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Case 3 > Applied Physiology and Biochemistry of the Upper Gastrointestinal Tract > Flashcards

Applied Physiology and Biochemistry of the Upper Gastrointestinal Tract Flashcards

1
Q

What is the composition of the primary secretion of saliva

A

Plasma-like (isotonic)

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2
Q

How is the saliva modified in the ducts

A

The ducts are relatively impermeable to water meaning that sodium and chloride ions are removed. Saliva therefore is hypotonic to plasma

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3
Q

Where is saliva formed

A

In the acinar cells of the acinus

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4
Q

What effect does parasympathetic activity have on saliva secretion

A

It increases secretion rate. Also peptides (kalikreins) released from nerves cause vasodilation in the secretory glands

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5
Q

What does the increase in secretory rate of saliva result in

A

A change in osmolarity and ionic composition of the saliva formed

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6
Q

Describe NKCC1

A

NKCC1 supports the initial secretion of chloride ions, NKCC1 is a co-transporter (Na, K, Cl ions)

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7
Q

What does the constituents of saliva vary with

A

Flow rate

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8
Q

Describe stimulated saliva

A

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

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9
Q

Describe ion exchange that occurs in the ducts

A

Ducts act to reabsorb Na+ and Cl-. Na+ out, H+ in. Cl- out, HCO3- (bicarbonate) in

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10
Q

Why does saliva become closer to plasma in composition at high rates of salivary flow

A

The exchange mechanisms don’t have enough time to remove Na+ and Cl-

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11
Q

What is the key role of the transport mechanism in the ducts

A

To remove ions (Na+ and Cl-) from the lumen of the duct

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12
Q

Describe what happens to saliva at low rates of flow

A

The transporters are able to remove ions more effectively (relatively impermeable to water) and leave behind water resulting in salivary fluid becoming more hypoosmotic

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13
Q

What are the 3 key phases of swallowing

A

Oral, pharyngeal and oesophageal

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14
Q

Which component of swallowing is voluntary

A

The oral (first) phase

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15
Q

Which components of swallowing are involuntary

A

Pharyngeal and oesophageal (relfex autonomic)

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16
Q

Describe the oral phase of swallowing

A

When food hits the sensory receptors on the soft palate the involuntary phase of swallowing is initiated (oral phase initiates involuntary phase)

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17
Q

Describe the pharyngeal phase of swallowing

A

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

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18
Q

Describe the oesophageal phase of swallowing

A

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

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19
Q

What pushes the bolus down the oesophagus

A

A peristaltic wave that starts during the pharyngeal phase continues to push the bolus down the oesophagus

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20
Q

What are the pharyngeal and oesophageal phases controlled by

A

Involuntary and controlled by the medulla and lower pons

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21
Q

What is dysphagia

A

Difficulty in swallowing

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22
Q

What can dysphagia be caused by

A

A number of different reasons such as a lesion in a cranial nerve (such as trigeminal nerve) or drug related (anticholinergic drugs)

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23
Q

What type of muscle does the upper part of the oesophagus consist of

A

Striated muscle under involuntary control

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24
Q

What is peristalsis organised by in the upper part of the oesophagus

A

The brainstem

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25
Q

What type of muscle does the lower oesophagus consist of

A

Smooth muscle

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26
Q

What is peristalsis organised by in the lower part of the oesophagus

A

ENS (enteric nervous system)

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27
Q

Describe the lower oesophageal sphincter

A

Maintains resting tone, displays receptive relaxation

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28
Q

How does the lower oesophageal sphincter remain closed

A

By lying below the diaphragm meaning that abdominal pressure helps keep it closed

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29
Q

Why can reflux of acid occur in pregnancy

A

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

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30
Q

What volume is gastric juice at rest

A

~30ml

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31
Q

What happens to pH on arrival of a meal

A

pH first rises (food buffering) and then falls (activation of H+/K+ ATPase)

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32
Q

What effect does arrival of a meal have on the parietal cells

A

They secrete intrinsic factor and HCl

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33
Q

What does a lack of intrinsic factor result in

A

Anaemia

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34
Q

What happens to chief cells when a meal arrives

A

They secrete pepsinogen

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35
Q

What happens to stomach pressure when food arrives

A

Pressure stays the same due to accomodation

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36
Q

Describe the cephalic phase in gastric secretion

A

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)

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37
Q

Describe the gastric phase in gastric secretion

A

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)

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38
Q

Describe the intestinal phase in gastric secretion

A

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)

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39
Q

What is the role of mucus neck cells

A

Important in secreting mucus which helps to protect the cell surface of the stomach.

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40
Q

Which nerve are mucus neck cells stimulated by

A

The vagus

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41
Q

What effect does alcohol have on surface mucus secreting cells

A

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

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42
Q

What do G-cells release

A

The hormone gastrin

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43
Q

What do D-cells release

A

Somatostatin (largely inhibitory agent)

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44
Q

What do H-cells release

A

(ECL) release histamine

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45
Q

What happens when you stimulate the parietal cells

A

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

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46
Q

What happens once the proton pump in the tubulovesicles has been stimulated

A

It pumps out H+ ions in exchange for K+. The hydrogen ions acidify the lumen of the stomach

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47
Q

What are hydrogen ions in the tubulovesicles produced by

A

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

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48
Q

Describe the activity at the apical membrane of the tubulovesicles

A

H+-K+-ATPase is inserted and chloride ions can leave through two routes

49
Q

Describe the activity at the basolateral membrane

A

Bicarbonate leaves exchanging with chloride ions

50
Q

What are the 3 phases of nervous and hormonal mechanisms controlling gastric secretion

A

Cephalic, Gastric and Intestinal

51
Q

Describe the cephalic phase

A

30% response, food in mouth causes an increase in vagal outflow. Vagus innervates ENS lining the stomach and stimulates parietal cells and G cells

52
Q

Describe the gastric phase

A

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

53
Q

When is gastrin secretion inhibited

A

At low pH (2-3)

54
Q

What does the vago-vagal reflex do

A

In gastric phase, further stimulates acid secretion

55
Q

Describe the intestinal phase

A

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

56
Q

What do G cells in the duodenum respond to

A

Increased amount of protein digestion products

57
Q

Describe the inhibitory effect of the intestinal phase

A

Due to duodenal release of secretin and CCK & GIP. Inhibitory products largely inhibit acid secretion

58
Q

What is secretin released in response to

A

Increase in acid

59
Q

What are CCK and GIP released in response to

A

An increase in fat digestion products

60
Q

What are the parietal cell main receptors

A

Cholingeric, gastrin, histamine, somatostatin, prostaglandin

61
Q

Describe the cholinergic receptor pathway

A

Activate Gq to increase PKC and increase Ca2+

62
Q

Describe the gastrin receptor pathway

A

Activate Gq to increase PKC and increase Ca2+

63
Q

Describe the histamine receptor pathway

A

Activate Gs to increase PKA, potentiates gastrin effect

64
Q

Describe the somatostatin receptor pathway

A

Activate Gi to decrease PKA, helps switch off HCl secretion

65
Q

Describe the prostaglandin receptor pathway

A

Active Gi to decrease PKA, acts to help keep HCl secretion switched off at rest

66
Q

Why do you get gastric erosion when you take aspirin

A

It blocks the product of prostaglandins removing the inhibitory effects and so at rest you get acid secretion= gastric erosion

67
Q

What effect does the presence of fat have on gastric emptying

A

Presence of lipid results in slower emptying of the stomach

68
Q

What are the natural mechanisms for switching off acid secretion

A

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

69
Q

What is the central mechanism of feedback control of gastrin secretion

A

Somatostatin release from D-cells via paracrine and endocrine pathways

70
Q

Describe the role of the gastric phase in the control of gastrin secretion

A

Via pH-H+ stimulation of D cells (which increases the inhibitory effects of somatostatin)

71
Q

Describe the role of the intestinal phase in the control of gastrin secretion

A

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+

72
Q

What inhibit gastric G and gastric P cells

A

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

73
Q

What are the functions of the exocrine pancreas

A

Alkaline and enzyme rich fluid into the GI tract

74
Q

What are the two major components of pancreatic juice

A

Aqueous and enzymatic

75
Q

What nature does the pancreas have

A

A lobular nature

76
Q

What cells does the exocrine pancreas consist of

A

Acinar cells

77
Q

What do acinar cells produce

A

Enzymes, HCl and most enzymes in an inactive from so that the pancreas doesn’t autodigest

78
Q

What part of the pancreaseis responsible for producing bicarbonate

A

The duct cells

79
Q

What is bicarbonate in the pancreas needed for

A

Neutraliation of HCl that enter the duodenum from the pyloric sphincter

80
Q

How does the pancreas release substances into the duodenum

A

From the common bile duct via the sphincter of Oddi

81
Q

What is the duct of santori and why is it important

A

An axillary duct which is important when considering blockages of the ducts

82
Q

Describe the intestinal phase of pancreatic secretion

A

Responsible for the majority of stimulation. Secretin is secreted by the S-cells in response to the presence of acid in the duodenum

83
Q

What is pancreatic juice

A

Enzyme-rich secretions from acinar cells and bicarbonate rich fluid secreted by duct cells

84
Q

What is the role of secretin

A

Stimulating bicarbonate release from the duodenum and inhibits acid release from the stomach (integrated nature of the control of the GI tract)

85
Q

What are responsible for parasympathetic stimulation of the pancrease

A

CCK and ACh

86
Q

What do CCK and ACh do in the pancreas

A

Stimulate acinar cells to secrete enzyme and Cl- rich secretion

87
Q

What does the release of chloride into the acinus form

A

A hypertonic solution

88
Q

What does the fact that ducts are water soluble mean

A

Have isosmotic solution (different to saliva cells)

89
Q

Describe the aqueous component of pancreatic juice

A

High in bicarbonate, composition depends on rate of secretion

90
Q

Describe the enzymes in pancreatic juice

A

Stored in acinar cells- zymogen granules (are acidic which helps keep enzymes inactive)

91
Q

How do the duct cells modify primary acinar secretions

A

Enzyme carbonic anhydrase, on the apical membrane have bicarbonate chloride exchanger, have sodium hydrogen exchanger on basolateral membrane

92
Q

What do duct cells utilize to modify primary acinar secretions

A

Intracellular: carbonic anhydrase
Apical: HCO3-/ Cl- exchange
Basolateral: Na+/ H+ exchange

93
Q

What effect does secretin have on the duct cells

A

Stimulates HCO3-/ Cl- exchange via activation of Gs leads to increase PKA activity which phosphorylates Cl- channels (cystic fibrosis transmembrane regulator).

94
Q

What do the effects on duct cell antagonists result in

A

An increase in bicarbonate rich fluid

95
Q

How does the juice composition changes with stimulation of flow rate

A

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.

96
Q

What effects does the cephalic phase have on the pancreas

A

Acinar cells and duct cells via parasympathetic vagal efferent nerves

97
Q

What effects does the gastric phase have on the pancreas

A

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

98
Q

What effects does the intestinal phase have on the pancreas

A

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

99
Q

Dsecribe the actions of CCK in relation to the pancreas

A

CCK contracts the gall bladder and relaxes the sphincter of Oddi.

100
Q

When would gall stones causes pain after a meal

A

CCK is released 2-3 hours after a meal therefore gallstones would result in increased pressure and pain 2-3 hours after a meal

101
Q

Describe the pentagastrin test

A

Looks at stomach acidity levels and can detect a specific autoimmune disease (medullary thyroid carcinoma) where the parietal cells have been damaged

102
Q

What is bile formed from

A

Cholesterol- forms primary bile acid

103
Q

How are bile salts reused many times

A

Recycled from the terminal ileum back to the liver, about 3g circulates 8x per day

104
Q

Describe bile secretion

A

94% of bile salts that enter the

intestine are reabsorbed (solid line= conjugated bile salts, broken line = deconjugated bile salts)

105
Q

What role does the gall bladder play in relation to bile

A

Acts as a reservoir, it concentrates bile and empties mainly by CCK

106
Q

Where are bile salts stored when the sphincter of Oddi is closed

A

Gall bladder

107
Q

What does the gall bladder do

A

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

108
Q

What is the major factor in regulation of bile secretion

A

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)

109
Q

Describe cholesterol gall stones

A

Excess cholesterol results in crystal formation, these act as nuclei for Ca2+ and PO4 salts

110
Q

Describe bilirubin excretion

A

With glucuronic acid (bilirubin is a breakdown product of haemoglobin and is conjugated with glucuronic acid)

111
Q

Describe jaundice

A

Raised plasma bilirubin, yellow colouration eyes and sclera and itchy feeling of skin due to irritant nature of bilirubin

112
Q

What are the two mechanisms of bile secretion

A

BAD- bile acid dependent 1. BAI- bile acid independent 2.

113
Q

Describe BAD

A

Bile acid dependent 1- depends on the rate of bile acid return

114
Q

Describe BAI

A

Bile acid independent 2- secretion of electrolytes and water by hepatocytes and duct cells

115
Q

Describe bile acid secretion

A

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

116
Q

What do choleretic do

A

Increase the rate of bile secretion

117
Q

What do cholagogues do

A

Increase the flow of bile via emptying of gallbladder e.g. contracting the gallbladder

118
Q

What effect does secretin have on ductal cells

A

Stimulation. Produces bicarbonate rich watery fluid

Case 3 (9 decks)

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