Applied Physiology and Biochemistry of the Upper Gastrointestinal Tract Flashcards
What is the composition of the primary secretion of saliva
Plasma-like (isotonic)
How is the saliva modified in the ducts
The ducts are relatively impermeable to water meaning that sodium and chloride ions are removed. Saliva therefore is hypotonic to plasma
Where is saliva formed
In the acinar cells of the acinus
What effect does parasympathetic activity have on saliva secretion
It increases secretion rate. Also peptides (kalikreins) released from nerves cause vasodilation in the secretory glands
What does the increase in secretory rate of saliva result in
A change in osmolarity and ionic composition of the saliva formed
Describe NKCC1
NKCC1 supports the initial secretion of chloride ions, NKCC1 is a co-transporter (Na, K, Cl ions)
What does the constituents of saliva vary with
Flow rate
Describe stimulated saliva
Stimulated saliva (saliva st high rates of flow) becomes nearer iso-osmotic to plasma because the ducts don’t have as much time to modify the saliva
Describe ion exchange that occurs in the ducts
Ducts act to reabsorb Na+ and Cl-. Na+ out, H+ in. Cl- out, HCO3- (bicarbonate) in
Why does saliva become closer to plasma in composition at high rates of salivary flow
The exchange mechanisms don’t have enough time to remove Na+ and Cl-
What is the key role of the transport mechanism in the ducts
To remove ions (Na+ and Cl-) from the lumen of the duct
Describe what happens to saliva at low rates of flow
The transporters are able to remove ions more effectively (relatively impermeable to water) and leave behind water resulting in salivary fluid becoming more hypoosmotic
What are the 3 key phases of swallowing
Oral, pharyngeal and oesophageal
Which component of swallowing is voluntary
The oral (first) phase
Which components of swallowing are involuntary
Pharyngeal and oesophageal (relfex autonomic)
Describe the oral phase of swallowing
When food hits the sensory receptors on the soft palate the involuntary phase of swallowing is initiated (oral phase initiates involuntary phase)
Describe the pharyngeal phase of swallowing
Soft palate is raised by superior constrictor muscles which close off the oropharynx and stop food entering the nose, Also the epiglottis closed the entrance to the trachea and a neuronal reflex called deglutition apnoea meaning that you momentarily stop breathing
Describe the oesophageal phase of swallowing
Food begins to enter into the oesophagus, the upper oesophageal sphincter opens before the bolus gets to it, the lower oesophageal sphincter also relaxes ahead of the bolus
What pushes the bolus down the oesophagus
A peristaltic wave that starts during the pharyngeal phase continues to push the bolus down the oesophagus
What are the pharyngeal and oesophageal phases controlled by
Involuntary and controlled by the medulla and lower pons
What is dysphagia
Difficulty in swallowing
What can dysphagia be caused by
A number of different reasons such as a lesion in a cranial nerve (such as trigeminal nerve) or drug related (anticholinergic drugs)
What type of muscle does the upper part of the oesophagus consist of
Striated muscle under involuntary control
What is peristalsis organised by in the upper part of the oesophagus
The brainstem
What type of muscle does the lower oesophagus consist of
Smooth muscle
What is peristalsis organised by in the lower part of the oesophagus
ENS (enteric nervous system)
Describe the lower oesophageal sphincter
Maintains resting tone, displays receptive relaxation
How does the lower oesophageal sphincter remain closed
By lying below the diaphragm meaning that abdominal pressure helps keep it closed
Why can reflux of acid occur in pregnancy
The foetus causes an upwards pressure and often causes the lower oesophageal sphincter to be pushed above the diaphragm resulting in reflux of acid which erodes the oesophagus lining
What volume is gastric juice at rest
~30ml
What happens to pH on arrival of a meal
pH first rises (food buffering) and then falls (activation of H+/K+ ATPase)
What effect does arrival of a meal have on the parietal cells
They secrete intrinsic factor and HCl
What does a lack of intrinsic factor result in
Anaemia
What happens to chief cells when a meal arrives
They secrete pepsinogen
What happens to stomach pressure when food arrives
Pressure stays the same due to accomodation
Describe the cephalic phase in gastric secretion
35% of the total. Sight, smell, taste of food, chewing -> vagal stimulation -> secretion of acetylycholine by nerve endings -> parietal cells and chief cells and secretion of gastrin by G-cells of the stomach-> gastric secretions (HCl and pepsinogen)
Describe the gastric phase in gastric secretion
60% of total. Distention of the stomach -> vago-vagal and local reflexes -> secretion of acetlycholine by nerve endings -> parietal cells and chief cells and secretion of gastrin by G-cells of the stomach-> gastric secretions (HCl and pepsinogen)
Describe the intestinal phase in gastric secretion
5% of total. Protein digestion products in duodenum -> secretion of secretin, CCK, GIP (which inhibits secretion of gastrin by G-cells of stomach and parietal cells) and stimulation of G-cells in intestine -> chief cells -> gastric secretions (HCl and pepsinogen)
What is the role of mucus neck cells
Important in secreting mucus which helps to protect the cell surface of the stomach.
Which nerve are mucus neck cells stimulated by
The vagus
What effect does alcohol have on surface mucus secreting cells
Stimulated by alcohol. When stimulated tend to produce an insoluble mucus which means hat the protective function of the mucus is lost and gastric erosion takes place
What do G-cells release
The hormone gastrin
What do D-cells release
Somatostatin (largely inhibitory agent)
What do H-cells release
(ECL) release histamine
What happens when you stimulate the parietal cells
A large morphological change occurs. The tubulovesciles which store the proton pump fuse with the apical membrane and incorporate pump allowing the activity to increase and acidifying the lumen of the stomach. The tubulovesicles have a limited K+ permeability which holds the pump inactive inside the cells
What happens once the proton pump in the tubulovesicles has been stimulated
It pumps out H+ ions in exchange for K+. The hydrogen ions acidify the lumen of the stomach
What are hydrogen ions in the tubulovesicles produced by
The action of carbonic anhydrase that generate bicarbonate. The bicarbonate is transported across the basolateral membrane causing the alkaline tide where venous blood around the stomach becomes more alkaline and is used to bring in chloride ions that are then transported across the apical membrane. Once transported the chloride ions join the hydrogen ions to form hydrochloric acid
Describe the activity at the apical membrane of the tubulovesicles
H+-K+-ATPase is inserted and chloride ions can leave through two routes
Describe the activity at the basolateral membrane
Bicarbonate leaves exchanging with chloride ions
What are the 3 phases of nervous and hormonal mechanisms controlling gastric secretion
Cephalic, Gastric and Intestinal
Describe the cephalic phase
30% response, food in mouth causes an increase in vagal outflow. Vagus innervates ENS lining the stomach and stimulates parietal cells and G cells
Describe the gastric phase
60% response, two principle triggers: stomach distention and chemical content activate chemo and mechano receptors. There are short and long loop stimulators. Stimulation of G cells results in gastrin entering the blood stream and gastrin stimulated by the parietal cells
When is gastrin secretion inhibited
At low pH (2-3)
What does the vago-vagal reflex do
In gastric phase, further stimulates acid secretion
Describe the intestinal phase
5% response. Partially digsted food enters duodenum via pyloric sphincter. Stimulatory- due to duodenal release of gastrin. Biggest effect of the intestinal phase is inhibitory
What do G cells in the duodenum respond to
Increased amount of protein digestion products
Describe the inhibitory effect of the intestinal phase
Due to duodenal release of secretin and CCK & GIP. Inhibitory products largely inhibit acid secretion
What is secretin released in response to
Increase in acid
What are CCK and GIP released in response to
An increase in fat digestion products
What are the parietal cell main receptors
Cholingeric, gastrin, histamine, somatostatin, prostaglandin
Describe the cholinergic receptor pathway
Activate Gq to increase PKC and increase Ca2+
Describe the gastrin receptor pathway
Activate Gq to increase PKC and increase Ca2+
Describe the histamine receptor pathway
Activate Gs to increase PKA, potentiates gastrin effect
Describe the somatostatin receptor pathway
Activate Gi to decrease PKA, helps switch off HCl secretion
Describe the prostaglandin receptor pathway
Active Gi to decrease PKA, acts to help keep HCl secretion switched off at rest
Why do you get gastric erosion when you take aspirin
It blocks the product of prostaglandins removing the inhibitory effects and so at rest you get acid secretion= gastric erosion
What effect does the presence of fat have on gastric emptying
Presence of lipid results in slower emptying of the stomach
What are the natural mechanisms for switching off acid secretion
Withdrawl of vagal activity. Increased splanchnic nerve activity. Inhibition of gastrin release by antral pH below 3: this is via physiological role of somatostatin. Enterogastrones hormones that respond to digestive products in the duodenum) releases from the small intestine in response to acid, hypertonic solutions, fatty acids, monoglycerides
What is the central mechanism of feedback control of gastrin secretion
Somatostatin release from D-cells via paracrine and endocrine pathways
Describe the role of the gastric phase in the control of gastrin secretion
Via pH-H+ stimulation of D cells (which increases the inhibitory effects of somatostatin)
Describe the role of the intestinal phase in the control of gastrin secretion
Via enterogastrones that enter into the circulation- those stimulating gastric D cells: gastric inhibitory peptide (from K cells) released by e.g. fatty acids and secretin released from S-cells by H+
What inhibit gastric G and gastric P cells
Cholecyctokinin (CCK) released from I-cells e.g. by fatty acids, amino acids have a more direct inhibitory effect on G cells and P cells, somatostatin released from D-cells by e.g. glucose, fats. NB: integrated effect on acid production both in terms of stimulation and inhibition
What are the functions of the exocrine pancreas
Alkaline and enzyme rich fluid into the GI tract
What are the two major components of pancreatic juice
Aqueous and enzymatic
What nature does the pancreas have
A lobular nature
What cells does the exocrine pancreas consist of
Acinar cells
What do acinar cells produce
Enzymes, HCl and most enzymes in an inactive from so that the pancreas doesn’t autodigest
What part of the pancreaseis responsible for producing bicarbonate
The duct cells
What is bicarbonate in the pancreas needed for
Neutraliation of HCl that enter the duodenum from the pyloric sphincter
How does the pancreas release substances into the duodenum
From the common bile duct via the sphincter of Oddi
What is the duct of santori and why is it important
An axillary duct which is important when considering blockages of the ducts
Describe the intestinal phase of pancreatic secretion
Responsible for the majority of stimulation. Secretin is secreted by the S-cells in response to the presence of acid in the duodenum
What is pancreatic juice
Enzyme-rich secretions from acinar cells and bicarbonate rich fluid secreted by duct cells
What is the role of secretin
Stimulating bicarbonate release from the duodenum and inhibits acid release from the stomach (integrated nature of the control of the GI tract)
What are responsible for parasympathetic stimulation of the pancrease
CCK and ACh
What do CCK and ACh do in the pancreas
Stimulate acinar cells to secrete enzyme and Cl- rich secretion
What does the release of chloride into the acinus form
A hypertonic solution
What does the fact that ducts are water soluble mean
Have isosmotic solution (different to saliva cells)
Describe the aqueous component of pancreatic juice
High in bicarbonate, composition depends on rate of secretion
Describe the enzymes in pancreatic juice
Stored in acinar cells- zymogen granules (are acidic which helps keep enzymes inactive)
How do the duct cells modify primary acinar secretions
Enzyme carbonic anhydrase, on the apical membrane have bicarbonate chloride exchanger, have sodium hydrogen exchanger on basolateral membrane
What do duct cells utilize to modify primary acinar secretions
Intracellular: carbonic anhydrase
Apical: HCO3-/ Cl- exchange
Basolateral: Na+/ H+ exchange
What effect does secretin have on the duct cells
Stimulates HCO3-/ Cl- exchange via activation of Gs leads to increase PKA activity which phosphorylates Cl- channels (cystic fibrosis transmembrane regulator).
What do the effects on duct cell antagonists result in
An increase in bicarbonate rich fluid
How does the juice composition changes with stimulation of flow rate
As rate of secretion increases the concentration of chloride ions decreases, and the concentration of bicarbonate increases. The concentration of chloride ions decreases as chloride ions are used in exchange for HCO3-.
At around 140mmol HCO3-= acidity of HCl and therefore neutralisation occurs.
What effects does the cephalic phase have on the pancreas
Acinar cells and duct cells via parasympathetic vagal efferent nerves
What effects does the gastric phase have on the pancreas
Acinar cells via release of antrum gastrin (G-gastrin is structurally similar to CCK and therefore acts on the same receptor). Acinar and duct cells via vago-vagal gastro-pancreatic reflex
What effects does the intestinal phase have on the pancreas
70% of total secretion (largest stimulation). Acinar cells- CCK stimulates enzyme rich fluid. Duct cells- secretin increases bicarbonate rich fluid.
Secretin and CCK (hormone in blood) potentiates (increases power) each other as secretory effects
Dsecribe the actions of CCK in relation to the pancreas
CCK contracts the gall bladder and relaxes the sphincter of Oddi.
When would gall stones causes pain after a meal
CCK is released 2-3 hours after a meal therefore gallstones would result in increased pressure and pain 2-3 hours after a meal
Describe the pentagastrin test
Looks at stomach acidity levels and can detect a specific autoimmune disease (medullary thyroid carcinoma) where the parietal cells have been damaged
What is bile formed from
Cholesterol- forms primary bile acid
How are bile salts reused many times
Recycled from the terminal ileum back to the liver, about 3g circulates 8x per day
Describe bile secretion
94% of bile salts that enter the
intestine are reabsorbed (solid line= conjugated bile salts, broken line = deconjugated bile salts)
What role does the gall bladder play in relation to bile
Acts as a reservoir, it concentrates bile and empties mainly by CCK
Where are bile salts stored when the sphincter of Oddi is closed
Gall bladder
What does the gall bladder do
Holds 50-60ml of fluid, it removes sodium and chloride, and water moves with the ions resulting in the crystallisation and precipitation of bile salts
What is the major factor in regulation of bile secretion
Return of bile salts. Secretion of bicarbonate-rich watery fluid by ductal cells enhanced by secretin (secretin is produced due to acidity in the duodenum and therefore neutralisation is needed so duct cells are stimulated to produce a bicarbonate rich fluid)
Describe cholesterol gall stones
Excess cholesterol results in crystal formation, these act as nuclei for Ca2+ and PO4 salts
Describe bilirubin excretion
With glucuronic acid (bilirubin is a breakdown product of haemoglobin and is conjugated with glucuronic acid)
Describe jaundice
Raised plasma bilirubin, yellow colouration eyes and sclera and itchy feeling of skin due to irritant nature of bilirubin
What are the two mechanisms of bile secretion
BAD- bile acid dependent 1. BAI- bile acid independent 2.
Describe BAD
Bile acid dependent 1- depends on the rate of bile acid return
Describe BAI
Bile acid independent 2- secretion of electrolytes and water by hepatocytes and duct cells
Describe bile acid secretion
Nutrient rich fluid enters into the sinusoids where it is processed across the liver cells, then get formation of bile moving down into the bile ducts. Sodium dependent transporter transports bile salts into the hepatocytes and the bile salts the exit through the canaliculus
What do choleretic do
Increase the rate of bile secretion
What do cholagogues do
Increase the flow of bile via emptying of gallbladder e.g. contracting the gallbladder
What effect does secretin have on ductal cells
Stimulation. Produces bicarbonate rich watery fluid
