Stomach - Malley Flashcards
What is helicobacter pylori?
Can you describe it?
Bacteria that colonizes gastric epithelium
Spiral shaped, microaerophilic, gram negative
Broadly: What functions are served by the stomach?
Store and digest food,
optimize absorption,
expel indigestible and toxic matter,
defend from pathogens,
and alert the body to dysfunction.
What motor functions are served by the proximal and distal stomach?
Proximal: Expand to accommodate large volumes of food
Distal: Undergo weak contractions to push food into the antrum and against the pylorus.
Muscle activity in the stomach is tonic; describe the baseline activity and its pacemaker.
Slow wave activity is mediated by the interstitial cells of cajal, and occur about 3/min.
How does the pylorus distinguish between liquid and (large) solid food?
How does it contribute to digestion?
The sphincter is mostly shut, acting as a sieve to block the egress of large solid matter. Liquid or small solid food can pass.
Large food that is blocked is retropelled to the antrum; this repeated grinding is known as triturition and will eventually break down the food into liquid or small solid chunks.
How do the duodenum and small intestine influence the rate of gastric emptying?
Receptors for specific nutrients, acidity, and distension feedback along neural and hormonal pathways to slow gastric emptying; resulting in a delivery of 1-4kcal per minute.
Each of the following factors slows gastric emptying. Name the origin and stimulus for secretion for each.
Secretin
Somatostatin
Cholecystokinin
Secretin released by the duodenum in response to lipids, amino acids, or acid.
Somatostatin released from intestines (actually many sites) in response to amino acids or acid.
Cholecystokinin released from duodenum in response to lipids (longer chain = greater response).
How is H. pylori diagnosed?
Endoscope biopsy
Urea breath testing
Stool antigen testing
Serology (false positive after treatments)
(False negative on all above with PPI or Abx)
What is the only discussed humoral factor that promotes gastric emptying?
**Ghrelin **(the “hunger hormone”); it also induces the onset of the migrating motor complex.
How does the stomach respond to each of the following:
Non-caloric liquids (eg water)
Solid foods (eg POTATO DUMPLINGS)
Indigesible matter (eg marbles)
Non-caloric liquids are cleared quickly (no humoral feedback as no nutrients are delivered; liquid also passes sieve)
Solid foods are cleared slowly (triturition takes hours)
Indigestible matter is only cleared by MMCs when all other food has been cleared (effectively fasting).
What is atrophic metaplastic gastritis? What subtypes are there?
Destruction of mucosa and metaplasm from the resulting damage
Type A hits the body and fundus of the stomach and is autoimmune
Type B hits the antrum and is typically caused by H pylori
Describe the method and application of gastric empting scintigraphy.
Consumption of radiolabeled food or drink allows for monitoring of the rate of gastric emptying, and is useful in diagnosing motor disorders eg Gastroparesis.
What is NSAID gastric toxicity?
COX-1 inhibition reduces blood flow and oxygen delivery, limiting secretion and proliferation of epithelial cells. This results in mucosal damage.
What is contraction failure, and what are its consequences?
Failure of the stomach to properly churn and/or clear its contents.
Delivery to the intestines is delayed, gastric contents are retained and cause pain, bloating, early satiety, N/V, and poor drug delivery.
What is accomodation failure? What are its symptoms?
Failure of the stomach to expand sufficiently, usually resulting in inappropriate clearance of contents.
Causes pain/bloating, early satiety, N/V, weight loss.
There are many consequences to accomodation failure. Try to name them and why they occur.
- Small bowel distention causes discomfort (bloating/pain)
- Fluid shifting from the vascular compartment causes hypotension
- Digestion and absorption become discoordinated (weight loss, nutrient deficiencies)
- Unabsorbed food reaches the colonic flora (flatus, diarrhea, cramps)
- Humoral responses become disregulated (post-prandial hypoglycemia)
- Too much unbuffered acid reaches the duodenum (ulceration, destruction of pancreatic enzymes causing maldigestion)
What are symptoms of an ulcer?
- epigastric pain (worse with meals if gastric, 2-3 hours post-prandial if duodenal)
- perforation
- nausea
- anorexia/weight loss
- B12/Iron deficiency
- pancreatitis
- blood in vomit, stool
- vomitting or diarrhea
Define gastroparesis and name its symptoms. How is it diagnosed?
Delayed gastric emptying; patients report early satiety, bloating, abdominal pain, and N/V.
It is diagnosed by symptomology, gastric emptying tests, and exclusion of obstruction.
How can gastroparesis occur in someone with intact motor and neural structures?
(non-pharmacological)
- Hypokalemia
- Hyperglycemia
- Uremia
- Hypothyroidism
- Mesenteric Ischemia
- Cortical effects (stress, motion sickness)
What drugs can delay gastric emptying?
- Anti-cholinergics
- painkillers (opiate or NSAID)
- pramlintide (amylin analog)
- exenatide (GLP-1 agonist)
- cyclosporine?
What motor abnormalities can cause gastroparesis?
- Pyloric stenosis
- Visceral myopathies
- Connective tissue diseases (scleroderma)
- Gastric resection
- Fundoplication wrap (eg for acid reflux)
What neural disorders can cause gastroparesis?
- Parkinson’s disease
- Multiple sclerosis
- Amyloidosis
- Viral infection
- Auto-immune diseases
- Hereditary neuropathies
- Paraneoplastic syndrromes
- Trauma
Injury to the vagal nerve usually occurs in the context of surgical trauma. What effect does this have on gastric emptying?
Poor accommodation means liquids empty more rapidly (not stored much).
Poor grinding means solids empty more slowly.
What causes visceral hypersensitivity?
What are its symptoms?
Stress, anxiety, and depression seem to contribute, but the mechanism is unknown.
Increased post-prandial pain in the absence of an ulcer. More pain with distention or acid.
How does Diabetes affect gastric emptying?
Diabetes mellitus causes damage mainly to neural structures (enteric neurons, cajal) but the hyperglycemia also reduces gasric emptying.
Vagal outflow is dysfunctional. (gastric emptying may increase or decrease)
How does gastric adenocarcinoma present grossly?
very diverse
- ulcer
- mass
- ulcerated mass
- linitis plastica
What causes damage in H**elicobacter pylori infections?
The immune response:
neutrophilic infiltration as well as lymphocyte, plasma cell, and macrophage activation cause tissue damage.
What is the virulence factor in Helicobacter pylori that can cause more intense damage?
CagA (cytotoxin associated gene A)
What happens during the early stage of H. pylori gastritis?
- H. pylori infection is contained in the antrum
- H. pylori inhibits somatostatin secretion
- Decreased somatostatin leads to increased acid
- Duodenal ulcers form b/c of increased acid
What happens during the later stages of H. pylori gastritis?
- H. pylori spreads to corpus and fundus
- Parietal cells are destroyed
- Ulcers develop in stomach
What happens after H. pylori infections are resolved?
Neutrophil infiltration resolves, but lymphocytic infiltration persists for a while.
Who does H. pylori typically infect?
- older people
- people in slums
- crowding and poverty
- transmitted fecal/oral or oral/oral
How is H. pylori diagnosed?
- Endoscope biopsy
- Urea breath testing
- Stool antigen testing
- Serology (false positive after treatments)
(False negative on all above with PPI or Abx)
What are some effects of H. pylori infection?
- Peptic ulcer
- Enteric infections
- Iron & B12 deficiency
- Gastric neoplasia (MALToma, adenocarcinoma, carcinoid)
- Possible decrese in atopic diseases
- Possible weight control benefits
What is autoimmune gastritis? Who is mostly likely to get it?
Lymphocyte destruction of parietal cells
Women (surprise!) and people with other autoimmune disorders (thyroid, celiac sprue, type 1 diabetes)
What is atrophic metaplastic gastritis? What subtypes are there?
Destruction of mucosa and metaplasia from the resulting damage.
- Type A hits the body and fundus of the stomach and is autoimmune
- Type B hits the antrum and is typically caused by H. pylori
What differentiates gastritis and gastropathy?
Gastritis has inflammation while gastropathy does not.
What is NSAID gastric toxicity?
NSAIDs build up in the epithelium, uncoupling oxidative phosphorylation and reducing energy production. Eventually, cell permeability is increased and the cells die, leading to mucosal injury.
What is an ulcer?
Destruction of the mucosa that extends to below the muscularis mucosa.
What are risk factors for NSAID associated ulcers?
- older age
- length and intensity of NSAID use
- prior ulcer
- concurrent use of aspirin, anticoagulants, glucocorticoids, clopidogrel, SSRIs
What can cause ulcers?
- NSAID use
- H. pylori
- Gastric malignancy
- Viral infection (Herpes/CMV)
- Bisphosphonates
- Gastric bypass
- Stress
- Crohn’s
- Zollenger-Ellison
- Radiation
- Treponema pallidum
What are symptoms of an ulcer?
- epigastric pain
- worse with meals if gastric
- worse 2-3 hours post-prandial if duodenal
- perforation
- nausea
- anorexia/weight loss
- B12/Iron deficiency
- pancreatitis
- blood in vomit, stool
- vomitting or diarrhea
What are risk factors for gastric adenocarcinoma globally?
- living in a higher latitude
- smoking
- high salt diet
- nitrate consumption
- living in a developing country
What are risk factors for gastric adenocarcinoma in the US?
- male
- older
- asian, black or hispanic
What are the two different subtypes of gastric adenocarcinoma?
What are the differences between them?
intestinal type versus diffuse type
Intestinal type is associated with H. pylori and is more common in older men
Diffuse type is associated with younger patients who have A blood and is typically more aggressive
What does diffuse gastric adenocarcinoma look like on histology?
“signet ring histology” - mucin vacuole displaces the nucleus
What gene is associated with hereditary diffuse adenocarcinoma?
How is hereditary diffuse adenocarcinoma inherited?
E-cadherin (CDH1)
Autosomal dominant with high penetrance
What is hereditary diffuse adenocarcinoma also associated with?
- Breast cancer
- Familial adenomatous polyposis (FAP)
- Lynch syndrome
- Peutz-Jeghers syndrome
- Li-Fraumeni syndrome
What is a non-genetic cause of diffuse gastric adenocarcinoma?
EBV
What are risk factors for adenocarcinoma of the cardia?
- Male
- obese
- smoker
- NOT H. pylori
How does gastric adenocarcinoma present grossly?
very diverse
- ulcer
- mass
- ulcerated mass
- linitis plastica
What is gastric lymphoma? How is it treated?
B cell lymphoma associated with H. pylori (80%).
It is cured by treating underlying H. pylori infection.
What are some risk factors for gastric lymphomas?
- immunodeficiency
- celiac disease
- autoimmune disease
If you diagnose a gastric lymphoma, what should you be suspicious of?
That it spread from another source. Primary gastric lymphomas are very rare.
What does a gastric lymphoma look like grossly?
looks very similar to normal tissue
- erythema
- thickened gastric folds
- nodularity
- ulcer
- mass
What are gastric carcinoid tumors?
Enterochromaffin-like cells that proliferate and transform in response to high gastrin levels
Who typically gets carcinoid tumors? What is the clinical course?
older women
multiple, small tumors; typically benign
What if gastric carcinoids are found in patients with normal gastrin levels?
The tumors are likely sporadic and more aggressive.
Name five secreted products of the stomach.
- Acid
- Intrinsic Factor
- Pepsinogens
- Lipase
- Bicarb/Mucous
Name five causes of elevated acid secretion by the stomach.
- Elevated gastrin
- Elevated vagal tone
- Elevated histamine
- mastocytosis
- basophilic leukemia
- Elevated parietal cell mass (idiopathic)
- Paraneoplastic (typically gastrin)
What anatomical part of the stomach produces gastrin?
What is responsible for physiologic elevated gastrin release?
- The antrum
- Reduced delivery of acid to the antrum (independent of acidification of the antrum itself)
What is Zollinger-Ellison Syndrome?
In what two major forms is it typically found?
Which has a better prognosis?
Hypersecretion of gastric acid due to a gastrin-secreting neuroendocrine tumor.
Typically appears as either:
- An isolated gastrinoma (75%)
- Better prognosis. Remove the tumor to cure.
- As a component of Multiple Endocrine Neoplasia I (MEN1) (25%)
- Worse prognosis. Multifocal. No curable. Other endocrine disturbances.
- What is a normal basal rate of stomach acid secretion? What rates are typically found in a patient with ZE Syndrome?
- What is a normal upper limit for gastrin? How much gastrin is typically found in a patient with ZE Syndrome?
- Acid secretion rate:
- Normal: <5mEq/hr
- ZE: ~15mEq/hr
- Gastrin:
- Normal: <100pg/ml
- ZE: >150pg/ml
- >1000 gastrin plus low pH is diagnostic for ZE
What can cause a false negative test for ZE Syndrome?
PPI use
What paradoxical finding is noted in ZE Syndrome that is useful in its diagnosis?
Paradoxical Secretin Response
Normally, secretion of secretin causes a decrease in gastrin.
In ZE Syndrome, gastrin increases in response to secretin [not important to know why - somehow the cell signalling pathway gets flipped.] Therefore, if a patient’s gastrin increases after bein given a dose of secretin, this suggests ZE or a similar neuroendocrine tumor.
When ZE Syndrome arises as an isolated gastrinoma, where is this tumor typically found in the body?
In the duodenum or pancreas.
In ZE Syndrome secondary to MEN1, what other endocrine tumors / derangements are often seen? Name three.
- Hyperparathyroidism
- Other pancreatic islet cell tumors
- Pituitary tumors
What are the clinical manifestations of ZE Syndrome?
-
Severe ulcer disease
- Extends to distal duodenum or jejunum
- Ulcers relapse, requires high-dose PPI to cure
-
Diarrhea
- Large acidic fluid volume
- Inactivation of pancreatic enzymes
- Due to more acidic pH in the duodenum
- Hypokalemia, steatorrhea, weight loss
Aside from ZE Syndrome, what are some other causes of gastrin-mediated high acid secretion?
- H. pylori (via reduced somatostatin)
- Antral G-cell hyperplasia
- Gastric outlet obstruction
- Retained antrum (following gastric surgery)
- Cysteamine treatment
- Short bowel syndrome
- [not enough bowel to send suitable feedback inhibition via secretin, etc.?]
- Renal failure (very rare)
What is** retained antrum syndrome** and how does it lead to high acid secretion?
- A potential adverse effect following an inadequate resection in certain partial gastrectomy / gastric bypass surgeries.
- Typically seen in surgeries in which distance is created between the proximal and distal stomach by the placement of limb anastomoses.
- If part of the stomach antrum is not resected during the surgery, it will now be exposed heavily to the alakaline duodenum but only minorly to the acidic proximal stomach
- The constant (relative) alkaline pH of the retained antrum therefore causes chronic secretion of gastrin, and secondary to that, acid.
Name 5 conditions that can cause low stomach acid secretion.
- Medications
- PPI
- H2RA
- Anti-cholinergics
- Inflammatory destruction of parietal cells (gastritis)
- Acute H. pylori infection
- Vagal injury or transfection
- VIP-producing tumors
What are the main consequences of low acid secretion?
How serious is low acid secretion?
- Consequences:
- Impaired protein digestion
- Impaired absorption of Fe, Ca, and B12
- Bacterial overgrowth, infections/TB in the stomach and/or small bowel
- Impaired delivery of certain drugs (that require acidification)
- Low acid is generally well tolerated with most modern diets.
- What cell type produces Intrinsic Factor (IF)? What else does that cell produce?
- What is IF and where does it act?
- Parietal cells (also produce HCl)
- IF is a carrier glycoprotein that binds B12 to permit its active transport in to the ileum.
Conditions that affect _____________ might also have an effect of IF secretion.
HCl!
Describe the Schilling Test for Vit B12 deficiency
A test used to narrow down the potential causes for a noted B12 deficiency.
- Replace B12 parenterally
- 24hr urine collection of radiolabelled B12
- If low, repeat while giving IF
- If still low, repeat after empiric treatment for SBBO
- If STILL low: suspect pancreatic insufficiency or terminal ileal disease.
- If still low, repeat after empiric treatment for SBBO
- If low, repeat while giving IF
- Generally, what conditions might lead to reduced secretion of pepsin/lipase?
- What functions do pepsin and lipase have?
-
Conditions that inhibit acid secretion
- Exception: lipase does not change with PPI usage
- Functions:
- Protein digestion
- Less important with modern diet)
- Play a role in killing ingested infectious agents
- Protein digestion
- What conditions might causes reduced secretion of bicarbonate and/or mucuous?
- What is the major consequence of low bicarb/mucous?
- Conditions:
- Similar to those that affect gastric acid secretion
- Inhibition of prostaglandin synthesis (NSAID use)
- Major consequence: mucosal injury due to autodigestion
