���������Gastric, Pancreas, Intestinal �Secretion �& �Regulation�

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Dr. Amar Chaudhary, ^{DVM, MS}

Assistant Professor

Department of Vet. Anatomy, Physiology and Biochemistry

Agriculture and Forestry University,

Rampur, Chitwan, Nepal

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Gastric glands

• Glandular mucosa of the stomach has many pores known as gastric pits.

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• Surface area of the stomach lining the pits is covered with mucous cells which secrete mucus to protect the surface epithelium

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• Secretions of gastric glands
• Cardiac glands secrete only mucus
• Parietal/fundic glands secrete HCl and pepsinogen
• Pyloric glands secrete mucus and gastrin.

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Gastric glands

Cell types of fundic glands

• Fundic gland contain three main types of cells.
• Body chief cells or peptic cells are locate at the base of the gland secrete proteolytic enzymes (Pepsin and Rennin)
• Parietal or oxyntic cells are present at the upper third of the gland is the site of HCl secretion.
• Neck chief cells, placed near the surface epithelium near the upper part of the gland secret mucus and a mucoprotein “Intrinsic factor" required for Vit.B₁₂ absorption from the intestine is necessary for erythropoiesis.

Cells types of pyloric glands

• The pyloric glands are structurally similar to the parietal glands
• Has body chief cells and neck chief cells only.
• Parietal cells are absent.
• “G” cells secrets Gastrin (Gut hormone).

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Gastric juice

• It is a colourless fluid, containing HCl, enzymes and mucus.
• Concentration of HCI in the stomach content varies with the nature of food, at digestion amount of saliva to be neutralized etc

Hydrochloric acid

• secreted by the parietal/oxyntic cells of the fundic glands derived from the oxidative metabolism
• Gastrin from G cells and Histamine from Enterochromafin cell which stimulate Gastric HCL secretion
• Function
• Activates pepsinogen, the inactive form of enzyme into active pepsin, hydrolysing enzyme of protein
• Slight hydrolysis of sucrose
• Also function as antiseptic in the stomach and kills bacteria
• Parietal cell also secreted Intrinsic factor of castle which helps in the absorption of vitamin B₁₂

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Gastric juice

Pepsin

• Proteolytic enzyme, involved in hydrolysis of proteins into polypeptides
• Synthesized as “Pepsinogen” (inactive form of pepsin)
• Pepsinogen is activated by HCl 
• Optimum pH of 1.5 – 3 is required for pepsin activity
• Secreted by peptic (chief) cell

Rennin(Chymosin, Rennet)

• It is a milk coagulating enzyme, present in young animals(Calf, Lamb, piglet etc.,)
• Secreted as pro-rennin (inactive form of rennin)
• Pro-rennin is activated by HCl
• Rennin reacts with casein (Milk protein)  in the presence of calcium ion forms calcium para-caseinate to delay the passage of milk through stomach for prolonged action of pepsin on casein 

Gastric lipase

• Acts on emulsified fat
• Hydrolysis fat in to fatty acids and glycerol
• Require the optimum pH of 5.5 – 7.5
• Its concentration in carnivores is low
• Absent in birds and ruminants.

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Function of Gastric Juices

• Digestive function:
• Digestion of protein: pepsin acts on the protein to break down up to the stage of peptide
• Rennin: acts on milk protein caseionogen to coagulate it into insoluble casein, which I sthen digested y other proteolytic enzymes present in the small intestine. In is present in stomach of young
• Digestion of fat: gastric lipase digest fats to some extent
• Antiseptic function:
• Many bacteria pass into the stomach with food m, they are killed by gastric HCL
• Function of HCL of gastric juices:
• HCl performs digestive ad protective functions
• Haempoietic functions:
• Intrinsic factor of castle of gastric juice helpss ansorption of extrinsic factors(vitamin B 12), essential for mtauration of RBc
• Lubricating function:
• Mucin of gastric juice lubricates any irritant, which might have gained entry into the stomach
• Protective function:
• Mucin is responsible for protecting the gastric mucosa from the action of HCl, thus stomach is non self digested
• Acid base balance:
• It is responsible for the alakline tide of blood , during seceretion of HCl
• Excretory functions:
• Some heavy metas(Bi, Pb), toxins, opium and other alkaloids are xcreted through the gastric juices

Mechanism of Secretion of Gastric HCL

• Gastric HCl is secreted by parietal (Oxyntic cell) of gastric gland
• At first CO2 combines with H2O to produce H2CO3 in a reaction catalyzed by carbonic anhydrase, H2CO3 dissociates into H+ and HCO₃
• The HCO3 is extruded by an anitiport in the basolateral membrane of the parietal cells that exchanges HCO3 for Cl-
• The H+ formed by dossociation of H2CO3 is secreted into the gastric lumen in exchange for K+ by H+/K+ Pump. This H+/ K+ pump is called Proton Pump
• The Cl- which enters the parietal cells in excahnge of HCO₃ is secreted into the gastric lumen down its electrochemical gradient through channels that activated by cAMP
• Finally, Parietal cell secertion becomes a solution of HCl

Regulation of Gastric Juice Secretion

• In man and horse, the secretion of gastric juice is continuous but it is intermittent in dogs and cats.
• Rate of secretion increases during feed intake.
• Gastric juice secretion occurs at cephalic phase, gastric phase and intestinal phase. This secretion is regulated by-
• Neural mechanism
• Hormonal mechanism
• Basic factors that stimulate gastric secretions are
• Acetylcholine
• Gastrin
• Histamine

Acetylcholine stimulates secretion of all the cells of gastric glands, including secretions of pepsinogen by the peptic cells, HCl by the parietal cells and mucus by the mucus cells

Histamine and gastrin specifically stimulate strongly the secretions of acid by parietal cells but have little effect in stimulating other gastric secretory cells

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Regulation of gastric secretion

Cephalic phase(neural):

• cephalic influences are vagally mediated responses induced by activity in the CNS,
• it takes place before food enters into stomach, especially while it is being eaten

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• Food in mouth and sight, smell, taste, thought of food, sound

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• Sensory signals arise from retina, ears , nose, cerebral cortex or in appetite centers of amygdala or Hypothalamus

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• Signals to the dorsal nuclei of vagus

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• Signal come to stomach via vagus nerve

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• Release of acetylcholine(Ach)

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• Ach cause HCL, pepsinogen & mucous secretion(20% of gastric secretion)

Regulation of gastric secretion

• Gastric Phase

Regulation of gastric secretion

Intestinal phase:

• Presence of food in the upper small intestine releases some gastrin by duodenal mucosa.
• Gastrin causes the stomach to secrete small amount of gastric juice

Inhibition of gastric secretion by post stomach intestinal factors:

Although intestinal chyme stimulates gastric secretion during the intestinal phase of secretion, it paradoxically often inhibits gastric secretion by two influences:

• Reverse enterogastric reflex: presence of food in the small intestine initiates a reverse enterogastric reflex that inhibits gastric secertion
• Presence of acid, fats, protein breakdown of products, hypersomotic or hypoosmotic fluid or any irritating factors in the upper small intestine causes release of several intestinal hormones
• eg Secretin, GIP, VIP, Somatostatin that inhibit gastric secretion

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• Other influences of gastric secretion
• Emotions: Anger, Hostility= Increase secretion while
• Fear, depression = decrease secretion
• Hypoglycemia = Increased secretion
• Alcohol & caffeine = Increased secretion

Drugs that inhibit gastric HCl secretion

• H2 receptor blocker(Binds with H2 receptor)
• Ranitidine
• Cimetidine
• Nizatidine
• Famotidine
• Proton pump( H⁺/K⁺ pump) inhibitor (PPI)
• Omeprazole
• Pantoprazole
• Esomeprazole
• Rabeprazole
• Lansopazole
• Antimuscarinic drugs:
• Pirenzepine
• dicyclomine

Intestinal glands

• Two types namely: Crypts of Lieberkuhn and Brunner's glands.
• They are tubular structure that occur throughout the small intestine between the villi.
• They secrete digestive enzyme and mucus.
• The crypts have at the base Paneth cells and argentaffin
• The walls of the small intestine are lined with a dense mucosa with many glands that both secrete and absorb
• In the jejunum and the ileum, the mucosa secretes small amounts of digestive enzymes and lubricating mucus while absorbing nutrients from your food

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Enzyme in intestinal juices

• Enterokinase: activates trypsinogen to trypsin.
• Dipeptidase   : converts proteases to peptones and amino acids. 
• Aminopeptidases : converts peptones to amino acids. 
• Maltase : converts maltose to glucose 
• Lactases : converts lactase to glucose and galactose 
• Sucrase   : coverts sucrose to glucose and fructose 
• Nuclease : converts nucleic acids to mononucleotides. 
• Nucleotidase and nucleosidases: convert nucleic acids to purines, pyrimidine bases,.
• Lipases : act on fat liberating fatty acids and glycerol. 
• Amylases : act on starch resulting in dextrins and maltose

Pancreas

• Pancreas  has both endocrine and exocrine portions.
• The endocrine portion of the pancreas is made up of islets of langerhans, secrets hormones like glucagon (alpha cells), insulin (beta cells) and somatostatin (delta cells) into the blood.
• The  major portion of pancreas is exocrine in function.
• Secretions 
• The enzymes of the pancreatic juice are synthesized and secreted by the acinar cells. 
• The small duct system contain high level of carbonic anhydrase is responsible for the secretion of water and electrolytes. 
• In most species, the pancreatic duct empties directly into duodenum. 
• Horse, Dog and Fowl usually have two pancreatic ducts.
• In Sheep, pancreatic duct joins with common bile duct before entering into duodenum. 

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Composition of pancreatic juice

Pancreatic juice is a clear alkaline fluid made up of the secretions of  two separate phases , aqueous(Hydrolytic type)and organic (Echbolic type)phases

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The aqueous phase causes a higher concentration of HCO₃ and lesser amounts of Cl.

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The HCO₃ is important for partial neutralisation of the acid chyme from the stomach and  maintenance of H⁺ ion concentration suitable for digestive activities of pancreatic enzymes.

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The organic phase produces more of pancreatic enzymes. 

Amount of juice secreted in

• Horse: 10 to 12L /100kg body weight/day
• Cattle – 3 to 5L /100kg body weight/day
• Sheep – 0.5 to 1L/100kg body weight/day

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Pancreatic Juice

Function of pancretic secertion

• Hydrolytic type
• Copious , thin, watery secretion rich in bicarbonate with almost no enzymes is called hydrolytic type of secretion
• Echbolic type:
• Thick,viscid and lesscopious juice rich in enzymes, poor in HCO3 is called echbolic type of secretion

Regulation of Pancreatic secretion

Pancreatic juice secretion is primarily under hormonal control, Neural mechanism also plays some role

Three basic stimuli are important in causing pancreatic secretion

• Acetylcholine: acts on acinar cells of pancreas
• Cholecystokinin: (CCK): acts on acinar cells of Pancreas
• Secretin: acts on ductal cell of pancreas

Nervous regulation : In three phases

• Cephalic phase.
• Gastric phase.  
• Hormonal regulation
• Intestinal phase (Secretin and CCK)

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• Cephalic phase:  The cephalic phase of gastric secretions , simultaneously transmit the impulses  along the vagus to pancreas; results in pancreatic secretion  rich in enzymes, but little water and electrolytes. 
• Gastric phase: Distension of stomach due to entry of food into the stomach cause   reflex stimulation of pancreatic secretion through vasovagal reflex.  
• Intestinal phase: Distension of intestine following the entry of food into  the small intestine, stimulates the  production of pancreatic enzymes and their secretion.

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Regulation of Pancreatic Juice(Neural Mechanism)

Cephalic Phase

• Food in mouth or sight, smell, taste, sound and thought of food

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• Sensory signal from retina,ears, nose, cerebral cortex or in appetite centers of amygdala or Hypothalamus
• Signal go to dorsal nucleus of Vagus

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• Signal come to stomach via vagus nerve

• Release of Acetylcholine

Gastric Phase

• Food in stomach

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• Local vagovagal reflex

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• Local enteric reflex

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• Release of Acetylcholine

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• Acetylcholine acts on acinar cells of pancreas

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• Release of pancreatic juice rich in enzyme but poor in bicarbonate

Regulation of Pancreatic Juice(Humoral Mechanism)

• Fat and protein in duodenum

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• Release of Cholecystokinin by duodenal mucosa

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• CCK goes to the pancreas via blood

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• Acts on Pancreatic acini

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• Release of pancreatic juice rich in enzyme, poor in bicarbonate( Echbolic type)

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• Acidic chyme in duodenum

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• Release of secretin by duodnal mucosa

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• Secretion goes to pancreas via blood

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• Acts on pancreatic duct

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• Release of pancreatic juice rich in bicarbonate but poor in enzyme( Hydrolytic type)

It is the most important mechanism for secretion of pancreatic juice, it ocuurs in intestinal pahse by two local hormones

1. Secretin
2. Cholecystokin (CCK)