GI Lecture 4 Flashcards
Secretion
The addition of fluids, enzymes, and mucus to the GI lumen.
Main cause of secretion
Presence of food, with the quantity corresponding to the amount of food for proper digestion. Type of enzyme also specific.
Daily secretory volume
6500, coming from the saliva (1000), gastric secretion (1500), pancreatic secretion (1000), bile (1000), small intestine secretion (1800), large intestinal secretion (200).
Secretion with lowest pH
Gastric secretion (1-3.5)
Secretion with highest pH
Pancreatic secretion (8-8.3)
Parotid glands
Serous, secrete saliva.
Submandibular and sublingual glands
Mixed mucous and serous, secrete saliva.
Smaller glands in oral cavity like buccal glands
Only mucus.
Structure of submandibular gland
- Acinar cells secrete salivary amylase
- mucus cells secrete mucins
- intercalated duct drains into salivary duct which consists of striated and excretory ducts
Primary secretion of saliva
The amylase containing primary secretion is nearly isotonic - levels of Na, K, Cl, and HCO3 are similar to plasma.
Secondary secretion of saliva
Hypotonic (reduced concentration)- ductal cells reabsorb Na and Cl ions from the saliva and secrete K and HCO3 into the saliva.
Explain how flow rate affects saliva composition
The faster the flow rate, the less time there is for ductal cells to act. Therefore, saliva is closer to isotonic during high rate of saliva flow.
What is the pH range of saliva
6-7
What are the functions of saliva
- Lubrication (by mucins)
- Protection
- Solubilization
- Oral hygiene
- Initiate carbohydrate digestion by alpha amylase (ptyalin) enzyme
- Initiate lipid digestion by lingual lipase enzyme
How is salivation controlled
Autonomic nervous system. Mainly parasympathetic, but sympathetic can slightly modify the content of saliva.
What are the two pathways of salivary secretion.
Salivatory nucleus of medulla sends parasympathetic signal to:
- Otic ganglion -> ACh NT -> Parotid gland -> increased salivary secretion via effects on acinar secretion and vasodilation.
- Submandibular ganglion -> ACh NT -> submandibular gland -> increased salivary secretion via effects on acinar secretion and vasodilation
What may stimulate the salivatory nucleus of the medulla?
Higher centres (smell, taste, etc)
Sleep, Fatigue, Fear
Pressure in mouth
Xerostomia
Dry mouth.
• Several different conditions can cause decreased saliva secretion. (E.g., Sjögren’s syndrome, side effect of many drugs, secondary to head and neck radiation).
• Decreased pH in the mouth leads to tooth decay and esophageal erosions.
• Difficulty swallowing
How much gastric secretion is produced a day? At what pH?
1.5-2L. ph 1-3.5.
Where do gastric secretions come from?
Surface epithelial cells, mucous neck cells, gastric glands. Largest volume from parietal cells.
What are the main electrolytes of gastric secretions
H, Na, K, Cl - mainly isotonic.
Mucus cells of gastric mucosa
Secrete mucus that coats and lubricates the gastric surface and protects the epithelium.
Parietal cells of stomach body
secrete HCl and intrinsic factor
Chief (peptic) cells of stomach body
Secrete pepsinogen (pepsin precursor)
G-cells of stomach antrum
Secrete gastrin hormone
Bariatric surgery effect on gastric secretion
Results in lowered gastric secretions after a meal.
Gastric oxyntic gland
Located in the body of the stomach; a duct included mucus neck cells, parietal cells and chief cells leading to the mucosae. Secrete HCL and intrinsic factor.
3 types of gastric acid secretion
- Proton (H/K) pump to pump H into lumen of gland in exchange for K.
2/ Cl- ions flow into lumen via Cl ion channels into lumen - HCO3- absorbed into blood stream in exchange for Cl.
Pepsins
A group of proteasses that are secreted as inactive pepsinogens by chief (peptic) cells.
What stimulates pepsinogen release
Vago-vagal reflex and gastrin release
Intrinsic Factor
Secreted by gastric parietal cells.
Essential for B12 absorption in the ileum.
The only gastric function that is essential for human life.
Vitamin B12
Aka Cobalamin (Cbl) Is involved with synthesis of all cells, especially affecting the DNA synthesis.
Pernicious anemia
Red blood cells fail to mature because of the problem in IF profuction and B12 absorption.
Describe, in a detailed manner, the role of G cells in gastric secretory regulation.
Vagus nerve innervates G cells to release gastrin (which in turn regulate parietal cells) and also directly the parietal cells to release HCl, Distention of the antrum stimulates G cells to release gastrin. Vagus nerve acts on G cells using GRP (gastrin releasing peptide) and distention acts on G cell with ACh, and vagus nerve acts on parietal cells with ACh.
Ulcer Disease
Breaks in the stomach (gastric ulcers) or in the duodenal mucosa (duodenal ulcers).
Both types of ulcers relate to thecorrosive action of pepsin and HCl on the upper gastrointestinal tract mucosa.
What are the main causes of peptic ulcer disease
Either excess secretion of acid and pepsin by the gastric mucosa or diminished ability of gastric mucosal barrier to protect.
Main cause is Helicobacter pylori bacteria that colonizes in the stomach.
What are other causes of peptic ulcer disease
Non‐steroidal anti‐inflammatory drugs (NSAIDS) or Alcohol. Break down the mucosal barrier.
Smoking. Increases nervous stimulation of the secretory glands in stomach.
Gastrinoma (Zollinger‐Ellison Syndrome). Rare tumor that releases gastrin hormone leading to excessive HCl secretion.
What are major structural components of pancreatic secretion?
Duodenum, common bile duct from gallbladder, pancreatic duct, pancreas, exocrine cells (enzymes), endocrine cells of pancreas, duct cells (bicarbonate).
Describe the pH of pancreatic secretions
Aqueous component has high bicarbonate concentration that neutralizes the chyme in the duodenum (pH ~8)
What enzymes are in pancreatic secretions?
- Protein digestion - proteases
- Carbohydrate digestion - amylases
- Lipid digestion - lipases
Volume and ion concentration of pancreatic secretions?
1L/day
Isotonic with plasma
What are the means of secretion in pancreatic fluids?
Acinar cells secrete the enzyme component.
Ductal cells secrete aqueous component, and includes bicarbonate.
Cl- secretion occurs via a CFTR type channel.
What type of exchangers are there between interstitial fluid, the pancreatic duct cell, and the lumen of the small intestine?
CFTR for Cl- Na+/H+ exchanger Na+/K+ ATPase exchanger K+ channel Na+ pump
How does flow rate affect ion concentration of pancreatic secretion?
Increased secretory flow rate
- Decreases Cl- concentration
- Increases HCO3- concentration (which is already above plasma at all rates)
- Does not affect Na+
Describe regulation of pancreatic enzymes
Amino acids, small peptides and fatty acids stimulate I cells, which release CCK, that affect acinar cells to release IP3, Ca2+ and activate enzyme release.
ACh also potentiates acinar cells.
Describe regulation of aqueous ion concentration
H+ stimulate S cells which release secretin to activate cAMP in ductal cells, which in tern results in aqueous secretion of Na+ and HCO3-.
ACh and CCK also potentiate ductal cells.
Why is pancreatic insufficiency rare
Pancreatic enzymes are secreted in excess. Secretion can drop down to 10% of normal without any effect on nutrient absorption.
Cystic Fibrosis
Pancreatic ducts are inefficient to secrete bicarbonate and water. Because of this the enzymes cannot be flushed properly from the pancreas, and limited quantities reach the intestinal lumen. Enzymes
that reach the lumen are inactive because of the failure to neutralize gastric acid. Enzymes provided as supplements.
Pancreatitis
Inflammation of the pancreas. Autodigestion of pancreatic tissue due to enzyme retention. Can be caused by gallstones in the duct, malignancy, alcohol abuse. Medical emergency.
Bile
Secreted continuously by the liver (1L/day) with intermittant flow in the duodenum. Has a PH of 7.8-8.6 and is isotonic with Na, K, HCO3, Cl.
What happens to bile in interdigestive periods
Bile is diverted to the gallbladder, where it undergoes concentration of solids, acidification, and increase in viscosity.
Gallbladder is relaxed, sphincterof Oddi is closed, and gallbladder fills with bile.
What are biliary solids?
- Bile acids - synthesized from cholesterol in the liver. In the small intestine they exist as bile salts that are more soluble.
- Phospholipids - major ones lecithins
- Cholesterol - small amount
- Bile pigments - major one is bilirubin
What happens to bile flow shortly after eating
- CCK release induces concentration of the gallbladder and relaxation of the sphincter of Oddi.
- Bile flows to duodenum and from there to ileum.
- From the ileum bile salts are recirculated.
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs, or other substances from the liver to the gallbladder, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver via the portal circulation.
Primary bile acids
> 90% of the bile salts are reabsorbed from the ileum into the portal blood, cleared
and resecreted by the liver.
Includes cholic acid and chenodeoxycholic acid.
Secondary bile acids
A small amount of bile salts are dehydroxylated by
colonic bacteria to form secondary bile salts which are also reabsorbed, returned to the liver, and resecreted. Includes deoxycholic acid and lithocholic acid.
Gallstones
Collection of solid material (mainly cholesterol) in main gallbladder.
Symptoms of gallstones
Often asymptomatic. Abdominal pain (upper middle or right), nausea, jaundice, fever.
What might cause hypersecretion of cholesterol
Obesity, oral contraceptives, estrogen, old age, sudden weight loss, genetic factors.
What might occur if enterohepatic circulation is interrupted
Diminished bile acid pool
Cholecystectomy
Gal bladder removal. Gallbladder is not essential for normal digestive function, thus removal has no effect on life expectancy or metabolic status.
Consequences of cholecystectomy
No effect on cholesterol composition of hepatic bile
Balance of specific bile acids may change
Inability to form concentrated bile and to secrete it when the meal enters the duodenum - thus may be less able to tolerate large fatty meals.
May have diarrhea for many years, as bile acids can have a laxative effect.
Symptoms of Crohn’s
Early onset, teenage to twenties, abdominal cramps, diarrhea, weight loss, fever, anemia, ulcers, fistulae, abscess.
Possible causes of Crohn’s
- Abnormal immune response to intestinal bacteria
2. Mutations in NOD2 gene
Anatomical locations of inflammation in Chron’s
Can affect the full thickness of bowel wall. 5% small intestine 35% right colon 20% colon 35% distal ileum 5% gastroduodenal
Treatment for Crohn’s
Dietary adjustments.
Medication - anti-inflammatory drugs and immunosuppressants for long term and antibiotics and pain killers, maybe laxatives, for short term.
Surgery - ileal resection (however, bile salts are depleted in this process so fat absorption and vitamin, iron and calcium absorption may be affected).
