Exam 3/Lecture 2 Flashcards

Question

# Esophagitis: injury & inflammation * What can promote an inflammatory esophageal reaction? * What also can cause esophageal injury and inflammation? * Esophagitis resulting from what?

Answer 1

* Lacerations from severe vomiting (acidic so damage) or physical trauma can promote an inflammatory esophageal reaction * Chemicals (medications) can also cause esophageal injury & inflammation * Esophagitis resulting from infection by viruses (herpes simplex, CMV) or by fungal organisms (Candida albicans)-> or chronic inflam.

Answer 2

esophagus is sensitive to acid damage

Answer 3

can promote acid reflux from stomach = **gastroesophageal reflux disease (GERD)**

Answer 4

* Often from **abnormal function of the lower esophageal sphincter** * Pts > 40 years old, heartburn dysphagia, sour-tasting regurgitation * Usually see **eosinophils** in mucosa, hyperemia (redness) * Complications include ulceration, stricture development, **Barrett’s esophagus = premalignant lesion**

Answer 5

* Prolonged reflux can result in **metaplasia** of gastric mucosa at gastroesophageal junction to that in small intestine (with Goblet cells) known as **Barrett's esophagus** * White males 40-60 yrs most affected * Presents endoscopically as patches of red mucosa travelling up from GE junction * Treated with surgery, laser ablation * Ablation of high-grade dysplasia may delay or prevent development of invasive adenocarcinoma, but when lymph node metastases occur, tumor is incurable by surgery * Barrett’s esophagus (**pre-malignant lesion**) increases risk for adenocarcinoma

Answer 6

adenocarcinoma & squamous cell carcinoma

Answer 7

* **Adenocarcinoma**: usually from GERD/ **Barrett’s esophagus** that has progressed to in situ carcinoma * Risk increased by tobacco use, obesity (diet), prior radiation therapy * Highest in Western countries, > males * 50% esophageal carcinoma in US is adenocarcinoma * Incidence rising, can be associated with mutations in p53 gene

Answer 8

* Pts present with dysphagia, weight loss, vomiting, chest pain, odynophagia * When diagnosed at late stage due to **lymphatic spread**, 5-yr survival < 25%-> spread quick * Tumors arise in **distal 1/3 of esophagus** with mucin-producing glands * May have involvement of gastric cardia

Answer 9

* **Squamous cell carcinoma found > males, > 45 yrs, more common in African Americans** * Strongly associated with smoking and heavy alcohol consumption * HPV and/or environmental/nutritional factors may increase risk for squamous cell carcinoma * Tumors occur in **middle 1/3 of esophagus** often causing strictures * Tumors easily **metastasize via lymph nodes** surrounding esophagus

Answer 10

* 5-yr survival < 10% with advanced disease * Microscopically presents with nests of s**quamous epithelial cells & keratin pearls** * Arises from squamous dysplasia (**carcinoma in situ**) * Pts present with dysphagia, odynophagia, obstruction

Answer 11

* Initiates enzymatic and mechanical digestion, **very low pH** * Helps kill ingested microorganisms * Stomach is composed of: **gastric cardia, fundus, body and antrum** * Gastric cardia adjoins tubular esophagus

Answer 12

* **Cardia** is lined by mucin-secreting foveolar cells (secrete mucin) arranged in shallow glands * **Fundus** contains chief cells (secrete digestive enzymes – pepsin) & parietal cells (secrete stomach acid) * **Antrum** contains mucus & neuroendocrine cells, which produce gastrin

Answer 13

* All regions have gastric pits receiving products of mucus-secreting gland cells * Muscular wall at gastric outlet in pylorus is thickened & forms a functional sphincter * Stomach prone to **inflammatory disease & cancer**

Answer 14

* Gastritis: acute and chronic * Chronic gastritis can lead to gastric/peptic ulcers (lesion on skin/mucosal surface with superficial loss of tissue, with inflammation)

Answer 15

* **Transient & self-limiting** inflammatory reaction * Caused by nonsteroidal anti-inflammatory drugs, heavy alcohol consumption, excessive acid secretion, infection and other systemic diseases that predispose to breakdown of protective mucous layer * **Epithelial layer is intact, neutrophils** (arrow) present indicate acute gastritis * If inciting cause of erosion persists, deeper extension of inflammation or necrosis can lead to **chronic gastritis** or formation of **peptic ulcer** (focal peptic injury leading to tissue erosion). * Pts present with pain, nausea, **emesis** (vomiting), **hematemesis** (vomiting blood)

Answer 16

* Persistent inflammatory reaction in gastric mucosa characterized by **lymphocytes & plasma cells in lamina propria** * Ongoing inflammatory damage to epithelial cells & underlying mucosa, can lead to **ulcers** * Pts present with pain, some vomiting (**emesis**), rare **hematemesis** (blood in vomit) * Common cause is chronic infection by **Helicobacter pylor**i live in low pH environment * Bacterial urease generates ammonia increases pH * Bacterial cytotoxins promote epithelial damag

Answer 17

* Chronic gastritis Increases risk for peptic ulcers (erosion or ulceration of stomach lining) * Chronic gastritis increases risk for **intestinal metasplasia** increases risk for gastric carcinoma * Eradicated with antibiotics

Answer 18

peptic ulcer disease (PUD)

Answer 19

* **PUD**: chronic gastritis (NSAID, H. pylori infection) causing hyperacidity * Commonly occurs in **gastric antrum & first portion of duodenum** * **Pain 1-3 hours after eating, worse at night, relieved by food or alkali** * Nausea, vomiting, bloating & belching may occur * Males> females, middle-older adults, 5000 deaths annually, 3 million pts/yr

Answer 20

* Managed by reducing acid secretion or antibiotics * Ulcers present as **solitary, round lesions, sharply punched-out defect** * Chronic ulcers result in **perforation** and release of gastric contents into peritoneal cavity causing **peritonitis or massive GI hemorrhage** * Intractable peptic ulcers can arise in **Zollinger-Ellison syndrome** (patients with gastrinomas producing abnormal secretion of hormone **gastrin** in stomach)

Answer 21

Gastric Intestinal Metaplasia

Answer 22

correspond to dilation of fundic glands, most common stomach polyp, are benign, rarely transform

Answer 23

* Usually arise from chronic gastritis (**inflammation**) * Pts may benefit from antibiotics if H. pylori is present * Epithelia **hyperplasia, benign** * Potential for dysplasia with larger polyps, **low risk for malignant transformation**

Answer 24

* Gastric adenomas (adenomatosis polyps): **precursors of adenocarcinoma.** * Account for 10% gastric polyps * Located in antrum, display epithelial **dysplasia**, most common **neoplastic polyp**

Answer 25

* Adenocarcinomas account for >90% gastric cancers * Early symptoms include dyspepsia (indigestion), **dysphagia**, nausea * Increased incidence related to increased Barrett esophagus * Pts at later stages present with weight loss, anorexia, altered bowel habits, anemia, hemorrhage * Overall 5-year survival is < 30% because diagnosed at late stage * Gastric adenocarcinomas classified as **intestinal & diffuse**

Answer 26

* **Intestinal** gastric adenocarcinoma: **bulky tumors, glandular** elements resembling colon where glandular elements secrete mucin * Develops following **intestinal mucosal metaplasia** * Stage (depth of invasion & nodal involvement) is dominant prognostic factor * 90% 5-yy survival after surgery for early stage * < 20% 5-year survival after surgery for late stage * Besides *H. pylori* infections, germline mutations in APC gene associated with β- catenin alterations in FAP increase risk for intestinal type gastric cancer

Answer 27

* **Diffuse gastric adenocarcinoma** thickens gastric wall without forming a discrete mass * **Infiltrative** growth pattern composed of discohesive cells * Infiltration by tumor cells produces "leather bottle" appearance called **linitis plastica** * Characterized by ***signet ring cells***, contain large mucin droplets & indented nucleus

Answer 28

* Signet ring cells (asterisk) invade gastric wall with **desmoplastic stromal response** that stiffens gastric wall * **Desmoplasia (arrows): fibroblastic hyperplasia** & disproportionate **fibrous CT** * Germline mutations coding for **E-cadherin** reduce epithelial integrity are found in familial gastric cancer of diffuse type * Signet ring cells do not express E-cadherin & have constitutively active of Wnt signaling

Answer 29

* **Small intestine** * Further digestion food after it leaves stomach and absorb nutrients, fats, iron * Lined by simple columnar epithelium with **abundant enterocytes**, some goblet cells, occasional enteroendocrine cells, **Paneth cells**, basal stem cells

Answer 30

* **Large intestine** absorbs water, electrolytes and forms/propels feces toward rectum for elimination * Lined by simple columnar epithelium, **many goblet cells**, endocrine cells and basal stem cells, but **no Paneth cells**

Answer 31

* Intestines prone to obstruction, inflammatory disease, benign proliferation & cancer * Intestinal diseases often present with **diarrhea**

Answer 32

* **Anatomical obstructions** include hernias, adhesions, volvulus, intussusceptions (infolding) * Anatomical abnormalities can be congenital or inherited * Present with abdominal distention, pain, vomiting and constipation * Dysfunction of small intestine leads to malabsorption & **diarrhea** * Dysfunction of large intestine results in diarrhea, fluid loss & anemia * Treated surgically

Answer 33

* 1:5000 births, males > females * Symptoms appear shortly after birth with failure to clear meconium & with subsequent constipation * Further consequences include **enterocolitis**, electrolyte imbalance & potential intestinal perforations * Congenital abnormality of the intrinsic nervous system due to **aganglionosis** in distal colon/rectum * Arises as congenital colonic innervation defect because neural crest cells fail to migrate and differentiate throughout the entire length of the colon * Results in **failure of peristalsis** * Normal colon immediately proximal to the **aganglionic segment is severely dilated** * Surgical removal of the aganglionic segment of intestine is curative

Answer 34

* **Diverticula** are luminal outpouchings of intestinal tract * Are congenital or acquired * **Acquired diverticulosis** occurs in patients with chronic constipation (increased intraluminal pressure from straining) causes focal luminal herniation * **Chronic diverticulitis** results in fibrosis and stenosis of large intestinal lumen * **Overgrowth of bacteria** in diverticula and luminal blockage by fecal material can result in **acute diverticulitis**, which can progress to abscess formation and peritonitis

Answer 35

* Genetically inherited or arises as autoimmune disease, dietary **gluten sensitivity** * Classically appears 6-24 months of age with irritability, abdominal distention, anorexia, **diarrhea**, weight loss * Serologic tests indicate **IgA** antibodies to **gliadin4** * T cells creating inflammatory reaction & tissue damage with IL-mediated expansion of CD8+ T cells * Pts at risk for T cell lymphoma and small intestinal adenocarcinoma * Removal of gluten from diet results in remission of disease | TYPE 2 REACTION

Answer 36

Celiac Disease * T-cell-mediated inflammatory process due to an immunoreaction to gluten results in atrophy of small intestinal villi (right)

Answer 37

* **IBD** is chronic inflammatory condition * Females>males, adolescence/young adults * Two forms are distinguished: **Crohn's disease and ulcerative colitis (UC)**

Answer 38

UC: * UC occurs in colon & rectum * UC extends only into mucosa & submucosa * Surgery can be curative for UC Crohn's: * Crohn’s occurs throughout small & large intestine * Crohn’s is usually transmural, **skip lesions** present Both: * UC & Crohn’s intestinal inflammation waxes and wanes * Anti-inflammatory therapies reduce and/or relieve severity of disease symptoms

Answer 39

* Can involve both large and small intestine in segmental manner (**skip lesions**) * Begins as ulcers that coalesce & promote **fissures** that perforate mucosa & deeper layers of the intestinal wall (**transmural - probe**) * **Creeping fat (arrows**) often surrounds the serosal surface

Answer 40

* Focal **granulomatous inflammation, lymphoid involvement** is common * **Intestinal thickening** from serosal inflammation & muscular fibrosis promotes **stricture** formation, resulting in **intestinal obstruction** * **Malabsorption of nutrients** by primary disease or following surgical resection * Pts present with intermittent **diarrhea**, fever, abdominal pain

Answer 41

* Distorted glandular epithelium * **Metaplasia** to gastric antral glands * **Paneth cell metaplasia** in **descending colon** (Paneth cells normally not present here) * **Granulomas** usually present (arrow) * Risk of **metaplasia/dysplasia which can lead to carcinoma**

Answer 42

* Mutations in Nucleotide-binding oligomerization domain-containing protein 2 gene, **NOD2**, increase risk for **Crohn**’s * **NOD2** recognizes bacterial peptidoglycans & stimulates IR * Altered TH1 & TH17 cell response in Crohn’s * Epithelial barrier defects may also promote bacterial invasion (altered tight junctions in Crohn’s) * **Abnormal Paneth** cell granules (reduced α-defensins) in Crohn’s * **Altered bacterial/microbial fauna** with IBD

Answer 43

* Contiguous involvement of **rectum ± large intestine = pancolitis**, small intestine is usually normal * **Flat ulcers** present, diffuse & **superficial ulcers** * Chronic disease leads to mucosal atrophy/thin mucosa * **Lack of skip areas** in UC distinguishes UC from Crohn’s

Answer 44

* **Mild fibrosis, lacks granulomas & fistulas** * Loss of crypts & formation of abnormal branched crypts (arrow) * Mucosal inflammation (dashed arrow) results in intestinal dysfunction with **diarrhea** * Chronic inflammation predisposes to epithelial **dysplasia and adenocarcinoma**

Answer 45

* Can be found in both UC and Crohn’s * Slender, **finger-like/worm-like projections of mucosa and sub-mucosa** * Pseudopolys **do not contain** fibrovascular core (found in polyp), do not have (flowerly) head, extensive branching presen

Answer 46

* Caused by **bacterial, viral or parasitic** infections responsible for 1⁄2 worldwide deaths by 5 yrs * Bacteria intestinal disease depends on ability to (1) adhere to intestinal mucosal cells (2) produce toxins, and (3) invade through the mucosal barrier * Bacterial **gastroenteritis** generally spread via the **oral-fecal route** * **Killing of commensal bacteria** by antibiotics allows expansion of resistant microorganisms that can cause disease

Answer 47

* Seasonal incidence during warm weather * Non-invasive, remains in the intestinal lumen * Cholera toxin that stimulates adenylate cyclase to increase cAMP which open CF receptors resulting in increased luminal chloride causing secretory diarrhea * **Watery diarrhea** (1L/hr) after 1-5 day bacterial incubation * Massive fluid loss leading to shock

Answer 48

* Invasive pathogen involves full thickness of the intestinal wall, can produce **septicemia**. * Presents with acute vomiting, **bloody diarrhea**, abdominal pain followed by flu-like phase and lastly high fever phase * Seasonal incidence during warm weather

Answer 49

* Transmitted though contaminated food/water and person-to-person * ‘Cruise-ship’ disease, very common * Presents with nausea, vomiting, **watery diarrhea** and abdominal pain * Self-limiting disease

Answer 50

* Most common severe childhood diarrhea * Ages 6 months – 2 years * Infects and **destroys mature adsorptive enterocytes** * Villus surface epithelial cells are replaced with immature & ineffective adsorptive cells resulting in **malabsorptive (fatty) diarrhea**

Answer 51

* Giardia is **flagellated protozoan** * Most common parasitic infection in humans * **Cysts** are transmitted though contaminated food/water * Non-invasive **trophozoites** are released from cysts in stomach * Giardia evades immune surveillance by modulating surface antigens * Giardia **reduces brush border** enzymes, damages small intestinal epithelial cells * Parasites can cause **bloody diarrhea**, malabsorption, and GI hemorrhage

Answer 52

* Colorectal cancer as 2nd cause of cancer death in US annually * Most adenocarcinomas of intestine arise from precursor polyps * macroscopic tissue mass that bulges outward from normal surface * Distinguish between non-neoplastic (**inflammatory, hyperplastic**) and pre-neoplastic (**adenoma**) polyps

Answer 53

* **Whitish** appearance due to **lymphocyte** infiltration * **Normal glandular** appearance with **Goblet cells** * Usually occur as solitary rectal polyps * Arise from chronic abrasion * No risk for malignant transformation

Answer 54

* Usually found in colon, >50 years * <5mm diameter * May occur singly or in groups * **Goblet** and absorptive cells present (normal/differentiated epithelium) * Thought to arise from ‘delayed shedding’ of old epithelial cells * No significant risk for malignant conversion

Answer 55

* **Potential** for adenoma polyps to develop into carcinoma * Sessile (flat) or pedunculated polyps ranging from 0.3 to 10 cm in diameter * Histologic examination reveals characteristic **epithelial dysplasia** * Size > 4 cm & epithelial dysplasia are greatest risk for cancer * Hereditary syndromes increase risk for cancer * Adenomatous polyps contain **stromal cores** * Recommended screening beginning at 45 years

Answer 56

* Adenomatous polyps vary in architectural, mostly as **tubular or villous polyps**, but both contain **epithelial dysplasia** * Cytologic features of adenomatous polyps include **increased N/C ratio**, loss of differentiated features, dyplasia * **Villous polyps** have a **greater risk** to progress to adenocarcinoma than tubular adenomas * **Sessile serrated adenomas lack epithelial dysplasia**, but present with **serrated architecture** throughout full length of highly differentiated glands

Answer 57

* 130,000 cases/yr & 55,000 deaths/yr US * 2nd to lung cancer deaths * Peak age of onset 60-70 yrs * Associated with high fat, high sugar, low fiber diet (alcohol, smoking) * Occur most frequently in **colon/rectum** compared with small intestine * Colon cancer frequently has an **exophytic or ulcerating** growth pattern

Answer 58

* Ascending colon derived from **midgut** * **> Women** * **Older age, poorer prognosis** * Pts can present with occult **bleeding**, pain * Changed bowel habits (**diarrhea**) * Weight loss (50%), **anemia**

Answer 59

* Tumors grow as larger, **exophytic**, polypoid masses * Extend along the wall of the ascending colon (creep along surface) * **Rarely cause obstruction** * Usually diagnosed with **higher TNM** score than descending colon carcinomas

Answer 60

* Descending colon derived from **hindgut** * **>Men** * **Younger age, better prognosis** * Changed bowel habits (**constipation**)

Answer 61

* Tumors grow as **invasive or constrictive rings (napkin rings)** along the distal colon * Usually diagnosed with **lower TNM** score than ascending colon carcinomas * Weight loss (15%) * Can cause GI **obstruction**

Answer 62

* Histological pattern of left & right colon CA is same * * Present as well to poorly differentiated adenocarcinoma * **Highly mucinous tumors with signet ring cells** (similar to gastric adenocarcinoma) are more invasive & associated with a worse prognosis * Important prognostic factors are depth of CA invasion & lymph node metastases * Most colonic **adenocarcinomas** form recognizable glands

Answer 63

one copy of APC tumor suppressor gene

Answer 64

* Thousands of (adenoma) polyps in large intestine * Can also develop less numerous adenomatous polyps in small intestine & stomach. * >100 polyps necessary for FAP diagnosis though thousands may be present * Morphologically same as sporadic adenomas

Answer 65

* Develops into colorectal cancer in 100% untreated pts * Early age disease onset * Treated with surgical intervention * APC mutations can also contribute to: * **Gardner** syndrome (intestinal polyps + osteomas, dental abnormalities) * **Turcot** syndrome (intestinal polyps + CNS tumors)

Answer 66

* HNPCC aka Lynch syndrome * **Familial cancer clusters of colon, ovary, endometrium, stomach, ureter, brain, skin, liver**-> O cubless * Do not present with hundreds- thousands of polyps, but rather from **single adenoma polyp** * HNPCC colon cancers develop earlier than sporadic colon cancers * Often **descending** colon cancer * Arises from mutations in DNA mismatch repair genes (**MSH2, MLH1**)

Answer 67

* Narrow lumen of appendix predisposes to obstruction by fecal material * Obstruction results in bacterial overgrowth and acute inflammation of mucosa, possibly progressing to acute **appendicitis** * Obstruction promotes increased intraluminal pressure and pain

Answer 68

* Common in adolescents/young adults, lifetime risk is 7%; males > females * May be difficult to diagnose * **Rare carcinoid tumors** are common in appendix, rarely metastasize bz slow growing, treated with surgery * Histologic features: monotonous tumor cells with salt and pepper chromatin, inconspicuous nucleoli, moderate to abundant eosinophilic cytoplasm

Exam 3/Lecture 2 Flashcards

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