M104 T1 L5 Flashcards
How much fluid is secreted into the GI tract each day?
approx 7 litres
What happens to the majority of secreted fluid in the GI tract?
it will be reabsorbed as the contents moves through the GI tract
After reabsorption of secreted fluid in the GI tract, how much is actually excreted daily?
about 100 mls
What is the pH of salivary secretions?
pH 6-7
What are the three Major salivary glands?
Parotid
Submandibular
Sublingual
Where are dispersed minor salivary glands?
throughout the mucosa of the mouth and tongue
these occur in the in the lips, cheeks, palate and in the tongue
Where is the parotid gland located?
anterior and inferior to the ear
between the skin and the muscle
Where is the duct of the parotid gland located?
it enters the oral cavity just above the second molar
What does the parotid gland secrete?
Serous, watery secretions containing salivary amylase for starch digestion
What does the submandibular gland secrete?
a mixture of serous and mucus containing saliva
Where is the submandibular gland located?
inferior to the mandible
Where is the duct of the submandibular gland located?
lateral to the lingual frenulum
Where is the sublingual gland located?
in the floor of the oral cavity
What does the sublingual gland secrete?
thicker mucus dominant secretions for lubrication
Where is the duct of the sublingual gland located?
they enter the oral cavity under the tongue
What type of cells does the sublingual gland contain?
mucin secreting cells
What percent of saliva is produced by the parotid and submandibular glands?
90%
What percent of saliva is made up of water?
99.5%
What is the purpose of water in saliva?
acts as a solvent which dissolves components of the food to aid in taste
helps with swallowing, initiation of digestion, oral hygiene - keeps bacterial load down in the oral cavity
What is the purpose of electrolytes in saliva?
have a buffering capacity, particularly for acidic foods in the oral cavity
What are key enzymes in saliva? (LacLAK)
Lactoferrin Lysozyme Lingual lipase (serous salivary glands of tongue) a-amylase Kallikrein
What is the role of a-amylase in saliva?
digests starch via hydrolysis of the a-1,4 glycosidic bonds
What three substances does a-amylase degrade starch into?
disaccharide maltose
trisaccharide maltotriose
a-dextrin
Up to what percentage of starch digestion can occur through the action of amylase?
75%
When does amylase stop digesting starch?
when it’s neutralised by the acidic pH of the stomach
What is the role of a-amylase in digestion?
to hydrolyse peptidoglycans in the wall of gram negative bacteria so it can keep the level of bacteria in the oral cavity down
What is the role of lingual lipase in digestion?
to hydrolyse lipid triglycerides to fatty acid and diglycerides
What enzymes are produced by von Ebner glands ?
lingual lipase
amylase
What are the optimal conditions for lingual lipase?
acidic pH
What is the role of Lactoferrin in digestion?
has anti-microbial properties through the chelation of iron to prevent microbes from multiplying
What is the role of Kallikrein in digestion?
converts plasma protein a-2- globulin into bradykinin
What is the role of Secretory IgA in digestion?
it prevents microbial attachment to epithelium
What is the role of myoepithelial cells?
they surround the acinar cells and are contractile in nature
they help to drive the primary secretions along the duct
What is the role of ductal cells?
modifying primary saliva
What are the unique properties of salivary glands?
there is a large volume of saliva produced compared to mass of gland
the saliva produced has a low osmolarity compared to blood plasma
there is a relatively high K+ concentration
What happens in Stage 1 of hypotonic saliva formation?
an isotonic plasma-like saliva, which contains water, electrolytes and enzymes, is secreted into a salivary duct by acinar cells
What happens in Stage 2 of hypotonic saliva formation?
as the saliva moves along the duct lumen, ductal cells secrete HCO3- and K+ ions and reabsorb NaCl, all through membrane transporter proteins
produces a HCO3- and K+ rich hypotonic saliva
What are the ions in NaCl reabsorbed in exchange for in Stage 2 of hypotonic saliva formation?
Na+ reabsorbed in exchange of K+
Cl- reabsorbed for carbonate ions
What is a consequence of the salivary duct being relatively impermeable to water?
AAR there is limited movement of water by osmosis out of the duct lumen following NaCl reabsorption
What is the effect of the formation of hypotonic saliva?
the production of a K and bicarbonate-rich hypotonic saliva compared to plasma and the interstitial fluid
What is composition of saliva and can this change?
the composition of saliva is always hypotonic
but it can change with flow rate
What is the electrolyte composition of saliva at a high rate of secretion compared to that of saliva at a low rate of secretion?
Na+ & Cl- are always low
K+ & HCO3- are high
What happens during a low rate of secretion?
there is a maximum reabsorption of electrolytes
hypotonic saliva is produced
What are the electrolytes like in hypotonic saliva?
lower concentration of osmotically active electrolytes
What happens during a high rate of secretion?
there is reduced reabsorption of electrolytes
alkaline, HCO3- rich saliva is produced
What is the osmolality like in hypotonic saliva?
has an increased osmolality closer to that of primary isotonic saliva
How is salivary secretion innervated?
by the autonomic NS parasymp stimulation (more important) symp (less)
What happens when there is a stimuli for salivation?
a signal is created via thesalivatorynuclei in the medulla
different nerves are stimulated for the activation of different glands
Which two glands does the facial nerve supply?
sublingual
submandibular
Which gland does the glossopharyngeal nerve supply?
the parotid gland
What is the effect of parasympathetic stimulation on the salivary glands?
Increase salivary secretion
increases vasodilation
increases myoepithelial cell contraction
What are the inhibitors of salivary secretion?
fatigue, sleep, fear, dehydration
What is the effect of the symp NS on salivary secretion?
secretion rate increases
saliva is higher in mucin and enzymes
What nerve conveys symp NS action to the salivary glands?
superior cervical ganglion
How is an initial vasoconstriction activated in the salivary glands?
noradrenaline is released
it stimulates alpha adrenergic receptors on the blood vessels surrounding the glands
How is a later vasodilation activated in the salivary glands?
the kallikrein enzyme is released
it goes on to act on a-2 globulin
it forms the vasodilator bradykinin - results in vasodilation
What are two examples of conditions associated with salivary gland dysfunction?
Sjögren’s syndrome
Xerostomia
What are the effects of Sjögren’s syndrome?
commonly affects tear and saliva production
dry eyes and dry mouth
(destroys exocrine glands)
What are the effects of xerostomia?
dry mouth
bacterial overgrowth
What can bacterial overgrowth in the oral cavity cause?
dental caries
halitosis
What can a dry mouth cause?
inadequate lubrication of the oral cavity
difficulty speaking
difficulty swallowing solid food
What do gastric pits branch into?
gastric glands
What type of cells do gastric glands contain?
secretory cells
What is the role of exocrine cells?
responsible for excreting the components of the gastric juice
What is the role of mucous neck cells?
secrete a thin mucus
joins mucus secreted by surface mucus cells
What is the role of parietal cells?
secretes HCl and IF
What substances do chief cells secrete?
pepsinogen
rennin
gastric lipase
What are the three types of exocrine cells?
mucous neck cells
parietal cells
chief cells
What endocrine cells are present in gastric glands?
G cells
What two types of cells are present in gastric glands?
endocrine cells
exocrine cells
What do G cells secrete?
the hormone gastrin
What do ECL cells secrete?
histamine
Where are the two main types of gastric glands?
(80%) gastric/oxyntic glands - body and fundus
(20%) pyloric glands - antrum
What are the exocrine secretions of the gastric/oxyntic glands into the body and fundus of the stomach?
HCl, IF
pepsinogen
mucus
What substances are secreted by the paracrine glands in the body and the fundus of the stomach?
histamine by ECL cells
somatostatin by Delta cells
What substances are secreted by the pyloric glands in the antrum of the stomach?
mucus gastrin (endocrine) somatostatin (endo and exocrine)
What are the components of gastric juice?
Water and electrolytes Mucus (glycoprotein mucin) Pepsinogen pro-enzyme Rennin in neonates only Gastric lipase HCl (pH 1-3) IF
What is the role of water and electrolytes in gastric juice?
they act as a medium for the action of assets and enzymes
they allow for the digestion of organic substances to occur
What is the role of mucus in gastric juice?
protective function - coats the surface of the stomach
protects it from the harmful effects of acid and the enzyme pepsin
What is the role of Pepsinogen pro-enzyme in gastric juice?
cleaves peptide bonds (protein to smaller peptides)
What is the role of renin in gastric juice?
coagulates milk through casein proteolysis
What is the role of Gastric lipase in gastric juice?
converts triglycerides to fatty acid and diglycerides
What do parietal cells secrete?
HCl and IF
What is the pH of the stomach?
pH 1 - 3
What are the roles of HCl in the stomach?
converts pro-enzyme pepsinogen to pepsin
denatures proteins
kills microorganisms
What is the role of IF in the stomach?
allows for the absorption of vitamin B12 in the ileum
What is vitamin B12 used for?
erythropoiesis in the bone marrow
What condition is caused by a vitamin B12 deficiency?
pernicious anaemia
What is the structure of parietal cells?
an intracellular branched canalicular structure
are packed with tubulovesicles in resting state
What are parietal cells packed with?
mitochondria
tubulovesicles
What do the tubulovesicles in parietal cells contain?
carbonic anhydrase
other enzymes
HK-ATPase
What happens to tubulovesicles when the cell is stimulated to produce acid?
they fuse with the canalicular membrane to form microvilli
HCl is formed at these microvilli and secreted
Where are tubulovesicles located?
on the apical membrane
How is acid secreted into the gastric lumen from parietal cells?
its driven by the presence of a H / K - ATP proton pump in the apical membrane of the parietal cell
it drives the active secretion of H+
HCO3- exchanged for Cl- in the basal lateral membrane of the parietal cell
causes an alkaline tide - when the gastric venous blood becomes alkaline postprandially
Cl- diffuses into lumen
Where are hydrogen ions derived from?
from the activity of carbonic anhydrase
when it catalyses the formation of bicarbonate ions from co2 and water
What are the three major routes by which gastric acid is secreted?
ACh release
gastrin release
histamine release
How does gastrin release result in the secretion of gastric acid?
is released from G cells
enters the bloodstream
returns to parietal cell membrane
What is the effect of vagal innervation on gastric acid secretion?
results in the secretion of ACh
this regulates hydrogen secretion
What is the effect of histamine release on gastric acid secretion?
released from ECL cells
histamine binds to the H2 receptors on the parietal cell membrane
How do all gastric acid secretion pathways work?
by second messenger intracellular pathways
What is the chain of events by which gastrin and ACh trigger HCl secretion from parietal cells?
activate PLC
catalyses the formation of IP3
causes the release of intracellular calcium stores
histamine binds to the H2 receptor
it activates adenylate cyclase to form cAMP
activates protein kinase
this ultimately triggers acid secretion from the parietal cell
What substances interrupt stages of the parietal cell acid secretion pathway?
somatostatin
mucosal prostaglandin
How does somatostatin reduce acid secretion from parietal cells?
it works as an antagonist against histamine at the H2 receptor
How do NSAIDs increase acid secretion from parietal cells?
they inhibit somatostatin (antagonist against histamine)
so secretion increases
How do prostaglandins interact with the parietal cell acid secretion pathway?
released by D cells to inhibit AC (adenylate cyclase)
so they stop histamine from causing acid secretion
What three pharmalogical drugs inhibit gastric acid? (OCA)
Omeprazole
Cimetidine
Atropine
What is the role of the H+/K+-ATPase?
proton pump - to pump out H+ of the acid from parietal cells into the gastric lumen
What drug inactivates the H+/K+-ATPase proton pump?
Omeprazole
What is the effect of Cimetidine?
it inhibits stimulus for acid secretion
it antagonises the activity of histamine at the H2 receptor
What is the effect of Atropine?
it inhibits muscarinic receptors and vagal stimulation of acid secretion
What is the secretion of gastrin triggered by?
vagus nerve
distention of the stomach
the presence of partially digested peptide fragments
How does gastrin increase the rate of digestion once released into circulation?
it acts on parietal cells and chief cells to upregulate the secretion of acid and pepsinogen
it is responsible for lower oesophageal sphincter contraction
it increases motility in the stomach for mixing and peristalsis
it relaxes the pyloric sphincter so that the contents of the stomach move into the duodenum
What are the three phases of gastric secretion?
Cephalic
Gastric
Intestinal (excitatory & inhibitory)
What type of innervation is cephalic gastric secretion regulated by?
vagal innervation - the sight, smell of food
What triggers the “gastric” phase of gastric secretion?
once the bolus hits the stomach
What is the effect of the vagus relating to cephalic gastric secretion?
it stimulates the production of gastric juice by parietal and chief cells
it stimulates the production of the hormone gastrin
What type of innervation is “gastric” secretion regulated by?
local neural secretatory reflexes
vagal stimulation
What is the effect of “gastric” secretion?
promotes the secretions of parietal, chief, mucal and G cells
How does “gastric” secretion stimulate parietal cells?
directly
indirectly - via ECL histamine release
What are the two types of intestinal gastric secretion phase?
Excitatory
Inhibitory
What triggers the intestinal phase of gastric secretion?
when chyme enters the duodenum
What happens during the excitatory intestinal phase of gastric secretion?
when chyme is pH3 or more, peptides in the duodenum will stimulate gastric secretions via vagus and gastrin
What happens during the inhibitatory intestinal phase of gastric secretion?
when chyme is pH2 or less
mechanical distention
the presence of protein breakdown products
the presence of hypo/hyper-osmotic products
What substances inhibit gastric secretion during the inhibitatory intestinal phase? (CGS)
CCK
GIP
Secretin
Why is the gastric mucosa not damaged by the presence of pH1 and peptide digesting enzymes?
viscous mucosal barrier
tight paracellular junctions
What is the mucus layer of the gastric mucosa made by?
the glands in the surface mucous secreting it
What is the main gastric mucosa made up of?
mucopolysaccharides
proteins
How does the mucus layer in the gastric mucosa help to neutralise hydrogen ions?
the basic side chains in mucin
the HCO3- secreted from surface epithelial cells
How do tight junctions between epithelial cells help to protect the gastric mucosa?
they act as a barrier to any acid moving paracellularly and damaging the underlying cell surface
What is the barrier like that protects the gastric mucosa from damage?
there is an unstirred mucus layer of pH 7
pepsinogen is not activated so it prevents enzymatic and chemical damage
What condition is triggered when the gastric mucosal barrier fails?
Gastritis
What is gastritis most commonly caused by?
an infection by the bacteria Helicobacter pylori
What is the primary cause of peptic ulcer disease?
the bacteria Helicobacter pylori
Why is Helicobacter pylori bacteria in the gastric mucosal barrier a problem?
Gram negative bacteria produce urease which forms ammonia from urea
Ammonia neutralizes bactericidal acid and is toxic to mucosal barrier
What are the less common causes of gastritis?
smoking, large amounts of alcohol
NSAIDs
chronic stress
How do NSAIDs cause gastritis?
they inhibit COX to reduce the synthesis of acid regulatory prostaglandin
What occurs when the gastric mucosal barrier has sustained acute damage?
rapid regeneration via restitution - rapid division of stem cells located in the neck of gastric glands
What is Autoimmune atrophic gastritis caused by?
the antibody mediated destruction of gastric parietal cells
What are the effects of autoimmune atrophic gastritis?
hypochlorhydria
IF deficiency
What type of cells release somatostatin?
delta cells
Where are delta cells located? (SIP)
stomach
intestine
pancreatic islets
How is the somatostatin hormone circulated from delta cells?
paracrine - acts locally
endocrine - systemic via bloodstream
What substances are inhibited when somatostatin is released from the hypothalamus?
growth hormone and TSH
What substances are inhibited when somatostatin is released from the pancreas?
pancreatic hormones such as insulin and glucagon
What are the cells in the pancreas?
alpha beta delta exocrine (duct and acinar cells) f cells
What do alpha cells secrete?
glucagon
What do beta cells secrete?
insulin
What do acinar cells secrete?
digestive enzymes
What do f cells cells secrete?
pancreatic PPTs
What is the main role of Histamine 2 receptors?
to stimulate gastric acid secretion
What are some of the roles of H2 receptors?
to stimulate gastric acid secretion
to regulate GI motility
to regulate intestinal secretion
What are alpha2 globulins involved in?
inflammation
What are beta globulins involved in?
transporting substances
immunity
What is the difference between endocrine and exocrine glands?
exocrine - secretes to an epithelial surface
endocrine - secrete directly into the bloodstream
What is the effect of ACh on
vasodilation, slows HR
increases bodily secretions
contracts SMOOTH muscles
What NS is ACh an NT of?
parasymp NS
Which NT do cholinergic neurons mainly use?
ACh
What does AChE hydrolyse ACh into?
acetic acid and choline
What are the symptoms of a cholinergic crisis?
SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis)
What area does [the upper (“neck”) region of the fundic glands] actually refer to?
near the glands’ openings into the bottoms of gastric pits
What is the main role of gastric inhibitory peptide?
to stimulate insulin secretion
What is the largest salivary gland?
the parotid glands