0205 - Gastric Secretions Flashcards

1
Q

What are the primary active constituents of saliva?

A

Lingual lipase and salivary amylase, secreted by tongue and salivary glands respectively.

Also contains: mucins (lubrication) lysozyme (break down bacterial cell wall) lactoferrin (bind iron, bacteriostatic) Proline rich proteins, (protect teeth and bind tannins)

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2
Q

What are the functions of saliva?

A

Lubricate food to form a bolus and facilitate swallowing.

Act as a solvent to facilitate taste

Act as a lubricant to facilitate speech.

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3
Q

Where does saliva come from?

A

Secreted by salivons, crypts in the glands.

Parotid = 25%, watery secretion

Sublingual = 5%, viscous secretion

Submandibular = 70%, mixed secretion

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4
Q

Why does saliva osmolarity increase with production rate?

A

Primary saliva has a similar composition to plasma, and is altered to become hypotonic.

As production rates increase, the process to make it hypotonic lags behind the production rate, thereby increasing osmolarity.

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5
Q

What is the electrolyte composition of saliva?

A

Predominantly Na and Cl, with HCO3- and K+ as well.

Na and Cl are resorbed into the cell, and HCO3- and K+ are excreted. However, final saliva is still much higher in NaCl than the other two.

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6
Q

What are the most important cells for gastric secretions? What is the location and function of each?

A

Parietal cells (Corpus only) - H+ and Intrinsic Factor

Chief Cells (Corpus and antrum) - Pepsinogens

Endocrine Cells (mostly antrum, some corpus) - Gastrin (G cells, antrum only), Somatostatin (D cells, corpus and antrum)

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7
Q

Briefly outline stomach parietal cells.

A

Produce acid and intrinsic factor.

Abundant mitochondria (lots of ATP needed for acid)

When activated, open canaliculi greatly increase surface area to allow more pumps to secrete acid into lumen.

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8
Q

What is intrinsic factor?

A

Glycoprotein that binds to vitamin B12 (cyanocobalamin), and is essential for endocytosis of B12 in the small intestine.

Thus, gastrectomy or autoimmune destruction of cells may eventually (years) lead to Vit B12 deficiency and pernicious anaemia.

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9
Q

Describe the process of stomach acid secretion

A

Takes place in the Corpus only.

H+/K+ ATPase (active exchanger) in the luminal membrane pumps out H+ in exchange for K+, which returns to lumen via a luminal K+ channel.

H2O dissociates, providing H+, and CA forms HCO3- with CO2. HCO3- exchanges with extracellular Cl, which then exits to lumen (giving HCl).

Other H+ from H2O exits via Na/H exchanger, and Na leaves via Na/K-ATPase, providing K required by H/K-ATPase.

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10
Q

How much gastric juice is produced per day?

A

Stomach glands produce 2L/day of isotonic fluid.

Acid production takes place in the corpus only.

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11
Q

What 3 substances induce gastric acid secretion? How do they work?

A

ACh (from ENS) - directly and indirectly

Gastrin (from G-cells) - directly and indirectly

Histamine (from ECL cells) - directly.

Directly - straight onto parietal cell.

Indirectly - onto ECL cell, stimulating histamine.

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12
Q

How is gastric acid secretion regulated?

A

Secretagogues:

ACh, Histamine (via H2), and Gastrin (via CCKb) all act as direct secretagogues. ACh and gastrin both also act indirectly by activating ECL cells to produce histamine.

Inhibitors:

Somatostatin (from endocrine D cells in corpus and antrum) is primary inhibitor, working both directly and indirectly.

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13
Q

Name two drugs that can reduce acid secretion.

A

Omeprazole (blocks H/K-ATPase)

Cimetidine (antagonist of H2 histamine receptor) - ACh and Gastrin still have an effect.

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14
Q

What is the role of Somatostatin?

A

Major inhibitory mechanism of gastric acid secretion. Made by endocrine D-cells in corpus and antrum. Acts directly and indirectly.

Directly - Binds to SS receptors on parietal cells (inhibiting effect of histamine). Is both endocrine (if produced in antrum) and paracrine (if from Corpus), as parietal cells are only found in Corpus.

Indirectly - In corpus, reduces histamine release from ECL cells. In antrum, reduces Gastrin release from G-cells.

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15
Q

Briefly outline gastrin.

A

Purpose is to stimulate acid secretion and gastric mucosal growth. Released in the antrum and duodenum via gastrin-releasing peptide. Release controlled by ENS, as well as stomach wall stretching and protein fragments in stomach.

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16
Q

What are the four phases of gastric acid secretion?

A

Basal - inter-digestive phase (i.e. most of the time)

3 distinct phases during a meal

Cephalic - (Vagus-mediated, 30% of acid secretion)

Gastric (Gastrin-mediated, 50-60% of acid secretion)

Intestinal (5-10% of acid secretion)

17
Q

Briefly outline the cephalic phase of gastric acid secretion.

A

Activated by sight, smell, taste, thought of food, and swallowing. Commences before food reaches stomach. Four distinct phases:

  1. Direct stimulation of parietal cells (ACh-mediated)
  2. Release of histamine from ECL cells (ACh-mediated)
  3. Release of gastrin from G-cells (gastrin-releasing peptide mediated)
  4. Decrease in somatostatin release from D-cells (ACh-mediated)
18
Q

Briefly outline the gastric phase of gastric acid secretion.

A

Entry of food causes 2 stimuli for H+ secretion:

  1. Distension of gastric wall - (corpus and antrum) activates vagovagal reflex (same as cephalic response) and local ENS reflex (ACh-mediated activation of parietal cell).
  2. Partially digested proteins (peptones) stimulate antral G-cells.
19
Q

Briefly outline the intestinal phase of gastric acid secretion.

A

Stimulated by peptones and amino acids in proximal small intestine.

  1. Peptones stimulate duodenal G-cells (gastrin release)
  2. “Entero-oxyntin” stimulates parietal cells.
  3. Absorbed amino acids stimulate H+ secretion by an unknown mechanism.
20
Q

Briefly outline the basal state of gastric acid secretion.

A

Takes place most of time, following circadian rhythm (lowest in morning, highest in evening). Secretion proportional to number of parietal cells, with high variability in basal state (pH3-7).

21
Q

How can the intestine reduce gastric acid secretion?

A

Intestinal chyme during gastric phase inhibits gastric acid secretion (Reverse enterogastric reflex). This slows down release of chyme from the stomach, allowing intestine to properly absorb it.

22
Q

What is pepsinogen? Briefly outline pepsinogen secretion

A

Pepsinogens are zymogens (inactive enzymes) that initiate protein digestion. Secreted by chief cells in response to Secretin (via cAMP), or ACh/Gastrin/CCK (via Ca++). They are released by compound exocytosis (two vesicles are joined in the cytoplasm and then exocytosed). It then needs to be activated.

23
Q

How is pepsin activated?

A

Need to cleave an N-terminal fragment, which can only happen at pH less than 5 (i.e. acid secretion). Lower the pH, more cleavage. Presence of pepsin results in even more acid, catalysing more pepsinogen to pepsin. Ideal pH 1.8-3.5, irreversibly inactivated at pH >7.2.

24
Q

What are the 3 broad categories of intestinal secretions?

A

Mucus (rich in HCO3-)

Electrolytes

Water

25
Q

What are the duodenal secretion/s? What produces the secretion/s?

A

Brunner’s Glands secrete mucus rich in HCO3-. Mucous protects duodenum from gastric acid and HCO3- helps to neutralise it.

26
Q

What cells produce the secretions of the small intestines?

A

Goblet cells - produce mucus.

Enterocytes - secrete water and electrolytes at slightly alkaline pH - fluid secretion at similar rate to absorption.

Basically no enzymes are secreted, but are present in the brush border of mucosal enterocytes.

27
Q

What are the secretions of the large intestine? What is the purpose of the mucus?

A

Richer in mucus and smaller in volume than small intestine. Rich in K+ and HCO3- (pH 8.0). Mucus protects against abrasion, adheres fecal matter, and together with alkalinity, protects against fecal bacteria.