MED2042 WEEK 6 - Gastroenterology (GI secretions)
Terms
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- What are the GI-tract secretions?
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1. Saliva
2. Gastic secretions
3. Bile
4. Pancreatic secretions - How is saliva secreted?
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3 pairs of extrinsic salivary glands + small intrinsic saliary glands (buccal glands) throughout the oral cavity mucosa = continuously secrete saliva to keep mouth moist
Mumps = inflammation of parotid gland (myxovirus); spreads in saliva; causes discomfort with chewing - What are the two types of secretory cells in salivary glands?
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Serous cells (stain purple)
Serous secretion = H2O, ions and ptyalin (an alpha-amylase)
Mucous cells (stain blue)
Mucous secretion = mucin (lubricates and protects surfaces) - What is the daily saliva secretion?
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800-1500mL (average 1000mL)
~0.05ml/min during sleep
~0.5ml/min awake
~7-8mil/min with acid (e.g. lemon) - What is the composition of saliva?
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H2O (97-99.5%)
ions (Na+, K+, Ca2+, Mg2+, PO4 3-, HCO3- and Cl-)
Salivary amylase (ptyalin
Mucin
Immunoglobulins
pH 6-7 - What are the functions of saliva?
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1. Lubrication (mucins)
2. Digestion (alpha-amylase)
3. Protection (oral and dental health = fluid rinses mouth & alkaline pH buffers food acids)
4. Control of H2O intake (thirst)
5. Speech
6. Absorption of low molecular weight molecules in the mouth (e.g. glycerol trinitrate)
7. Taste sensation (chemicals dissolved in saliva detected by taste receptors) - What is xerostomia?
- dry mouth from insufficient saliva secrtion
- When is saliva secreted?
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Saliva is secreted in response to:
1. Approach of food
2. Presence of food int he mouth
3. Thought of food
This is mediated via parasympathetic nerves and involves two reflexes:
1. Conditioned reflex (Ivan Pavlov 1904 Nobel prize - PAVLOV'S DOGS = fed his dogs in association with the ringing of a bell (learned response))
2. Unconditioned reflex (Activation of taste buds triggers salivation (gustatory pathway) - How does the sensation of taste lead to salivation?
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Taste depends on the solubilisation of food by saliva and the detection of chemicals (tastants) in saliva
Four taste modalities: salt, sour (acidic = most potent), sweet, bitter
1. Tastants diffuse into pore and bind to taste receptors on hairs
2. Receptor activation depolarises gustatory cells & releases and excitatory neurotransmitter
3. Neurotransmitter activates afferent sensory neurons that transmit impulses via cranial nerves to the brainstem
4. Sensory neurons transmit impulses to the brainstem (tractus solitarius)
5. This initiates reflexes (via synapses with parasympathetic nuclei) that increase saliva secretion.
Facial = submandibular & sublingual
Glossopharyngeal = parotid - How are gastric secretions secreted?
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Gatric secretions - HCl, pepsinogen, intrinsic factor
Gastric glands of fundus & body contain 4 main secretory cells:
1. Mucous neck cells
2. Chief cells produce pepsinogen (inactive from pepsin, activated by apical HCl)
3. Parietal cells secrete HCl (pH ~0.8) & intrinsic facor (vit B12)
4. Enteroendocrine cells - release hormones or hormone-like produces (e.g. enterochromaffin-like/ECL cells secrete histamine) - How is HCl secreted?
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Parietal cells are the only cells that secrete HCl.
HCL secretion is stimulated by:
1. Histamine (released from mast cells or ECL cells (gastric body)
2. Gastrin (secreted from G cells (gastric antrum))
3. Acetylcholine (from parasympathetic nerves) - Describe the control of HCL secretion by Histamine.
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- acids on histamine (H2) receptors
- this activates the enzyme adenylyl cyclase (AC) leading to cAMP production
- cAMP activates protein kinase A leading activation of H+/K+ ATPase
- (pumps H+ into lumen and K+ into cell = involves ATP hydrolysis becausem lumen [H+] > cytoplasm - Describe the control of HCl secretion by acetylcholine & gastrin.
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Acetylcholine binds to muscarinic (M3) receptors
Gastrin binds to gastrin (G) receptors
This leads to increased cytosolic Ca2+ (binds to calmodulin) leading to PKA and H+/K+ATPase activation.
Note = gastrin and acetylcholine also stimulate histamine secretion from ECL cells - What happens in parietal HCL secretion?
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1. CO2 +H2O = carbonic acid, dissociates to H+ and HCO3-
2. HCO3- diffuses into extracellular fluid in exchange for Cl- (blood draining from stomach is more alkaline than blood serving stomach)
3. H+ actively secreted into the gastric lumen in exchange for K+ - What are the three phases of gastric secretory activity?
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These may be occuring at the same time.
1. CEPHALIC (head
- approach of food & presence of food in th e mouth
- takes minutes
- 20% gatric secretion with a meal
2. GASTRIC (stomach)
- presence of food in the stomach
- takes 3-4 hours
- 70% gastric secretion with a meal
3. INTESTINAL (small intestine)
- presence of food in small intestine
- 10% gatric secretion with a meal
- inhibition of gastric secretion decreases the acidity (duodenal digestive enzymes & micelle formation require neutral or alkaline pH) - Describe the Cephalic phase of gastric secretory activity.
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- Triggered by aroma, taste, sight, thought of food
- Inputs from activated olfatory & taste receptors relayed to hypothalamus
- vagal nuceli of medulla oblongata stimulated
- activation of parasympatetic nerves innervating the gut (acetylcholine)
- enhances secretory activty (HCl & pepsinogen) - Describe the Gastric phase of gastric secretory activity.
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- food reaches the stomach
- distension activates stretch receptor initiating local myenteric and long vaso-vagal reflexes (acetylcholine)
- rising pH, partially digested proteins (peptides) and caffeine stimulate gastrin secretion. - Describe the Intestinal phase of gastric secretory activity.
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Excitatory - partially idgested food in duodenum stimulates intestinal mucosal cells to secrete intestinal gastrin (rapidly inactivated by chyme)
Inhiitory = entero-gastric reflex: inhibition of vagal nuclei in the medulla, inhibition of local neuronal reflexes, activation of sympathetic fibres (cause phyloric sphincter to tighten)
- secretin, cholecystokinin, vasoactive intestinal peptide and gastric inhibitory pepde also secreted (inhibit gatric secretion, thus increase pH) - What is the protective gastric mucosal barrier:
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The stomach mucosa is protected from corrosive acidic gatric juice by:
1) HCO3- rich mucous (secreted by globlet cells in gastric mucosa)
2) mucosal epithelial cells joined by tight junctions
3) luminal faces of glandular cells deep in gastric glands impermeable to HCl
4) damaged epithelial cells shed and rapidly replaced by division of undifferentiated stem cells (found where gastric pits join glands)
N.b the stomach surface epithelium is renewed every 3-6 day - What are peptic ulcers?
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Peptic ulcers are sensitive, raw patches which form a break in the lining of the stomac (gastric ulcers) or the duodenum (duodenal ulcers).
Causes:
1. high acid and peptic content
2. irritation
3. poor blood supply
4. poor secretion of mucus
5. infection, H.pylori
Important cause = Helicobacter pylori. Present in nearly all patients with duodenal ulcer and at least 80% of patients with gastric ulcers.
Treament: antibiotics and acid suppressing drug (e.g. the antihistramine ranitidine = reduces gastric secretions by ~80%) - What is bile?
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- hexagonal liver lobules = hepatocytes plates radiating out from central vein
- between hepatocyte plates = enlarged leaky sinusoids - How is bile secreted?
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1. Secreted by hepatocytes into bile canaliculi
2. Canaliculi empty into terminal bile ducts - hepatic duct - common bile duct - duodenum (during a meal) or diverted (between meals) and stored in gall bladder - What is the composition of bile and its functions?
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250-1000mL secreted a day.
Yellow-green alkaline solution containing
- H20
- bile salts (cholesterol derivatives) - Intestinal tract = 1) emulsifying fats, 2) form micelles that aid in the absorption of fatty acids, monoglycerides and cholesterol
- bile pigments - bilirubin = produced by breakdown of haemoglobin or myoglobin; reddish brown; intermediate product, biliverdin = green pigment present in bile
- cholesterol - precursor of bile salts
- lecithin (phospholipid) - combines with bile salts to form micelles
- electrolytes (Na+, K+. Ca2+, Cl-, HCO3-) - Describe how bile salts help emulsify fats?
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Fats (triglycerides) become associated with bile salts and lecithin to form micelles
Hydorphilic (polar) ends of the molecules face water, hydrophobic (nonpolar) core contains fat-soluble vitamins and cholesterol molecules - What are the mechanisms promoting bile secretion?
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1. Acidic, fatty cyme entering duodenum causes release of cholecystokinin and secretion from duodenal wall enteroendocrine cells
2. Cholecystokinin and secretin enter the bloodstream
3. Bile salts and secretin transported via bloodstream stimulate liver to produce bile more rapidly
4. Vagal stimulation cuases weak contractions of gallbladder
5. Cholecystokinin (via bloodstream) causes gallbladder to contract and hepatopancreatic sphincter to relax and bile enters duodenum
6. Bile salts reabsorbed into blood. - What are gallstones (biliary calculi)?
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What are th causes of gallstones?
1. Too much absorbtion of water from bile
2. Too much absorption of bile acids from bile
3. too much cholestrol in bile
4. Inflammation of epithelium - How are pancreatic secretions produced?
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Exocrine pancreas
The pancreas is a gland that contains:
1. Exocrine tissue = pancreatic juice secreted via ducts to duodenum
2. Endocrine tissue = secretes the hormones insulin & glucagon directly into blood - What are the functions of the exocrine pancreas?
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1) Secretes alkaline pancreatic juice = together with other alkaline secretions, bile and intestinal juices, act in the small intestine to neutralise acidic chyme
Why neutral or slightly alkaline pH?
1. pancreatic enzyme activity
2. micelle formation
3. protects intestinal mucosa from excess acid
2) Secretes pancreatic enzymes = aid in digestion of carbohydrats, prtoeins and fats - What are the enzyme-producing tissue of the pancreas?
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Epithelial duct cells secrete alkaline fluid
Clusters of secretory cells (acini) surround teh pancreatic ducts
Within acinar cells; contain digestive enzymes - What is the composition of pancreatic juice?
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1. Pancreatic digestive enzymes
- inactive precursors of prteolytic enzymes (trypsin, chymotrypsin, carboxypeptidase and elastase)
- active enzymes lipase, cholesterol esterase, phospholipase (fats), alpha-amylase (carbohydrates), ribonuclease & deoxyribonuclease (nucleic acids)
2. Aqueous alkaline secretion
- HCO3- and H2O (also Na+, K+, Mg2+, Ca2+, Cl- in similar concentrations to plasma, thus alkaline due to high HCO2- content)
- HCO3- neutralises HCl empties into duodenum from stomach (Hcl +NaHCO3 --> NaCl + H2CO3) - Describe the activation of pancreatic proteases in the duodenum.
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- Trypsinogen is activated to trypsin by enterokinase (intestinal brush border enzyme)
- trypsin activates proteases chymotrypsin & carboxypeptidase
- trypsinogen can also be autocatalytically activated by trypsin (from previously secreted trypsinogen) - Describe the regulation of pancreatic juice secretion.
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Acetylcholine and CCK: stimulate acinar cells, thus production of pancreatic enzymes
Secretin: stimulates large amounts of HCO3- and H2O from ductal epithelium - What happens in mumps?
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Mumps = inflammation of parotid glands (myxovirus).
Spreads in saliva; causes discomfort with chewing