**2. Functional dyspepsia: Pathophysiologic mechanisms and their relation to symptom pattern**

Several pathophysiologic mechanisms explain underlie dyspeptic symptoms. These include delayed gastric emptying, impaired gastric accommodation to a meal, and hypersensitivity to gastric distension, *H. pylori* infection, altered response to duodenal lipids or acid, abnormal duodenojejunal motility, or central nervous system dysfunction. At present, the pathophysiol‐ ogy of functional dyspepsia is only partially elucidated. However, there is growing evidence that functional dyspepsia is in fact a very heterogeneous disorder and different subgroups can be identified based on different demographic, clinical, and pathophysiologic features [2].

**1.** Delayed gastric emptying

of clinical, biochemical, endoscopic, and ultrasonographic evidence of organic disease that

from visible abdominal distension. Nausea Queasiness or sick sensation; a feeling of the need to vomit.

Pain refers to a subjective, unpleasant sensation; some patients may feel that tissue damage is occurring. Other pain sensations could be throbbing, shooting, stabbing, cramping, gnawing, burning or aching. By questioning the patient, pain should be

A subjective, unpleasant sensation or feeling that is not interpreted as pain according to the patient and which, if fully assessed, can include any of the symptoms below. Early satiety A feeling that the stomach is overfilled soon after starting to eat, out of

may or may not occur post-prandially (slow digestion).

proportion to the size of the meal being eaten, so that the meal cannot

Unpleasant sensations like the persistence of food in the stomach; this

Tightness located in the upper abdomen; it should be distinguished

On the basis of the most bothersome or predominant single symptom, identified by the patient,

Pain centred in the upper abdomen is the predominant (most bothersome) symptom [9].

Symptoms do not fulfil the criteria for ulcer-like or dysmotility-like dyspepsia [9].

An unpleasant or troublesome non-painful sensation (discomfort) centred in the upper abdomen is the predominant symptom; this sensation may be characterized by or associated

• No evidence of organic disease (including at upper GI endoscopy) that is likely to explain the symptoms; • No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool

would account for the symptoms [1] (Table 2).

**Symptom Definition**

2 Dyspepsia - Advances in Understanding and Management

Pain centered in the upper

Discomfort centered in the

upper abdomen

abdomen

frequency or stool form (i.e., not irritable bowel).

**1.** Ulcer-like dyspepsia

**2.** Dysmotility-like dyspepsia

**3.** Unspecified (non-specific) dyspepsia

**Table 2.** Rome III diagnostic criteria for functional dyspepsia [1, 9]

12 weeks minimum, that need not be consecutive, in the preceding 12 months of: • Persistent or recurrent symptoms (pain or discomfort centred in the upper abdomen);

**Table 1.** The spectrum of dyspepsia symptoms and recommended definitions [4, 5]

distinguished from discomfort.

Fullness after meal

Bloating in the upper abdomen be finished.

functional dyspepsia is further classified into various subgroups [4, 9]:

with upper abdominal fullness, early satiety, bloating, or nausea [9].

Delayed gastric emptying is traditionally considered a major pathophysiologic mechanism underlying symptoms in functional dyspepsia and idiopathic gastroparesis [10]. Several large single-centre studies from Europe found association between delayed gastric emptying and the prevalence and severity of symptoms like post-prandial fullness, nausea, and vomiting [10]. Similarly, other reports have investigated the relationship between delayed gastric emptying and symptom pattern and severity [2]. Depending on the study, the percentage of dyspeptic patients with delayed gastric emptying ranges from 20% to 50%. In a meta-analysis of 17 studies involving 868 dyspeptic patients and 397 controls, significant delay of solid gastric emptying was present in almost 40% of patients with functional dyspepsia [11]. Various causes of delayed gastric emptying are summarized in table 3.

**2.** Impaired gastric accommodation to a meal

The motor functions of the proximal and distal stomach differ remarkably. The proximal stomach (body) serves mainly as a reservoir. In contrast, the distal stomach (antrum) regulates gastric emptying of solids by grinding and sieving the contents until the particles are small enough to pass the pylorus. The stomach accommodates to a meal by relaxing of the proximal stomach, providing the meal with a reservoir and enabling an increase in volume without an increase in pressure. Scintigraphic and ultrasonographic studies have shown an abnormal intragastric distribution of food in patients with functional dyspepsia, with preferential accumulation in the distal stomach. These findings suggest defective postprandial accommo‐ dation of the proximal stomach [12, 13].

**3.** Hypersensitivity to gastric distension

Physiologic stimuli during the digestive process are not normally perceived but in some circumstances may induce conscious sensations. Patients with functional gastrointestinal diseases may have a sensory dysfunction of the gut (termed visceral hypersensitivity), with normal physiological stimuli perceived as discomfort or pain [14]. Patients with functional dyspepsia appear to have enhanced sensitivity to gastric distension [10, 15, 16].

**4.** Altered duodenal sensitivity to lipids or acid

The symptoms of dyspepsia are usually exacerbated by meals which are rich in fat [20]. Similarly the duodenum is more sensitive to acid in those with functional dyspepsia. The duodenal motor response to acid is decreased in patients with functional dyspepsia, resulting in reduced clearance of exogenous duodenal acid [21].

**3. Causes of delayed gastric emptying**

**Acute (Transient) Delayed**

**Chronic Delayed Gastric**

**Pharmacological Agents and**

**Table 3.** Causes of Delayed Gastric Emptying [23].

**4. Diagnostic investigations of dyspepsia**

**Gastric Emptying**

**Emptying**

**Hormones**

components of dyspepsia.

breath or stool testing.

3 [23].

The various causes that are related to delayed gastric emptying are summarized here in Table

Functional dyspepsia is usually a diagnosis of exclusion; the diagnosis is made after eliminat‐ ing organic disease or a structural basis for symptoms. The physician must decide how many investigations to order before deciding that the patient has a functional disorder (Table 4). The heterogeneity of presentation and the extensive differential diagnosis including significant organic disease mandates rapid exclusion of pathologies like peptic ulcer disease, reflux esophagitis and malignancy of the stomach or esophagus. Another perspective is the test-andtreat approach that includes acid suppression, treatment of *H.pylori* infection and early endoscopy. Patients with "alarm features" (Fig 1), or those older than 40-50 years (depending on ethnicity) require a more aggressive strategy such as early endoscopy. It must also be understood that there are many patients who can have both organic as well as functional

Initial investigations may include blood counts, electrolytes, fasting blood sugar, renal function tests and thyroid function tests. Testing for celiac disease and stool examination for occult blood or parasites may also be considered. *H.pylori* infection can be diagnosed by serology,

Gastric accommodation can be assessed by gastric barotest. The barotest measures gastric tone and comprises of a bag that can be maintained at a constant pressure by feedback mechanisms (termed a barostat). Volume changes in the bag thus represent variation in gut - the bag

Parenteral nutrition,

Somatostatin

Cigarette smoking, Alcohol, Viral gastroenteritis, Hyperglycemia, Acidosis, Hypokalemia, Immobilization, Myxoedema, Hypocalcaemia, Hypercalaemia, Hypomagnesaemia, Hepatic coma, Postoperative ileus,

Diagnostic Testing for Functional Dyspepsia http://dx.doi.org/10.5772/57088 5

Gastric ulcer disease, Functional dyspepsia, Gastroesophageal reflux disease, Diabetes Mellitus, Hypothyroidism, Post gastric surgery, Addison's diseases, Pernicious anaemia, Achlorhydria, Connective tissue diseases, Anorexia nervosa, Depression, Neurologic disorders (Multiple sclerosis, Parkinsonism, paraneoplastic syndrome etc).

Antacids (aluminium hydroxide), Opiates, Anticholinergics, Tricyclic antidepressants, Beta adrenergic agonists, Levodopa, Calcium channel blockers, Progesterone, Birth control pills, Gastrin, Cholecystokinin,

#### **5.** Inflammation

About a third of patients with irritable bowel syndrome or dyspepsia describe the onset of symptoms after an acute enteric infection. It is possible that mucosal inflammation may have a part in the creation of the visceral hypersensitivity.

**6.** H. Pylori infection

The discovery of *H. pylori* led to uncovering a causal relationship between *H. pylori* infection and the occurrence of duodenal and gastric ulcers [17]. The role of *H. pylori* is less clear in functional dyspepsia. Systematic reviews of the epidemiologic evidence on a relationship between *H. pylori* infection and functional dyspepsia have found no evidence for a strong association [18, 19].

<sup>\*</sup>The alarm features are unintended weight loss, progressive dysphagia, recurrent or persistent vomiting, evidence of gastrointestinal bleeding, anemia, fever, family history of gastric cancer, new onset dyspepsia in the subjects over 40 years of age in population with high prevalence of upper gastrointestinal malignancy and over 45 and 50 years in populations with intermediate and low prevalence, respectively. \*\*Adapted from reference [22]

**Figure 1.** Diagnostic algorithm for functional (functional) dyspepsia\*\*
