Gastrointestinal secretions and their control Flashcards
Water flow into and out of gut in 24 hours
-Most of the water is absorbed by small intestine
-Colon’s job is more to change stool consistency from liquid to solid
Saliva secretion
-Primary secretion made by acinar cells
-Driven by Na pump on basolateral side of cells
-Water follows Na resulting in watery secretion which is isotonic with plasma
Passage of saliva
Primary secretion modified as it passes along the duct:
-Na+ and Cl- re-absorbed
-K+ added
-HCO3- added
-Final outcome is a bicarbonate rich, hypotonic secretion
-Exact composition depends on flow rate
Other components of saliva
Other ions:
-Ca2+
-phosphate
Large molecule components:
-mucins (glycoproteins)
-lysozyme and amylase, released from acinar cells by exocytosis
Immunoglobulin A:
-made by nearby plasma cells (B lymphocytes)
-binds to a receptor on the basolateral side of acinar cells
-transported into the lumen of the gland
Functions of saliva
-Lubricating food (for chewing and swallowing)
-Amylase initiates starch digestion
-Several of the other components have antimicrobial activities
-pH, and particular mix of Ca2+ and phosphate ions also contained in saliva, protect the teeth from demineralisation
Differences in salivary secretions between glands
Parotid: amylase >mucus
Submandibular: amylase < mucus
Sublingual: only mucus
Highest flow rates:
Basal condition: submandibular
Stimulated: parotid
Salivary control by ANS
Parasympathetic stimulation
-Increase in formation of fluid and electrolyte components of saliva
Sympathetic stimulation
-Increase in release of macromolecular components
Oesophageal secretions of saliva
-Widespread minor glands, which produce only mucus
-Secretion is neurally controlled
Cephalic phase of digestion (CNS control)
-Thinking about food, presence of food in mouth: promotes salivary and gastric secretions
-Chewing helps to break food down into small particles
-Amylase in saliva initiates digestion of starch
Intestinal phase (CNS, ENS and hormonal control)
-Food entering small intestine gradually causes release of hormones that inhibit gastric secretion and motility
-Some of the same hormones provoke the release of biliary and pancreatic secretions into the duodenum
-During this phase, most of the digestion takes place, followed by absorption of the nutrients
Gastric phase of digestion (CNS, ENS and hormonal control)
-Stomach secretes (acid, pepsinogen, etc) in response to presence of food in stomach
-Gastric motility causes further mechanical breakdown of food particles
-Digestion of proteins starts
Main gastric secretions
-Chief cells release pepsinogen
-Parietal cells release HCL and intrinsic factor
-Other main secretions:
-Mucus from surface enterocytes
-Gastric lipase
-Water
Mechanism of acid secretion
- ATP needed to drive H+ secretion into lumen against concentration gradient
- Cl- obtained from blood via exchanger on basolateral side of cell
- H+ secretion therefore results in net HCO3- movement into blood
- Net ion movement into lumen accompanied by water (by osmosis)
How is acid secretion increased in response to stimulation?
-In resting condition (basal secretion), many of the proton pumps are confined to intracellular ‘tubulovesicles’
-On stimulation, the tubulovesicles rearrange and fuse with canaliculi continuous with the lumenal membrane, increasing the surface area for HCL secretion
Regulation of acid secretion by parietal cells
-Positive direct control on parietal cell secretion by ACh, histamine and gastrin
-Inhibitory effect on parietal cell secretion by somatostatin
-Regulation is neural, endocrine, paracrine
Endocrine factors affecting the stomach
Gastrin from pyloric antrum
-release stimulated by proteins, coffee, alcohol
-release inhibited by low gastric pH
-induces gastric secretions, increases motility
CCK (Cholecystokinin)
-release from duodenal wall stimulated by fats etc
-depresses gastric motility and secretion
Secretin
-release from duodenal wall stimulated by acid
-Inhibits gastric secretion
GIP (from SI) and GLP-1 (from ileum/colon)
-release stimulated by fat & chyme in the lumen
-inhibit gastric motility & secretion
Small intestine secretions
-Mucus (from goblet cells)
-Isotonic saline (from crypt cells)
-Alkaline mucus (from Brunner’s glands)
-Surface enterocytes (on villi) also make many digestive enzymes which are embedded in the glycocalyx of their brush border, and a bicarbonate rich fluid
Pancreatic and biliary secretions into the duodenum
-Made separately, but generally discharged together into duodenum
-Sphincter of Oddi relaxes to allow secretions to pass into duodenum
Pancreas exocrine secretions
1) Alkaline fluid rich in bicarbonate
-Produced largely by cells of the pancreatic duct
-Role is to neutralise the acidic chyme entering the small intestine from the stomach
2) Digestive enzymes
-Includes endopeptidases, carboxypeptidase, amylase, lipase
-Produced largely by the acinar cells, and stored intracellularly as inactive precursor forms in ‘zymogen’ granules
-Released by exocytosis
-Role is to break down most macromolecules found in food
Hormones affecting pancreatic exocrine secretion
Main regulators are:
-CCK
-Released from duodenal wall by fats
-Induces release of enzyme-rich secretions
-Secretin
-Released from duodenal wall by acidic chyme
-Induces release of bicarbonate-rich secretions
Mechanism of alkaline fluid secretion by pancreatic duct cells
-CO2 from blood, and formation of H2CO3 catalysed by carbonic anhydrase
-Energy provided ultimately by Na pump on basal side of cell
-HCO3- efflux on lumenal side via anion exchanger
Cystic fibrosis effect in pancreas
-Defect in Cl- channel (CTFR type) results in failure to produce this secretion
-No delivery of enzymes
How is secretion of pancreatic alkaline fluid matched to the acid load arriving from the stomach?
CCK release in response to chyme in the duodenum
Bile features
-Made in the liver
-Stored in gall bladder
-Secretion under control of neural and hormonal effects
-Breaks down fats
Summary of control of secretions
Gut hormones released in response to digestion of food
-GIP (from SI)stimulates insulin release (feed forward function to ensure prompt rise in circulating insulin when glucose, amino acids, etc are absorbed)
-GLP-1 (from ileum/colon)stimulates insulin release (feedforward function again) & inhibits glucagon release; promotes satiety
-CCK (from SI)promotes satiety
Gut hormone release inhibited by digestion of food
-Ghrelin (from stomach, and other parts of GI tract) - promotes appetite and feeding behaviour
Colon secretions
-Mucus (for lubrication)
-Secretion of HCO3- (in exchange for Cl-)
-Some secretion of K+
How do colon secretions work?
-These cells have a luminal Na channel
-Absorption of more Na+ than Cl- leaves net negative potential in lumen
-This drives K+ movement into lumen, via paracellular pathway
Consequences of dysfunction of saliva secretion
-Inadequate salivary production (‘dry mouth’) leading to difficulties in swallowing, enamel damage, and reduced microbiological protection
Consequences of dysfunction of gastric secretion
-Gastric atrophy - lack of intrinsic factor, pernicious anaemia
-Gastritis (e.g. due to H. pylori infection) - failure of mucosal barrier, and exposure to acid & proteases leads to gastric & duodenal ulcers
-Excess acid production – leading to duodenal ulcers, SI malabsorption, diarrhoea
Consequences of dysfunction of pancreatic secretion
-Pancreatitis - leading to malabsorption because of inadequate production of digestive enzymes
-Cystic fibrosis – reduced Cl- conductance reduces formation of pancreatic alkaline juice, and therefore reduces delivery of enzymes to duodenum
Consequences of dysfunction of biliary secretion
-Failure to make enough and/or to deliver it to duodenum - leads to malabsorption because of inadequate fat digestion
