Stomach (Hertz) Flashcards
cardia produces
mucin (to protect the esophagus)
gastric body produces
acid and intrinsic factor
antrum produces
G cells there make gastrin
Acute Gastritis
Gastritis is a mucosal inflammatory process. When neutrophils are present, the lesion is referred to as acute gastritis. When inflammatory cells are rare or absent, the term gastropathy is applied
Hypertrophic gastropathy
is applied to a specific group of diseases exemplified by Ménétrier disease and Zollinger-Ellison Syndrome
things that disrupt stomach protective mechanisms
*Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit cyclooxygenase- (COX) dependent synthesis of prostaglandins E2 and I2, which stimulate nearly all of the above defense mechanisms including mucus, bicarbonate, and phospholipid secretion, mucosal blood flow, and epithelial restitution while reducing acid secretion.
The gastric injury that occurs in uremic patients and those infected with urease-secreting *H. pylori may be due to inhibition of gastric bicarbonate transporters by ammonium ions.
- Reduced mucin and bicarbonate secretion have been suggested as factors that explain the increased susceptibility of older adults to gastritis.
- Decreased oxygen delivery may account for an increased incidence of acute gastritis at high altitudes.
Clinical Features
of gastropathy and acute gastritis
varies according to etiology, and the two cannot be distinguished on clinical grounds.
Patients with NSAID-induced gastropathy may be asymptomatic or have persistent epigastric pain that responds to antacids or proton pump inhibitors.
In contrast, pain associated with bile reflux is typically refractory to such therapies and may be accompanied by occasional bilious vomiting
Stress-Related Mucosal Disease
Stress ulcers are most common in individuals with shock, sepsis, or severe trauma.
Also Curling and Cushing ulcers.
Curling ulcers
Ulcers occurring in the proximal duodenum and associated with severe burns or trauma are called Curling ulcers.*
Cushing ulcers
Gastric, duodenal, and esophageal ulcers arising in persons with intracranial disease are termed Cushing ulcers and carry a high incidence of perforation.
Dieulafoy lesion
is caused by a submucosal artery that does not branch properly within the wall of the stomach. This results in a mucosal artery with a diameter of up to 3 mm, or 10 times the size of mucosal capillaries. Dieulafoy lesions are most commonly found along the lesser curvature, near the gastroesophageal junction. Erosion of the overlying epithelium can cause gastric bleeding that, while usually self-limited, can be copious. Bleeding is often associated with NSAID use and may be recurrent.
GAVE
is responsible for 4% of non-variceal upper gastrointestinal bleeding. It can be recognized endoscopically as longitudinal stripes of edematous erythematous mucosa that alternate with less severely injured, paler mucosa, and is sometimes referred to as *watermelon stomach. The erythematous stripes are created by ectatic mucosal vessels. Histologically, the antral mucosa shows reactive gastropathy with dilated capillaries containing fibrin thrombi. While most often idiopathic, GAVE can also be associated with cirrhosis and systemic sclerosis. Patients may present with occult fecal blood or iron deficiency anemia.
associated with NSAIDs*
Chronic Gastritis
The most common cause of chronic gastritis is infection with the bacillus H. pylori. Autoimmune gastritis, the most common cause of diffuse atrophic gastritis, represents less than 10% of cases of chronic gastritis, but is the most common form of chronic gastritis in patients without H. pylori infection.
Helicobacter pylori Gastritis
H. pylori infection most often presents as a predominantly *antral gastritis with normal or increased acid production
- Flagella, which allow the bacteria to be motile in viscous mucus
- Urease, which generates ammonia from endogenous urea and thereby elevates local gastric pH and enhances bacterial survival
- Adhesins that enhance bacterial adherence to surface foveolar cells
- Toxins, such as cytotoxin-associated gene A (CagA), that may be involved in disease progression
Comparison: H pylori vs autoimmune gastritis
H pylori- in antrum, neutrophils and subepithelial plasma cells are the inflammatory infiltrate, gastrin is normal to decreased, other lesions: hyperplastic/ inflammatory polyps. Serology: antibodies to H. pylori. Sequelae: peptic ulcer, adenocarcinoma, MALToma. Associations: low socioeconomic status, povery, residence in rural areas
Autoimmune: located in body of stomach. lymphocytes and macrophages as infiltrate. Acid production decreased, gastrin increased. Other lesions: neuroendocrine hyperplasia. Serology: atibodies to parietal cells (H+, K+, ATPase, intrinsic factor). Sequelae: atrophy, pernicious anemia, adenocarcinoma, carcinoid tumor. Associations: autoimmune disease, thyroiditis, diabetese mellitus, graves disease
Clinical features (and detection) of H pylori
In addition to histologic identification of the organism, several diagnostic tests have been developed including a noninvasive serologic test for antibodies to H. pylori, *fecal bacterial detection, and the urea breath test based on the generation of ammonia by the bacterial urease.
Gastric biopsy specimens can also be analyzed by the *rapid urease test, bacterial culture, or bacterial DNA detection by PCR.
Effective treatments for H. pylori infection include combinations of antibiotics and proton pump inhibitors. Individuals with H. pylori gastritis usually improve after treatment, although relapses can occur after incomplete eradication or reinfection, which is common in regions with high endemic colonization rates.
Autoimmune Gastritis- what do we find?
Autoimmune gastritis accounts for less than 10% of cases of chronic gastritis. In contrast to H. pylori–associated gastritis, autoimmune gastritis typically spares the antrum and is associated with hypergastrinemia*
-Antibodies to parietal cells and intrinsic factor that can be detected in serum and gastric secretions
-Reduced serum pepsinogen I concentration
-Endocrine cell hyperplasia
Vitamin B12 deficiency
-Defective gastric acid secretion (achlorhydria)
Autoimmune Gastritis- cellular stuff
Autoimmune gastritis is associated with loss of parietal cells, which are responsible for secretion of gastric acid and intrinsic factor
CD4+ T cells directed against parietal cell components, including the H+,K+-ATPase, are considered to be the principal agents of injury in autoimmune gastritis
Autoantibodies to parietal cell components, most prominently the H+,K+-ATPase, or proton pump, and intrinsic factor are present in up to 80% of patients with autoimmune gastritis
diagnosis, clinical features of autoimmune gastritis and pernicious anemia
Because of the slow onset and variable progression, patients are generally diagnosed only after being affected for many years; the median age at diagnosis is 60.
Pernicious anemia and autoimmune gastritis are often associated with other autoimmune diseases including Hashimoto thyroiditis, insulin-dependent (type I) diabetes mellitus, Addison disease, primary ovarian failure, primary hypoparathyroidism, Graves disease, vitiligo, myasthenia gravis, and Lambert-Eaton syndrome
Clinical presentation may be linked to symptoms of anema. Vitamin B12 deficiency may also cause atrophic glossitis, in which the tongue becomes smooth and beefy red, epithelial megaloblastosis, malabsorptive diarrhea, peripheral neuropathy, spinal cord lesions, and cerebral dysfunction.
neuro features of autoimmune gastritis
Neuropathic changes include demyelination, axonal degeneration, and neuronal death. The most frequent manifestations of peripheral neuropathy are paresthesias and numbness.
The spinal lesions result from demyelination of the dorsal and lateral spinal tracts, giving rise to a clinical picture that is often referred to as subacute combined degeneration of the cord.
It is associated with a mixture of loss of vibration and position sense, sensory ataxia with positive Romberg sign, limb weakness, spasticity, and extensor plantar responses.
Complications of Chronic Gastritis
Peptic ulcer disease (PUD) refers to chronic mucosal ulceration affecting the duodenum or stomach. Nearly all peptic ulcers are associated with H. pylori infection, NSAIDs, or cigarette smoking. The most common form of peptic ulcer disease (PUD) occurs within the gastric antrum or duodenum as a result of chronic, H. pylori-induced antral gastritis, which is associated with increased gastric acid secretion, and decreased duodenal bicarbonate secretion
Epidemiolog of Peptic Ulcer Disease
Epidemiology. The incidence of PUD is falling in developed countries along with reduced prevalence of H. pylori, infection. However, a new group of duodenal PUD patients older than 60 years of age has emerged as a result of increased NSAID use
PUD results from imbalances between mucosal defense mechanisms and damaging factors that cause chronic gastritis
Risk factors for PUD
h. pylori infection
smoking
COPD
illicit drugs (cocaine) that reduce mucosal blood flow
NSAIDS (potentiated by corticosteroids)
alcoholic cirrhosis (primarily duodenal PUD)
psychological stress (can increase gastric acid secretion)
Endocrine cell hyperplasia (can stimulate parietal cell growth adn gastric acid secretion)
Zollinger-Ellison Syndrome (PUD of stomach, duodenum and jejunum)
Viral infection (CMV, herpes simplex virus)
Clinical Features
of PUD
The majority of peptic ulcers come to clinical attention because of epigastric burning or aching pain, although a significant fraction present with complications such as iron deficiency anemia, hemorrhage, or perforation.
The pain tends to occur 1 to 3 hours after meals during the day, is worse at night (usually between 11 PM and 2 AM), and is relieved by alkali or food. Nausea, vomiting, bloating, belching, and significant weight loss are additional manifestations.
With penetrating ulcers the pain is occasionally referred to the back, the left upper quadrant, or the chest, where it may be misinterpreted as cardiac in origin.
complications of PUD
bleeding
perforation
obstruction (mostly in chronic ulcers)
Treatment
of PUD
Current therapies for PUD are aimed at *H. pylori eradication and neutralization of gastric acid, primarily with proton pump inhibitors. It is also important to withdraw other offending agents, such as NSAIDs, including selective COX-2 inhibitors, that may interfere with mucosal healing. While peptic ulcers were previously notorious for their recurrence, the recurrence rate is now less than 20% following successful clearance of H. pylori.
A variety of surgical approaches were formerly used to treat PUD, including antrectomy to remove gastrin-producing cells and vagotomy to prevent the acid-stimulatory effects mediated by the vagus nerve.
However, the success of proton pump inhibitors and H. pylori eradication has relegated surgical intervention to treatment of bleeding or perforated peptic ulcers
Hypertrophic Gastropathies
Hypertrophic gastropathies are uncommon diseases characterized by giant “cerebriform” enlargement of the rugal folds due to epithelial hyperplasia without inflammation
Ménétrier disease and Zollinger-Ellison syndrome
Ménétrier Disease
Ménétrier disease is a rare disorder associated with excessive secretion of transforming growth factor α (TGF-α)
Makes a lot of protein
Treatment
of Menetrier disease
is supportive, with intravenous albumin and parenteral nutritional supplementation. In severe cases gastrectomy may be needed. More recently, agents that block TGF-α-mediated activation of the epidermal growth factor receptor have shown promise.
ZES
Zollinger Ellison Syndrome
gastric acid hypersecretion
tumor of pancreas
Peptic ulcers
Zollinger-Ellison syndrome is caused by gastrin-secreting tumors
treatment of ZES
Treatment of individuals with Zollinger-Ellison syndrome includes blockade of acid hypersecretion.
This can be accomplished in almost all patients with proton pump inhibitors. Acid suppression allows peptic ulcers to heal and prevents gastric perforation, allowing treatment to focus on the gastrinoma, which becomes the main determinant of long-term survival.
Although they grow slowly, 60% to 90% of gastrinomas are malignant. Tumors are sporadic in 75% of patients. These tend to be solitary and can be surgically resected. The remaining 25% of patients with gastrinomas have multiple endocrine neoplasia type I (MEN I)
Gastrinoma triangle
90% of gastrinomas are located within this anatomic triangle
half duodenum, half pancreas
Gastric Polyps and Tumors
- inflammatory and hperplastic
Up to 75% of all gastric polyps are inflammatory or hyperplastic polyps
Gastric Adenoma
Similar to other forms of gastric dysplasia, adenomas almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia
Adenocarcinoma is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers
Gastric adenocarcinoma is often separated morphologically into intestinal type, which tends to form bulky masses, and a diffuse type, which infiltrates the wall diffusely, thickens it, and is typically composed of signet ring cells
gastric cancer precursors and rates
Gastric dysplasia and adenomas are recognizable precursor lesions associated with gastric adenocarcinoma
In the United States, gastric cancer rates dropped by more than 85% during the twentieth century
The cause of the overall reduction in gastric cancer is most closely linked to decreases in H. pylori prevalence
heaped up margins, rugal folds going out in a spoke, big central ulcer is what?
intestinal adenocarcinoma
key step in the development of diffuse gastric cancer
The loss of E-cadherin (an adhesion molecule)
In contrast to diffuse gastric cancers, sporadic intestinal-type gastric cancers are strongly associated with mutations that result in increased signaling via the Wnt pathway. These include loss-of-function mutations in the adenomatous polyposis coli (APC) tumor suppressor gene and gain-of-function mutations in the gene encoding β-catenin
Linitis plastica
the gastric wall is markedly thickened and rugal folds are partially lost.
desmoplastic
leather bottle
clinical features of intestinal-type gastric cancer
predominates in high-risk areas and develops from precursor lesions, including flat dysplasia and adenomas
The depth of invasion and the extent of nodal and distant metastases at the time of diagnosis remain the most powerful prognostic indicators in gastric cancer
Loves to go to celiac lymph node
Lymphoma
Although extranodal lymphomas can arise in virtually any tissue, they do so most commonly in the GI tract, particularly the stomach
Nearly 5% of all gastric malignancies are primary lymphomas, the most common of which are indolent extranodal marginal zone B-cell lymphomas.
In the gut these tumors are often referred to as lymphomas of mucosa-associated lymphoid tissue (MALT), or MALTomas*
In the stomach, MALT is induced, typically as a result of chronic gastritis
translocations in MALToma
Three translocations are associated with gastric MALToma, the t(11;18)(q21;q21) and the less common t(1;14)(p22;q32) and t(14;18)(q32;q21).
Clinical Features
of MALTomas
The most common presenting symptoms are dyspepsia and epigastric pain.
Hematemesis, melena, and constitutional symptoms such as weight loss can also be present.
Because gastric MALTomas and H. pylori gastritis often coexist and have overlapping clinical symptoms and endoscopic appearances, diagnostic difficulties may arise, particularly in small biopsy specimens
tumor in the submucosa is classically
a carcinoid tumor.
Well-differentiated neuroendocrine tumors
Clinical Features
of carcinoid tumors
The peak incidence of carcinoid tumors is in the sixth decade, but they may appear at any age.
Symptoms are determined by the hormones produced. For example, tumors that produce *gastrin may cause Zollinger-Ellison syndrome, while * ileal tumors may cause carcinoid syndrome, which is characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis.
Foregut carcinoid tumors
those found within the stomach, duodenum proximal to the ligament of Treitz, and esophagus, rarely metastasize and are generally cured by resection. This is particularly true for gastric carcinoid tumors that arise in association with atrophic gastritis, while gastric carcinoid tumors without predisposing factors are often more aggressive.
Midgut carcinoid tumors
that arise in the jejunum and ileum are often multiple and tend to be aggressive. In these tumors, greater depth of local invasion, increased size, and the presence of necrosis and mitoses are associated with a worse outcome.
Hindgut carcinoids
arising in the appendix and colorectum are typically discovered incidentally. Those in the appendix occur at any age and are generally located at the tip. These tumors are rarely more than 2 cm in diameter and are almost always benign. Rectal carcinoid tumors tend to produce polypeptide hormones and, when symptomatic, present with abdominal pain and weight loss. Because they are usually discovered when small, metastasis of rectal carcinoid tumors is uncommon
Gastrointestinal Stromal Tumor
A wide variety of mesenchymal neoplasms may arise in the stomach.
Many are named according to the cell type they most resemble; for example, smooth muscle tumors are called *leiomyomas or leiomyosarcomas, nerve sheath tumors are termed schwannomas, and those resembling glomus bodies in the nail beds and at other sites are termed glomus tumors
*GI stromal tumor (GIST) is the most common mesenchymal tumor of the abdomen
where do GISTs come from?
Approximately 75% to 80% of all GISTs have oncogenic, gain-of-function mutations in the receptor tyrosine kinase KIT
Pemphigus is what?
blisters
Linear is what?
CMV because it likes the blood vessels
pseudomembrane is what?
candida
punched-out is what?
herpes
clinical features of GISTs
Symptoms of GISTs at presentation may be related to mass effects. Mucosal ulceration can cause blood loss, and approximately half of individuals with GIST present with anemia or related symptoms. GISTs may also be discovered as an incidental finding during radiologic imaging, endoscopy, or abdominal surgery performed for other reasons
Complete surgical resection is the primary treatment for localized gastric GIST. The prognosis correlates with tumor size, mitotic index, and location, with gastric GISTs being less aggressive than those arising in the small intestine. Recurrence or metastasis is rare for gastric GISTs smaller than 5 cm but common for mitotically active tumors larger than 10 cm. Many tumors fall into an intermediate category where the malignant potential of the lesion cannot be predicted with certainty on the basis of histology alone.
Those with mutations in *KIT or PDGFRA often respond to the tyrosine kinase inhibitor imatinib
ulcer vs erosion
ulcer violates the basement membrane
