Gastric & Peritoneal Pathology - Nelson Flashcards
1
Q
What are the normal damaging forces and defensive forces acting on the gastric mucosa?
A
- Damaging forces:
- Gastric acidity
- Peptic enzymes
- Defensive forces:
- Surface mucus secretion
- Bicarbonate secretion
- Mucosal blood flow
- Apical surface membrane transport
- Epithelial regenerative capacity
- Elaboration of prostaglandins
2
Q
What are the main mechanisms of gastric mucosal injury?
A
- NSAIDs
- Aspirin
- Cigarettes
- Alcohol
- Gastric hyperacidity
- Duodenal-gastric reflux
- H. pylori infection
3
Q
What is the difference between a mucosal erosion and a mucosal ulcer?
A
- mucosal erosion = loss and necrosis of surface epithelium, confined to the lamina propria, i.e. mucosa
- acute ulceration = necrotizing process extends beyond the mucosa into the submucosa and even into and through the muscle wall
4
Q
What are the main causes of acute gastric ulceration?
A
- Acute infection with Helicobacter organisms
- First time use of large doses of NSAIDs and aspirin (cyclooxygenase inhibition)
- Ingestion of large quantities of alcohol (direct toxic effect)
- Patients with shock, trauma, sepsis, uremia, severe burns, and intracranial disease can get acute stress ulcers (burns – Curling’s ulcers in duodenum; CNS injury – Cushing’s ulcers)
5
Q
What is the most common pathologic finding in H. pylori gastritis?
A
active chronic gastritis
- typically begins in the antrum and can progress to involve the fundus
- morphologic findings of gastric atrophy can also be present
6
Q
What are the complications of H. pylori infection?
A
- high acid production
- mucosal erosions
- peptic ulcers
- Complications also include MALT-lymphoma and gastric adenocarcinoma.
7
Q
How does one typically acquire H. helmannii gastritis?
A
This organism has reservoirs in cats, dogs, pigs, and nonhuman primates.
8
Q
Which H. pylori diagnostic tests indicate active infection?
A
- Rapid urease testing
- Urea Breath test
- Direct antigen test (stool antigen test)
9
Q
What is the pathogenesis of autoimmune gastritis?
A
- Autoimmune CD4+ T-cell mediated destruction of parietal cells
- Chief cells are also lost during destruction of the gastric glands (“bystander damage”).
- Antibodies to parietal cells and intrinsic factor are also produced as part of the autoimmune response, but are not pathogenic (can be used as a diagnostic test).
10
Q
What are the key clinical findings in autoimmune gastritis?
A
- Clinical findings develop after many years and are related to vitamin B12 deficiency:
- Megaloblastic anemia (macrocytic anemia)
- Atrophic glossitis
- Malabsorptive diarrhea
- Peripheral neuropathy:
- Secondary to subacute combined degeneration of the dorsal and lateral spinal columns.
- Patients can present with paresthesias and ataxia associated with loss of vibration and position sense, and can progress to severe weakness, spasticity, clonus, paraplegia, and fecal and urinary incontinence.
- CNS alterations can also occur, including mild personality changes, memory loss, and psychosis.
11
Q
What are the common causes of chronic reactive gastropathy?
A
- chemical mucosal injury
- NSAIDs
- aspirin
- bile reflux
- alcohol ingestion
12
Q
What are the two common causes of peptic ulcer disease?
A
- Most cases are due to either:
- H. pylori chronic gastritis
- chronic use of NSAIDs
13
Q
What are the three complications of peptic ulcer disease?
A
- Bleeding
- clinical hemorrhage as well as iron deficiency anemia
- Perforation
- Obstruction
- particularly when the ulcer is located in the pyloric channel
- secondary to edema and fibrosis
14
Q
What are the key pathologic and clinical features of eosinophilic gastritis?
A
- Pathologic:
- eosinophil rich inflammation, in the absence of a known cause for eosinophilia
- e.g. reaction to drugs, parasitic infections, malignancy
- most cases secondary to some type of allergic reaction to a food allergen
- e.g. cow’s milk or soy protein in children
- eosinophil rich inflammation, in the absence of a known cause for eosinophilia
- Clinical:
- Lesions may present as a mass, large ulcer, or with pyloric obstruction
15
Q
What are the key pathologic and clinical features of granulomatous gastritis?
A
- Pathologic:
- gastritis with granulomatous inflammation
- Clinical:
- Most cases are secondary to an underlying disorder, such as Crohn’s disease, sarcoidosis, mycobacterial or fungal infections.
16
Q
What are the key pathologic and clinical features of lymphocytic gastritis?
A
- Pathologic:
- gastritis characterized by marked intraepithelial lymphocytic inflammation (CD8+ T lymphocytes).
- Clinical:
- Can be seen as an isolated finding, or in patient’s with either co-existing celiac disease or in patients with co-existing lymphocytic/collagenous colitis.
17
Q
What is the pathogenic mechanism of Menetrier’s disease?
A
- Very rare disorder caused by excessive secretion of transforming growth factor alpha (TGF-α).
- This results in marked diffuse hyperplasia of the foveolar epithelium of the body and fundus of the stomach
- Some cases of Menetrier’s disease are associated with an infection (e.g. CMV in children)
18
Q
What is the pathogenic mechanism of Zollinger-Ellison syndrome?
A
- Caused by gastrin secreting tumors
- gastrinomas: a functioning type of neuroendocrine tumor
- most commonly found in the pancreas and small bowel
- Results in:
- elevated gastrin
- marked increase in the number of parietal cells, with increased gastric acid production
- hyperplasia of mucus neck cells with mucin hyperproduction
- proliferation of endocrine cells in the stomach which can result in gastric carcinoid tumors
19
Q
What are the key features of hyperplastic polyps?
A
- Most occur in association with chronic gastritis
- H. pylori gastritis, chronic reactive gastropathy, autoimmune gastritis
- 75% of all gastric polyps
- most occur in the gastric antrum, followed by the body
- These polyps may represent an exaggerated mucosal response to tissue injury and inflammation.
- Rarely, dysplasia and adenocarcinoma can develop in hyperplastic polyps.
20
Q
What are the key features of cystic fundic gland polyps?
A
- AKA = Fundic Polyp
- Most occur in association with the use of proton pump inhibitors,
- secondary to increased gastrin secretion in response to decreased gastric acid.
- These polyps can also be seen in individuals with familial adenomatous polyposis (FAP).
21
Q
What are the key features of gastric adenomas?
A
- Neoplastic polyp morphologically similar to other adenomas found in the GI tract (e.g. colon).
- Incidence of gastric adenomas increases with age, with most occurring in patients age 50 years and older.
- Gastric adenomas are also increased in incidence in patients with FAP.
22
Q
What are the key features of inflammatory fibroid polyps?
A
- Mesenchymal polypoid proliferation composed of a mixture of stromal spindle cells, small blood vessels, and inflammatory cells, particularly eosinophils.
- Can occur anywhere in the GI tract but stomach and small intestine are the most common sites.
- Usually occur in middle aged females, and are felt to represent a reactive “pseudotumor.”
23
Q
What is the clinical presentation and treatment of congenital hypertrophic pyloric stenosis?
A
- Clinical presentation:
- Occurring in 1 of 300 to 900 live births, it is 3-4 times more common in males.
- Patients typically present in the second or third week of life with new-onset regurgitation and persistent, projectile, non-bilious vomiting.
- Physical examination may reveal a firm abdominal ovoid mass.
- Treatment:
- Surgical myotomy is curative.
24
Q
What are the risk factors for gastric adenocarcinoma?
A
- Chronic gastritis, such as H. pylori gastritis and autoimmune gastritis (intestinal metaplasia-dysplasia-carcinoma sequence).
- Dietary carcinogens (nitrosamines, smoked foods).
- Menetrier’s disease.
- Diets lacking in fruits/vegetables (antioxidants).
- Patients with familial adenomatosis polyposis (FAP).
25
What are the two morphologic patterns of gastric adenocarcinoma?
* Intestinal type:
* can present as a polypoid invasive mass or invasive ulcer.
* Microscopically, tumor shows glandular differentiation.
* Diffuse type:
* presents as diffuse involvement and thickening of the gastric wall (mucosa, submucosa, and muscularis propria).
* Microscopically, see signet-ring cells.
* Diffuse involvement of the gastric wall can produce rigidity and a leather bottle appearance (linitis plastica).
26
What is the most common location for GIST (Gastrointestinal stromal tumors) tumor?
Can arise anywhere in the GI tract, but **stomach** is the most common site (60% stomach, 30% jejunum and ileum, 5% duodenum, \<5% colorectum).
27
What types of cells do GIST tumor cells differentiate into?
interstitial cells of Cajal
(specialized cells involved in gut peristalsis)
28
What is the key genetic defect in GIST tumors?
Most GISTs (85%) have a oncogenic, gain-of-function mutations of the gene encoding receptor tyrosine kinase KIT.
29
What is the rationale for the use of Gleevec in treatment of GIST tumors?
* Gleevec = tyrosine kinase inhibitor imatinib mesylate
* targets mutation directly
30
What is the most common risk factor for gastric MALT lymphoma?
* Chronic Inflammation
* persistent infection with chronic antigenic stimulation results in activation of transcription factors that promote B-cell growth and survival
* persistent H. pylori antigenic stimulation can activate transcription and induce a MALT lymphoma without genetic translocations
31
What is the remarkably simple first line therapy used for primary treatment of gastric MALT lymphoma.
Antibiotics
32
What are the key pathologic features and clinical presentation of “carcinoid syndrome”?
* Clinical:
* cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right sided valvular fibrosis
* Pathologic:
* symptoms are produced by bioactive substances secreted by the tumor
* such as seratonin, histamine, and bradykinin
* as these substances are typically metabolized by the liver, the presence of carcinoid syndrome strongly suggests that metastatic disease may be present.
33
What is a helpful diagnostic test that can assist in diagnosis of "carcinoid syndrome"?
the detection of **24 hour urinary** 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of seratonin
34
What is peritonitis?
inflammation of the thin, mesothelial covered layer of tissue that lines the abdominal cavity (peritoneum) and covers most of the abdominal organs (serosa)
35
What are some of the causes of peritonitis?
* **Bacterial** peritonitis: can be secondary to perforation of a viscus
* e.g. acute appendicitis, peptic ulcer, acute cholecystitis, diverticulitis, ischemic bowel, trauma), acute salpingitis, and peritoneal dialysis.
* Also can occur as spontaneous bacterial peritonitis
* **Bile** peritonitis: leakage of bile causes chemical irritation
* Acute **hemorrhagic necrotizing pancreatitis**
* **Foreign material**, either exogenous (e.g. talc or sutures), or endogenous (ruptured dermoid cyst of ovary induces foreign body reaction).
* **Endometriosis**: localized hemorrhage.
36
What is ascites?
accumulation of excess fluid in the peritoneal cavity
37
What are some of the causes of ascites?
* Most common = portal hypertension associated with cirrhosis
* decreased osmotic pressure
* e.g. hypoalbuminemia
* “exudative” processes such as peritoneal disease resulting in extravasation of exudative fluid
* e.g. peritoneal malignancy
38
By a wide margin, what is the most common cause of ascites?
portal hypertension associated with cirrhosis
39
What is the most significant complication of ascites?
spontaneous bacterial peritonitis
40
What is the rationale for the use of laboratory tests of ascitic fluid, including cell count, gram stain, culture, albumin, total protein, and cytologic examination?
Analysis of the ascitic fluid can help determine the cause of ascites as well as determine if the fluid is infected (a frequent clinical concern).
* Cell count with differential white cell count (neutrophil count greater than 250/ml indicates possible infection).
* Culture of the ascitic fluid, gram stain (gram stain positive in only 10% of cases of spontaneous bacterial peritonitis).
* Albumin (for determining serum ascites- albumin gradient, which can be used to determine if the fluid is an exudate or transudate).
* Total protein (exudate or transudate)
* Fluid cytology (if malignancy suspected).
41
Which two metastatic tumors are the most common cause of malignant ascites?
ovarian and pancreatic carcinomas
42
What is idiopathic retroperitoneal fibrosis?
dense fibrosing process that can result in renal failure due to ureteral obstruction
