Robbins Flashcards
1-2 decades of life, Extremely painful, recurrent sores, associated with IBD, Celiac, and Behcet disease?
Aphthous ulcers
Shallow hyperemic ulcerations covered by gray exudate and surrounded by rim of erythema?
Aphthous ulcer
Recurrent oral ulcers, genital ulcers, and uvietis?
Behcet disease
Superficial, curdlike exudate gray/white inflammatory membrane composed of matted organisms in a fibrinosuppurative exudate that can be easily scraped off?
Oral candidiasis
Submucosal nodular lesion that forms due to chronic irritation causing reactive CT hyperplasia?
Fibroma
Pedunculated, richly vascularized, red-purple masses usually found on gingiva of children, adults, pregnant women?
Pyogenic Granuloma
“White patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease?
Leukoplakia-> considered pre-cancerous until proven otherwise
Red velvety eroded area that is fat and depressed relative ti the surrounding mucosa?
Erythroplakia-> High risk of Cancer than Leuloplakia
Most common risk factor for Leukoplakia and erythroplakia?
Smoking
What are the two major RF for Oral SCC?
Smoking-> P53 + NOTCH1 mutations
HPV16-> p16 mutation + located in tonsillar crypts and base of tongue (better prognosis)
Mumps virus is known to causes inflammation of what 3 organs?
Parotid gland-
Orchitis-> sterility
Pancreatitis
Toddlers, fluctuant swelling of lower lip, cyst with Mac infiltrations that may change in size is association with meals?
Mucocele
Bacterial sialadenitis is often predisposed by what factors and caused by what organisms?
RF= Stones, dehydration, injury, phenothiazine use Organisms= S, aureus + Strep viridans
The likelihood that a salivary gland tumor is malignant is inversely related to what?
ITS SIZE
submandibular- 45% malignant
Sublingual= 90% malignant
What are the 2 most common salivary tumors?
Pleomorphic adenoma (50%) Warthin tumor (5%)
Most common Malignant tumors?
Mucoepidermoid carcinoma (15%) Acinic cell carcinoma (6%) Adenocarcinoma NOS (6%)
Painless, slow growing, mobile parotid gland mass?
Pleomorphic adenoma= consist of ductal and myoepithelial cells
Parotid mass displaying Heterogenic histology with evidence of cartilage and bone?
Pleomorphic adenoma
parotid gland Tumor containing cords, sheets or cysts lined by squamous, mucous, or intermediate cells?
Mucoepidermoid carcinoma
Cystic growth arising around crown of unruptured tooth resulting in degeneration of dental follicle, lined by squamous epithelium as a sign of Chronic inflammation?
Dentigerous cysts
Ora cyst that is locally aggressive and high recurrence rate?
Odontogenic keratocyst
Benign cystic tumor of parotid gland with abundant lymphocytes and Germinal centers?
Warthin tumor
Parotid gland tumor consisting of mucinous and squamous cells commonly damaging Facial nerve?
Mucoepidermoid carcinoma
Swollen, painful, parotid gland with purulent discharge. MCC?
Acute Sialadenitis= S. aureus
Episodic pain and swelling of parotid gland prior to eating a meal. MCC?
Chronic Sialadenitis== Due to Sialotlith (STONE)
Middle aged female, slow growing, painless, movable, firm mass for years NOW rapidly growing?
Pleomorphic Adenoma–> Becoming Malignant Carcinoma
Round, well circumscribed, non tender, movable rubbery mass on 50 yo female parotid gland. What is the most likely pathology?
Pleomorphic Adenoma= Encapsulated + Ductal or cystic formations with Epithelium + Myxoid or chondroid matrix (2 Germ layers)
MC complication of Pleomorphic adenoma treatment?
Facial nerve injury
60 yo male smoker, with Slow growing mass, painless, firm @ the tail of Parotid gland?
Warthins tumor
What is the histology of Warthins tumor?
Cystic spaces lined by double layer of oncocytes, and Prominent LYMPHOID STROMA + GERMINAL CENTERS
59 yo female, parotid gland mass that is asymptomatic. Biopsy shows mixture of mucous and squamous cells. What is the prognosis of this mass dependent on?
Mucoepidermpoid Carcinoma=
GRADE
location
Stage
What esophageal abnormalities are discovered shorty after birth due to regurgitation during feeding?
Atresia
Fistulas
Duplications
Atresia are often associated with Eso-Tracheal fistulas causing what pathologies?
Aspiration pneumonia
Suffocation
Severe fluid and electrolyte imbalance
Characterized by the triad of:
- incomplete LES relaxation
- Increased LES tone
- Esophageal aperistalsis
Esophageal Achalasia (Chalasia= Relaxation) primary-> idopathic
What is the MCC of secondary Esophageal Achalasia?
Chagas Dz= Trypanosoma cruzi
What is the pathogenesis of Chagas disease causing Achalasia?
Trypanosoma cruzi destroys the myenteric plexus= failure of LES relaxation + esophageal dilation
What are some other causes of Achalasia like disease?
Diabetic autonomic neuropathy Malignancy Amyloidosis Sarcoidosis Polio
What are the 2 MCC of Esophageal varices?
Cirrhosis
Schistosomiasis
MCC of death of advanced Cirrhosis patient?
Esophageal varices
Chronic alcoholics and bulimics present with Hematemesis due to GEJ tears?
Mallory-Weiss tears = Linear + longitudinally oriented tears heal rapidly
Transmural esophageal tears and Mediastinitis caused by Chronic vomiting?
Boerhaave syndrome= (Cutaneous Emphysema)
What conditions decrease LES tone and contribute to GERD?
Tobacco ETOH Obesity-> increase Abdominal pressure CNS depressants Pregnancy Hiatal hernia Delayed gastric emptying Increased Gastric volume
What can be seen on the Esophagus during mild or Severe GERD?
Mild= Hyperemia (redness) Severe= Eosinophils + PMNs + Basal zone Hyperplasia
Pt with dysphagia, feeding intolerance, and large # of Eosinophils in esophageal biopsy far from GEJ?
Eosinophilic Esophagitis
Endoscopy shows patches of red, velvety mucosa extending upward from GEJ will most likely reveal what on microscopy?
Metaplastic Columnar cells with GOBLET cells= Barrett’s esophagus
**increased risk for Adenocarcinoma
MC esophageal neoplasm in US?
Adenocarcinoma= Due to GERD
Chronic alcoholic presents with Dysphagia, Odynophagia, wght loss, chest pain, and vomiting needs to be checked for what?
Adenocarcinoma= Barrett esophagus
What are the risk factors for Esophageal SCC?
ETOH Tobacco Poverty Achalasia Plummer-Vinson syndrome HOT TEA previous radiation
What is the lymph node spread for Esophageal SCC?
upper 1/3= Cervical LN
middle 1/3= Thoracic LN
Lower 1/3= Celiac LN
Esophagitis is most frequent in what kind of patients?
Immunocomprimised pts= Candidiasis is sign of HIV-> AIDS
What are foveolar cells?
Mucus secreting cells in the Antrum (cardia) of stomach
What factors lead to developing Gastritis/ damage stomach mucosa?
H pylori NSAIDS ETOH Radiation/ Chemo Aspirin Smoking Hyperacidity Duodenal-gastric reflux
What is the significant finding indicating inflammation of the Stomach lining?
PMNs above basement membrane–> IN direct contact with Epithelial cells
What are the defensive forces that protect the stomach lining?
Mucus HCO3 in mucus Mucosal Blood flow Apical membrane transport Epithelial regeneration Elaboration of PGs
What are the mCC of focal acute peptic injury?
NSAIDs
STRESS–> hypoxia induced
Peptic injury most commonly occurring in critically ill pts with Shock, sepsis, or severe trauma?
Stress Ulcers–> Systemic Acidosis
Peptic injury occurring in the proximal duodenum associated with severe burns or trauma?
Curling Ulcers
Peptic injury arising in stomach, duodenum, or esophagus of persons with intracranial disease with High incidence of perforations?
Cushing Ulcers–>
Intracranial injury= Increased Vagus stimulation= Acid Hypersecretion
What are the protective affects of PGs?
Induce HCO3 secretion
Enhance mucosal blood flow
Patient with nausea, vomiting, and “Coffee ground” hematemesis?
Gastric Ulcer
Nausea, upper abdominal discomfort, vomiting, but no Hematemesis?
Chronic Gastritis
MCC of chronic + atrophic?
Chronic= H pylori Atrophic= Autoimmune
*less common= Radiation or Chronic bile reflux
What manifests as predominately antral gastritis with HIGH acid production despite Hypogastrinemia?
H pylori infection= increased risk for Duodena ulcers and ANTRAL gastritis
What are the four virulence factors of H pylori that allow it to infect the stomach?
Flagella= confers motility in mucus Urease= generates NH3 from Urea to Lower pH Adhesions= adhere to foveolar cells Toxins= Cytotoxin-associated gene A (CagA) increases risk for ULCERS + CANCER
Chronic antral H pylori gastritis may progress to Pangastritis resulting in multifocal atrophic gastritis with Reduced acid secretion which Increases risk of what?
Metaplasia–> ADENOCARCINOMA
What tests can be used to detect H pylori infection?
Biopsy to identify organism or PCR
Serology for Anti- H pylori antibodies
Fecal bacterial detection
Urea breath test
What antibodies can be detected in serum and gastric secretions in autoimmune gastritis?
Antibodies to Parietal cells and Intrinsic factor
Gastric disorder characterized by Reduced serum Pepsinogen I levels Antral endocrine cell Hyperplasia V B12 deficiency Defective gastric acid secretion (achlorhydria)?
Autoimmune Gastritis
What is the pathogenesis for the findings in Autoimmune Gastritis?
Antibodies destroy Parietal cells
Reduced HCl = Increased Gastrin release
Increased Gastrin= Hyperplasia of antrum G cells
Reduced IF= V B12 def= megaloblastic anemia
Chief cell loss= Reduced Pepsinogen
What is often associated with both Achlorhydria and pernicious anemia?
Autoimmune Gastritis
Contrast the difference in location differences btwn H pylori and AI gastritis?
H pylori= ANTRUM
AI= BODY and FUNDUS
Gastic pathology associated with: PMNs and Subepithelial plasma cells Increased Acid secretion Normal Gastrin release Hyperplastic/inflammatory polyps What is RF and sequelae?
H pylori induced Antral Gastritis
RF: Low SE status + poverty + Rural areas
Sequelae: Peptic Ulcers + adenocarcinoma + Lymphoma
Gastric pathology defined by: Lymphocytes and Macs invasion Decreased HCl production Increased Gastrin Neuroendocrine hyperplasia What is the Dx test and Sequelae?
Autoimmune Gastritis
Dx test: Antibodies to Parietal cells (Proton pump or IF)
Sequelae: Atrophy, Pernicious anemia, Adenocarcinoma, Carcinoid tumor
What are the MC sites of PUD?
Antrum + 1st part of Duodenum
PUD occurring in the small intestines of a child is often secondary to what?
Gastric heteropia within–>Meckel Diverticulum
What is the fundamental cause of PUD?
Gastric Hyperacidity= MCC by H pylori
What are some known Cofactors for developing PUD?
chronic NSAIDS Cigarettes-> impairs blood flow/ healing ETOH HD Corticosteroids= Inhibit PG synthesis/healing Hyperparathyroidism Chronic Renal failure
What is the pathogenesis for Hyperparathyroidism and Chronic Renal failure causing PUD?
HYPERCALCEMIA= stimulates Gastrin release
MC in the proximal duodenum, sharply punched-out lesion with smooth and richly vascularized granulation tissue?
PUD
Pt complains of epigastric burning or aching, anemia, with pain occurring 1-3 hrs after meals and Worse at NIGHT. N/V and bloating?
PUD
Causes increased Gastric production and MALT transformation into Lymphoma?
H pylori gastritis
Found in patients with Hx of Familial adenomatous polypsosis and increased risk with proton pump inhibitors (due to Increased Gastrin)?
Fundic gland Polyps
What are the MC risk factors for Gastric adenocarcinoma?
Mutations- CDH1 + APC genes
H pylori
EBV–> Diffuse with Lymphocytic infiltrates
CDH1 mutation increased the risk of what type of gastric neoplasia and why?
Adenocarcinoma
Mutation= LOSS of E-cadherins
Lauren classification of Gastric adenocarcinoma:
1: Elevated mass with heaped boarders and central ulceration
2. Dischohesive cells with SIGNET RING cells + Desmoplastic reaction causing Loss of RUGAE = Linitis plastic?
- Intestinal Adenocarcinoma-> closely associated with Atrophic gastritis
- Diffuse Adenocarcinoma= “leather bottle”
What are the most powerful diagnostic indicators of Gastric adenocarcinomas?
Depth of invasion-> Locally invades
Nodal/ distant mets
What are the most common types of Lymphomas in the GI tract?
Diffuse Large B cell
MALTomas
Tan intramural or submucosal masses that elicit intense desmoplastic reaction causing kinking or bowel obstruction and histology shows trabeculae/ sheets of uniforms cells with Stippled nuclei?
Carcinoid tumor
Often causes Cutaneous flushing, sweating. bronchospasms, colicky abdominal pain, diarrhea, and right sided cardiac valvular fibrosis?
Carcinoid tumor secreting Vasoactive substances
What is the pathogenesis of 75-80% of Gastrointestinal stromal tumors (GIST)?
cKIT or PDGFRA mutations–> tyrosine Kinase
**Arises from Interstitial cells of CAJAL
What is the most important factor when i comes to Carcinoid tumors?
LOCATION
Small intestines= Malignant
Appendix= Benign
Small flask-like outpouchings that occur in btwn taeniae coli of the Sigmoid colon most commonly in pts >60yo?
Diverticulosis
Thinning of the diverticula walls and fecal entrapment can lead to?
Diverticulitis –> perforation
Often asymptomatic, or 60 yo male with Low fiber diet with intermittent cramping, lower abdominal pain, constipation, and diarrhea?
Diverticulosis
Chronic condition of bowl resulting from inappropriate mucosal immune activation?
Inflammatory bowel disease
Inflammation limited to COLON and RECTUM, and extends only into mucosa and submucosa?
Ulcerative colitis
Transmural inflammation of Ileum leading to Strictures?
Crohn disease
Skip lesions, transmural inflammation, ulcerations, and fissures?
Crohn disease
Continuous colonic involvement beginning at RECTUM, and pseudo polyps and ulcer formations?
Ulcerative colitis
What are the genetic links for Crohns vs. ulcerative colitis?
Crohn= 50% rate in monozygotic twins UC= 16% rate in monozygotic twins
What is the gene responsible for increase susceptibility to Crohns disease?
NOD2= protein binds bacterial peptidoglycans and activated NF-kB
What immune cells are the primary target of Crohns disease therapy?
Th1 and Th17 cells
**Th1 secrete IFN= activates Macs= Granulomas
What cells are overreacting in ulcerative colitis?
Th2 –> overproduce IL-13
What epithelial defects are associated with Crohsna and UC?
Defective intestinal epithelial tight junctions= NOD2
Paneth Cell granules= abnormal in Crohns
How do appendicitis and smoking affect Crohns and UC?
Appendicitis= reduced risk of UC Smoking= Reduced risk of UC + increased Crohns
Most common site of Crohn disease involvement?
Terminal Ileum
Ileocecal valve
Cecum
What is the earliest lesion in Crohns disease?
Aphthous ulcer–> Cobblestone appearing–> Fissures between mucosal folds
Transmural inflammation of Crohns causes what kind of reaction in Small bowel wall?
Wall thickening
Submucosal fibrosis
hypertrophy of muscularis propria
Creeping fat= strictures or perforations
What are the microscopic features of Crohn disease?
Crypt abscess= PMNs within crypt + ulcers + branching crypts + GRANULOMAS
Paneth cell metaplasia in Left colon + noncaseating granulomas are a hallmark of what disease?
Crohn disease
Pt with mild NON-bloody diarrhea + fever, and abdominal pain?
Crohn disease
What are the Extraintestinal manifestations of Crohn disease?
Uveitis Migratory polyarthritis sacroiliitis ankylosing spondylitis Ertythema Nodosum Clubbing
Always involves Rectum and ascends into colon?
Ulcerative colitis
Colonic mucosa appearing as granular, broad-based ulcers, mucosal atrophy, NO Strictures?
Ulcerative colitis
Pt with ulcerative colitis develops a condition caused by inflammation and inflammatory mediators damaging muscularis mucous and disturb the neuromuscular function?
Toxic megacolon
What are the histological features of Ulcerative colitis?
Generalized superficial Inflammation Crypt abscesses Crypt distortion Epithelial metaplasia NO GRANULOMAS
Pt with attacks of Bloody diarrhea, expulsion of stringy mucoid material, and Lower abdominal pain and cramping relieved by defecation?
Ulcerative colitis
30 yo white female, abdominal cramps, bloody stool for 6 mo, wght loss, oral ulcers, blood on rectal exam and Fistula draining foul smelling fluid?
Crohn Disease
What is the DDx for Toxic megacolon?
- C. difficile pseudomembranous colitis
- IBD (UC or Crohn dz)
- Obstruction: tumor or inflammation
- Functional disorder associated with psychiatric disease or meds
- Chagas Disease
What is associated with failure of urorectal septum formation in cloaca (wk7) or failure of anal membrane opening (wk8) or Down syndrome?
Anorectal stenosis or Atresia
Male 60 yo, with chronic gastritis and atrophy/ intestinal metaplasia is diagnosed with gastric adenoma. The risk of this lesion becoming an adenocarcinoma is related to what?
SIZE= >2cm = Higher risk
Familial diffuse gastric adenocarcinoma is associated with what genetics?
CDH1 mutation= Loss of E-cadherins
Patients with FAP have a mutation in what gene that increases their risk for Intestinal Gastric adenocarcinoma?
APC= deactivates Beta catenin
Pt with sweating, redness, colicky abdominal pain, bronchospasms, diarrhea, and Right sided valvular fibrosis?
Carcinoid syndrome
75% of GIST have what gain of function mutation and arises from what GI cells?
c-KIT= Tyrosine kinase
Interstitial cells of Cajal
Microscopic examination of intestines reveals atrophy and sloughing of surface epithelial cells but hyperplastic crypts?
Ischemic bowel
Older patient with sudden severe abdominal pain, tenderness, N/V, bloody diarrhea, and melanotic stool?
Acute transmural intestinal infarction
**Decreased bowel sounds-> shock
Patient present with rectal bleeding, mucus discharge, and inflammatory lesion on anterior rectal wall?
Solitary rectal ulcer syndrome
**caused by impaired relaxation of anorectal sphincter
5 yo male with rectal bleeding, and prolapsed mass in the rectum?
Juvenile polyp
**SMAD4 mutation
AD disorder characterized by multiple GI hamartomatous polyps in small intestines and mucocutaneous hyper-pigmentation?
Peutz Jeghers syndrome
Smooth nodular protrusions of mucosa, most common in Left colon, with SERRATED glands and lots of goblet cells?
Hyperplastic polyps
Pre-cancerous colonic lesions in 50 yo patients?
Adenomas
Polyp with surface erosions, cystically dilated crypts filled with mucus, PMNs, and debris in a childs rectum?
Juvenile polyp
Polyp in small intestine with complex glandular architecture and bundles of Smooth Muscle?
Peutz-Jeghers polyp
Pt with intestinal polyps, osteomas of mandible, and desmoid and thyroid tumors?
Gardners Syndrome
Pt with intestinal adenomas, CNS tumors
(medulloblastomas or glioblastomas)?
Turcot syndrome
DNA mismatch repair mutation or MSH2/MLH1, causing predominately RIGHT sided sessile serrated adenomas or mucinous adenocarcinomas?
HNPCC
APC/WNT pathway mutation causing LEFT sided colonic tubular or villous adenomas or adenocarcinoma?
Sporadic Colon cancer
What syndrome was described as a familial clustering of colorectal, endometrial, stomach, ovarian, ureter, brain, small bowel, and skin cancers?
LYNCH syndrome or HNPCC
Describe the APC/Beta catenin pathway to colonic adenocarcinoma?
APC is negative regulator of Beta catenin
Beta catenin is part of WNT proliferative pathway
Mutation in APC= Increased Beta catenin
Beta catenin-> translocates into nucleus and activates MYC and cyclin D= Increased Prolif
Describe the molecular changes in the adenoma-carcinoma sequence?
Normal= Inherited APC mutation
Second HIT= LOSS of APC= Increased Bcatenin
Adenoma-Early > KRAS mutations
Adenoma Late–> SMAD 2+4 + p53 mutations
Carcinoma- Telomerase mutation
What are the Early and Late mutations in the Adenoma-> carcinoma sequence of colon cancer?
Early= KRAS Late= p53
What is microsatellite instability?
DNA mismatch repair deficiency mutations accumilate in microsatellite repeats
**Silence unless in BAX or TGF-beta encoding sequences
What is the molecular changes leading to colonic carcinoma in the mismatch repair pathway?
Normal= Inherited MSH2 + MLH 1 mutations
Sessile serrated adenoma= Microsatellite instability
Carcinoma= BAX & BRAF mutations
What kind of tumors are found in the RIGHT vs LEFT colon?
Right= polypoid, exophytic, bleeding Left= Annular + obstructive
Hyperplastic polyps must be distinguished from what due to their malignant potential?
Sessile serrated polyps
What is the difference in cancer transformation timelines btwn FAP and HNPCC?
FAP= develop cancer EARLY (<30yo) HNPCC= Cancer late in life
Comma shaped organism found in warm waters around Ganges valley in India and Bangladesh causing severe watery diarrhea?
V cholera
What are the complication associated with C jejuni infections?
Guillian Barre
Erythema Nodosum
Reactive arthritis= HLA-B27 +
G- bacillus, Uncapsulated and nonmotile. Important cause of Bloody diarrhea?
Shigellosis
Pt with 6 days of diarrhea that started off watery but changes to Bloody, and complications include Reiters syndrome (“cant pee, see, climb Tree”)?
Shigella
Primary cause of Travelers diarrhea, Expresses LT that acts similar to Cholera toxin and ST that increases cGMP intracellular?
ETEC (enterotoxigenic E coli)
After inadequately cooked ground beef consumption patients develops dysentery and kidney failure caused by what organism that secrete Shiga like toxin?
EHEC (O157:H7)
Serotype of normal GI flora that causes bloody diarrhea via invasion of gut epithelium but does NOT produce toxins?
Enteroinvasive E coli
Causes gastroenteritis via spread through uncooked poultry and eggs?
Salmonella enteritidis
What is the pathogenesis of Salmonella induce gastroenteritis?
- *T3 secretion system transfers Bacterial proteins into M cells
- *Proteins activate host Rho GTPase causing bacterial endocytosis
- *Causes chemoattractant release- PMNs damage mucosa
Pt with acute onset of abdominal pain, N/V, bloody diarrhea, progresses to HIGH fever, small maculopapular lesions, and in LLQ?
Salmonella typhi= Typhoid fever
- *Rose spots= maculopapular lesions
- *SCD= Osteomyelitis
What is the morphology seen in MCC of antibiotic associated colitis?
C difficile= Pseudomembranes
Hospitalized patient with fever, leukocytosis, abdominal pain, cramps, Hypoalbuminemia, watery diarrhea, and dehydration?
C difficile
30 yo Pt returning from cruise suffer acute onset of N/V, watery diarrhea and abdominal pain. Fecal culture show no bacterial growth. Most likely diagnosis?
Norovirus infection
MCC of severe childhood (6-24mo) diarrhea and related deaths worldwide?
Rotavirus
What is the pathogenesis of Rotavirus induced bacteria?
Selectively infects and destroys Mature Enterocytes in small intestines
Villus surface is repopulated by IMMATURE cells causing decreased Absorption= Osmotic diarrhea
Nematode that infects intestinal mucosa by ingested eggs that hatch and penetrate mucosa, Circulate to LIVER and cause Abscesses and even Pneumonitis?
Ascaris lumbricoides
Larvae lives in fecally contaminated soil and penetrates broken skin. Larvae mature in intestines , release eggs and cause LIFE long auto infections?
Stronglyoides
This parasite is the leading cause of IRON deficiency anemia in the developing World?
Hookworms
Most common human parasitic infections, resistant to chloride treatment, Decreases Brush boarder enzymes and causes apoptosis of epithelial cells. Causes CHRONIC diarrhea and malabsorption?
Giardia
