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Flashcards in Week 2 Deck (109):

mucosal neck cell

secrete mucus,


parietal cell

secrete HCl, intrinsic
factor, gastroferrin


chief cell

secrete pepsinogen


cardiac, body and pyloric cells

cardiac 50% gland- lots of mucous cells,
body 70% gland- lots of parietal, chief cells
pyloric 40% gland- mucous cells and enteroendocrine



Hormone gastrin is secreted from G cells in the antrum, which activates parietal cells in the fundus/corpus to secrete acid
Gastrin is polypeptide with variable length and sequence that binds to CCK2 receptors
Triggers for Gastrin release from G cells in the antrum1. Seeing food or stomach distension causes vagal stimulation causing release of Gastrin-releasing peptide2. Aromatic amino acids in the lumen


How do you get acid secretion?

Gastrin, histamine (H2), and ACh activate acid secretion of parietal cells via cAMP or Ca++ dependent pathways
Acetylcholine, the neurotransmitter released from vagal fibers and enteric neural excitatory fibers:
Binds muscarinic receptors on parietal cells

Gastrin released into the blood by G cells
Binds to parietal cells
Activates ECL cells release of histamine

Histamine released from ECL cells binds parietal cells.


Ion transport by parietal cells

1. Sodium, potassium ATPase in basolateral membrane and potassium flows out into the lumen.2. Protons are generated in cytosol via carbonic anhydrase II (C.A. II)
2. Proton pump- H+, K+ ATPase pumps protons into the lumen (lots of mitochondria)
3. Bicarbonate ions are exported from the basolateral side by vesicular fusion or the chloride/bicarbonate exchanger and enters blood stream creating alkaline tide
4. Cl- moves passively down the electrical gradient when the luminal Cl- channel opens and water follows.


Inhibitor of gastrin release

Somatostatin is secreted from D cells in the antrum when pHDuring gastric phase, food enters the stomach raising the pH leading to a decrease in somatostatin secretion and an increase in Gastrin levels

Somatostatin when pH


Phases of Gastric Secretion

Interdigestive Phase: Low acid secretion, D cells secrete somatostatin to maintain low levels of Gastrin

Cephalic Phase – dorsal vagal complex integrates input from higher centers (seeing and tasting food) to activate Vagus nerves. GRP activates gastrin release and Ach activates ECL and parietal cells.

Gastric Phase – distension of the stomach activates vagal afferents and the enteric nervous system. Amino acids activate gastrin secretion and food raises pH decreasing somatostatin secretion.

Intestinal Phase – introduction of the gastric contents into the small intestine activates duodenal G cell secretion of gastrin. Activation of secretin and other enterogastrones and neural reflex decreases gastric secretion.


Intrinsic Factor

Glycoprotein secreted by parietal cells that
mediates uptake of B12 in ileum.
Protein-pump inhibitor drugs act on parietal cells but do not inhibit secretion of intrinsic factor.

B12 deficiency results in pernicious anemia
and neurologic deficiencies
Caused by autoimmune destruction of parietal cells or intrinsic factor, bypass surgery



Pepsinogen is a group of inactive proenzyme proteases.

Secreted by Chief Cells in gastric glands in response to acetylcholine and gastrin… inhibited by secretin

Activated by acidic environment of stomach to pepsin which is a potent proteolytic enzyme.

Pepsin is an endopeptidase and further activate pepsinogen by autolysis.

Chief cells also secrete gastric lipase, which releases fatty acids


Mucous Secretion

Surface epithelial cells secrete mucus and bicarbonate in response to PGE2

pH at surface is 7 and and drops to 2 in the lumen

H+ ions and pepsin crossing the barrier are neutralized by bicarbonate

NSAIDs block PGE2 effects leading to reduced mucus secretion, which contributes to gastric irritation.

Catecholamines suppress mucosal bicarbonate secretion… contributing to gastric irritation and the formation of “stress ulcers”.


Zollinger-Ellison Syndrome

Usually caused by a Gastrin-secreting tumor in the pancreas or small intestine
Results in excess H+ secretion as well as hyperplasia and hypertrophy of parietal cells
95% of patients develop gastric ulcers

Zollinger-Ellison excess H+ overwhelms the buffering capacity of bicarbonate in the duodenum. Leading to inactivation of pancreatic lipase (more sensitive to pH than proteases)


Peptic Ulcers Disease

- Hyperacidity
- Deterioration of the gastro-mucosal barrier


Gastric and duodenal ulcers

Infection – Helicobactor pylori
Poor secretion of mucus, bicarbonate by the surface epithelium
Stress (may contribute but doesn’t cause)
Irritation by alcohol, acid, digestive enzymes, bile
Treat with antibiotics and proton pump inhibitor. Stop NSAID


GI peptic ulcer pathophysiology

Gastrin levels often increased in gastric ulcers since somatostatin inhibition of gastrin during the fasting state is not activated (may be related to urease activity of H. pylori)
Increased gastrin can cause acid hypersecretion, pepsin secretion, hyperplasia of ECL and Parietal cells and stomach contractions.
Subset of individuals with hypochlorhydria is related to gastritis and destruction of the gastric epithelial cells.
Inflammatory response to H. pylori or loss of protective factors due to NSAID inhibition of PG synthesis further contributes to ulcer formation.
Infection and high acidity can spread to duodenum resulting in decreased bicarbonate and duodenal ulcers



reduced acid secretion
Caused by aging, gastric resection, genetic factors, auto-immune attack of the H+/K+ ATPase, taking proton pump inhibitor, infection– atrophic gastritis
Bacterial overgrowth, diarrhea, pneumonia
Hip fractures and iron deficient anemia- decreased Ca++ and iron absorption
Decrease in pepsin activation doesn’t seem to cause problems (no increase in nitrogen excretion)


Gastroileal reflex

Expansion of the stomach signals forward along the enteric nervous system to empty more distal segments.
Gastroileal reflex- causes ileoceccal valve to relax transfer contents from small to large bowel


Gastrocolic reflex

Expansion of the stomach signals forward along the enteric nervous system to empty more distal segments.
Gastrocolic reflex- induces the need to defecate after ingesting a meal


Gastric absorption

Lipid soluble substance such as alcohol and aspirin can be absorbed by diffusion but there is no active transport
Absorption of these substances is associated with gastritis.


Basic Electrical Rhythm

Peristalsis occurs at the Basic Electrical Rhythm (BER) is 3 to 5 waves per minute in the stomach.
- This establishes the maximum frequency of the wave that is propagated over the stomach.
- The amplitude of the BER can be altered by neural (ACh causes calcium influx) and hormonal (Gastrin) input. - The number of action potentials on the crests of the slow waves determines the magnitude of the contraction.
- Contractions strengthen and speed up as they approach the closed pyloric sphincter.


Gastric contractions and gastric emptying are inhibited by:

- acid in the duodenum via neural (enteric and vagal) and hormonal (secretin and somatostatin) mechanisms
- fat in the duodenum via hormonal (CCK) mechanisms and via enteric neural mechanisms
- osmolality of the duodenal contents via enteric neural mechanisms and perhaps hormonal mechanisms (GIP)


Pyloric Stenosis

congenital condition where pylorus fails to relax after a meal leading to malnutrition and dehydration. Treated with surgical myotomy.



reduced gastric emptying often due to diabetic neuropathy involving the vagus and enteric nerves in the stomach such that the stomach fails to generate enough force to empty the stomach. Other causes include drugs and cancer treatments. Results in nausea, vomiting, bloating, poor digestion, weight loss, malnutrition, impaired absorption of medications, and impaired glycemic control. Treat with prokinetic drugs.


Dumping Syndrome

rapid gastric emptying often resulting from gastric bypass surgery, vagotomy, and high sugar-containing meals. Rapid entry of gastric contents into the duodenum represents an osmotic challenge, water moves into the lumen resulting in hypovolemia and reduced blood pressure. Results in nausea, weakness, dizziness, sweating, shakiness, diarrhea, heart palpitations


Peptic ulcer disease

scarring and ulcers near the pylorus can delay emptying or in duodenal ulcers can lead to rapid gastric emptying due to loss of duodenal negative
feedback mechanisms.


How to suppress vomiting?

The neurotransmitters that regulate vomiting are poorly understood, but inhibitors of dopamine, histamine, and serotonin are all used to suppress vomiting.


Summary of Motility

Receptive relaxation of the proximal stomach allows the stomach to function as a reservoir
The antral stomach uses phasic contractions driven by the basal electrical rhythm of the stomach to grind the meal
Emptying of the stomach involves tonic contractions of the proximal portions and pylorus opens only partially and intermittently in response to feedback from the duodenum.
Liquids leave most quickly and fats leave the stomach slowly permitting emulsification.
During fasting, phase III of the MMC is stimulated by the GI hormone motilin and acts to remove undigested material
Vomiting requires somatic and gastrointestinal muscles, and involves retrograde propulsion of the gastric contents out of the body.


Periodontal Disease

Periodontal disease is infectious disease destroying supporting structures of teeth

Affects more than 30% of population worldwide

Mild and common form: gingivitis. Involves the gums.



infection of underlying tissues and bones

having periodontitis may be associated with:
Heart attack
Lung disease
Premature birth or having a baby with low birth weight, in women



Biofilms consist of two or more species of bacterial microcolonies that are enclosed in a glycocalyx.
Glycocalyx is composed of polysaccharides and constitutes up to 50-95% of the biofilm
Other components of the biofilm include proteins and DNA
Can be hundreds of species in a biofilm
Formation of a biofilm:
Weak adherence of cells to a surface
Stronger adherence, likely co-adhesion mediated
Multiplication of cells
Polysaccharide formation
Changing of microbial composition over time
Why live in a biofilm:
Protection from the immune system
Protection from antibiotics
Symbiotic (but also anti-symbiotic) relationships
Local conditions of pH, etc, in a normally inhospitable environment


Tip for id-ing bad oral microbes?

Microbes that cause caries are usually located in plaques on tooth surfaces, often in crevices or between teeth
Tip: they’re often gram positive

Microbes that cause periodontal disease do their destruction primarily below the gumline – in the subgingival space
Tip: they’re often gram negative


Strep Mutans

Gram + Cocci
Catalase -
Facultative anaerobe
a hemolytic
optochin resistant

Mutans Streptococci have well-known virulence factors:
adhesin-like surface-associated proteins (e.g. AgI/II family) that are capable of binding to receptors in the pellicle

extracellular glucosyltransferases (Gtfs) are constituents of the pellicle and are capable of synthesizing glucans (a type of polysaccharide) in situ from sucrose. Glucans provide additional S. mutans binding sites, as it binds avidly and in large numbers to these polymers


Strep Mitis v Mutans?

Mitis is usually benign, mutant causes caries.


Porphyromonas gingivalis

Gram (-)




Black-pigmented colonies on blood agar plates

Bacitracin resistant

Porphyromonas gingivalis

Cause periodontal disease


Candida albicans

Oral Thrush (Oral candidiasis

Most common in babies, elderly, immunocompromised



Hairy leukoplakia
Fuzzy white patches on side of tongue
Unlike thrush, it cannot be wiped away


Bacterial: alpha-hemolytic streptococci, staphylococci and bacteroides groups

Ludwig’s angina
complication of severe tooth infection or periodontal disease

Skin infection on floor of the mouth, usually results from untreated dental infections.
Swelling of infected area may block the airway or prevent swallowing of saliva.

Symptoms include:
Breathing difficulty
Confusion or other mental changes
Neck pain
Neck swelling
Redness of the neck
Weakness, fatigue, excess tiredness



Creamy white lesions, usually on the tongue or inner cheeks. Sometimes oral thrush may spread to the roof of the mouth, gums, tonsils, or pharynx (or esophagus)

Esophageal form is dangerous

Diagnosis: May diagnose entirely on symptoms, but scraping on microscope slide can be performed (look for hyphae forms)

Treatment: Must treat with prescription antifungal
Most commonly a topical treatment: clotrimazole lozenge and nystatin suspension (swish and swallow).
Unresponsive cases: a systemic antifungal such as fluconazole
Worst case: IV administration of amphotericin B (significant side effects)

Untreated infections can lead to an invasive candidiasis.


Candida albicans

Hyphael forms


Non-spore Forming


Candida albicans


S. pyogenes

Gram (+)


Catalase (-)

b Hemolytic

Bacitracin Sensitive

S. pyogenes


C. diphtheriae


Gram (+)


Non-spore Forming


C. diphtheriae


Epstein-barr virus

Double stranded




Epstein-barr virus


Helicobacter pylori

Gram (-)

Flagellated helix-shaped rod (spirilli)


Catalase and oxidase (+)

Urease (+)

Helicobacter pylori
Virulence factors:
adhesins, urease (raises pH), immune evasion, motility and chemotaxis, VacA, TFSS, CagA

Diagnosis: A variety of methods are available, know the principles behind each test
Endoscopy + culture
Breath Test
Stool test
Blood test

Diagnosis considerations:
For test selection consider:
purpose (diagnosis or follow-up)

Treatment: a week of “Triple therapy” is currently used
Antibiotics will be necessary (often clarithromycin and amoxicillin; the 1,2) to remove H. pylori
Proton pump inhibitor (3rd arm of triple therapy) to aid in the healing of ulcer


Chronic gastritis vs Gastric ulcer

Symptoms of gastritis:
Inflammation of the gastric mucosa (transient or chronic)
Gnawing or burning ache in upper abdomen. May become either worse or better with eating
A feeling of fullness in your upper abdomen after eating

Symptoms of gastric ulcer:
Open sores that develop on the inside stomach lining.

Most common: burning abdominal pain
Felt anywhere from navel to breastbone
Worse when stomach is empty
Flare at night
Often temporarily relieved by eating foods that buffer stomach acid
Disappear and then return for a few days or weeks



H. Pylori virulence factor
Pore forming cytotoxin that allows leakage of Ca+ from epithelial cell



H. Pylori virulence factor
Type 4 secretion system (TFSS) is a needle through which CagA travels into the host cytosol and affects the proliferative activities, adhesion, and cytoskeletal organization of epithelial cells. The entire system is also highly proinflammatory.
CagA is now known to interact with at least ten host proteins


How to cause an ulcer

1. Attract inflammatory cells
2. Inflammatory cells cannot kill easily
3. Host damages itself by continual, ineffective immune response!



Gold standard test
…but invasive, $$$
Guided biopsy, then:
rapid urease testing


Breath test

urease makes ammonia
Detects radioactive CO2
Good for diagnosis
Good for confirming cure
Requires skilled technician


Blood test

Detects H. pylori antibodies
Useful for initial diagnosis only
Not useful for confirming cure


Stool antigen test

Good for diagnosis
Good for confirming cure


H. pylori associated Carcinoma and Lymphoma

Less frequently, H. pylori infection results in cancers:

Mucosa-associated lymphoid tissue (MALT lymphoma or MALToma) in the stomach is termed “gastric MALT”
Indigestion, heartburn (stomach pain)
Long term inflammation is culprit
Tumors of B cells
Antibiotics are still part of the treatment strategy

Gastric carcinoma
Indigestion, heartburn (stomach pain)
Long term inflammation is culprit
Cancer of stomach lining (epithelial cells)
H. pylori a risk factor in only 65-80% of gastric carcinoma
potential mechanism by which CagA could contribute to gastric carcinogenesis: association with inactivation of tumor suppressor proteins

Note: Infection with H. pylori is also associated with a reduced risk of esophageal adenocarcinoma. (Can you think of a hypothesis for mechanism??)



Characterized by acute neutrophilic inflammation of the mucosa, often with hyperemia and hemorrhage (acute hemorrhagic gastritis).

The inflammatory changes can be complicated by gastric mucosal erosion (loss and necrosis of surface epithelium, confined to the lamina propria, i.e. mucosa) or an acute ulceration (necrotizing process extends beyond the mucosa into the submucosa and even into and through the muscle wall).

Many causes:
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)

Complications of acute gastric ulceration include bleeding and perforation.



Chronic gastritis demonstrates morphologic findings of chronic inflammation (lymphocytes, plasma cells) or evidence of chronic injury (as in chronic reactive gastropathy). Often varying degrees of acute inflammation may also be present (when acute inflammation is present along with chronic inflammation, the histologic findings are described as active chronic gastritis).

Most common causes of chronic gastritis include:
H. pylori gastritis
Autoimmune gastritis
Chronic reactive gastropathy

Complications of chronic gastritis include gastric mucosal erosions, peptic ulcer disease, gastric atrophy, intestinal metaplasia, dysplasia, and malignancy.


H. pylori gastritis

most common pathologic finding is active chronic gastritis, which typically begins in the antrum and can progress to involve the fundus. Morphologic findings of gastric atrophy can also be present. Patients can have high acid production and can get mucosal erosions and peptic ulcers. Complications also include MALT-lymphoma and gastric adenocarcinoma.


Helicobacter heilmannii

can also cause disease similar to H. pylori; this organism has reservoirs in cats, dogs, pigs, and nonhuman primates.


Autoimmune gastritis

Due to 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).
The autoimmune damage results in:
Decreased gastric acid secretion (achlorhydria).
Compensatory hypergastrinemia and hyperplasia of antral gastrin-producing G cells, along with endocrine cell hyperplasia in the fundus and body of the stomach.
Vitamin B12 deficiency due to loss of secreted intrinsic factor (pernicous anemia with increased RBC MCV).
Reduced serum pepsinogen I concentration.
Inflammatory mucosal damage and atrophy of the gastric mucosa in the body and fundus with sparing of the antrum and cardia.
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.


Chronic reactive gastropathy

Pattern of chronic gastric injury characterized by foveolar hyperplasia, mucin depletion, vascular congestion, edema, and lamina propria fibrosis. Changes are due to chemical mucosal injury, associated with use of NSAIDs, aspirin, bile reflux, and alcohol ingestion. Patients can get gastric erosions and ulceration.

Chronic reactive gastropathy is very common, so make sure you understand the implications when a gastric biopsy is signed out as “gastritis with changes of chronic reactive gastropathy.”


Peptic ulcer disease (PUD)

Chronic ulceration of the GI tract associated with exposure to gastric type acid, typically occurring in the stomach and first portion of the duodenum (duodenum most common site).

Most cases are due to either H. pylori chronic gastritis or due to chronic use of NSAIDs. H. pylori can produce hyperchlorhydric chronic gastritis which then damages the mucosa. NSAIDs cause direct chemical irritation and can suppress prostaglandin synthesis which is necessary for mucosal protection. It is estimated that 70% of patients with PUD have H. pylori infection, although only about 20% of H. pylori infected individuals will develop PUD.

Other causes of ulceration associated with exposure to gastric acid include Zollinger-Ellison syndrome, GERD (with esophageal ulceration), and heterotopic gastric mucosa in a Meckel’s diverticulum (small intestinal ulceration). Other factors implicated in ulceration include cigarette smoking, and chronic use of high dose corticosteroids.
Complications of chronic ulceration in PUD include:

Bleeding (clinical hemorrhage as well as iron deficiency anemia).


Obstruction, particularly when the ulcer is located in the pyloric channel, secondary to edema and fibrosis.

Clinically, patients present with epigastric burning or aching pain, (often occurring 1-3 hours after eating and relieved with food), GI bleed, iron deficiency anemia, or perforation.

Treatment is eradication of H. pylori if present, and neutralization of gastric acid with proton-pump inhibitors. Limiting use of offending medications such as NSAIDs is also recommended. Perforated ulcers can produce free air in the abdomen which can be seen on upright radiographs. These perforated ulcers may require surgical treatment.


Eosinophilic gastritis

defined as eosinophil rich inflammation, in the absence of a known cause for eosinophilia (e.g. reaction to drugs, parasitic infections, malignancy).

Most cases are thought secondary to some type of allergic reaction to a food allergen (e.g. cow’s milk or soy protein in children). Patients may have peripheral blood eosinophilia and elevated IgE levels.

Isolated eosinophilic gastritis is rare; most cases have involvement at multiple GI sites (e.g. esophagus, duodenum, in addition to the stomach – “eosinophilic gastroenteritis” when small bowel and stomach are involved).

Lesions may present as a mass, large ulcer, or with pyloric obstruction.


Lymphocytic gastritis

gastritis characterized by marked intraepithelial lymphocytic inflammation (CD8+ T lymphocytes). 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.


Collagenous gastritis

gastritis that appears morphologically similar to collagenous colitis. It can occur in patients with co-existing collagenous colitis, and also as an isolated disease involving the stomach only.


Granulomatous gastritis

defined as gastritis with granulomatous inflammation. Most cases are secondary to an underlying disorder, such as Crohn’s disease, sarcoidosis, mycobacterial or fungal infections.


Menetrier’s disease

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. Patients also experience protein losing enteropathy and hypoproteinemia, with diarrhea, weight loss, and peripheral edema. Some cases of Menetrier’s disease are associated with an infection (e.g. CMV in children).

Patients are also at risk for gastric adenocarcinoma.


Zollinger-Ellison syndrome

Caused by gastrin secreting tumors (gastrinomas, a functioning type of neuroendocrine tumor, to be discussed later), which are most commonly found in the pancreas and small bowel.

Elevated gastrin (diagnostic test) results in marked increase in the number of parietal cells, with increased gastric acid production. In addition, there is hyperplasia of mucus neck cells with mucin hyperproduction, and proliferation of endocrine cells in the stomach which can result in gastric carcinoid tumors.

Patients will often present with PUD or chronic diarrhea. Treatment consists of removal of the gastrinoma and administration of proton-pump inhibitors.

Gastrinomas are sporadic in 75% of patients, and the remainder are associated with MEN type I. The sporadic tumors tend to be solitary, whereas those associated with MEN type I may be multiple. Overall, 60-90% of gastrinomas exhibit malignant behavior.


Hyperplastic polyp

Most occur in association with chronic gastritis (H. pylori gastritis, chronic reactive gastropathy, autoimmune gastritis); 75% of all gastric polyps are of this type, and 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.


Cystic fundic gland polyp (also known as 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).


Gastric adenoma

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.

Since gastric adenomas often occur in association with chronic gastritis and intestinal metaplasia, some believe they represent polypoid areas of dysplasia.


Inflammatory fibroid polyp

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.”


Hamartomatous polyps

stomach can be involved by polyps as seen in Peutz-Jeghers syndrome, juvenile polyposis, and Cronkite-Canada syndrome (these will be discussed in the lower GI tract lecture).


Pancreatic heterotopia

ectopic pancreatic rests in the stomach can produce a polypoid lesion.


Gastric xanthoma

consist of small,
sessile, yellow mucosal nodules
composed of aggregates of
lipid laden macrophages in the
lamina propria. Most commonly
seen in chronic gastritis, and
may represent a reaction to
tissue injury.


Congenital hypertrophic pyloric stenosis

Stenosis is due to hyperplasia of the pyloric muscularis propria. 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. Surgical myotomy is curative.


Dieulafoy’s lesion

Unusually large-diameter mural arteriole penetrates into the submucosa; these large vessels can erode through the mucosa and cause massive bleeding.


Gastric adenocarcinoma

Most common malignancy of the stomach (90%).

Significant variation in incidence worldwide, with countries such as Japan having 4-fold higher incidence than North America. This is believed to be secondary to environmental influences.

In USA, incidence of gastric cancer has declined dramatically in the 20th century, perhaps because of reduced intake of possible dietary carcinogens as well as decreased H. pylori prevalence (see chart).

Risk factors for gastric adenocarcinoma include:
-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).

Patients often present with symptoms of dyspepsia, dysphagia, and nausea (like chronic gastritis). Gastric adenocarcinomas typically occur in adults. Most adenocarcinomas involving the stomach occur at the GE junction, but these tumors are usually considered to be distal esophageal adenocarcinomas if their epicenter is within 5 cm of the GE junction and there is extension into the distal esophagus (typically see Barrett’s esophagus with these). Thus, most true gastric adenocarcinomas occur in the antrum.

Morphologic types:

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. Sometimes, this type of tumor can occur in younger adults. Diffuse involvement of the gastric wall can produce rigidity and a leather bottle appearance (linitis plastica).

Tumors can spread to regional lymph nodes and liver (common occurrence), or exhibit peritoneal spread in the abdomen (Sister Mary Joseph umbilical nodule). Sometimes the first evidence of disease will be metastasis to the left supraclavicular lymph node (Virchow’s node).

Treatment is with surgery, including regional lymph node dissection. Chemotherapy is used for those with unresectable disease and/or metastases. Overall survival is poor, with 5-year survival rate of 20%.


Gastrointestinal stromal tumors (GIST)

Can arise anywhere in the GI tract, but stomach is the most common site (60% stomach, 30% jejunum and ileum, 5% duodenum,


Gastric lymphomas

Stomach can be involved by a variety of lymphomas, but the most common lymphoma is the extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma, also known as MALTomas), followed by diffuse large B-cell lymphoma (DLBCL).

MALT lymphomas can arise in virtually any mucosal site (e.g. lung, GI tract, salivary gland, with stomach the most common site) and are typically associated with chronic inflammation. In the stomach, most MALT lymphomas are associated with H. pylori infection. It is believed that persistent infection with chronic antigenic stimulation results in activation of transcription factors that promote B-cell growth and survival. In some cases this is due to specific translocations resulting in fusion genes with transcription activation. In other cases, persistent H. pylori antigenic stimulation can activate transcription and induce a MALT lymphoma without genetic translocations.

Importantly, eradication of H. pylori infection with antibiotics will cause regression of gastric MALT lymphoma in 60-90% of cases! Gastric MALT lymphomas due to translocations are associated with a lack of response to antibiotic therapy.

As with H. pylori infection, patients present with dyspepsia and epigastric pain. Diagnosis is established by findings on the biopsy.
Gastric DLBCL is typically seen in older individuals, and may arise de novo or from high grade transformation of a lower grade lymphoma such as MALT lymphoma. These lymphomas may present as large ulcerated masses with transmural involvement.


GI neuroendocrine tumor/carcinoma (general comments)

These are tumors that arise from the diffuse endocrine cells that are found in the GI tract. The more well differentiated tumors have historically been called carcinoid tumors; however, as this term can give the false impression that the tumor will behave in a benign fashion, a revised classification scheme (which is still in evolution) has been proposed based on degree of differentiation, mitotic rate, and other findings that can predict the ability of the tumor to metastasize (i.e. behave in a malignant fashion).

The difficulty with GI neuroendocrine tumors is that most of them appear well differentiated histologically, and the appearance under the microscope does not allow one to predict their biological behavior.

Mitotic rate is often times measured with these tumors, either by counting the number of mitoses per 10 high power fields (HPF) or by measuring the percent of cells in the proliferative phase with an immunohistochemical stain (Ki-67).

The most important factors determining biologic behavior are the grade (as determined above), location, and stage of the tumor. In general, the benign (grade 1) tumors are of small size (2 cm in size, with invasion beyond the submucosa. Functioning tumors of any size that do not show poorly differentiated features are considered to be grade 3. The poorly differentiated grade 4 tumors appear malignant histologically, and look similar to small cell carcinoma or large cell neuroendocrine carcinoma as can be seen in the lung. Tumors are staged by site using the T,N,M classification.

GI neuroendocrine tumors/carcinomas can occur throughout the GI tract, but small intestine is the most common site (see chart).

Tumors typically occur in middle age or older adults.

Tumors may be functioning, resulting in symptoms. For example, tumors producing gastrin can result in the Zollinger-Ellison syndrome. Some tumors may cause the “carcinoid syndrome” of cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right sided valvular fibrosis. In this syndrome, the 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.

Most of the neuroendocrine tumors producing carcinoid syndrome are of midgut origin (jejunum and ileum, appendix, ascending colon).

A helpful diagnostic test for carcinoid syndrome is the detection of 24 hour urinary 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of seratonin.

In the stomach, these tumors typically present as a mass lesion or polyp. Most gastric neuroendocrine tumors are well-differentiated and non-functioning, and are most often confined to the mucosa or submucosa. These lesions rarely metastasize.

In autoimmune gastritis, one can see hyperplasia of the endocrine cells in the atrophic fundic mucosa. Neuroendocrine tumors associated with autoimmune gastritis often behave in an indolent fashion. Gastric neuroendocrine tumors that arise without a predisposing condition have a greater likelihood to exhibit malignant behavior.



defined as inflammation of the thin, mesothelial covered layer of tissue that lines the abdominal cavity (peritoneum) and covers most of the abdominal organs (serosa). Many possible causes


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 (bacterial infection occurring in the setting of ascites, without obvious source of contamination).



defined as the accumulation of excess fluid in the peritoneal cavity.

Many causes, but portal hypertension associated with cirrhosis is the most common cause (see list).

Mechanisms for the development of ascites include “transudative” processes such as portal hypertension, decreased osmotic pressure (e.g. hypoalbuminemia), and “exudative” processes such as peritoneal disease resulting in extravasation of exudative fluid (e.g. peritoneal malignancy). In portal hypertension with cirrhosis, the mechanisms of fluid accumulation are multifactorial, involving splanchnic vasodilation with increased sodium and water retention, hepatic sinusoidal hypertension with increased hepatic lymph fluid (this process also augmented by hypoalbuminemia), and percolation of the hepatic lymphatic fluid into the peritoneal cavity.

In obese individuals, detecting the presence of ascites by physical exam can be problematic. Imaging studies can be used, with abdominal ultrasound preferred over CT scan.

A complication of ascites can be spontaneous bacterial peritonitis, a bacterial infection developing in the absence of a known contaminating source. An exudate of acute neutrophilic inflammation and fibrin is present on the serosal and peritoneal surfaces, and the ascitic fluid exhibits increased numbers of neutrophils. Organism is detected with gram stain and culture.


idiopathic retroperitoneal fibrosis

a dense fibrosing process that can result in renal failure due to ureteral obstruction. CT image shows obstructive uropathy (arrowheads) resulting from ureteral involvement that precluded contrast administration. Note that calcified abdominal aorta is not elevated from underlying lumbar spine and relatively smooth peripheral margins of abnormal soft tissue (arrows). Some cases of idiopathic (i.e. not due to some other cause) retroperitoneal fibrosis may be manifestations of IgG4-related autoimmune disease (discussed later).


Plicae circulares

Prominent circular folds in duodenum and upper jejunum
Disappear in ileum
May increase surface area by a factor of 3


Lamina propria

Forms c.t. core of each villus
Contains a central lymphatic vessel (lacteal)
Capillaries and venules present
Very cellular connective tissue:
Lymphocytes, eosinophils, plasma cells, macrophages, fibroblasts, mast cells, smooth muscle cells, etc.


Crypts of Lieberkuhn

Open at base of villi
Extend to muscularis mucosae
Paneth cells at base of crypts
Many mitotic cells present
Cells turnover every 3-6 days
Cells migrate to tips of villi where they are shed


Brunner’s glands

Secrete an alkaline mucus (pH 8.1-9.3) into lumen of duodenum; neutralizes acid chyme arriving from stomach
Glands are located in submucosa and lamina propria


Histologic features of Duodenum

Brunner’s glands
Secrete an alkaline mucus (pH 8.1-9.3) into lumen of duodenum; neutralizes acid chyme arriving from stomach
Glands are located in submucosa and lamina propria
Many plicae circulares
Adventitia present


Histologic features of Ileum

Peyer’s patches
Aggregates of lymphatic nodules
M-cells: in epithelium above patches
Endocytose antigen and transport it to underlying lymphatic tissue
Provide precursors of intestinal plasma cells that produce IgA
Plicae very sparse or absent
Goblet cells are increasing in numbers


What kind of gland is the pancreas?

Exocrine and endocrine gland


Zymogen granules

Basis for eosinophilic staining of apical cytoplasm
Contain enzyme precursors (proenzymes)
Trypsinogen; chymotrypsinogen; proelastases; procarboxypeptidases; lipolytic enzymes (lipases); alpha-amylases; nucleases



Reservoir for bile
Concentrates bile
Releases bile to duodenum
Attached by cystic duct to common bile duct


Hydrolysis occurs where?

Enzymatic hydrolysis of carbohydrates and proteins occur in duodenum lumen through pancreatic enzymes, at the microvillous membrane, and in the enterocytes for peptides



What are causes?
Lactose in breast milk is major source of carbohydrates for infants
Decrease in lactase normal condition for most of the world’s adult population
Secondary after injury to absorptive cells due to Crohn’s disease, celiac disease, alcohol

Symptoms: Bacterial fermentation of lactose leads to gas accumulation/pain, Lactic acid production increases osmotic load and water enters the lumen resulting in increased peristalsis and diarrhea.


Monosaccharide uptake

Monosaccharide uptake occurs in duodenum and jejunum Two major apical transportersSGLT1 – sodium-glucose/galactose cotransporter-1GLUT5- fructose transporter
Glucose (and galactose) are actively taken up through a Na+-monosaccharide symporter, SGLT1 (2 Na+/1 sugar) This is a secondary active transport process, critically dependent upon low intracellular Na+ generated by the Na+/K+ pump
- Fructose uptake is promoted by a facilitated transporter, Glut5.
- All monosaccharides leave the basolateral membrane via Glut2 and go to the liver.


Protein Digestion

7 essential amino acids must be obtained from the diet since they can not be synthesized de novo - Digestion is initiated in the stomach by pepsin (cleaves at neutral aas) and is inactive at pH>4.5-Pancreatic proteases include endopeptidases and carboxypeptidases that require brush border enzyme enteropeptidase (enterokinase) for activation-Glycosylated and proline rich proteins are resistant to digestion
Amino acid absorption-Occurs in villi of duodenum and jejunum.
- Digestion is aided by brush border endo- and exopeptidases generating single amino acids
- Amino acids are transported across the apical membrane by Na+ dependent symporters dependent on the basolateral Na+/K+ pump (secondary active transport).
- Many of these enyzmes and transporters are degraded and resynthesized with each meal
-Peptide transporter 1 PEPT1 cotransports peptides with protons
- Apical sodium/hydrogen exchanger (NHE) supplies the luminal H+ ion and is supported by the basolateral Na+/K+ ATPase.
- Absorbed peptides are further digested by cytosolic proteases.
- Basolateral transporters export surplus amino acids into the blood.
- Peptides are cotransported with H+
- Amino acids are cotransported with Na+ - For first 6 months, intact proteins are absorbed by endocytosis. Mechanism of passive immunity in infants.
- M cells take up proteins which are transferred to lymphocytes as antigens


Digestion of Lipids

-dense in calories, includes fat soluble vitamins, and add flavor-
90% of dietary lipids are triglycerides
- 10% cholesterol, phospholipids, lipid soluble vitamins and toxins
- Chewing and churning facilitate emulsification increasing water to oil surface area and reducing surface tension.

Emulsfied particles are stabilized by coating with bile salts and phospholipids
Chief cells secrete gastric lipase- not required but facilitates 10-30% of lipolysis

Gastric lipase optimal pH is 5.4 and has a prominent role in neonates due to developmental delay of pancreatic enzyme expression and in people with pancreatic insufficiency.

Free fatty acids in the duodenum trigger the release of CCK that activates pancreatic acinar secretion of lipase and procolipase.

Pancreatic lipase activity is inhibited by low pH and bile acids prevent lipase binding to fat droplets.Colipase is activated by trypsin and binds bile acids recruiting lipase to cleave fatty acids.

Pancreas acinar cells produce additional enzymes that contribute to lipid digestion and many become active in the duodenum which contains higher levels of calcium. Cholesterol esterase has broad specificity and can hydrolyze the 2-position fatty acid left untouched by lipase

Secreted Phospholipase A2 converts phospholipids (cell membranes) into fatty acids and lysophospholipids

Bile salts and phospholipids act to break up (emulsify) large fat globules into droplets.

- Products are taken up by epithelial cell or are "packaged" into small bile salt-coated cylinders called "micelles”.

- Bile salts must be present at a certain minimum level (critical micelle concentration) before micelles will form and fat soluble vitamins must be packaged into micelles for uptake.

Lipids enter enterocytes by (1) nonionic diffusion, (2) collision with the membrane, or (3) carrier mediated transport

Most of absorbed fatty acids are reassembed into triglycerides and coated with apoproteins to form chylomicrons

- Fatty acid-binding protein and a sterol-binding protein transport fatty acids and cholesterol to the smooth ER where the 2-mono-glycerides are re-esterified into triglycerides.
- Re-synthesized products are packaged in lipid droplets, coated with -lipoproteins (apoproteins) and then extruded from the cell as chylomicrons.
- Chylomicrons are taken up by lacteals in the villi and flow with the intestinal lymph through the thoracic lymphatic duct into the venous circulation


Cholesterol esterase

Cholesterol esterase has broad specificity and can hydrolyze the 2-position fatty acid left untouched by lipase


Phospholipase A2

Secreted Phospholipase A2 converts phospholipids (cell membranes) into fatty acids and lysophospholipids



Ezetimibe reduces uptake of cholesterol from the lumen by inhibiting
Niemann Pick C1 Like 1 and is used to treat patients with hypercholestolemia


Colipase or lipase deficiency

Colipase or lipase deficiency- chronic pancreatitis or congenital mutations (triglycerides only need 10-15% of normal enzyme levels). Treat with pancreatic enzyme supplements



Nutrigenetics –
Refers to functional changes in the nucleic acid code that influences a persons response to nutrients
Variation may be associated with geographic ancestry
A gene variant may allow the better use of a specific nutrient by the organism


Necessary and Sufficient

If a SNP (or variant) is necessary (required) but not sufficient it would mean that it is always present but is not the only requirement for the condition.
Sufficient means that the SNP (or variant) is the actual cause of the condition,
could also be assisted by other SNPs in the same gene or in another location, which might modulate its behavior in a positive or negative manner.



seeks to identify environmental factors that effect gene expression (global gene expression/or single gene variants)


lipid absorption

The major products of lipid digestion - fatty acids and 2-monoglycerides - enter the enterocyte by simple diffusion across the plasma membrane. A considerable fraction of the fatty acids also enter the enterocyte via a specific fatty acid transporter protein in the membrane.
Lipids are transported from the enterocyte into blood by a mechanism distinctly different from what we've seen for monosaccharides and amino acids.
Once inside the enterocyte, fatty acids and monoglyceride are transported into the endoplasmic reticulum, where they are used to synthesize triglyeride. Beginning in the endoplasmic reticulum and continuing in the Golgi, triglyceride is packaged with cholesterol, lipoproteins and other lipids into particles called chylomicrons. Remember where this is occurring - in the absorptive enterocyte of the small intestine.
Transport of lipids into the circulation is also different from what occurs with sugars and amino acids. Instead of being absorbed directly into capillary blood, chylomicrons are transported first into the lymphatic vessel that penetrates into each villus. Chylomicron-rich lymph then drains into the system lymphatic system, which rapidly flows into blood.


acute edematous pancreatitis

Parenchymal edema and peripancreatic fat necrosis occurs first. This is called acute edematous pancreatitis.


hemorrhagic or necrotizing pancreatitis

When necrosis involves the parenchyma along with hemorrhage and gland dysfunction it is described as hemorrhagic or necrotizing pancreatitis


pancreatitis labs

Increased Amylase/ lipase
Lipase is both more sensitive and specific than amylase

Lipase and amylase may often be normal or only slightly elevated in chronic


Value of Ranson’s Criteria

predict mortality after 48 hours of acquired information. You must wait to get the information at 48 hours. The criteria are not used to predict mortality at admission with only initial labs.