gastrointestinal Pathology Flashcards
(38 cards)
Sialolithiasis
Stone(s) in salivary gland duct. Can occur in 3
major salivary glands (parotid, submandibular,
sublingual). Single stone more common in
submandibular gland (Wharton duct).
Presents as recurrent pre-/periprandial pain and
swelling in affected gland.
Caused by dehydration or trauma.
Treat conservatively with NSAIDs, gland
massage, warm compresses, sour candies (to
promote salivary flow).
Sialadenitis—inflammation of salivary gland due
to obstruction, infection, or immune-mediated
mechanisms.
Salivary gland tumors
Most commonly benign and in parotid gland. Tumors in smaller glands more likely malignant.
Typically present as painless mass/swelling. Facial pain or paralysis suggests malignant
involvement of CN VII.
. Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor A .
Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or
ruptured intraoperatively. May undergo malignant transformation.
.Mucoepidermoid carcinoma—most common malignant tumor, has mucinous and squamous
components.
.Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal
centers. Typically found in smokers. Bilateral in 10%; multifocal in 10%.
Achalasia
Failure of LES to relax due to loss of myenteric
(Auerbach) plexus due to loss of postganglionic
inhibitory neurons (which contain NO and
VIP).
Manometry findings include uncoordinated
or absent peristalsis with high LES resting
pressure progressive dysphagia to solids and
liquids (vs obstruction—solids only). Barium
swallow shows dilated esophagus with an area
of distal stenosis (“bird’s beak”
risk of esophageal cancer.
2° achalasia (pseudoachalasia) may arise
from Chagas disease (T cruzi infection) or
extraesophageal malignancies (mass effect or
paraneoplastic).
Esophageal pathologies
Boerhaave syndrome
Eosinophilic esophagitis
Esophageal strictures
Esophageal varices
Esophagitis
Gastroesophageal reflux disease
Mallory-Weiss syndrome
Plummer-Vinson syndrome
Sclerodermal esophageal dysmotility
Boerhaave syndrome-Transmural, usually distal esophageal rupture with pneumomediastinum due to
violent retching. Subcutaneous emphysema may be due to dissecting air (crepitus may be felt in
the neck region or chest wall). Surgical emergency.
Eosinophilic esophagitis-Infiltration of eosinophils in the esophagus often in atopic patients. Food allergens –>dysphagia, food impaction. Esophageal rings and linear furrows often seen on endoscopy. Typically unresponsive to GERD therapy.
Esophageal varices- Dilated submucosal veins in lower 1 ⁄3 of esophagus A 2° to portal hypertension. Common in cirrhotics, may be source of life-threatening hematemesis.
Esophagitis-Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill esophagitis (eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).
Gastroesophageal reflux disease-Commonly presents as heartburn, regurgitation, dysphagia. May also present as chronic cough, hoarseness (laryngopharyngeal reflux). Associated with asthma. Transient decreases in LES tone.
Esophageal pathologies
Mallory-Weiss syndrome-Partial-thickness mucosal lacerations at gastroesophageal junction due to severe vomiting. Often presents with hematemesis. Usually found in alcoholics and bulimics
Plummer-Vinson syndrome- Triad of Dysphagia, Iron deficiency anemia, and Esophageal webs. May be associated with glossitis. Increased risk of esophageal squamous cell carcinoma (“Plumbers DIE ”).
Sclerodermal esophageal dysmotility- Esophageal smooth muscle atrophy–> decreased LES pressure and dysmotility –> acid reflux and dysphagia–> stricture, Barrett esophagus, and aspiration. Part of CREST syndrome.
Barrett esophagus-Specialized intestinal metaplasia —replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells [stained blue in B ))in distal esophagus. Due to chronic gastroesophageal reflux disease (GERD). Associated with
increased risk of esophageal adenocarcinoma.
Esophageal cancer-Typically presents with progressive dysphagia (first solids, then liquids) and weight loss; poorprognosis.
Squamous cell carcinoma- affects upper 2/3 of esophagus, risk factors: Alcohol, hot liquids, caustic
strictures, smoking, achalasia.
Adenocarcinoma-affects lower 1/3 of esophagus. risk factors: Chronic GERD, Barrett esophagus, obesity, smoking, achalasia
Gastritis
Acute gastritis- Erosions can be caused by:
. NSAIDs—decreased PGE2 –> decreased gastric mucosa
protection
. Burns (Curling ulcer)—hypovolemia–> mucosal ischemia
. Brain injury (Cushing ulcer)—increased vagalstimulation –> increased ACh–> increased H+ production
Chronic gastritis-Mucosal inflammation, often leading to atrophy (hypochlorhydria–>hypergastrinemia) and intestinal metaplasia (increased risk of gastric cancers).
H. Plyori-affects antrum first and spread to body of stomach
autoimmune- autoantibodies to the H/K ATPase on parietal cells and to intrinsic factor. increased risk of pernicious anemia
affects the body/fundus of stomach
Ménétrier disease
Hyperplasia of gastric mucosa –> hypertrophied rugae (look like brain gyri A ). Causes excess mucus production with resultant protein loss and parietal cell atrophy with decreased acid production.
Precancerous.
Presents with epigastric pain, anorexia, weight loss, vomiting, edema (due to protein loss).
Gastric cancer
Most commonly gastric adenocarcinoma; lymphoma, GI stromal tumor, carcinoid (rare). Early aggressive local spread with node/liver metastases. Often presents late, with weight loss, abdominal pain, early satiety, and in some cases acanthosis nigricans or Leser-Trélat sign. Associated with blood type A
Intestinal—associated with H pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis. Commonly on lesser curvature; looks like ulcer with raised margins.
Diffuse—not associated with H pylori; signet ring cells (mucin-filled cells with peripheral nuclei) ; stomach wall grossly thickened and leathery (linitis plastica).
Virchow node—involvement of left supraclavicular node by metastasis from stomach.
Krukenberg tumor—bilateral metastases to ovaries. Abundant mucin-secreting, signet ring cells
Sister Mary Joseph nodule—subcutaneous periumbilical metastasis.
Peptic ulcer disease
what is the differences bewteen gastric ulcer and duodenal ulcer
when do you feel pain
what percentage of H. pylori is involved
mechanism?
other causes?
risk of carcinoma?
Gastric ulcer
PAIN Can be Greater with meals—weight loss
H PYLORI INFECTION ~ 70%
MECHANISM decreased mucosal protection against gastric acid
OTHER CAUSES NSAIDs
RISK OF CARCINOMA increased
OTHER Biopsy margins to rule out malignancy
Duodenal ulcer
PAIN Decreases with meals—weight gain
H PYLORI INFECTION ~ 90%
MECHAISM decreased mucosal protection or increased gastric acid secretion
other causes: Zollinger-Ellison syndrome
Risk of Carcinoma: Generally benign
Other: Hypertrophy of Brunner glands
Ulcer complications
Hemorrhage-Gastric, duodenal (posterior > anterior). Most common complication. Ruptured gastric ulcer on the lesser curvature of stomach –> bleeding from left gastric artery. An ulcer on the posterior wall of duodenum –> bleeding from gastroduodenal artery.
Obstruction-Pyloric channel, duodenal.
Perforation-Duodenal (anterior > posterior). May see free air under diaphragm with referred pain to the shoulder via irritation of phrenic nerve.
Malabsorption syndromes
Celiac disease
Lactose intolerance
Pancreatic insufficiency
Tropical sprue
Whipple disease
celiac disease- Gluten-sensitive enteropathy, celiac sprue. Autoimmune-mediated intolerance of gliadin (gluten protein found in wheat)–> malabsorption and steatorrhea. Associated with HLA-DQ2, HLA-DQ8
Findings: IgA anti-tissue transglutaminase (IgA tTG), anti-endomysial, anti-deamidated gliadin peptide antibodies; villous atrophy,crypt hyperplasia, intraepithelial lymphocytosis. Moderately increased risk of malignancy (T-cell lymphoma)
decreased mucosal absorption primarily affects distal duodenum and/or proximal jejunum.
d-xylose test: passively absorbed in proximal small intestine; blood and urine levels decreased with mucosa defects or bacterial overgrowth, normal in pancreatic insufficiency
Treatment: gluten-free diet.
Lactose intolerance
Normal-appearing villi, except when 2° to injury at tips of villi (eg, viral enteritis). Osmotic diarrhea with decreased stool pH (colonic bacteria ferment lactose).
Lactose hydrogen breath test
Pancreatic insufficiency
Due to chronic pancreatitis, cystic fibrosis, obstructing cancer. Causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12.
decreased duodenal pH (bicarbonate) and fecal elastase.
Tropical sprue
Similar findings as celiac sprue (affects small bowel), but responds to antibiotics. Cause is unknown, but seen in residents of or recent visitors to tropics
decreased mucosal absorption affecting duodenum and jejunum but can involve ileum with time. Associated with megaloblastic anemia due to folate deficiency and, later, B12 deficiency
Whipple disease
Infection with Tropheryma whipplei (intracellular gram ⊕); PAS ⊕ foamy macrophages in intestinal lamina propria , mesenteric nodes. Cardiac symptoms, Arthralgias, and Neurologic symptoms are common. Diarrhea/steatorrhea occur later in disease course. Most common in older men.
Crohn disease
LOCATION Any portion of the GI tract, usually the terminal ileum and colon. Skip lesions, rectal sparing.
GROSS MORPHOLOGY Transmural inflammation –> fistulas. Cobblestone mucosa, creeping fat, bowel wall thickening (“string sign” on barium swallow x-ray ), linear ulcers, fissures)
MICROSCOPIC MORPHOLOGY Noncaseating granulomas and lymphoid aggregates. Th1 mediated.
complications: fistula
INTESTINAL MANIFESTATION Diarrhea that may or may not be bloody.
EXTRAINTESTINAL MANIFESTATIONS: Kidney stones (usually calcium oxalate), gallstones. May be ⊕ for anti-Saccharomyces cerevisiae antibodies (ASCA).
TREATMENT Corticosteroids, azathioprine, antibiotics (eg, ciprofloxacin, metronidazole), infliximab, adalimumab.
Ulcerative colitis
LOCATION Colitis = colon inflammation. Continuous colonic lesions, always with rectal involvement.
GROSS MORPHOLOGY Mucosal and submucosal inflammation only. Friable mucosa with superficial and/or deep ulcerations (compare normal B with diseased C ). Loss of haustra –> “lead pipe”
MICROSCOPIC MORPHOLOGY Crypt abscesses and ulcers, bleeding, no granulomas. Th2 mediated.
complications: Fulminant colitis, toxic megacolon, perforation.
INTESTINAL MANIFESTATION Bloody diarrhea.
EXTRAINTESTINAL MANIFESTATIONS 1° sclerosing cholangitis. Associated with p-ANCA.
TREATMENT 5-aminosalicylic preparations (eg, mesalamine), 6-mercaptopurine, infliximab, colectomy
For Crohn, think of a fat granny and an old crone skipping down a cobblestone road away from the wreck (rectal sparing
Ulcerative colitis causes ULCCCERS:
Ulcers
Large intestine
Continuous,
Colorectal carcinoma,
Crypt abscesses
Extends proximally
Red diarrhea
Sclerosing cholangitis
Diverticulum-Blind pouch protruding from the alimentary tract that communicates with the lumen of the gut. Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed “false diverticula.”
“True” diverticulum—all gut wall layers outpouch (eg, Meckel).
“False” diverticulum or pseudodiverticulum— only mucosa and submucosa outpouch. Occur especially where vasa recta perforate muscularis externa.
Diverticulosis
Many false diverticula of the colon , commonly sigmoid. Common (in ~ 50% of people > 60 years). Caused by INCREASED intraluminal pressure and focal weakness in colonic wall. Associated with obesity and diets low in fiber, high in total fat/red meat.
Complications include diverticular bleeding (painless hematochezia), diverticulitis
Diverticulitis Inflammation of diverticula with wall thickening classically causing LLQ pain, fever, leukocytosis. Treat with antibiotics.
Complications: abscess, fistula (colovesical fistula –> pneumaturia), obstruction (inflammatory stenosis), perforation (–> peritonitis).
Zenker diverticulum
Pharyngoesophageal false diverticulum. Esophageal dysmotility causes herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor. Presenting symptoms: dysphagia, obstruction, gurgling, aspiration, foul breath, neck mass. Most common in elderly males
Elder MIKE has bad breath.
Elderly
Males
Inferior pharyngeal constrictor
Killian triangle
Esophageal dysmotility
Halitosis
Meckel diverticulum
True diverticulum. Persistence of the vitelline (omphalomesenteric) duct. May contain ectopic acid–secreting gastric mucosa and/or pancreatic tissue. Most common congenital anomaly of GI tract. Can cause hematochezia/ melena (less commonly), RLQ pain, intussusception, volvulus, or obstruction near terminal ileum.
Contrast with omphalomesenteric cyst = cystic dilation of vitelline duct
Diagnosis: pertechnetate study for uptake by heterotopic gastric mucosa.
The rule of 2’s:
2 times as likely in males.
2 inches long.
2 feet from the ileocecal valve.
2% of population.
Commonly presents in first 2 years of life.
May have 2 types of epithelia (gastric/ pancreatic).
Hirschsprung disease
Congenital megacolon characterized by lack of ganglion cells/enteric nervous plexuses (Auerbach and Meissner plexuses) in distal segment of colon. Due to failure of neural crest cell migration. Associated with mutations in RET
Presents with bilious emesis, abdominal distention, and failure to pass meconium within 48 hours –> chronic constipation. Normal portion of the colon proximal to the aganglionic segment is dilated, resulting in a “transition zone.”
Risk INCREASED with Down syndrome. Explosive expulsion of feces (squirt sign)–> empty rectum on digital exam
Diagnosed by absence of ganglionic cells on rectal suction biopsy. Treatment: resection
Malrotation
Anomaly of midgut rotation during fetal development improper positioning of bowel (small bowel clumped on the right side)
formation of fibrous bands (Ladd bands). Can lead to volvulus, duodenal obstruction.
Volvulus
Twisting of portion of bowel around its mesentery; can lead to obstruction and infarction. Can occur throughout the GI tract. Midgut volvulus more common in infants and children. Sigmoid volvulus (coffee bean sign on x-ray)
more common in elderly.
Intussusception
Telescoping of proximal bowel segment into a distal segment, commonly at ileocecal junction.
Compromised blood supply –> intermittent abdominal pain often with “currant jelly” stools. Patient may draw legs to chest to ease pain. Exam may reveal sausageshaped mass. Ultrasound shows “target sign.” Often due to a lead point, but can be idiopathic.
Most common pathologic lead point is a Meckel diverticulum (children) or intraluminal mass/tumor (adults). Majority of cases occur in children; unusual in adults
May be associated with rotavirus vaccine, Henoch-Schönlein purpura, and recent viral infection (eg, adenovirus; Peyer patch hypertrophy creates lead point).
Other intestinal disorders
Acute mesenteric ischemia
Chronic mesenteric ischemia
Colonic ischemia
Angiodysplasia
Adhesion
Ileus
Meconium ileus
Necrotizing enterocolitis
Acute mesenteric ischemia-Critical blockage of intestinal blood flow (often embolic occlusion of SMA) –> small bowel necrosis–>abdominal pain out of proportion to physical findings. May see red “currant jelly” stools.
Chronic mesenteric ischemia–>“Intestinal angina”: atherosclerosis of celiac artery, SMA, or IMA–> intestinal hypoperfusion–> postprandial epigastric pain–> food aversion and weight loss.
Colonic ischemia-Reduction in intestinal blood flow causes ischemia. Crampy abdominal pain followed by hematochezia. Commonly occurs at watershed areas (splenic flexure, distal colon). Typically affects elderly. Thumbprint sign on imaging due to mucosal edema/hemorrhage.
Angiodysplasia-Tortuous dilation of vessels–>hematochezia. Most often found in the right-sided colon. More common in older patients. Confirmed by angiography. Associated with aortic stenosis and von Willebrand disease.
Adhesion-Fibrous band of scar tissue; commonly forms after surgery. Most common cause of small bowel obstruction, demonstrated by multiple dilated small bowel loops on x-ray
Ileus-Intestinal hypomotility without obstruction–>constipation and decreased flatus; distended/tympanic abdomen with decreased bowel sounds. Associated with abdominal surgeries, opiates, hypokalemia, sepsis. Treatment: bowel rest, electrolyte correction, cholinergic drugs (stimulate intestinal motility).
Meconium ileus-In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.
Necrotizing enterocolitis-Seen in premature, formula-fed infants with immature immune system. Necrosis of intestinal mucosa (primarily colonic) with possible perforation, which can lead to pneumatosis intestinalis, free air in abdomen, portal venous gas.
Colonic polyps-Growths of tissue within the colon. May be neoplastic or non-neoplastic. Grossly characterized as flat, sessile, or pedunculated (on a stalk) on the basis of protrusion into colonic lumen. Generally classified by histologic type.
Malignant potential
Adenomatous polyps-Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS. Tubular histology has less malignant potential than villous (“villous histology is villainous”); tubulovillous has intermediate malignant potential. Usually asymptomatic; may present with occult bleeding.
Serrated polyps-Premalignant. Characterized by CpG island methylator phenotype (CIMP; cytosine base followed by guanine, linked by a phosphodiester bond). Defect may silence MMR gene (DNA mismatch repair) expression. Mutations lead to microsatellite instability and mutations in BRAF. “Sawtooth” pattern of crypts on biopsy. Up to 20% of cases of sporadic CRC.
Polyposis syndromes
Familial adenomatous polyposis-Autosomal dominant mutation of APC tumor suppressor gene on chromosome 5q21. 2-hit hypothesis. Thousands of polyps arise starting after puberty; pancolonic; always involves rectum. Prophylactic colectomy or else 100% progress to CRC.
Gardner syndrome-FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium, impacted/supernumerary teeth.
Turcot syndrome-FAP/Lynch syndrome + malignant CNS tumor (eg, medulloblastoma, glioma). Turcot = Turban
Peutz-Jeghers syndrome-Autosomal dominant syndrome featuring numerous hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia. Associated with increased risk of breast and GI cancers (eg, colorectal, stomach, small bowel, pancreatic).
Juvenile polyposis syndrome-Autosomal dominant syndrome in children (typically < 5 years old) featuring numerous hamartomatous polyps in the colon, stomach, small bowel. Associated with increased risk of CRC.
Lynch syndrome
Previously known as hereditary nonpolyposis colorectal cancer (HNPCC). Autosomal dominant mutation of DNA mismatch repair genes with subsequent microsatellite instability. ∼ 80% progress to CRC. Proximal colon is always involved. Associated with endometrial, ovarian, and skin cancers.
Colorectal cancer
EPIDEMIOLOGY Most patients are > 50 years old. ~ 25% have a family history
RISK FACTORS Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed meat with low fiber
PRESENTATION Rectosigmoid > ascending > descending.
Ascending—exophytic mass, iron deficiency anemia, weight loss.
Descending—infiltrating mass, partial obstruction, colicky pain, hematochezia.
Rarely, presents with S bovis (gallolyticus) bacteremia
Right side bleeds; left side obstructs (narrower lumen).
Diagnosis
Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion
Screen low-risk patients starting at age 50 with colonoscopy ; alternatives include flexible sigmoidoscopy, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), and CT colonography. Patients with a first-degree relative who has colon cancer should be screened via colonoscopy at age 40, or starting 10 years prior to their relative’s presentation. Patients with IBD have a distinct screening protocol.
Apple core” lesion seen on barium enema x-ray
CEA tumor marker: good for monitoring recurrence, should not be used for screening.
Molecular pathogenesis of colorectal cancer
Chromosomal instability pathway: mutations in APC cause FAP and most sporadic CRC (via adenoma-carcinoma sequence; (firing order of events is AK-53).
Microsatellite instability pathway: mutations or methylation of mismatch repair genes (eg, MLH1) cause Lynch syndrome and some sporadic CRC (via serrated polyp pathway).
Overexpression of COX-2 has been linked to colorectal cancer, NSAIDs may be chemopreventive
Cirrhosis and portal hypertension
Cirrhosis—diffuse bridging fibrosis (via stellate cells) and regenerative nodules (red arrows in A ; white arrows show splenomegaly) disrupt normal architecture of liver; increased risk for hepatocellular carcinoma (HCC). Etiologies include alcohol, nonalcoholic steatohepatitis, chronic viral hepatitis, autoimmune hepatitis, biliary disease, genetic/metabolic disorders.
Portal hypertension—increased pressure in portal venous system. Etiologies include cirrhosis (most common cause in Western countries), vascular obstruction (eg, portal vein thrombosis, BuddChiari syndrome), schistosomiasis
Spontaneous bacterial peritonitis-Also known as 1° bacterial peritonitis. Common and potentially fatal bacterial infection in patients with cirrhosis and ascites. Often asymptomatic, but can cause fevers, chills, abdominal pain, ileus, or worsening encephalopathy. Commonly caused by aerobic gram ⊝ organisms (eg, E coli, Klebsiella) or less commonly gram ⊕ Streptococcus
Diagnosis: paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3. Empiric first-line treatment is 3rd generation cephalosporin (eg, cefotaxime).
Serum markers of liver pathology
Aspartate aminotransferase and alanine aminotransferase
increased in most liver disease: ALT > AST increased in alcoholic liver disease: AST > ALT
AST > ALT in nonalcoholic liver disease suggests progression to advanced fibrosis or cirrhosis
Alkaline phosphatase-increased in cholestasis (eg, biliary obstruction), infiltrative disorders, bone disease
γ-glutamyl transpeptidase-increased in various liver and biliary diseases (just as ALP can), but not in bone disease; associated with alcohol use
