Secretion in Upper Digestive Tract Flashcards
How much saliva do we produce per day?
1 - 1.5 L
What secretes saliva?
Salivary glands have high rate of metabolism and blood flow
Describe the blood flow of salivary glands
Blood flow is 10x that supplied to actively contracting skeletal msucle
What are the symptoms of lacking functional salivary glands?
Dry mouth
Dental caries
Infection of buccal mucosa
Background secretion is important
How do infection of buccal mucosa prevent functioning of salivary glands?
Infections of the buccal mucosa, such as bacterial or viral infections, can potentially lead to inflammation and swelling of the mucosal tissues. While the infection primarily affects the mucosa, it can indirectly impact the functioning of salivary glands due to the inflammatory response and associated swelling
How does the parasympathetic nervous system mediate salivary secretion?
Be release of ACh that
Binds muscarinic receptors = watery saliva is secreted
How does the sympathetic nervous system mediate salivary secretion?
Release of norepinepthrine
Binds alpha and beta adrenergic receptors = thicker saliva secreted
What organic constituents of saliva are found in large amounts?
Mucin = glycoprotein
Alpha-amylase = active pH 4-11
What is the role of mucin?
Lubricate food
Name organic constituents of saliva present in small amounts
RNAase & DNAase
Lingual lipase
Lactoferrin
Secretory IgA
Lysozyme
Name some functions of saliva
Antifungal, antibacterial and antifungal
Wound healing
Buffer
Teeth mineralization
Food digestion
Coating & lubrication
Role of Parietal cells
Secrete HCl = kills most ingested bacteria
Except helicobacter pylori
Secrete intrinsic factor
What is intrinsic factor?
Glycoproteins produced by the parietal cells of the gastric glands in the stomach.
These factors play a crucial role in the absorption of vitamin B12 (cobalamin) in the small intestine
They are the only gastric secretion requried for life
Role of Chief cells
Secrete pepsinogens
Pepsinogens are cleaved to pepsin by the acidic effects of HCl
What hormone is secreted in stomach?
Gastrin = regulates gastric acid secretion
Role of mucus secreted by gastric gland
Protect gastric mucosa from mechanical and chemical destruction
What enzymes are secreted in infancy and diminish as we become adults?
Renin and gastric lipase
Gastric lipase activity is more significant in newborns and infants, contributing to the digestion of milk fats (especially in breast milk), its activity diminishes in adults
What is the composition of gastric juice?
99.5% water
0.5% solids = organic and inorganic substances
Describe the conc of K+ in gastric juice
K+ conc is always higher in gastri juice than plasma
What happens to ion conc in prolonged vomiting?
Hypokalemia
What does ionic composition of gastric juice depend on?
Rate of secretion of H+ ions
As secretory rate increases so do H+ and Cl- conc in gastric juice = because of co-traport by parietal cells
Na+ decreases in concentration
K+ stays relatively the same conc
Is the rate of gastric acid secretion the same in everyone?
No, it varies among individuals partly due to variation in number of acid secreting cells
What is the basal rate of gastric acid secretion?
1-5 mM per hour
Basal rate = unstimulated
What is the rate of gastric acid secretion at maximum stimulation?
6-40 mM per hour
What is the rate of gastric acid secretion in a gastric ulcer patient?
Hyposecretion of acid
The increased acidity in the stomach due to the presence of ulcers can activate negative feedback mechanisms to inhibit further acid secretion. One such mechanism involves the release of somatostatin, a hormone that inhibits the secretion of gastric acid.
Somatostatin is released by various cells in the stomach lining, including D cells and enterochromaffin-like (ECL) cells.
They don’t produce acid because of the feedback mechanism
So antacid drugs won’t help
What is the rate of gastric acid secretion in a duodenal ulcer patient?
Hypersecretion of acid
Basal rate = higher than 5mM per hour
Acid is leaking out from stomach
But when there is food in the stomach this is not a problem because pH increases
What is the rate of gastric acid secretion in a pernicious anemia patient?
Hyposecretion of acid
What is pernicious anemia?
Pernicious anemia is a type of anemia characterized by a deficiency of vitamin B12 (cobalamin) due to impaired absorption in the gastrointestinal tract, typically resulting from the lack of intrinsic factor (IF) secretion by the gastric parietal cells. Intrinsic factor is a glycoprotein produced by parietal cells of the gastric mucosa, and it is essential for the absorption of vitamin B12 in the small intestine
What are the major stimulators of HCl secretion?
Secondary messengers = Ca2+ and cAMP
Transmit message from blood to lumen
Name the inhibitors of HCl secretion
Substituted benximidazoles
Prostaglandin E = block cAMP via GCPR
H2-antagonist
Anticholinergics
Gastrin antagonists
What is the function of gastrin?
Stimulate HCl secretion
Increase gastric and intestinal motility
Increase pancreatic secretion
Proper growth of GI mucosa
How does gastrin cause its effects?
Enters bloodstream then goes back to stomach affectin gparietal cells
How does gastrin stimulate HCl secretion?
Gastrin receptor is coupled to GPCR
Activation of PLC = PIP2»_space;> IP3 + DAG
IP3 = increases intracellular calcium releasing from ER store
DAG activates PKC
Calcium and PKC increase the H+/K+ ATPase pumps
These proton pumps actively transport hydrogen ions (H+) from the cytoplasm into the gastric lumen in exchange for potassium ions (K+).
How does gastrin increase pancreatic secretion?
GPCR activates PLC
Elevated intracellular calcium levels trigger the exocytosis of zymogen granules within pancreatic acinar cells.
These granules contain digestive enzymes such as amylase, lipase, and proteases (e.g., trypsin, chymotrypsin), as well as bicarbonate ions (HCO3-), which are essential for pancreatic enzyme function and neutralizing acidic chyme in the duodenum.
Describe the conversion of pepsinogen into pepsin at low pH
Autocatlytic = more rapid conversion at low pH
What is pepsin’s optimal pH?
Less than 3
Where is pepsin inactivated irreversible?
In duodenum pH = 7
What does pepsin digest?
10-20% of total dietary protein
What is intrinsic factor, where it is secreted and what is its function?
Glycoprotein
Secreted by parietal cells in fundus =
What is the fundus?
The “fundus” refers to the upper portion of the stomach, which is located above the body of the stomach and below the esophagus.
It is the part of the stomach that expands and contracts as food is swallowed and enters the stomach.
`The fundus is a relatively thin-walled region that can accommodate swallowed food and gastric juices.
How does intrinsic factor help with Vit B12 absorption?
Forms complex with B12 which is highly resistant to digestion
Complex is absorbed at terminal ileum
Binds to cubilin receptors, the vitamin B12-intrinsic factor complex is endocytosed into the ileal enterocytes
Vitamin B12 then binds to another protein called transcobalamin II (TC-II), which protects it from degradation and facilitates its transport within the bloodstream to various tissues and organs throughout the body
Within cells, vitamin B12 plays essential roles in various cellular processes, including DNA synthesis, red blood cell production (erythropoiesis), and neurological function. Deficiency of vitamin B12 can lead to anemia, neurological disorders, and other health problems
What stimulates intrinsic factor secretion?
Gastrin stimulates IF and HCl secretion
But their secretion is NOT linked
So omeprezole has no effect on IF secretion
Where is mucin found, and what is its function?
Mucin = main constituent of gastric mucus
Function = coat and lubricate mucosa surface
Mucin properties?
Large molecules with CHO side chains
Insoluble in acid pH
Destroyed by pepsin
How is mucin regulated?
Regulated by ACh
Stimulated by food
What does ACh do to HCl secretion?
Enhances its secretion
What effect do prostaglandins have on other gastric mucosal cells?
Paracrine effect = the ability of prostaglandins to act locally within the gastric mucosa to influence the function of neighbouring cells.
Prostaglandins are lipid compounds that are synthesized and released by various cells, including epithelial cells, in response to different stimuli.
What is the function of prostaglandins?
Direct inhibition of parietal cell secretion = as part of the stomach’s defence mechanism to protect the gastric mucosa from damage caused by excessive acid production.
Mediate mucosal defence by:
Stimulation of mucus, phospholipid, and HCO3- secretion
Enhancement of mucosal blood flow
Stimulation of mucosal cell turnover
What happens when someone has a prostaglandin deficiency?
Predisposes them to gastric mucosal injury
What drugs cause gastric mucosal injuries?
COX inhibitors = aspirin & NSAIDs
What does the gastric mucosal barrier consist of?
Thick mucous layer = 1mm
Consists of mucins and HCO3-
What is the function of gastric mucosal barrier and how does it work?
Protect against abrasions, HCl & pepsin
The unstirred layer slows the inward diffusion of H+ and outward diffusion of HCO3-
How is the mucus and HCO3- secretion regulated in the gastric mucosal barrier?
Calcium and cholinergic agonists stimulate HCO3- secretion
Adrenergic agonists decrease HCO3- secretion
Aspirin and NSAIDs inhibit mucus and HCO3- secretion
What is the maximum HCO3- secretion?
10% of HCl secretion
What does decrease in HCO3- secretion cause?
Too much acid = leading to ulcers
Describe the gastric mucosal barrier turnover rate?
High gastric mucosa turnover rate = entire mucosa is replaced in 1-3 days
What is used as ulcer therapy?
Antacids = neutralize HCl
Omeprazol = prevent acid release
Antibiotic = helicobacter pyori bacillus
Misoprostrol = prostaglandin agonist
What enzyme breaks down carbohydrates?
Salivary alpha-amylase
Denatured at low pH
Describe fat digestion in stomach
Minimal fat digestion
How does high acidity affect fat digestion?
Inhibits fats from emulsifying into small droplets
This means they stay insoluble
What substances are absorbed in the stomach?
Nutrients
Very little absorption takes place
For gastric absorption, what properties do the substances have to have?
Highly lipid-soluble substances = ethanol
What is gastritis?
Inflammation of the lining of the stomach
What is heartburn?
Painful or burning sensation in the chest
What mechanisms causes heartburn?
Increase in gastric acid secretion
Backflush of acidic chyme into esophagus
What factors cause heartburn?
Overeating, fatty foods
Smoking, alcohol, coffee
Lying down immediately after a meal
Tight clothing
