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Physiology Flashcards

1
Q

What is the term used to describe when food moves in the direction of mouth to anus?

A

Aboral

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2
Q

What is the term used to describe when food moves from the anus to mouth direction?

A

Oral direction

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3
Q

Name the accessory structures of the alimentary canal

A
  • salivary glands
  • the pancreas
  • the liver and gall bladder (hepatobiliary system)
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4
Q

Describe the basic function of mouth and oropharynx

A
  • chops and lubricates food
  • starts carbohydrate digestion
  • delivers food to oesophagus
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5
Q

Describe the basic function of the oesophagus

A

Propels food to stomach

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6
Q

Describe the basic function of the stomach

A
  • stores / churns food
  • continues carbohydrate digestion
  • initiates protein
  • digestion
  • regulates delivery of chyme to duodenum
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7
Q

Describe the basic function of the small intestine

A
  • duodenum, jejunum, ileum

- principal site of digestion and absorption of nutrients

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8
Q

Describe the basic function of the large intestine

A
  • caecum, appendix and colon
  • colon reabsorbs fluids and electrolytes
  • stores faecal matter before delivery to rectum
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9
Q

Describe the basic function of the rectum and anus

A

Regulated expulsion of faeces

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10
Q

What are sphincters?

A

Muscular constrictions

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11
Q

What is chyme?

A

Small particles of food

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12
Q

Name the four layers of the digestive tract wall

A
  • mucosa
  • submucosa
  • muscularis externa
  • serosa
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13
Q

Describe the mucosa

A
  • mucous membrane (epithelial, exocrine gland and endocrine gland cells)
  • lamina propria (capillaries, enteric neurones, gut-associated lymphoid tissues)
  • muscularis mucosae
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14
Q

Describe the submucosa

A
  • connective tissue
  • larger blood and lymph vessels
  • submucous plexus (neurone network)
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15
Q

Describe the muscularis externa

A
  • circular muscle layer
  • myenteric plexus (neurone network)
  • longitudinal muscle layer
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16
Q

Describe the serosa

A

Connective tissue

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17
Q

Name the four major functions of the digestive tract

A
  • motility
  • secretion
  • digestion
  • absorption
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18
Q

Describe motility

A

Mechanical activity mostly involving smooth muscle (skeletal at mouth, pharynx, upper oesophagus and external anal sphincter)

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19
Q

Describe secretion

A

Into the lumen of the digestive tract occurs from itself and accessory structure in response to the presence of food, hormonal and neural signals. Required for digestion, protection and lubrication

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20
Q

Describe digestion

A

Chemical breakdown by enzymatic hydrolysis of complex foodstuffs to smaller, absorbable units

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21
Q

Describe absorption

A

Transfer of the absorbable products of digestion (with water, electrolytes and vitamins) from the digestive tract to the blood, or lymph - largely mediated by numerous transport mechanisms

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22
Q

What is the gastrointestinal motility mostly due to?

A

The activity of the smooth muscle

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23
Q

The activity of the smooth muscle includes which muscles?

A
  • circular
  • longitudinal
  • muscularis mucosae
  • skeletal muscle is important in the mouth, pharynx, upper oesophagus and external anal spinchter
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24
Q

Describe circular muscle contraction

A

Lumen becomes narrower and longer

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25
Q

Describe longitudinal muscle contraction

A

Intestine becomes shorter and fatter

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26
Q

Describe muscularis mucosae contraction

A

Change in absorptive and secretory area of mucosa (folding), mixing activity

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27
Q

Adjacent smooth muscle cells are coupled by what?

A
  • gap junctions

- electrical currents flow from cell to cell

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28
Q

Describe a synchronous wave

A
  • hundreds of cells are depolarised and contract at the same time a synchronous wave
  • ie. single unit smooth muscle as opposed to multiunit smooth muscle
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29
Q

Spontaneous activity across the coupled cells is driven by what?

A

Specialised pacemaker cells

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30
Q

Spontaneous activity across the coupled cells is modulated by what?

A
  • intrinsic (enteric) and extrinsic (autonomic) nerves

- numerous hormones

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31
Q

Describe slow waves

A
  • in the stomach, small and large intestine spontaneous electrical activity occur as slow waves
  • rhythmic patterns of membrane depolarisation and repolarisation that speed from cell to cell via gap junctions
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32
Q

Slow waves determine what?

A

Determines the frequency, direction and velocity of rhythmic contractions

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33
Q

Slow waves are driven by what cells?

A
  • interstitial cells of cajal (ICCs)
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34
Q

What are interstitial cells of cajal?

A

Pacemaker cells located largely between the circular and longitudinal muscle layers

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35
Q

Describe the interstitial cells of cajal

A
  • form gap junctions with each other and smooth muscle cells electrically coupling them
  • slow waves in ICCs drive slow waves in the smooth muscle cells coupled to them
  • some ICCs forma bridge between nerve endings and smooth muscle cells
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36
Q

How does contraction in the intestine occur?

A

Occurs only if the slow wave amplitude is sufficient to reach a threshold to trigger smooth muscle cell calcium action potentials (spikes)

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37
Q

Force is related to what?

A

The number of action potentials discharged (driven in turn by the duration of the slow wave that is above threshold)

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38
Q

What is the upstroke and the downstroke of the action potential due to?

A
  • upstroke mediated by voltage- activated Ca2+ channels

- downstroke by voltage activated K+ channels

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39
Q

What is the basic electrical rhythm also known as?

A

Slow waves

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40
Q

What does whether slow wave amplitude reaches the threshold depend on?

A
  • neuronal stimuli
  • hormonal stimuli
  • mechanical stimuli

Generally act to depolarise smooth muscle cells rather than influence slow waves directly, depolarisation shifts slow wave peak to threshold

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41
Q

Describe the parasympathetic innervation of the GI tract

A

Preganglionic fibres (releasing ACh) synapse with ganglion cells (in essence post-ganglionic neurones) within the enteric nervous system (ENS)

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42
Q

Describe the excitatory influences of the parasympathetic innervation of the GI tract

A
  • increased gastric, pancreatic and small intestinal secretion
  • blood flow
  • smooth muscle contraction
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43
Q

Describe the inhibitory influences of the parasympathetic innervation of the GI tract

A

Relaxation of some sphincters, receptive relaxation of the stomach

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44
Q

Describe the sympathetic innervation of the GI tract

A

Preganglionic fibres (releasing ACh) synapse in the prevertebral ganglia. Postganglionic fibres (releasing NA) innervate mainly enteric neurones, but also other structures

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45
Q

Describe the excitatory influences of the sympathetic innervation of the GI tract

A

Increased sphincter tone

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46
Q

Describe the inhibitory influences of the sympathetic innervation of the GI tract

A

Decreased motility, secretion and blood flow

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47
Q

The enteric nervous system neurones are mostly located in ganglia connected by fibre tracts within what?

A
  • myenteric (auerbachs) plexus

- submucous (meissners) plexus

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48
Q

Describe the main role of the myenteric plexus

A

Mainly regulates motility and blood vessels

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49
Q

Describe the main role of the submucous plexus

A

Mainly modulates epithelia and blood vessels

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50
Q

The enteric nervous system coordinates muscular, secretive and absorptive activities via what?

A
  • sensory neurones; mechanoreceptors, chemoreceptors, thermoreceptors
  • interneurons; the majority, co-ordinating reflexes and motor programmes
  • effector neurones; excitatory and inhibitory motor neurones supplying both smooth muscle layers, secretory epithelium, endocrine cells and blood vessels
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51
Q

Motor and secretory activity are controlled by what?

A

Nerve reflexes

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52
Q

Name an example of a local reflex

A

Peristalsis

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53
Q

Name an example of a short reflex

A

Intestino-intestinal inhibitory reflex

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54
Q

What is the intestino-intrstine reflex?

A

Local distension activates sensory neurones exciting sympathetic pre-ganglionic fibres that cause inhibition of muscle activity in adjacent areas

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55
Q

Name an example of a long reflex

A

Gastroileal reflex (a vasovagal reflex)

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56
Q

Describe the gastroileal reflex

A

Increase in gastric activity causes increased propulsive activity in the terminal ileum

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57
Q

Describe peristalsis

A

A wave of relaxation, followed by contraction, that normally proceeds a short distance along the gut in an aboral direction, triggered by distension of the gut wall

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58
Q

Describe the altered activity of motorneurones in the propulsive segment of peristalsis

A
  • circular muscle contracts (release of ACh and substance P from excitatory motoneurone)
  • longitudinal muscle relaxes (release of VIP and NO from inhibitory motoneurone)
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59
Q

Describe the altered activity of motoneurones in the receiving segment during peristalsis

A
  • longitudinal muscle contracts (release of ACh and substance P from excitatory motoneurone)
  • circular muscle relaxes (release of VIP and NO from inhibitory motoneurone)
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60
Q

Describe segmentation

A
  • mixing or churning movements
  • rhythmic contractions of the circular muscle layer that mix and divide luminal contents
  • occurs in the small intestine (in the fed state) and in the large intestine (where it is called haustration)
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61
Q

Describe colonic mass movement

A

Powerful sweeping contraction that forces faeces into the rectum, occurs a few times a day

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62
Q

Describe the migrating motor complex (MMC)

A

Powerful sweeping contraction from stomach to terminal ileum

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63
Q

Describe tonic contractions

A
  • sustained contractions
  • low pressure; organs with a major storage function (eg. stomach)
  • high pressure; sphincters
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64
Q

How many sphincters of the GI tract are there (excluding the sphincter of oddi) ?

A

6

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65
Q

Describe sphincters

A
  • composed of specialised circular, generally smooth muscle
  • act as essentially one way valves by maintaining a positive resting pressure relative to two adjacent structures (eg. oesophagus and stomach)
  • in general, stimuli (pressure) proximal and distal to a sphincter cause opening and closing respectively
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66
Q

Describe the upper oesophageal sphincter

A
  • skeletal muscle
  • relaxes to allow swallowing
  • closes during inspiration
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67
Q

Describe the lower oesophageal sphincter

A
  • relaxes to permit entry of food to the stomach

- closes to prevent reflux of gastric contents to the oesophagus

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68
Q

Describe the pyloric sphincter

A
  • regulates gastric emptying

- usually prevents duodenal gastric reflux

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69
Q

Describe the ileocaecal valve

A
  • regulated flow from ileum to caecum

- distension of ileum opens, distension of proximal colon closes

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70
Q

Describe the internal and external anal sphincters

A
  • internal = smooth muscle
  • external = skeletal muscle
  • are regulated by the defaecation reflex
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71
Q

What is energy homeostasis?

A

Physiological process whereby energy intake is matched to energy expenditure over time
- promotes body fuel stability- energy primarily stored as fat

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72
Q

What is not a single disorder but a heterogeneous group of conditions with multiple causes?

A

Obesity

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73
Q

Name the major influencing factors of obesity

A
  • genetics

- environment

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74
Q

What is the energy balance disturbance?

A

Difference between energy intake and expenditure

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75
Q

Name some consequences of obesity

A
  • stroke (hypertension)
  • respiratory disease (sleep apnoea)
  • heart disease (lipids, diabetes, hypertension)
  • gallbladder disease
  • osteoarthritis
  • dementia (alzheimers)
  • NAFLD (fatty liver)
  • diabetes
  • cancer (uterus, breast, prostate, colon)
  • hyperuricemia, gout
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76
Q

Why is fat needed?

A
  • energy storage
  • prevention of starvation
  • energy buffer during prolonged illness
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77
Q

Name a survival adaptation for starvation and infection

A

Adipose tissue accumulation

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78
Q

The CNS influences energy balance and body weight by?

A
  • behaviour; feeding and physical activity
  • ANS activity; regulates energy expenditure
  • neuroendocrine system; secretion of hormones
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79
Q

The site of integration is where?

A

The brain

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80
Q

The neural centre responsible is what?

A

Hypothalamus

eg. lesioning ventromedial hypothalamus causes obesity, lesioning lateral hypothalamus causes leanness

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81
Q

Name the three basic concepts that underlie the control of energy intake and body weight system

A
  • satiety signalling
  • adiposity negative feedback signalling
  • food reward
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82
Q

What is satiation?

A

Sensation of fullness generated during a meal

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83
Q

What is satiety?

A

Period of time between termination of one meal and the initiation of the next

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84
Q

What is adiposity?

A

The state of being obese

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85
Q

What regulate meal initiation, termination and inter-meal frequency?

A

Short-term processes

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86
Q

When do satiation signals increase?

A

During meal to limit meal size

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87
Q

Name the five satiation signals

A
  • cholecystokinin (CCK)
  • peptide YY (PYY 3-36)
  • glucagon like peptide 1 (GLP-1)
  • oxyntomodulin (OXM)
  • obestatin
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88
Q

Describe cholecystokinin (CCK)

A

Secreted from enteroendocrine cells in duodenum and jejunum. Released in proportion to lipids and proteins in meals. Signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract (NTS))

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89
Q

Describe peptide YY (PYY3-36)

A

Secreted from endocrine mucosal L-cells of GI tract. Levels increase rapidly post-prandially. Inhibits gastric motility, slows emptying and reduces food intake (hypo)

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90
Q

Describe glucagon-like peptide 1 (GLP-1)

A

Product of pro-glucagon gene. Also released from L cells in response to food ingestion. Inhibits gastric emptying and reduces food intake (hypo, NTS)

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91
Q

Describe oxyntomodulin (OXM)

A

Also from pro-glucagon gene and released from oxyntic cells and L-cells of small intestine after meal. Acts to supress appetite - mechanism and site unclear

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92
Q

Describe obestatin

A

Peptide produced from gene that encodes ghrelin and released from cells lining stomach / small intestine. Suggested to reduce food intake - may act to antagonise the actions of ghrelin - actions unclear

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93
Q

What is the hunger signal?

A

Grehlin

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94
Q

Describe ghrelin

A
  • octanoylated peptide, produced and secreted by oxyntic cells in stomach
  • ghrelin levels increase before meals and decrease after meals
  • levels are raised by fasting and hypoglycaemia
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95
Q

What does ghrelin stimulate?

A

Stimulates food intake, decreases energy expenditure and decreases fat utilisation - increases body weight

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96
Q

Overall energy balance is controlled by what?

A

Feedback loops which act to maintain constancy of total body energy stores

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97
Q

Which two hormones, produced in peripheral tissues act on hypothalamic neurons?

A

Adiposity signals

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98
Q

What is the effect of glutamate, gaba and opioids when injected into hypothalamic centres?

A

Increase food intake - effect modest / short lasting

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99
Q

Which two hormones report fat status to the brain?

A

Leptin and insulin

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100
Q

Where is leptin made and released from?

A

Fat cells

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101
Q

Where is insulin made and released from?

A

Pancreatic beta cells

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102
Q

Describe leptin

A
  • member of the cytokine family
  • made and secreted from adipocytes
  • circulates in proportion to body adiposity
  • specific transport system for leptin to enter brain
  • high levels of leptin receptors in hypothalamus
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103
Q

What type of hormone is leptin?

A

A pleiotropic hormone

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104
Q

Describe the biological roles of leptin

A
  • food intake / energy expenditure / fat deposition
  • peripheral glucose homeostasis / insulin sensitivity
  • maintenance of immune system
  • maintenance of reproductive system
  • angiogenesis
  • tumourigenesis
  • bone formation
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105
Q

What would result in leptin resistance and why?

A
  • diet-induced obesity
  • defective leptin transport into brain
  • altered signal transduction following leptin binding to its receptor
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106
Q

What is the starting point for digestion of proteins?

A

The stomach by pepsin and HCL, continues carbohydrate digestion (by salivary amylase)

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107
Q

Describe the stomach

A

J shaoed bag, 50>1000ml capacity, orad region relaxes receptively (driven by vagus) to accommodate food from oesophagus

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108
Q

The stomach mixes food with what to produce chime?

A

Gastric secretions to produce semi-liquid chyme

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109
Q

What does the stomach secrete?

A

Approx. 2 litres/day of gastric juice from gastric glands in the gastric mucosa

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110
Q

Describe the mechanical activity of the stomach

A
  • occurs as two types
  • orad stomach (fundus and proximal body) - tonic ie. maintained
  • caudad stomach (distal body and antrum) - phasic ie. intermittent
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111
Q

Describe the orad region of the stomach

A
  • relaxation driven by vagus occurs during a swallow
  • no slow wave activity
  • tonic contractions, when they occur, are weak due to relatively thin musculature
  • contents propelled intermittently to caudad region by low amplitude tonic contractions of about 1 min duration - decrease stomach size as it empties
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112
Q

What allows for carbohydrate partial digestion by salivary amylase in the stomach?

A

Minimal mixing of contents for long 1hr periods

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113
Q

Which hormone decreases contractions and hence rate of stomach emptying?

A

Gastrin

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114
Q

Describe the caudad region

A
  • slow waves occur continuously but only those reaching threshold elicit contraction
  • phasic peristaltic contractions driven by suprethreshold slow waves progress from midstomach to gastroduodenal junction (the antral wave or pump) propelling contents towards pylorus through which a very small volume of chime flows into the duodenum
  • velocity of contraction increases towards the junction, overtaking the movement of chime that rebounds against constricted distal antrum back into the relaxed body of the stomach - this is retropulsion
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115
Q

What does retropulsion do?

A

Mixes gastric contents reducing chime (grinding function) to small particle that pass through the pylorus

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116
Q

What empties the stomach?

A

The antral pump

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117
Q

What determine escape of chime through the pyloric sphincter?

A

The strength of antral wave, or pump, determines escape

governed by; gastric factors and duodenal factors

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118
Q

Describe gastric factors of control of stomach emptying

A
  • rate of emptying proportional to volume of chime in stomach -
  • distension increases motility due to; stretch of smooth muscle, stimulation of intrinsic nerve plexuses, increased vagus nerve activity and gastrin release
  • consistency of chime; emptying facilitated by thin liquid chyme
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119
Q

How does the duodenum delay emptying?

A
  • neuronal response; the enterogastric reflex, decreases antral activity by signals from intrinsic nerve plexuses and the ANS
  • hormonal response;’ release of enterogastrones (eg CCK) from duodenum inhibits stomach contraction
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120
Q

Name stimuli within the duodenum that drives the neuronal and hormone responses

A
  • FAT; particularly potent, delay in gastric emptying required for digestion and absorption in small intestine
  • ACID; time is required for neutralisation of gastric acid by bicarbonate secreted from the pancreas - important for optimal function of pancreatic digestive enzymes
  • HYPERTONICITY; products of carbohydrate and protein digestion are osmotically active and draw water into the small intestine - danger of reduced plasma volume and circulatory disturbance (eg. dumping syndrome)
  • distension
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121
Q

The oxyntic gland area is where?

A

Proximal stomach including the fundus and body

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122
Q

Where is the pyloric gland area?

A

Distal stomach, designated the antrum

123
Q

The gastric mucosa is composed of what?

A
  • a surface lining the stomach
  • pits, invaginations of the surface
  • glands, at the base of the pits responsible for several secretions
124
Q

Describe HCl

A
  • activates pepsinogen to pepsin
  • denatures protein
  • kills most (not all) micro-organisms ingested with food
125
Q

Describe pepsinogen

A
  • inactive precursor of the peptidase, pepsin

- not pepsin once formed activated pepsinogen (autocatalytic)

126
Q

Describe intrinsic factor and gastroferrin

A
  • bind vitamin B12 and Fe2+ respectively, facilitating subsequent absorption
127
Q

Describe histamine

A

Stimulated HCl secretion

128
Q

Describe mucus

A

Protective

129
Q

Describe gastrin

A

Stimulated HCl secretion

130
Q

Describe somatostatin

A

Inhibits HCl secretion

131
Q

What does the gastric parietal cell secrete?

A

HCl

132
Q

Name the three important secretagogues that induce acid secretion from the parietal cells

A
  • ACh
  • gastrin
  • histamine
133
Q

Describe the direct pathway of HCL secretion

A

In the direct pathway, ACh, gastrin and histamine stimulate the parietal cell, triggering the secretion of H+ into the lumen

134
Q

Describe the indirect pathway of HCl secretion

A

In the indirect pathway, ACh and gastrin also stimulate the ECL cell, resulting in secretion of histamine. This histamine then acts on the parietal cell

135
Q

Stimuli for secretion of H+ act by what?

A

Both PLC - IP3 (gastrin ACh) and cAMP - PKA (histamine) signalling pathways

136
Q

Stimuli for inhibition of secretion of H+ act by what?

A

cAMP-PKA (somatostatin, prostaglandins) signalling pathways

137
Q

What molecules stimulate and inhibit adenylate cyclase?

A
  • histamine stimulates

- somatostatin and prostaglandins inhibit

138
Q

Secretagogues cause what?

A

Trafficking of the H+/K+ATPase

139
Q

Describe the resting state of the parietal cell

A

H+/K+ATPase is largely within cytoplasmic tubulovesicles

140
Q

Describe the stimulate state of the parietal cell

A

H+/K+ATPase traffics to the apical membrane taking residence in extended microvilli

141
Q

Rate of gastric secretion is controlled by what?

A

Stimulatory and inhibitory mechanisms that occur in three overlapping phases

142
Q

Name the three phases of gastric acid secretion

A
  • cephalic phase
  • gastric phase
  • intestinal phase
143
Q

Describe the cephalic phase of gastric acid secretion

A
  • in the head
  • before food reaches the stomach preparing the stomach to receive food
  • driven directly and indirectly by the CNS and vagus nerves (CNX)
144
Q

Describe the gastric phase of gastric acid secretion

A
  • when food is in the stomach

- involves both physical and chemical mechanisms

145
Q

Describe the intestinal phase of gastric acid secretion

A
  • after food has left the stomach
  • chyme entering the upper small intestine causes weak stimulation of gastric secretion via neuronal and hormonal mechanisms
146
Q

The vagus stimulates enteric neurones that do what during the cephalic phase?

A
  • release ACh directly activating parietal cells (neurotransmitter action)
  • via release of GRP causes release of gastrin from G cell into systemic circulation that activates parietal cells (endrocrine action)
  • via release of histamine from ECL cells that locally activates parietal cells (paracrine action)
  • via inhibition of D cells decreases the inhibitory effect of ss on G cells
147
Q

Describe the cephalic phase in relation to inhibition of gastric acid secretion

A
  • vagal nerve activity decrease upon cessation of eating and following stomach emptying
148
Q

Describe the gastric phase in relation to inhibition of gastric acid secretion

A
  • antral pH falls when food exits stomach (due to decreased buffering of gastric HCl), release of somatostatin from D cells recommences, decreasing gastrin secretion
  • prostaglandin E2 (PGE2) continually secreted by the gastric mucosa acts locally to reduce histamine - and gastrin mediated HCL secretion
149
Q

Describe the intestinal phase in relation to inhibition of gastric acid secretion

A

The factors that reduce gastric motility also reduce gastric secretion (eg. neuronal reflexes, enterogastrones)

150
Q

The small intestine receives what?

A
  • chyme from stomach (via the pylori sphincter)
  • pancreatic juice from the pancreas
  • bile from liver and gall bladder (both via the sphincter of oddi)
151
Q

The small intestine secretes what?

A

Intestinal juice (succus entericus)

152
Q

Motility of the small intestine causes what?

A
  • mixing of the chyme with digestive juices (segmentation)
  • slow propulsion of the chyme aborally (peristalsis)
  • removal of undigested residues to the large intestine via the ileocaecal valve (the migrating motor complex; MMC)
153
Q

How is the small intestine well adapted for absorption?

A
  • circular folds (of kerckring)
  • villi
  • microvilli (brush border)
154
Q

Name the two steps involved in the mixing and propulsion of chyme in the small intestine

A
  • segmentation (mixing) in the digestive state

- peristalsis in the interdigestive or fasting state

155
Q

Describe segmentation (mixing) in the digestive state

A
  • chopping moves chyme back and forth, very vigorour after a meal, little or none between meals
  • alternating contraction and relaxation of segments of circular muscle
  • initiated by small intestine pacemaker cells causing the BER which is continuous, at threshold activates segmentation which in the duodenum is primarily due to distension by entering chyme
  • duodenum has frequent segmentation contractions, ileum has fewer, net movement is slightly aboral
  • movement is slow
  • strength of segmentation enhanced and decreased by parasympathetic and sympathetic activity, respectively
  • segmentation in the empty ileum is triggered by gastrin from the stomach (gastroileal reflex)
156
Q

Describe peristalsis in the interdigestive or fasting state

A
  • a few localise contractions
  • the migrating motor complex
  • note macrolide antibiotic eg. erythromycin mimic effect of motilin and may cause GI disturbances
157
Q

Describe the migrating motor complex (MMC)

A
  • occur between meals every 90-120 minutes
  • strong peristaltic contraction slowly passing length of the intestine (stomach > ileocaecal valve)
  • clears small intestine of debris, mucus and sloughed epithelial cells between meals ; housekeeper function
  • inhibited by feeding and vagal activity
  • triggered by motilin, supressed by gastrin and CCK
158
Q

Which peptide hormones does the small intestine secrete into the blood?

A
  • gastrin
  • secretin
  • cholecystokinin CCK
  • glucose dependent insulinotropic peptide
  • glucagon like peptide 1
  • motilin
  • ghrelin
159
Q

Describe glucose-dependent insulinotropic peptide

A
  • from K cells of duodenum and jejunum
  • released in response to glucose, amino acid and fatty acids
  • stimulates release of insulin from pancreatic beta cells (incretin action)
  • inhibits gastric emptying
160
Q

Describe glucagon like peptide 1

A
  • from L cells of the small intestine
  • stimulates insulin secretion
  • inhibits glucagon secretion from pancreatic alpha cells
  • decreases gastric emptying and appetite
161
Q

Describe motilin

A
  • from M cells of duodenum and jejunum, secreted during fastin state
  • initiates the migrating motor complex
162
Q

All peptide hormones act on what?

A

G protein coupled receptors

163
Q

Incretins act upon what?

A

Beta cells of the pancreas in essentially feed-forward manner to stimulate the release of insulin

164
Q

Describe the control mechanisms of succus entericus secretion

A
  • distension / irritation
  • gastrin
  • CCK
  • secretin
  • parasympathetic nerve activity

^^ all enhance

  • sympathetic nerve activity decreases
165
Q

Succus entericus secretion lacks digestive enzymes but contains what?

A
  • mucus; for lubrication / protection (from goblet cells)

- aqueous salt; for enzymatic digestion (mostly from the crypts of lieberkuhn)

166
Q

Name the endocrine secretions from the pancreas

A

Insulin and glucagon - secreted to blood

167
Q

Name the exocrine secretion from the pancreas

A

Digestive enzymes (acinar cells), aqueous NaHCO3- solution (duct cells0) - secreted to the duodenum collectively as pancreatic juice

168
Q

Describe secretion of the pancreatic duct cells

A
  • secrete 1-2 litres of alkaline (HCO3- rich) fluid into the duodenum per day
  • neutralised acidic chyme for entering the duodenum; provides optimum pH for pancreatic enzyme function, protects the mucosa from erosion by acid
169
Q

Which enzymes can completely digest food in the absence of all other enzymes?

A

Pancreatic enzymes

170
Q

Define digestion

A

The enzymatic conversion of complex dietary substances to a form that can be absorbed

171
Q

Luminal digestion is mediated by what?

A

Mediated by enzymes secreted into the duodenum

172
Q

Membrane digestion is mediated by what?

A

Enzymes at the brush border of epithelial cells

173
Q

Define absorption

A

The processes by which the absorbable products of digestion are transferred across both the apical and basolateral membranes of enterocytes (absorptive cells of the intestinal epithelium)

174
Q

What is assimilation?

A

The overall process of digestion and absorption

175
Q

What provides 45% of total energy requirements?

A

Digestible carbohydrate

176
Q

All dietary carbohydrate must be converted to what for absorption?

A

Monosaccharides

177
Q

Describe the role of endoenzyme

A
  • breaks down linear internal alpha 1, 4 linkages but not terminal alpha 1,4 linkages - hence no production of glucose
  • cannot cleave alpha 1,6 linkages at branch points (in amylopectin) or alpha 1,4 linkages adjacent to branch points
  • products are thus linear glucose oligomers (maltotriose, maltose) and alpha limit dextrins
178
Q

Name the integral membrane proteins with a catalytic domain that faces the lumen of the GI tract

A

Oligosaccharidases

179
Q

Lactase has how many substrates?

A

Only one - breaks down lactose to glucose and galactose

180
Q

Describe maltase

A

Can degrade the alpha 1,4 linkages in straight chain oligomers up to nine monomers in length

181
Q

Describe sucrase

A

Specifically responsible for hydrolysing sucrose to glucose and fructose

182
Q

Describe isomaltase

A

Is unique in that it is the only enzyme that can split the branching alpha 1,6 linkages of alpha limit dextrins

183
Q

Describe absorption of the final products of carbohydrate digestion (glucose, galactose and fructose)

A
  • occurs in the duodenum and jejunum
  • is a two step process involving entry and exit from enterocytes via the apical and basolateral membranes, respectively
  • glucose and galactose are absorbed by secondary active transport mediated by SGLT1; fructose by facilitated diffusion mediated by GLUT 5
  • exit for all monosaccharides is mediated by facilitated diffusion by GLUT 2
184
Q

For transport via SGLT1 the substrate must be what?

A
  • a hexose in the beta conformation

- one that can form a pyranose ring

185
Q

Describe the mode of operation of SGLT1

A
  • 2 NA+ binds
  • affinity for glucose increases, glucose binds
  • NA+ and glucose translocate from extracellular to intracellular
  • 2 Na+ dissociate, affinity for glucose fall - glucose dissociates
  • cycle is repeated
186
Q

Protein, after the first 6 months of life, must be digested to what?

A

To oligopeptides and amino acids for efficient absorption

187
Q

How many major pathways exist for protein digestion?

A

Four

188
Q

What accounts for 10-15% of daily energy intake?

A

Protein assimilation

189
Q

Where are additional proteases present?

A
  • at the brush border

- within the cytoplasm of the enterocyte

190
Q

Brush border peptidases are?

A
  • numerous because each enzyme attacks a limited number of peptide bonds and the oligopeptides to be digested are extremely varied in their structure
  • have affinity for larger oligopeptides
  • either endopeptides or exopeptides
  • the latter comprising both aminopeptidases and carboxypeptidases
191
Q

Describe cytoplasmic peptidases

A
  • are less numerous than brush border peptidases

- primarily hydrolyse dipeptides, or tripeptides

192
Q

Describe amino acids in relation to protein absorption

A
  • brush border; at least 7 different mechanisms are present
  • 5 are Na+ dependent co transporters mediating uphill movement (secondary active transport)
  • 2 are Na+ independent
193
Q

Dysfunction in the 2 Na+ independent reactions can lead to what?

A

Cystinuria

194
Q

Dysfunction in the 5 Na+ dependent reactions can lead to what?

A

Hartnup disease

195
Q

Describe the basolateral membrane in relation to amino acids

A
  • at least 5 different mechanisms
  • 3 mediate efflux of amino acids and are Na+ independent
  • 2 mediate influx and are Na+ dependent (supplying the enterocytes nutritional requirements along with absorbed amino acids)
  • net movement is thus bidirectional
196
Q

Describe di, tri and tetra-peptides transport

A
  • via H+ dependent mechanism (pepT1, SLC15A) at brush border (co-transport)
  • further hydrolysed to amino acids within the enterocyte
  • Na+ independent systems at the basolateral membrane (facilitated transport)
197
Q

Ingested lipids comprise of what?

A
  • fats/oils; triacylglycerols. Fatty acids may be saturated, unsaturated, ratio is high in animal fats and low in plant
  • phospholipids; mostly glycerophospholipids eg. lecithin
  • cholesterol and cholesterol esters
  • fatty acids
198
Q

Emulsification of ingested lipids occurs by what?

A
  • mouth; chewing
  • stomach; gastric churning and squirting through the narrow pylorus, context mixed with digestive enzymes from mouth and stomach
  • small intestine; segmentation and peristalsis mix the luminal content with pancreatic and biliary secretions
199
Q

How are emulsion droplets stabilised?

A
  • by the addition of a coat of amphiphilic molecules that form a surface layer on the droplets that includes;
  • certain products of lipid digestion itself (eg. fatty acids, monoacylglycerols)
  • biliary phospholipids
  • cholesterol
  • bile salts (when the droplets have progressively been reduced to unilamellar and mixed micelles)
200
Q

Droplets produced by mechanical disruption provide what?

A

Provide a vast increase in the surface area to volume ratio that increases the area of the oil water interface at which digestion by lipases and other esterases can accomplish digestion

201
Q

Lipid digestion of TAG by lipases proceeds as

A
  • mouth; lingual phase
  • stomach; gastric phase by gastric lipase (and lingual lipase in saliva)
  • gastric lipase secreted in response to gastrin from chief cells
202
Q

Describe gastric lipase

A
  • has a pH optimum of 4 and is resistant to pepsin
  • is inactive in the duodenum due to digestion by pancreatic protease and unfavourable pH
  • preferentially hydrolyses TAGs at the 3 position
203
Q

Which chain fatty acids are absorbed into the stomach and which ones are not?

A
  • short and medium chain fatty acids are absorbed

- long chain fatty acids are not

204
Q

What does diacylglycerol + free fatty acids do?

A

Stimulates CCK release from duodenum and secretion of pancreatic lipase

205
Q

Digestion by pancreatic lipase produces what?

A

2-monoacylglycerol and free fatty acids

206
Q

Pancreatic lipase is secreted from where?

A
  • acinar cells of pancreas in response to CCK which also stimulates bile flow
207
Q

Full activity of pancreatic lipase

A
  • colipase co-factor
  • alkaline pH
  • Ca2+
  • bile salts
  • fatty acids
208
Q

Pancreatic lipase mainly hydrolyses TAGs where?

A

At the 1 and 3 positions

209
Q

Describe the role of bile salt

A
  • bile salts released into the duodenum in bile from the gall bladder in response to CCK act as detergents to help emulsify large lipid droplets to small droplets
  • bile salts are amphipathic
  • increase surface area for attack by pancreatic lipase but blocks access of the enzyme to the TAGs
210
Q

Failure to secrete bile salts results in what?

A
  • lipid malabsorption- steatorrhoea (fat in faeces)

- secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A,D,E and K)

211
Q

Describe colipase

A
  • an amphipathic molecule
  • secreted with lipase by the pancreas
  • binds to bile salts and lipase allowing access by the latter to tri and di-acylglycerols
  • colipase is secreted as inactive procolipase which is activated by trypsin
212
Q

Where are the final products of lipid digestion stored in are released from?

A

Mixed micelles

213
Q

What happens as TAGs towards the surface of the emulsion droplets are hydrolysed?

A

They are replaced by TAGs within the core, decreasing droplet size until a mixed micelle results

214
Q

Short chain and medium fatty acids diffuse through where?

A
  • the enterocyte

- exit through the basolateral membrane and enter the villus capillaries

215
Q

Long chain fatty acids and monoglycerides are re-synthesised to what?

A

Triglycerides in the endoplasmic reticulum and are subsequently incorporated into chylomicrons

216
Q

Describe the absorption of Ca2+

A
  • occurs by passive (ie. paracellular, the whole length of small intestine) and active (ie. transcellular, mainly duodenum and upper jejunum) transport mechanisms
  • with Ca2+ in chyme absorption is mainly active
  • active Ca2+ absorption is regulated by 1,25 dihydroxyvitamin D3 (calcitrol) and parathyroid hormone
217
Q

Describe iron

A
  • one of the most abundant elements on earth
  • an important constituent of haemoglobin and myoglobin and acts as co-factor for numerous enzyme-mediated processes
  • crucially important in carriage of oxygen by haemoglobin
  • daily loss of iron from the body (via urine, sweat and desquamated enterocytes) is an unregulated process
  • iron balance within the body, long term, depends upon tightly regulated absorption of iron across the duodenum which matches losses
218
Q

Describe dietary iron

A
  • mainly in the oxidised form, Fe3+, present in meat or vegetables as inorganic iron, haem or ferratin
  • required in only minor amounts daily
219
Q

Describe absorption of iron

A
  • a complex and tightly regulated process contributing to a balances level of the element in the body
  • Fe2+ absorbed across the apical membrane by transport processes
  • Fe2+ conveyed to basolateral membrane via a molecular chaperone
  • Fe2+ transported across the basolateral membrane by transport process
  • Fe2+ oxidised yo Fe3+ and then transported to tissues
  • import of haem across apical membrane followed by cytoplasmic metabolism to release Fe2+
220
Q

What does iron deficiency cause?

A
  • microcytic anaemia
221
Q

What dose excess iron cause?

A
  • excess is toxic due to accumulation in liver pancreas and heat
  • molecularly the production of hydroxyl radicals and hydroxide ions
222
Q

Describe the absorption of vitamin B12

A
  • ingested in food bound to proteins
  • stomach acid releases vitamin B12 from protein
  • haptocorin, secreted in saliva binds vitamin B12 released in stomach
  • stomach parietal cells release intrinsic factor
  • pancreatic proteases digest haptocorin in small intestine, vitamin B12 released
  • vitamin B12 binds to intrinsic factor in small intestine
  • vitamin B12 intrinsic factor complex absorbed in terminal ileum by endocytosis
223
Q

Describe absorption of fat soluble vitamins

A
  • A,D,E and K
  • absorption requires adequate bile secretion and an intact intestinal mucosa
  • incorporated into mixed micelles
  • usually passively transported into enterocytes
  • incorporated into chylomicrons or VLDLs
  • distributed by intestinal lymphatics
224
Q

Describe the metabolic functions of the liver

A
  • regulation of carbohydrate, lipid and amino acid metabolism
225
Q

Describe carbohydrate metabolism in the liver

A
  • hormonally regulated
  • gluconeogenesis; to produce glucose from amino acids
  • glycolysis; to form pyruvate then lactate(anaerobic), or acetyl-coA (aerobic)
  • glyconeogenesis; to store polymerised glucose as glycogen
  • glycogenolysis; to release glucose as required
226
Q

Describe fat metabolism in the liver

A
  • breakdown and synthesis
  • processing of chylomicron remnants
  • synthesis of lipoproteins (eg. VLDLs, HDLs for export) and cholesterol (for steroid hormone and bile acid synthesis)
  • ketogenesis (in starvation) important for neuronal function
227
Q

Describe protein metabolism in the liver

A
  • synthesis of plasma proteins
  • transamination and deamination of amino acids
  • conversion of ammonia to urea
228
Q

Which hormones are deactivation in the liver?

A
  • insulin
  • glucagon
  • anti-diuretic hormone (ADH, vasopressin)
  • steroid hormones
229
Q

Which hormones are activated in the liver?

A
  • conversion of thyroid hormone (by deiodination of thyroxine T4, to the more reactive triiodothyronine T3)
  • conversion of vitamin D to 25-hydroxyvitamin D2 (calcifediol), further activation to 1,25 dihydroxyvitamin D3 (calcitrol) occurs in the kidney
230
Q

What are the categories of major function of the liver?

A
  • storage of
  • synthesis of proteins
  • protection
  • detoxification
231
Q

Describe the storage function of the liver

A

Storage of;

  • fat soluble vitamin
  • water soluble vitamin B12
  • iron, copper
  • glycogen
232
Q

Describe the synthesis of proteins in the liver

A
  • for the metabolic processes of the organ
  • for export
  • coagulation factors 2,7,8, 10 also proteins C and S
  • albumin
  • complement proteins
  • apolipoproteins
  • carrier proteins
233
Q

Describe the protection function of the liver

A
  • Kupffer cells (liver phagocytes) digest/destroy particulate matter eg. bacteria and senescent (old) erythrocytes
  • production of immune factors, host defence proteins (acute phase proteins)
234
Q

Describe the detoxification function of the liver

A
  • many endogenous substances (eg. bilirubin as a metabolite of haemoglobin breakdown)
  • exogenous substances (xenobiotics), drugs, ethanol (alcohol)
235
Q

Describe the secretion of bile

A
  • participates in the digestion and absorption of fats and the excretion of products of metabolism (including drug metabolites)
  • produced continuously (0.6-1.2 litres per day by combined secretion from hepatocytes and bile duct cells)
236
Q

Describe the secretion of bile between meals

A
  • stored and concentrated in gall bladder (sphincter of oddi closed)
237
Q

Describe secretion of bile during a meal

A
  • chime in duodenum stimulates gallbladder smooth muscle to contract (via CCK and vagal impulses)
  • sphincter of oddi opens (via CCK)
  • bile spurts into duodenum via cystic and common bile ducts (mixed with bile from liver)
238
Q

Neutral / slightly alkaline bile assists what?

A
  • micelle formation
  • neutralisation of chyme
  • pH adjustment for digestive enzyme action
  • protection of the mucosa
239
Q

What is secreted from hepatocytes?

A
  • primary bile acids, mainly cholic and chenodeoxycholic acids
  • water and electrolytes including Na+, K+, Ca2+, Cl- and HCO3-
  • lipids and phospholipids eg. lecithin
  • cholesterol
  • IgA
  • bilirubin
  • metabolic wastes and conjugated drug metabolites
240
Q

Describe bilirubin

A
  • breakdown product of the porphyrin component of haemoglobin
  • pigment rendering urine yellow and faeces brown
  • when present in excess causes jaundice
241
Q

What is the most common pathology of the biliary tract?

A

Cholelithiasis

242
Q

How do gall stones form?

A

Concentration of bile in the gall bladder (caused by reabsorption of water) produces a supersaturated solution that is unstable. Cholesterol may crystallise and over time grow into a gall stone

243
Q

What is the best treatment for symptomatic stones (eg. causing cholangitis or pancreatitis)

A

Laproscopic cholecystectomy

244
Q

When would ursodeoxycholic acid be suitable for patients?

A

May be suitable for patients with unimpaired gall bladder function who have small / medium sized radiolucent stones (CH stones) which it dissolves. Diarrhoea is an adverse effect

245
Q

Why may morphine make colic pain worse?

A

May worsen pain dut to constriction of the sphincter of oddi and increased intrabiliary pressure. Alternatives are buprenorphine and pethidine

246
Q

Biliary spasm can be relieved by what?

A

Atropine or GTN

247
Q

What is enterohepatic recycling?

A

only a small fraction of bile salts entering the duodenum is lost in the faeces, most is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling

248
Q

Loss of bile acid is matched by what?

A

Synthesis requiring utilisation of hepatic cholesterol

249
Q

A fraction of the primary bile acids (cholic and chenodeoxycholic) are dehydroxylated by what?

A

By bacteria in the gut to form the secondary bile acids (deoxycholic and lithocholic) all of which are returned to the liver

250
Q

What happens to secondary bile acids upon returning to the liver?

A

They are conjugated with glycine or taurine and recycle as bile salts (of Na+ and K+)

251
Q

Name some examples of bile acid sequestrants (resins)

A
  • colveselam
  • colestipol
  • colestyramine
252
Q

Describe the function of bile acid sequestrants (resins)

A
  • neither digester nor absorbed by the gut
  • act by binding to bile acids, preventing their reabsorption
  • lower plasms LDL cholesterol indirectly
253
Q

Describe how bile acid sequestrants (resins) lower plasma LDL cholesterol indirectly

A
  • promote hepatic conversion of cholesterol to bile acids
  • increase cell surface expression of LDL receptor in hepatocytes
  • increase clearance of LDL-cholesterol from plasma
254
Q

Describe the clinical uses of bile acid sequestrants (resins)

A
  • hyperlipidaemia (limited effect)
  • cholestatic jaundice (itch)
  • bile acid diarrhoea
255
Q

Describe the limitations and adverse effects of bile acid sequestrants (resins)

A
  • unpalatable, inconvenient (large doses)
  • frequently cause diarrhoea
  • reduced absorption of fat-soluble vitamins and some drugs (thiazide diuretics)
256
Q

Drugs are xenobiotics - drug metabolism acts to?

A
  • covert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney (from the renal tubes), facilitating excretion
  • convert drugs to metabolites that are usually pharmacologically less active than the parent compound
257
Q

Describe phase 1 of drug metabolism

A
  • oxidation
  • reduction
  • hydrolysis
  • makes drug more polar, adds a chemically reactive group (a handle) permitting conjugation (functionalisation)
258
Q

Describe phase 2 of drug metabolism

A
  • conjugation
  • adds an endogenous compound increasing polarity
  • eg. with glucuronyl, sulphate, methyl, acetyl, glycyl or glutathione groups
259
Q

Which haem proteins located in the endoplasmic reticulum of liver hepatocytes mediates oxidation reactions (
phase 1) of many lipid soluble drugs?

A

The cytochrome P450 family of monooxygenases

260
Q

Name the main gene families of cytochrome P450 in human liver

A
  • CYP1
  • CYP2
  • CYP3
261
Q

Describe phase 2 reactions

A
  • usually result in inactive products
  • largely occurs in the liver
  • involves conjugation of chemically reactive groups eg. hydroxyl, thiol or amino with glucoronyl, sulphate, methyl or acetyl groups
262
Q

Describe glucouronidation

A

A common reaction involving the transfer of glucuronic acid to electron-rich atoms of the substrate (N,O or S) forming an amide, ester or thiol bonds

263
Q

Many endogenous substances are subject to what?

A

To glucouronidation (eg. bilirubin, adrenal corticosteroids)

264
Q

What can happen in severe hepatic failure? eg. fulminant liver failure

A
  • detoxification of ammonia (NH3) via the urea cycle to urea (excreted by kidneys) fails
  • blood NH3 levels rise (hyperammonemia) exerting a toxic effect upon the CNS that causes incoordination, drowsiness, coma and ultimately death due to cerebral oedema
265
Q

What is a therapeutic option for hepatic encephalopathy

A
  • lactulose
  • antibiotics (neomycin, rfiamixin) that are minimally absorbed, supress colonic flora and thus inhibit ammonia generation
266
Q

Describe lactulose

A
  • a semi-synthetic disaccharide of fructose and lactose which;
  • is not digested or absorbed in the small intestine
  • when broken down in the colon acidifies the stool (reduces pH)
  • converts ammonia to ammonium which is not absorbed
267
Q

Absorption of water is a what process driven by what?

A
  • a passive process

- driven by the transport of solutes (particularly Na+) form the lumen of the intestine to the bloodstream

268
Q

Water ingested and secreted is usually in balance with what?

A

With water absorbed

269
Q

What are the typical values of water absorption in the body?

A
  • 9.3 litres entering tract per day
  • 8.3 litres absorbed by small intestine
  • 1 litre enters large intestine of which 90% is absorbed
270
Q

Faeces usually contain how much water and cellulose, bilirubin and bacteria?

A
  • around 100ml water

- 50ml cellulose, bilirubin and bacteria

271
Q

Define diarrhoea

A

A loss of fluid and solutes from the GI tract in excess of 500ml per day

272
Q

Absorption of water in the GI tract is largely driven by what?

A

Reabsorption of Na+

273
Q

Intestinal fluid movement is always couple to what?

A

Solute movement

274
Q

Water may move via which routes?

A

Transcellular or paracellular routes

275
Q

Reabsorption of Na+ provides what?

A

A local osmotic force for reabsorption of water

276
Q

Describe the principal mechanisms of reabsorption of Na+

A
  • Na+/glucose co-transport
  • Na+ / amino acid co-transport
  • Na+ / H+ exchange
  • parallel Na+ /H+ and Cl- / HCO3- exchange
  • epithelial Na+ channels (ENAC)
277
Q

Where does Na+/ glucose co-transport and Na+/ amino acid co-transport take place?

A
  • occurs throughout the small intestine and is most important in the postprandial period (also occurs in the colon in new born)
278
Q

Where does Na+ /H+ exchange take place?

A

Occurs in the duodenum and jejunum and is stimulated by luminal HCO3-

279
Q

Where does parallel Na+ / H+ and Cl- / HCO3- exchange take place?

A

Occurs in the ileum and colon most important in the interdigestive period

280
Q

Where does epithelial Na+ channels (ENAC) occur?

A

Occurs in the colon (distal particularly) and is regulated by aldosterone

281
Q

What are the major mechanisms of postprandial Na+ absorption in the jejunum?

A

Na+ / glucose and Na+/ amino acid co transport

282
Q

Describe Na+/ H+ exchange in the jejunum

A
  • occurs at both the apical (NHE2 and NHE3) and basolateral (NHE1) membranes, but only NHE2 and NHE3 contribute to trans-epithelial movement of Na+ and the regulation of intracellular pH
283
Q

Which molecule is a ‘cellular pH housekeeper’?

A

NHE1

284
Q

Exchange at the apical membrane, in the jejunum is stimulated by what?

A

The alkaline environment of the lumen (ie. high pH = low proton concentration) due to the presence of bicarbonate from the pancreas

285
Q

What is the primary mechanism of Na+ absorption in the inter-digestive period?

A

Na+/H+ and Cl=/HCO3- exchange in parallel

Occurs in the ileum and proximal colon

Does not greatly contribute to postprandial absorption

286
Q

What mediates electrogenic Na+ absorption in the distal colon?

A

Epithelial Na+ channels (ENAC)

287
Q

What are the three actions of aldosterone?

A
  • opens ENAC (seconds)
  • inserts more ENAC into membrane from intracellular vesicle pool (minutes)
  • increases synthesis of ENAC and Na+/K+ ATPase (hours)
288
Q

How can Cl- absorption occur passively?

A

Via the transcellular or paracellular routes

289
Q

What is the driving force provided in the small intestine for Cl- absorption?

A

Provided by lumen negative potential due to electrogenic transport of Na+

290
Q

What is the driving force provided in the large intestine for Cl- absorption?

A

Provided by lumen negative potential due to electrogenic movement of Na+ through NEAC

291
Q

Name the other mechanisms of Cl- absorption

A
  • Cl- HCO3- exchange (ileum, proximal and distal colon)

- parallel Na+ H+ and Cl– HCO3- exchange (ileum and proximal colon)

292
Q

Cl- secretion occurs at what rate and is usually overshadowed by what?

A
  • occurs at a basal rate

- usually overshadowed by a higher rate of absorption

293
Q

Cl- secretion occurs from what cells?

A

Crypt cells

294
Q

Name the three process involved in Cl- secretion on the basolateral membrane

A
  • Na/K+ ATPase
  • Na+/K+/2Cl- co transported (NKCC1)
  • K+ channels (IK1 and BK)
295
Q

Secretion occurs when CFTR is indirectly activated by what?

A
  • bacterial enterotoxins (eg. cholera toxin, heat stable enterotoxin, c diff)
  • hormones and neurotransmitters (eg. vasoactive intestinal peptide, guanylin, Ach, bradykinin, 5-HT)
  • immune cell products (eg. histamine, prostaglandins)
  • some laxatives (eg. bile acids)
296
Q

Activation of CFTR occurs indirectly as a result of what?

A
  • second messengers that include;
  • cAMP
  • cGMP
  • Ca2+
297
Q

The Cl- conductance mediated by CFTR results from what?

A
  • opening of channels at the apical membrane
  • insertion of channels from intracellular vesicle into the membrane
  • overall effect is secretory diarrhoea
298
Q

Misoprostol enhances secretion of what?

A

CFTR

299
Q

Name causes of diarrhoea

A
  • impaired absorption of NaCl
  • non-absorbable or poorly absorbable solutes in intestinal lumen
  • hypermotility
  • excessive secretion
300
Q

What exploits SGLT1?

A

Rehydration therapy

301
Q

Oral rehydration salts contain what?

A
  • glucose 20g
  • sodium chloride 3.5g
  • sodium bicarbonate 2.5g
  • potassium chloride 1.5g
  • dissolved in a volume of 1l drinking water
302
Q

Describe SGLT1

A
  1. 2 Na+ bind
  2. affinity for glucose increases, glucose binds
  3. Na+ and glucose translocate from extracellular to intracellular
  4. Na+ dissociate affinity for glucose falls
  5. glucose dissociates
  6. cycle is repeated
303
Q

The actions of opiods on the alimentary tract include what?

A
  • inhibition of enteric neurones (hyperpolarisation via activation of u-opiod receptors)
  • decreased peristalsis, increased segmentation ( ie constipating)
  • increased fluid absorption
  • constriction of pyloric, ileocaecal and anal sphincters
  • increased tone of large intestine
304
Q

The major opioid agonists used in diarrhoea are?

A
  • codeine
  • diphenoxylate (low CNS penetration, low solubility in water, decreased abuse potential, many preparations contain atropine)
  • loperamide (low CNS penetration, low solubility in water, undergoes enterohepatic recycling)

GI (11 decks)

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