10 Stomach: Physiology and Disease 2 Flashcards Preview

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Flashcards in 10 Stomach: Physiology and Disease 2 Deck (20):
1

Zollinger Ellison Syndrome (p.41-44)

  • frequency
  • defined by 
    • excess gastrin secretion/
      • The high gastric levels lead to/
      • The excess acid secretion results in/
    • elevated somatostatin/
  • The ultimate goal in treatment

  • rare
  • defined by
    • excess gastrin secretion through an endocrine tumor (carcinoid), which is typically located in the upper abdomen, most commonly in the pancreas.
      • The high gastric levels lead to hypertrophy of gastric folds with proliferated parietal cells.
      • The excess acid secretion results in mucosal injury and very difficult-to-treat reflux and/or peptic ulcer disease.
    • elevated somatostatin used to diagnose and treat the disease. 
  • The ultimate goal in treatment
    • finding and removing the responsible tumor.

2

Gastritis and Gastropathies (p.45-47)

  • Gastritis
    • ?
    • diagnosis
  • Gastropathy
  • presence of gastritis vs. symptoms. 
    • symptoms or macroscopic findings on endoscopy or radiographic contrast studies/
    • If we find gastritis, we need to determine/

  • Gastritis
    • inflammation of the stomach, typically the mucosa
    • should be a microscopic diagnosis
  • Gastropathy
    • mucosal alteration, such as changes seen in patients with bile reflux or chronic aspirin use, in the absence of an inflammatory infiltrate
  • poor association between the presence of gastritis and symptoms.
    • symptoms or macroscopic findings on endoscopy or radiographic contrast studies are not sufficient to diagnose gastritis.
    • If we find gastritis, we need to determine the cause as infections, chemicals, autoimmune and systemic diseases may underlie this abnormality and require specific therapy.

3

Infectious Etiologies

  • Bacteria
    • most common cause of gastritis
    • Rare causes
  • Viruses
    • Viral gastritides/
    • found primarily in/
  • Fungi
    • frequency
    • include/
  • Parasites
    • protozoans
    • nematodes

  • Bacteria
    • most common cause of gastritis
      • Helicobacter pylori
    • Rare causes
      • Mycobacterial organisms: Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC).
        • MAC is primarily encountered in immunocompromised patients and typically involves other parts of the gut as well.
      • Treponema pallidum is the etiologic spirochete in syphilitic gastritis.
  • Viruses
    • Viral gastritides (primarily CMV and HSV)
    • found primarily in immunocompromised or immunosuppressed hosts.
  • Fungi
    • extremely rare
    • include Candida albicans, Aspergillus fumigatus, Histoplasma capsulatum, and mucormycosis.
  • Parasites
    • protozoans
      • Cryptosporidium and Giardia lamblia,
    • nematodes
      • Anisakis marina (anisakiasis from the larval form present in ingested fish) and Strongyloides stercoralis.

4

Infectious Etiologies:
Helicobacter pylori (p.48-49)

  • able to/
  • the most common cause of/
  • infection with H.pylori is a major risk factor for/
  • The organism is a/
  • found/
  • most typically causes/
  • transmitted/
  • prevalence
  • ​Infection causes/
    • The local production of cytokines may directly affect/
    • This in turn causes/

  • able to not only survive but even thrive in the acidic stomach. 
  • the most common cause of gastric infection in humans.
  • infection with H.pylori is a major risk factor for peptic ulcer disease.
  • The organism is a gram-negative, microaerophilic, curved bacillus
  • found only on the gastric mucosa.
  • most typically causes duodenal ulcers by affecting metaplastic areas that are often described as ‘non-specific duodenitis.’
  • transmitted feco-orally,
  • prevalence
    • higher prevalence in poorly developed areas of the world.
    • age-dependent increase in prevalence.
      • age-dependent prevalence of H.pylori is decreasing due to improved living conditions.
    • the role of H.pylori in ulcer disease is declining
  • ​Infection causes an inflammatory infiltrate.
    • The local production of cytokines may directly affect epithelial cells and alter acid secretion through activation of ECL cells.
    • This in turn causes mucosal injury and may ultimately lead to ulcerations.

5

Infectious Etiologies:
Helicobacter pylori:
Chronic infection may lead to important complications (p.50-53)

  • H.pylori-associated atrophic gastritis
    • intestinal metaplasia/
    • The higher pH allows/
    • Eradication of the infection has been shown to/
    • H.pylori is classified as/
    • When you look for it and obtain a positive test result/
  • Mucosa associated lymphoid tissue (MALT) lymphoma
    • caused by/
    • develops/
    • While low-grade, eradication of H. pylori/
      • If allowed to progress to high-grade lymphoma/

  • H.pylori-associated atrophic gastritis
    • intestinal metaplasia extends proximally, leading to a decrease in acidity.
    • The higher pH allows bacterial colonization, which increases the concentration of potential carcinogens through fermentation of ingested foods.
    • Eradication of the infection has been shown to lower the cancer risk in areas with a high prevalence of gastric cancer.
    • H.pylori is classified as a class I carcinogen.
    • When you look for it and obtain a positive test result, you should initiate treatment
  • Mucosa associated lymphoid tissue (MALT) lymphoma
    • caused by
      • ongoing stimulation of the immune system in chronic infection
      • a low-grade clonal proliferation of B-lymphocytes.
    • develops rarely in patients with H.pylori infection.
    • While low-grade, eradication of H. pylori alone will effectively treat the lymphoma in around 70% of cases.
      • If allowed to progress to high-grade lymphoma, antibiotic therapy will no longer be an adequate treatment.

6

Infectious Etiologies:
Helicobacter pylori (p.54-55)

  • Why additional tests are required
  • urease activity
  • histological examination
  • Culture
  • serologic testing
  • H. pylori is most effectively treated with

  • Why additional tests are required
    • There is no macroscopic feature that distinguishes mucosal changes in H.pylori infected patients from those with other lesions.
  • urease activity
    • Most of them rely on detection of urease activity, as the organism expresses this enzyme to alkalize its environment.
    • Urease activity can be detected in mucosal biopsy or using radioactive urea with breath tests.
  • histological examination
    • can show the organism with conventional or special stains.
  • Culture
    • can be performed,
    • but is cumbersome and expensive due to the slow growth in microaerophilic environment.
  • serologic testing
    • If patients have not been treated, chronic infection can be easily and inexpensively identified with serological testing.
  • H. pylori is most effectively treated with a combination of an acid suppressing medication (proton-pump inhibitor or H2 blocker) with two antibiotics or with one antibiotic plus a colloidal bismuth compound.

7

Atrophic Gastritis (p.56-59)

  • Atrophic gastritis
    • characterized by/
    • classified according to/
    • All types may be accompanied by/
    • associated with atrophic gastritis
  • Type A gastritis
    • process
    • associated with/
    • involves/
      • can therefore lead to/
    • what may result
  • Type B gastritis
    • predominantly/
    • frequently associated with/
    • gastrin levels/

  • Atrophic gastritis
    • characterized by atrophy of the gastric mucosa.
    • classified according to the region of mucosal involvement, which differs according to underlying pathogenesis.
    • All types may be accompanied by hypochlorhydria and and metaplasia of the gastric mucosa to an intestinal-type epithelium (intestinal metaplasia).
    • Development of gastric carcinoid tumors, gastric polyps, and gastric adenocarcinoma has been associated with atrophic gastritis.
  • Type A gastritis
    • an autoimmune process
    • associated with anti-parietal cell antibodies and autoimmune disorders of other organs.
    • involves the corpus predominantly,
      • can therefore lead to reduced secretion of HCl and IF.
    • what may result
      • hypochlorhydria,
      • pernicious anemia (due to vitamin B12 malabsorption)
      • due to hypochlorhydria, gastrin levels may be elevated.
  • Type B gastritis
    • antral-predominant,
    • frequently H. pylori-associated.
    • Gastrin levels are usually normal.

8

Other Causes of Gastritis (p.60)

  • rely on/
  • may benefit from/
  • The most common form of gastropathy is due to/
  • we can also see other disorders, which are/

  • rely on biopsies
  • may benefit from specific therapy
    • e.g., Crohn’s disease involving the proximal GI tract, eosinophilic gastritis, lymphocytic gastritis in the context of celiac disease
  • The most common form of gastropathy is due to medication
  • we can also see other disorders, which are quite rare (e.g., Menetrier disease).

9

Peptic Ulcer Disease (p.61-63)

  • Gastroduodenal ulcers 
    • frequency
    • may lead to/
  • 10% of patients first present with
    • most/
  • The leading complaint
    • similar symptoms are also present in patients with/
  • To establish the diagnosis/

  • Gastroduodenal ulcers
    • common
    • may lead to significant complications, including bleeding, perforation or stricture formation.
  • 10% of patients first present with complications,
    • most have prior symptoms.
  • The leading complaint is a burning pain in the epigastrium that typically appears at night and a few hours after food intake and is relieved by antacids or a meal.
    • similar symptoms are also present in patients with non-ulcer dyspepsia.
  • To establish the diagnosis, endoscopy or UGI contrast studies are required.
    • endoscopy is superior as up to 20 % of ulcers are missed radiographically.

10

Peptic Ulcer Disease (p.64)

  • Mucosal lesions result from/
  • what assures mucosal integrity
  • in patients with duodenal ulcers

  • Mucosal lesions result from an imbalance between defensive and injurious influences.
  • what assures mucosal integrity
    • The protective mucous layer, intracellular bicarbonate concentrations, mucosal blood flow and cellular regeneration 
    • despite the acidic environment in the stomach and proximal duodenum.
  • in patients with duodenal ulcers
    • increases in acid output
    • decreases in protective bicarbonate secretion

11

Peptic Ulcer Disease:
Definition (p.65-68)

  • Erosions
  • ulcers
  • this distinction is associated with strikingly different complication risks
    • Involvement of the submucosa may lead to/
    • Penetration through all layers of the stomach into the peritoneal cavity (perforation) is/
    • Healing of large and deep lesions may cause/
      • erosions typically/
  • skilled endoscopies/

  • Erosions are superficial lesions of the mucosa which do not penetrate the mucularis mucosae.
  • ulcers are defined by their extension into deeper layers.
  • this distinction is associated with strikingly different complication risks.
    • Involvement of the submucosa may lead to erosion of large vessels and severe hemorrhage.
    • Penetration through all layers of the stomach into the peritoneal cavity (perforation) is another medical emergency.
    • Healing of large and deep lesions may cause scars and stricture formation,
      • erosions typically heal without any residual abnormality.
  • skilled endoscopies can reliably make the distinction between ulcers and erosions.

12

Peptic Ulcer Disease:
Etiology (p.69-70)

  • The most important causes for ulcer development 
  • Other, less common causes
  • duodenal ulcers are never due to/
  • stomach ulcers can be due to/
  • it is important to rule out/

  • The most important causes for ulcer development
    • Helicobacter pylori
    • the use of NSAIDs or aspirin,
  • Other, less common causes
    • vascular problems, stress ulcerations, Crohn’s disease, infections with organisms other then H.pylori, radiation, chemotherapy and Zollinger Ellison syndrome (ZES).
  • duodenal ulcers are never due to malignancies,
  • stomach ulcers can be due to carcinomas.
  • it is important to rule out malignancy in patients with gastric ulcers.

13

Peptic Ulcer Disease:
NSAID and Aspirin (p.71-75)

  • exert their effects by/
  • Two isoforms
    • COX-1 is constitutively expressed/
    • COX-2 is induced by/
  • The inhibition of prostaglandin synthesis/
  • most of these pharmacologic agents are/
  • they increase the likelihood of/
    • This risk increases further in/
  • alternative treatments should be considered/
  • what leads to lower complication rates if NSAID therapy is necessary
  • misoprostol 

  • exert their effects by inhibiting the enzyme cyclooxygenase (COX).
  • Two isoforms
    • COX-1 is constitutively expressed in many tissues, including the gastrointestinal tract,
    • COX-2 is induced by inflammation.
  • The inhibition of prostaglandin synthesis decreases the production of protective factors (mucous, bicarbonate) in the gastric mucosa.
  • most of these pharmacologic agents are weak acids that are protonated in the acidic environment of the stomach, and subsequently diffuse into the mucosa, where they are trapped within cells.
  • they increase the likelihood of complicated ulcers (bleeding, perforation) between 2 and 3-fold.
    • This risk increases further in elderly or persons with prior ulcers.
  • alternative treatments should be considered whenever possible.
  • If NSAID therapy is indeed necessary, the use of a COX-2 specific inhibitor and/or the concomitant use of a proton pump inhibitor lead to much lower complication rates.
  • misoprostol
    • prostaglandin analogue
    • similarly effective,
    • the higher rate of side effects and the need for multiple daily doses limits the use of this agent.

14

Gastric Motility Disorders (p.76+78-79)

  • Disturbances in gastric motility usually present clinically as/
  • Symptoms are non-specific, but may include/
    • While not as common/
  • accommodation/
    • Impaired receptive relaxation similarly can cause significant symptoms with/

  • Disturbances in gastric motility usually present clinically as gastroparesis, or delayed gastric emptying.
  • Symptoms are non-specific, but may include nausea, vomiting, bloating, abdominal distention or fullness, early satiety, or weight loss.
    • While not as common, accelerated gastric emptying may cause similar symptoms.
  • accommodation is an important function of the stomach.
    • Impaired receptive relaxation similarly can cause significant symptoms with fullness, nausea and even pain in the absence of changes in gastric emptying.

15

Gastric Motility Disorders:
Etiology (p.77+80-81)

  • Mechanistically, we can differentiate/
    • leading causes for gastric dysmotility
      • The best understood example
    • More commonly, we deal with /
      • The most extensively studied example
  • Poor metabolic control 
    • leads to/
    • can affect and contribute to/
      • this may not necessarily/
    • what can lead to gastroparesis
    • inherited smooth muscle abnormalities are/
    • what may directly or indirectly affect the contractility of gastrointestinal smooth muscle
    • when treating patients with abnormal gastric emptying, always consider/
    • what significantly alters gastric emptying

  • Mechanistically, we can differentiate abnormal function of nerves (neuropathic), the pacemaker cells (interstitial cells of Cajal) or effector cells (myopathic) as causes for motility disturbances.
    • Impaired functioning of intrinsic and extrinsic nerves are probably the leading causes for gastric dysmotility.
      • The best understood example is hypertrophic pyloric stenosis of infancy
      • In this case, the structure and function of the enteric nervous system is abnormal.
    • More commonly, we deal with degenerative rather than inherited changes.
      • The most extensively studied example is diabetes.
  • Poor metabolic control
    • leads to diabetic neuropathy,
    • can affect the autonomic nerves and contribute to the development of diabetic gastroparesis.
      • this may not necessarily trigger the symptoms mentioned above, as the afferent innervation is often equally affected.
    • what can lead to gastroparesis
      • infections and intentional or accidental injury of the vagus.
    • inherited smooth muscle abnormalities are an exceedingly rare cause of gastroparesis.
    • Scleroderma, dermatomyositis and amyloidosis may directly or indirectly affect the contractility of gastrointestinal smooth muscle.
    • when treating patients with abnormal gastric emptying, always consider drug effects
    • Anticholinergic drugs, opioids, L-DOPA, and calcium channel blockers significantly alter gastric emptying.

16

Gastric Motility Disorders:
Diagnosis

  • what should be ruled out before a diagnosis of gastroparesis is made
  • tests developed to study gastric emptying. 

  • what should be ruled out before a diagnosis of gastroparesis is made
    • Mechanical obstruction of the GI tract
  • tests developed to study gastric emptying.
    • Clinically, scintigraphic tests are used most commonly.
    • The most sensitive and specific clinically available test is the radionuclide solid-phase gastric emptying study.
      • radiolabeled scrambled eggs (typically 99Tc) and/or meat are consumed by the patient, who then is placed in front of a collimator which detects the emitted radioactivity, and therefore enables the operator to determine the time at which half of the ingested food has passed from the stomach into the small bowel.
      • This gastric-emptying half-time (t1/2) is compared against an established range for normal controls.
      • While a t1/2 longer than the upper limits of the normal range defines gastric emptying delay or gastroparesis, symptoms poorly correlate with test results.

17

Gastric Motility Disorders:
Treatment (p.82)

  • Cornerstone in the treatment of patients with gastroparesis
  • Successful management of gastroparesis typically includes 

  • Cornerstone in the treatment of patients with gastroparesis
    • Appropriate hydration and correction of metabolic abnormalities
    • because poor metabolic control (especially in diabetics) and electrolyte abnormalities impair gastrointestinal motility
  • Successful management of gastroparesis typically includes
    • appropriate dietary therapy with multiple small meals,
    • a low-residue diet,
    • symptomatic therapy with anti-emetics,
    • in the setting of exacerbations or severe disease, a liquid diet or enteral feeding via jejunal feeding tube with or without venting gastrostomy.

18

Gastric Motility Disorders:
Treatment:
Two prokinetic agents:
Metoclopramide (p.83-85)

  • ?
  • Its central dopamine-blocking effect provides/
  • If used long-term/
  • available/

  • ?
    • a central and peripheral dopamine antagonist,
    • a cholinergic agonist via indirect presynaptic effects on enteric motor neurons.
  • Its central dopamine-blocking effect provides the added benefit of antiemetic activity, but is also responsible for its side effects of drowsiness and acute dystonias.
  • If used long-term, tardive dyskinesia may result, prompting federal regulatory agencies to issue a ‘black box’ warning.
  • available in a parenteral form as well, which is frequently administered to patients admitted to hospital with an acute exacerbation of chronic gastroparesis.

19

Gastric Motility Disorders:
Treatment:
Two prokinetic agents:
Erythromycin (p.83-85)

  • ?
  • available/
  • its use in setting of chronic gastroparesis is limited by/
  • the strong gastric contractions/
  • It is particularly useful as/

  • ?
    • macrolide antibiotic
    • a motilin receptor agonist and cholinergic agonist,
    • a strong prokinetic agent.
  • available in parenteral and oral forms.
  • its use in setting of chronic gastroparesis is limited by tachyphylaxis in some patients.
  • the strong gastric contractions (mimicking the lumen-obliterating, stomach-to-small-intestine wave-like contractions of the MMC) induced by this agent may contribute to abdominal pain and nausea, and even diarrhea in some patients.
  • It is particularly useful as a parenteral agent for administration in the setting of an acute exacerbation of chronic diabetic gastroparesis.

20

Summary (p.86-87)

  • frequency of gastrointestinal symptoms
  • what can trigger many of the symptoms seen in patients with gastric disorders
  • functional dyspepsia 

  • Gastrointestinal symptoms are common.
  • systemic influences (e.g. sepsis; metabolic abnormalities), drugs and diseases of the central nervous system can trigger many of the symptoms seen in patients with gastric disorders.
  • functional dyspepsia
    • an upper gut equivalent of the irritable bowel syndrome.
    • location of discomfort is different,
    • symptoms are not associated with altered bowel patterns, but rather triggered or alleviated by food intake.