the salivary glands
Mucoepidermoid carcinoma, adenocarcinoma, acinic cell carcinoma, adenoid cystic carcinoma, malignant mixed tumor, squamous cell carcinoma, other carcinoma
Which salivary gland do tumors most frequently occur
Parotid
Which salivary glands are more likely to house malignant tumors
Sublingual is most likely, then minor salivary then submandibular **likelihood of salivary gland tumor being malignant is inversely proportional to size of the gland
What population do salivary gland tumors occur in
Mostly adult females
Which salivary gland tumor appears more in males than females
Warthin tumors; *smoking is predisposing factor
When do the benign vs malignant salivary gland tumors occur
Benign: 5th-6th decade; malignant: later
Are malignant or benign tumors of the salivary gland detected quicker
Malignant because grow faster
What are pleomorphic adenoma
Benign tumors that consist of ductal (epithelial) and myoepithelial cells (mesenchyme); most common in parotid; contain myxoid, hyaline, chondroid and osseous tissue; radiation exposure increases risk; some are assoc w/ PLAG1 rearrangements (overexpression)
What is the morphology of pleomorphic adenoma
Round, well demarcated masses; encapsulated (in some areas - palate - not fully)blue translucent areas of chondroid; histo: heterogeneity
How do pleomorphic adenoma present
Painless, slow growing mobile, discrete masses
What is carcinoma ex pleomorphic adenoma
Malignant mixed tumor; usually takes form of adenocarcinoma or undifferentiated carcinoma;very aggressive
What is a warthin tumor
Aka papillary cystadenoma lymphomatosum; benign; second most common salivary gland neoplasm; arises almost exclusively in parotid; more common in males; 10% are b/l; smokers are increased risk
What is the morphology of warthin tumor
Round to oval encapsulated masses; pale gray; filled w/ mutinous or serous secretions; histo: lined by double layer of neoplastic epithelial cells and sometimes bear germinal centers; numerous mitochondria present (oncocytic)
Where else have warthin tumors been found to originate
cervical LN *dont mistake w/ Mets
What are mucoepidermoid carcinomas
Composed of squamous cells, mucus-secreting cells, and intermediate cells; occur most often inparotid; associated w/ balanced (11;19) (q21;p13) translocation that creates a fusion gene MECT1-MAML2 gene; most common form of primary malignant tumor of salivary glands
What is the morphology of mucoepidermoid carcinomas
No capsule; infiltrative at margins; pale and gray-white; contain mucin-containing cysts; histo: cords, sheets, or cystic configurations of squamous, mucous or intermediate cells
What is the clinical course of mucoepidermoid carcinomas
Depends on grade; low grade rarely met; high grade: difficult to excise so recur and met )=
What is adenoid cystic carcinoma
Uncommon tumor; found in minor salivary glands, in particular palatine glands; cribriform pattern on histo; spaces btw often filled w/ hyaline; slow growing and invade perineural spaces; highly recurrent; disseminate widely; *minor salivary glands have poorer prognosis than parotid glands
What is acinic cell carcinoma
Compose of cells that resemble the normal serous acinic cells of the salivary glands; uncommon; most arise in parotid, rest in submandibular; rarely involves minor glands; can be b/l; clear cytoplasm; miccrocystic, glandular, follicular, or papillary patterns on histo; recurrence is uncommon but can met to LN
An atresia, fistula or duplication of the GI tract would be discovered early on if located where?
When in the esophagus, discovered shortly after birth (regurgitation)
Esophageal atresia is what kind of obstruction
Mechanical
Where does esophageal atresia most commonly occur
At bifurcation of trachea; usually associated with a fistula connecting the upper or lower esophageal pouches to a bronchus or trachea; fistula can also be present w/o atresia
What are developmental abnormalities of the esophagus associated with
Congenital heart defects, GU malformations, neuro dz
What does intestinal atresia most commonly involve
Duodenum; less common than esophageal atresia
What is imperforate anus
Most common form of congenital intestinal atresia; caused by failure of cloacal diaphragm to involute
What is stenosis
Incomplete form of atresia; congenital forms or acquired as consequence of inflamm scarring (GERD, irradiation, systemic sclerosis, caustic injury); esophagus and SI are most commonly affected
What is a diaphragmatic hernia
Occurs when incomplete formation of the diaphragm causes ab viscera to herniate into thoracic cavity; can cause pulmonary hypoplasia that can be incompatible w/ life
What is an omphalocele
When closure of the ab mm is incomplete and ab viscera can herniate into ventral membranous sac; can be repaired surgically; assoc w/ other defects
What is gastroschisis
Similar to omphalocele except involves ALL layers of ab wall from peritoenum to skin
What is the most frequent site of ectopic gastric mucosa
Upper third of esophagus - referred to as inlet patch
Where can ectopic pancreatic tissue be found
Stomach or esophagus; most often asymptomatic but produce damage and local inflammation sometimes; when present in pylorus can lead to obstruction; can mimic invasive cancer
What can gastric heterotopia present with
(Small patches of ectopic gastric tissue in small bowel or colon); blood loss due to peptic ulceration of adjacent mucosa
What causes Merkel diverticulum
Failed involution of vitelline duct (connects lumen of developing gut to yolk sac)
What are the features of Merkel diverticulum
Extends from antimesenteric side of bowel; occurs in 2% of pop, present w/in 2 feet of ileocecal valve; 2 inches long, twice as common in males, most often symptomatic by age 2 (only 4% are ever symptomatic)
What symptoms can Merkel diverticulum have
If has gastric tissue, ulceration and blood loss; can resemble acute appendicitis or obstruction
What is the difference between meckel’s and other diverticulum
Meckel’s is congenital and has all 3 layers of bowel wall; acquired diverticula either lack musculature entirely or have attentuated muscularis propria *most common site of acquired is sigmoid colon
What are the features of pyloric stenosis
Congenital is More common in males; high rate of concordance in monozygotic twins; also increased risk of siblings; Turner syndrome and trisomy 18 have increased risk; erythromycin and azithromycin exposure in first 2 weeks of life linked to increased incidence
When does congenital hypertrophic pyloric stenosis present
Btw 3rd and 6th week of life as projectile, nonbilious vomiting after feeding and frequent demands for refereeing; PE reveals firm ab mass; can have abnormal left to right hyperperistalsis during feeding and before vomiting; results from hyperplasia of pyloric muscularis propria; surgical splitting of muscularis (myotomy) is curative
What causes acquired pyloric stenosis
Antral gastritis or peptic ulcers close to pylorus; carcinomas of distal stomach and pancreas can also cause this
What other dz is hirschprung dz associated with
Downs
What is another name for hirschsprung dz
Congenital aganglionic megacolon; abnormal NC migration from cecum to rectum; distal intestinal segment lacks both Meissen submucosal and auerbach myenteric plexus
What are the underlying mechanisms that cause hirschsprung dz
Genetic component present in nearly all cases; heterozygous LOF mutations in RET (RTK) account for most familial cases and some sporadic cases; mutations in endothelium and its receptor have also been described; *more common in males, but when present in females involves longer aganglionic segments
What stain can you use to diagnose hirschsprung
Stain for acetylcholinesterase (used to identify ganglion cells)
What are the clinical features of hirschsprung
Failure to pass meconium; obstruction and constipation, bilious vomiting; can pass stool if only affects few centimeters of rectum; *threats to life are enterocolitis, fluid and electrolyte disturbances, perforation, and peritonitis
What cause acquired megacolon
Chagas dz, obstruction by neoplasm or inflammation, toxic megacolon complicating UC, visceral myopathy, functional psychosomatic disorders; *chagas is the only one associated with loss of ganglion cells
What does the esophagus develop from
Cranial portion of foregut; recognizable by 3rd week gestation
What is a functional obstruction
Disruption of peristalsis
What is nutcracker esophagus
High amplitude contractions of distal esophagus that are due to loss of normal coordination of inner circular layer and outer longitudinal layer smooth m contraction
What is diffuse esophageal spasm
Repetitive simultaneous contractions of distal esophageal smooth m
What is hypertensive lower esophageal sphincter
Absence of altered patterns of esophageal contraction
What can esophageal dysmotility ultimately lead to
Development of small diverticulum (epiphrenic diverticulum - located above lower esophageal sphincter) or zenker (pharyngoesphageal) caused by impaired relaxation and spasm of cricopharyngeus m after swallowing
When do zenker diverticulum develop
Usually after 50; *halitosis
How do mechanical obstructions of the esophagus present
Progressive dysphagia that begins with inability to swallow solids; develops slowly
What is benign esophageal stenosis
Narrowing of lumen; caused y fibrous thickening of submucosal and atrophy of muscularis propria and secondary epithelial damage; usually able to maintain diet and weight (malignant strictures associated with weight loss)
What are esophageal mucosal webs
Idiopathic ledge like protrusions of mucosa; uncommon; occur in women older than 40 and associate w/ GERD, chronic graft vs host dz, or blistering skin dz; in upper esophagus, can cause iron deficiency anemia, glossitis, and cheilosis (Paterson-Brown-Kelly or Plummer-Vinson syndrome); main symptom is non progressive dysphagia assoc w/ incompletely chewed food
What are esophageal rings
Aka schatzki rings; circumferential rings that include mucosa, submucosal and hypertrophic muscularis propria; when present in distal esophagus, termed A rings and are covered by squamous mucosa; when located at squamocolumnar junction of lower esophagus, B rings and can ha be gastric cardia-type mucosa
What is achalasia
Incomplete LES relaxation, increased LES tone, aperistalisis of esophagus; NO and vasoactive polypeptide from inhibitory neurons and interruption of cholinergic signaling usually allows LES to relax (doesn’t happen here); sx: dysphagia for solids and liquids, difficulty belching, chest pain; some risk for esophageal cancer, but not great enough for screening
What is primary achalasia
Result of distal esophageal inhibitory neuronal generation; degenerative changes in vagus n or dorsal motor nucleus of vagus can also occur; cause unknown
What is secondary achalasia
Can be caused by chagas (trypanosomiasis cruzi causes destruction of myenteric plexus, failure of peristalsis and esophageal dilation)
What can cause achalasia-like dz
Diabetic autonomic neuropathy, malignancy, amyloidosis, sarcoidosis, lesions of dorsal motor nuclei (polio), Downs, Allgrove (triple A syndrome -> AR disorder characterized by achalasia, alacrity, and ACTH resistant adrenal insufficiency; can also be driven by autoimmune destruction of inhibitor esophageal neurons
What are treatments for primary and secondary achalasia
Laparoscopic myotomy and pneumatic balloon dilation; Botox to inhibit cholinergic neurons can also be effective
What are Mallory-Weiss tears
Longitudinal mucosal tears near GE jxn; assoc w. Vomiting or retching secondary to acute alcohol intoxication; relaxation of GE musculature usually precedes vomiting -> fails here; do not require surgery, healing is rapid
What is boerhaave syndrome
Less common than Mallory Weiss syndrome; more serious; trans mural tearing and rupture of distal esophagus; produces severe mediastinitis and requires surgery; present w/ chest pain, tachypnea and shock and can be confused with MI
What is odynophagia
Pain on swallowing
What causes esophageal chemical injury in children and adults
Children: accidental ingestion of cleaning items; adults: suicide attempts
What is pill-induced esphagitis
When pill get stuck and dissolves in esophagus vs stomach
What are esophageal infections usually due to
Very uncommon in healthy individuals; due to HSV, CMV, or fungi (candida, muco, and aspergillosis)
What is the morphology of esophagitis
Neutrophils present but can be absent following chemical injury (necrosis); candidiasis can cause gray-white pseudomembranes of fungal hyphae on esophageal mucosa; HSV causes punched out ulcers, CMV causes shallower ulceration and nuclear and cytoplasmic inclusions, graft vs host dz show basal epithelial cell apoptosis, mucosal atrophy w/o inflammatory infiltrates
What is the most common cause of esophagitis
Reflux; most common outpatient GI diagnosis as well
What causes GERD
LES relaxation due to gastric dissension, mild pharyngeal stimulation that does not trigger swallowing, and stress; increase in ab pressure (coughing, straining, or bending), alc and tobacco use, obesity, CNS depressants, pregnancy, hiatal hernia, delayed gastric emptying, increased gastric volume
What is the morphology of GERD
Usually unremarkable in mild GERD; more severe: eosinophils recreated followed by neutrophils; basal zone hyperplasia
What are the clinical features of GERD
Most common > 40; heartburn, dysphagia, regurgitation of sour tasting contents; rx w/ PPI; complications: ulcer, hematemeis, melena, stricture, Barrett
What is hiatal hernia
Can resemble GERD; separation of diaphragmatic courage and protrusion of stomach into thorax
What are the symptoms of eosinophilic esophagitis
Food impaction, dysphagia in adults; feeding intolerance or GERD like sx in children; histo: large intraepithlial eosinophils; reflux NOT prominent and PPIs provide no relief; most are atopic and many have atopic dermatitis, allergic rhinitis, asthma, or peripheral eosinophilia; tx: modify diet to remove food allergens or corticosteroids
Besides alcoholic liver dz, what is the next most common cause of esophageal varies
Hepatic schistosomiasis
Where are the esophageal varices found
Submucosal of distal esophagus and proximal stomach
How do you treat variceal hemorrhage
Inducing splanchnic vasoconstriction or sclerotherapy (injection of thrombotic agents), balloon tamponade, or variceal ligation
What are risk factors for variceal hemorrhage
Large varices, elevated hepatic venous pressure gradient, previous bleeding, advanced liver dz; treat prophylactically w/ beta blockers to reduce portal blood flow
What population is Barrett esophagus most common in
White males btw 40 and 60
What is the most common cancer of the esophagus worldwide
SCC; adenocarcinoma in US
What is the most common benign tumor of the esophagus
Leiomyomas
What can reduce the risk of adenocarcinoma of the esophagus
Diets rich in fresh fruits and vegetables, some serotypes of H pylori (reduced gastric acid secretion nand reflux)
What population is adenocarcinoma of the esophagus most common in
White males
What mutations are seen in the progression from Barrett esophagus to adenocarcinoma
TP53, downregulation of CDKN2A (p16/INK4a) detected at early stages (hypermethylation and alleluia loss); later stages - amplification of EGFR, ERBB2, MET, cyclin D1, Cyclin E
What part of the esophagus is usually affected by adenocarcinoma
Distal 1/3; can invade gastric cardia
What are the clinical features of esophageal adenocarcinoma
Difficulty or pain on swallowing, progressive weight loss, hematemesis, chest pain, vomiting; by time sx appear, usually spread to submucosal lymph vessels; not a good prognosis
Where is squamous cell carcinoma most commonly found in the esophagus?
Mid-esophagus
What population is usually affected by squamous cell carcinoma of the esophagus
Males; tobacco use, poverty, caustic esophageal injury, achalasia, tylosis, Plummer-Vinson syndrome, diets deficient in fruits and veggies, frequent consumption of hot beverages *African Americans
What mutations have been found to cause esophageal squamous cell carcinoma
Amplification of SOX2 (transcription factor); over expression of cyclin D1 and LOF of TP53, e-Cadherin, and NOTCH1
What is the in situ lesion before squamous cell carcinoma called
Squamous dysplasia
Where does squamous cell carcinoma of the esophagus spread
Upper 1/3: cervical LN
Middle 1/3: mediastinal, paratracheal and tracheobronchial
Lower 1/3: gastric and celiac nodes
What is commonly the first symptom of SCC of esophagus
Aspiration of food b/c of tracheoesophageal fistula
What lines the cardia and antrum of the stomach
Mucin-secreting foveolar cells that form small glands
What glands are found in the body and fundus
Chief cells (produce pepsin)
What is acute gastritis
Mucosal inflammation when neutrophils are present
What is gastropathy
When inflammatory cells are rare or absent; includes diverse set of disorders marked by gastric injury or dysfunction; *NSAIDs, alcohol, bile, and stress induced injury; acute mucosal erosion or hemorrhage (ie: curling ulcers or lesions following disruption in blood flow) can also cause gastropathy
What is hypertrophic gastropathy
Specific group of diseases exemplified by menetrier dz and zollinger Ellison syndrome
What protects the gastric mucosa from the acidity of the lumen
Mucin forms layer of mucus and phospholipids that prevents large food particulates from directly touching epithelium and has a neutral pH b/c of bicarbonate secretion from surface epithelial cells; replacement of foveolar cells every few days is needed to maintain this
Disruption of which protective mechanisms can lead to gastropathy, acute gastritis, and chronic gastritis
- NSAIDs inhibit COX dependent synthesis of prostaglandins E and I which stimulate mucus, bicarbonate, and phospholipid secretion, mucosal blood flow, and epithelial restitution while reducing acid secretion; greatest risk w/ nonselective inhibitors (aspirin, ibuprofen and naproxen); COX 2 only are celecoxib
- gastric injury in uremic patients and H pylori infxn: inhibits gastric bicarbonate transporters
- reduced mucin and bicarbonate secretion
- decreased oxygen delivery at high altitudes
What is the morphology of gastropathy and acute gastritis
Surface epithelium intact but foveolar cell hyperplasia w/ corkscrew profiles and epithelial proliferation are typical; not many immuno cells; presence of neutrophils above BM is abnormal in all parts of GI tract and signifies active inflammation (gastritis NOT gastropathy)
Can you distinguish gastritis and gastropathy by clinical sx
No
When does stress related mucosal dz occur
Patients w/ severe trauma, burns, intracranial dz, major surgery, serious medical dz; result of local ischemia
What are stress ulcers
Most common in individuals w/ shock sepsis or severe trauma
What are curling ulcers
Occur in proximal duodenum and are associated w/ burns and trauma
What are Cushing ulcers
Gastric, duodenal, and esophageal ulcers in ppl w/ intracranial dz; *high incidence of perforation
What causes stress-related mucosal dz
Hypotension, reduced blood flow by stress induced splanchnic vasoconstriction, upregulation of NO synthase and increased release of endothelin-1 (constricts); *increase in COX-2 is protective
What are gastric lesions associated with intracranial injury though to be caused by
Direct stimulation of vagal nuclei -> causes hypersecretion of gastric acid; will see systemic acidosis
What is the difference between acute stress ulcers and peptic ulcers
Stress ulcers are found anywhere in stomach and most often multiple; stress ulcers do not have scarring and blood vessel thickening that characterize chronic peptic ulcers
What is dieulafoy lesion
Caused by submucosal artery that does not branch properly w/in the wall of the stomach; results in artery 10 times the size of capillaries; most commonly found around lesser curvature near GE jxn
What is GAVE
Gastric antral vascular ectasia; responsible for upper GI bleeding; longitudinal stripes of edematous erythematous mucosa that alternate w/ less severely injured paler mucosa *watermelon stomach; stripes are created by ecstatic mucosal vessels; histo: reactive gastropathy w/ dilated cap containing fibrin thrombi; most idiopathic, but some assoc w/ cirrhosis and systemic sclerosis
What is the most common cause of chronic gastritis
Infection w/ H. Pylori (bacillus)
What is the most common cause of diffuse atrophic gastritis
Autoimmune gastritis
What kind of atrophic gastritis can H. Pylori cause
Multifocal rather than diffuse
Is hematemesis common with chronic gastritis
No
What is risk of h.pylori infection associated with
Poverty, household crowding, limited education, AA or Mexican, residence in rural areas, birth outside of US; transmitted via fecal/oral route
How does H pylori present
Antral gastritis w/ normal or increased local acid production; hypergastrinemia (gastric in serum) is very uncommon; can progress to involve body and fundus (multifocal atrophic gastritis) which is assoc w/ reduced parietal cell mass and acid secretion, intestinal metaplasia and increased risk of gastric adenocarcinoma; inverse relationship in duodenal ulcer and adenocarcinoma
What contributes to the virulence of h pylori
Flagella; urease, adhesins (enhance adhesion to surface foveolar cells), and toxins (CagA - cytotoxin-associated gene A) which is involved in progression
What is associated with increased risk of gastric cancer with h pylori infection
Cag A expressing strains
What pays a role in outcome of h pylori infection
Genetic polymorphism that leads to increased expression of TNF and IL-1beta or decreased expression of IL-10 are associated with development of pangastritis, atrophy and gastric cancer; iron deficiency is also a risk for development of cancer
What stain is used to view h pylori
Warthin starry silver stain
Besides biopsy, how else can h pylori infection be diagnosed
Serum test for abs, fecal bacterial detection, urea breath test
What is the treatment for h pylori
Abx and PPI
What are the features of autoimmune gastritis
Spares the antrum and is associated with hypergastrinemia; characterized by abs to parietal cells and IF (detected in serum in gastric secretions), reduced serum pepsinogen I, endocrine cell hyperplasia, vit B12 def, and defective gastric acid secretion (achlorhydria)
What is the inflammatory infiltrate found in h pylori vs autoimmune gastritis
H pylori: neutrophils and subepithelial plasma cells
Autoimmune: lymphocytes and macrophages
What is the gastrin level in h pylori vs autoimmune gastritis
H pylori: normal or decreased
Autoimmune: increased
What other lesions are seen w/ h pylori vs autoimmune gastritis
H pylori: hyperplastic and inflammatory polyps
Autoimmune: neuroendocrine hyperplasia
What would you find in the serology w/ h pylori vs autoimmune gastritis
H pylori: abs to h pylori
Autoimmune: abs to parietal cells, H+, K+ ATPase, IF)
What can happen down stream as a result of h pylori vs autoimmune gastritis
H pylori: peptic ulcer, adenocarcinoma, MALToma
Autoimmune: atrophy, pernicious anemia, adenocarcinoma, carcinoid tumor
What other conditions are associated with autoimmune gastritis
Autoimmune dz, thyroiditis, DM, graves dz, Addison, primary ovarian failure, primary hypoparathyroidism, vitiligo, myasthenia, lambert-Eaton syndrome
What do parietal cells secrete
IF and gastric acid
What is the pathogenesis of autoimmune gastritis
Loss of parietal cells -> loss of acid -> gastrin release stimulated -> hyperplasia of antral gastrin producing G cells; chief cell destruction -> loss of pepsinogen I
What is the principal agent of injury in autoimmune gastritis
CD4 T cells directed against parietal cell components (H+, K+ ATPase); no autoimmune rxn to chief cells (lost through gastric gland destruction); gastric stem cells survive so if treated, glands can repopulate
What is the morphology of autoimmune gastritis
Rugal folds lost; endocrine cell hyperplasia demonstrated by immunostains for chromogrannin A
What is the age of diagnosis of autoimmune gastritis
Median: 60; progression is slow; more women than men
Are there any HLA genes linked to autoimmune gastritis
No
What is the clinical presentation of autoimmune gastritis
Sx of anemia; b12 def can cause atrophic glossitis (tongue becomes smooth and beefy red), epithelial megaloblastosis, malabsorptive diarrhea, peripheral neuropathy, spinal cord lesions, and cerebral dysfunction
What is eosinophilic gastritis
Characterized by eosinophils in the mucosa and muscularis in antral or pyloric regions; assoc w/ peripheral eosinophilia and increased IgE; caused by allergic rxn and immune disorders (systemic sclerosis and polyomyositis), parasite infxn and H pylori
What are the characteristics of lymphocytic gastritis
Primarily affects women; nonspecific ab sx; idiopathic; assoc w/ celiac; affects entire stomach; referred to as varioliform gastritis b/c shows thickened folds covered by nodules w/ central aphthous ulceration
What is the most common cause of granulomatous gastritis
Crohns; also caused by sarcoidosis and mycobacterium, fungi, CMV, and H pylori infxn
What is the most common form of peptic ulcer dz
H pylori induced antral gastritis; results in increased gastric acid and decreased bicarbonate
What is PUD w/in the body or fundus assoc w/
Not suceptible to antral or duodenal ulcers b/c dont produce enough gastric acid
What are the risk factors for peptic ulcer dz
H pylori, cigarettes, COPD, illicit drugs, NSAIDs, alcoholic cirrhosis (duodenal), psych stress, endocrine cell hyperplasia, zollinger Ellison (stomach, duodenum and jejunum), viral infxn (CMV, HSV)
What is diff about the margins of ulcers and cancer
Ulcers: level w/ mucosa
Cancer: heaped up margins
How can perforation be detected
Free air under diaphragm on radiology
What are the clinical features of peptic ulcers
Pain 1-3 hrs after meals, worse at night, relieved by alkali or food; N/V/belching and bloating; referred to back, LUQ or chest (mistaken for MI)
What are the complicating of PUD
Bleeding, perforation, obstruction (w/ pyloric channel ulcers; rarely causes total obstruction)
What is intestinal metaplasia
Chronic gastritis of body and fundus can lead to loss of parietal cells (oxyntic atrophy) which can be assoc w/ metaplasia, which includes presence of goblet cells -» increased risk of gastric adenocarcinoma (greatest in autoimmune gastritis)
How can you tell the difference between dysplasia and reactive epithelial cells (regenerative epithelium)
Dysplasia remains immature, but reactive epithelial cells mature
What is gastritis cystica
Reactive epithelial proliferation associated with entrapment of epithelial lined cysts; found in submucosal (gastritis cystica polyposa) or deeper layers of gastric wall (gastric cystica profunda) *trauma induced (assoc w/ gastrectomy and gastritis); can mimic adenocarcinoma
What are hypertrophic gastropathies
Uncommon* giant cerebriform enlargement of rugal folds due to epi hyperplasia w/o inflammation; *excessive growth factor release
What are the 2 examples of hypertrophic gastropathies
Menetrier and zollinger Ellison
What is menetrier dz
Rare; assoc w/ excessive secretion of TGF alpha; diffuse hyperplasia of foveolar epithelium of body and fundus and hypoproteinemia due to protein losing enteropathy; secondary sx: weight loss, diarrhea, peripheral edema; sx in children similar to adults but children is self limited and often follows resp infxn; risk of gastric adenocarcinoma increases in adults
What is the treatment for menetrier dz
Supportive; IV albumin, parenteral nutritional supplements; gastrectomy needed if severe; TGF alpha blockers
Are there any risk factors of menetrier dz
No
What is zollinger Ellison syndrome
Gastrin secreting tumors found in SI or pancreas; duodenal ulcers, diarrhea; doubling of oxyntic mucosal thickness due to increase in number of parietal cells; gastrin also induces hyperplasia of mucous neck cells, mucin hyperproduction, and proliferation of endocrine cells (can produce carcinoid tumors)
What is the treatment of zollinger Ellison
PPI
Are gastrinomas malignant
60-90% of the time they are
What is associated with non-sporadic zollinger Ellison
MEN I; treat w/ stomatostatin analogues
What inflammatory infiltrate is seen in zollinger Ellison
Neutrophils
Is zollinger Ellison assoc w/ adenocarcinoma
No
What are the majority of gastric polyps
Inflammatory or hyperplastic
What are the features of inflammatory and hyperplastic polyps
Most common btw 50 and 60 y/o; usually develop in assoc w/ chronic gastritis (h pylori); polyps can regress after tx of h pylori
Which polyps should be resected and examined
Polyps larger than 1.5 cm; dysplasia correlates with size
What are fundic gland polyps
Occur sporadically and in ppl w/ familial adenomatous polyposis (FAP); has increased recently b/c of PPIs (inhibit acid which leads to increased gastrin and oxyntic gland growth); asymptomatic or assoc w/ N/V/epi pain
Where do fundic gland polyps form
Fundus and body; smooth surface; can be single or multiple; inflammation absent; composed of dilated glands lined by parietal, chief and foveolar cells
Do sporadic fundic gland polyps have a cancer risk
No
Do males or females get gastric adenomas more frequently
Males
Who is at an increased risk of developing gastric adenomas
FAP
What is the morphology of gastric adenomas
Usually solitary lesions in the antrum; composed of columnar epithelium that exhibits dysplasia; high grade dysplasia will show glandular budding and gland within glad (cribriform) structures; premalignant *cancer transformation is much higher in gastric adenomas than intestinal adenomas
What are the two types of gastric adenocarcinoma
Intestinal: form bulky masses
Diffuse: infiltrates wall, thickens it and is composed of signet rings
What are the most common sites of metastasis of gastric adenocarcinoma
Supraclavicular node, periumbilical (sister Mary joseph), left Axillary LN (iris node), ovary (krukenberg tumor) or pouch of Douglas (blumer shelf)
What groups are more likely to get gastric adenocarcinoma
Low SES, ppl w/ multifocal mucosal atrophy and intestinal metaplasia; NOT PUD, but ppl who have partial gastrectomy due to PUD are at increased risk (due to hypochlorhydria, bile reflux and chronic gastritis)
Cancer of what part of the stomach is on the rise
Cardia; related to Barrett esophagus and may reflect increased GERD
What mutations is familial gastric cancer associated with
LOF in CDH1 (tumor suppressor; encodes E-Cadherin) -> also present in sporadic forms *loss of E-cadherin is key step in development of diffuse gastric cancer; CDH1 mutation also common in familiar lobular carcinoma of breast which tends to infiltrate as single cells (like diffuse gastric cancer); ppl w/ BRCA2 at increased risk of gastric cancer
What mutations are associated with only the sporadic intestinal type gastric cancers
Mutations that result in increased WNT signaling; LOF of APC (adenomatous polyposis coli) and GOF in gene encoding beta-catering; LOF of TGF beta signaling, BAX, and CDK2A; *FAP have increased risk of intestinal type gastric cancer (more common in Japan)
Where are gastric adenocarcinoma most often found
Lesser curvature; antrum
What is the difference in the morphology of gastric tumors with an intestinal morphology and diffuse infiltrative growth pattern
Intestinal morph: bulky, composed of glandular structures; dont usually penetrate; form exophytic mass or ulcerated tumor; contain mucin
Diffuse: composed of singet ring cells; dicohesive cells; mucin vacules that expand cytoplasm and push nucleus to periphery which creates signet ring cells; mistaken for inflammatory cells
What diagnostic clue is helpful in diagnosing diffuse gastric cancer
Evoke desmoplastic reaction that stiffens the gastric wall; when large areas of infiltration, rugal flattening and thickened wall can impart leather bottle appearance *linitis plastica
What are the geographic locations of diffuse vs intestinal gastric cancer
Diffuse: equal across all countries, no precursor lesions, similar rate in M and F
Intestinal: high risk areas, precursor lesions, more likely in males
What are the most useful prognostic indicators in gastric cancer
Depth of invasion and extent of nodal and distant Mets; local invasion to duodenum, pancreas, and retroperitoneum is common; surgical resection is preferred rx
Where is the most common location of extranodal lymphomas
GI tract; particularly stomach
What is the most common site of EBV + lymphoproliferations in hematopoietic stem cell and organ transplant pts
Bowel; most likely because of oral immunosuppressive agents
What is the most common primary lymphoma in the stomach
Extranodal marginal zone B cell lymphomas (MALTomas)
What translocations are associated with MALTomas
(11;18)(q21;q21) -> brings together apoptosis inhibitor 2 (API2) w/ mutated in MALT lymphoma (MLT), (1;14)(p22;q32) and (14;18)(q32;q21) -> increased expression of intact MALT1 and BCL-10 proteins respectively
What is the pathogenesis of MALToma as a result of the translocation
Increased activation of NFkB; requires both BCL-10 and MLT
When is eradictation of h pylori effective vs ineffective in treatment of MALTomas
If doesn’t contain translocation, effective; if does have translocation or has required other mutations (p53 or p16), ineffective
What is the morphology of MALTomas
Dense lymphocytic infiltrate in lamina propria; infiltrates gastric glands vocally to create diagnostic lymphoepithelial lesions; express CD19 and 20, do not express CD5 or 10, but are positive for CD43 in some cases
What are the common presenting features of MALTomas
Dyspepsia and epigastric pain; hematemesis, melena and weight loss can be present
Where are most carcinoid tumors found
Aka well differentiated neuroendocrine tumors; most found in SI, then tracheobronchial tree and lungs
What are gastric carcinoid tumors associated with
Endocrine cell hyperplasia, autoimmune chronic atrophic gastritis, MEN I, and zollinger Ellison
Where do carcinoid typically arise in the stomach
Within oxyntic mucosa; overlying mucosa can be intact or ulcerated; in intestines can invade deeply to involve messengers; yellow or tan in color and very firm (can cause kinking and obstruction)
What is the histo of carcinoid tumors
Islands, trabeculae, strands, glands, or sheets of uniform cells w/ scant pink cytoplasm and stippled nucleus; minimal pleomorphism; positive for synaptophysin and chromogranin A
What are the clinical features of carcinoid tumors
Peak incidence in 6th decade; sx determined by hormones produced; ie: ileal tumors cause carcinoid syndrome (cutaneous flushing, sweating, bronchospasm, colicky ab pain, diarrhea, and right sided cardiac valvular fibrosis)
What is carcinoid syndrome associated with
Metastasis in the liver b/c vasoactive products released directly into circulation (if in intestine, goes through first pass effect)
What is the most important prognostic factor for GI carcinoid tumors
Location
What are the features of foregut carcinoid tumors
Stomach, duodenum proximal to lig of treitz and esophagus; rarely met; cured by resection; gastric carcinoid tumors w/o predisposing factors more aggressive
What are the features of midgut carcinoid tumors
Arise in jejunum and ileum; often multiple and aggressive; greater depth of local invasion, increased size, necrosis and mitosis associated w/ worse outcome
What are the features of hindgut carcinoid
Arise in appendix and colorectum; discovered incidentally; in appendix, benign; rectal produce polypeptide hormones and present w/ ab pain and weight loss (met uncommon)
Where do a majority of GI carcinoid form
Jejunum and ileum
Hat do stomach carcinoid produces
Histamine, somatostain, serotonin; causes sx of gastritis, ulcer
What produces do duodenum carcinoids produce
Gastrin, somatostatin, CCK; sx: peptic ulcer, biliary obstruction, ab pain; assoc w/ zollinger Ellison and NF-1
What are the products of jejunal and ileal carcinoids
Serotonin, substance P, polypeptide YY; sx: obstruction ,Mets; aggressive
What is the most common mesenchymal tumor of the abdomen
GI stromal tumor (GIST); more than half occur in stomach; arises from interstitial cells of Cajal
What is the chromatin structure seen with carcinoid tumors usually described as
Salt and pepper pattern
What is the carney triad
Nonhereditary syndrome of unknown etiology seen mostly in young females that includes gastric GIST, paraganglioma, and pulmonary chondroma
What dz is associated with an increased incidence of GIST
NF-1
What mutations are seen in GIST
GOF in KIT (RTK) and PDGFRA (overrepresented in stomach GISTs); those w/out these mutations commonly have mutations in genes encoding components of mitochondrial succinctness DH complex (SDHA-D) - LOF cause increased risk of GIST and paraganglioma (carney-stratakis syndrome NOT triad); mutation of KIT or PDGFRA is early even in sporadic cases (insufficent for tumor production) - need deletion of chrom 14 and 22 or 9 p (poor prognosis if have increased numbers of chrom alterations)
What is the morphology of gastric GISTs
Can be large, usually form solitary fleshy mass covered by ulcerated or intact mucosa and can project outward; cut surface shows *whorled appearance; can met to abdomen but rare elsewhere; *spindle cell and epithelioid type
What is the treatment for GIST
Resection
What does the prognosis of GIST depend on
Tumor size, mitotic index, location (gastric less aggressive); recurrence is rare for small but common for mitotically active tumors larger than 10 cm
How can you treat unresectable GIST
If have mutations in KIT or PDGFRA, RTK inhibitor imatinib; w/o these mutations associated w/ drug insensitivity
What is the most common site of GI neoplasia
Colon
Where in the GI tract does obstruction most often occur
SI
What is the most frequent cause of obstruction world wide
Hernias
What kind of hernias is obstruction most commonly associated with
Inguinal; pressure at pouch impairs venous drainage and resultant stasis increase the bulk of loop leading to permanent entrapment (incarceration) and strangulation
What can cause adhesions
Surgery, infection, peritoneal inflammation (endometriosis)
What is an internal hernia
Does not protrude into external pouch; ie: as a result of adhesions
What is the most common cause of intestinal obstruction in the US
Adhesions
Where do volvulus most often occur
Sigmoid colon
What is intussesception
When segment of intestine that is constricted by peristalsis telescopes into distal segment; pushed by peristalsis and pulls mesentery with it; can lead to obstruction and compression of mesenteric vessels
What is the most common cause of intestinal obstruction in children younger than 2
Intusseception; usually otherwise healthy; has been associated with rotavirus vaccine (reactive hyperplasia of Peyers patches)
What can be used diagnostically and therapeutically for idiopathic intussesceptoin in infants and children
Contrast enemas or air enemas; but if a mass is present, needed surgery (generally adults)
What causes transmural infarction
Typically acute vascular obstruction; mural and mucosal can be either acute or chronic
What are causes of acute arterial obstruction
Atheroscerosis, AAA, hypercoagulable states, OCP, embolization of cardiac vegetation’s or aortic atheromas
What is intestinal hypoperfusion associated with
Cardiac failure, shock, dehydration or vasoconstrictive drug use; systemic vasculitides (polyarateritis nodosa, Enoch-school Erin purpura, or granulomatosis w/ poly Angie is (wegener granulomatosis); mesenteric venous thrombosis (caused by cirrhosis, inherited hypercoag states)
What are the two phases of the intestinal response to ischemia
- hypoxia injury: epithelial cells lining intestine resistant to transient hypoxia
- repercussion injury: damage; can trigger multi organ failure; leakage of gut lumen bacterial products systemically
What are the watershed zones of the intestines
Splenic flexure (where SMA and IMA terminate) and sigmoid colon and rectum (where IMA, pudendal and iliac end); if see focal colitis of splenic flexure think ischemic dz
What part of the intestine is susceptible to infarction
Surface epithelium moreso than crypts; surface epithelium atrophy or necrosis/sloughing with normal or hyper proliferative crypts is signative of ischemic intestinal dz
What is the morphology of transmural infarction
Well demarcated line btw ischemia and normal; ischemic bowel is congested and dusky to purple-red; later blood-tinged mucus or accumulates in lumen and wall become edematous and rubbery; coagulation necrosis of muscularis propria in 1-4 days
What is the morphology of chronic ischemia
Fibrous scarring of lamina propria
Who does ischemic dz of the colon occur more frequently in
> 70 y/o female; drugs, cardiac dz, PVD, endothelial damage from CMV or E. coli O157:H7, strangulated hernia
How does acute colonic ischemia present
Sudden onset of cramping, left lower ab pain, desire to defecate and passage of blood or bloody diarrhea
When should you consider surgical intervention for acute colonic ischemia
If peristaltic sounds diminish or disappear (paralytic ileus) or guarding and rebound tenderness develop
What increases the mortality of acute colonic ischemia
Patients with right sided colonic dz (b/c supplied by SMA which also supplies SI); COPD and persistence of sx for more than 2 wks indicate poorer prognosis
What can chronic ischemia present at
Can masquerade as IBD w/ episodes of blood diarrhea with periods of healing
What infection can cause ischemic GI dz
CMV; tropism for endothelial cells
What is radiation enterocolitis
When GI tract is irradiated, can cause vascular injury and can produce ischemic dz; *radiation fibroblasts w/in s tromp; acute enteritis manifests as anorexia, ab cramps, malabsorptive diarrhea; chronic can present as inflammatory enterocolitis
What is necrotizing enterocolitis (NEC)
Acute disorder of small and large intestines that can result in transmural necrosis; *most common acquired GI emergency in neonates (premature) and presents when oral feeding is initiated
What is Angiodysplasia
Lesion characterized by malformed submucosal and mucosal bv; occurs most often in cecum or right colon usually in 6th decade; thought to be caused by normal distinction and contraction which intermittently occludes submucosal v -> focal dilation of vessels -> wall tension; liked to meckel; tortuous veins, venules, and caps
What are the most commonly encountered chronic malabsorptive disorders in the US
Pancreatic insufficiency, crohns and celiac
What can cause malabsorption after allogeneic hematopoietic stem cells transplant
Intestinal graft vs host dz
What are the phases of nutrient absorption that, if disrupted, will lead to malabsorption
- intraluminal digestion: proteins, fats, carbs broken down
- terminal digestion: hydrolysis of carbs and peptides in brush border
- transepithelial transport
- lymphatic transport
What can inadequate absorption of vit and minerals lead to
Anemia and mucositis due to pyridoxine, folate, or B12 def, bleeding due to K, osteopenia and tetany (calcium, Mg, and vit D), peripheral neuropathy (A and B12)
What is the definition of diarrhea
Increase in stool mass, frequency or fluidity greater than 200 mg per day
What is dysentery
Painful, bloody, small volume diarrhea
What are the classes of diarrhea
- secretory: isotonic stool and persists during fasting
- osmotic: ie - lactase deficiency, due to excessive osmotic forces exerted by unabsorbed solutes; diarrhea fluid > 50 mOsm; abates w/ fasting
- malabsorptive: failure of nutrient absorption; assoc w/ steatorrhea; relieved by fasting
- exudative: due to inflamm dz; purulent, bloody stools that continue during fasting
Which diseases have defects in terminal digestion
Celiac, environmental enteropathy, autoimmune enteropathy, disaccharidase deficiency, viral gastroenteritis, bacterial gastroenteritis, IBD
Which absorption diseases have a defect in transepithelial transport
Celiac, environmental enteropathy, primary bile acid malabsorption, carcinoid syndrome, autoimmune enteropathy, abetalipoproteinemia, viral and bacterial gastroenteritis, parasitic gastroenteritis, IBD
Which malabsorptive disease have defects in intraluminal digestion
Chronic pancreatitis, CF, primary bile acid malabsorption, IBD
Which malabsorptive dz has a defect in lymphatic transport
Whipple dz
What causes malabsorption in CF
Problems with bicarbonate, Cl, Na, and water secretion -> defective luminal hydration -> pancreatic introductions concretions; exocrine pancreas dysfunction; failure of intraluminal phase of digestion
What part of gluten contains the disease-producing components
Gliadin
How is gluten digested
By luminal and brush border enzymes into AA and peptides, including alpha-gliadin that is resistant to degradation by gastric, pancreatic and SI proteases
What is the pathogenesis of celiac dz
Gliadin induces epithelial cells to express IL-15 which triggers activation of CD8 cells that express NKG2D (NK cell marker and receptor fo MIC-A); enterocytes that express MIC-A are attacked by these; this allows gliadin to access the lamina propria where they are Deaminated by tissue transglutaminase -> interact with HLA-DQ2 or 8 and can stimulate CD4 to produce cytokines
What diseases is Celiac assoc w
T1DM, thyroiditis, Sjogren, IgA nephropathy, neuro disorders (ataxia, autism, depression, epilepsy, downs, turner)
Which section should be biopsied for diagnosis of celiac
Second portion of duodenum or proximal jejunum
What is the histo of celiac
Increased intraepithlial CD8 cells, crypt hyperplasia, bullous atrophy; increased rates of epithelial turnover doesn’t allow maturation of absorptive enterocytes (dont express proteins for transepithelial transport); increased # of plasma, mast cells, and eosinophils
What do you need to diagnose celiac dz
Combo of biopsy and serology (ie: lymphocytic infiltration not only indicative of celiac)
What are the clinical features of celiac
Presents btw 30 and 60; can have silent (+ serology and atrophy w/o sx) or latent (+ serology w/o atrophy); diarrhea, bloating, fatigue, often asymptomatic; more in women (except pediatric - equal)
What can children with no classic sx of celiac present with
At older ages w/ ab pain, N/V/D, bloating, constipation; arthritis or joint pain, aphthous stomatitis, iron def anemia, delayed puberty and short stature; dermatitis herpetiformis(itchy,blister) in 10% of patients
What are the complications of a gluten free diet
Anemia, female infertility, osteoporosis and cancer
What do you test for in serology to diagnose Celiac
IgA abs against tissue transglutaminase; anti-endomysial abs can also be present; IgG anti-tissue transglutaminase present in ppl w/ IgA deficiency; HLA does NOT confirm diagnosis, but is useful to rule out
What is the most common celiac disease associated cancer
Enteropathy-associated T cell lymphoma; aggressive; also small intestinal adenocarcinoma more frequent; must consider cancer if have sx after gluten-free diet
What is environmental enteropathy
Tropical sprue; prevalent in areas with poor sanitation and hygiene; suffer from malabsorption, stunted growth, and defective intestinal mucosal immune fxn
What is autoimmune enteropathy
X-linked; severe persistent diarrhea and AI dz; mostly in young children; IPEX* familial form - immune dysregulation, polyendocrinopathy, enteropathy, and X-linkage due to mut in FOXP3; rx: w/ cyclosporine or hematopoietic stem cell transplant
What are the two types of lactase deficiency
- congenital: mutation in gene encoding lactase; AR; explosive diarrhea w/ watery and frothy stools; ab distinction upon milk ingestion; sx abate when exposure to milk is terminated; fatal prior to development of soy based infant formula
- acquired: down regulation of lactase gene expression; common among Native American, AA, and Chinese; can develop following viral or bacterial infxn an can resolve; diarrhea and flatulence
What is abetalipoproteinemia
AR; inability to secrete triglyceride rich lipoproteins; mutation in MTP (microsomes triglyceride transfer protein) which catalyze transfer of lipids to nascent apoplipoprotein B polypeptides w/in RER; results in intracellular lipid accumulation; failure of intraepithlial processing and transport; *highlighted by oil red-O stain particularly after fatty meal; presents in infancy (failure to thrive, diarrhea, steatorrhea; absence of plasma lipoproteins) *presence of ancanthocytic red cells (burr cells) on blood smears due to lipid membrane defects
How can enterocolitis present
Diarrhea, ab pain, urgency, perinatal discomfort, incontinence, hemorrhage
What is vibrio cholerae
Comma shaped, gram negative bacteria; non-invasive
What factors are important for the pathogenesis of cholera
Flagella, hemagglutinin and metalloproteinase important for shedding into stool
How does cholera toxin cause cholera
B subunit binds GM1 ganglioside on surface of intestinal epithelial cells and is carried by endoytosis into ER (retrograde transport); A subunit is reduced by disulfide isomerase, unfolded and released; A subunit refolds in cytosol to resist degradation and interacts w/ ADP ribosylation factors to ribosylate and activate Gsalpha -> opens CFTR and inhibits Cl and Na reabsorption by cAMP increase; no histo alterations
What are the sx of cholera
Massive rice water stool with fishy odor, dehydration, hypotension, Anuria, m cramping, shock, death; treat with oral rehydration
What is the most common bacterial enteric pathogen in developed countries
Campylobacter jejuni; assoc w/ improperly cooked chicken or contaminated water; *food poisoning
What is the pathogenesis of campylobacter
Virulence: motility, adherence, toxin, invasion; assoc with dysentery in small minority; enteric fever occurs when bacteria proliferate w/in lamina propria and mesenteric LN; *can result in reactive arthritis (in pts with HLA-B27), also can cause erythema nodosum and guillaine barre
What is the morphology of campylobacter
Gram negative; diagnosis by stool samples histo: non specific; crypt architecture preserved
Do you generally treat campylobacter
No - self limiting
What are the characteristics of shigella
Gram negative unencapsulated nonmotile faculative anaerobes; *bloody diarrhea; fecal-oral route or contaminated water; low ineffective dose b/c resistant to stomach acidity
What is the pathogenesis of shigella
taken up by M cells (microfold), proliferate, escape into lamina propria and phagocytosis by macrophages (induce apoptosis) -> access to basoateral membrane of colonic epithelial cells (where they invade); virulence: plasmid that encode type III secretion system (directly inject into host cytoplasm); also releases shiva toxin (inhibits eukaryotic protein synthesis)
What is the morphology of shigella
Most prominent in left colon,but ileum may also be involved; mucosa is hemorrhagic and ulcerated, pseudomembranes may be present; destruction of crypt architecture
What are the complications of shigella
Sterile reactive arthritis, urethritis, and conjunctivitis (HLA-B27 positive); hemolytic uremic syndrome (also associated with EHEC) if serotype 1 that secretes shiga toxin
Can you give anti-diarrheal medicine to someone with shigella
No; contraindicated b/c can prolong sx and delay shigella clearance
What are the characteristics of salmonella
Grade negative bacilli; S. Enteritidis most common in young children and older adults; peak in summer and fall; food poisoning in raw meat
Who is more suceptible to salmonella
People with atrophic gastritis or on PPI’s; also those w/ Th17 deficiency (limits response)
What is the pathogenesis of salmonella
Type III secretion system (transfers bacterial proteins into M cells and enterocytes), which activate host Rho GTPases and. Trigger actin rearrangement and bacterial endocytosis -> bacterial growth w/in endosomes; flagellin activates TLR5 and increases local inflamm response; LPS activates TLR4; also secretes molecule that induces epithelial cell release of eicosanoid hepoxilin A3, drawing neutrophils into lumen
What are the clinical features of salmonella
Stool can be either watery or dysenteric; abx not recommended b/c can prolong carrier state; risk of severe illness increased in ppl w/ malignancy, immunosuppression, alcoholism, CV dysfunction, sickle cell, and hemolytic anemia
What causes typhoid fever
S. Enterica (subtypes s. Typhi and s. Paratyphi) paratyphi associated more w/ travelers; assoc w/ travel to India, Mexico, Philippines and Haiti; transferred from person to person or via contaminated water; *gallbladder colonization
What is the pathogenesis of s typhi
Survive in gastric acid, taken up by M cells in small intestine and invade; bacteria engulfed by macrophages; *can disseminate via lymph and bv (s enteritidis cannot do this); cause reactive hyperplasia of lymphoid tissue throughout body
What is the morphology of s typhi
Peyers patches in terminal ileum enlarge to plateau like elevations; mesenteric LN enlarged; neutrophils in superficial lamina propria and plasma cells and macrophages as well; oval ulcers; spleen is enlarged and soft w/ pale red pulp, obliterated follicular markings; liver shows Fock of parenchyma necrosis in which hepatocytes replaced by macrophage aggregates (typhoid nodules) -> also present in BM and LN
What are the clinical features of s typhi
Anorexia, ab pain, bloating, N/V/bloody D, short asymptomatic phase follows then fever w/ flulike symptoms; blood cultures positive during febrile phase and abx can prevent further dz progression; rose spots (maculopapular lesions) on chest and abdomen; systemic dissemination can cause encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia, cholecystitis; *sickle cell = suceptible to osteomyelitis
Which yersinia infections affect the GI tract
Y. Enterocolitica and Y. pseudotuberculosis ; more common Europe and North America; linked to ingestion of pork, raw milk, and contaminated water; cluster in winter
What is the pathogenesis of yersinia
Invade M cells and use adhesions to bind to host cell beta1 integrity; encodes iron uptake system that mediates iron capture and transport *iron enhances virulence and stimulates systemic dissemination *reason why ppl w/ increase non-heme iron (chronic anemia or hemochromatosis) are more likely to develop sepsis
What is the morphology of yersinia
Invade ileum, appendix, and right colon; multiply extracellularly in lymphoid tissue; bowel wall thickening; ulceration can develop
What are the clinical features of yersinia
Ab pain, N/V/D; mimics appendicitis; pharyngitis, athralgia, erythema nodosum occur frequently; complications: reactive arthritis, urethritis, conjunctivitis, myocarditis, erythema nodosum and kidney dz
What are the features of E. coli
Gram negative; colonize healthy GI tract
What are the features of Enterotoxigenic E. coli (ETEC)
Traveler’s diarrhea; spread via contaminated water; produces heat label toxin and stable toxin (both induce Cl and water secretion and inhibit fluid absorption) LT similar to cholera; ST binds to guanylate Cyclase and increases cGMP; secretory, noninflammtory diarrhea, dehydration
What are the features of Enteropathogenic E. coli (EPEC)
Produce attaching and effacing (A/E) lesions where bacteria attach tightly to enterocytes apical membranes and cause local loss (effacement of microvilli) -> encoded by locus of enterocytes effacement including Tir (inserts into intestinal epithelium plasma membrane; receptor for intimin -encoded by espE- and is used for diagnosis of EPEC) type III secretion system
What are the features of Enterohemorrhagic E. coli (EHEC)
O157:H7 and non O157:H7 serotypes; undercooked beef; both produce shiga-like toxin; hemolytic uremia with O157:H7 strain as well as ischemic colitis; *NO abx b/c killing bacteria increases release of shiga-like toxin - increased risk of hemolytic uremic syndrome
What are the features of enteroinvasive E. coli (EAEC)
Unique pattern of adherence; attach via fimbriae and aided by dispersin (neutralizes negative surface charge of LPS); lesions only visible by EM; nonbloody diarrhea prolonged in ppl with AIDS
What is the pathogenesis of C diff
Toxins released cause ribosylation of GTPases such as Rho and lead to disruption of epithelial cytoskeleton, tight junction barrier loss, cytokines release, and apoptosis
What is the morphology of c diff
Epithelium is denuded and superficial lamina propria contains infiltrate of neutrophils and fibrin thrombi w/in caps; superficially damaged crypts distended by exudate that formed an eruption (volcano); these come to gather to form pseudomembranes
What are the clinical features of c diff
Fever, leukocytes is, ab pain, cramps, watery diarrhea, dehydration; protein loss can lead to hypoalbuminemia; fecal leukocytes; bloody diarrhea uncommon; diagnose by presence of toxin, not culture
How do you treat c diff
Metronidazole or vancomycin; if resistant, monoclonal abs against toxins A and B, and fecal microbial transplants can be effective
What is whipple dz
Rare, multivisceral and chronic; malabsorption, LAD, arthritis; caused by gram positive Tropheryma whippellii; organism laden macrophages accumulate w/in SI lamina propria and mesenteric LN causing lymph obstruction; malabsorptive diarrhea due to impaired lymph transport
Who is whipple dz most common in
White males; particularly farmers or exposure to animals and soil
What is the presentation of whipple dz
Diarrhea, weight loss, arthralgia; fever, LAD and neuro, pulm, or cardiac dz can exist before malabsorption
What is the morphology of whipple dz
Accumulation of distended foamy macrophages in SI lamina propria; PAS positive, diastase resistant granules stuffed with partially digested bacteria; *similar presentation in intestinal tuberculosis (tell the difference by acid fast staining); villous expansion causes shaggy gross appearance to mucosa; lymphatic dilation and mucosal lipid deposition; macrophages accumulate in mesenteric LN, synovial membranes, cardiac valves and brain
What organisms is the most common cause of acute gastroenteritis requiring medical attention
Norovirus; second to rotavirus in kids
