The stomach is divided into three parts and contains gastric glands that secrete hydrochloric acid and digestive enzymes like pepsin. The gastric juice contains hydrochloric acid which kills bacteria and activates pepsin. Pepsin breaks down proteins into smaller fragments. Gastric secretion is regulated by nerves, hormones, and feedback mechanisms and occurs in several phases including cephalic, gastric, and intestinal phases in response to eating. The pancreas contains acini that secrete digestive enzymes and bicarbonate into the small intestine to break down proteins, lipids, carbohydrates, and nucleic acids to aid in absorption.

1. STOMACH

2. STOMACH Stomach is the sac-like dilated part of the gut in between oesophagus and duodenum. Its capacity may vary from 50 ml to 5 litre, on an average it is about 1.5 litre. It has the same general structure of the gut which is composed of four layers but it has an additional muscle layer (the innermost oblique layer).

3. STRUCTURE The stomach is divided into three parts: fundus, body and pylorus. The oesophageal end of the stomach is called cardia and is guarded by a physiological sphincter. The pyloric sphincter is situated in between the stomach and the duodenum.

5. GASTRIC RUGAE The mucous membrane of stomach is thick and is thrown into folds, called gastric rugae seen only in empty stomach (this arrangement helps to accommodate extravolume of food without stretching the mucous membrane). The lining cells of the mucous membrane are of simple columnar type which secrete mucin and are covered by a thick layer of gastric mucin.

6. GASTRIC GLANDS The gastric glands are situated within the mucous membrane in the groups of 2 to 7, which together communicate with the gastric lumen through the gastric pits. These glands are of three types: - the cardiac glands are small in number, situated at the cardiac end and secrete mainly mucin; - the glands in the fundus and body are highest in number and secrete the acidic juice; - the pyloric glands are again of mucous type.

8. Some important cells in the gastric glands I) Chief cells or Peptic cells: These cells secrete pepsinogens and are situated in the wall of the glands near the base. II) The oxyntic cells are also called parietal cells. These are situated mainly towards the neck of the glands. These cells secrete hydrochloric acid and the intrinsic factor.

9. Some important cells in the gastric glands III) The Amine precursor uptake and decarboxylation cells (APUD cells) form the group, which secrete different hormones: histamine, serotonin and various local hormones like bombesin, somatostatin, glucagon. IV) The G cells of stomach are present in the pyloric glands and secrete gastrin. V) The D cells are situated in the vicinity of G cells and secrete somatostatin which has the paracrine effect on the G cells.

10. NERVE SUPPLY The stomach is richly supplied by parasympathetic fibres from both the vagi. Parasympathetic efferent fibres are responsible for glandular secretion, relaxation and contraction of muscles. The afferent fibres carry the sensation of distension, hunger, nausea and also the necessary information for different reflexes.

12. NERVE SUPPLY The sympathetic supply comes from T 6 to T 12 segments of the spinal cord. The sympathetic efferent fibres are mainly involved in regulation of blood vessels and thus of blood flow in the stomach. They also cause inhibition of the muscles of the body of stomach and contraction of the sphincters. They are involved in regulation of secretion particularly via gastrin mechanism. Sympathetic afferents also carry pain sensation from the stomach.

13. NERVE SUPPLY Along with these, there is the intrinsic nervous system with the myenteric and the submucous plexuses as elsewhere in the gut.

14. THE GASTRIC JUICE It is the mixture of secretions from all the glands present in stomach. It is also mixed with the swallowed saliva and refluxed duodenal contents. Total amount of gastric juice secreted per day is about 1 to 1.5 litre. It is highly acidic (pH 0.9 to 1.5).

15. HYDROCHLORIC ACID HCl is present in gastric juice in high amount. Normal concentration is 40 to 60 meq/litre (highest possible concentration - 160 meq/L). Oxyntic cells secrete HCl obviously at a very high concentration but it is mixed with other components and becomes diluted. The HCl gives the antiseptic property to the gastric juice. It converts pepsinogens into pepsins and stimulates secretion of different hormones from the small intestine.

16. HYDROCHLORIC ACID HCl is secreted by the oxyntic cells but not as HCl. H and Cl are secreted separately in the microcanaliculi (within the cell) where the HCl is formed. Therefore no HCl is formed within the cytoplasm of the cell otherwise the cell would die.

17. PEPSINOGENS These are pro-enzymes and are converted into pepsins, the protheolytic enzymes of gastric juice. These pepsinogens can grouped into: (i) pepsinogen I, found in body and fundus; (ii) pepsinogen II, which is found throughout the whole stomach. These are secreted by the chief cells of the gastric glands and the secretion is caused mainly by vagal stimulation. The pepsinogens are activated to pepsin at a pH<6 by HCl. This also occurs by an autocatalytic process by the pepsin itself. Pepsin is a proteolytic enzyme (endopeptidase) which breaks the protein molecules from within into pieces, called peptones. It acts best at pH 1.5 to 3.5 and is inactivated at pH 9.

19. INTRINSIC FACTOR IF is secreted by the oxyntic cells of gastric mucous membrane. It combines with the extrinsic factor (vitamin B 12 ) and helps in the absorbtion of the latter. It also stimulates endocytosis of vitamin B 12 in the terminal ileum.

20. GASTRIC MUCIN It provide defence against the damage which may be caused by the acid. It is of two types: insoluble and soluble mucin. Both the types of mucins are glycoproteins. They resistant to acid-peptic digestion as their protein core protected by a coat of carbohydrate on the surface. Secretion of gastric mucin increases by vagal stimulation and by irritant foods. Some prostaglandins also stimulate its production.

21. REGULATION OF GASTRIC SECRETION Secretion of gastric juice is influenced both by nerves and chemicals. The nerves are the autonomic and the intrinsic plexuses. Parasympathetic supply is provided by both the vagi. Vagal fibres usually end on the intrinsic neurons and directly on the glands also. Vagal stimulation leads to increased acid and pepsinogen secretion, increased movement of stomach and relaxation of fundus. It also increases gastrin secretion through release of GRP (Gastrin releasing polypeptide).

22. REGULATION OF GASTRIC SECRETION The intrinsic plexuses are composed of various types of neurons. The cholinergic neurons stimulate secretion of acid, pepsinogen, intrinsic factor and also affect the smooth muscle activity. The adrenergic neurons inhibit the cholinergic action. There are also neurons which secrete VIP (vasoactive intestinal polypeptide), encephalins, substance-P, ATP, etc.

23. REGULATION OF GASTRIC SECRETION The chemicals involved in the regulation of gastric secretion are general hormones as well as local chemicals. Gastrin stimulates HCl secretion along with other functions. Somatostatin, a local hormone from the D cells, inhibits HCl secretion, so also the prostaglandins (PGE2). Histamine, a local chemical from the mast cells has important role in acid secretion. General hormones like cortisol, ACTH, insulin, parathormone stimulate HCl secretion. Enterogastrone inhibits gastric secretion and motility.

25. PHASES OF GASTRIC SECRETION There are four phases of gastric secretion in relation to a meal. These phases are: a) cephalic phase, b) gastric phase, c) intestinal phase, d) interdigestive phase.

26. CEPHALIC PHASE Cephalos means head and in this phase information for secretion comes from the brain via the vagus nerves. Vagi are stimulated reflexly for this purpose as a result of conditioned and unconditioned reflexes. Stimuli for unconditioned reflex are the presence of food in the mouth, taste of the food, act of chewing and swallowing. Conditioned reflex is initiated by sight of food, thought of food, smell of food. Conditioned reflex can also be elicited by non-physiological stimuli like sounding of bell if properly paired with a physiologic stimulus.

28. CEPHALIC PHASE Secretion in this phase starts with a latency of less than 5 minutes and continues for 30 to 120 minutes at the rate of 250 to 750 ml/hour. The juice secreted is rich in acid and pepsin. It has got high digestive power. It is not related to chemical composition of food and is called psychic juice or appetite juice which prepares the stomach in anticipation of a meal.

29. GASTRIC PHASE This phase is initiated by the presence of food in the stomach and all the stimuli for secretion arise in the stomach. The neural and chemical factors work in this phase. Neural mechanism operates through long vago-vagal reflex. This reflex starts due to presence of food and the distension of the stomach. The impulse then travels along the afferent vagal fibres to the brain where from the impulse comes to the stomach through efferent vagal fibres. Short local reflexes within the wall of the stomach through the intrinsic nerves are also important. Stimulus for thise reflexes is stretch (presence of the food stretches the stomach).

31. GASTRIC PHASE The main hormone involved in this phase is gastrin. It secreted from the G cells and reaches the oxyntic cells. Gastrin mediated secretion increases by reflex vagal stimulation, Ca, product of protein digestion, histamine. Gastrin mediated secretion is inhibited by acidity (pH < 2.5), somatostatin, secretin. This phase has a latency of 15 minutes and continues as long as there is food in the stomach. Composition of the juice depends on the composition of the food. A protein food stimulates secretion of more acid and pepsin. The rate of secretion is 40 to 70 ml/hour.

32. INTESTINAL PHASE Presence of food (called chyme) in the intestine also causes slight but prolonged stimulation of gastric secretion. The chemicals involved are bombesin and gastrin secreted from duodenum. Latency of this phase is 2 to 3 hours and continues for 8 to 10 hours. The rates of secretion may be 40 to 60 ml/hour. In the intestinal phase many inhibitory influences operate. They are both neural and chemical. The situations like high fat content, high tonicity and high volume of chyme in the small intestine lead to inhibition of gastric secretion and motility.

33. INTER-DIGESTIVE PHASE It means the phase when there is no food either in the stomach or small intestine. It is also called basal secretion. Obviously there is no important stimulus acting in this phase but there is always some secretion in the stomach. This resting acid secretion becomes very high in abnormal condition.

34. FUNCTIONS OF STOMACH It provides the gastric juice, acts as temporary reservoir of food. It mixes and grinds the food. It empties the content into the duodenum in a suitable manner. There is some digestion and absorption in stomach. The stomach also excretes some substances.

35. FUNCTIONS OF GASTRIC JUICE It contains hydrocholoric acid so it is antiseptic. Due to acid and pepsin it can digest proteins. Digestion of some lipids and carbohydrates (hydrolysis by acid) is achieved by gastric juice. It helps the absorption of extrinsic factor, so, helps in haemopoesis. It helps to form the chyme.

36. Functions of HCl It is antiseptic and kills almost all the germs entering with food. It activates pepsinogens to pepsin and help in protein digestion. HCl inhibits gastrin secretion. In duodenum it stimulates secretion of secretin. It causes hydrolisis of some foodstuff like cane sugar.

38. Pavlov's pouch Pouch means a pocket. Gastric pouch is made up of gastric mucous membrane. This may remain attached to the stomach with the blood supply and nerve supply intact. In Pavlov's pouch the nerve supply is same as stomach that means it is under the influence of the nerve as well as of the hormones coming via blood. If it is connected through a cannula, the gastric juice can be collected unmixed with food through all the phases. It helps to study different factors influencing the secretion including the different types of food.

40. Heiden-Hain pouch It is a denervated pouch made of gastric mucous membrane in the stomach or elsewhere, e.g., gastric mucous membrane implanted in the mammary gland of a pig. Secretion from this occurs only by the influence of blood-borne chemicals. So, it helps to study the hormonal control on gastric secretion.

41. EMOTION AND GASTRIC SECRETION Emotion has profound effects on gastric secretion. It may be due to the fact that the higher connection of sympathetic and parasympathetic system is with the hypothalamus which is intimately related to the emotional mechanism. The effects of emotion on gastric secretion had been observed by scientists through permanent gastric fistula (hole on the anterior abdominal wall communicating with the stomach produced due to injury). It is seen that emotions of grief, sudden pain, fear, etc. cause reduction of acid secretion but chronic anger, deep anxieties, etc. lead to stimulation of gastric secretion.

44. EXOCRINE PANCREAS The pancreas is unique beacause it acts both as endocrine as well as exocrine gland. The exocrine pancreas and other glands of the alimentary system secrete into the lumen of the gut which is connected to outside, therefore they pour their secretion to outside. The endocrine portion of pancreas is composed of the islets of Langerhans.

45. SECRETORY UNITS The secretory units are called acini (singular-acinus). These acini are formed of glandular cells which are pyramidal in shape and each acinus is connected to a duct (intercalated duct). There are centroacinar cells at the junction of the acinus with the duct and these cells project into the lumen of the acinus.

46. PANCREATIC DUCTS The first generation ducts join to form several generations and ultimately form the main collecting duct, named duct of Wirsung. The head part of the gland sometimes drains through the accessory pancreatic duct (duct of Santorini), which drains separately into the duodenum. The main duct drains into the duodenum along with the common bile duct. This opening is guarded by a composite sphincter (sphincter of Oddi).

48. SECRETORY FUNCTION The main secretory function, i.e., enzyme secretion is the function of the acinar cells. The centro-acinar cells secrete fluid and electrolytes. The earlier generation of ducts actively take part in the modification of the secretion. The ducts are thus responsible for the major part of the fluid and electrolytes of the pancreatic juice.

49. BLOOD & NERVE SUPPLY The pancreas is richly supplied with blood by the branches of the coeliac trunk. The veins drain into the portal vein. Nerve supply is by autonomic nerves. Sympathetic supply comes from coeliac and superior mesenteric plexuses. The sympathetic fibres supply the blood vessels and also carry pain sensation. Parasympathetic supply comes via both the vagi and are secretomotors (stimulate the secretion).

50. PANCREATIC JUICE It is alkaline and has the highest digesting power. About 1 to 1.5 litre of pancreatic juice of pH 8 to 8.3 is secreted per day. It is watery (Sp. gr. 1010 to 1030).

51. PROTEOLYTIC ENZYMES These are secreted as inactive proenzymes: trypsinogens, chymotrypsinogens, procarboxypeptidases, proelastase, procollagenase, etc. These are converted into active enzymes in the small intestine by trypsin which is initially formed by the enterokinase secreted from the small intestine and then by autocatalytic process. Both trypsin and chymotrypsin are endopeptidases, and act in alkaline medium but trypsin is more important. They hydrolyse protein molecules into peptones and proteoses.

52. PROTEOLYTIC ENZYMES The trypsin inhibitor present in the pancreatic juice prevents activation of the enzymes inside the pancreas which is thus protected from autodigestion. Carboxypeptidases are exopeptidases and hydrolyse proteins into amino acids. The elastase and collagenase act on elastin and collagen respectively. Nucleoproteins are acted upon by the proteolytic enzymes and the nucleic acids (RNA and DNA) by ribonuclease and deoxyribonuclease respectively.

53. CARBOHYDRATE SPLITTING ENZYME Pancreatic amylase has strong amylolytic (starch splitting) activity. It is activated in presence of Cl; it acts best at pH 6.8 but can also act in neutral and slightly alcaline medium. It is an cc-amylase and acts both on boiled as well as on unboiled starch to produce maltose, cc-limit dextrin, etc. (salivary amylase acts only on boiled starch). A slight amount of amylase is also found in blood which increases in acute pancreatitis. Amylase is also found in urine.

54. LIPOLYTIC ENZYMES Triacylglycerol hydrolase is the most important enzyme from the pancreas. This is because there are other sources of amylolytic and proteolytic enzymes but for lipolytic enzymes pancreas is the only effective source (barring the lingual lipase). Pancreatic deficiency first manifests as steatorrhoea (undigested fat in stool), i.e., deficiency of lipase. This lipase digests neutral lipids into fatty acids and monoglycerides mainly. Colipase helps the lipase. There is another lipase, called bile salt activated lipase, which also acts on phospholipids and cholesterol esters. Phospholipases act on the phospholipids. Cholesterol ester hydrolase is another enzyme which splits the cholesterol esters to cholesterol and fatty acids.

55. BICARBONATE It neutralises the acidic chyme coming from the stomach and maintains an alkaline pH in the small intestine. This is very much essential for proper activity of the digestive enzymes in the small intestine. It also inactivates the pepsin in the chyme. When the rate of secretion is high, HCO, concentration of the juice is also high (100 meq/L) but in low rate of secretion, HCO decreases and Cl increases in the juice. These two ions together form about 154 meq/L.

56. MECHANISM OF SECRETION Enzymes are secreted by the acinar cells. After being synthesised, these enzymes are stored as zymogen granules in the acinar cells. The contents of these granules are discharged by exocytosis into the lumens of the pancreatic acini. The fluid and electrolytes of the pancreatic juice are secreted by the centro-acinar cells and mainly by the cells lining the earlier generations of ducts. HCO; is formed within the cells by hydration of C0 2 and the other ions found in the juice are transferred from blood.

57. MECHANISM OF SECRETION Stimulation for secretion from the cells comes via nerve (parasympathetic) and also via hormones. The nerves are the vagi and the ncurolransmitter is acetylcholine (Ach) and VIP. The hormones are cholecystokinin (CCK-PZ) and secretin. All these act through their receptors and by releasing second messengers. Gastrin also helps the process of secretion. The secretin acts mainly on the centro-acinar cells and ductular cells. Ach acts on acinar cells mainly for enzyme secretion. But CCK-PZ helps both in enzyme and electrolyte secretion.

58. CONTROL OF PANCREATIC SECRETION Pancreatic secretion is regulated like the gastric secretion in phases in relation to a meal. These are cephalic, gastric and intestinal phases. Both hormonal and neural factors are involved in the regulation. Parasympathetic stimulates and sympathetic inhibits secretion. The hormones involved are CCK-PZ, secretin, gastrin, etc.

59. CEPHALIC PHASE Stimuli like smell, taste and sight of food converge to brain and the efferent impulse for secretion comes down via the vagi to the pancreas. This leads to enzyme secretion. The cephalic phase of gastric secretion contains plenty of HCl which when comes to the small intestine stimulates secretin secretion. Together with this secretin, gastrin secreted in the cephalic phase due to vagal stimulation, leads to a secretion rich in bicarbonate.

60. GASTRIC PHASE Presence of food in the stomach stimulates the vagal afferents mainly through stretching of the stomach and also by the composition of the food. This initiates vago-vagal reflexes (gastro-pancreatic reflex) which lead to increased secretion from the pancreas. Along with this, the secretin released by the acid and the gastrin secreted in the gastric phase act as strong stimulators of pancreatic secretion. So, the amount and composition of food in the stomach determines pancreatic secretion in this phase.

61. INTESTINAL PHASE It is the most important phase of pancreatic secretion. This phase is mainly effected by two hormones: cholecystokinin-pancreozymin and secretin and is also controlled by the conditions in the small intestine. Acid in the intestine stimulates secretin secretion which in turn stimulates a secretion rich in bicarbonate. This continues as long as the intestinal contents are acidic. The secretin acts mainly on the centro-acinar cells and ductular cells. Ach acts on acinar cells mainly for enzyme secretion. But CCK-PZ helps both in enzyme and electrolyte secretion.

62. CONTROL OF PANCREATIC SECRETION Products of digestion of lipid and protein in the intestine stimulate CCK-PZ secretion which in turn increases pancreatic secretion rich in enzymes. These enzymes produce more products of digestion so more CCK-PZ is secreted which stimulates secretion of more pancreatic enzymes. This goes on in a positive feedback manner as long as there is food in the intestine. An entero-pancreatic reflex initiated by the stimulation of chemoreceptors in the intestine by the products of digestion is also responsible for pancreatic secretion. The pancreatic secretion which occurs upto the gastric phase is viscid and rich in enzyme. Fluid and electrolyte secretion occurs mainly in the intestinal phase .

63. PANCREATIC FUNCTION TESTS The pancreas supplies the key enzymes for digestion. So, deficiency of pancreas will reflect as indigestion. The most prominent one is the defect in fat digestion as the lipase has no other significant source like the other enzymes. So, in pancreatic deficiency, as in chronic pancreatitis, there is an increase in the fat content of stool leading to steatorrhoea.

64. PANCREATIC FUNCTION TESTS Normal value of faecal fat is 4 to 7 g/day. If this amount increases the test is taken as positive, when the value is more than 40 g/day, it indicates a gross deficiency. (Creatorrhoea means passage of undigested protein with stool as in pancreatic insufficiency). Now-a-days, as the pure form of the enzymes CCK-PZ and secretin are available, these are used to test pancreatic secretion. The hormones can be injected separately and pancreatic juice is collected against each hormone and analysed for emzymes, bicarbonate, etc.

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