The anatomical divisions of the stomach (fig 10.1)consist of cardia, fundus, body, pyloric antrum and pylorus.
Fig 10. 1 (A) Gross anatomy of the stomach, (B) histology of the glands of body of the stomach. (( Use Fig 6.1 Pathophysiology))
The stomach receives both sympathetic and parasympathetic innervation. The sympathetic fibers reach the stomach via celiac plexus. The parasympathetic fibers reach the stomach through the left and right vagus nerves. The anterior vagal trunk, which is derived mainly from the left vagus nerve, enters the abdominal cavity through the esophageal hiatus in the diaphragm. Its gastric branches are distributed on the anterio-superior surface. The posterior vagal trunk, which is derived mainly from the right vagus nerve, also enters the abdomen through the esophageal hiatus in the diaphragm on the posterior surface of the esophagus. Its gastric branches are distributed on the posterio-inferior surface of the stomach.
Besides the extrinsic innervation described above, the stomach contains an extensive enteric nervous system in the form of submucosal Meissner’s plexus and Auerbach’s plexus situated between the two layers (circular and longitudinal) of the muscle coat. Various neurons of the enteric nervous system produce norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), substance P, somatostatin, or nitric oxide.
The sympathetic supply chiefly controls the blood vessels and muscular coat of the stomach. Sympathetic stimulation decreases gastric motility. Parasympathetic stimulation increases gastric motility as well as the secretion of oxyntic (parietal) cells, chief cells and G cells of the gastric mucosa.
Secretory Functions of stomach
Mucosal glands of the fundus and body of the stomach secrete gastric juice rich in acid and pepsinogen (Fig 10.1 B). Mucosa of the pyloric regions secretes bicarbonate-rich soluble mucus. The surface of the entire gastric mucosa is lined by columnar cells that produce a viscid bicarbonate-rich mucus that adheres to the cells. The cell source and the main functions of the stomach are summarized in Table 10.1 . .
Table 10.1 The cell source and chief functions of various constituents of gastric juice and endocrine gastric secretions.
Endocrine gastric secretion
G cells (in pyloric antrum)
Increased secretion of oxyntic and chief cells of the stomach and of exocrine pancreatic acini
D cells (all over gastric mucosa)
Suppression of acid secretion
Feedback control of gastric acid regulation
Several specialized cells in the gastric mucosa contribute to the control of acid secretion. G cells in the gastric antrum release the hormone gastrin. Gastrin acts on the enterochromaffin-like cells in the gastric corpus to release histamine, which stimulates parietal cells to secrete acid. Gastrin also stimulates parietal cells directly and promotes growth of enterochromaffin-like and parietal cells.
Fig 10.2. Feedback control of gastric acid. S = somatostatin secreting cell; G = G-cell : P Parietal cell; ECL = enterochromaffin-like cell.
Histamine H2 receptor antagonists act by blocking the effect of histamine on parietal cells. Proton pump inhibitors act by inhibiting the enzyme in parietal cells that catalyses acid production for release into the gastric lumen. G cells, enterochromaffin-like cells, and parietal cells are all regulated by release of the inhibitory peptide somatostatin from somatostatin cells, which are distributed throughout the stomach. The effect of HÂ pylori infection on acid secretion depends on which part of the stomach is most inflamed because this determines which of these cells are affected most.
Motor functions of stomach
Storage of ingested food.
Empty stomach has a capacity of 50 ml only. As food is ingested, the gastric capacity gradually increases. At the end of a meal, the stomach may contain 1000-1500 ml of food, water and gastric juice. The storage function of the stomach is chiefly served by the fundus and body regions, which undergo a gradually increasing vagally mediated reflex receptive relaxation. That is why; after vagotomy, the patients often complain of early satiety as well as post-prandial epigastric fullness.
Mixing, grinding and sieving function
Peristaltic waves passing down the body and pyloric part of stomach produce thorough mixing of food with the gastric juice. The food is macerated into a semi-liquid chyme. The narrow pyloric sphincter acts like a sieve and allows particles less than 1 mm in size to leave the stomach in to the first part of duodenum.
Regulation of gastric emptying:
Distention of stomach or increased gastrin secretion increases the strength of gastric peristalsis. On the other hand, presence of highly acid chyme, hyperosmolar chyme or fat-rich chyme in the duodenum decreases the strength of gastric peristalsis. These duodenal inhibitory influences on gastric emptying ensure that amount of chyme containing acid, and food particles is ideal for the proper digestion and absorption in the small intestine.
Small intestine: functional anatomy and physiology
The small intestine measures approximately, 2.5-3 cm in diameter and 6 meters in length during life. The ligament of Treitz demarcates duodenum from jejunum. Below the duodenum, the upper 40 % of the small intestine is called the jejunum and the remaining 60 % as ileum. There is no anatomic demarcation between jejunum and ileum. The villi, a characteristic feature of small intestinal mucosa are largest and most numerous in the duodenum and jejunum, and become fewer and smaller in the ileum. The ileum ends with the ileocecal valve (sphincter), which regulates the movement of chyme into the large intestine and prevents backward movement of material from the large intestine.
Small intestine is the site of final digestion and absorption of foodstuffs. Most of the digestive enzymes that act in the small intestine are secreted by the pancreas (Table 10.2). In addition bile salts present in the bile (formed in the liver) are essential for proper digestion and absorption of dietary fats. The pancreatic and bile ducts open in the second part of duodenum. As a small bolus of chyme leave the stomach, its intimate mixing with pancreatic juice and bile helps in proper digestion and absorption. Presence of food in the upper small intestine is essential for the release of gastrointestinal hormones such as secretin and cholecystokinin which increase the secretion of pancreas and bile. When the duodenum is bypassed (e.g. Billroth II operation) malabsorption commonly occurs. The optimum pH for the activity of pancreatic enzymes is 6-7. Such pH is achieved by neutralization of the highly acidic chyme that leaves the stomach by the alkaline pancreatic and bile juices.
The intestinal digestion of foodstuffs results in production of monosaccharides, amino acids and fatty acids. These products and various other components of food such as vitamins, minerals and water are absorbed in specific parts of the small intestine (Table 10. 3). This knowledge becomes significant when a part of the small intestine is to be resected as a treatment of some disorder (e.g. Crohn’s disease). Extensive resection of small intestine is most likely to result in intestinal malabsorption (short bowel or short gut syndrome). Short bowel syndrome usually develops when less than 2 meters of the small intestine left after surgery.
Table 10.3. Site of absorption of various foodstuffs in the GIT.
Colon : Functional anatomy and physiology
Colon or the large intestine is a tube about 6 cm in diameter and 1.5 meters in length. Mucus (pH 8) is the chief secretion of colon. Absorption of water and electrolytes is the chief function of the large intestine. The colon contains a large number of bacteria which synthesize vitamin K, folic acid and a number of other vitamins included in B complex, which are absorbed in blood circulation
Large intestine cannot absorb carbohydrates, amino acids or fatty acids. These products reach the colon in patients with inadequate digestion / absorption of foodstuffs in the small intestine (maldigestive / malabsorption syndrome). The fermentation of undigested carbohydrates by the colonic bacteria produces large amount of gases (flatus). Undigested fats are hydrolyzed by the bacteria in to fatty acids, which cannot be absorbed. Fatty acids act as irritant to the colonic mucosa, producing diarrhea. Undigested proteins are broken down to by the bacterial deaminases. Thus, even in a case with severe maldigestion, the stools contain the degraded products rather than macromolecules of carbohydrates, fats or proteins as such.
Infantile Hypertrophic Pyloric Stenosis
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis (IHPS), is the most common cause of intestinal obstruction in infancy. Although less common in Asian population, IHPS is by no means a rarity. It is 4 times more common in male children. Although it can occur any time from the day of birth to about 3 to 4 months, most common presentation is between the 3rd and 6th week of age. The presenting symptoms are almost always projectile non-bilious vomiting in a baby hitherto normal with no other accompanying findings of upper respiratory infection etc. The presence of an ovoid olive-shaped mass in the right upper quadrant area close to the epigastrium is a very important sign.
The lesion is characterized by gastric outlet obstruction and multiple anatomic abnormalities of the pyloric antrum. There is marked hypertrophy and hyperplasia of the mainly circular, but also longitudinal, muscle fibers of pylorus . The antropyloric muscle is abnormally innervated (see below). In addition, further the luminal narrowing is caused by crowded and redundant mucosa. The mucosa usually is edematous and thickened. In advanced cases, the stomach becomes markedly dilated in response to near-complete obstruction.
Fig 10.3 The pyloric sphincter in a normal infant and in a case of hypertrophic pyloric stenosis.
Nitric oxide has been demonstrated as a major inhibitory nonadrenergic, noncholinergic neurotransmitter in the GI tract, causing relaxation of smooth muscle of the myenteric plexus upon its release. Impairment of this neuronal nitric oxide synthase (nNOS) synthesis has been implicated in IHPS, in addition to achalasia, diabetic gastroparesis, and Hirschsprung disease.
The gastric outlet obstruction due to the hypertrophic pylorus impairs emptying of gastric contents into the duodenum. As a consequence, all ingested food and gastric secretions can only exit via vomiting, which can be of a projectile nature. The vomited material does not contain bile because the pyloric obstruction prevents entry of duodenal contents (containing bile) into the stomach. This results in loss of gastric acid (hydrochloric acid), leading to metabolic alkalosis. Persistent vomiting is accompanied by loss of not only acid but also fluids from the stomach. The resulting hypovolemia leads to a secondary hyperaldosteronism. The high aldosterone levels cause the kidneys to: (a) avidly retain Na+ (to correct the intravascular volume depletion), and (b)excrete increased amounts of K+ and H+ into the urine , resulting in hypokalemia and further aggravation of alkalosis.
Pathophysiology of peptic ulcer
It is a physiological marvel that gastric juice can easily digest the swallowed pieces of meat but normally, it has no corrosive action on the gastric mucosa itself. Several factors seem to be involved in the protection of gastric mucosa from autodigestion. These factors, collectively known as gastric mucosal barrier, include:
(a) Mucus secreted by surface epithelial cells and mucus neck glands which forms a water insoluble visco-elastic gel with poor diffusion coefficient for H+ .
Bicarbonate secreted by surface epithelial cells into the boundary zone between the epithelial cells and the mucus layer. The secretion of mucus and bicarbonate is believed to be mediated through prostaglandins.
Tight junctions between the adjacent cells of gastric surface epithelium.
Rapid turnover of surface epithelial cells, and rich blood supply.
Prostaglandins. Endogenous prostaglandins stimulate secretion of gastric mucus as well as gastric and duodenal mucosal bicarbonate. Prostaglandins also participate in the maintenance of gastric mucosal blood flow and integrity of mucosal barrier and promote epithelial cell renewal in response to mucosal injury.
Under normal conditions, a physiologic balance exists between peptic acid secretion and gastro-duodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H pylori, alcohol, cigarette smoking, psychogenic stress (excessive acid, and pepsin) or Zollinger Ellison syndrome can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury.
Mechanisms of injury differ distinctly between duodenal and gastric ulcers. Duodenal ulcer is essentially an H. pylori-related disease and is caused mainly by an increase in acid and pepsin load, and gastric metaplasia in the duodenal cap. Gastric ulcer, at least in Western countries, is most commonly associated with NSAID ingestion, although H. pylori infection might also be present. Chronic, superficial and atrophic gastritis predominate in patients with gastric ulcers, when even normal acid levels can be associated with mucosal ulceration. Basically in both conditions, ulcer is associated with an imbalance between protective and aggressive factors, with inflammation being a leading cause of this imbalance.
Fig. 10.4. Helicobactor pylori bacterium.
Role of Helicobacter pylori
Helicobacter pylori is a gram-negative bacillus responsible for one of the most common infections found in humans worldwide. H pylori organisms are spiral-shaped gram-negative bacteria that are highly motile because of multiple unipolar flagella. They are microaerophilic (need less oxygen) and potent producers of the enzyme urease. H pylori inhabits the mucus adjacent to the gastric mucosa. The most common route of H pylori infection is either oral-to-oral: kissing (stomach contents are transmitted from mouth to mouth) or fecal-to-oral (from stool to mouth) contact. Parents and siblings seem to play a primary role in transmission
Helicobacter pylori bacteria colonize the stomach and induces chronic gastritis. It is widely believed that in the absence of treatment, H. pylori infection-once established in its gastric niche-persists for life. In Western countries the prevalence of Helicobacter pylori infections roughly matches age (i.e., 20% at age 20, 30% at age 30, 80% at age 80, etc). Prevalence is higher in third world countries. Most individuals infected by H. pylori will never experience clinical symptoms despite having chronic gastritis. Approximately 10-20% of those colonized by H. pylori will ultimately develop gastric and duodenal ulcers. A larger proportion of people will get non-specific discomfort, abdominal pain or gastritis (Fig. 10.5). The severity of the inflammation is likely to underlie H. pylori-related diseases. Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances.
The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization. In those with duodenal ulcer, H. pylori colonizes the antrum. The inflammatory response to the bacteria causes destruction of somatostatin-producing D cells in the pylorus. Consequently, the G cells in the antrum secrete more of the hormone gastrin, which travels through the bloodstream to the corpus. Gastrin stimulates the parietal cells in the corpus to secrete more acid into the stomach lumen. Chronically increased gastrin levels eventually cause the number of parietal cells to also increase, further escalating the amount of acid secreted. The increased acid load damages the duodenum, and ulceration may eventually result.
In contrast, gastric ulcers are often associated with normal or reduced gastric acid production, suggesting that the mechanisms that protect the gastric mucosa are defective. In these patients H. pylori can also colonize the corpus of the stomach, where the acid-secreting parietal cells are located. However, chronic inflammation induced by the bacteria causes further reduction of acid production, and eventually atrophy of the stomach lining. Gastric atrophy may lead to gastric ulcer and increases the risk for stomach cancer.
H pylori infection and its association with gastric malignancy have been well described in several epidemiologic studies. However, the course of progression from inflammation to cancer remains unclear. One model describes the stepwise progression of H pylori infection to hypochlorhydria, chronic gastritis, atrophic gastritis, intestinal metaplasia, and gastric cancer. Increased production of the cytokine interleukin -1Î² has been linked to an increased risk of hypochlorhydria and gastric cancer in infected subjects.
Fig.10.5 . Consequences of H pylori infection.
Complications of peptic ulcers
Hemorrhage: Mild to severe hemorrhage is the most common complication of peptic ulcer disease. It may occur even when the ulcer pain is not severe. Symptoms include hematemesis (fresh blood or “coffee ground” material); passage of bloody stools or black tarry stools (melena); and weakness, syncope, thirst, and sweating caused by blood loss. However, small amounts of blood in the stool may not be noticeable but, if persistent, can still lead to anemia
A peptic ulcer may penetrate the wall of the stomach. If adhesions prevent leakage into the peritoneal cavity, free penetration is avoided and confined perforation occurs. Ulcers on the front surface of the duodenum, or less commonly the stomach, can go through the wall, creating an opening to the free space in the abdominal cavity. Perforation often leads to catastrophic consequences. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain. Posterior wall perforation leads to pancreatitis; pain in this situation often radiates to the back.
An ulcer may penetrate the muscular wall of the stomach or duodenum and continue into an adjacent organ, such as the liver or pancreas.
Gastric outlet obstruction: Gastric outlet obstruction is the third most frequent complication of peptic ulcer disease after bleeding and perforation. It can occur during the acute phase of the disease or in chronic disease. Gastric outlet obstruction has traditionally been considered synonymous with pyloric stenosis as a result of peptic ulcer disease in adults.
Obstruction may be caused by scarring, spasm, or inflammation from an ulcer. Symptoms include recurrent, large-volume vomiting, occurring more frequently at the end of the day and often as late as 6 h after the last meal. Loss of appetite with persistent bloating or fullness after eating also suggests gastric outlet obstruction. Prolonged vomiting may cause weight loss, dehydration, and alkalosis.