Lecture 7 Flashcards

1
Q

What is the gastrointestinal (GI) tract?

A

A continuous muscular digestive tube. Functions change all the way along the tube.

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2
Q

What is the GI tract involved in?

A

Ingestion, Propulsion, Mechanical digestion, Chemical digestion, Absorption, Defaecation

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3
Q

What are the 4 main layers of the GI tract?

A

Lumen in the centre, Mucosa (in contact with lumen), Submucosa, Muscularis externa, Serosa

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4
Q

What are the key features of the mucosa?

A

Innermost epithelial layer, Secretion: mucus, enzymes and hormones, Absorption: digestive end products, Barrier function

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5
Q

What are the key features of the submucosa?

A

Connective tissue, Blood and lymphatic vessels, Neurones

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6
Q

What are the key features of the muscularis externa?

A

Smooth muscle (circular and longitudinal)

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7
Q

What are the key features of the serosa?

A

Protective outer layer –> called the visceral peritoneum

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8
Q

How does the innermost mucosal layer change as you move through the GI tract?

A

In esophagus: Mainly squamous epithelial cells; In stomach: Dark cells = secretory, Has invaginations/pits; In small intestine: Has villus folds to increase surface area for absorption; In large intestine: Increased musculature to push contents through lumen, Water absorption occurs here as well

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9
Q

What are some of the additional functional considerations of the GI tract?

A

Substances in GI tract lumen are essential outside of the body, Multiple sensors and receptors line the GI tract to monitor contents and respond to conditions, Controls: Intrinsic through endocrine secretion (local control), Extrinsic (CNS)

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10
Q

What types of hormones are identified from the gut? How many have been identified and how do they work?

A

Over 2 dozen GI hormones identified, All peptide hormones, Many are also produced in other places, Act in both a paracrine and endocrine way

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11
Q

Describe the structure of the mucosal layer of the stomach

A

Mucosal layer has pits, These are crypt-like structures that extend down into the mucosal layers, There is a change from the epithelial state to more glandular cells at the base of the pits, Chief cells predominate the pits, These produce pepsinogen, Parietal cells secrete HCl, Enteroendocrine cells secrete gastrin

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12
Q

Which endocrine cells are found in the stomach?

A

Chief cells, Enteroendocrine cells, Parietal cells

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13
Q

Why does the stomach mucosa need to be a low pH?

A

Pepsinogen is the inactive form of pepsin, To activate and form pepsin, need acidity, Parietal cells secrete HCl required to make stomach more acidic

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14
Q

What receptors do enteroendocrine cells express? What happens when these are stimulated?

A

They express G protein-coupled receptors (GPCRs), These are homologous to taste receptors, Ultimate effect of stimulating GPCR = calcium influx into cells, This stimulates docking of peptide hormone-containing vesicles in enteroendocrine cell to the cell membrane and allows release of hormone

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15
Q

How many peptide hormones can one enteroendocrine cell secrete?

A

Only 1 type (e.g. have a specific enteroendocrine cell that secretes gastrin)

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16
Q

What do the GPCRs on enteroendocrine cells (taste receptors) recognise?

A

Recognise digestion products of food, e.g products of proteins/lipids/carbohydrates

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17
Q

What do G cells secrete?

18
Q

How does gastrin directly affect parietal cells? What is the effect of this?

A

Gastrin can bind to CCK-2R receptors on parietal cells, This causes parietal cell to alter its H+/K+ exchanger to pump more H+ into the lumen, Increases acidity, The increase in acidity negatively regulates gastrin by acting on G cells to inhibit gastrin secretion

19
Q

How does gastrin indirectly affect parietal cells?

A

Gastrin released from G cells binds to and stimulates CCK-2R expressed on surface of ECL cells, Allows indirect action on parietal cells, Stimulates ECL cells to release histamine, Histamine travels to parietal cells and affects function, Allows indirect regulation of parietal cells

20
Q

What is the trophic effect of gastrin?

A

Gastrin has a trophic function of stimulating growth, Also has effects on gastric motility

21
Q

What are the 2 processes that regulate gastrin and parietal cells?

A

Neural inputs (Cholinergic activation of ECL and D cells in lumen body, Inhibition of D cells in lumen of antrum), Hormonal regulation (Somatostatin –> SS28 peptide produced from D cells)

22
Q

What do D cells do?

A

Produce and secrete somatostatin

23
Q

What is the structure of parietal cells?

A

Odd, canicular membrane shape, Loads of membrane-bound vesicles

24
Q

How does the structure of parietal cells change under stimulation from gastrin/histamine?

A

When cells are stimulated by gastrin/histamine/ACh, huge movement of membrane occurs, Vesicles fuse which shifts the membrane, Causes shift in the membrane and shunts the H+/K+ exchangers to the membrane, Allows them to rapidly pump H+/K+ to increase acidity, Shift in membrane allows microvilli to expand and increase apical surface area

25
What is the secretion point and what is the pH here?
Secretion point = extracellular side of parietal cells, pH can be as low as 0.8 (very acidic)
26
What is the net effect of the ion transport carried out by the parietal cells?
Pumping of H+ and Cl- into the lumen acidifies the environment for pepsinogen to convert to pepsin
27
What is dyspepsia and how can it be treated?
Dyspepsia = indigestion, Caused by excess acid secretion, Can treat with antacids (outdated), Can now target mechanisms of acid secretion (e.g. proton pump inhibitors like Omeprazole)
28
What is intrinsic factor? What is it important in?
Intrinsic factor = glycoprotein required for vitamin B12 absorption in the ileum, Secreted by parietal cells
29
What is the consequence of a lack of intrinsic factor and how can that be caused?
Insufficient vitamin B12 (e.g. due to lack of intrinsic factor) leads to pernicious anaemia, Primary cause of pernicious anaemia = loss of parietal cells and intrinsic factor, Pernicious anaemia can cause gastritis, Careful when targeting drugs to parietal cells as we still need them to secrete certain substances, e.g. intrinsic factor
30
How is gastrin synthesised?
Gastrin = peptide hormone, Synthesized from gene, mRNA is translated to form pre-pro-hormone, Pre-pro-hormone is processed in the ER to form pro-hormone
31
What are the 2 forms of gastrin and when are they primarily seen?
Longer form (G34) seen in fasting, Shorter form (G17) seen after a meal, Longer form is cleaved after the meal to become the shorter form
32
What is a secretagogue? Give an example
A substance that stimulates the secretion of another substance, e.g. gastrin stimulates secretion of histamines from ECL cells
33
What could be used to treat indigestion?
Anti-histamines, Disrupts the gastrin pathway, Counteracts histamine release from ECL cells and prevents it from acting on parietal cells, reduces acid secretion, Not great as they can cross the BBB and make you sleepy
34
In which places does somatostatin have inhibitory actions?
Stomach, Pancreas, Gall bladder, Intestines
35
What effects does somatostatin have in the stomach?
Reduces gastric acid production and pepsinogen secretion from chief cells, Also has paracrine activity
36
What effects does somatostatin have in the pancreas?
Inhibits pancreatic enzyme, fluid and bicarbonate secretion
37
What effects does somatostatin have in the gall bladder?
Reduces bile flow
38
What effects does somatostatin have in the intestines?
Inhibits motility and reduces nutrient and fluid transport
39
What is the broad trophic effect of somatostatin on the GI system?
Inhibits tissue growth throughout the GI tract
40
What is somatostatin considered to be?
General inhibitory factor of the GI tract and endocrine systems
41
What are the paracrine actions of somatostatin?
Occur in the stomach, Acts on neighbouring chief cells and G cells in a paracrine manner
42
What is Zollinger-Ellison syndrome?
Caused by excessive secretion of acid, Gastrin-secreting tumours in pancreas/duodenum, These are not under normal negative regulation, Affects ~1 in 1,000,000 people, Causes stomach to produce too much acid leading to ulcers, Treatment reduces acid production and heals ulcers, Surgery to remove tumours