General medicine

Gastroenterology

Introduction

The human abdomen is divided into quadrants and regions by anatomists and physicians for the purposes of study, diagnosis, and treatment. Nine regions of the abdomen can be marked using two horizontal and two vertical dividing lines. The vertical lines are the mid-clavicular lines taken from the mid-point of each clavicle. The upper horizontal line is the subcostal line taken from the inferior parts of the lowest costal cartilages. The lower horizontal line is the intertubercular line connecting the tubercles of the pelvis.

The three main centrally positioned regions are the epigastric region, the umbilical region, and the hypogastric region also known as the pubic region. On the sides of the abdomen, the other six regions are the left and right hypochondriac regions, on either side of the epigastrium; the left and right lumbar regions, on either side of the umbilical region, and the left and right iliac or inguinal regions on either side of the hypogastrium.

We can simplify the division using two lines:

• Right/left upper quadrant
• Right/left lower quadrant

In the right upper part, we have the liver and the last part of the stomach. Left upper: stomach. Lower: intestine.

Esophagus

The esophagus is a 25-cm long muscular tube that connects the pharynx to the stomach. The esophagus has three constrictions in its vertical course, as follows:

1. The first constriction is at 15 cm from the upper incisor teeth, where the esophagus commences at the cricopharyngeal sphincter; this is the narrowest portion of the esophagus and approximately corresponds to the sixth cervical vertebra.
2. The second constriction is at 23 cm from the upper incisor teeth, where it is crossed by the aortic arch and left main bronchus.
3. The third constriction is at 40 cm from the upper incisor teeth, where it pierces the diaphragm; the lower esophageal sphincter (LES) is situated at this level.

Stomach

The stomach is the first intra-abdominal part of the gastrointestinal (GI), or digestive, tract. It is a muscular organ, highly vascular, bag-shaped, and distensible, taking varying shapes depending on the build and posture of the person and the state of fullness of the organ. The stomach lies in the left upper quadrant of the abdomen.

The microstructure is composed of:

• Mucosa
• Submucosa with blood vessels which provide nutrients/vascularization
• Muscularis with different orientation of layers
• Serosa (tumors are usually found in serosa)

Gastric acid secretion

The stomach consists of three anatomical (fundus, corpus, and antrum) and two functional areas (oxyntic and pyloric). The oxyntic area comprises approximately 80 percent of the stomach and contains parietal cells that produce gastric acid.

Role of gastric acid and phases of secretion

Gastric acid facilitates the digestion of protein and the absorption of iron, calcium, vitamin B12, and is necessary for the absorption of some drugs. Gastric acid, by lowering pH, kills ingested microorganisms and limits bacterial growth in the stomach and prevents intestinal infections such as Clostridioides difficile.

The physiologic stimulation of acid secretion has classically been divided into three interrelated phases: cephalic, gastric, and intestinal.

1. Cephalic phase — The cephalic phase is activated by the thought, taste, smell, and sight of food, and swallowing. It is mediated mostly by cholinergic/vagal mechanisms.
2. Gastric phase — The gastric phase is due to the chemical effects of food and distension of the stomach. Gastrin appears to be the major mediator since the response to food is largely inhibited by blocking gastrin action at its receptors.
3. Intestinal phase — The intestinal phase accounts for only a small proportion of the acid secretory response to a meal; its mediators remain controversial.

Cells of the mucosa not only secrete gastric acid but also allow to constitute a mucous bicarbonate barrier. In this way, cells are protected from the acid environment which is just above this barrier.

Dyspepsia

Dyspepsia is a common symptom with an extensive differential diagnosis and a heterogeneous pathophysiology ("upset stomach", "indigestion").

Patients with dyspepsia usually describe:

• Postprandial fullness
• Early satiety
• Bloating
• Epigastric (in the central region just below the chest) pain/burning

Postprandial fullness is the most intense symptom in patients with meal-induced symptoms. Symptoms may be severe enough to limit usual activities. Some patients may have:

• Nausea
• Vomiting
• Heartburn, however, these symptoms are usually infrequent

Frequency: Dyspepsia occurs in at least 20% of the population, but most affected people do not seek medical care. Although dyspepsia does not affect survival, it is responsible for substantial health care costs and significantly affects quality of life.

Approximately 25% of patients with dyspepsia have an underlying organic cause. However, up to 75% of patients have functional (idiopathic or nonulcer) dyspepsia with no underlying cause on diagnostic evaluation (cause can’t be identified in most patients).

Dyspepsia secondary to organic disease (25%)

Although there are several organic causes for dyspepsia, the main causes are peptic ulcer disease, gastroesophageal reflux, medications (nonsteroidal anti-inflammatory agents being the most common offender), and gastric malignancy. Although gastric cancer as a cause of dyspepsia is a concern for both healthcare providers and patients, it is uncommon in the western world.

1. Peptic ulcer disease
2. Chronic gastritis
3. Gastroesophageal malignancy
4. Biliary pain (gallstones)
5. Drug-induced dyspepsia
6. Other causes, including celiac disease, chronic pancreatitis, infiltrative diseases of the stomach, intestinal angina, …

The principal diseases are due to helicobacter pylori (1, 2, and 3).

Gastroesophageal malignancy

Gastroesophageal malignancy is an uncommon cause of chronic dyspepsia in the Western hemisphere but the incidence is higher in patients of Asian, Hispanic, or Afro-Caribbean extraction. The incidence of gastroesophageal malignancy increases with age. When present, abdominal pain tends to be epigastric, vague, and mild early in the disease but more severe and constant as the disease progresses. In addition, other symptoms and signs typically evolve with disease progression (e.g., anemia, fatigue, weight loss).

Biliary pain (gallstones)

Classic biliary pain is characterized by episodic intense dull pain located in the right upper quadrant, epigastrium, or (less often) substernal area that may radiate to the back (particularly the right shoulder blade). The pain is often associated with diaphoresis, nausea, and vomiting. The pain is constant and not colicky. It is not exacerbated by movement and is not relieved by squatting, belching, bowel movements, or passage of flatus. The pain typically lasts at least 30 minutes, plateauing within an hour. The pain then starts to subside, with an entire attack usually lasting less than six hours.

Drug-induced dyspepsia

Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase 2 (COX-2) selective inhibitors can cause dyspepsia even in the absence of peptic ulcer disease. However, several other drugs have been implicated in drug-induced dyspepsia.

Helicobacter pylori

Gastric organisms were first observed more than 100 years ago and their association with gastritis has been recognized since the 1970s. The true implication of these microbes was not fully realized, however, until 1982 when Marshall and Warren identified and subsequently cultured the gastric bacterium, Campylobacter pyloridis, later reclassified as Helicobacter pylori (H. pylori). This organism is now known to cause chronic gastritis, most peptic ulcers, and gastric adenocarcinoma and lymphoma.

Gastric adaptation of H. Pylori

The organism's urease, motility, and ability to adhere to gastric epithelium are factors that allow it to survive and proliferate in the gastric milieu. There are three peculiar characteristics:

1. Bacterial urease hydrolyzes gastric luminal urea to form ammonia that helps neutralize gastric acid and form a protective cloud around the organism, enabling it to penetrate the gastric mucus layer.
2. Its spiral shape, flagella, and the mucolytic enzymes which it produces facilitate its passage through the mucus layer to the gastric surface epithelium.
3. H. pylori then attaches to gastric epithelial cells by means of specific receptor-mediated adhesion.

Although attachment is dependent upon binding of bacterial surface adhesins to specific epithelial cell receptors, host factors can modulate this process. As an example, certain individuals may express H. pylori specific surface receptors or greater numbers of receptors, making them more susceptible to attachment and colonization.

(It causes chronic forms of inflammations. Chronic can lead to tumor and lymphoma. The peculiarity is that it has several characteristics that explain how it can resist gastric acid of the stomach. There are three peculiar characteristics: it has bacterial urease and its peculiar shape facilitates the passage through the mucus.)

Transmission

The route by which infection occurs remains unknown. H. pylori person-to-person transmission through either fecal/oral or oral/oral exposure seems most likely. Humans appear to be the major reservoir of infection. Iatrogenic infection has been documented following the use of a variety of inadequately disinfected gastric devices, endoscopes, and endoscopic accessories. In addition, gastroenterologists and nurses appear to be at increased risk for acquiring this infection, presumably due to occupational exposure to infected gastric secretions.

Clinical manifestations of H. pylori infection

H. pylori Patients with acute infection are asymptomatic or develop mild self-limited dyspeptic symptoms. Few examples of spontaneous acute infection have been recognized since the majority of patients who develop nonspecific dyspeptic complaints (which may signal acute infection) may not seek medical attention and thus are not immediately investigated.

The ability of H. pylori to cause acute gastritis was first demonstrated after healthy volunteers ingested the organisms and developed a mild illness (consisting of epigastric pain, nausea, and vomiting without fever) associated with acute inflammatory changes on gastric biopsy. Acute gastritis almost always evolves into active chronic gastritis unless the patient is treated with appropriate antibiotics.

The usual natural history of gastritis is of an antral predominant early stage of infection with only minimal corpus involvement. This stage is associated with an increase in acid secretion, enough to cause duodenal ulcers in some patients. With continued inflammation, gastrin-producing (G) cells and acid-producing parietal cells are gradually lost, precipitating a fall in acid secretion and the development of atrophy with intestinal metaplasia.

(Last part of the stomach: in this portion of the stomach there is less gastric acid secretion) These changes facilitate the proximal migration of the bacteria, leading to corpus gastritis. Thus, the natural history of gastritis is of diffuse antral inflammation spreading to the corpus, resulting in an atrophic front of advancing corpus injury with concomitant reduction in acid secretion. This scenario is accelerated by hypochlorhydria such as that caused by chronic therapy with proton pump inhibitors (PPIs).

Endoscopic and histopathologic features

The endoscopic appearance of acute gastritis is variable and, in severe cases, can resemble lymphoma or gastric carcinoma. Histologic changes of acute gastritis include intense neutrophilic infiltration of the mucous neck region and lamina propria. When severe, pit abscesses occur, along with mucin loss, erosion of the juxtaluminal cytoplasm, and desquamation of surface foveolar cells. Both neutrophils and bacteria are responsible for the destruction of the epithelium. Lymphoid follicles appear within one week after the onset of H. pylori acute infection. In general, lymphoid follicles represent an immune response to the organism and are composed of aggregates of lymphocytes and other lymphoid cells associated with a central germinal center made up of larger, paler mononuclear cells.

H. pylori gastritis

Lymphoid follicles accompanying H. pylori gastritis are involved in the genesis of primary gastric B cell lymphoma. The pathogenesis may involve stimulation of B cells by activated T cells within the follicles. How can we be aware of and individuate this alteration? We can directly visualize the stomach by performing an endoscopy. The endoscope goes from the mouth into the esophagus and until the stomach. In this way, we can visualize the inner surface of the stomach thanks to the ability of the endoscope to retroflex and visualize the stomach up to the pyloric portion. The normal appearance is substituted with a shape and an aspect which is usually found in the intestine.

Once we have helicobacter pylori, we may have chronic gastritis, gastric atrophy, intestinal metaplasia, dysplasia, and cancer. Not all patients can have dysplasia and then cancer, but helicobacter can favor all these gastric events. Therefore, finding helicobacter pylori is useful to avoid this sequence of events. (By performing a biopsy, we can also analyze the histology.)

Functional dyspepsia (75%)

Functional (idiopathic or nonulcer) dyspepsia requires exclusion of other organic causes of dyspepsia. It is defined by the presence of one or more of the following:

• Postprandial fullness
• Early satiation
• Epigastric pain
• Burning
• No evidence of structural disease to explain the symptoms

The prevalence of functional dyspepsia ranges from 5 to 11 percent worldwide.

Pathophysiology

The pathophysiology of functional dyspepsia is not well understood. However, several potential mechanisms have been suggested, including:

• Gastric motility and compliance – mild delays in gastric emptying, rapid gastric emptying, antral hypomotility, gastric dysrhythmias, and impaired gastric accommodation in response to a meal
• Visceral hypersensitivity – lowered threshold for induction of pain in the presence of normal gastric compliance
• Helicobacter pylori infection – may cause smooth muscle dysfunction due to the induction of an inflammatory response
• Altered gut microbiome – dyspeptic symptoms are more likely to occur after an episode of gastroenteritis
• Duodenal inflammation – An association between functional dyspepsia and increased duodenal eosinophilia has been reported, with an increase in duodenal eosinophils in patients with early satiety
• Psychosocial dysfunction – Dyspepsia has been associated with generalized anxiety disorder, somatization, and major depression

Initial evaluation

A history, physical examination, and laboratory evaluation are the first steps in the evaluation of a patient with new onset of dyspepsia. The goal of the initial evaluation is to identify alarm features for gastroesophageal malignancy, which will direct the diagnostic approach.

1. History
2. Physical examination
3. Laboratory evaluation

1. History (may provide useful clues) - A detailed history is necessary to determine the underlying cause and to identify patients with alarm features. As examples:
   • A dominant history of heartburn or regurgitation is suggestive of gastroesophageal reflux disease (GERD).
   • Aspirin and other NSAID use raises the possibility of NSAID dyspepsia and peptic ulcer disease.
   • Radiation of pain to the back or personal or family history of pancreatitis may be indicative of underlying chronic pancreatitis.
   • Significant weight loss, anorexia, vomiting, dysphagia, odynophagia, and a family history of gastrointestinal cancers suggest the presence of an underlying gastroesophageal malignancy.
   • The presence of severe episodic epigastric or right upper quadrant abdominal pain lasting at least 30 minutes is suggestive of symptomatic cholelithiasis.
   • Nausea and vomiting, with or without weight loss, occurring with recurrent or persistent upper abdominal pain raises the possibility of gastroparesis, especially in patients with risk factors.

2. Physical examination - The physical examination in patients with dyspepsia is usually normal, except for epigastric tenderness. The presence of epigastric tenderness cannot accurately distinguish organic dyspepsia from functional dyspepsia. Other informative findings on physical examination include a palpable abdominal mass (e.g., hepatoma) or lymphadenopathy (e.g., left supraclavicular or periumbilical in gastric cancer), jaundice (e.g., secondary to liver metastasis), or pallor secondary to anemia. Ascites may indicate the presence of peritoneal carcinomatosis. Patients with an underlying malignancy may have evidence of muscle wasting, loss of subcutaneous fat, and peripheral edema due to weight loss.

3. Laboratory tests - It is more useful than physical examination. Routine blood counts and blood chemistry, including liver function tests, serum lipase, and amylase, should be performed to identify patients with alarm (= high risk of cancer) features (e.g., iron deficiency anemia).

Diagnostic strategies and initial management

The approach to, and extent of diagnostic evaluation of a patient with dyspepsia is based on the clinical presentation, the patient's age, and the presence of alarm features.

• Patients' age ≥ 60 years
• Patients' age < 60 years
• Selected cases (If we have no alarm features, our approach depends on age; cancer is more common when age increases)

Patient age ≥ 60 years

An upper endoscopy might be indicated to evaluate dyspepsia in patients age ≥ 60 years. Biopsies of the stomach should be obtained to rule out H. pylori. Patients with H. pylori should receive eradication therapy.