Lecture 5 and 6: Integrated Response to a Meal - The Gastric Phase Flashcards by B 32

What are the major functions of the stomach

1) Storage
2) Secretion (H+, IF, mucus, HCO3, water)
3) Motor activity (mixing)
4) Coordination of emptying

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What does intrinsic factor do?

absorbs vitamin B12

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What is responsible for regulating motor and secretory functions of the stomach?

Neural, endo and paracrine

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What is the paracrine signaling to the stomach?

Histamine (signals to release H+)

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What is the endocrine signaling in the stomach?

1) Gastrin (from stomach and duodenum) stimulate gastric acid secretion
2) Somatostatin (stomach, duodenum, pancreas) INHIBITS gastric secretion

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What are the 2 secretions at the two ends of the stomach (cardiac and pyloric sphincters)?

1) mucus

2) HCO3

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Where does mixing and grinding of food in the stomach occur?

Antrum and pylorus region

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What is the function of the fundus and body of the stomach?

reservoir (storage)

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The lining of the stomach contains _______ epithelium

columnar (folded into gastric pits where glands empty)

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What are the 6 types of secretory cells in the stomach?

1) Parietal (HCl and IF)
2) Mucous neck cells (mucus)
3) Chief cells (pepsinogen)
4) Enterochromaffin-like cells ECL (histamine –> stimulates HCl)
5) D cells (somatostatin –> inhibits HCl secretion)
6) G cells (Gastrin –> HCl secretion)

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Where are G cells found?

stomach AND duodenum

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What are the 4 major gastric secretions?

1) HCl
2) Pepsinogen
3) HCO3 and mucus
4) IF

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What secretion is the only ESSENTIAL component of gastric juice? (the others are redundant)

Intrinsic factor

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What is the hallmark of a resting parietal cell?

Tubulovesicular system = cytoplasm with many tubules and vesicles (membranes have transport proteins for secretion of H+ and Cl-)

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What happens to the tubulovesicular system in the activated parietal cell?

fuses with plasma membrane of secretory canaliculi and opens to lumen of the gland

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What is the importance of intracellular carbonic anhydrase?

converts H2O and CO2 into H2CO3 which then dissociates into H+ and HCO3

that H+ is needed to be secreted by parietal cells

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What transporter carries H+ ions across the luminal membrane in the parietal cells?

H+/K+ ATPase (K comes in, H goes out)

ACTIVE PROCESS (ATP driven because both ions are going up their conc gradient)

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What does omeprazole do?

block the H/K transporter to reduce acid secretion

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How does Cl leave the parietal cell to enter the lumen?

Cl channels

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How does cAMP and intracellular Ca++ levels influence Cl conduction?

increased cAMP and int. Ca++ increases Cl and K conduction

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On the basolateral membrane, how does HCO3 get into the blood?

Cl/HCO3 exchanger (Cl into the cell, HCO3 out of it)

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Why is venous blood alkaline after a meal?

increased HCO3 absorption due to increased HCl secretion

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What else do surface epithelial cells of the stomach secrete to contribute to alkaline blood?

watery fluid of Na, Cl, K, and HCO

Na and Cl concentrations are similar to plasma but K and HCO conc are higher

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Mucus is 80% what biomolecule?

carbohydrates

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What is the basic unit of mucus and what is its shape?

Mucins; glycoprotein tetramer (which has vulnerable central portion susceptible to proteolytic digestion by pepsins)

What two substances are responsible for protecting the surface of the stomach from H+ and pepsin?

1) mucus | 2) bicarb

What makes up the gastric mucosal barrier?

protective mucus layer and alkaline secretions trapped within it (that bicarb neutralizes the H+ so it cannot hurt the epithelia)

What does heliobacter pylori do the the stomach?

pokes holes in the epithelia so it damages the cells (doesn't affect the secretions, per se, but hurts the cells)

What is the strongest stimulant for gastric H+ secretion?

PARASYMP via vagus (stimulates parietal, ECL and G cells) acetylcholine

What are the 3 things that stimulate H+ secretion by parietal cells?

1) Ach (neuro) 2) Histamine (paracrine) 3) Gastrin (endocrine)

Ach acts via _________ receptors on the parietal cells to stimulate H+ release

muscarinic

the secondary messengers of Ach H+ stim are_______

IP3 and Ca++

Histamine is released from _______ cells

ECL

The secondary messengers of histamine H+ stim are _____

cAMP

Which drug blocks Ach stimulation of parietal cells? Histamine stimulation of parietal cells?

Atropine; cimetidine

Histamine works via ____ receptors on the parietal cells to elicit H+ release

Gastrin works via _______ receptors on the parietal cells to stimulate acid release

CCKB (aka CCK2)

The secondary messengers of gastrin H+ stim are ______

IP3 and Ca++

Define potentiation

The observation that the rate of acid secretion can be regulated by Ach, histamine, and gastrin independently AS WELL AS by interactions among the 3

Which two signals on the parietal cells share the same secondary messengers?

Ach and gastrin (IP3 and calcium)

What ramifications does potentiation have for certain treatments?

cannot target just one since it will affect the others (ex: cimetidine doesn't stop just histamine but also the histamine-potentiated effects of Ach and gastrin)

During the cephalic and oral phase, _____ of total HCl is secreted

30%

During the cephalic and oral phase, HCl secretion is both direct and indirect. What is direct and what is indirect?

1) DIRECT: Vagus Ach 2) INDIRECT: G cell stimulation by Vagus via Gastrin-releasing peptide (GRP) ECL cell stimulation by Vagus (Ach) and gastrin (CCKB) to produce histamine

What are the 2 effects of gastrin?

1) DIRECT: binds to CCK receptors on parietal cells | 2) INDIRECT: stimulates ECL cells

During the gastric phase, _____ of total HCl is secreted

60%

What are the 3 stimuli for HCl secretion in the gastric phase?

1) distention of stomach 2) presence of amino acids 3) small peptides

What are the 2 new mechanisms present here that are not found during the cephalic and oral phases?

1) distention of stomach activating vagovagal reflex (stimulating gastrin release) 2) direct effect of AA and small peptides on G cells (stimulating gastrin release)

Alcohol and caffeine ________ (stimulate/inhibit) HCl secretion

stimulate

During intestinal phase, ____ of total HCl is secreted

10%

What is the signal responsible for triggering the negative feedback inhibition of acid secretion?

acidic chyme in the distal stomach (antrum)

What hormone responds to low pH in the distal stomach?

somatostatin

Which cells produce somatostatin?

D cells (somadddddostatin)

What are the direct and indirect ways somatostatin inhibits acid release?

DIRECT: binds to receptors in parietal cells and inhibits release of histamine INDIRECT: inhibits histamine release from ECL cells and gastrin release from G cells

What happens to the negative feedback loop in patients on proton pump inhibitors?

it disappears - no proton pump to make stomach acidic, no signal to turn on negative feedback loop

In addition to somatostatins, what else has a negative feedback on acid release?

prostaglandins (inhibit stimulatory effect of histamine)

Pepsin only digests ____% of proteins

What happens to amylase activity in the stomach?

It is inactivated by the low pH unless its active site is occupied by carbs, then it keeps digesting but that work is minimal

Where does digestion of lipids start?

in the stomach (10%) normally very negligible but becomes important in patients with pancreatic disorders

As the stomach progresses from the orad to the caudad region, the wall _______ (thickens/thins)

thickens

Receptive relaxation causes the reciprocal relaxation of what in response to relaxation of the LES?

Orad stomach

receptive relaxation is mediated by what neural input?

vagovagal reflex (mecahnoreceptors sense stomach distention, relay that to CNS then CNS sends efferent to relax orad)

receptive relaxation is mediated by which neurotransmitter?

VIP

What is retropulsion?

the movement most of the bolus takes back towards the orad region of the stomach to get broken down more

What 3 important things does the vagovagal response control?

1) acid secretion 2) distention of gastric wall 3) gastric motility

Parasympathetic innervation via the vagus is ________ (excitatory/inhibitory) in the lower stomach

EXCITATORY

Parasymp promotes increased motility via which neurotransmitters?

Ach and substance P

Does neural input control rate or magnitude of antral contractions?

MAGNITUDE (gastric pacemaker controls rate)

What is the purpose of antral contractions?

to grind food and push it thru the pylorus

Which empties from the stomach faster, glucose or proteins?

Glucose

Isotonic, hypotonic, or hypertonic leave stomach fastest?

ISOTONIC

What size must solids be reduced to in order to pass on thru to the duodenum?

less than 1 cubic mm

Antrum contracts while the initial portion of the duodenum _______

relaxes

What are the 3 functions of the gastroduodenal junction?

1) filter large size particles of food 2) empty gastric content at a rate consistent with duodenum's ability to digest chyme 3) prevent reflux of bolus into stomach

Which two neurotransmitters from the vagal inhibitory fibers promote gastric emptying via pyloric relaxation?

1) VIP | 2) NO

Which promote pyloric constriction, slowing emptying?

NE and Ach | and CCK, Gastrin, GIP, Secretin

What are peptic ulcers?

lesions of gastric or duodenal mucosa caused by erosive action of H+ and pepsin (can be gastric or duodenal)

In gastric ulcers caused by H. pylori, what is the infectious toxin?

cagA (destroys protective barrier)

In gastric ulcer patients, is H+ secretion lower or higher?

LOWER (damaged cells) so gastrin secretion is higher (dont achieve the low pH necessary to turn on the negative feedback)

Duodenal ulcers form because H_ secretion rates are ______ (higher/lower)

higher! so excess H+ is delivered to duodenum overpowering the HCO3 buffering

What is Zollinger-Ellison Syndrome?

gastrinoma in pancreas (secretes lots of gastrin)

Why is high gastrin secretion dangerous?

increases H+ secretion (causing duodenal ulcers) as well parietal cell mass (by increasing cell number)

Why do gastrinomas lead to steatorrhea?

low duodenal pH inactivates pancreatic lipase so lipids are not digested properly

Why does somatostatin not keep the gastrin release in check?

No somatostatin receptors on the tumor in the pancreas

Other than surgically removing the tumor, how else are gastrinomas treated?

proton pump inhibitors (keep the acid secretion in check) cimetidine and omeprazole