Lecturer Dr.Mustafa Ghani Histology Digestive System The oesophagus:It is a straight muscular tube that transports food from the pharynx to the stomach. It is about 25cm long. Its wall consists of the usual 4 layers :1. The mucosa:a) It is lined by a protective, non-keratinized stratified squamous epithelium with mitotic figures in its basal layer, indicating a constant shedding & renewal of the cells. b) Lamina propria :- consists of loose C.T. , in the lamina propria of the region near the stomach are groups of glands , the oesophageal cardiac glands that secrete mucus. c) Muscularis mucosae:- it is thick & consists of longitudinal smooth muscle fibers. In the lower part of the oesophagus, the muscularis mucosae may be formed of inner circular & outer longitudinal muscles fibers. 2. The branched submucosa:tubuloalveolar contains the oesophageal glands which are glands. mucous in These nature, are their ducts open on the epithelial surface. 3. The muscularis externa:- consists of 2 layers, of which the outer is mainly longitudinal & the inner mainly circular. In the upper part of the oesophagus, the muscle fibers are striated, in the middle are mixed (striated & smooth) & in the lower part all the muscle fibers are smooth. In the region of the cardiac sphincter the circular muscle is" greatly thickened. Between the 2 muscle plexus. 1 layers there is Auerbach's 4. The adventitial- consists of loose C.T. continuous with that of the surrounding structures. There is a serous layer only on the abdominal part of the oesophagus. Oesophagogastric junction:At this junction the stratified squamous epithelium of the oesophagus ends abruptly to be replaced by the simple columnar epithelium of the stomach. The oesophageal glands stop & the gastric glands appear in the lamina propria. Lymph nodules are frequent around the junction. The oesophagogastric junction is an important site of the pathologic abnormality. Lower oesophagus is an important site of common diseases, particularly ulceration, stricture & cancer. The epithelium of the oesophagus is protected from exposure to the gastric acid by:l. The anatomical arrangement of the oesophagogastric junction. 2. The cardiac sphincter which prevents reflux of the gastric contents into the lower oesophagus. Reflux of acid gastric secretions may occur into the lower esophagus causing inflammation & pain. Under the constant irritating effect of reflux of acidic gastric secretions, the epithelium in the lower esophagus changes to a gastric type. Stratified The squameus columnar non-keratinized epith → simple ulceration & epithelium prone to→ columnar inflammation and predispose to the development of one type of oesophageal cancer. Healing of such ulcers can lead to scarring of the lower end of the oesophagus & thereby narrowing of stricture) → difficulty of swallowing. 2 its lumen (i.e oesophageal Stomach:It is both endocrine & exocrine organ that digests food & secretes hormones. It is a dilated segment of the digestive tract. The main functions of the stomach:1. Continuation of digestion of carbohydrates initiated in the oral cavity (mouth) by salivary amylase which starts the digestion of carbohydrates & this process will continue in the stomach. 2. Secretion of acids (HCl) together with the muscular activity of the muscles of the stomach will transform the digested food into a viscous mass known as chyme. 3. The stomach initiates the digestion of proteins by the enzyme pepsin so the stomach secretes pepsinogen which is converted into pepsin which initiates the digestion of proteins. 4. The stomach secretes or produces gastric lipase. Gastric lipase together with the help of lingual lipase (Von Ebner's gland) start the digestion of triglycerides. For descriptive purpose or anatomically the stomach can be divided into 4 divisions :1. Cardia 2. Fundus 3. Body 4. Pylorus or pyloric region Because the fundus & body are identical in microscopic structure, only 3 histologic regions are recognized. In empty, contracted stomach, the mucosa & submucosa form numerous longitudinal folds known as rugae. When the stomach is filld with food, these folds flatten out. 3 The wall of the stomach consists of the usual 4 layers of digestive tract :1. The mucosa:- consists of: A) Surface epithelium ( simple columnar epithelium):- their cells secrete mucin(mucus) & they are known as surface mucous cells. The- mucus forms a thick layer that protects these cells from the effects of the strong acid secreted by the stomach. The surface epithelium invaginates to various extents into the lamina propria, forming gastric pits (lined by the same epithelium). Emptying into the gastric pits are branched tubular glands (cardiac, fundic & pyloric) characteristic of each region of the stomach. The surface mucous cells are thought to produce blood group substances. Tight junctions present around surface & pits cells also form part of the barrier to acid. Stress & other psychosomatic factor; ingested substances such as aspirin or ethanol & some microorganisms (e.g. Helicobacter pylori) can disrupt this epithelial layer & lead to ulceration. B) The lamina propria:- is occupied by the gastric glands. These are branched tubular glands, separated by little amount of C.T.. They open into the bases of the gastric pits. Types of gastric glands:1) The cardiac glands:- are present in the cardiac region. They are simple or branched tubular glands, lined by mucus secreting columnar cells similar to the mucous neck cells of the gastric gland proper. They secrete mucus & lysozyme. 2) Fundic glands (gastric gland proper):- are present in the lamina propria of the fundus & body of the stomach. They are branched, tubular glands, 3 to 7 of which open into the bottom of each gastric pit. The glands are composed of the following cells:- 4 a) Mucous neck cells:- are located between the parietal cells in the neck of the gland. The cells are large irregular in shape, with clear cytoplasm & the nucleus is flattened at the base of the cell. They secrete mucus which protects the stomach wall from the action of the HC1 & proteolytic enzymes. Peptic (chief or zymogenic)cells:- they predominate in the lower part of the gland & have all the characteristics of the protein synthesizing & exporting cells. Their basophilia is due to the abundant RER(rough endoplasmic reticulum). The granules in their cytoplasm contain the inactive enzyme pepsinogen, the precursor of pepsin. In human, chief cells also produce the enzymes, lipase & rennin. The E.M shows the presence of small irregular microvilli on their free surfaces, a well developed Golgi apparatus (complex) located in the supranuclear region, large amount of basally located RER & many apical secretory granules. c) Parietal(oxyntic) cells:- are present mainly in the upper half of the gland. They are large rounded or pyramidal cells with one centrally placed spherical nucleus & intensely eosinophilic cytoplasm. The most striking features of the active secreting cell seen in the electron microscope are an abundance of mitochondriaf eosinophilic) & a deep circular invagination of the apical plasma membrane, forming the intracellular secretory canaliculus lined with abundant microvilli. In the resting cell, a number of tubulovesicular structures can be seen in the apical region of the cell. At this stage, the cell has few microvilli. When stimulated to produce HC1, tubulovesicles fuse with the cell membrane to form the canaliculus & more microvilli, suggesting that tubulovesicles are involved in secretion. The parietal cells secrete the HC1 & gastric intrinsic factor (a glycoprotein that binds to vitamin B12 & facilitate its absorption by the intestine). Lack of the intrinsic factor can lead to vit. B12 deficiency → pernicious anaemia. In cases of atrophic gastritis, both parietal and peptic cells are much less numerous, and the gastric juice has little or no acid or pepsin activity, and no intrinsic factor → pernicious anaemia. Parietal cells have abundant carbonic anhydrase, which is thought to play a vital role 5 in generating H+ ions for the production of HCL d) Enteroendocrine enterochromaffin chromium cells:- cells, stains. the so-called APUD were owing Most cells of formerly to the (amine their cells called, affinity have precursor for the uptake argentaffin & silver & characteristics of & decarboxylation), which are wide spread in the body (found in the epithelium of GIT, respiratory tract, in the pancreas & thyroid gland). Their cytoplasm contains either polypeptide hormones or the biogenic amines epinephrine, norepinephrine, or tryptamine (serotonin). These cells 5-hydroxy have characteristics of diffuse neuroendocrine system(DNES).These cells can be identified & localized by immunocytochemical methods or other cytochemical techniques for specific amines. The enteroendocrine cells are small pyramidal cells found near the bases of gastric glands. They are characterized by the presence of abundant dense secretory granules, always located at the base of the cell between the nucleus'& basal lamina. This suggests that they are endocrine cells that liberate their secretion into the blood vessels in the lamina propria rather than into lumen of the gland. Some of these cells are known as paracrine because they produce hormones that diffuse into the surrounding extracellular fluid to regulate the function of neighboring cells without passing through the vascular system. Polypeptide-secreting cells of the digestive tract fall into 2 classes:1) The open type:- in which the apex of the cell presents microvilli & contacts the lumen of the organ. 2) The closed type:- in which the cellular apex is covered by other epithelial cells. In the fundus of the stomach, serotonin is one of the principal secretory carcinoids, products. are Tumors responsible arising for from the clinical overproduction of the serotonin. 6 these cells symptoms are called caused by d) Stem cells (undifferentiated cells):- are found in the neck region of all gastric glands (cardiac, fundic & pyloric). These cells have a high rate of mitosis; some of them move upward to replace the pit & surface mucous cells, which have a turnover time of 4-7 days. Other daughter cells migrate more deeply into the glands & differentiate into the different types of cells of the glands. These cells are replaced much more slowly than are surface mucous cells. 3) Pyloric glands:- are present in the pyloric region of the stomach & are similar to the cardiac glands. However, the pits are longer & the glands are shorter & coiled, opposite to that of cardiac glands. The pyloric glands secrete mucus as well as appreciable amounts of the enzyme lysozyme. These glands also have enteroendocrine cells as follows:1. G cells release gastrin which stimulates the secretion of the acid by the parietal cells. 2 D cells secrete somatostatin, which inhibits the release of some other hormones, including gastrin. C) The muscularis mucosae:- consists of smooth m. arranged as an inner circular & an outer longitudinal layer, in some parts there is a third outer layer of circular fibres. Strands of muscle extend from the inner layer into the lamina propria between the glands, their contraction helps to empty the glands. 2. Submucosa:- is composed of dense C.T. containing blood & lymph vessels & Meissner's plexus. 3. Muscularis externa:- consists of 3 illdefined layers of smooth m., an inner oblique, a middle circular & an outer longitudinal. .At the pylorus, the middle layer is greatly thickened to form the pyloric sphincter. Auerbach's plexus is found 7 between the muscles. e) Serosa:- derived from the visceral peritoneum consists of a thin layer of loose C.T. covered by mesothelium (simple squamous epithelium). 8 Regions of the stomach. The stomach is a muscular dilation of the digestive tract where mechanical and chemical digestion occurs. The muscularis consists of three layers for thorough mixing of the stomach contents as chyme: an outer longitudinal layer, a middle circular layer, and an inner oblique layer. The stomach mucosa shows distinct histological differences in the cardia, the fundus/body, and the pylorus. Cells that secrete HCl and pepsin are restricted mainly to the body and fundus regions. Glands of the cardia and pylorus produce primarily mucus. Wall of the stomach with rugae. Low magnification micrograph of the stomach wall at the fundus shows the relative thickness of the four major layers: the mucosa (M), the submucosa (SM), the muscularis externa (ME), and the serosa (S). Two rugae (folds) cut transversely and consisting of mucosa and submucosa are included. The mucosa is packed with branched tubular glands penetrating the full thickness of the lamina propria so that this sublayer cannot be distinguished at this magnification. The muscularis mucosae (arrows), immediately beneath the basal ends of the gastric glands, is shown. The submucosa is largely loose connective tissue, with blood vessels (V) and lymphatics. X12. H&E. 9 Esophagogastric junction. At the junction of the esophagus (E) and the cardiac region of the stomach (C) there is an abrupt change in the mucosa from stratified squamous epithelium to simple columnar epithelium invaginating as gastric pits (GP). The mucosa contains many mucus—secreting esophageal cardiac glands (ECG), whose function is supplemented by mucous cardiac glands (CG) opening into the superficial gastric pits. Strands of muscularis mucosae (arrow) separate the mucosa and submucosa (SM). X60. H&E. 10 Gastric pits and glands. (a): SEM of the stomach lining cleared of its mucus layer reveals closely placed gastric pits (P) surrounded by polygonal apical ends of surface mucous cells. X600. (b): Micrograph of the same lining shows that these surface mucous cells are part of a simple columnar epithelium continuous with the lining of the pits (P). Each pit extends into the lamina propria and then branches into several tubular glands. These glands branch further, coil slightly, and fill most of the volume of the mucosa. Around the glands, which contain other cells besides columnar cells, a small amount of connective tissue comprising the lamina propria is also seen. X200. H&E. 11 Pyloric glands. The pyloric region of the stomach has deep gastric pits (P) leading to short, coiled pyloric glands (G) in the lamina propria. Cardial glands are rather similar histologically and functionally. Cells of these glands secrete mucus and lysozyme primarily, with a few G cells also present. The glands and pits are surrounded by cells of the lamina propria (LP), connective tissue also containing lymphatics and MALT. Immediately beneath the glands is the smooth muscle layer of the muscularis mucosae. X140. H&E. 12 Gastric glands. Throughout the fundus and body regions of the stomach the gastric pits lead to glands with various cell types. (a): In the neck of the glands are mucous neck cells (MN), scattered or present as clusters of irregular, low columnar cells with basophilic, granular cytoplasm and basal nuclei. These cells produce mucus with a higher content of glycoproteins than that made by surface mucous cells. Among the neck mucous cells are stem cells that give rise to all epithelial cells of the glands. In the upper half of the glands are also numerous distinctive parietal cells (P), large rounded cells often bulging from the tubules, with large central nuclei surrounded by intensely eosinophilic cytoplasm with unusual ultrastructure. These cells produce HCl and the numerous mitochondria required for this process cause the eosinophilia. Around these tubular glands are various cells and microvasculature in connective tissue. (b): Near the muscularis mucosae (MM), the bases of these glands contain fewer parietal cells, but another cell type, chief cells (C), is abundant here. Chief cells are also known as peptic or zymogenic cells. They are seen as clusters of cells with condensed, basal nuclei and basophilic cytoplasm. From their apical ends chief cells secrete pepsinogen, the zymogen precursor for pepsin, a major protease. Zymogen granules are often removed or stain poorly in routine preparations. Both X200. H&E. 13 Parietal cells and chief cells. A plastic section of a gastric gland’s basal portion shows better detail of parietal and chief cells than routine histological sections often allow. The large parietal cells’ characteristic intracellular canaliculi (arrowheads) can be seen, along with the numerous acidophilic mitochondria. The smaller chief cells have cytoplasm containing numerous large red secretory (zymogen) granules. X400. PT. 14 Synthesis of HCl by parietal cells. Diagram showing the main steps in the synthesis of hydrochloric acid. Active transport by ATPase is indicated by arrows and diffusion is indicated by dotted arrows. Under the action of carbonic anhydrase, carbonic acid is produced from CO2. Carbonic acid dissociates into a bicarbonate ion and a proton (H+), which is pumped into the stomach lumen in exchange for K+. A high concentration of intracellular K+ is maintained by the Na+, K+ ATPase, while HCO3– is exchanged for Cl− by an antiport. The tubulovesicles of the cell apex are seen to be related to hydrochloric acid secretion, because their number decreases after parietal cell stimulation as microvilli increase. Most of the bicarbonate ion returns to the blood and is responsible for a measurable increase in blood pH during digestion, but some is taken up by surface mucous cells and used to raise the pH of mucus. 15